The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of FCH and double SH3 domains 2 (FCHSD2); 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 2 (FCHSD2) 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 1958645935  16 NIQGEQMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRDWPGIKTDDRNDYRSMYPVWKSFLEATM 95
Cdd:cd07677     1 NIQVEQMTKLQAKHQAECKLLEDEREFSQKIAAIESEYAQKEQKLASQYLKSDWRGMKADERADYRSMYTVWKSFLEGTM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935  96 QVAQSRINICENYKNFISEPARAVRSLKEQQLKRCVDQLTKIQTELQETVKDLVKGKKKYFETEQMAHAVREKADIEAKS 175
Cdd:cd07677    81 QVAQSRINICENYKNLISEPARTVRLYKEQQLKRCVDQLTKIQAELQETVKDLAKGKKKYFETEQMAHAVREKADIEAKS 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935 176 KLSLFQSRISLQKASVKLKARRTECNTKATHARNDYLLTLAAANAHQDRYYQTDLLNIMKALDGNVYDHLKDYLIAFSRT 255
Cdd:cd07677   161 KLSLFQSRISLQKASVKLKARRSECNSKATHARNDYLLTLAAANAHQDRYYQTDLVNIMKALDGNVYDHLKDYLMAFSRT 240

                         250       260
                  ....*....|....*....|
gi 1958645935 256 ELEACQAMQNTFQFLLENSS 275
Cdd:cd07677   241 ELETCQAVQNTFQFLLETSS 260

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 1958645935 495 PLTCKVVYSYKASQPDELTIEEHEVLEVIEDGDMEDWVKARNKVGQVGYVPEKYLQF 551
Cdd:cd11761     1 PVTCKVLYSYEAQRPDELTITEGEELEVIEDGDGDGWVKARNKSGEVGYVPENYLQF 57

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of FCH and double SH3 domains 2 (FCHSD2); 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 2 (FCHSD2) 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 1958645935  16 NIQGEQMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRDWPGIKTDDRNDYRSMYPVWKSFLEATM 95
Cdd:cd07677     1 NIQVEQMTKLQAKHQAECKLLEDEREFSQKIAAIESEYAQKEQKLASQYLKSDWRGMKADERADYRSMYTVWKSFLEGTM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935  96 QVAQSRINICENYKNFISEPARAVRSLKEQQLKRCVDQLTKIQTELQETVKDLVKGKKKYFETEQMAHAVREKADIEAKS 175
Cdd:cd07677    81 QVAQSRINICENYKNLISEPARTVRLYKEQQLKRCVDQLTKIQAELQETVKDLAKGKKKYFETEQMAHAVREKADIEAKS 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935 176 KLSLFQSRISLQKASVKLKARRTECNTKATHARNDYLLTLAAANAHQDRYYQTDLLNIMKALDGNVYDHLKDYLIAFSRT 255
Cdd:cd07677   161 KLSLFQSRISLQKASVKLKARRSECNSKATHARNDYLLTLAAANAHQDRYYQTDLVNIMKALDGNVYDHLKDYLMAFSRT 240

                         250       260
                  ....*....|....*....|
gi 1958645935 256 ELEACQAMQNTFQFLLENSS 275
Cdd:cd07677   241 ELETCQAVQNTFQFLLETSS 260

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 1958645935 495 PLTCKVVYSYKASQPDELTIEEHEVLEVIEDGDMEDWVKARNKVGQVGYVPEKYLQF 551
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 1958645935  497 TCKVVYSYKASQPDELTIEEHEVLEVIEDGDmEDWVKARNKVGQVGYVPEKYLQ 550
Cdd:smart00326   4 QVRALYDYTAQDPDELSFKKGDIITVLEKSD-DGWWKGRLGRGKEGLFPSNYVE 56

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 1958645935 597 KALYDYEGQTDDELSFPEGAIIRIVNKEnqdDDGFWEGEF-SGRIGVFPS 645
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKS---EDGWWKGRNkGGKEGLIPS 47

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958645935   30 QAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQylkrdWPGiKTDDRNDYRSMYPVWKSFLEATMQVAQSRINI 104
Cdd:smart00055  19 KNGLRLLEDLKKFMRERAKIEEEYAKKLQKLSKK-----LRA-VRDTEPEYGSLSKAWEVLLSETDALAKQHLEL 87

