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Conserved domains on  [gi|755493441|ref|XP_006496527|]
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dedicator of cytokinesis protein 10 isoform X2 [Mus musculus]

Protein Classification

C2_Dock-D and DHR2_DOCK10 domain-containing protein( domain architecture ID 10570949)

protein containing domains DUF3398, PH_DOCK-D, C2_Dock-D, and DHR2_DOCK10

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
1695-2142 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also called Zizimin3, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock10 is preferentially expressed in lymphocytes and may play a role in interleukin-4 induced activation of B cells. It may also play a role in the invasion of tumor cells. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock10, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


:

Pssm-ID: 212572  Cd Length: 446  Bit Score: 962.20  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1695 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGYWKMEKICTPPLLPEDTQPCDSNLLLTTPGGGSMFSM 1774
Cdd:cd11699     1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGYWKMEKICTSSMLPEDSQVYDSNLLLTTSTGGSMFSM 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1775 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYD 1854
Cdd:cd11699    81 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKRLSELYYD 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1855 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 1934
Cdd:cd11699   161 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEGKE--YIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1935 KVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVK 2014
Cdd:cd11699   239 KVNPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHSFPYVK 318
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 2015 KRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ 2094
Cdd:cd11699   319 KRIQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ 398
                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....*...
gi 755493441 2095 VKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2142
Cdd:cd11699   399 VKLLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHYRDMLSEL 446
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
670-859 5.71e-98

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 classes of Dock family proteins. The members here include: Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Dock-D are Cdc42-specific GEFs. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-D members contain a functionally uncharacterized domain and a PH domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The PH domain broadly binds to phospholipids and is thought to be involved in targeting the plasma membrane. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


:

Pssm-ID: 176079  Cd Length: 185  Bit Score: 313.49  E-value: 5.71e-98
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  670 YKNQIYVYPKHLKYDSQKCFNKARNITVCIEFKNSDDDGAKPMKCIYGKPGGPlFTSSAYTAVLHHSQNPDFSDEVKIEL 749
Cdd:cd08697     1 YKNHLYVYPLHLKYDSQKTFAKARNIAVCIEFRDSDEEDAKPLKCIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIEL 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  750 PTQLHGKHHLLFSFYHITCDInaKANAKKKEALETSVGYAWLPLMK-HDQIASQEYNIPIATTL---PPNYLSIQDPtsa 825
Cdd:cd08697    80 PTQLHEKHHLLFTFYHVSCDI--NKKGKKKDGVETPVGYAWLPLLKdKGRLNSEEQTPPVANLLpnyPDGYLSIQPH--- 154
                         170       180       190
                  ....*....|....*....|....*....|....
gi 755493441  826 khgGSDIKWVDGGKPLFKVSTFVVSTVNTQDPHV 859
Cdd:cd08697   155 ---GPEVKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
181-301 2.19e-63

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270087  Cd Length: 126  Bit Score: 211.80  E-value: 2.19e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYKGNFNST-VNNTVTVRSFKKRYFQLTQLPDNSYIMNFYKDEKiSKEPKGCIFLDSCTGVVQNNRLRKYAFEL 259
Cdd:cd13267     6 ITKEGYLYKGPENSSdSFISLAMKSFKRRFFHLKQLVDGSYILEFYKDEK-KKEAKGTIFLDSCTGVVQNSKRRKFCFEL 84
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 755493441  260 KMNDLTYFVLAAETESDMDEWIHTLNRILQISPEGPLQGRKS 301
Cdd:cd13267    85 RMQDKKSYVLAAESEAEMDEWISKLNKILQSSKEQSIQKKRS 126
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
44-154 8.34e-44

Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the DOCK-C subfamily (DOCK 6, 7, 8) and DOCK-D subfamily (DOCK 9, 10, 11). DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases, required during several cellular processes, such as cell motility and phagocytosis. DOCK proteins are categorized into four subfamilies based on their sequence homology: DOCK-A (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11).


:

Pssm-ID: 463380  Cd Length: 112  Bit Score: 155.12  E-value: 8.34e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441    44 PRLLDPLDYETVIEELEKTYRDDPLQDLLFFPSDDFSTATVSWDIRTLYSTVPEEAEHRAESlLVKEACKFYSSQWYVVN 123
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAEKEADP-LVRECIKTYTSDWHVVN 79
                           90       100       110
                   ....*....|....*....|....*....|...
gi 755493441   124 YKYEQYSGDIRQLPRAE--HKPEKLPSHSFEVD 154
Cdd:pfam11878   80 YKYEDYSGDFRQLPKSKrrERPEKLPKQVFEID 112
 
Name Accession Description Interval E-value
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
1695-2142 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also called Zizimin3, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock10 is preferentially expressed in lymphocytes and may play a role in interleukin-4 induced activation of B cells. It may also play a role in the invasion of tumor cells. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock10, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212572  Cd Length: 446  Bit Score: 962.20  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1695 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGYWKMEKICTPPLLPEDTQPCDSNLLLTTPGGGSMFSM 1774
Cdd:cd11699     1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGYWKMEKICTSSMLPEDSQVYDSNLLLTTSTGGSMFSM 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1775 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYD 1854
Cdd:cd11699    81 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKRLSELYYD 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1855 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 1934
Cdd:cd11699   161 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEGKE--YIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1935 KVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVK 2014
Cdd:cd11699   239 KVNPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHSFPYVK 318
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 2015 KRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ 2094
Cdd:cd11699   319 KRIQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ 398
                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....*...
gi 755493441 2095 VKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2142
Cdd:cd11699   399 VKLLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHYRDMLSEL 446
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
670-859 5.71e-98

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 classes of Dock family proteins. The members here include: Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Dock-D are Cdc42-specific GEFs. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-D members contain a functionally uncharacterized domain and a PH domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The PH domain broadly binds to phospholipids and is thought to be involved in targeting the plasma membrane. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176079  Cd Length: 185  Bit Score: 313.49  E-value: 5.71e-98
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  670 YKNQIYVYPKHLKYDSQKCFNKARNITVCIEFKNSDDDGAKPMKCIYGKPGGPlFTSSAYTAVLHHSQNPDFSDEVKIEL 749
Cdd:cd08697     1 YKNHLYVYPLHLKYDSQKTFAKARNIAVCIEFRDSDEEDAKPLKCIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIEL 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  750 PTQLHGKHHLLFSFYHITCDInaKANAKKKEALETSVGYAWLPLMK-HDQIASQEYNIPIATTL---PPNYLSIQDPtsa 825
Cdd:cd08697    80 PTQLHEKHHLLFTFYHVSCDI--NKKGKKKDGVETPVGYAWLPLLKdKGRLNSEEQTPPVANLLpnyPDGYLSIQPH--- 154
                         170       180       190
                  ....*....|....*....|....*....|....
gi 755493441  826 khgGSDIKWVDGGKPLFKVSTFVVSTVNTQDPHV 859
Cdd:cd08697   155 ---GPEVKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
181-301 2.19e-63

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270087  Cd Length: 126  Bit Score: 211.80  E-value: 2.19e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYKGNFNST-VNNTVTVRSFKKRYFQLTQLPDNSYIMNFYKDEKiSKEPKGCIFLDSCTGVVQNNRLRKYAFEL 259
Cdd:cd13267     6 ITKEGYLYKGPENSSdSFISLAMKSFKRRFFHLKQLVDGSYILEFYKDEK-KKEAKGTIFLDSCTGVVQNSKRRKFCFEL 84
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 755493441  260 KMNDLTYFVLAAETESDMDEWIHTLNRILQISPEGPLQGRKS 301
Cdd:cd13267    85 RMQDKKSYVLAAESEAEMDEWISKLNKILQSSKEQSIQKKRS 126
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
670-858 1.68e-59

C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical GTP/GDP exchange factors for the small GTPases Rac and Cdc42 and are implicated cell-migration and phagocytosis. Across all Dock180 proteins, two regions are conserved: C-terminus termed CZH2 or DHR2 (or the Dedicator of cytokinesis) whereas CZH1/DHR1 contain a new family of the C2 domain.


Pssm-ID: 464171  Cd Length: 185  Bit Score: 203.22  E-value: 1.68e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441   670 YKNQIYVYPKHLKYDSQKcFNKARNITVCIEFKNSDddgAKPM-KCIYGKPGGPlFTSSAYTAVLHHSQNPDFSDEVKIE 748
Cdd:pfam14429    4 YRNDLYVTPKSGNFSKQK-KSSARNIEVTVEVRDSD---GEPLpNCIYGGSGGP-FVTEFKSTVYYHNKSPTWYEEIKIA 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441   749 LPTQLHGKHHLLFSFYHITCDinakanaKKKEALETSVGYAWLPLMKHDQ--IASQEYNIPIATT--LPPNYLSIQDPTS 824
Cdd:pfam14429   79 LPAELTPKHHLLFTFYHVSCD-------EKKDKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYKYdeLPPGYLSLPWSSG 151
                          170       180       190
                   ....*....|....*....|....*....|....
gi 755493441   825 AKHGGSDIKWVDGGKPLFKVSTFVVSTVNTQDPH 858
Cdd:pfam14429  152 GEKESSALPGLKGGKDLFKVRTRLCSTKYTQDEH 185
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
1682-1864 3.80e-55

DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic dedicator of cytokinesis proteins (DOCK), which are guanine nucleotide exchange factors (GEFs), that activate some small GTPases by exchanging bound GDP for free GTP such as Rac. These proteins have a DOCK-homology region 1 (DHR-1, also known as DOCK-type C2 domain) at the N-terminus and a DHR-2 (also known as DOCKER domain) at the C-terminal. The DHR-2 is a GEF catalytic domain organized into three lobes, A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe A, formed from an antiparallel array of alpha helices that adopts a tetratricopeptide repeat-like fold, which through extensive contacts with lobe B, stabilizes DHR-2 domain.


Pssm-ID: 462040 [Multi-domain]  Cd Length: 154  Bit Score: 189.43  E-value: 3.80e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  1682 DLQYSLANSYASTPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKgywkmekictppllpedtqpcdsnl 1761
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK------------------------- 55
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  1762 llttpgGGSMFSMGWPAFLSITPNI-KEEGAMKEDSGMQDTP-YNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVF 1839
Cdd:pfam06920   56 ------GKIPNPLGASAFEKISPNIlREESALKDDSGVCDSPhFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIY 129
                          170       180
                   ....*....|....*....|....*
gi 755493441  1840 EKQRDFKKLSDLYYDIHRSYLKVAE 1864
Cdd:pfam06920  130 ESRRDYKKLSECHGKLAEAYEKIVE 154
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
44-154 8.34e-44

Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the DOCK-C subfamily (DOCK 6, 7, 8) and DOCK-D subfamily (DOCK 9, 10, 11). DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases, required during several cellular processes, such as cell motility and phagocytosis. DOCK proteins are categorized into four subfamilies based on their sequence homology: DOCK-A (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11).


