The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810932  16 LRFLEQLSILQTWQQREADLLEDIRSYSKQRAAIEREYGQALQKLAGPFLKREGHRSG---EMDSRGRTVFGAWRCLLDA 92
Cdd:cd07678    1 LRFLEQLSILQTKQQRDAELLEDIRSYSKQRAAIEREYGQALQRLASQFLKRDWHRGGnetEMDRSVRTVWGAWREGTAA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810932  93 TVAGGQTRLQASDRYRDLAGGTGRSAKEQVLRKGTENLQRAQAEVLQSVRELSRSRKLYGQRERVWALAQEKAADVQARL 172
Cdd:cd07678   81 TGQGRVTRLEAYRRLRDEAGKTGRSAKEQVLKKSTEQLQKAQAELLETVKELSKSKKLYGQLERVSEVAKEKAADVEARL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810932 173 NRSDHGIFHSRTSLQKLSTK-------------------------------------------ALVSELSEHLRDPLTSL 209
Cdd:cd07678  161 NKSDHGIFHSKASLQKLSAKfsaqsaeysqqlqaarneyllnlvaanahldhyyqeelpaimkALDGDLYERLRDPLTSL 240

                        250       260
                 ....*....|....*....|...
gi 578810932 210 SHTELEAAEVILEHAHRGEQTTS 232
Cdd:cd07678  241 SHTELEACEVTQEHFHRIEQATS 263

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 578810932 427 PCPAHVVFRYQAGREDELTITEGEWLEVIEEGDADEWVKARNQHGEVGFVPERYLNF 483
Cdd:cd11761    1 PVTCKVLYSYEAQRPDELTITEGEELEVIEDGDGDGWVKARNKSGEVGYVPENYLQF 57

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of FCH and double SH3 domains 1 (FCHSD1); F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. FCH and double SH3 domains 1 (FCHSD1) contains an N-terminal F-BAR domain and two SH3 domains at the C-terminus. It has been characterized only in silico, and its biological function is still unknown. F-BAR domains form banana-shaped dimers with a positively-charged concave surface that binds to negatively-charged lipid membranes. They can induce membrane deformation in the form of long tubules.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810932  16 LRFLEQLSILQTWQQREADLLEDIRSYSKQRAAIEREYGQALQKLAGPFLKREGHRSG---EMDSRGRTVFGAWRCLLDA 92
Cdd:cd07678    1 LRFLEQLSILQTKQQRDAELLEDIRSYSKQRAAIEREYGQALQRLASQFLKRDWHRGGnetEMDRSVRTVWGAWREGTAA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810932  93 TVAGGQTRLQASDRYRDLAGGTGRSAKEQVLRKGTENLQRAQAEVLQSVRELSRSRKLYGQRERVWALAQEKAADVQARL 172
Cdd:cd07678   81 TGQGRVTRLEAYRRLRDEAGKTGRSAKEQVLKKSTEQLQKAQAELLETVKELSKSKKLYGQLERVSEVAKEKAADVEARL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810932 173 NRSDHGIFHSRTSLQKLSTK-------------------------------------------ALVSELSEHLRDPLTSL 209
Cdd:cd07678  161 NKSDHGIFHSKASLQKLSAKfsaqsaeysqqlqaarneyllnlvaanahldhyyqeelpaimkALDGDLYERLRDPLTSL 240

                        250       260
                 ....*....|....*....|...
gi 578810932 210 SHTELEAAEVILEHAHRGEQTTS 232
Cdd:cd07678  241 SHTELEACEVTQEHFHRIEQATS 263

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 578810932 427 PCPAHVVFRYQAGREDELTITEGEWLEVIEEGDADEWVKARNQHGEVGFVPERYLNF 483
Cdd:cd11761    1 PVTCKVLYSYEAQRPDELTITEGEELEVIEDGDGDGWVKARNKSGEVGYVPENYLQF 57

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 578810932   505 AFLAQALYSYTGQSAEELSFPEGALIRLLpraqDGVDDGFWRGEFG-GRVGVFPSLLVE 562
Cdd:smart00326   2 GPQVRALYDYTAQDPDELSFKKGDIITVL----EKSDDGWWKGRLGrGKEGLFPSNYVE 56

