PREDICTED: beta-chimaerin-like isoform X2 [Priapulus caudatus]
Protein Classification
List of domain hits
| Name | Accession | Description | Interval | E-value | ||||
| RhoGAP super family | cl02570 | RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ... |
252-444 | 3.29e-84 | ||||
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. The RhoGAPs are one of the major classes of regulators of Rho G proteins. The actual alignment was detected with superfamily member cd04372: Pssm-ID: 470621 [Multi-domain] Cd Length: 194 Bit Score: 256.68 E-value: 3.29e-84
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| C1_CHN | cd20806 | protein kinase C conserved region 1 (C1 domain) found in the chimaerin family; Chimaerins are ... |
191-243 | 2.86e-36 | ||||
protein kinase C conserved region 1 (C1 domain) found in the chimaerin family; Chimaerins are a family of phorbolester- and diacylglycerol-responsive GTPase activating proteins (GAPs) specific for the Rho-like GTPase Rac. Alpha1-chimerin (formerly known as N-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. Alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. : Pssm-ID: 410356 Cd Length: 53 Bit Score: 127.43 E-value: 2.86e-36
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| SH2 super family | cl15255 | Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ... |
6-84 | 2.70e-34 | ||||
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others. The actual alignment was detected with superfamily member cd10352: Pssm-ID: 472789 Cd Length: 91 Bit Score: 123.24 E-value: 2.70e-34
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| Name | Accession | Description | Interval | E-value | ||||
| RhoGAP_chimaerin | cd04372 | RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
252-444 | 3.29e-84 | ||||
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239837 [Multi-domain] Cd Length: 194 Bit Score: 256.68 E-value: 3.29e-84
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| RhoGAP | smart00324 | GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ... |
265-440 | 1.15e-58 | ||||
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers. Pssm-ID: 214618 Cd Length: 174 Bit Score: 190.17 E-value: 1.15e-58
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| RhoGAP | pfam00620 | RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. |
268-416 | 5.37e-55 | ||||
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. Pssm-ID: 459875 Cd Length: 148 Bit Score: 179.66 E-value: 5.37e-55
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| C1_CHN | cd20806 | protein kinase C conserved region 1 (C1 domain) found in the chimaerin family; Chimaerins are ... |
191-243 | 2.86e-36 | ||||
protein kinase C conserved region 1 (C1 domain) found in the chimaerin family; Chimaerins are a family of phorbolester- and diacylglycerol-responsive GTPase activating proteins (GAPs) specific for the Rho-like GTPase Rac. Alpha1-chimerin (formerly known as N-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. Alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410356 Cd Length: 53 Bit Score: 127.43 E-value: 2.86e-36
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| SH2_a2chimerin_b2chimerin | cd10352 | Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ... |
6-84 | 2.70e-34 | ||||
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198215 Cd Length: 91 Bit Score: 123.24 E-value: 2.70e-34
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| C1_1 | pfam00130 | Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the ... |
192-244 | 2.42e-21 | ||||
Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the Protein kinase C conserved region 1 (C1) domain. Pssm-ID: 395079 Cd Length: 53 Bit Score: 86.73 E-value: 2.42e-21
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| SH2 | smart00252 | Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ... |
6-74 | 1.52e-17 | ||||
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae. Pssm-ID: 214585 [Multi-domain] Cd Length: 84 Bit Score: 77.27 E-value: 1.52e-17
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| SH2 | pfam00017 | SH2 domain; |
6-73 | 7.60e-17 | ||||
SH2 domain; Pssm-ID: 425423 [Multi-domain] Cd Length: 77 Bit Score: 74.94 E-value: 7.60e-17
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| C1 | smart00109 | Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol ... |
192-241 | 1.80e-16 | ||||
Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains. Pssm-ID: 197519 Cd Length: 50 Bit Score: 72.89 E-value: 1.80e-16
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| Name | Accession | Description | Interval | E-value | ||||
| RhoGAP_chimaerin | cd04372 | RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
252-444 | 3.29e-84 | ||||
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239837 [Multi-domain] Cd Length: 194 Bit Score: 256.68 E-value: 3.29e-84
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| RhoGAP | smart00324 | GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ... |
265-440 | 1.15e-58 | ||||
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers. Pssm-ID: 214618 Cd Length: 174 Bit Score: 190.17 E-value: 1.15e-58
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| RhoGAP | cd00159 | RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ... |
268-439 | 2.19e-57 | ||||
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. The RhoGAPs are one of the major classes of regulators of Rho G proteins. Pssm-ID: 238090 [Multi-domain] Cd Length: 169 Bit Score: 186.74 E-value: 2.19e-57
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| RhoGAP | pfam00620 | RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. |
268-416 | 5.37e-55 | ||||
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. Pssm-ID: 459875 Cd Length: 148 Bit Score: 179.66 E-value: 5.37e-55
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| RhoGAP_p190 | cd04373 | RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
252-437 | 4.30e-45 | ||||
RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p190-like proteins. p190, also named RhoGAP5, plays a role in neuritogenesis and axon branch stability. p190 shows a preference for Rho, over Rac and Cdc42, and consists of an N-terminal GTPase domain and a C-terminal GAP domain. The central portion of p190 contains important regulatory phosphorylation sites. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239838 Cd Length: 185 Bit Score: 155.31 E-value: 4.30e-45
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| RhoGAP_ARHGAP21 | cd04395 | RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
252-444 | 5.21e-44 | ||||
RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP21-like proteins. ArhGAP21 is a multi-domain protein, containing RhoGAP, PH and PDZ domains, and is believed to play a role in the organization of the cell-cell junction complex. It has been shown to function as a GAP of Cdc42 and RhoA, and to interact with alpha-catenin and Arf6. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239860 Cd Length: 196 Bit Score: 152.55 E-value: 5.21e-44
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| RhoGAP_GMIP_PARG1 | cd04378 | RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ... |
252-439 | 2.11e-43 | ||||
RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein) and PARG1 (PTPL1-associated RhoGAP1). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239843 Cd Length: 203 Bit Score: 151.42 E-value: 2.11e-43
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| RhoGAP_fRGD1 | cd04398 | RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
252-444 | 8.92e-41 | ||||
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD1-like proteins. Yeast Rgd1 is a GAP protein for Rho3 and Rho4 and plays a role in low-pH response. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239863 Cd Length: 192 Bit Score: 144.08 E-value: 8.92e-41
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| RhoGAP_ARHGAP27_15_12_9 | cd04403 | RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ... |
252-437 | 1.47e-39 | ||||
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP27 (also called CAMGAP1), ARHGAP15, 12 and 9-like proteins; This subgroup of ARHGAPs are multidomain proteins that contain RhoGAP, PH, SH3 and WW domains. Most members that are studied show GAP activity towards Rac1, some additionally show activity towards Cdc42. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239868 [Multi-domain] Cd Length: 187 Bit Score: 140.60 E-value: 1.47e-39
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| RhoGAP_Graf | cd04374 | RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase ... |
273-439 | 7.25e-39 | ||||
RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase regulator associated with focal adhesion kinase); Graf is a multi-domain protein, containing SH3 and PH domains, that binds focal adhesion kinase and influences cytoskeletal changes mediated by Rho proteins. Graf exhibits GAP activity toward RhoA and Cdc42, but only weakly activates Rac1. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239839 Cd Length: 203 Bit Score: 139.45 E-value: 7.25e-39
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| RhoGAP_ARAP | cd04385 | RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ... |
268-439 | 7.42e-39 | ||||
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239850 Cd Length: 184 Bit Score: 138.60 E-value: 7.42e-39
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| RhoGAP_myosin_IX | cd04377 | RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ... |
252-437 | 1.60e-38 | ||||
RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in class IX myosins. Class IX myosins contain a characteristic head domain, a neck domain, a tail domain which contains a C6H2-zinc binding motif and a RhoGAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239842 Cd Length: 186 Bit Score: 137.95 E-value: 1.60e-38
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| RhoGAP_CdGAP | cd04384 | RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
250-439 | 6.19e-38 | ||||
RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of CdGAP-like proteins; CdGAP contains an N-terminal RhoGAP domain and a C-terminal proline-rich region, and it is active on both Cdc42 and Rac1 but not RhoA. CdGAP is recruited to focal adhesions via the interaction with the scaffold protein actopaxin (alpha-parvin). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239849 [Multi-domain] Cd Length: 195 Bit Score: 136.48 E-value: 6.19e-38
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| RhoGAP_MgcRacGAP | cd04382 | RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ... |
274-436 | 1.74e-37 | ||||
RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in MgcRacGAP proteins. MgcRacGAP plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling. ii) after phosphorylation by aurora B MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain a N-terminal C1-like domain, and a C-terminal RhoGAP domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239847 Cd Length: 193 Bit Score: 135.11 E-value: 1.74e-37
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| RhoGAP_GMIP | cd04408 | RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP ... |
252-439 | 4.61e-37 | ||||
RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239873 Cd Length: 200 Bit Score: 134.56 E-value: 4.61e-37
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| C1_CHN | cd20806 | protein kinase C conserved region 1 (C1 domain) found in the chimaerin family; Chimaerins are ... |
191-243 | 2.86e-36 | ||||
protein kinase C conserved region 1 (C1 domain) found in the chimaerin family; Chimaerins are a family of phorbolester- and diacylglycerol-responsive GTPase activating proteins (GAPs) specific for the Rho-like GTPase Rac. Alpha1-chimerin (formerly known as N-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. Alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410356 Cd Length: 53 Bit Score: 127.43 E-value: 2.86e-36
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| RhoGAP_nadrin | cd04386 | RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
248-444 | 9.00e-36 | ||||
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Nadrin-like proteins. Nadrin, also named Rich-1, has been shown to be involved in the regulation of Ca2+-dependent exocytosis in neurons and recently has been implicated in tight junction maintenance in mammalian epithelium. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239851 Cd Length: 203 Bit Score: 131.04 E-value: 9.00e-36
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| RhoGAP-p50rhoGAP | cd04404 | RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
242-444 | 5.65e-35 | ||||
RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p50RhoGAP-like proteins; p50RhoGAP, also known as RhoGAP-1, contains a C-terminal RhoGAP domain and an N-terminal Sec14 domain which binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). It is ubiquitously expressed and preferentially active on Cdc42. This subgroup also contains closely related ARHGAP8. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239869 [Multi-domain] Cd Length: 195 Bit Score: 128.61 E-value: 5.65e-35
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| SH2_a2chimerin_b2chimerin | cd10352 | Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ... |
6-84 | 2.70e-34 | ||||
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198215 Cd Length: 91 Bit Score: 123.24 E-value: 2.70e-34
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| RhoGAP_myosin_IXB | cd04407 | RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ... |
252-438 | 6.43e-34 | ||||
RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXB. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239872 [Multi-domain] Cd Length: 186 Bit Score: 125.49 E-value: 6.43e-34
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| RhoGAP_Bcr | cd04387 | RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr ... |
252-418 | 1.02e-33 | ||||
RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr (breakpoint cluster region protein)-like proteins. Bcr is a multidomain protein with a variety of enzymatic functions. It contains a RhoGAP and a Rho GEF domain, a Ser/Thr kinase domain, an N-terminal oligomerization domain, and a C-terminal PDZ binding domain, in addition to PH and C2 domains. Bcr is a negative regulator of: i) RacGTPase, via the Rho GAP domain, ii) the Ras-Raf-MEK-ERK pathway, via phosphorylation of the Ras binding protein AF-6, and iii) the Wnt signaling pathway through binding beta-catenin. Bcr can form a complex with beta-catenin and Tcf1. The Wnt signaling pathway is involved in cell proliferation, differentiation, and cell renewal. Bcr was discovered as a fusion partner of Abl. The Bcr-Abl fusion is characteristic for a large majority of chronic myelogenous leukemias (CML). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239852 [Multi-domain] Cd Length: 196 Bit Score: 125.43 E-value: 1.02e-33
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| RhoGAP_PARG1 | cd04409 | RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
252-439 | 5.34e-33 | ||||
RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of PARG1 (PTPL1-associated RhoGAP1). PARG1 was originally cloned as an interaction partner of PTPL1, an intracellular protein-tyrosine phosphatase. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239874 Cd Length: 211 Bit Score: 123.76 E-value: 5.34e-33
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| RhoGAP_ARHGAP22_24_25 | cd04390 | RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ... |
241-444 | 6.06e-32 | ||||
RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP22, 24 and 25-like proteins; longer isoforms of these proteins contain an additional N-terminal pleckstrin homology (PH) domain. ARHGAP25 (KIA0053) has been identified as a GAP for Rac1 and Cdc42. Short isoforms (without the PH domain) of ARHGAP24, called RC-GAP72 and p73RhoGAP, and of ARHGAP22, called p68RacGAP, has been shown to be involved in angiogenesis and endothelial cell capillary formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239855 [Multi-domain] Cd Length: 199 Bit Score: 120.63 E-value: 6.06e-32
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| C1_betaCHN | cd20857 | protein kinase C conserved region 1 (C1 domain) found in beta-chimaerin and similar proteins; ... |
187-246 | 2.73e-31 | ||||
protein kinase C conserved region 1 (C1 domain) found in beta-chimaerin and similar proteins; Beta-chimaerin, also called beta-chimerin (BCH) or Rho GTPase-activating protein 3 (ARHGAP3), is a GTPase-activating protein (GAP) for p21-rac. Insufficient expression of beta-2 chimaerin is expected to lead to higher Rac activity and could therefore play a role in the progression from low-grade to high-grade tumors. Beta-chimaerin contains a functional SH2 domain that can bind to phosphotyrosine motifs within receptors, a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410407 Cd Length: 61 Bit Score: 114.37 E-value: 2.73e-31
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| RhoGAP_srGAP | cd04383 | RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ... |
250-425 | 6.62e-31 | ||||
RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in srGAPs. srGAPs are components of the intracellular part of Slit-Robo signalling pathway that is important for axon guidance and cell migration. srGAPs contain an N-terminal FCH domain, a central RhoGAP domain and a C-terminal SH3 domain; this SH3 domain interacts with the intracellular proline-rich-tail of the Roundabout receptor (Robo). This interaction with Robo then activates the rhoGAP domain which in turn inhibits Cdc42 activity. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239848 Cd Length: 188 Bit Score: 117.52 E-value: 6.62e-31
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| C1_alphaCHN | cd20856 | protein kinase C conserved region 1 (C1 domain) found in alpha-chimaerin and similar proteins; ... |
188-243 | 4.03e-30 | ||||
protein kinase C conserved region 1 (C1 domain) found in alpha-chimaerin and similar proteins; Alpha-chimaerin, also called A-chimaerin, N-chimaerin (CHN), alpha-chimerin, N-chimerin (NC), or Rho GTPase-activating protein 2 (ARHGAP2), is a GTPase-activating protein (GAP) for p21-rac and a phorbol ester receptor. It is involved in the assembly of neuronal locomotor circuits as a direct effector of EPHA4 in axon guidance. Alpha-chimaerin contains a functional SH2 domain that can bind to phosphotyrosine motifs within receptors, a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410406 Cd Length: 57 Bit Score: 110.93 E-value: 4.03e-30
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| RhoGAP_SYD1 | cd04379 | RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ... |
252-418 | 8.99e-29 | ||||
RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239844 Cd Length: 207 Bit Score: 112.17 E-value: 8.99e-29
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| RhoGAP_myosin_IXA | cd04406 | RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ... |
252-437 | 3.12e-27 | ||||
RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXA. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239871 Cd Length: 186 Bit Score: 107.39 E-value: 3.12e-27
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| RhoGAP_fBEM3 | cd04400 | RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of ... |
252-411 | 5.42e-26 | ||||
RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of fungal BEM3-like proteins. Bem3 is a GAP protein of Cdc42, and is specifically involved in the control of the initial assembly of the septin ring in yeast bud formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239865 [Multi-domain] Cd Length: 190 Bit Score: 103.98 E-value: 5.42e-26
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| RhoGAP_FAM13A1a | cd04393 | RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
250-420 | 1.57e-24 | ||||
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of FAM13A1, isoform a-like proteins. The function of FAM13A1a is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by up several orders of magnitude. Pssm-ID: 239858 [Multi-domain] Cd Length: 189 Bit Score: 99.84 E-value: 1.57e-24
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| RhoGAP_ARHGAP18 | cd04391 | RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
251-444 | 5.26e-24 | ||||
RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP18-like proteins. The function of ArhGAP18 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239856 Cd Length: 216 Bit Score: 99.34 E-value: 5.26e-24
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| RhoGAP_ARHGAP20 | cd04402 | RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
251-444 | 1.45e-23 | ||||
RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP20-like proteins. ArhGAP20, also known as KIAA1391 and RA-RhoGAP, contains a RhoGAP, a RA, and a PH domain, and ANXL repeats. ArhGAP20 is activated by Rap1 and induces inactivation of Rho, which in turn leads to neurite outgrowth. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239867 Cd Length: 192 Bit Score: 97.37 E-value: 1.45e-23
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| RhoGAP_ARHGAP6 | cd04376 | RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
263-444 | 2.01e-23 | ||||
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP6-like proteins. ArhGAP6 shows GAP activity towards RhoA, but not towards Cdc42 and Rac1. ArhGAP6 is often deleted in microphthalmia with linear skin defects syndrome (MLS); MLS is a severe X-linked developmental disorder. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239841 Cd Length: 206 Bit Score: 97.51 E-value: 2.01e-23
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| C1_PKD_rpt1 | cd20795 | first protein kinase C conserved region 1 (C1 domain) found in the protein kinase D (PKD) ... |
192-241 | 3.53e-23 | ||||
first protein kinase C conserved region 1 (C1 domain) found in the protein kinase D (PKD) family; PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs contain N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the first C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410345 Cd Length: 56 Bit Score: 91.98 E-value: 3.53e-23
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| C1_1 | pfam00130 | Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the ... |
192-244 | 2.42e-21 | ||||
Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the Protein kinase C conserved region 1 (C1) domain. Pssm-ID: 395079 Cd Length: 53 Bit Score: 86.73 E-value: 2.42e-21
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| C1_cPKC_nPKC_rpt2 | cd20793 | second protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) ... |
192-241 | 1.92e-20 | ||||
second protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) protein kinase C (cPKC), novel protein kinase C (nPKC), and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. nPKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs (aPKCs) only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. This family includes classical PKCs (cPKCs) and novel PKCs (nPKCs). There are four cPKC isoforms (named alpha, betaI, betaII, and gamma) and four nPKC isoforms (delta, epsilon, eta, and theta). Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410343 Cd Length: 50 Bit Score: 84.25 E-value: 1.92e-20
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| C1_nPKC_theta-like_rpt2 | cd20837 | second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ... |
192-241 | 3.66e-20 | ||||
second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) theta, delta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410387 Cd Length: 50 Bit Score: 83.25 E-value: 3.66e-20
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| C1 | cd00029 | protein kinase C conserved region 1 (C1 domain) superfamily; The C1 domain is a cysteine-rich ... |
192-241 | 5.35e-20 | ||||
protein kinase C conserved region 1 (C1 domain) superfamily; The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains. It contains the motif HX12CX2CXnCX2CX4HX2CX7C, where C and H are cysteine and histidine, respectively; X represents other residues; and n is either 13 or 14. C1 has a globular fold with two separate Zn(2+)-binding sites. It was originally discovered as lipid-binding modules in protein kinase C (PKC) isoforms. C1 domains that bind and respond to phorbol esters (PE) and diacylglycerol (DAG) are referred to as typical, and those that do not respond to PE and DAG are deemed atypical. A C1 domain may also be referred to as PKC or non-PKC C1, based on the parent protein's activity. Most C1 domain-containing non-PKC proteins act as lipid kinases and scaffolds, except PKD which acts as a protein kinase. PKC C1 domains play roles in membrane translocation and activation of the enzyme. Pssm-ID: 410341 Cd Length: 50 Bit Score: 82.95 E-value: 5.35e-20
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| RhoGAP_fSAC7_BAG7 | cd04396 | RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ... |
267-443 | 1.67e-19 | ||||
RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal SAC7 and BAG7-like proteins. Both proteins are GTPase activating proteins of Rho1, but differ functionally in vivo: SAC7, but not BAG7, is involved in the control of Rho1-mediated activation of the PKC-MPK1 pathway. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239861 Cd Length: 225 Bit Score: 87.08 E-value: 1.67e-19
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| C1_PKD_rpt2 | cd20796 | second protein kinase C conserved region 1 (C1 domain) found in the family of protein kinase D ... |
192-242 | 8.11e-19 | ||||
second protein kinase C conserved region 1 (C1 domain) found in the family of protein kinase D (PKD); PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs contain N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410346 Cd Length: 54 Bit Score: 79.64 E-value: 8.11e-19
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| C1_nPKC_epsilon-like_rpt2 | cd20838 | second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ... |
192-241 | 1.60e-18 | ||||
second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) epsilon, eta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410388 Cd Length: 55 Bit Score: 78.85 E-value: 1.60e-18
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| RhoGAP_p85 | cd04388 | RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ... |
268-437 | 5.41e-18 | ||||
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in the p85 isoforms of the regulatory subunit of the class IA PI3K (phosphatidylinositol 3'-kinase). This domain is also called Bcr (breakpoint cluster region protein) homology (BH) domain. Class IA PI3Ks are heterodimers, containing a regulatory subunit (p85) and a catalytic subunit (p110) and are activated by growth factor receptor tyrosine kinases (RTKs); this activation is mediated by the p85 subunit. p85 isoforms, alpha and beta, contain a C-terminal p110-binding domain flanked by two SH2 domains, an N-terminal SH3 domain, and a RhoGAP domain flanked by two proline-rich regions. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239853 Cd Length: 200 Bit Score: 81.84 E-value: 5.41e-18
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| C1_PKD3_rpt1 | cd20841 | first protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and ... |
190-241 | 5.82e-18 | ||||
first protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and similar proteins; PKD3 is also called PRKD3, PRKCN, serine/threonine-protein kinase D3 (nPKC-D3), protein kinase C nu type (nPKC-nu), or protein kinase EPK2. It converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. It is involved in the regulation of the cell cycle by modulating microtubule nucleation and dynamics. PKD3 acts as a key mediator in several cancer development signaling pathways. PKD3 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the first C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410391 Cd Length: 75 Bit Score: 78.16 E-value: 5.82e-18
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| SH2 | smart00252 | Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ... |
6-74 | 1.52e-17 | ||||
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae. Pssm-ID: 214585 [Multi-domain] Cd Length: 84 Bit Score: 77.27 E-value: 1.52e-17
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| C1_PKD1_rpt1 | cd20839 | first protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and ... |
190-241 | 2.21e-17 | ||||
first protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and similar proteins; PKD is also called PKD1, PRKD1, protein kinase C mu type (nPKC-mu), PRKCM, serine/threonine-protein kinase D1, or nPKC-D1. It is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. PKD contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the first C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410389 Cd Length: 72 Bit Score: 76.21 E-value: 2.21e-17
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| C1_Sbf-like | cd20827 | protein kinase C conserved region 1 (C1 domain) found in the myotubularin-related protein Sbf ... |
192-241 | 3.56e-17 | ||||
protein kinase C conserved region 1 (C1 domain) found in the myotubularin-related protein Sbf and similar proteins; This group includes Drosophila melanogaster SET domain binding factor (Sbf), the single homolog of human MTMR5/MTMR13, and similar proteins, that show high sequence similarity to vertebrate myotubularin-related proteins (MTMRs) which may function as guanine nucleotide exchange factors (GEFs). Sbf is a pseudophosphatase that coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. It also functions as a GEF that promotes Rab21 GTPase activation associated with PI(3)P endosomes. Vertebrate MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Members of this family contain these domains and have an additional C1 domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410377 Cd Length: 53 Bit Score: 75.14 E-value: 3.56e-17
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| C1_PKD2_rpt2 | cd20843 | second protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and ... |
192-245 | 3.59e-17 | ||||
second protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and similar proteins; PKD2, also called PRKD2, HSPC187, or serine/threonine-protein kinase D2 (nPKC-D2), is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion. PKD2 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410393 Cd Length: 79 Bit Score: 75.78 E-value: 3.59e-17
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| C1_cPKC_rpt2 | cd20836 | second protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) ... |
192-241 | 4.82e-17 | ||||
second protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) protein kinase C (cPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410386 Cd Length: 54 Bit Score: 74.68 E-value: 4.82e-17
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| C1_SpBZZ1-like | cd20824 | protein kinase C conserved region 1 (C1 domain) found in Schizosaccharomyces pombe protein ... |
191-241 | 5.22e-17 | ||||