Pssm-ID: 463380  Cd Length: 112  Bit Score: 155.12  E-value: 8.34e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441    44 PRLLDPLDYETVIEELEKTYRDDPLQDLLFFPSDDFSTATVSWDIRTLYSTVPEEAEHRAESlLVKEACKFYSSQWYVVN 123
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAEKEADP-LVRECIKTYTSDWHVVN 79
                           90       100       110
                   ....*....|....*....|....*....|...
gi 755493441   124 YKYEQYSGDIRQLPRAE--HKPEKLPSHSFEVD 154
Cdd:pfam11878   80 YKYEDYSGDFRQLPKSKrrERPEKLPKQVFEID 112
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
181-289 5.03e-14

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 69.88  E-value: 5.03e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441    181 VFKSGWLYKgnfnstvNNTVTVRSFKKRYFQLTqlpdNSYIMnFYKDEK--ISKEPKGCIFLDSCT---GVVQNNRLRKY 255
Cdd:smart00233    1 VIKEGWLYK-------KSGGGKKSWKKRYFVLF----NSTLL-YYKSKKdkKSYKPKGSIDLSGCTvreAPDPDSSKKPH 68
                            90       100       110
                    ....*....|....*....|....*....|....
gi 755493441    256 AFELKMNDLTYFVLAAETESDMDEWIHTLNRILQ 289
Cdd:smart00233   69 CFEIKTSDRKTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
181-288 8.36e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 63.74  E-value: 8.36e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441   181 VFKSGWLYK-GNFNSTvnntvtvrSFKKRYFQLTqlpdNSYIMnFYKDEKI--SKEPKGCIFLDSCTGV---VQNNRLRK 254
Cdd:pfam00169    1 VVKEGWLLKkGGGKKK--------SWKKRYFVLF----DGSLL-YYKDDKSgkSKEPKGSISLSGCEVVevvASDSPKRK 67
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 755493441   255 YAFELKMNDLTY---FVLAAETESDMDEWIHTLNRIL 288
Cdd:pfam00169   68 FCFELRTGERTGkrtYLLQAESEEERKDWIKAIQSAI 104
 
Name Accession Description Interval E-value
DHR2_DOCK10 cd11699
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also ...
1695-2142 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 10; Dock10, also called Zizimin3, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock10 is preferentially expressed in lymphocytes and may play a role in interleukin-4 induced activation of B cells. It may also play a role in the invasion of tumor cells. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock10, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212572  Cd Length: 446  Bit Score: 962.20  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1695 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGYWKMEKICTPPLLPEDTQPCDSNLLLTTPGGGSMFSM 1774
Cdd:cd11699     1 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGYWKMEKICTSSMLPEDSQVYDSNLLLTTSTGGSMFSM 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1775 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYD 1854
Cdd:cd11699    81 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENTLVEQLELCVDYLWKSERYELIADVNKPVIAVFEKQRDFKRLSELYYD 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1855 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 1934
Cdd:cd11699   161 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQGFFEEEEGKE--YIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1935 KVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVK 2014
Cdd:cd11699   239 KVNPKELDPKFAYIQVTYVTPYFDEKEQEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVEEQCKRRTILTTSHSFPYVK 318
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 2015 KRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ 2094
Cdd:cd11699   319 KRIQVVSQTSTELNPIEVAIDEMSKKVSELNQLCTMEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ 398
                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....*...
gi 755493441 2095 VKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2142
Cdd:cd11699   399 VKLLKEIFRQFAEACGQALDVNERLIKEDQLEYQEEMRSHYRDMLSEL 446
DHR2_DOCK_D cd11694
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK ...
1696-2142 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class D, also called the Zizimin subfamily, includes Dock9, 10 and 11. Class D Docks are specific GEFs for Cdc42. Dock9 plays important roles in spine formation and dendritic growth. Dock10 and Dock11 are preferentially expressed in lymphocytes. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class D DOCKs, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212567  Cd Length: 376  Bit Score: 675.21  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1696 ELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKgywkmekictppllpedtqpcdsnlllttpgggsmfsmg 1775
Cdd:cd11694     1 ELRKTWLESMARIHEKNGNFSEAAMCYIHIAALVAEYLKRK--------------------------------------- 41
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1776 wpaflsitpnikeegamkedsgmqdtpyneNILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYDI 1855
Cdd:cd11694    42 ------------------------------DLLLELLEACVEGLWKAERYELLGELYKLIIPIYEKRRDFEQLADCYRTL 91
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1856 HRSYLKVAEVVNSEKRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNK 1935
Cdd:cd11694    92 HRAYEKVVEVMESGKRLLGTYYRVAFYGQAFFEEEDGKE--YIYKEPKVTSLSEISERLLKLYGDKFGSENVKLIQDSGK 169
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1936 VNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVKK 2015
Cdd:cd11694   170 VNPKDLDPKYAYIQVTHVTPYFDEKELEDRKTEFERNHNIRRFVFETPFTLSGKARGAVEEQWKRRTILTTSHSFPYVKK 249
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 2016 RIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQV 2095
Cdd:cd11694   250 RIPVVQREIIELSPIEVAIDEMQSKVKELEELISTEPVDMKKLQLRLQGSVSVQVNAGPLAYARAFLEPTTVKNYPDDQV 329
                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....*..
gi 755493441 2096 KLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2142
Cdd:cd11694   330 EDLKDVFRDFIKACGQALELNERLIKEDQREYHEVLKENYRKMVKEL 376
DHR2_DOCK9 cd11698
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also ...
1696-2145 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 9; Dock9, also called Zizimin1, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. It plays important roles in spine formation and dendritic growth. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock9, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212571  Cd Length: 415  Bit Score: 654.02  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1696 ELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGywkmekictppllpedtqpcdsnlllttpgggsMFSMG 1775
Cdd:cd11698     1 ELRKTWLDSMARIHVKNGDLSEAAMCYVHVAALVAEYLTRKG---------------------------------MFRQG 47
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1776 WPAFLSITPNIKEEGAMKEDSGMQDTPYNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYDI 1855
Cdd:cd11698    48 CTAFRVITPNIDEEASMMEDVGMQDVHFNEDVLMELLEQCADGLWKAERYELIADIYKLIIPIYEKRRDFERLAHLYDTL 127
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1856 HRSYLKVAEVVNSEKRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNK 1935
Cdd:cd11698   128 HRAYSKVTEVMHSGKRLLGTYFRVAFFGQGFFEDEDGKE--YIYKEPKLTPLSEISQRLLKLYSDKFGSENVKMIQDSGK 205
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1936 VNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVKK 2015
Cdd:cd11698   206 VNPKDLDSKYAYIQVTHVTPYFDEKELQERKTDFERSHNIRRFMFEMPFTQSGKRQGGVEEQCKRRTILTAIHCFPYVKK 285
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 2016 RIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQV 2095
Cdd:cd11698   286 RIPVMYQHHTDLNPIEVAIDEMSKKVAELRQLCSSAEVDMIKLQLKLQGSVSVQVNAGPLAYARAFLDDTNTKRYPDNKV 365
                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|
gi 755493441 2096 KLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSELSAI 2145
Cdd:cd11698   366 KLLKEVFRQFVEACGQALAVNERLIKEDQLEYQEEMKANYREMAKELSEI 415
DHR2_DOCK11 cd11700
Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also ...
1695-2142 0e+00

Dock Homology Region 2, a GEF domain, of Class D Dedicator of Cytokinesis 11; Dock11, also called Zizimin2 or activated Cdc42-associated GEF (ACG), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPase Cdc42 by exchanging bound GDP for free GTP. Dock11 is predominantly expressed in lymphocytes and is found in high levels in germinal center B lymphocytes after T cell dependent antigen immunization. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock11, which contains the catalytic GEF activity for Cdc42. Class D DOCKs also contain a Pleckstrin homology (PH) domain at the N-terminus.


Pssm-ID: 212573  Cd Length: 413  Bit Score: 627.41  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1695 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKgywkmekictppllpedtqpcdsnlllttpgggSMFSM 1774
Cdd:cd11700     1 PELRKTWLDSMAKIHVKNGDFSEAAMCYVHVAALVAEFLHRK---------------------------------KLFPS 47
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1775 GWPAFLSITPNIKEEGAMKEDSGMQDTPYNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYD 1854
Cdd:cd11700    48 GCAAFKKITPNIDEEGAMKEDIGMMDVHYSEEVLVELLEQCVDGLWKAERYELISEISKLIIPIYEKRREFEKLTQLYRT 127
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1855 IHRSYLKVAEVVNSEKRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 1934
Cdd:cd11700   128 LHGAYAKILEVMHTGKRLLGTFFRVAFYGQGFFEEEDGKE--YIYKEPKLTGLSEISHRLLKLYGEKFGSENVKIIQDSN 205
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1935 KVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVK 2014
Cdd:cd11700   206 KVNQKDLDPKYAHIQVTYVKPYFDDKEMAERKTEFERNHNIQRFVFETPYTLSGKKQGGVEEQCKRRTILTTANSFPYVK 285
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 2015 KRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ 2094
Cdd:cd11700   286 KRIPVNGEKQTNLKPIDVATDEIKDKTAELQKLCSNQDVDMIQLQLKLQGCVSVQVNAGPLAYARAFLDDSQASKYPNKK 365
                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....*...
gi 755493441 2095 VKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2142
Cdd:cd11700   366 VKELKEMFRKFIQACSIALELNERLIKEDQVEYHEGLKSNFRDMVKEL 413
DHR2_DOCK_C cd11695
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK ...
1695-2142 1.92e-115

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class C, also called the Zizimin-related (Zir) subfamily, includes Dock6, 7 and 8. Class C DOCKs have been shown to have GEF activity for both Rac and Cdc42. Dock6 regulates neurite outgrowth. Dock7 plays a critical roles in the early stages of axon formation, neuronal polarity, and myelination. Dock8 regulates T and B cell numbers and functions, and plays essential roles in humoral immune responses and the proper formation of B cell immunological synapses. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Class C Docks, which contains the catalytic GEF activity for Rac and Cdc42.