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of FCH and double SH3 domains 2 (FCHSD2); 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 2 (FCHSD2) 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 1958645935  16 NIQGEQMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRDWPGIKTDDRNDYRSMYPVWKSFLEATM 95
Cdd:cd07677     1 NIQVEQMTKLQAKHQAECKLLEDEREFSQKIAAIESEYAQKEQKLASQYLKSDWRGMKADERADYRSMYTVWKSFLEGTM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935  96 QVAQSRINICENYKNFISEPARAVRSLKEQQLKRCVDQLTKIQTELQETVKDLVKGKKKYFETEQMAHAVREKADIEAKS 175
Cdd:cd07677    81 QVAQSRINICENYKNLISEPARTVRLYKEQQLKRCVDQLTKIQAELQETVKDLAKGKKKYFETEQMAHAVREKADIEAKS 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935 176 KLSLFQSRISLQKASVKLKARRTECNTKATHARNDYLLTLAAANAHQDRYYQTDLLNIMKALDGNVYDHLKDYLIAFSRT 255
Cdd:cd07677   161 KLSLFQSRISLQKASVKLKARRSECNSKATHARNDYLLTLAAANAHQDRYYQTDLVNIMKALDGNVYDHLKDYLMAFSRT 240

                         250       260
                  ....*....|....*....|
gi 1958645935 256 ELEACQAMQNTFQFLLENSS 275
Cdd:cd07677   241 ELETCQAVQNTFQFLLETSS 260

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 1958645935  19 GEQMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRDWPGIKTDDRNDyRSMYPVWKSFLEATMQVA 98
Cdd:cd07678     4 LEQLSILQTKQQRDAELLEDIRSYSKQRAAIEREYGQALQRLASQFLKRDWHRGGNETEMD-RSVRTVWGAWREGTAATG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935  99 QSRINICENYKNFISEPARAVRSLKEQQLKRCVDQLTKIQTELQETVKDLVKGKKKYFETEQMAHAVREKA-DIEA---K 174
Cdd:cd07678    83 QGRVTRLEAYRRLRDEAGKTGRSAKEQVLKKSTEQLQKAQAELLETVKELSKSKKLYGQLERVSEVAKEKAaDVEArlnK 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935 175 SKLSLFQSRISLQKASVKLKARRTECNTKATHARNDYLLTLAAANAHQDRYYQTDLLNIMKALDGNVYDHLKDYLIAFSR 254
Cdd:cd07678   163 SDHGIFHSKASLQKLSAKFSAQSAEYSQQLQAARNEYLLNLVAANAHLDHYYQEELPAIMKALDGDLYERLRDPLTSLSH 242

                         250       260
                  ....*....|....*....|.
gi 1958645935 255 TELEACQAMQNTFQFLLENSS 275
Cdd:cd07678   243 TELEACEVTQEHFHRIEQATS 263

The Extended FES-CIP4 Homology (FCH) or F-BAR (FCH and Bin/Amphiphysin/Rvs) domain, a dimerization module that binds and bends membranes; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. F-BAR domain containing proteins, also known as Pombe Cdc15 homology (PCH) family proteins, include Fes and Fer tyrosine kinases, PACSINs/Syndapins, FCHO, PSTPIP, CIP4-like proteins and srGAPs. Many members also contain an SH3 domain and play roles in endocytosis. 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. These tubules have diameters larger than those observed with N-BARs. The F-BAR domains of some members such as NOSTRIN and Rgd1 are important for the subcellular localization of the protein.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935  21 QMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRDWPGiktddrndYRSMYPVWKSFLEATMQVAQS 100
Cdd:cd07610     1 GFELLEKRTELGLDLLKDLREFLKKRAAIEEEYAKNLQKLAKKFSKKPESG--------KTSLGTSWNSLREETESAATV 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935 101 RINICENYKNFISEPARAVRSLKEQQLKRCVDQLTKIQTELQETVKDLVKgkkkyfeteqmahavrekadieaksklslf 180
Cdd:cd07610    73 HEELSEKLSQLIREPLEKVKEDKEQARKKELAEGEKLKKKLQELWAKLAK------------------------------ 122

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935 181 qsrislqkasvKLKARRTECNTKATHARNDYLLTLAAANAHQDRYYqTDLLNIMKALDGNVYDHLKDYLIAFSRTELEAC 260
Cdd:cd07610   123 -----------KADEEYREQVEKLNPAQSEYEEEKLNKIQAEQERE-EERLEILKDNLKNYINAIKEIPQKIQQELEQSI 190

                  .
gi 1958645935 261 Q 261
Cdd:cd07610   191 N 191

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 1958645935 595 FVKALYDYEGQTDDELSFPEGAIIRIVNKE-NQDDDGFWEGEFSGRIGVFPSVLVEE 650
Cdd:cd11762     1 LVRALYDYEAQSDEELSFPEGAIIRILRKDdNGVDDGWWEGEFNGRVGVFPSLVVEE 57