protein kinase C conserved region 1 (C1 domain) found in Schizosaccharomyces pombe protein BZZ1 and similar proteins; BZZ1 is a syndapin-like F-BAR protein that plays a role in endocytosis and trafficking to the vacuole. It functions with type I myosins to restore polarity of the actin cytoskeleton after NaCl stress. BZZ1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. Schizosaccharomyces pombe BZZ1 also harbors a C1 domain, but Saccharomyces cerevisiae BZZ1 doesn't have any. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410374 Cd Length: 53 Bit Score: 74.66 E-value: 5.22e-17
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| RhoGap_RalBP1 | cd04381 | RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ... |
267-414 | 7.04e-17 | ||||
RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in RalBP1 proteins, also known as RLIP, RLIP76 or cytocentrin. RalBP1 plays an important role in endocytosis during interphase. During mitosis, RalBP1 transiently associates with the centromere and has been shown to play an essential role in the proper assembly of the mitotic apparatus. RalBP1 is an effector of the Ral GTPase which itself is an effector of Ras. RalBP1 contains a RhoGAP domain, which shows weak activity towards Rac1 and Cdc42, but not towards Ral, and a Ral effector domain binding motif. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239846 [Multi-domain] Cd Length: 182 Bit Score: 78.25 E-value: 7.04e-17
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| SH2 | pfam00017 | SH2 domain; |
6-73 | 7.60e-17 | ||||
SH2 domain; Pssm-ID: 425423 [Multi-domain] Cd Length: 77 Bit Score: 74.94 E-value: 7.60e-17
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| RhoGAP-ARHGAP11A | cd04394 | RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
251-437 | 8.15e-17 | ||||
RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP11A-like proteins. The mouse homolog of human ArhGAP11A has been detected as a gene exclusively expressed in immature ganglion cells, potentially playing a role in retinal development. The exact function of ArhGAP11A is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239859 [Multi-domain] Cd Length: 202 Bit Score: 78.67 E-value: 8.15e-17
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| C1_PIK3R-like_rpt2 | cd20830 | second protein kinase C conserved region 1 (C1 domain) found in uncharacterized ... |
192-243 | 1.13e-16 | ||||
second protein kinase C conserved region 1 (C1 domain) found in uncharacterized phosphatidylinositol 3-kinase regulatory subunit-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate phosphatidylinositol 3-kinase regulatory subunits (PIK3Rs), which bind to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulate their kinase activity. Unlike typical PIK3Rs, members of this family have two C1 domains. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410380 Cd Length: 52 Bit Score: 73.44 E-value: 1.13e-16
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| C1_RASGRP | cd20808 | protein kinase C conserved region 1 (C1 domain) found in the RAS guanyl-releasing protein ... |
192-241 | 1.29e-16 | ||||
protein kinase C conserved region 1 (C1 domain) found in the RAS guanyl-releasing protein (RASGRP) family; The RASGRP family includes RASGRP1-4. They function as cation-, usually calcium-, and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. RASGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII) or Ras guanyl-releasing protein, activates the Erk/MAP kinase cascade and regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B-lymphocyte antigen receptors to Ras. RASGRP1 also regulates NK cell cytotoxicity and ITAM-dependent cytokine production by activation of Ras-mediated ERK and JNK pathways. RASGRP2, also called calcium and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Cdc25-like protein (CDC25L), or F25B3.3 kinase-like protein, specifically activates Rap and may also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. RASGRP2 is involved in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation, as well as in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. RASGRP3, also called calcium and DAG-regulated guanine nucleotide exchange factor III (CalDAG-GEFIII), or guanine nucleotide exchange factor for Rap1, is a guanine nucleotide-exchange factor activating H-Ras, R-Ras and Ras-associated protein-1/2. It functions as an important mediator of signaling downstream from receptor coupled phosphoinositide turnover in B and T cells. RASGRP4 may function in mast cell differentiation. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410358 Cd Length: 52 Bit Score: 73.53 E-value: 1.29e-16
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| C1_MRCK | cd20809 | protein kinase C conserved region 1 (C1 domain) found in the Myotonic dystrophy kinase-related ... |
192-241 | 1.67e-16 | ||||
protein kinase C conserved region 1 (C1 domain) found in the Myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) family; MRCK is thought to be a coincidence detector of signaling by the small GTPase Cdc42 and phosphoinositides. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. MRCK has been shown to promote cytoskeletal reorganization, which affects many biological processes. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. MRCK consists of a serine/threonine kinase domain, a cysteine rich (C1) region, a PH domain and a p21 binding motif. This model corresponds to C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410359 Cd Length: 53 Bit Score: 73.07 E-value: 1.67e-16
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| C1 | smart00109 | Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol ... |
192-241 | 1.80e-16 | ||||
Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains. Pssm-ID: 197519 Cd Length: 50 Bit Score: 72.89 E-value: 1.80e-16
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| RhoGAP_KIAA1688 | cd04389 | RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ... |
265-439 | 1.83e-16 | ||||
RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in KIAA1688-like proteins; KIAA1688 is a protein of unknown function that contains a RhoGAP domain and a myosin tail homology 4 (MyTH4) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239854 Cd Length: 187 Bit Score: 77.05 E-value: 1.83e-16
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| C1_cPKC_nPKC_rpt1 | cd20792 | first protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) ... |
192-241 | 2.28e-16 | ||||
first protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) protein kinase C (cPKC), novel protein kinase C (nPKC), and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. nPKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs (aPKCs) only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. This family includes classical PKCs (cPKCs) and novel PKCs (nPKCs). There are four cPKC isoforms (named alpha, betaI, betaII, and gamma) and four nPKC isoforms (delta, epsilon, eta, and theta). Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410342 Cd Length: 53 Bit Score: 72.66 E-value: 2.28e-16
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| RhoGAP_DLC1 | cd04375 | RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
252-411 | 2.97e-16 | ||||
RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of DLC1-like proteins. DLC1 shows in vitro GAP activity towards RhoA and CDC42. Beside its C-terminal GAP domain, DLC1 also contains a SAM (sterile alpha motif) and a START (StAR-related lipid transfer action) domain. DLC1 has tumor suppressor activity in cell culture. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239840 Cd Length: 220 Bit Score: 77.46 E-value: 2.97e-16
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| C1_MTMR-like | cd20828 | protein kinase C conserved region 1 (C1 domain) found in uncharacterized proteins similar to ... |
192-241 | 6.26e-16 | ||||
protein kinase C conserved region 1 (C1 domain) found in uncharacterized proteins similar to myotubularin-related proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate myotubularin-related proteins (MTMRs), such as MTMR5 and MTMR13. MTMRs may function as guanine nucleotide exchange factors (GEFs). Vertebrate MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Members of this family contain these domains and have an additional C1 domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410378 Cd Length: 57 Bit Score: 71.71 E-value: 6.26e-16
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| SH2_csk_like | cd09937 | Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ... |
6-79 | 1.17e-15 | ||||
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198190 Cd Length: 98 Bit Score: 72.32 E-value: 1.17e-15
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| C1_RASGRP4 | cd20863 | protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 4 ... |
192-242 | 1.19e-15 | ||||
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 4 (RASGRP4) and similar proteins; RASGRP4 functions as a cation- and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. It may function in mast cell differentiation. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410413 Cd Length: 57 Bit Score: 70.96 E-value: 1.19e-15
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| C1_PKD3_rpt2 | cd20844 | second protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and ... |
192-242 | 1.99e-15 | ||||
second protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and similar proteins; PKD3 is also called PRKD3, PRKCN, serine/threonine-protein kinase D3 (nPKC-D3), protein kinase C nu type (nPKC-nu), or protein kinase EPK2. It converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. It is involved in the regulation of the cell cycle by modulating microtubule nucleation and dynamics. PKD3 acts as a key mediator in several cancer development signaling pathways. PKD3 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410394 Cd Length: 69 Bit Score: 70.81 E-value: 1.99e-15
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| SH2_ABL | cd09935 | Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ... |
6-82 | 2.21e-15 | ||||
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198189 Cd Length: 94 Bit Score: 71.27 E-value: 2.21e-15
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| C1_PKD2_rpt1 | cd20840 | first protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and ... |
190-241 | 2.32e-15 | ||||
first protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and similar proteins; PKD2, also called PRKD2, HSPC187, or serine/threonine-protein kinase D2 (nPKC-D2), is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion. PKD2 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the first C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410390 Cd Length: 73 Bit Score: 70.47 E-value: 2.32e-15
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| C1_nPKC_theta-like_rpt1 | cd20834 | first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ... |
187-241 | 2.69e-15 | ||||
first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) theta, delta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410384 Cd Length: 61 Bit Score: 70.04 E-value: 2.69e-15
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| SH2 | cd00173 | Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ... |
6-74 | 4.52e-15 | ||||
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others. Pssm-ID: 198173 [Multi-domain] Cd Length: 79 Bit Score: 69.79 E-value: 4.52e-15
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| C1_CeDKF1-like_rpt1 | cd20797 | first protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine ... |
192-241 | 5.33e-15 | ||||
first protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine/threonine-protein kinase DKF-1 and similar proteins; DKF-1 converts transient diacylglycerol (DAG) signals into prolonged physiological effects, independently of PKC. It plays a role in the regulation of growth and neuromuscular control of movement. It is involved in immune response to Staphylococcus aureus bacterium by activating transcription factor hlh-30 downstream of phospholipase plc-1. Members of this group contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410347 Cd Length: 56 Bit Score: 69.04 E-value: 5.33e-15
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| RhoGAP_fLRG1 | cd04397 | RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
252-443 | 6.22e-15 | ||||
RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal LRG1-like proteins. Yeast Lrg1p is required for efficient cell fusion, and mother-daughter cell separation, possibly through acting as a RhoGAP specifically regulating 1,3-beta-glucan synthesis. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239862 Cd Length: 213 Bit Score: 73.55 E-value: 6.22e-15
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| C1_PKD1_rpt2 | cd20842 | second protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and ... |
192-242 | 6.83e-15 | ||||
second protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and similar proteins; PKD is also called PKD1, PRKD1, protein kinase C mu type (nPKC-mu), PRKCM, serine/threonine-protein kinase D1, or nPKC-D1. It is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. PKD contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410392 Cd Length: 94 Bit Score: 70.04 E-value: 6.83e-15
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| C1_RASSF1 | cd20885 | protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing ... |
192-241 | 1.42e-14 | ||||
protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing protein 1 (RASSF1) and similar proteins; RASSF1 is a member of a family of RAS effectors, of which there are currently 8 members (RASSF1-8), all containing a Ras-association (RA) domain of the Ral-GDS/AF6 type. RASSF1 has eight transcripts (A-H) arising from alternative splicing and differential promoter usage. RASSF1A and 1C are the most extensively studied RASSF1 with both localized to microtubules and involved in regulation of growth and migration. RASSF1 is a potential tumor suppressor that is required for death receptor-dependent apoptosis. It contains a C1 domain, which is descibed in this model. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410435 Cd Length: 54 Bit Score: 67.68 E-value: 1.42e-14
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| C1_RASGRP1 | cd20860 | protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 1 ... |
191-241 | 3.22e-14 | ||||
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 1 (RASGRP1) and similar proteins; RASGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII) or Ras guanyl-releasing protein, functions as a calcium- and diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. It activates the Erk/MAP kinase cascade and regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B-lymphocyte antigen receptors to Ras. RASGRP1 also regulates NK cell cytotoxicity and ITAM-dependent cytokine production by activation of Ras-mediated ERK and JNK pathways. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410410 Cd Length: 55 Bit Score: 66.88 E-value: 3.22e-14
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| C1_CeDKF1-like_rpt2 | cd20798 | second protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine ... |
192-241 | 2.03e-13 | ||||
second protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine/threonine-protein kinase DKF-1 and similar proteins; DKF-1 converts transient diacylglycerol (DAG) signals into prolonged physiological effects, independently of PKC. It plays a role in the regulation of growth and neuromuscular control of movement. It is involved in immune response to Staphylococcus aureus bacterium by activating transcription factor hlh-30 downstream of phospholipase plc-1. Members of this group contain two copies of the C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410348 Cd Length: 54 Bit Score: 64.44 E-value: 2.03e-13