Pssm-ID: 212568  Cd Length: 368  Bit Score: 371.25  E-value: 1.92e-115
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1695 PELRRTWLESMAKIHARNGDLSEAAMCYIHIAALiaeylkrkgywkmekictppllpedtqpcdsnlllttpgggsmfsm 1774
Cdd:cd11695     2 PDLRLTWLQNMAEKHYERKNFAEAAQCLVHAAAL---------------------------------------------- 35
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1775 GWPAflsitpnikeegamkedsgmqdtpyneniLVEQlymCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYD 1854
Cdd:cd11695    36 GLVG-----------------------------LLEQ---AAESFSKAGMYEAVNEVYKLLIPILEANRDYKKLAEIHGK 83
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1855 IHRSYLKVAEVVNsEKRLFGRYYRVAFYGqavGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSN 1934
Cdd:cd11695    84 LQDAFTKIEKQQG-GKRMFGTYFRVGFYG---SKFGDLDGKEFIYKEPAITKLPEISHRLETFYGERFGEERVEVIKDSN 159
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1935 KVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVK 2014
Cdd:cd11695   160 PVDTSKLDPDKAYIQITYVEPYFDEYELKERTTYFERNYNLRRFMYATPFTPDGKAHGELAEQYKRKTILTTENSFPYVK 239
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 2015 KRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEE-TNAKKYPDN 2093
Cdd:cd11695   240 TRLQVVNREEIVLTPIEVAIEDVQKKTRELAAATTQEPPDPKMLQMVLQGSIGTTVNQGPLEVANVFLSDiPLDPKELDR 319
                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....*....
gi 755493441 2094 QVKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2142
Cdd:cd11695   320 HQNKLRLCFKEFSKKCYDALEKNKELIGPDQKEYQKELERNYENFKEKL 368
DHR2_DOCK8 cd11701
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also ...
1693-2142 3.54e-105

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 8; Dock8, also called Zizimin-related 3 (Zir3), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac1 and Cdc42 by exchanging bound GDP for free GTP. Dock8 is highly expressed in the immune system and it regulates T and B cell numbers and functions. It plays essential roles in humoral immune responses and the proper formation of B cell immunological synapses. Dock8 deficiency is a primary immune deficiency that results in extreme susceptibility to cutaneous viral infections, elevated IgE levels, and eosinophilia. It was originally described as an autosomal recessive form of hyper IgE syndrome (AR-HIES). DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock8, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212574  Cd Length: 422  Bit Score: 343.94  E-value: 3.54e-105
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1693 STPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKrkgywkmekictpplLPEDTqpcdsnlllttpgggSMF 1772
Cdd:cd11701     1 TSPDLRLTWLQNMAEKHTKRKCFTEAAMCLVHAAALVAEYLS---------------MLEDH---------------SYL 50
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1773 SMGWPAFLSITPNIKEEGAMKEDSGMQDTP-------YNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDF 1845
Cdd:cd11701    51 PVGSVSFQNISSNVLEESAVSDDILSPDEDgvcsgryFTENGLVGLLEQAAELFSTGGLYETVNEVYKIVIPILEAHRDF 130
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1846 KKLSDLYYDIHRSYLKVAEvvNSEKRLFGRYYRVAFYGQAVGFFEEEEgkeYIYKEPKLTGLSEISQRLLKLYADKFGAD 1925
Cdd:cd11701   131 RKLASTHDKLQKAFDNIIN--KGHKRMFGTYFRVGFYGSKFGDLDEQE---FIYKEPAITKLPEISHRLEGFYGQCFGDD 205
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1926 NVKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLT 2005
Cdd:cd11701   206 VVEVIKDSTPVDKSKLDPNKAYIQITFVEPYFDDYEMKDRVTYFEKNFNLRRFMYTTPFTLDGRPRGELSEQYKRKTILT 285
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 2006 TSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEET 2085
Cdd:cd11701   286 TMHAFPYIKTRINVIQKEEFDLTPIEVAIEDMQKKTRELAEATHQEPPDAKMLQMVLQGSVGATVNQGPLEVAQVFLAEI 365
                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 755493441 2086 NAKKYPDNQVKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2142
Cdd:cd11701   366 PADPKLYRHHNKLRLCFKEFIMRCGEAVEKNKRLITADQREYQQELKKNYNKLRENL 422
DHR2_DOCK cd11684
Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins ...
1696-2142 1.65e-103

Dock Homology Region 2, a GEF domain, of Dedicator of Cytokinesis proteins; DOCK proteins comprise a family of atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate the small GTPases Rac and Cdc42 by exchanging bound GDP for free GTP. They are also called the CZH (CED-5, Dock180, and MBC-zizimin homology) family, after the first family members identified. Dock180 was first isolated as a binding partner for the adaptor protein Crk. The Caenorhabditis elegans protein, Ced-5, is essential for cell migration and phagocytosis, while the Drosophila ortholog, Myoblast city (MBC), is necessary for myoblast fusion and dorsal closure. DOCKs are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1 (or Dock180), 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1, and DHR-2 (also called CZH2 or Docker). This alignment model represents the DHR-2 domain of DOCK proteins, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212566 [Multi-domain]  Cd Length: 392  Bit Score: 338.12  E-value: 1.65e-103
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1696 ELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKGywkmekictPPLLPEDTQPCDSNlllttpgggsmfsmg 1775
Cdd:cd11684     1 ELYIRYLHKLADLHEERGNYVEAALCLLLHADLYAWDLKALV---------PALAESLSFPEQTS--------------- 56
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1776 wpaflsitpnikEEgamkedsgmqdtpyneniLVEQLY-MCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYD 1854
Cdd:cd11684    57 ------------FE------------------RKEALYkKAIDLFDKGKAWEFAIALYKELIPQYENNFDYAKLSEVHRK 106
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1855 IHRSYLKVAEVvnseKRLFGRYYRVAFYGQAvgFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKfgadnvKIIQDSN 1934
Cdd:cd11684   107 IAKLYEKIAEK----DRLFPTYFRVGFYGKG--FPESLRGKEFIYRGPEFERLGDFCERLKSLYPGA------EIIQSSE 174
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1935 KVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRK----TDFEMHHNINRFVFETPFTLSGKK-HGGVAEQCKRRTVLTTSHL 2009
Cdd:cd11684   175 EPDDEILDSEGQYIQITSVEPYFDDEDLVSRAapgvRQFYRNNNINTFVYERPFTKGGKKsQNEITDQWKERTILTTEES 254
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 2010 FPYVKKRIQVISQSSTELNPIEVAIDEMSRKVSELNQLC----TTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEET 2085
Cdd:cd11684   255 FPTILRRSEVVSIEEIELSPIENAIEDIEKKTEELRSLInkyrSGDSPNVNPLQMLLQGTVDAAVNGGPVAYAEAFLSEE 334
                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 755493441 2086 NAKKYP-DNQVKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2142
Cdd:cd11684   335 YLSNYPeAEKVKKLKEAFEEFLEILKRGLALHAKLCPPEMAPLHEELEEGFEKLFKEL 392
DHR2_DOCK7 cd11703
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also ...
1655-2157 1.12e-98

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 7; Dock7, also called Zizimin-related 2 (Zir2), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac1 and Cdc42 by exchanging bound GDP for free GTP. It plays a critical role in the initial specification of axon formation in hippocampal neurons. It affects neuronal polarity by regulating microtubule dynamics. Dock7 also plays a role in controlling myelination by Schwann cells. It may also play important roles in the function and distribution of dermal and follicular melanocytes. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock7, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212576  Cd Length: 473  Bit Score: 327.42  E-value: 1.12e-98
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1655 DLTKRIRTVLMATAQMKEHEKDPEMLVDLQYSLANSYASTPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLK 1734
Cdd:cd11703     1 DLVFNLHMILSDTVKMKEHQEDPEMLIDLMYRIAKGYQTSPDLRLTWLQNMAGKHSERSNHAEAAQCLVHSAALVAEYLS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1735 rkgywkmekictpplLPEDTQpcdsnlllttpgggsMFSMGWPAFLSITPNIKEEGAMKEDSGMQDTP-------YNENI 1807
Cdd:cd11703    81 ---------------MLEDRK---------------YLPVGCVTFQNISSNVLEESAVSDDVVSPDEEgicsgkyFTEAG 130
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1808 LVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFKKLSDLYYDIHRSYLKVaeVVNSEKRLFGRYYRVAFYGQAVG 1887
Cdd:cd11703   131 LVGLLEQAAASFSMAGMYEAVNEVYKVLIPIHEANRDAKKLATIHGKLQEAFSKI--VHQDGKRMFGTYFRVGFYGTKFG 208
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1888 FFEEEEgkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKT 1967
Cdd:cd11703   209 DLDEQE---FVYKEPAITKLAEISHRLEGFYGERFGEDVVEVIKDSNPVDKCKLDPNKAFIQITYVEPYFDTYEMKDRIT 285
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1968 DFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSRKVSELNQL 2047
Cdd:cd11703   286 YFDKNYNLRRFMYCTPFTLDGRAHGELHEQFKRKTILTTSHAFPYIKTRINVIHKEEIILTPIEVAIEDMQKKTQELAFA 365
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 2048 CTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKLLKEIFRQFADACGQALDVNERLIKEDQLEY 2127
Cdd:cd11703   366 THQDPADPKMLQMVLQGSVGTTVNQGPLEVAQVFLSEIPSDPKLFRHHNKLRLCFKDFTKRCEDALRKNKSLIGPDQKEY 445
                         490       500       510
                  ....*....|....*....|....*....|
gi 755493441 2128 QEELRSHYKDMLSELSAIMNEQLcrgPCLY 2157
Cdd:cd11703   446 QRELERNYHRLKEALQPLINRKI---PQLY 472
C2_Dock-D cd08697
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 ...
670-859 5.71e-98

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-D is one of 4 classes of Dock family proteins. The members here include: Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Dock-D are Cdc42-specific GEFs. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-D members contain a functionally uncharacterized domain and a PH domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The PH domain broadly binds to phospholipids and is thought to be involved in targeting the plasma membrane. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176079  Cd Length: 185  Bit Score: 313.49  E-value: 5.71e-98
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  670 YKNQIYVYPKHLKYDSQKCFNKARNITVCIEFKNSDDDGAKPMKCIYGKPGGPlFTSSAYTAVLHHSQNPDFSDEVKIEL 749
Cdd:cd08697     1 YKNHLYVYPLHLKYDSQKTFAKARNIAVCIEFRDSDEEDAKPLKCIYYGPGGG-FTTSAYAAVLHHNQNPEFYDEIKIEL 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  750 PTQLHGKHHLLFSFYHITCDInaKANAKKKEALETSVGYAWLPLMK-HDQIASQEYNIPIATTL---PPNYLSIQDPtsa 825
Cdd:cd08697    80 PTQLHEKHHLLFTFYHVSCDI--NKKGKKKDGVETPVGYAWLPLLKdKGRLNSEEQTPPVANLLpnyPDGYLSIQPH--- 154
                         170       180       190
                  ....*....|....*....|....*....|....
gi 755493441  826 khgGSDIKWVDGGKPLFKVSTFVVSTVNTQDPHV 859
Cdd:cd08697   155 ---GPEVKWVDGGKPLFKVSTHLVSTVYTQDQHL 185
DHR2_DOCK6 cd11702
Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also ...
1694-2135 3.60e-97

Dock Homology Region 2, a GEF domain, of Class C Dedicator of Cytokinesis 6; Dock6, also called Zizimin-related 1 (Zir1), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates the small GTPases Rac and Cdc42 by exchanging bound GDP for free GTP. It is widely expressed and shows highest expression in the dorsal root ganglion and the brain. It regulates neurite outgrowth. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class C includes Dock6, 7 and 8. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock6, which contains the catalytic GEF activity for Rac and/or Cdc42.