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Cdc42-Interacting Protein 4 and similar proteins; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4), Formin Binding Protein 17 (FBP17), FormiN Binding Protein 1-Like (FNBP1L), and similar proteins. CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. Members of this subfamily typically contain an N-terminal F-BAR domain and a C-terminal SH3 domain. In addition, some members such as FNBP1L contain a central Cdc42-binding HR1 domain. 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 1958645935  21 QMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRDwpgiKTDDRNDYrSMYPVWKSFLEATMQVAQS 100
Cdd:cd07653     6 QFDNLEKHTQKGIDFLERYGKFVKERAAIEQEYAKKLRKLVKKYLPKK----KEEDEYSF-SSVKAFRSILNEVNDIAGQ 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935 101 RINICENYKNFISEPARAVRSLKEQQLKRCVDQLTKIQTELQETVKDLVKGKKKY----FETEQmAHAVREKADIEAKsk 176
Cdd:cd07653    81 HELIAENLNSNVCKELKTLISELRQERKKHLSEGSKLQQKLESSIKQLEKSKKAYekafKEAEK-AKQKYEKADADMN-- 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935 177 lslfQSRISLQKASVKLKARRTECNtkatHARNDYLLTLAAANAHQDRYYQTDL---LNIMKALDGNVYDHLKDYLIAFS 253
Cdd:cd07653   158 ----LTKADVEKAKANANLKTQAAE----EAKNEYAAQLQKFNKEQRQHYSTDLpqiFDKLQELDEKRINRTVELLLQAA 229

                         250
                  ....*....|..
gi 1958645935 254 RTELEACQAMQN 265
Cdd:cd07653   230 EIERKVIPIIAK 241

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 1958645935 596 VKALYDYEGQTDDELSFPEGAIIRIVNKENQdDDGFWEGEFSGRIGVFPSVLVEE 650
Cdd:cd11875     2 ARVLFDYEAENEDELTLREGDIVTILSKDCE-DKGWWKGELNGKRGVFPDNFVEP 55

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 1958645935 595 FVKALYDYEGQTDDELSFPEGAIIRIVNKEnqdDDGFWEGEFSGRI-GVFPSVLVEE 650
Cdd:cd11825     1 TVKALYDYRAQRPDELSFCKHAIITNVEKE---DGGWWRGDYGGKKqKWFPANYVEE 54

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. 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 1958645935 596 VKALYDYEGQTDDELSFPEGAIIRIVNKEnqdDDGFWEGEFSGRIGVFPSVLVEE 650
Cdd:cd11877     2 VRAKFNFEGTNEDELSFDKGDIITVTQVV---EGGWWEGTLNGKTGWFPSNYVKE 53

Fes/CIP4, and EFC/F-BAR homology domain; Alignment extended from. Highly alpha-helical. The cytosolic endocytic adaptor proteins in fungi carry this domain at the N-terminus; several of these have been referred to as muniscin proteins. These N-terminal BAR, N-BAR, and EFC/F-BAR domains are found in proteins that regulate membrane trafficking events by inducing membrane tubulation. The domain dimerizes into a curved structure that binds to liposomes and either senses or induces the curvature of the membrane bilayer to cause biophysical changes to the shape of the bilayer; it also thereby recruits other trafficking factors, such as the GTPase dynamin. Most EFC/F-BAR domain-family members localize to actin-rich structures.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935  21 QMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRdwpgiKTDDRNDYRSMYPVWKSFLEATMQVAQS 100
Cdd:pfam00611   1 GFKVLLKRLKQGIKLLEELASFLKERAEIEEEYAKKLQKLAKKFLKK-----KKKPEDDGGTLKKAWDELLTETEQLAKQ 75

                  ...
gi 1958645935 101 RIN 103
Cdd:pfam00611  76 HLK 78

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Fes (feline sarcoma) and Fer (Fes related) tyrosine kinases; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Fes (feline sarcoma), also called Fps (Fujinami poultry sarcoma), and Fer (Fes related) are cytoplasmic (or nonreceptor) tyrosine kinases that play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Although Fes and Fer show redundancy in their biological functions, they show differences in their expression patterns. Fer is ubiquitously expressed while Fes is expressed predominantly in myeloid and endothelial cells. Fes and Fer contain an N-terminal F-BAR domain, an SH2 domain, and a C-terminal catalytic kinase domain. 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. The F-BAR domain of Fes is critical in its role in microtubule nucleation and bundling.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935  25 LQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKrdwpgiktDDRNDYRSMYPVWKSFLEATMQVAQSRINI 104
Cdd:cd07657    10 LLKRQDAELRLLETMKKYMAKRAKSDREYASTLGSLANQGLK--------IEAGDDLQGSPISKSWKEIMDSTDQLSKLI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935 105 CENYKNFISEPARAVRSL---KEQQLKRCVDQLTKIQTELQETVKDLVKGKKKYFETEQMAHAVREKADiEAKSKlslfQ 181
Cdd:cd07657    82 KQHAEALESGTLDKLTLLikdKRKAKKAYQEERQQIDEQYKKLTDEVEKLKSEYQKLLEDYKAAKSKFE-EAVVK----G 156