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| C1_VAV | cd20810 | protein kinase C conserved region 1 (C1 domain) found in VAV proteins; VAV proteins function ... |
192-239 | 2.06e-13 | ||||
protein kinase C conserved region 1 (C1 domain) found in VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and as scaffold proteins, and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410360 Cd Length: 52 Bit Score: 64.59 E-value: 2.06e-13
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| C1_Stac | cd20817 | protein kinase C conserved region 1 (C1 domain) found in the SH3 and cysteine-rich ... |
192-243 | 3.25e-13 | ||||
protein kinase C conserved region 1 (C1 domain) found in the SH3 and cysteine-rich domain-containing protein (Stac) family; Stac proteins are putative adaptor proteins that are important for neuronal function. There are three mammalian members (Stac1, Stac2 and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. Stac proteins contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410367 Cd Length: 51 Bit Score: 63.89 E-value: 3.25e-13
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| C1_RASSF1-like | cd20820 | protein kinase C conserved region 1 (C1 domain) found in the Ras association domain-containing ... |
192-241 | 1.65e-12 | ||||
protein kinase C conserved region 1 (C1 domain) found in the Ras association domain-containing protein 1 (RASSF1)-like family; The RASSF1-like family includes RASSF1 and RASSF5. RASSF1 and RASSF5 are members of a family of RAS effectors, of which there are currently 8 members (RASSF1-8), all containing a Ras-association (RA) domain of the Ral-GDS/AF6 type. RASSF1 has eight transcripts (A-H) arising from alternative splicing and differential promoter usage. RASSF1A and 1C are the most extensively studied RASSF1; both are localized to microtubules and involved in the regulation of growth and migration. RASSF1 is a potential tumor suppressor that is required for death receptor-dependent apoptosis. RASSF5, also called new ras effector 1 (NORE1), or regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), is expressed as three transcripts (A-C) via differential promoter usage and alternative splicing. RASSF5A is a pro-apoptotic Ras effector and functions as a Ras regulated tumor suppressor. RASSF5C is regulated by Ras related protein and modulates cellular adhesion. RASSF5 is a potential tumor suppressor that seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. RASSF1 and RASSF5 contain a C1 domain, which is descibed in this model. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410370 Cd Length: 52 Bit Score: 61.69 E-value: 1.65e-12
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| C1_MRCKalpha | cd20864 | protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related ... |
190-241 | 2.24e-12 | ||||
protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related Cdc42-binding kinase alpha (MRCK alpha) and similar proteins; MRCK alpha, also called Cdc42-binding protein kinase alpha, DMPK-like alpha, or myotonic dystrophy protein kinase-like alpha, is a serine/threonine-protein kinase expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. MRCK alpha is an important downstream effector of Cdc42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410414 Cd Length: 60 Bit Score: 61.96 E-value: 2.24e-12
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| C1_Munc13 | cd20807 | protein kinase C conserved region 1 (C1 domain) found in the Munc13 family; The Munc13 gene ... |
192-242 | 2.46e-12 | ||||
protein kinase C conserved region 1 (C1 domain) found in the Munc13 family; The Munc13 gene family encodes a family of neuron-specific, synaptic molecules that bind to syntaxin, an essential mediator of neurotransmitter release. Munc13-1 is a component of presynaptic active zones in which it acts as an essential synaptic vesicle priming protein. Munc13-2 is essential for normal release probability at hippocampal mossy fiber synapses. Munc13-3 is almost exclusively expressed in the cerebellum. It acts as a tumor suppressor and plays a critical role in the formation of release sites with calcium channel nanodomains. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410357 Cd Length: 53 Bit Score: 61.34 E-value: 2.46e-12
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| C1_TNS2-like | cd20826 | protein kinase C conserved region 1 (C1 domain) found in tensin-2 like (TNS2-like) proteins; ... |
190-243 | 3.94e-12 | ||||
protein kinase C conserved region 1 (C1 domain) found in tensin-2 like (TNS2-like) proteins; The TNS2-like group includes TNS2, and variants of TNS1 and TNS3. Tensin-2 (TNS2), also called C1 domain-containing phosphatase and tensin (C1-TEN), or tensin-like C1 domain-containing phosphatase (TENC1), is an essential component for the maintenance of glomerular basement membrane (GBM) structures. It regulates cell motility and proliferation. It may have phosphatase activity. TNS2 reduces AKT1 phosphorylation, lowers AKT1 kinase activity and interferes with AKT1 signaling. Tensin-1 (TNS1) plays a role in fibrillar adhesion formation. It may be involved in cell migration, cartilage development and in linking signal transduction pathways to the cytoskeleton. Tensin-3 (TNS3), also called tensin-like SH2 domain-containing protein 1 (TENS1), or tumor endothelial marker 6 (TEM6), may play a role in actin remodeling. It is involved in the dissociation of the integrin-tensin-actin complex. Typical TNS1 and TNS3 do not contain C1 domains, but some isoforms/variants do. Members of this family contain an N-terminal region with a zinc finger (C1 domain), a protein tyrosine phosphatase (PTP)-like domain and a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains. This model corresponds to C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410376 Cd Length: 52 Bit Score: 60.86 E-value: 3.94e-12
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| C1_Munc13-1 | cd20858 | protein kinase C conserved region 1 (C1 domain) found in Munc13-1 and similar proteins; ... |
192-244 | 2.61e-11 | ||||
protein kinase C conserved region 1 (C1 domain) found in Munc13-1 and similar proteins; Munc13-1, also called protein unc-13 homolog A (Unc13A), is a diacylglycerol (DAG) receptor that plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. It is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Loss of MUNC13-1 function causes microcephaly, cortical hyperexcitability, and fatal myasthenia. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410408 Cd Length: 60 Bit Score: 58.95 E-value: 2.61e-11
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| SH2_Grb2_like | cd09941 | Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ... |
6-74 | 3.16e-11 | ||||
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 199828 Cd Length: 95 Bit Score: 59.59 E-value: 3.16e-11
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| C1_RASGRP3 | cd20862 | protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 3 ... |
192-241 | 3.18e-11 | ||||
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 3 (RASGRP3) and similar proteins; RASGRP3, also called calcium and DAG-regulated guanine nucleotide exchange factor III (CalDAG-GEFIII), or guanine nucleotide exchange factor for Rap1, is a guanine nucleotide-exchange factor activating H-Ras, R-Ras and Ras-associated protein-1/2. It functions as an important mediator of signaling downstream from receptor coupled phosphoinositide turnover in B and T cells. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410412 Cd Length: 59 Bit Score: 58.51 E-value: 3.18e-11
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| C1_ARHGEF-like | cd20832 | protein kinase C conserved region 1 (C1 domain) found in uncharacterized Rho guanine ... |
192-241 | 3.24e-11 | ||||
protein kinase C conserved region 1 (C1 domain) found in uncharacterized Rho guanine nucleotide exchange factor (ARHGEF)-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate Rho guanine nucleotide exchange factors ARHGEF11 and ARHGEF12, which may play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Unlike typical ARHGEF11 and ARHGEF12, members of this family contain a C1 domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410382 Cd Length: 53 Bit Score: 58.15 E-value: 3.24e-11
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| C1_DGKtheta_typeV_rpt1 | cd20803 | first protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, ... |
192-241 | 4.66e-11 | ||||
first protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, DAG kinase theta, and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase theta, also called diglyceride kinase theta (DGK-theta), is the only isoform classified as type V; it contains a pleckstrin homology (PH)-like domain and an additional C1 domain, compared to other DGKs. It may regulate the activity of protein kinase C by controlling the balance between the two signaling lipids, diacylglycerol and phosphatidic acid. DAG kinase theta contains three copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410353 Cd Length: 56 Bit Score: 57.70 E-value: 4.66e-11
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| RhoGAP_ARHGAP19 | cd04392 | RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
283-445 | 5.90e-11 | ||||
RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP19-like proteins. The function of ArhGAP19 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239857 Cd Length: 208 Bit Score: 61.71 E-value: 5.90e-11
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| SH2_Cterm_RasGAP | cd10354 | C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ... |
4-74 | 6.66e-11 | ||||
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198217 Cd Length: 77 Bit Score: 58.20 E-value: 6.66e-11
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| C1_Raf | cd20811 | protein kinase C conserved region 1 (C1 domain) found in the Raf (Rapidly Accelerated ... |
192-241 | 9.86e-11 | ||||
protein kinase C conserved region 1 (C1 domain) found in the Raf (Rapidly Accelerated Fibrosarcoma) kinase family; Raf kinases are serine/threonine kinases (STKs) that catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. They act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain (C1), and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410361 Cd Length: 49 Bit Score: 56.54 E-value: 9.86e-11
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| SH2_C-SH2_PLC_gamma_like | cd09932 | C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ... |
6-73 | 2.17e-10 | ||||
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198186 Cd Length: 104 Bit Score: 57.28 E-value: 2.17e-10
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| C1_nPKC_epsilon-like_rpt1 | cd20835 | first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ... |
180-241 | 4.18e-10 | ||||
first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) epsilon, eta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410385 Cd Length: 64 Bit Score: 55.55 E-value: 4.18e-10
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| SH2_Src_family | cd09933 | Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ... |
6-77 | 1.76e-09 | ||||
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src family kinases are nonreceptor tyrosine kinases that have been implicated in pathways regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. It is thought that transforming ability of Src is linked to its ability to activate key signaling molecules in these pathways, rather than through direct activity. As such blocking Src activation has been a target for drug companies. Src family members can be divided into 3 groups based on their expression pattern: 1) Src, Fyn, and Yes; 2) Blk, Fgr, Hck, Lck, and Lyn; and 3) Frk-related kinases Frk/Rak and Iyk/Bsk Of these, cellular c-Src is the best studied and most frequently implicated in oncogenesis. The c-Src contains five distinct regions: a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Src exists in both active and inactive conformations. Negative regulation occurs through phosphorylation of Tyr, resulting in an intramolecular association between phosphorylated Tyr and the SH2 domain of SRC, which locks the protein in a closed conformation. Further stabilization of the inactive state occurs through interactions between the SH3 domain and a proline-rich stretch of residues within the kinase domain. Conversely, dephosphorylation of Tyr allows SRC to assume an open conformation. Full activity requires additional autophosphorylation of a Tyr residue within the catalytic domain. Loss of the negative-regulatory C-terminal segment has been shown to result in increased activity and transforming potential. Phosphorylation of the C-terminal Tyr residue by C-terminal Src kinase (Csk) and Csk homology kinase results in increased intramolecular interactions and consequent Src inactivation. Specific phosphatases, protein tyrosine phosphatase a (PTPa) and the SH-containing phosphatases SHP1/SHP2, have also been shown to take a part in Src activation. Src is also activated by direct binding of focal adhesion kinase (Fak) and Crk-associated substrate (Cas) to the SH2 domain. SRC activity can also be regulated by numerous receptor tyrosine kinases (RTKs), such as Her2, epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 199827 Cd Length: 101 Bit Score: 54.90 E-value: 1.76e-09
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| C1_cPKC_rpt1 | cd20833 | first protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) ... |
190-241 | 1.97e-09 | ||||
first protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) protein kinase C (cPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410383 Cd Length: 58 Bit Score: 53.18 E-value: 1.97e-09
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| C1_Munc13-2-like | cd20859 | protein kinase C conserved region 1 (C1 domain) found in Munc13-2, Munc13-3 and similar ... |
192-242 | 2.74e-09 | ||||
protein kinase C conserved region 1 (C1 domain) found in Munc13-2, Munc13-3 and similar proteins; Munc13-2, also called protein unc-13 homolog B (Unc13B), plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. It is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Munc13-2 is essential for normal release probability at hippocampal mossy fiber synapses. Munc13-3 is almost exclusively expressed in the cerebellum. It acts as a tumor suppressor and plays a critical role in the formation of release sites with calcium channel nanodomains. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410409 Cd Length: 82 Bit Score: 53.53 E-value: 2.74e-09
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| C1_Myosin-IX | cd20818 | protein kinase C conserved region 1 (C1 domain) found in the unconventional myosin-IX family; ... |
192-241 | 4.79e-09 | ||||
protein kinase C conserved region 1 (C1 domain) found in the unconventional myosin-IX family; Myosins IX (Myo9) is a class of unique motor proteins with a common structure of an N-terminal extension preceding a myosin head homologous to the Ras-association (RA) domain, a head (motor) domain, a neck with IQ motifs that bind light chains, and a C-terminal tail containing cysteine-rich zinc binding (C1) and Rho-GTPase activating protein (RhoGAP) domains. There are two genes for myosins IX in humans, IXa and IXb, that are different in their expression and localization. IXa is expressed abundantly in brain and testis, and IXb is expressed abundantly in tissues of the immune system. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410368 Cd Length: 56 Bit Score: 52.30 E-value: 4.79e-09