Pssm-ID: 212575  Cd Length: 423  Bit Score: 321.19  E-value: 3.60e-97
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1694 TPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKrkgywkmekictpplLPEDTQpcdsnlllttpgggsMFS 1773
Cdd:cd11702     1 SPDLRLTWLQNMAGKHSERGNHAEAAHCLVHSAALVAEYLS---------------MLEDCR---------------HLP 50
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1774 MGWPAFLSITPNIKEEGAMKEDSGMQDTP-------YNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVFEKQRDFK 1846
Cdd:cd11702    51 VGCVSFQNISSNVLEESAVSDDILSPDEEgicsgkyFTELGLVGLLEQAAASFNMGGLYEAVNEVYKILIPIHEANRDYK 130
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1847 KLSDLYYDIHRSYLKVAEVVNSEKRLFGRYYRVAFYGqavGFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGADN 1926
Cdd:cd11702   131 KLAVVHGKLQEAFNKITNQSSGWERMFGTYFRVGFYG---CKFGDLDEQEFVYKEPSITKLAEISHRLEEFYTERFGDEV 207
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1927 VKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTT 2006
Cdd:cd11702   208 VEIIKDSNPVDKSKLDPNKAYIQITYVEPFFDTYELKDRVTYFDKNYNLRTFLFCTPFTLDGRAHGELHEQYKRKTILTT 287
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 2007 SHLFPYVKKRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETn 2086
Cdd:cd11702   288 SHAFPYIKTRINVLHREEIVLIPVEVAIEDMQKKTQELAFATHQDPADAKMLQMVLQGCVGTTVNQGPLEVAQVFLSEI- 366
                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 755493441 2087 akkyPDNQvKL------LKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHY 2135
Cdd:cd11702   367 ----PEDP-KLfrhhnkLRLCFKDFTKRCEDALRKNKALIGPDQKEYHRELERNY 416
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
181-301 2.19e-63

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270087  Cd Length: 126  Bit Score: 211.80  E-value: 2.19e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYKGNFNST-VNNTVTVRSFKKRYFQLTQLPDNSYIMNFYKDEKiSKEPKGCIFLDSCTGVVQNNRLRKYAFEL 259
Cdd:cd13267     6 ITKEGYLYKGPENSSdSFISLAMKSFKRRFFHLKQLVDGSYILEFYKDEK-KKEAKGTIFLDSCTGVVQNSKRRKFCFEL 84
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 755493441  260 KMNDLTYFVLAAETESDMDEWIHTLNRILQISPEGPLQGRKS 301
Cdd:cd13267    85 RMQDKKSYVLAAESEAEMDEWISKLNKILQSSKEQSIQKKRS 126
DOCK-C2 pfam14429
C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical ...
670-858 1.68e-59

C2 domain in Dock180 and Zizimin proteins; The Dock180/Dock1 and Zizimin proteins are atypical GTP/GDP exchange factors for the small GTPases Rac and Cdc42 and are implicated cell-migration and phagocytosis. Across all Dock180 proteins, two regions are conserved: C-terminus termed CZH2 or DHR2 (or the Dedicator of cytokinesis) whereas CZH1/DHR1 contain a new family of the C2 domain.


Pssm-ID: 464171  Cd Length: 185  Bit Score: 203.22  E-value: 1.68e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441   670 YKNQIYVYPKHLKYDSQKcFNKARNITVCIEFKNSDddgAKPM-KCIYGKPGGPlFTSSAYTAVLHHSQNPDFSDEVKIE 748
Cdd:pfam14429    4 YRNDLYVTPKSGNFSKQK-KSSARNIEVTVEVRDSD---GEPLpNCIYGGSGGP-FVTEFKSTVYYHNKSPTWYEEIKIA 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441   749 LPTQLHGKHHLLFSFYHITCDinakanaKKKEALETSVGYAWLPLMKHDQ--IASQEYNIPIATT--LPPNYLSIQDPTS 824
Cdd:pfam14429   79 LPAELTPKHHLLFTFYHVSCD-------EKKDKVEKPFGYAFLPLLDDDGafLRDGEHTLPVYKYdeLPPGYLSLPWSSG 151
                          170       180       190
                   ....*....|....*....|....*....|....
gi 755493441   825 AKHGGSDIKWVDGGKPLFKVSTFVVSTVNTQDPH 858
Cdd:pfam14429  152 GEKESSALPGLKGGKDLFKVRTRLCSTKYTQDEH 185
DHR-2_Lobe_A pfam06920
DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic ...
1682-1864 3.80e-55

DHR-2, Lobe A; This entry represents a conserved region within a number of eukaryotic dedicator of cytokinesis proteins (DOCK), which are guanine nucleotide exchange factors (GEFs), that activate some small GTPases by exchanging bound GDP for free GTP such as Rac. These proteins have a DOCK-homology region 1 (DHR-1, also known as DOCK-type C2 domain) at the N-terminus and a DHR-2 (also known as DOCKER domain) at the C-terminal. The DHR-2 is a GEF catalytic domain organized into three lobes, A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe A, formed from an antiparallel array of alpha helices that adopts a tetratricopeptide repeat-like fold, which through extensive contacts with lobe B, stabilizes DHR-2 domain.


Pssm-ID: 462040 [Multi-domain]  Cd Length: 154  Bit Score: 189.43  E-value: 3.80e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  1682 DLQYSLANSYASTPELRRTWLESMAKIHARNGDLSEAAMCYIHIAALIAEYLKRKgywkmekictppllpedtqpcdsnl 1761
Cdd:pfam06920    1 DLQYSLANSYKSSPDLRLTWLENLAEKHLENGNFSEAAQCLIHIAALIAEYLKLK------------------------- 55
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  1762 llttpgGGSMFSMGWPAFLSITPNI-KEEGAMKEDSGMQDTP-YNENILVEQLYMCVEFLWKSERYELIADVNKPIIAVF 1839
Cdd:pfam06920   56 ------GKIPNPLGASAFEKISPNIlREESALKDDSGVCDSPhFTEDGLVGLLEEAIDYLDKAERYELAIELYKLLLPIY 129
                          170       180
                   ....*....|....*....|....*
gi 755493441  1840 EKQRDFKKLSDLYYDIHRSYLKVAE 1864
Cdd:pfam06920  130 ESRRDYKKLSECHGKLAEAYEKIVE 154
C2_Dock-C cd08696
C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 ...
670-859 3.68e-53

C2 domains found in Dedicator Of CytoKinesis (Dock) class C proteins; Dock-C is one of 4 classes of Dock family proteins. The members here include: Dock6/Zir1, Dock7/Zir2, and Dock8/Zir3. Dock-C members are GEFs for both Rac and Cdc42. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-C members contain a functionally uncharacterized domain upstream of the C2 domain. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176078  Cd Length: 179  Bit Score: 184.86  E-value: 3.68e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  670 YKNQIYVYPKHLKYDSQKcfNKARNITVCIEFKNSDDDGAKPMKCIYGKpGGPLFTSSAYTAVLHHSQNPDFSDEVKIEL 749
Cdd:cd08696     1 YRNLLYVYPQSLNFSNRL--GSARNIAVKVQLMSGEDESQALPVIFKGS-SPEEFLTEAYTAVTYHNKSPDFYDEIKIKL 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  750 PTQLHGKHHLLFSFYHITCdinakANAKKKEALETSVGYAWLPLMKHDQIASQEYNIPIATTLPPNYLSIQDPTSAKHGg 829
Cdd:cd08696    78 PADLTDNHHLLFTFYHISC-----QKKQEGGSVETPIGYTWLPLLRNGRLQSGEFNLPVSLEKPPSNYSPDSPEVKLPG- 151
                         170       180       190
                  ....*....|....*....|....*....|
gi 755493441  830 sdIKWVDGGKPLFKVSTFVVSTVNTQDPHV 859
Cdd:cd08696   152 --TKWVDNHKGVFSVSVEAVSSVHTQDSYL 179
DOCK_C-D_N pfam11878
Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the ...
44-154 8.34e-44

Dedicator of cytokinesis C/D, N terminal; This entry represents the N-terminal domain of the DOCK-C subfamily (DOCK 6, 7, 8) and DOCK-D subfamily (DOCK 9, 10, 11). DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases, required during several cellular processes, such as cell motility and phagocytosis. DOCK proteins are categorized into four subfamilies based on their sequence homology: DOCK-A (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11).


Pssm-ID: 463380  Cd Length: 112  Bit Score: 155.12  E-value: 8.34e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441    44 PRLLDPLDYETVIEELEKTYRDDPLQDLLFFPSDDFSTATVSWDIRTLYSTVPEEAEHRAESlLVKEACKFYSSQWYVVN 123
Cdd:pfam11878    1 PKVVEPLDYEEFISQHLTQIENDPLRDLLLFPDDDIEVSVIPRECRTLQPTVPEEAEKEADP-LVRECIKTYTSDWHVVN 79
                           90       100       110
                   ....*....|....*....|....*....|...
gi 755493441   124 YKYEQYSGDIRQLPRAE--HKPEKLPSHSFEVD 154
Cdd:pfam11878   80 YKYEDYSGDFRQLPKSKrrERPEKLPKQVFEID 112
DHR-2_Lobe_C pfam20421
DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
2043-2143 1.63e-38

DHR-2, Lobe C; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange factors (GEFs) that activate some small GTPases, such as Rac or Cdc42, by exchanging bound GDP for free GTP to control cell migration, morphogenesis, and phagocytosis. These proteins share a DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1) at the N-terminal, and the DHR-2 domain (also termed the DOCKER domain) at the C-terminal. DHR-2 is the GEF catalytic domain organized into three lobes A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe C which form an antiparallel four alpha-helical bundle and contains a loop known as the nucleotide sensor characterized by a conserved valine residue essential for catalytic activity.