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 578810932   432 VVFRYQAGREDELTITEGEWLEVIEEGDaDEWVKARNQHGEVGFVPERYL 481
Cdd:smart00326   7 ALYDYTAQDPDELSFKKGDIITVLEKSD-DGWWKGRLGRGKEGLFPSNYV 55

Fes/CIP4 homology domain; Alignment extended from original report. Highly alpha-helical. Also known as the RAEYL motif or the S. pombe Cdc15 N-terminal domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810932    20 EQLSILQTWQQREADLLEDIRSYSKQRAAIEREYGQALQKLAGpflKREGHRSGEMdsRGRTVFGAWRCLLDATVAGGQT 99
Cdd:smart00055   9 DGFEALLSRLKNGLRLLEDLKKFMRERAKIEEEYAKKLQKLSK---KLRAVRDTEP--EYGSLSKAWEVLLSETDALAKQ 83

                   ...
gi 578810932   100 RLQ 102
Cdd:smart00055  84 HLE 86

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of FCH and double SH3 domains 1 (FCHSD1); F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. FCH and double SH3 domains 1 (FCHSD1) contains an N-terminal F-BAR domain and two SH3 domains at the C-terminus. It has been characterized only in silico, and its biological function is still unknown. F-BAR domains form banana-shaped dimers with a positively-charged concave surface that binds to negatively-charged lipid membranes. They can induce membrane deformation in the form of long tubules.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810932  16 LRFLEQLSILQTWQQREADLLEDIRSYSKQRAAIEREYGQALQKLAGPFLKREGHRSG---EMDSRGRTVFGAWRCLLDA 92
Cdd:cd07678    1 LRFLEQLSILQTKQQRDAELLEDIRSYSKQRAAIEREYGQALQRLASQFLKRDWHRGGnetEMDRSVRTVWGAWREGTAA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810932  93 TVAGGQTRLQASDRYRDLAGGTGRSAKEQVLRKGTENLQRAQAEVLQSVRELSRSRKLYGQRERVWALAQEKAADVQARL 172
Cdd:cd07678   81 TGQGRVTRLEAYRRLRDEAGKTGRSAKEQVLKKSTEQLQKAQAELLETVKELSKSKKLYGQLERVSEVAKEKAADVEARL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578810932 173 NRSDHGIFHSRTSLQKLSTK-------------------------------------------ALVSELSEHLRDPLTSL 209
Cdd:cd07678  161 NKSDHGIFHSKASLQKLSAKfsaqsaeysqqlqaarneyllnlvaanahldhyyqeelpaimkALDGDLYERLRDPLTSL 240

                        250       260
                 ....*....|....*....|...
gi 578810932 210 SHTELEAAEVILEHAHRGEQTTS 232
Cdd:cd07678  241 SHTELEACEVTQEHFHRIEQATS 263

Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 578810932 507 LAQALYSYTGQSAEELSFPEGALIRLLPRAQDGVDDGFWRGEFGGRVGVFPSLLVEEL 564
Cdd:cd11895    1 LARALYSYTGQSPEELSFPEGALIRLLPRAQDGVDDGFWRGEFGGRVGVFPSLLVEEL 58

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 578810932 507 LAQALYSYTGQSAEELSFPEGALIRLLPRAQDGVDDGFWRGEFGGRVGVFPSLLVEE 563
Cdd:cd11762    1 LVRALYDYEAQSDEELSFPEGAIIRILRKDDNGVDDGWWEGEFNGRVGVFPSLVVEE 57

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578810932 509 QALYSYTGQSAEELSFPEGALIRLLPRaQDGVDDGFWRGEFGGRVGVFPSLLVEE 563
Cdd:cd11894    3 KALYDYEGQTDDELSFPEGAIIRILNK-ENQDDDGFWEGEFNGRIGVFPSVLVEE 56

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 578810932 508 AQALYSYTGQSAEELSFPEGALIRLLPRaqdgVDDGFWRGEF-GGRVGVFPS 558
Cdd:cd00174    2 ARALYDYEAQDDDELSFKKGDIITVLEK----DDDGWWEGELnGGREGLFPA 49