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| C1_KSR | cd20812 | protein kinase C conserved region 1 (C1 domain) found in the kinase suppressor of Ras (KSR) ... |
192-241 | 6.93e-09 | ||||
protein kinase C conserved region 1 (C1 domain) found in the kinase suppressor of Ras (KSR) family; KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. KSR proteins contain a SAM-like domain, a zinc finger cysteine-rich domain (C1), and a pseudokinase domain. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410362 Cd Length: 48 Bit Score: 51.56 E-value: 6.93e-09
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| SH2_Nterm_shark_like | cd10347 | N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ... |
6-81 | 7.16e-09 | ||||
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198210 Cd Length: 81 Bit Score: 52.38 E-value: 7.16e-09
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| C1_ScPKC1-like_rpt2 | cd20823 | second protein kinase C conserved region 1 (C1 domain) found in Saccharomyces cerevisiae ... |
188-241 | 1.06e-08 | ||||
second protein kinase C conserved region 1 (C1 domain) found in Saccharomyces cerevisiae protein kinase C-like 1 (ScPKC1) and similar proteins; ScPKC1 is required for cell growth and for the G2 to M transition of the cell division cycle. It mediates a protein kinase cascade, activating BCK1 which itself activates MKK1/MKK2. The family also includes Schizosaccharomyces pombe PKC1 and PKC2, which are involved in the control of cell shape and act as targets of the inhibitor staurosporine. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410373 Cd Length: 59 Bit Score: 51.15 E-value: 1.06e-08
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| SH2_Cterm_shark_like | cd10348 | C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ... |
6-77 | 1.18e-08 | ||||
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in its carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198211 Cd Length: 86 Bit Score: 52.04 E-value: 1.18e-08
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| SH2_Grb7_family | cd09944 | Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ... |
6-73 | 1.25e-08 | ||||
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. There are 3 members of the Grb7 family of proteins: Grb7, Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR). Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198197 [Multi-domain] Cd Length: 108 Bit Score: 52.42 E-value: 1.25e-08
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| C1_DEF8 | cd20819 | protein kinase C conserved region 1 (C1 domain) found in differentially expressed in FDCP 8 ... |
192-237 | 1.39e-08 | ||||
protein kinase C conserved region 1 (C1 domain) found in differentially expressed in FDCP 8 (DEF-8) and similar proteins; DEF-8 positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts. It is involved in bone resorption. DEF-8 contains a protein kinase C conserved region 1 (C1) domain followed by a putative zinc-RING and/or ribbon. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410369 Cd Length: 62 Bit Score: 51.13 E-value: 1.39e-08
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| SH2_DAPP1_BAM32_like | cd10355 | Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ... |
6-73 | 1.49e-08 | ||||
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( DAPP1)/B lymphocyte adaptor molecule of 32 kDa (Bam32)-like proteins; DAPP1/Bam32 contains a putative myristoylation site at its N-terminus, followed by a SH2 domain, and a pleckstrin homology (PH) domain at its C-terminus. DAPP1 could potentially be recruited to the cell membrane by any of these domains. Its putative myristoylation site could facilitate the interaction of DAPP1 with the lipid bilayer. Its SH2 domain may also interact with phosphotyrosine residues on membrane-associated proteins such as activated tyrosine kinase receptors. And finally its PH domain exhibits a high-affinity interaction with the PtdIns(3,4,5)P(3) PtdIns(3,4)P(2) second messengers produced at the cell membrane following the activation of PI 3-kinases. DAPP1 is thought to interact with both tyrosine phosphorylated proteins and 3-phosphoinositides and therefore may play a role in regulating the location and/or activity of such proteins(s) in response to agonists that elevate PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2). This protein is likely to play an important role in triggering signal transduction pathways that lie downstream from receptor tyrosine kinases and PI 3-kinase. It is likely that DAPP1 functions as an adaptor to recruit other proteins to the plasma membrane in response to extracellular signals. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198218 Cd Length: 92 Bit Score: 51.71 E-value: 1.49e-08
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| SH2_N-SH2_SHP_like | cd10340 | N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ... |
6-85 | 1.53e-08 | ||||
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [IVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198203 Cd Length: 99 Bit Score: 52.02 E-value: 1.53e-08
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| SH2_Nck_family | cd09943 | Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ... |
6-73 | 1.74e-08 | ||||
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198196 Cd Length: 93 Bit Score: 51.75 E-value: 1.74e-08
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| C1_DGK_typeI_rpt1 | cd20799 | first protein kinase C conserved region 1 (C1 domain) found in type I diacylglycerol kinases; ... |
192-241 | 2.10e-08 | ||||
first protein kinase C conserved region 1 (C1 domain) found in type I diacylglycerol kinases; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. Type I DAG kinases (DGKs) contain EF-hand structures that bind Ca(2+) and recoverin homology domains, in addition to C1 and catalytic domains that are present in all DGKs. Type I DGKs, regulated by calcium binding, include three DGK isozymes (alpha, beta and gamma). DAG kinase alpha, also called 80 kDa DAG kinase, or diglyceride kinase alpha (DGK-alpha), is active upon cell stimulation, initiating the resynthesis of phosphatidylinositols and attenuating protein kinase C activity. DAG kinase beta, also called 90 kDa DAG kinase, or diglyceride kinase beta (DGK-beta), exhibits high phosphorylation activity for long-chain diacylglycerols. DAG kinase gamma, also called diglyceride kinase gamma (DGK-gamma), reverses the normal flow of glycerolipid biosynthesis by phosphorylating diacylglycerol back to phosphatidic acid. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. DGK-alpha contains atypical C1 domains, while DGK-beta and DGK-gamma contain typical C1 domains that bind DAG and phorbol esters. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410349 Cd Length: 62 Bit Score: 50.45 E-value: 2.10e-08
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| C1_DGKeta_rpt1 | cd20848 | first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase eta (DAG ... |
176-241 | 2.57e-08 | ||||
first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase eta (DAG kinase eta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase eta, also called diglyceride kinase eta (DGK-eta), plays a key role in promoting cell growth. It is classified as a type II DAG kinase (DGK), containing pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. The diacylglycerol kinase eta gene, DGKH, is a replicated risk gene of bipolar disorder (BPD). DAG kinase eta contains two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410398 Cd Length: 86 Bit Score: 50.93 E-value: 2.57e-08
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| C1_DGK_typeII_rpt1 | cd20800 | first protein kinase C conserved region 1 (C1 domain) found in type II diacylglycerol kinases; ... |
192-241 | 2.62e-08 | ||||
first protein kinase C conserved region 1 (C1 domain) found in type II diacylglycerol kinases; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. Type II DAG kinases (DGKs) contain pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. Three DGK isozymes (delta, eta and kappa) are classified as type II. DAG kinase delta, also called 130 kDa DAG kinase, or diglyceride kinase delta (DGK-delta), is a residential lipid kinase in the endoplasmic reticulum. It promotes lipogenesis and is involved in triglyceride biosynthesis. DAG kinase eta, also called diglyceride kinase eta (DGK-eta), plays a key role in promoting cell growth. The DAG kinase eta gene, DGKH, is a replicated risk gene of bipolar disorder (BPD). DAG kinase kappa is also called diglyceride kinase kappa (DGK-kappa) or 142 kDa DAG kinase. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410350 Cd Length: 60 Bit Score: 50.01 E-value: 2.62e-08
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| C1_RASGRP2 | cd20861 | protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 2 ... |
192-241 | 3.08e-08 | ||||
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 2 (RASGRP2) and similar proteins; RASGRP2, also called calcium and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Cdc25-like protein (CDC25L), or F25B3.3 kinase-like protein, functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. It may also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. RASGRP2 is also involved in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation, as well as in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410411 Cd Length: 56 Bit Score: 49.89 E-value: 3.08e-08
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| C1_A_C-Raf | cd20870 | protein kinase C conserved region 1 (C1 domain) found in A- and C-Raf (Rapidly Accelerated ... |
192-242 | 3.25e-08 | ||||
protein kinase C conserved region 1 (C1 domain) found in A- and C-Raf (Rapidly Accelerated Fibrosarcoma) kinases, and similar proteins; This group includes A-Raf and C-Raf, both of which are serine/threonine-protein kinases. A-Raf, also called proto-oncogene A-Raf or proto-oncogene A-Raf-1, cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. C-Raf, also known as proto-oncogene Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around mid-gestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. Both A- and C-Raf are mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain (C1), and a catalytic kinase domain. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410420 Cd Length: 52 Bit Score: 49.57 E-value: 3.25e-08
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| C1_MRCKgamma | cd20866 | protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related ... |
192-238 | 3.45e-08 | ||||
protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related Cdc42-binding kinase gamma (MRCK gamma) and similar proteins; MRCK gamma (MRCKG), also called Cdc42-binding protein kinase gamma, DMPK-like gamma, myotonic dystrophy protein kinase-like gamma, or myotonic dystrophy protein kinase-like alpha, is a serine/threonine-protein kinase expressed in heart and skeletal muscles. It may act as a downstream effector of Cdc42 in cytoskeletal reorganization and contributes to the actomyosin contractility required for cell invasion, through the regulation of MYPT1 and thus MLC2 phosphorylation. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410416 Cd Length: 52 Bit Score: 49.75 E-value: 3.45e-08
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| SH2_SHC | cd09925 | Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide ... |
6-73 | 4.82e-08 | ||||
Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide variety of pathways including regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. An adapter protein, SHC has been implicated in Ras activation following the stimulation of a number of different receptors, including growth factors [insulin, epidermal growth factor (EGF), nerve growth factor, and platelet derived growth factor (PDGF)], cytokines [interleukins 2, 3, and 5], erythropoietin, and granulocyte/macrophage colony-stimulating factor, and antigens [T-cell and B-cell receptors]. SHC has been shown to bind to tyrosine-phosphorylated receptors, and receptor stimulation leads to tyrosine phosphorylation of SHC. Upon phosphorylation, SHC interacts with another adapter protein, Grb2, which binds to the Ras GTP/GDP exchange factor mSOS which leads to Ras activation. SHC is composed of an N-terminal domain that interacts with proteins containing phosphorylated tyrosines, a (glycine/proline)-rich collagen-homology domain that contains the phosphorylated binding site, and a C-terminal SH2 domain. SH2 has been shown to interact with the tyrosine-phosphorylated receptors of EGF and PDGF and with the tyrosine-phosphorylated C chain of the T-cell receptor, providing one of the mechanisms of T-cell-mediated Ras activation. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198179 Cd Length: 104 Bit Score: 50.81 E-value: 4.82e-08
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| SH2_C-SH2_SHP_like | cd09931 | C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ... |
6-73 | 5.72e-08 | ||||
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198185 Cd Length: 99 Bit Score: 50.36 E-value: 5.72e-08
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| C1_VAV3 | cd20869 | protein kinase C conserved region 1 (C1 domain) found in VAV3 protein; VAV3 is ubiquitously ... |
192-239 | 6.42e-08 | ||||
protein kinase C conserved region 1 (C1 domain) found in VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. Its function has been implicated in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410419 Cd Length: 59 Bit Score: 49.06 E-value: 6.42e-08
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| C1_TNS3_v | cd20889 | protein kinase C conserved region 1 (C1 domain) found in tensin-3 (TNS3) variant and similar ... |
191-247 | 6.95e-08 | ||||
protein kinase C conserved region 1 (C1 domain) found in tensin-3 (TNS3) variant and similar proteins; Tensin-3 (TNS3), also called tensin-like SH2 domain-containing protein 1 (TENS1), or tumor endothelial marker 6 (TEM6), may play a role in actin remodeling. It is involved in the dissociation of the integrin-tensin-actin complex. This model corresponds to the C1 domain found in TNS3 variant. Typical TNS3 does not contain C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410439 Cd Length: 56 Bit Score: 48.73 E-value: 6.95e-08
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| C1_Stac2 | cd20881 | protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich ... |
190-237 | 6.97e-08 | ||||
protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich domain-containing protein 2 (Stac2) and similar proteins; Stac2, also called 24b2/Stac2, or Src homology 3 and cysteine-rich domain-containing protein 2, plays a redundant role in promoting the expression of calcium channel CACNA1S at the cell membrane, and thereby contributes to increased channel activity. It slows down the inactivation rate of the calcium channel CACNA1C. Stac2 contains a cysteine-rich C1 domain and one SH3 domain at the C-terminus. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410431 Cd Length: 59 Bit Score: 49.06 E-value: 6.97e-08
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| C1_PDZD8 | cd20825 | protein kinase C conserved region 1 (C1 domain) found in PDZ domain-containing protein 8 ... |
189-239 | 7.22e-08 | ||||