Pssm-ID: 466570 [Multi-domain]  Cd Length: 103  Bit Score: 139.65  E-value: 1.63e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  2043 ELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKLLKEIFRQFADACGQALDVNERLIKE 2122
Cdd:pfam20421    1 ELEAAINAPPPNIKTLQMVLQGSVDVQVNAGPLEYAEAFLSEKNVDNYPAEKVEKLKEEFRDFLKVCGEALRLNKKLISE 80
                           90       100
                   ....*....|....*....|.
gi 755493441  2123 DQLEYQEELRSHYKDMLSELS 2143
Cdd:pfam20421   81 DQREYQEELEEGFEKLKEKLE 101
C2_DOCK180_related cd08679
C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was ...
670-859 2.85e-37

C2 domains found in Dedicator Of CytoKinesis 1 (DOCK 180) and related proteins; Dock180 was first identified as an 180kd proto-oncogene product c-Crk-interacting protein involved in actin cytoskeletal changes. It is now known that it has Rac-specific GEF activity, but lacks the conventional Dbl homology (DH) domain. There are 10 additional related proteins that can be divided into four classes based on sequence similarity and domain organization: Dock-A which includes Dock180/Dock1, Dock2, and Dock5; Dock-B which includes Dock3/MOCA (modifier of cell adhesion) and Dock4; Dock-C which includes Dock6/Zir1, Dock7/Zir2, and Dock8/Zir3; and Dock-D, which includes Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2/ACG (activated Cdc42-associated GEF). Most of members of classes Dock-A and Dock-B are the GEFs specific for Rac. Those of Dock-D are Cdc42-specific GEFs while those of Dock-C are the GEFs for both. All Dock180-related proteins have two common homology domains: the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker). DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176061  Cd Length: 178  Bit Score: 139.00  E-value: 2.85e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  670 YKNQIYVYPKHLKYDSQKcfNKARNITVCIEFKNSDDDGAKPMKCIYGKpgGPlFTSSAYTAVLHHSQNPDFSDEVKIEL 749
Cdd:cd08679     1 LRNDLYVYPQSGELSKAK--SKGRNIEITVEVRDDDGDIIEPCISAPGS--GS-ELRSEYTSVVYYHKNPVFNDEIKIQL 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  750 PTQLHGKHHLLFSFYHITCDinakanAKKKEALETSVGYAWLPLMKHDQ--IASQEYNIPIAT------TLPPNYLSiqD 821
Cdd:cd08679    76 PADLTPQHHLLFTFYHVSSK------KKQGDKEETPFGYAFLPLMDKDGafIKDGDHTLPVYKydkrpdVGPSGYLS--L 147
                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 755493441  822 PTSAkhggsdiKWVDGGKPLFKVSTFVVSTVNTQDPHV 859
Cdd:cd08679   148 PSTL-------ANGKSSKDTFKIKTRLCSTILTQDKSL 178
DHR-2_Lobe_B pfam20422
DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange ...
1933-2008 8.14e-37

DHR-2, Lobe B; DOCK (dedicator of cytokinesis) proteins are guanine nucleotide exchange factors (GEFs) that activate some small GTPases, such as Rac or Cdc42, by exchanging bound GDP for free GTP to control cell migration, morphogenesis, and phagocytosis. These proteins share a DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1) at the N-terminal, and the DHR-2 domain (also termed the DOCKER domain) at the C-terminal. DHR-2 is the GEF catalytic domain organized into three lobes A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe B which adopts an unusual architecture of two antiparallel beta sheets disposed in a loosely packed orthogonal arrangement. This lobe changes its position relative to lobe C and the bound GTPase, which suggests that lobe B distinguishes between the switch 1 conformations of Rac1 and Cdc42.


Pssm-ID: 466571 [Multi-domain]  Cd Length: 77  Bit Score: 133.89  E-value: 8.14e-37
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 755493441  1933 SNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGGVAEQCKRRTVLTTSH 2008
Cdd:pfam20422    1 SNPVDESILDPDKAYIQITSVEPYFDDSELNDRVTYFERNNNVNRFVFETPFTKSGKAQGEFEEQWKRRTILTTEH 76
DHR2_DOCK_A cd11697
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK ...
1808-2138 9.49e-17

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. Class A DOCKs are specific GEFs for Rac. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. Dock2 plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction. Dock5 functions upstream of Rac1 to regulate osteoclast function. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class A DOCKs, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212570  Cd Length: 400  Bit Score: 85.07  E-value: 9.49e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1808 LVEQLYM-CVEFLWKSERYELIADVNKPIIAVFEKQR-DFKKLSDLYYDIHRSYLKVAEVVNSEKRlfgrYYRVAFYGQA 1885
Cdd:cd11697    59 LKEALYYdIIDYFDKGKMWECAISLCKELAEQYENETfDYLQLSELLKRMATFYDNIMKTLRPEPE----YFRVGYYGQG 134
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1886 vgFFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKfgadnvkiiQDSNKVNPKDLDPKYA---YIQVTYVTPFFEE--- 1959
Cdd:cd11697   135 --FPSFLRNKVFIYRGKEYERLSDFSARLLNQFPNA---------ELMNTLTPPGDEIKESpgqYLQINKVDPVMDErpr 203
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1960 ---KEIEDRKTDFEMHHNINRFVFETPFTLSGKKHGG-VAEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAID 2035
Cdd:cd11697   204 fkgKPVSDQILNYYKVNEVQRFTFSRPFRRGTKDPDNeFANMWLERTTLTTAYKLPGILRWFEVVSTSTVEISPLENAIE 283
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 2036 EMSRKVSELNQLCTTEEVD----MIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKL--LKEIFRQFADAC 2109
Cdd:cd11697   284 TMEDTNKKIRDLILQHQSDptlpINPLSMLLNGIVDAAVMGGIANYEKAFFTEEYLDEHPEDQELIerLKDLIAEQIPLL 363
                         330       340
                  ....*....|....*....|....*....
gi 755493441 2110 GQALDVNERLIKEDQLEYQEELRSHYKDM 2138
Cdd:cd11697   364 EAGLKIHKQKAPESLRPLHERMEECFAKM 392
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
181-289 5.03e-14

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 69.88  E-value: 5.03e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441    181 VFKSGWLYKgnfnstvNNTVTVRSFKKRYFQLTqlpdNSYIMnFYKDEK--ISKEPKGCIFLDSCT---GVVQNNRLRKY 255
Cdd:smart00233    1 VIKEGWLYK-------KSGGGKKSWKKRYFVLF----NSTLL-YYKSKKdkKSYKPKGSIDLSGCTvreAPDPDSSKKPH 68
                            90       100       110
                    ....*....|....*....|....*....|....
gi 755493441    256 AFELKMNDLTYFVLAAETESDMDEWIHTLNRILQ 289
Cdd:smart00233   69 CFEIKTSDRKTLLLQAESEEEREKWVEALRKAIA 102
DHR2_DOCK_B cd11696
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK ...
1833-2142 3.73e-13

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. As GEFs, they activate small GTPases by exchanging bound GDP for free GTP. They are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. Dock3 is a specific GEF for Rac and it regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. Dock4 activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. It plays a role in regulating dendritic growth and branching in hippocampal neurons, where it is highly expressed. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of class B DOCKs, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212569  Cd Length: 391  Bit Score: 73.63  E-value: 3.73e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1833 KPIIAVFEKQRDFKKLSDlyydIHRSYLKVAEVVNSEKRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQ 1912
Cdd:cd11696    81 RELAELYESLYDYAKLSH----ILRMEASFYDNILTQLRPEPEYFRVGFYGKGFPLFLRNKQ--FVYRGLDYERIGAFTQ 154
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1913 RLLKLYAdkfgadNVKIIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKE------IEDRKTDFEMHHNINRFVFETPFtl 1986
Cdd:cd11696   155 RLQSEFP------QAHILTKNTPPDDAILQADGQYIQICNVKPVPERRPvlqmvgVPDKVRSFYRVNDVRKFQYDRPI-- 226
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1987 sgkkHGGVAEQCKR-------RTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIR-- 2057
Cdd:cd11696   227 ----HKGPIDKDNEfkslwieRTTLVTEHSLPGILRWFEVVSREVEEIPPVENACETVENKNQELRSLISQYQADPTRni 302
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 2058 --LQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDN--QVKLLKEIFRQFADACGQALDVNERLIKEDQLEYQEELRS 2133
Cdd:cd11696   303 npFSMRLQGVIDAAVNGGIAKYQEAFFTPEFILSHPEDaeHIARLRELILEQVQILEAGLALHGKLAPPEVRPLHKRLVE 382

                  ....*....
gi 755493441 2134 HYKDMLSEL 2142
Cdd:cd11696   383 RFTQMKQSL 391
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
181-287 1.75e-12

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270133  Cd Length: 112  Bit Score: 65.90  E-value: 1.75e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYKgnfnSTVNNTVTVRSFKKRYFQL--TQLPDNSYIMNFYKDEKiSKEPKGCIFLDSC----TGVVQNNRLRK 254
Cdd:cd13324     1 VVYEGWLTK----SPPEKKIWRAAWRRRWFVLrsGRLSGGQDVLEYYTDDH-CKKLKGIIDLDQCeqvdAGLTFEKKKFK 75
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 755493441  255 YA--FELKMNDLTYFvLAAETESDMDEWIHTLNRI 287
Cdd:cd13324    76 NQfiFDIRTPKRTYY-LVAETEEEMNKWVRCICQV 109
DHR2_DOCK5 cd11708
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an ...
1803-2101 2.61e-12

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 5; Dock5 is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It functions upstream of Rac1 to regulate osteoclast function. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock5, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock5, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212581  Cd Length: 400  Bit Score: 71.13  E-value: 2.61e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1803 YNENILVEQLYM-CVEFLWKSERYELIADVNKPIIAVFEKQR-DFKKLSDLYYDIHRSYlkvaEVVNSEKRLFGRYYRVA 1880
Cdd:cd11708    54 YTQQELKERLYQeIISFFDKGKMWEKAIELSKELADMYENQVfDYEGLGNLLKKQAQFY----ENIMKAMRPQPEYFAVG 129
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1881 FYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADKFGADNVKIIQDSNKVNPKDldpkyaYIQVTYVTPF---- 1956
Cdd:cd11708   130 YYGQGFPSFLRNKI--FIYRGKEYERLEDFSLKLLTQFPNAEKMTSTSPPGDEIKSSTKQ------YVQCFTVKPVmnlp 201
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1957 --FEEKEIEDRKTDFEMHHNINRFVFETPFTlSGKK--HGGVAEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEV 2032
Cdd:cd11708   202 shYKDKPVPEQILNYYRANEVQQFQYSRPFR-KGEKdpDNEFATMWIERTTFTTAYRFPGILKWFEVKQISTEEISPLEN 280
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 755493441 2033 AIDEM---SRKVSEL-NQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQ--VKLLKEI 2101
Cdd:cd11708   281 AIETMeltNEKISNLvQQHAWDRSLPVHPLSMLLNGIVDPAVMGGFSNYEKAFFTEKYLQEHPEDQekIELLKQL 355
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
183-286 3.55e-12