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 578810932  510 ALYSYTGQSAEELSFPEGALIRLLPRAqdgvDDGFWRGEFGGRVGVFPSLLVE 562
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIEES----EDGWWEGINTGRTGLVPANYVE 49

First Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the first C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 578810932 430 AHVVFRYQAGREDELTITEGEWLEVIEEGDADEWVKARNQHGEVGFVPERYL 481
Cdd:cd11912    2 AKVLYDYTASGDDEVSISEGEEVTVLEPDDGSGWTKVRNGSGEEGLVPTSYI 53

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 578810932 508 AQALYSYTGQSAEELSFPEGALIRLLPRaqdgVDDGFWRGEFGGR-VGVFPSLLVEE 563
Cdd:cd11825    2 VKALYDYRAQRPDELSFCKHAIITNVEK----EDGGWWRGDYGGKkQKWFPANYVEE 54

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 578810932 510 ALYSYTGQSAEELSFPEGALIRLlpraQDGVDDGFWRGEFGGRVGVFPSLLVEE 563
Cdd:cd11823    4 ALYSYTANREDELSLQPGDIIEV----HEKQDDGWWLGELNGKKGIFPATYVEE 53

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 578810932 508 AQALYSYTGQSAEELSFPEGALIRLLpraqDGVDDGFWRGEFGGRVGVFPSLLVEE 563
Cdd:cd11961    2 AKALYDYDAAEDNELSFFENDKIINI----EFVDDDWWLGECHGSRGLFPSNYVEL 53

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 578810932 430 AHVVFRYQAGREDELTITEGEWLEVIEEGDaDEWVKARNQHGEVGFVPERY 480
Cdd:cd00174    2 ARALYDYEAQDDDELSFKKGDIITVLEKDD-DGWWEGELNGGREGLFPANY 51

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 578810932 508 AQALYSYTGQSAEELSFPEGALIRLLPRaqDGVDDGFWRGEFGGRVGVFPSLLVEE 563
Cdd:cd11875    2 ARVLFDYEAENEDELTLREGDIVTILSK--DCEDKGWWKGELNGKRGVFPDNFVEP 55

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 578810932  436 YQAGREDELTITEGEWLEVIEEGDaDEWVKARNQHGEVGFVP 477
Cdd:pfam00018   6 YTAQEPDELSFKKGDIIIVLEKSE-DGWWKGRNKGGKEGLIP 46

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 578810932  509 QALYSYTGQSAEELSFPEGALIRLLpraqDGVDDGFWRGEF-GGRVGVFPS 558
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVL----EKSEDGWWKGRNkGGKEGLIPS 47

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 578810932 430 AHVVFRYQAGREDELTITEGEWLEVIEEGDADEWVKARNQHGEVGFVPERY 480
Cdd:cd11763    2 VRALYDFDSQPSGELSLRAGEVLTITRQDVGDGWLEGRNSRGEVGLFPSSY 52

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 578810932 510 ALYSYTGQSAEELSFPEGALIRLLPRAqdgvDDGFWRGEFGGRVGVFPSLLVE 562
Cdd:cd11826    4 ALYDYTADKDDELSFQEGDIIYVTKKN----DDGWYEGVLNGVTGLFPGNYVE 52

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578810932 508 AQALYSYTGQSAEELSFPEGALIRLLPRaqdgVDDGFWRGEFGGRVGVFPSLLVE 562
Cdd:cd11786    2 AKALYNYEGKEPGDLSFKKGDIILLRKR----IDENWYHGECNGKQGFFPASYVQ 52

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 578810932 509 QALYSYTGQSAEELSFPEGALIRLLPRaqdgVDDGFWRGEFGGRVG-VFPSLLVEEL 564
Cdd:cd11969    3 KALYDYRAKRSDELSFCKGALIHNVSK----ETGGWWKGDYGGKVQhYFPSNYVEDV 55

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 578810932 509 QALYSYTGQSAEELSFPEGALIRLLprAQDGVDDGFWRGEFGGRVGVFPSLLVEEL 564
Cdd:cd12057    3 KVLFPYEAQNEDELTIKEGDIVTLI--SKDCIDAGWWEGELNGRRGVFPDNFVKLL 56

Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578810932 431 HVV---FRYQAGREDELTITEGEWLEVIEEGDAD-EWVKARNQHGEVGFVPERYL 481
Cdd:cd11903    1 HVVqtlYPFSSVTEEELNFEKGETMEVIEKPENDpEWWKCKNSRGQVGLVPKNYV 55

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 578810932 508 AQALYSYTGQSAEELSFPEGALIRLlpRAQdgVDDGFWRGEFGGRVGVFPSLLVEE 563
Cdd:cd11781    2 ARALYPFKAQSAKELSLKKGDIIYI--RRQ--IDKNWYEGEHNGRVGIFPASYVEI 53

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 578810932 508 AQALYSYTGQSAEELSFPEGALIRLLPRAQDGVDdgFWRGEFGGRVGVFPS 558
Cdd:cd11841    2 VTALYSFEGQQPCDLSFQAGDRITVLTRTDSQFD--WWEGRLRGRVGIFPA 50

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578810932 508 AQALYSYTGQSAEELSFPEGALIRLLPRAQDgVDDGFWRGEFGGRVGVFPSLLVE 562
Cdd:cd11884    2 VVAVRAYITRDQTLLSFHKGDVIKLLPKEGP-LDPGWLFGTLDGRSGAFPKEYVQ 55

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 578810932 508 AQALYSYTGQSAEELSFPEGALIRLLPRaqdgVDDGFWRGEFGGRVGVFPS 558
Cdd:cd11817    2 AVALYDFTGETEEDLSFQRGDRILVTEH----LDAEWSRGRLNGREGIFPR 48

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 578810932 508 AQALYSYTGQSAEELSFPEGALIRLLPRAQDgvdDGFWRGEFGGRVGVFPSLLVEE 563
Cdd:cd11976    2 AKARYDFCARDRSELSLKEGDIIKILNKKGQ---QGWWRGEIYGRVGWFPANYVEE 54

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 578810932 510 ALYSYTGQSAEELSFPEGALIRLLPRAqdgvDDGFWRGEFGGRVGVFPSLLVE 562
Cdd:cd11995    5 GMYDYTAQNDDELAFSKGQIINVLNKE----DPDWWKGELNGQVGLFPSNYVK 53

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578810932 431 HVV---FRYQAGREDELTITEGEWLEVIEEGDAD-EWVKARNQHGEVGFVPERYL 481
Cdd:cd11904    1 HVVqalYPFSSSNDEELNFEKGEVMDVIEKPENDpEWWKCRKANGQVGLVPKNYV 55

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578810932 508 AQALYSYTGQSAEELSFPEGALIRLLpraqDGVDDGFWRGEFGGRVGVFPSLLVE 562
Cdd:cd11959    2 AVALYDYQAADDDEISFDPDDIITNI----EMIDEGWWRGVCRGKYGLFPANYVE 52

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 578810932 430 AHVVFRYQAGREDELTITEGEWLEVIEEGDADEWVKARNqhGEVGFVPERYL 481
Cdd:cd11824    2 YSVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERN--GQKGLVPGTYL 51

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 578810932 429 PAHVVFRYQAGREDELTITEGEWLEVIEEgDADEWVKARNqHGEVGFVPERY 480
Cdd:cd11766    1 PAVVKFNYEAQREDELSLRKGDRVLVLEK-SSDGWWRGEC-NGQVGWFPSNY 50

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578810932 508 AQALYSYTGQSAEELSFPEGALIRLLPRaqdgVDDGFWRGEFGGRVGVFPSLLVE 562
Cdd:cd11782    2 ARAKYNFNADTGVELSFRKGDVITLTRR----VDENWYEGRIGGRQGIFPVSYVQ 52

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578810932 508 AQALYSYTGQSAEELSFPEGALIRLLpraqDGVDDGFWRGEFGGRVGVFPSLLVE 562
Cdd:cd12073    3 AVALYDYQGEGDDEISFDPQETITDI----EMVDEGWWKGTCHGHRGLFPANYVE 53

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 578810932 510 ALYSYTGQSAEELSFPEGALIRLLprAQD-GV--DDGFWRGEFGGRVGVFPSLLVEE 563
Cdd:cd11876    4 ALFDYDARGEDELTLRRGQPVEVL--SKDaAVsgDEGWWTGKIGDKVGIFPSNYVAP 58