protein kinase C conserved region 1 (C1 domain) found in PDZ domain-containing protein 8 (PDZD8) and similar proteins; PDZD8, also called Sarcoma antigen NY-SAR-84/NY-SAR-104, is a molecular tethering protein that connects endoplasmic reticulum (ER) and mitochondrial membranes. PDZD8-dependent ER-mitochondria membrane tethering is essential for ER-mitochondria Ca2+ transfer. In neurons, it is involved in the regulation of dendritic Ca2+ dynamics by regulating mitochondrial Ca2+ uptake. PDZD8 also plays an indirect role in the regulation of cell morphology and cytoskeletal organization. It contains a PDZ domain and a C1 domain. This model describes the C1 domain, a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410375 Cd Length: 55 Bit Score: 48.81 E-value: 7.22e-08
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| SH2_Nterm_RasGAP | cd10353 | N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ... |
6-73 | 8.88e-08 | ||||
N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general the longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the N-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198216 Cd Length: 103 Bit Score: 50.22 E-value: 8.88e-08
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| RhoGAP_OCRL1 | cd04380 | RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ... |
248-420 | 9.00e-08 | ||||
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in OCRL1-like proteins. OCRL1 (oculocerebrorenal syndrome of Lowe 1)-like proteins contain two conserved domains: a central inositol polyphosphate 5-phosphatase domain and a C-terminal Rho GAP domain, this GAP domain lacks the catalytic residue and therefore maybe inactive. OCRL-like proteins are type II inositol polyphosphate 5-phosphatases that can hydrolyze lipid PI(4,5)P2 and PI(3,4,5)P3 and soluble Ins(1,4,5)P3 and Ins(1,3,4,5)P4, but their individual specificities vary. The functionality of the RhoGAP domain is still unclear. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239845 Cd Length: 220 Bit Score: 52.73 E-value: 9.00e-08
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| C1_RASSF5 | cd20886 | protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing ... |
197-241 | 1.05e-07 | ||||
protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing protein 5 (RASSF5) and similar proteins; RASSF5, also called new ras effector 1 (NORE1), or regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), is a member of a family of RAS effectors, of which there are currently 8 members (RASSF1-8), all containing a Ras-association (RA) domain of the Ral-GDS/AF6 type. It is expressed as three transcripts (A-C) via differential promoter usage and alternative splicing. RASSF5A is a pro-apoptotic Ras effector and functions as a Ras regulated tumor suppressor. RASSF5C is regulated by Ras related protein and modulates cellular adhesion. RASSF5 is a potential tumor suppressor that seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. It contains a C1 domain, which is descibed in this model. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410436 Cd Length: 50 Bit Score: 48.15 E-value: 1.05e-07
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| C1_ScPKC1-like_rpt1 | cd20822 | first protein kinase C conserved region 1 (C1 domain) found in Saccharomyces cerevisiae ... |
192-242 | 1.43e-07 | ||||
first protein kinase C conserved region 1 (C1 domain) found in Saccharomyces cerevisiae protein kinase C-like 1 (ScPKC1) and similar proteins; ScPKC1 is required for cell growth and for the G2 to M transition of the cell division cycle. It mediates a protein kinase cascade, activating BCK1 which itself activates MKK1/MKK2. The family also includes Schizosaccharomyces pombe PKC1 and PKC2, which are involved in the control of cell shape and act as targets of the inhibitor staurosporine. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410372 Cd Length: 52 Bit Score: 47.67 E-value: 1.43e-07
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| C1_VAV2 | cd20868 | protein kinase C conserved region 1 (C1 domain) found in VAV2 protein; VAV2 is widely ... |
192-238 | 1.59e-07 | ||||
protein kinase C conserved region 1 (C1 domain) found in VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410418 Cd Length: 58 Bit Score: 47.96 E-value: 1.59e-07
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| SH2_Fps_family | cd10361 | Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ... |
6-74 | 1.83e-07 | ||||
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related (Fes/Fps/Fer) proteins; The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature. Members here include: Fps/Fes, Fer, Kin-31, and In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198224 Cd Length: 90 Bit Score: 48.68 E-value: 1.83e-07
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| C1_aPKC | cd20794 | protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) ... |
192-241 | 2.34e-07 | ||||
protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. Members of this family contain one C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410344 Cd Length: 55 Bit Score: 47.26 E-value: 2.34e-07
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| C1_MRCKbeta | cd20865 | protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related ... |
192-241 | 2.76e-07 | ||||
protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related Cdc42-binding kinase beta (MRCK beta) and similar proteins; MRCK beta, also called Cdc42-binding protein kinase beta (Cdc42BP-beta), DMPK-like beta, or myotonic dystrophy protein kinase-like beta, is a serine/threonine-protein kinase expressed ubiquitously in many tissues. MRCK beta is an important downstream effector of Cdc42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410415 Cd Length: 53 Bit Score: 47.29 E-value: 2.76e-07
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| SH2_Nck2 | cd10409 | Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ... |
6-73 | 4.36e-07 | ||||
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198272 Cd Length: 98 Bit Score: 48.11 E-value: 4.36e-07
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| C1_Stac1 | cd20880 | protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich ... |
190-237 | 4.78e-07 | ||||
protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich domain-containing protein (Stac1) and similar proteins; Stac1, also called Src homology 3 and cysteine-rich domain-containing protein, promotes expression of the ion channel CACNA1H at the cell membrane, and thereby contributes to the regulation of channel activity. It plays a minor and redundant role in promoting the expression of calcium channel CACNA1S at the cell membrane, and thereby contributes to increased channel activity. It slows down the inactivation rate of the calcium channel CACNA1C. Stac1 contains a cysteine-rich C1 domain and two SH3 domains at the C-terminus. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410430 Cd Length: 57 Bit Score: 46.47 E-value: 4.78e-07
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| SH2_Src_Fyn_isoform_a_like | cd10418 | Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src ... |
6-73 | 4.89e-07 | ||||
Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform a type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198281 Cd Length: 101 Bit Score: 48.07 E-value: 4.89e-07
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| SH2_Src_Lck | cd10362 | Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ... |
6-79 | 5.25e-07 | ||||
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src non-receptor type tyrosine kinase family of proteins. It is expressed in the brain, T-cells, and NK cells. The unique domain of Lck mediates its interaction with two T-cell surface molecules, CD4 and CD8. It associates with their cytoplasmic tails on CD4 T helper cells and CD8 cytotoxic T cells to assist signaling from the T cell receptor (TCR) complex. When the T cell receptor is engaged by the specific antigen presented by MHC, Lck phosphorylase the intracellular chains of the CD3 and zeta-chains of the TCR complex, allowing ZAP-70 to bind them. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates Linker of Activated T cells (LAT), a transmembrane protein that serves as a docking site for proteins including: Shc-Grb2-SOS, PI3K, and phospholipase C (PLC). The tyrosine phosphorylation cascade culminates in the intracellular mobilization of a calcium ions and activation of important signaling cascades within the lymphocyte, including the Ras-MEK-ERK pathway, which goes on to activate certain transcription factors such as NFAT, NF-kappaB, and AP-1. These transcription factors regulate the production cytokines such as Interleukin-2 that promote long-term proliferation and differentiation of the activated lymphocytes. The N-terminal tail of Lck is myristoylated and palmitoylated and it tethers the protein to the plasma membrane of the cell. Lck also contains a SH3 domain, a SH2 domain, and a C-terminal tyrosine kinase domain. Lck has 2 phosphorylation sites, the first an autophosphorylation site that is linked to activation of the protein and the second which is phosphorylated by Csk, which inhibits it. Lck is also inhibited by SHP-1 dephosphorylation and by Cbl ubiquitin ligase, which is part of the ubiquitin-mediated pathway. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198225 Cd Length: 101 Bit Score: 47.94 E-value: 5.25e-07
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| RhoGAP_fRGD2 | cd04399 | RhoGAP_fRGD2: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
252-445 | 6.06e-07 | ||||
RhoGAP_fRGD2: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD2-like proteins. Yeast Rgd2 is a GAP protein for Cdc42 and Rho5. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239864 Cd Length: 212 Bit Score: 50.02 E-value: 6.06e-07
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| C1_B-Raf | cd20871 | protein kinase C conserved region 1 (C1 domain) found in B-Raf (Rapidly Accelerated ... |
192-242 | 7.53e-07 | ||||
protein kinase C conserved region 1 (C1 domain) found in B-Raf (Rapidly Accelerated Fibrosarcoma) kinase and similar proteins; Serine/threonine-protein kinase B-Raf, also called proto-oncogene B-Raf, p94, or v-Raf murine sarcoma viral oncogene homolog B1, activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain (C1), and a catalytic kinase domain. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410421 Cd Length: 60 Bit Score: 46.18 E-value: 7.53e-07
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| SH2_SLAP | cd10344 | Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ... |
5-80 | 7.92e-07 | ||||
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of adapter proteins that negatively regulate cellular signaling initiated by tyrosine kinases. It has a myristylated N-terminus, SH3 and SH2 domains with high homology to Src family tyrosine kinases, and a unique C-terminal tail, which is important for c-Cbl binding. SLAP negatively regulates platelet-derived growth factor (PDGF)-induced mitogenesis in fibroblasts and regulates F-actin assembly for dorsal ruffles formation. c-Cbl mediated SLAP inhibition towards actin remodeling. Moreover, SLAP enhanced PDGF-induced c-Cbl phosphorylation by SFK. In contrast, SLAP mitogenic inhibition was not mediated by c-Cbl, but it rather involved a competitive mechanism with SFK for PDGF-receptor (PDGFR) association and mitogenic signaling. Accordingly, phosphorylation of the Src mitogenic substrates Stat3 and Shc were reduced by SLAP. Thus, we concluded that SLAP regulates PDGFR signaling by two independent mechanisms: a competitive mechanism for PDGF-induced Src mitogenic signaling and a non-competitive mechanism for dorsal ruffles formation mediated by c-Cbl. SLAP is a hematopoietic adaptor containing Src homology (SH)3 and SH2 motifs and a unique carboxy terminus. Unlike c-Src, SLAP lacks a tyrosine kinase domain. Unlike c-Src, SLAP does not impact resorptive function of mature osteoclasts but induces their early apoptosis. SLAP negatively regulates differentiation of osteoclasts and proliferation of their precursors. Conversely, SLAP decreases osteoclast death by inhibiting activation of caspase 3. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198207 Cd Length: 104 Bit Score: 47.49 E-value: 7.92e-07
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| SH2_SHIP | cd10343 | Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ... |
6-73 | 8.75e-07 | ||||
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP); The SH2-containing inositol-5'-phosphatase, SHIP (also called SHIP1/SHIP1a), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3) to PI-3,4-P2. As a result, SHIP dampens down PIP3 mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. PIP3 recruits lipid-binding pleckstrin homology(PH) domain-containing proteins to the inner wall of the plasma membrane and activates them. PH domain-containing downstream effectors include the survival/proliferation enhancing serine/threonine kinase, Akt (protein kinase B), the tyrosine kinase, Btk, the regulator of protein translation, S6K, and the Rac and cdc42 guanine nucleotide exchange factor, Vav. SHIP is believed to act as a tumor suppressor during leukemogenesis and lymphomagenesis, and may play a role in activating the immune system to combat cancer. SHIP contains an N-terminal SH2 domain, a centrally located phosphatase domain that specifically hydrolyzes the 5'-phosphate from PIP3, PI-4,5-P2 and inositol-1,3,4,5- tetrakisphosphate (IP4), a C2 domain, that is an allosteric activating site when bound by SHIP's enzymatic product, PI-3,4-P2; 2 NPXY motifs that bind proteins with a phosphotyrosine binding (Shc, Dok 1, Dok 2) or an SH2 (p85a, SHIP2) domain; and a proline-rich domain consisting of four PxxP motifs that bind a subset of SH3-containing proteins including Grb2, Src, Lyn, Hck, Abl, PLCg1, and PIAS1. The SH2 domain of SHIP binds to the tyrosine phosphorylated forms of Shc, SHP-2, Doks, Gabs, CD150, platelet-endothelial cell adhesion molecule, Cas, c-Cbl, immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs). The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX(V/I), which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198206 Cd Length: 103 Bit Score: 47.05 E-value: 8.75e-07
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| C1_MgcRacGAP | cd20821 | protein kinase C conserved region 1 (C1 domain) found in male germ cell RacGap (MgcRacGAP) and ... |
190-245 | 1.09e-06 | ||||
protein kinase C conserved region 1 (C1 domain) found in male germ cell RacGap (MgcRacGAP) and similar proteins; MgcRacGAP, also called Rac GTPase-activating protein 1 (RACGAP1) or protein CYK4, plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling; and ii) after phosphorylation by aurora B, MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain an N-terminal C1 domain, and a C-terminal RhoGAP domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410371 Cd Length: 55 Bit Score: 45.47 E-value: 1.09e-06
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| C1_DGKdelta_rpt1 | cd20847 | first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase delta ... |
176-241 | 1.33e-06 | ||||
first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase delta (DAG kinase delta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase delta, also called 130 kDa diacylglycerol kinase, or diglyceride kinase delta (DGK-delta), is a residential lipid kinase in the endoplasmic reticulum. It promotes lipogenesis and is involved in triglyceride biosynthesis. It is classified as a type II DAG kinase (DGK), containing pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. DAG kinase delta contains two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410397 Cd Length: 85 Bit Score: 46.25 E-value: 1.33e-06