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 65.34  E-value: 3.55e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  183 KSGWLYK-GNFNstvnntvtvRSFKKRYFQLTqlpDNsyiMNFYKDEKISKEPKGCIFLDSCTgVVQNNRLRKYAFELKM 261
Cdd:cd13288    10 KEGYLWKkGERN---------TSYQKRWFVLK---GN---LLFYFEKKGDREPLGVIVLEGCT-VELAEDAEPYAFAIRF 73
                          90       100
                  ....*....|....*....|....*...
gi 755493441  262 NDL---TYfVLAAETESDMDEWIHTLNR 286
Cdd:cd13288    74 DGPgarSY-VLAAENQEDMESWMKALSR 100
DHR2_DOCK3 cd11704
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also ...
1846-2142 4.41e-12

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 3; Dock3, also called modifier of cell adhesion (MOCA), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. Dock3 is a specific GEF for Rac. It regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock3, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212577  Cd Length: 392  Bit Score: 70.42  E-value: 4.41e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1846 KKLSDLYYDihrsylkvaeVVNSEKRLFGRYYRVAFYGQAVgfFEEEEGKEYIYKEPKLTGLSEISQRLLKLYADKFGad 1925
Cdd:cd11704   100 RKMEAAYYD----------NIMEQQRLEPEFFRVGFYGRKF--PFFLRNKEYVCRGHDYERLEAFQQRMLSEFPQAIA-- 165
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1926 nvkiIQDSNKVNPKDLDPKYAYIQVTYVTPF------FEEKEIEDRKTDFEMHHNINRFVFETPFTLSGK-KHGGVAEQC 1998
Cdd:cd11704   166 ----MQHPNHPDDGILQCDAQYLQIYAVTPIpdnmdvLQMDRVPDRIKSFYRVNNVRKFRYDRPFHKGPKdKENEFKSLW 241
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1999 KRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSRKVSELNQLCTTEEVDMIR-----LQLKLQGSVSVKVNAG 2073
Cdd:cd11704   242 IERTTLTLTHSLPGISRWFEVERRELVEVSPLENAIQVVENKNQELRTLISQYQHKQLHgninlLSMCLNGVIDAAVNGG 321
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 755493441 2074 PMAYARAFLEETNAKKYPDNQVKL--LKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2142
Cdd:cd11704   322 IARYQEAFFDKDYISKHPGDAEKItqLKELMQEQVHVLGVGLAVHEKFVHPEMRPLHKKLIDQFQMMRSSL 392
PH pfam00169
PH domain; PH stands for pleckstrin homology.
181-288 8.36e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 63.74  E-value: 8.36e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441   181 VFKSGWLYK-GNFNSTvnntvtvrSFKKRYFQLTqlpdNSYIMnFYKDEKI--SKEPKGCIFLDSCTGV---VQNNRLRK 254
Cdd:pfam00169    1 VVKEGWLLKkGGGKKK--------SWKKRYFVLF----DGSLL-YYKDDKSgkSKEPKGSISLSGCEVVevvASDSPKRK 67
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 755493441   255 YAFELKMNDLTY---FVLAAETESDMDEWIHTLNRIL 288
Cdd:pfam00169   68 FCFELRTGERTGkrtYLLQAESEEERKDWIKAIQSAI 104
DHR2_DOCK2 cd11706
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a ...
1788-2138 1.11e-11

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 2; Dock2 is a hematopoietic cell-specific, class A DOCK and is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock2, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock2, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212579  Cd Length: 421  Bit Score: 69.25  E-value: 1.11e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1788 EEGAMKEDSGMQDTPYNENILVEQLY-MCVEFLWKSERYELIADVNKPIIAVFEKQ-RDFKKLSDLYYDIHRSYLKVAEV 1865
Cdd:cd11706    57 EQCASQVMQTGQQHPQTQRQLKETLYeTIIGYFDKGKMWEEAISLCKELAEQYEMEiFDYELLSQNLIQQAKFYESIMKI 136
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1866 VnsekRLFGRYYRVAFYGQAVGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYAdkfgadNVKIIQDSNKVNPKDLDPKY 1945
Cdd:cd11706   137 L----RPKPDYFAVGYYGQGFPSFLRNKV--FIYRGKEYERREDFQMQLMSQFP------NAEKLNTTSAPGDDIKNSPG 204
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1946 AYIQVTYVTPFFEE------KEIEDRKTDFEMHHNINRFVFETPFtlsgkKHGGV------AEQCKRRTVLTTSHLFPYV 2013
Cdd:cd11706   205 QYIQCFTVQPVLEEhprlknKPVPDQIINFYKSNYVQRFHYSRPV-----RKGPVdpenefASMWIERTTFVTAYKLPGI 279
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 2014 KKRIQVISQSSTELNPIEVAIDEMSRK----VSELNQLCTTEEVDMIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKK 2089
Cdd:cd11706   280 LRWFEVTHMSQTTISPLENAIETMSTTnekiLMMINQYQSDESLPINPLSMLLNGIVDPAVMGGFAKYEKAFFTEEYVRD 359
                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|.
gi 755493441 2090 YPDNQVKL--LKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDM 2138
Cdd:cd11706   360 HPEDQDKLtrLKDLIAWQIPLLGAGIKIHGKRVTDDLRPFHERMEECFKQL 410
PH_Gab2_2 cd13384
Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily ...
181-284 2.69e-11

Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. Members here include insect, nematodes, and crustacean Gab2s. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241535  Cd Length: 115  Bit Score: 62.46  E-value: 2.69e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYKgnfnSTVNNTVTVRSFKKRYFQLTQLP-DNSYIMNFYKDEKISKEpKGCIFLDSCTGVVQ-------NNRL 252
Cdd:cd13384     3 VVYEGWLTK----SPPEKRIWRAKWRRRYFVLRQSEiPGQYFLEYYTDRTCRKL-KGSIDLDQCEQVDAgltfetkNKLK 77
                          90       100       110
                  ....*....|....*....|....*....|..
gi 755493441  253 RKYAFELKMNDLTYFvLAAETESDMDEWIHTL 284
Cdd:cd13384    78 DQHIFDIRTPKRTYY-LVADTEDEMNKWVNCI 108
DHR2_DOCK4 cd11705
Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an ...
1839-2142 6.80e-11

Dock Homology Region 2, a GEF domain, of Class B Dedicator of Cytokinesis 4; Dock4 is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. It plays a role in regulating dendritic growth and branching in hippocampal neurons, where it is highly expressed. It may also regulate spine morphology and synapse formation. Dock4 activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class B includes Dock3 and 4. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock4, which contains the catalytic GEF activity for Rac and/or Cdc42. Class B DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212578  Cd Length: 391  Bit Score: 66.59  E-value: 6.80e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1839 FEKQRDFKKLSDLYYDIHRSYLKVAEvvnsEKRLFGRYYRVAFYGQAVgfFEEEEGKEYIYKEPKLTGLSEISQRLLKLY 1918
Cdd:cd11705    87 YESYYDYRNLSKMRMMEASLYDKIMD----QQRLEPEFFRVGFYGKKF--PFFLRNKEFVCRGHDYERLEAFQQRMLNEF 160
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1919 ADKFGadnvkiIQDSNKVNPKDLDPKYAYIQVTYVTPFFEEKEIEDR-------KTDFEMHHnINRFVFETPFTLSGK-K 1990
Cdd:cd11705   161 PHAIA------MQHANQPDETIFQAEAQYLQIYAVTPIPESQEVLQRdgvpdniKSFYKVNH-IWRFRYDRPFHKGTKdK 233
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1991 HGGVAEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAIDEMSRKVSELNQL---CTTEEVDMIR-LQLKLQGSV 2066
Cdd:cd11705   234 ENEFKSLWVERTTLTLVQSLPGISRWFEVEKREVVEMSPLENAIEVLENKNQQLRTLisqCQTRQMQNINpLTMCLNGVI 313
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 755493441 2067 SVKVNAGPMAYARAFLEETNAKKYPDNQVKL--LKEIFRQFADACGQALDVNERLIKEDQLEYQEELRSHYKDMLSEL 2142
Cdd:cd11705   314 DAAVNGGVSRYQEAFFVKEYILNHPEDGDKItrLRELMLEQAQILEFGLAVHEKFVPQDMRPLHKKLVDQFFVMKSSL 391
DHR2_DOCK1 cd11707
Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also ...
1808-2099 3.20e-10

Dock Homology Region 2, a GEF domain, of Class A Dedicator of Cytokinesis 1; Dock1, also called Dock180, is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. As a GEF, it activates small GTPases by exchanging bound GDP for free GTP. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. In the nervous system, it mediates attractive responses to netrin-1 and thus, plays a role in axon outgrowth and pathfinding. DOCK proteins are divided into four classes (A-D) based on sequence similarity and domain architecture; class A includes Dock1, 2 and 5. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate. This alignment model represents the DHR-2 domain of Dock1, which contains the catalytic GEF activity for Rac and/or Cdc42. Class A DOCKs, like Dock1, are specific GEFs for Rac and they contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus.


Pssm-ID: 212580  Cd Length: 400  Bit Score: 64.67  E-value: 3.20e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1808 LVEQLYM-CVEFLWKSERYELIADVNKPIIAVFEKQR-DFKKLSDLYYDIHRSYLKVAEVVNSEKRlfgrYYRVAFYGQA 1885
Cdd:cd11707    59 LKDQLYQeIIHYFDKGKMWEEAIALGKELAEQYENEMfDYEQLSELLKKQAQFYENIVKVIRPKPD----YFAVGYYGQG 134
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1886 VGFFEEEEGkeYIYKEPKLTGLSEISQRLLKLYADkfgADNVKiiqdsnKVNPKDLDPKYA---YIQVTYVTPF------ 1956
Cdd:cd11707   135 FPTFLRNKM--FIYRGKEYERREDFEARLLTQFPN---AEKMK------TTSPPGDDIKNSsgqYIQCFTVKPLlelppk 203
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441 1957 FEEKEIEDRKTDFEMHHNINRFVFETPFTlSGKKH--GGVAEQCKRRTVLTTSHLFPYVKKRIQVISQSSTELNPIEVAI 2034
Cdd:cd11707   204 FQNKPVSEQIVSFYRVNEVQRFQYSRPVR-KGEKDpdNEFANMWIERTTYVTAYKLPGILRWFEVKSVFMVEISPLENAI 282
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755493441 2035 DEMSRKVSELNQLCTTEEVD----MIRLQLKLQGSVSVKVNAGPMAYARAFLEETNAKKYPDNQVKLLK 2099
Cdd:cd11707   283 ETMQLTNEKINNMVQQHLNDpnlpINPLSMLLNGIVDPAVMGGFANYEKAFFTEKYMQEHPEDHEKIEK 351
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
183-284 5.15e-10

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 58.32  E-value: 5.15e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  183 KSGWLYKgnfnstvNNTVTVRSFKKRYFQLtqlpDNSYIMNFYKDEKISKEPKGCIFLDSCTGVVQNNRL-RKYAFELKM 261
Cdd:cd00821     1 KEGYLLK-------RGGGGLKSWKKRWFVL----FEGVLLYYKSKKDSSYKPKGSIPLSGILEVEEVSPKeRPHCFELVT 69
                          90       100
                  ....*....|....*....|...
gi 755493441  262 NDLTYFVLAAETESDMDEWIHTL 284
Cdd:cd00821    70 PDGRTYYLQADSEEERQEWLKAL 92
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
181-288 5.55e-10

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270083  Cd Length: 114  Bit Score: 58.93  E-value: 5.55e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYK-GNFnstvnntvtVRSFKKRYFQLtqlpdNSYIMNFYKDEKISKePKGCIFLDSCT-GVVQNNRLR--KYA 256
Cdd:cd13263     3 PIKSGWLKKqGSI---------VKNWQQRWFVL-----RGDQLYYYKDEDDTK-PQGTIPLPGNKvKEVPFNPEEpgKFL 67
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 755493441  257 FEL---------KMNDLTYfVLAAETESDMDEWIHTLNRIL 288
Cdd:cd13263    68 FEIipggggdrmTSNHDSY-LLMANSQAEMEEWVKVIRRVI 107
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
181-285 5.83e-09

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270068  Cd Length: 104  Bit Score: 55.36  E-value: 5.83e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYKgnfnstVNNTvTVRSFKKRYFQLTQlpdnsYIMNFYKDEKiSKEPKGCIFLDSCT---GVVQNNRLRKYAF 257
Cdd:cd13248     7 VVMSGWLHK------QGGS-GLKNWRKRWFVLKD-----NCLYYYKDPE-EEKALGSILLPSYTispAPPSDEISRKFAF 73
                          90       100
                  ....*....|....*....|....*...
gi 755493441  258 ELKMNDLTYFVLAAETESDMDEWIHTLN 285
Cdd:cd13248    74 KAEHANMRTYYFAADTAEEMEQWMNAMS 101
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
183-287 2.10e-08

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270108  Cd Length: 103  Bit Score: 54.01  E-value: 2.10e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  183 KSGWLYKGNFNStvnNTVTVRSFKKRYFQLTqlpDNsyIMNFYKDEKISKEPKGCIFLDSCTGVVQNNrLRKYAFELKMN 262
Cdd:cd13296     1 KSGWLTKKGGGS---STLSRRNWKSRWFVLR---DT--VLKYYENDQEGEKLLGTIDIRSAKEIVDND-PKENRLSITTE 71
                          90       100
                  ....*....|....*....|....*
gi 755493441  263 DLTYFvLAAETESDMDEWIHTLNRI 287
Cdd:cd13296    72 ERTYH-LVAESPEDASQWVNVLTRV 95
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
183-291 2.67e-08

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270095  Cd Length: 106  Bit Score: 53.86  E-value: 2.67e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  183 KSGWLYK-GNFnstvnntvtVRSFKKRYFQLTQlpdnSYIMNFyKDEKI--SKEPKGCIFLDSCTGV--VQNNRLRKYAF 257
Cdd:cd13276     1 KAGWLEKqGEF---------IKTWRRRWFVLKQ----GKLFWF-KEPDVtpYSKPRGVIDLSKCLTVksAEDATNKENAF 66
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 755493441  258 ELKMNDLTYFvLAAETESDMDEWIHTLNR-ILQIS 291
Cdd:cd13276    67 ELSTPEETFY-FIADNEKEKEEWIGAIGRaIVKHS 100
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
183-289 5.44e-08

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241282  Cd Length: 105  Bit Score: 52.98  E-value: 5.44e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  183 KSGWLYKGNFNSTvnntvtvRSFKKRYFQLtqlpDNSYIMnfYKDEKISKEPKGCIFLDSC-------TGVVQN-NRLRK 254
Cdd:cd01251     4 KEGYLEKTGPKQT-------DGFRKRWFTL----DDRRLM--YFKDPLDAFPKGEIFIGSKeegysvrEGLPPGiKGHWG 70
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 755493441  255 YAFELKMNDLTyFVLAAETESDMDEWIHTLNRILQ 289
Cdd:cd01251    71 FGFTLVTPDRT-FLLSAETEEERREWITAIQKVLE 104
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
183-289 8.12e-08

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269954  Cd Length: 119  Bit Score: 52.70  E-value: 8.12e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  183 KSGWLYK--GNfnstvnntvtVRSFKKRYFQLTqlpDNSYimnFYKDEKISKEPKGCIFLDSCTGVVQNNRLRKYAFEL- 259
Cdd:cd01252     5 REGWLLKlgGR----------VKSWKRRWFILT---DNCL---YYFEYTTDKEPRGIIPLENLSVREVEDKKKPFCFELy 68
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 755493441  260 --------------------KMNDLTYFvLAAETESDMDEWIHTLNRILQ 289
Cdd:cd01252    69 spsngqvikacktdsdgkvvEGNHTVYR-ISAASEEERDEWIKSIKASIS 117
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
183-289 1.15e-07

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 51.53  E-value: 1.15e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  183 KSGWLYK-GNfnstvnntvTVRSFKKRYFQLtqlpDNSYIMnFYKDEK-ISKEPKGCIFLDSCTGVVQNNRLRkyAFELK 260
Cdd:cd13282     1 KAGYLTKlGG---------KVKTWKRRWFVL----KNGELF-YYKSPNdVIRKPQGQIALDGSCEIARAEGAQ--TFEIV 64
                          90       100
                  ....*....|....*....|....*....
gi 755493441  261 MNDLTYFvLAAETESDMDEWIHTLNRILQ 289
Cdd:cd13282    65 TEKRTYY-LTADSENDLDEWIRVIQNVLR 92
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
183-284 3.46e-07

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270073  Cd Length: 94  Bit Score: 50.08  E-value: 3.46e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  183 KSGWLYKgnfNSTVNNTvtvRSFKKRYFQLtqlpDNSYIMnFYKDEKiSKEPKGCIFLDSCTGV--VQNNRlrkyaFELK 260
Cdd:cd13253     2 KSGYLDK---QGGQGNN---KGFQKRWVVF----DGLSLR-YFDSEK-DAYSKRIIPLSAISTVraVGDNK-----FELV 64
                          90       100
                  ....*....|....*....|....
gi 755493441  261 MNDLTyFVLAAETESDMDEWIHTL 284
Cdd:cd13253    65 TTNRT-FVFRAESDDERNLWCSTL 87
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
181-285 1.01e-06

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 49.16  E-value: 1.01e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYKgnfnstvnNTVTVRSFKKRYFQL--TQLpdnSYimnfYKDEKISKePKGCIFLDSCTGV-VQNNRLRKYAF 257
Cdd:cd13298     6 VLKSGYLLK--------RSRKTKNWKKRWVVLrpCQL---SY----YKDEKEYK-LRRVINLSELLAVaPLKDKKRKNVF 69
                          90       100
                  ....*....|....*....|....*...
gi 755493441  258 ELKMNDLTYFvLAAETESDMDEWIHTLN 285
Cdd:cd13298    70 GIYTPSKNLH-FRATSEKDANEWVEALR 96
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
183-285 2.95e-06

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 47.70  E-value: 2.95e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  183 KSGWLYKGNFnstvnntvTVRSFKKRYFQLTQlpdnsYIMNFYKDeKISKEPKGCIFLDSCTGVVQNNRLRK-YAFELKM 261
Cdd:cd10573     5 KEGYLTKLGG--------IVKNWKTRWFVLRR-----NELKYFKT-RGDTKPIRVLDLRECSSVQRDYSQGKvNCFCLVF 70
                          90       100
                  ....*....|....*....|....
gi 755493441  262 NDLTYFvLAAETESDMDEWIHTLN 285
Cdd:cd10573    71 PERTFY-MYANTEEEADEWVKLLK 93
PH_M-RIP cd13275
Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed ...
183-296 3.06e-06

Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed to play a role in myosin phosphatase regulation by RhoA. M-RIP contains 2 PH domains followed by a Rho binding domain (Rho-BD), and a C-terminal myosin binding subunit (MBS) binding domain (MBS-BD). The amino terminus of M-RIP with its adjacent PH domains and polyproline motifs mediates binding to both actin and Galpha. M-RIP brings RhoA and MBS into close proximity where M-RIP can target RhoA to the myosin phosphatase complex to regulate the myosin phosphorylation state. M-RIP does this via its C-terminal coiled-coil domain which interacts with the MBS leucine zipper domain of myosin phosphatase, while its Rho-BD, directly binds RhoA in a nucleotide-independent manner. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270094  Cd Length: 104  Bit Score: 47.71  E-value: 3.06e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  183 KSGWLYK-GNFNStvnntvtvrSFKKRYFQLTqlpDNSyiMNFYKDEKI--SKEPKGCIFLDSCTGVVQNNRLRKYAFEL 259
Cdd:cd13275     1 KKGWLMKqGSRQG---------EWSKHWFVLR---GAA--LKYYRDPSAeeAGELDGVIDLSSCTEVTELPVSRNYGFQV 66
                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 755493441  260 KMNDLTYFVLAAETESDMDEWIHTLNRILQISPEGPL 296
Cdd:cd13275    67 KTWDGKVYVLSAMTSGIRTNWIQALRKAAGLPSPPAL 103
PH_Gab1_Gab2 cd01266
Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily ...
181-292 3.43e-06

Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. The members in this cd include the Gab1 and Gab2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241297  Cd Length: 123  Bit Score: 48.40  E-value: 3.43e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYKgnfnSTVNNTVTVRSFKKRYF-----QLTQLPDnsyIMNFYKDEKiSKEPKGCIFLDSC----TGVVQNNR 251
Cdd:cd01266     4 VVCSGWLRK----SPPEKKLRRYAWKKRWFvlrsgRLSGDPD---VLEYYKNDH-AKKPIRVIDLNLCeqvdAGLTFNKK 75
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 755493441  252 --LRKYAFELKMNDLTYFvLAAETESDMDEWIHTLNRILQISP 292
Cdd:cd01266    76 elENSYIFDIKTIDRIFY-LVAETEEDMNKWVRNICDICGFNP 117
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
181-284 3.02e-05

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269959  Cd Length: 106  Bit Score: 44.97  E-value: 3.02e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYKgnfnstvnntvtVRSFKKRYFQL-TQLPDNSYIMNFYKDEK---ISKEPKGCIFLDSCTGVvqNNRL---R 253
Cdd:cd01257     3 VRKSGYLKK------------LKTMRKRYFVLrAESHGGPARLEYYENEKkfrRNAEPKRVIPLSSCFNI--NKRAdakH 68
                          90       100       110
                  ....*....|....*....|....*....|.
gi 755493441  254 KYAFELKMNDlTYFVLAAETESDMDEWIHTL 284
Cdd:cd01257    69 KHLIALYTKD-ECFGLVAESEEEQDEWYQAL 98
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
183-286 5.76e-05