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| C1_TNS1_v | cd20888 | protein kinase C conserved region 1 (C1 domain) found in tensin-1 (TNS1) variant and similar ... |
190-245 | 1.39e-06 | ||||
protein kinase C conserved region 1 (C1 domain) found in tensin-1 (TNS1) variant and similar proteins; Tensin-1 (TNS1) plays a role in fibrillar adhesion formation. It may be involved in cell migration, cartilage development and in linking signal transduction pathways to the cytoskeleton. This model corresponds to the C1 domain found in TNS1 variant. Typical TNS1 does not contain C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410438 Cd Length: 57 Bit Score: 45.25 E-value: 1.39e-06
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| C1_DGKbeta_rpt1 | cd20845 | first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase beta (DAG ... |
192-249 | 1.47e-06 | ||||
first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase beta (DAG kinase beta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase beta, also called 90 kDa diacylglycerol kinase, or diglyceride kinase beta (DGK-beta), exhibits high phosphorylation activity for long-chain diacylglycerols. It is classified as a type I DAG kinase (DGK), containing EF-hand structures that bind Ca(2+) and a recoverin homology domain, in addition to C1 and catalytic domains that are present in all DGKs. As a type I DGK, it is regulated by calcium binding. DAG kinase beta contains two copies of the C1 domain. This model corresponds to the first one. DGK-beta contains typical C1 domains that bind DAG and phorbol esters. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410395 Cd Length: 66 Bit Score: 45.61 E-value: 1.47e-06
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| SH2_C-SH2_Zap70 | cd10402 | C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ... |
6-84 | 1.97e-06 | ||||
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198265 Cd Length: 105 Bit Score: 46.45 E-value: 1.97e-06
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| SH2_Nck1 | cd10408 | Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ... |
6-73 | 2.04e-06 | ||||
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198271 Cd Length: 97 Bit Score: 46.18 E-value: 2.04e-06
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| SH2_SAP1 | cd10342 | Src homology 2 (SH2) domain found in SLAM-associated protein (SAP)1; The X-linked ... |
1-74 | 2.59e-06 | ||||
Src homology 2 (SH2) domain found in SLAM-associated protein (SAP)1; The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX[VI], which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198205 Cd Length: 103 Bit Score: 45.79 E-value: 2.59e-06
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| C1_dGM13116p-like | cd20831 | protein kinase C conserved region 1 (C1 domain) found in Drosophila melanogaster GM13116p and ... |
192-241 | 3.38e-06 | ||||
protein kinase C conserved region 1 (C1 domain) found in Drosophila melanogaster GM13116p and similar proteins; This group contains uncharacterized proteins including Drosophila melanogaster GM13116p and Caenorhabditis elegans hypothetical protein R11G1.4, both of which contain C2 (a calcium-binding domain) and C1 domains. This model describes the C1 domain, a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410381 Cd Length: 58 Bit Score: 44.25 E-value: 3.38e-06
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| C1_VAV1 | cd20867 | protein kinase C conserved region 1 (C1 domain) found in VAV1 protein; VAV1 is expressed ... |
191-238 | 4.00e-06 | ||||
protein kinase C conserved region 1 (C1 domain) found in VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410417 Cd Length: 57 Bit Score: 43.79 E-value: 4.00e-06
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| SH2_SH2D4B | cd10351 | Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains ... |
6-73 | 4.27e-06 | ||||
Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198214 Cd Length: 103 Bit Score: 45.27 E-value: 4.27e-06
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| C1_PIK3R-like_rpt1 | cd20829 | first protein kinase C conserved region 1 (C1 domain) found in uncharacterized ... |
192-243 | 4.68e-06 | ||||
first protein kinase C conserved region 1 (C1 domain) found in uncharacterized phosphatidylinositol 3-kinase regulatory subunit-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate phosphatidylinositol 3-kinase regulatory subunits (PIK3Rs), which bind to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulate their kinase activity. Unlike typical PIK3Rs, members of this family have two C1 domains. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410379 Cd Length: 53 Bit Score: 43.49 E-value: 4.68e-06
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| SH2_Src_Fyn | cd10368 | Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ... |
6-77 | 5.06e-06 | ||||
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198231 [Multi-domain] Cd Length: 101 Bit Score: 45.02 E-value: 5.06e-06
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| SH2_Vav2 | cd10406 | Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the ... |
6-86 | 5.63e-06 | ||||
Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav2 is a GEF for RhoA, RhoB and RhoG and may activate Rac1 and Cdc42. Vav2 has been shown to interact with CD19 and Grb2. Alternatively spliced transcript variants encoding different isoforms have been found for Vav2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198269 Cd Length: 103 Bit Score: 45.06 E-value: 5.63e-06
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| C1_aPKC_zeta | cd21095 | protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) ... |
191-242 | 5.78e-06 | ||||
protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) zeta type; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. Members of this family contain C1 domain found in aPKC isoform zeta. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410448 Cd Length: 55 Bit Score: 43.44 E-value: 5.78e-06
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| C1_aPKC_iota | cd21094 | protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) ... |
191-241 | 6.06e-06 | ||||
protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) iota type; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. Members of this family contain C1 domain found in aPKC isoform iota. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410447 Cd Length: 55 Bit Score: 43.45 E-value: 6.06e-06
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| SH2_Src_Src42 | cd10370 | Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ... |
6-77 | 9.06e-06 | ||||
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198233 Cd Length: 96 Bit Score: 44.03 E-value: 9.06e-06
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| SH2_N-SH2_Zap70_Syk_like | cd09938 | N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ... |
6-80 | 9.65e-06 | ||||
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198191 Cd Length: 104 Bit Score: 44.31 E-value: 9.65e-06
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| C1_DGKgamma_rpt1 | cd20846 | first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase gamma ... |
192-242 | 9.83e-06 | ||||
first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase gamma (DAG kinase gamma) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase gamma, also called diglyceride kinase gamma (DGK-gamma), reverses the normal flow of glycerolipid biosynthesis by phosphorylating diacylglycerol back to phosphatidic acid. It is classified as a type I DAG kinase (DGK), containing EF-hand structures that bind Ca(2+) and a recoverin homology domain, in addition to C1 and catalytic domains that are present in all DGKs. As a type I DGK, it is regulated by calcium binding. DGK-gamma contains two copies of the C1 domain. This model corresponds to the first one. DGK-gamma contains typical C1 domains that bind DAG and phorbol esters. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410396 Cd Length: 73 Bit Score: 43.38 E-value: 9.83e-06
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| SH2_Src_HCK | cd10363 | Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ... |
5-77 | 1.08e-05 | ||||
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in hemopoietic cells. HCK is proposed to couple the Fc receptor to the activation of the respiratory burst. It may also play a role in neutrophil migration and in the degranulation of neutrophils. It has two different translational starts that have different subcellular localization. HCK has been shown to interact with BCR gene, ELMO1 Cbl gene, RAS p21 protein activator 1, RASA3, Granulocyte colony-stimulating factor receptor, ADAM15 and RAPGEF1. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. HCK has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198226 Cd Length: 104 Bit Score: 44.19 E-value: 1.08e-05
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| SH2_nSH2_p85_like | cd09942 | N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ... |
8-60 | 1.18e-05 | ||||
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198195 Cd Length: 110 Bit Score: 44.24 E-value: 1.18e-05
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| SH2_SAP1a | cd10400 | Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a; The X-linked ... |
3-57 | 1.45e-05 | ||||
Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a; The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX[VI], which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198263 Cd Length: 103 Bit Score: 43.68 E-value: 1.45e-05
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| SH2_SHB_SHD_SHE_SHF_like | cd09945 | Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, ... |
6-73 | 1.98e-05 | ||||
Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, SHE, SHF); SHB, SHD, SHE, and SHF are SH2 domain-containing proteins that play various roles throughout the cell. SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. SHE is expressed in heart, lung, brain, and skeletal muscle, while expression of SHD is restricted to the brain. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198198 Cd Length: 98 Bit Score: 43.19 E-value: 1.98e-05
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| SH2_SH2D2A_SH2D7 | cd10349 | Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); ... |
6-73 | 2.18e-05 | ||||
Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); SH2D2A and SH7 both contain a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 199830 Cd Length: 77 Bit Score: 42.51 E-value: 2.18e-05
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| SH2_Vav_family | cd09940 | Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ... |
6-73 | 2.29e-05 | ||||
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198193 Cd Length: 102 Bit Score: 43.05 E-value: 2.29e-05
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| SH2_Src_Lyn | cd10364 | Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type ... |
6-77 | 2.74e-05 | ||||
Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in the hematopoietic cells, in neural tissues, liver, and adipose tissue. There are two alternatively spliced forms of Lyn. Lyn plays an inhibitory role in myeloid lineage proliferation. Following engagement of the B cell receptors, Lyn undergoes rapid phosphorylation and activation, triggering a cascade of signaling events mediated by Lyn phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the receptor proteins, and subsequent recruitment and activation of other kinases including Syk, phospholipase C2 (PLC2) and phosphatidyl inositol-3 kinase. These kinases play critical roles in proliferation, Ca2+ mobilization and cell differentiation. Lyn plays an essential role in the transmission of inhibitory signals through phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based inhibitory motifs (ITIM) in regulatory proteins such as CD22, PIR-B and FC RIIb1. Their ITIM phosphorylation subsequently leads to recruitment and activation of phosphatases such as SHIP-1 and SHP-1 which further down modulate signaling pathways, attenuate cell activation and can mediate tolerance. Lyn also plays a role in the insulin signaling pathway. Activated Lyn phosphorylates insulin receptor substrate 1 (IRS1) leading to an increase in translocation of Glut-4 to the cell membrane and increased glucose utilization. It is the primary Src family member involved in signaling downstream of the B cell receptor. Lyn plays an unusual, 2-fold role in B cell receptor signaling; it is essential for initiation of signaling but is also later involved in negative regulation of the signal. Lyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198227 Cd Length: 101 Bit Score: 43.05 E-value: 2.74e-05
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| SH2_C-SH2_Syk_like | cd10401 | C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ... |
6-84 | 2.74e-05 | ||||
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Syk. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198264 Cd Length: 99 Bit Score: 42.96 E-value: 2.74e-05
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| SH2_Src_Frk | cd10369 | Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ... |
6-77 | 2.90e-05 | ||||
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Frk has been demonstrated to interact with retinoblastoma protein. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation. Frk also plays a role in regulation of embryonal pancreatic beta cell formation. Frk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its activation loop. The tryosine involved is at the same site as the tyrosine involved in the autophosphorylation of Src. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 199831 Cd Length: 96 Bit Score: 42.56 E-value: 2.90e-05
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| C1_Stac3 | cd20882 | protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich ... |
189-233 | 3.16e-05 | ||||
protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich domain-containing protein 3 (Stac3) and similar proteins; Stac3 is an essential component of the skeletal muscle excitation-contraction coupling (ECC) machinery. It is required for normal excitation-contraction coupling in skeletal muscle and for normal muscle contraction in response to membrane depolarization. It plays an essential role for normal Ca2+ release from the sarcplasmic reticulum, which ultimately leads to muscle contraction. Stac3 contains a cysteine-rich C1 domain and two SH3 domains at the C-terminus. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410432 Cd Length: 59 Bit Score: 41.48 E-value: 3.16e-05
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| SH2_Src_Fyn_isoform_b_like | cd10419 | Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src ... |
6-77 | 3.22e-05 | ||||
Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform b type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198282 Cd Length: 101 Bit Score: 42.74 E-value: 3.22e-05
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| C1_TNS2 | cd20887 | protein kinase C conserved region 1 (C1 domain) found in tensin-2 and similar proteins; ... |
192-243 | 3.31e-05 | ||||