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269944 [Multi-domain]  Cd Length: 140  Bit Score: 45.30  E-value: 5.76e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  183 KSGWLYK----GNFNSTVNntvtvrsFKKRYFQLTqlpdNSYImNFYKDEKISK-EPKGCIFLDSCTGV--VQNNRL--R 253
Cdd:cd01238     1 LEGLLVKrsqgKKRFGPVN-------YKERWFVLT----KSSL-SYYEGDGEKRgKEKGSIDLSKVRCVeeVKDEAFfeR 68
                          90       100       110
                  ....*....|....*....|....*....|...
gi 755493441  254 KYAFELKMNDLTYFVLAAETESDmDEWIHTLNR 286
Cdd:cd01238    69 KYPFQVVYDDYTLYVFAPSEEDR-DEWIAALRK 100
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
181-286 1.56e-04

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270118  Cd Length: 113  Bit Score: 43.16  E-value: 1.56e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYKGNFNSTvnntvTVRSFKKRYFQLTQlpdnsYIMNFYKDEKiSKEPKGCIFLDSCTGVVQNNRLRKYAFELK 260
Cdd:cd13308     9 VIHSGTLTKKGGSQK-----TLQNWQLRYVIIHQ-----GCVYYYKNDQ-SAKPKGVFSLNGYNRRAAEERTSKLKFVFK 77
                          90       100       110
                  ....*....|....*....|....*....|
gi 755493441  261 M----NDLTYFVLAAETESDMDEWIHTLNR 286
Cdd:cd13308    78 IihlsPDHRTWYFAAKSEDEMSEWMEYIRR 107
PH_RhoGAP2 cd13378
Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 ...
181-288 2.44e-04

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241529  Cd Length: 116  Bit Score: 42.63  E-value: 2.44e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYKgnfnstvnNTVTVRSFKKRYFQLTQlpDNSYimnFYKDEKISKePKGCIFLDSctgvVQNNRLR------- 253
Cdd:cd13378     3 VLKAGWLKK--------QRSIMKNWQQRWFVLRG--DQLF---YYKDEEETK-PQGCISLQG----SQVNELPpnpeepg 64
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 755493441  254 KYAFEL-----------KMNDLTyFVLAAETESDMDEWIHTLNRIL 288
Cdd:cd13378    65 KHLFEIlpggagdrekvPMNHEA-FLLMANSQSDMEDWVKAIRRVI 109
PH_beta_spectrin cd10571
Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a ...
201-285 7.20e-04

Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a major component of the cytoskeleton underlying cellular membranes. Beta spectrin consists of multiple spectrin repeats followed by a PH domain, which binds to inositol-1,4,5-trisphosphate. The PH domain of beta-spectrin is thought to play a role in the association of spectrin with the plasma membrane of cells. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269975  Cd Length: 106  Bit Score: 41.06  E-value: 7.20e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  201 TVRSFKKRYFQLTQLpdnsyIMNFYKDEKISKEPKGC-----IFLDSCTG-VVQNNRLRKYAFELKMNDLTYFVLAAETE 274
Cdd:cd10571    19 SNRSWKNVYTVLRGQ-----ELSFYKDQKAAKSGITYaaeppLNLYNAVCeVASDYTKKKHVFRLKLSDGAEFLFQAKDE 93
                          90
                  ....*....|.
gi 755493441  275 SDMDEWIHTLN 285
Cdd:cd10571    94 EEMNQWVKKIS 104
PH_PLEKHD1 cd13281
Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH ...
181-306 1.42e-03

Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH domain; Human PLEKHD1 (also called UPF0639, pleckstrin homology domain containing, family D (with M protein repeats) member 1) is a single transcript and contains a single PH domain. PLEKHD1 is conserved in human, chimpanzee, , dog, cow, mouse, chicken, zebrafish, and Caenorhabditis elegans. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270099  Cd Length: 139  Bit Score: 41.15  E-value: 1.42e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYKGNFNSTVNNtvtvrsFKKRYFQLTQ-----LPDnSYIMNFYKDEKISKEPKGCIFLDSCTGVVQNNRLRKY 255
Cdd:cd13281    12 VQLHGILWKKPFGHQSAK------WSKRFFIIKEgfllyYSE-SEKKDFEKTRHFNIHPKGVIPLGGCSIEAVEDPGKPY 84
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 755493441  256 AFELKMNDLT-YFVLAAETESDMDEWIHTLNRILQISpegplqgRKSAELAE 306
Cdd:cd13281    85 AISISHSDFKgNIILAADSEFEQEKWLDMLRESGKIT-------WKNAQLGE 129
PH_RhoGap24 cd13379
Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ...
181-288 1.58e-03

Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ARHGAP24, p73RhoGAp, and Filamin-A-associated RhoGAP) like other RhoGAPs are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241530  Cd Length: 114  Bit Score: 40.34  E-value: 1.58e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYK-GNFnstvnntvtVRSFKKRYFQLTQlpDNSYimnFYKDEKISKePKGCIFLdsctgvvQNNRLR------ 253
Cdd:cd13379     3 VIKCGWLRKqGGF---------VKTWHTRWFVLKG--DQLY---YFKDEDETK-PLGTIFL-------PGNRVTehpcne 60
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 755493441  254 ----KYAFE---------LKMNDLTYFVLAAeTESDMDEWIHTLNRIL 288
Cdd:cd13379    61 eepgKFLFEvvpggdrerMTANHETYLLMAS-TQNDMEDWVKSIRRVI 107
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
183-286 2.52e-03

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270070  Cd Length: 98  Bit Score: 39.12  E-value: 2.52e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  183 KSGWLYKGNFNStvnntvtVRSFKKRYFQLtqlpDNSyiMNFYKdeKISKEpkgciflDSCTGVVQNNRL---------- 252
Cdd:cd13250     1 KEGYLFKRSSNA-------FKTWKRRWFSL----QNG--QLYYQ--KRDKK-------DEPTVMVEDLRLctvkptedsd 58
                          90       100       110
                  ....*....|....*....|....*....|....
gi 755493441  253 RKYAFELKMNDLTYfVLAAETESDMDEWIHTLNR 286
Cdd:cd13250    59 RRFCFEVISPTKSY-MLQAESEEDRQAWIQAIQS 91
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
181-285 2.96e-03

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP1 and TAPP2 contain two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270090  Cd Length: 114  Bit Score: 39.65  E-value: 2.96e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYK-GNfnstvnntvTVRSFKKRYFQLTqlpDNSyiMNFYKDEKiSKEPKGCIFLDSCTGV----VQNNRLRKY 255
Cdd:cd13271     8 VIKSGYCVKqGA---------VRKNWKRRFFILD---DNT--ISYYKSET-DKEPLRTIPLREVLKVheclVKSLLMRDN 72
                          90       100       110
                  ....*....|....*....|....*....|
gi 755493441  256 AFELKMNDLTYFVlAAETESDMDEWIHTLN 285
Cdd:cd13271    73 LFEIITTSRTFYI-QADSPEEMHSWIKAIS 101
C2_Dock-B cd08695
C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 ...
692-856 3.42e-03

C2 domains found in Dedicator Of CytoKinesis (Dock) class B proteins; Dock-B is one of 4 classes of Dock family proteins. The members here include: Dock3/MOCA (modifier of cell adhesion) and Dock4. Most of these members have been shown to be GEFs specific for Rac, although Dock4 has also been shown to interact indirectly with the Ras family GTPase Rap1, probably through Rap regulatory proteins. In addition to the C2 domain (AKA Dock homology region (DHR)-1, CED-5, Dock180, MBC-zizimin homology (CZH) 1) and the DHR-2 (AKA CZH2, or Docker), which all Dock180-related proteins have, Dock-B members contain a SH3 domain upstream of the C2 domain and a proline-rich region downstream. DHR-2 has the catalytic activity for Rac and/or Cdc42, but is structurally unrelated to the DH domain. The C2/DHR-1 domains of Dock180 and Dock4 have been shown to bind phosphatidylinositol-3, 4, 5-triphosphate (PtdIns(3,4,5)P3). The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176077  Cd Length: 189  Bit Score: 40.83  E-value: 3.42e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  692 ARNITVCIEFknSDDDGAKPMKCIYGKPGGPLftSSAY-TAVLHHSQNPDFSDEVKIELPTQLHGKHHLLFSFYHitCDI 770
Cdd:cd08695    22 AKNIEVTMVV--LDADGQVLKDCISLGSGEPP--CSEYrSFVLYHNNSPRWNETIKLPIPIDKFRGSHLRFEFRH--CST 95
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  771 NAKANAKKkealetsVGYAWLPLMKHD----QIASQE---YNIPIATTL--PPNYLSIqdPTSAKHGGSdikWVDGGKPL 841
Cdd:cd08695    96 KDKGEKKL-------FGFSFVPLMREDgttlPDGSHElyvYKCDENATFldPALYLGL--PCSKEDFQG---CPNSPSPL 163
                         170       180
                  ....*....|....*....|...
gi 755493441  842 FK--------VSTFVVSTVNTQD 856
Cdd:cd08695   164 FSrsskesfwIRTLLCSTKLTQN 186
PH1_TAPP1_2 cd13270
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, N-terminal ...
203-292 4.38e-03

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, N-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP1 and TAPP2 contain two sequential PH domains in which the C-terminal PH domain binds PtdIns(3,4)P2. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270089  Cd Length: 118  Bit Score: 39.03  E-value: 4.38e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  203 RSFKKRYFQLTQlpdNSYIMNFYKDEK----ISKEPKGCIFLDSCTGVVQNNRLR---KYAFELKMNDLTYFvLAAETES 275
Cdd:cd13270    23 GKFLRRYFILDT---AANLLLYYMDNPqnlpVGAAPVGSLNLTYISKVSDATKQRpkaEFCFVINALSRRYF-LQANDQQ 98
                          90
                  ....*....|....*..
gi 755493441  276 DMDEWIHTLNRILQISP 292
Cdd:cd13270    99 DLVEWVEALNNASKITV 115
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
181-294 6.92e-03

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270092  Cd Length: 110  Bit Score: 38.43  E-value: 6.92e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755493441  181 VFKSGWLYKGNFnstvnntvTVRSFKKRYFQLtqlpdNSYIMNFYKDEKIsKEPKGCIFLDSCTGV--VQNNRLRKYAFE 258
Cdd:cd13273     8 VIKKGYLWKKGH--------LLPTWTERWFVL-----KPNSLSYYKSEDL-KEKKGEIALDSNCCVesLPDREGKKCRFL 73
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 755493441  259 LKMNDLTYFVLAAETESDMdEWIHTLNRILQISPEG 294
Cdd:cd13273    74 VKTPDKTYELSASDHKTRQ-EWIAAIQTAIRLSQEG 108
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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