protein kinase C conserved region 1 (C1 domain) found in tensin-2 and similar proteins; Tensin-2 (TNS2), also called C1 domain-containing phosphatase and tensin (C1-TEN), or tensin-like C1 domain-containing phosphatase (TENC1), is an essential component for the maintenance of glomerular basement membrane (GBM) structures. It regulates cell motility and proliferation. It may have phosphatase activity. TNS2 reduces AKT1 phosphorylation, lowers AKT1 kinase activity, and interferes with AKT1 signaling. It contains an N-terminal region with a zinc finger (C1 domain), a protein tyrosine phosphatase (PTP)-like domain and a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410437 Cd Length: 53 Bit Score: 41.30 E-value: 3.31e-05
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| C1_Myosin-IXa | cd20883 | protein kinase C conserved region 1 (C1 domain) found in unconventional myosin-IXa and similar ... |
192-247 | 4.41e-05 | ||||
protein kinase C conserved region 1 (C1 domain) found in unconventional myosin-IXa and similar proteins; Myosin-IXa, also called unconventional myosin-9a (Myo9a), is a single-headed, actin-dependent motor protein of the unconventional myosin IX class. It is expressed in several tissues and is enriched in the brain and testes. Myosin-IXa contains a Ras-associating (RA) domain, a motor domain, a protein kinase C conserved region 1 (C1), and a Rho GTPase activating domain (RhoGAP). Myosin-IXa binds the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) GluA2 subunit, and plays a key role in controlling the molecular structure and function of hippocampal synapses. Moreover, Myosin-IXa functions in epithelial cell morphology and differentiation, such that its knockout mice develop hydrocephalus and kidney dysfunction. Myosin-IXa regulates collective epithelial cell migration by targeting RhoGAP activity to cell-cell junctions. Myosin-IXa negatively regulates Rho GTPase signaling, and functions as a regulator of kidney tubule function. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410433 Cd Length: 58 Bit Score: 41.11 E-value: 4.41e-05
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| RhoGAP_fMSB1 | cd04401 | RhoGAP_fMSB1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ... |
270-417 | 4.53e-05 | ||||
RhoGAP_fMSB1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal MSB1-like proteins. Msb1 was originally identified as a multicopy suppressor of temperature sensitive cdc42 mutation. Msb1 is a positive regulator of the Pkc1p-MAPK pathway and 1,3-beta-glucan synthesis, both pathways involve Rho1 regulation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. Pssm-ID: 239866 Cd Length: 198 Bit Score: 44.26 E-value: 4.53e-05
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| SH2_Grb7 | cd10413 | Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ... |
6-73 | 5.41e-05 | ||||
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb7 is part of the Grb7 family of proteins which also includes Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198276 Cd Length: 108 Bit Score: 42.20 E-value: 5.41e-05
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| SH2_Src_Fgr | cd10367 | Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ... |
6-80 | 6.55e-05 | ||||
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, Fgr; Fgr is a member of the Src non-receptor type tyrosine kinase family of proteins. The protein contains N-terminal sites for myristoylation and palmitoylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. Fgr is expressed in B-cells and myeloid cells, localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Multiple alternatively spliced variants, encoding the same protein, have been identified Fgr has been shown to interact with Wiskott-Aldrich syndrome protein. Fgr has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198230 Cd Length: 101 Bit Score: 41.82 E-value: 6.55e-05
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| SH2_Vav3 | cd10407 | Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ... |
6-73 | 7.46e-05 | ||||
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav3 preferentially activates RhoA, RhoG and, to a lesser extent, Rac1. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. VAV3 has been shown to interact with Grb2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198270 Cd Length: 103 Bit Score: 41.91 E-value: 7.46e-05
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| SH2_Grb14 | cd10414 | Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) ... |
6-73 | 1.39e-04 | ||||
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb14 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR) and weakly to the erbB2 receptor. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198277 Cd Length: 108 Bit Score: 41.07 E-value: 1.39e-04
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| SH2_SHD | cd10390 | Src homology 2 domain found in SH2 domain-containing adapter proteins D (SHD); The expression ... |
6-45 | 1.68e-04 | ||||
Src homology 2 domain found in SH2 domain-containing adapter proteins D (SHD); The expression of SHD is restricted to the brain. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198253 Cd Length: 98 Bit Score: 40.45 E-value: 1.68e-04
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| SH2_SHE | cd10391 | Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed ... |
6-43 | 2.50e-04 | ||||
Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed in heart, lung, brain, and skeletal muscle. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198254 Cd Length: 98 Bit Score: 39.94 E-value: 2.50e-04
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| SH2_SH2B2 | cd10411 | Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), ... |
6-58 | 3.44e-04 | ||||
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198274 Cd Length: 97 Bit Score: 39.60 E-value: 3.44e-04
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| SH2_SH2B_family | cd10346 | Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein ... |
6-72 | 5.46e-04 | ||||
Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein family has 3 members: SH2B1 (SH2-B, PSM), SH2B2 (APS), and SH2B3 (Lnk). SH2B family members contain a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198209 Cd Length: 97 Bit Score: 38.94 E-value: 5.46e-04
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| SH2_N-SH2_PLC_gamma_like | cd10341 | N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ... |
6-73 | 5.70e-04 | ||||
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 199829 Cd Length: 99 Bit Score: 38.87 E-value: 5.70e-04
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| CRIK | cd20814 | protein kinase C conserved region 1 (C1 domain) found in citron Rho-interacting kinase (CRIK) ... |
192-243 | 6.86e-04 | ||||
protein kinase C conserved region 1 (C1 domain) found in citron Rho-interacting kinase (CRIK) and similar proteins; CRIK, also called serine/threonine-protein kinase 21, is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger (C1 domain), and a pleckstrin homology (PH) domain, in addition to other motifs. This model corresponds to C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410364 Cd Length: 56 Bit Score: 37.61 E-value: 6.86e-04
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| SH2_SOCS_family | cd09923 | Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ... |
6-60 | 8.31e-04 | ||||
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198178 Cd Length: 81 Bit Score: 37.95 E-value: 8.31e-04
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| SH2_CRK_like | cd09926 | Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ... |
8-51 | 1.01e-03 | ||||
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the CRK proteins. CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the oncoprotein CRK. CRKs regulate transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. The SH2 domain of CRK associates with tyrosine-phosphorylated receptors or components of focal adhesions, such as p130Cas and paxillin. CRK transmits signals to small G proteins through effectors that bind its SH3 domain, such as C3G, the guanine-nucleotide exchange factor (GEF) for Rap1 and R-Ras, and DOCK180, the GEF for Rac6. The binding of p130Cas to the CRK-C3G complex activates Rap1, leading to regulation of cell adhesion, and activates R-Ras, leading to JNK-mediated activation of cell proliferation, whereas the binding of CRK DOCK180 induces Rac1-mediated activation of cellular migration. The activity of the different splicing isoforms varies greatly with CRKI displaying substantial transforming activity, CRKII less so, and phosphorylated CRKII with no biological activity whatsoever. CRKII has a linker region with a phosphorylated Tyr and an additional C-terminal SH3 domain. The phosphorylated Tyr creates a binding site for its SH2 domain which disrupts the association between CRK and its SH2 target proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198180 [Multi-domain] Cd Length: 106 Bit Score: 38.61 E-value: 1.01e-03
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| SH2_SHB | cd10389 | Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in ... |
4-73 | 1.07e-03 | ||||
Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198252 Cd Length: 97 Bit Score: 38.15 E-value: 1.07e-03
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| SH2_SH2D7 | cd10417 | Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ... |
6-73 | 1.15e-03 | ||||
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 199832 Cd Length: 102 Bit Score: 38.34 E-value: 1.15e-03
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| SH2_PTK6_Brk | cd10358 | Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast ... |
6-73 | 2.28e-03 | ||||
Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast tumor kinase (Brk); Human protein-tyrosine kinase-6 (PTK6, also known as breast tumor kinase (Brk)) is a member of the non-receptor protein-tyrosine kinase family and is expressed in two-thirds of all breast tumors. PTK6 (9). PTK6 contains a SH3 domain, a SH2 domain, and catalytic domains. For the case of the non-receptor protein-tyrosine kinases, the SH2 domain is typically involved in negative regulation of kinase activity by binding to a phosphorylated tyrosine residue near to the C terminus. The C-terminal sequence of PTK6 (PTSpYENPT where pY is phosphotyrosine) is thought to be a self-ligand for the SH2 domain. The structure of the SH2 domain resembles other SH2 domains except for a centrally located four-stranded antiparallel beta-sheet (strands betaA, betaB, betaC, and betaD). There are also differences in the loop length which might be responsible for PTK6 ligand specificity. There are two possible means of regulation of PTK6: autoinhibitory with the phosphorylation of Tyr playing a role in its negative regulation and autophosphorylation at this site, though it has been shown that PTK6 might phosphorylate signal transduction-associated proteins Sam68 and signal transducing adaptor family member 2 (STAP/BKS) in vivo. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198221 Cd Length: 100 Bit Score: 37.42 E-value: 2.28e-03
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| SH2_SH2D2A | cd10416 | Src homology 2 domain found in the SH2 domain containing protein 2A (SH2D2A); SH2D2A contains ... |
6-73 | 3.23e-03 | ||||
Src homology 2 domain found in the SH2 domain containing protein 2A (SH2D2A); SH2D2A contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198279 Cd Length: 102 Bit Score: 36.94 E-value: 3.23e-03
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| C1_p190RhoGEF | cd20876 | protein kinase C conserved region 1 (C1 domain) found in 190 kDa guanine nucleotide exchange ... |
192-249 | 3.96e-03 | ||||
protein kinase C conserved region 1 (C1 domain) found in 190 kDa guanine nucleotide exchange factor (p190RhoGEF) and similar proteins; p190RhoGEF, also called Rho guanine nucleotide exchange factor (RGNEF), Rho guanine nucleotide exchange factor 28 (ARHGEF28), or RIP2, is a brain-enriched, RhoA-specific guanine nucleotide exchange factor that regulates signaling pathways downstream of integrins and growth factor receptors. It is involved in axonal branching, synapse formation and dendritic morphogenesis, as well as in focal adhesion formation, cell motility and B-lymphocytes activation. In addition to the Dbl homology (DH)-PH domain, p190RhoGEF contains an N-terminal C1 (Protein kinase C conserved region 1) domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410426 Cd Length: 61 Bit Score: 35.49 E-value: 3.96e-03
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| SH2_SH2B3 | cd10412 | Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), ... |
6-53 | 4.45e-03 | ||||
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198275 Cd Length: 97 Bit Score: 36.41 E-value: 4.45e-03
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| C1_Myosin-IXb | cd20884 | protein kinase C conserved region 1 (C1 domain) found in unconventional myosin-IXb and similar ... |
192-241 | 5.04e-03 | ||||
protein kinase C conserved region 1 (C1 domain) found in unconventional myosin-IXb and similar proteins; Myosin-IXb, also called unconventional myosin-9b (Myo9b), is an actin-dependent motor protein of the unconventional myosin IX class. It is expressed abundantly in tissues of the immune system, like lymph nodes, thymus, and spleen, and in several immune cells including dendritic cells, macrophages and CD4+ T cells. Myosin-IXb contains a Ras-associating (RA) domain, a motor domain, a protein kinase C conserved region 1 (C1), and a Rho GTPase activating (RhoGAP) domain. Myosin-IXb acts as a motorized signaling molecule that links Rho signaling to the dynamic actin cytoskeleton. It regulates leukocyte migration by controlling RhoA signaling. Myosin-IXb is also involved in the development of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. Moreover, Myosin-IXb is a ROBO-interacting protein that suppresses RhoA activity in lung cancer cells. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410434 Cd Length: 58 Bit Score: 35.22 E-value: 5.04e-03
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| C1_DGKtheta_typeV_rpt2 | cd20804 | second protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, ... |
197-241 | 6.53e-03 | ||||
second protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, DAG kinase theta, and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase theta, also called diglyceride kinase theta (DGK-theta), is the only isoform classified as type V; it contains a pleckstrin homology (PH)-like domain and an additional C1 domain, compared to other DGKs. It may regulate the activity of protein kinase C by controlling the balance between the two signaling lipids, diacylglycerol and phosphatidic acid. DAG kinase theta contains three copies of the C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites. Pssm-ID: 410354 Cd Length: 57 Bit Score: 34.97 E-value: 6.53e-03
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| SH2_Src_Yes | cd10366 | Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ... |
6-77 | 8.92e-03 | ||||
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type tyrosine kinase family of proteins. Yes is the cellular homolog of the Yamaguchi sarcoma virus oncogene. In humans it is encoded by the YES1 gene which maps to chromosome 18 and is in close proximity to thymidylate synthase. A corresponding Yes pseudogene has been found on chromosome 22. YES1 has been shown to interact with Janus kinase 2, CTNND1,RPL10, and Occludin. Yes1 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. Pssm-ID: 198229 Cd Length: 101 Bit Score: 35.77 E-value: 8.92e-03
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