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958645935 182 SRISLQKASVKLKARRTECNTKATHarNDYLLTLAAANAHQDRYYQT---DLLNIMKALDGNVYDHLKDYLIAFSRT 255
Cdd:cd07657   157 GRGGRKLDKARDKYQKACRKLHLCH--NDYVLALLEAQEHEEDYRTLllpGLLNSLQSLQEEFITQWKKILQEYLRY 231

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Slit-Robo GTPase Activating Proteins; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs, all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. 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 1958645935  20 EQMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRDwpGIKTDDRNDYRSMYPV--WKSFLEATMQV 97
Cdd:cd07656     5 EQLKCLDLRTEAQVQLLADLQDYFRRRAEIELEYSRSLEKLADRFSSKH--KNEKSKREDWSLLSPVncWNTLLVQTKQE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935  98 AQSRINICENYKNFIS--------EPARAVRSLKEQQLKrCVDQLTKIQTELQETVK-------DLVKGKKKYFETEQMa 162
Cdd:cd07656    83 SRDHSTLSDIYSNNLVqrlgqmseDLQRISKKCREIGSQ-LHDELLRVLNELQTAMKtyhtyhaESKSAERKLKEAEKQ- 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958645935 163 havREKADIEAKSKLSLFQSRISLQKASVKLKARRTECNTKATHARNDYLLTLAAANAHQDRYYQTDLLNIMKALD 238
Cdd:cd07656   161 ---EEKQEQSPEKKLERSRSSKKIEKEVEKRQAKYSEAKLKCTKARNEYLLNLAAANATIHKYFVQDLSDLIDCMD 233

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 1958645935 597 KALYDYEGQTDDELSFPEGAIIRIVNKenqDDDGFWEGEFSGRIGVFPSVLVEE 650
Cdd:cd11823     3 KALYSYTANREDELSLQPGDIIEVHEK---QDDGWWLGELNGKKGIFPATYVEE 53

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 1958645935 597 KALYDYEGQTDDELSFPEGAIIRIVNKEnqdDDGFWEGEF-SGRIGVFPS 645
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKS---EDGWWKGRNkGGKEGLIPS 47

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). 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 1958645935 596 VKALYDYEGQTDDELSFPEGAIIRIVnkeNQDDDGFWEGEFSGRIGVFPSVLVEE 650
Cdd:cd11827     2 CKALYAYDAQDTDELSFNEGDIIEIL---KEDPSGWWTGRLRGKEGLFPGNYVEK 53

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958645935 595 FVKALYDYEGQTDDELSFPEGAIIRIVNKENQdDDGFWEGEFSGRIGVFPSVLVEEL 651
Cdd:cd12057     1 YCKVLFPYEAQNEDELTIKEGDIVTLISKDCI-DAGWWEGELNGRRGVFPDNFVKLL 56

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Slit-Robo GTPase Activating Protein 3; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs. srGAP3, also called MEGAP (MEntal disorder associated GTPase-Activating Protein), is a Rho GAP with activity towards Rac1 and Cdc42. It impacts cell migration by regulating actin and microtubule cytoskeletal dynamics. The association between srGAP3 haploinsufficiency and mental retardation is under debate. srGAP3 contains an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. 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 1958645935  20 EQMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRDWPGIKTDDRNDYRSMYPV--WKSFLEATMQV 97
Cdd:cd07684     5 EQFKCLEQQSESRLQLLQDLQEFFRRKAEIELEYSRSLEKLAERFSSKIRTSREHQFKKDQQLLSPVncWYLVLEQTRRE 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935  98 AQSRINICENYKNFISEPARAVRSLKEQQLKRCVDQLTKIQTELQETVKDLVKGKKKY--FETEQMAHAVR-------EK 168
Cdd:cd07684    85 SRDHATLNDIFNNNVIVRLSQISEDVIRLFKKSKEIGLQMHEELLKVTNELYTVMKTYhmYHAESISAESKlkeaekqEE 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935 169 ADIEAKSKLSLF--------QSRIS---LQKASVKLKARRTECNTKATHARNDYLLTLAAANAHQDRYYQTDLLNIMKAL 237
Cdd:cd07684   165 KQFNKSGDISSNllrheerpQRRSSvkkIEKMKEKRQAKYSENKLKCTKARNDYLLNLAATNAAVSKYYIHDVSDLIDCC 244

                  .
gi 1958645935 238 D 238
Cdd:cd07684   245 D 245

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958645935 598 ALYDYEGQTDDELSFPEGAIIRIVNKENqddDGFWEGEFSGRIGVFPSVLVE 649
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIEESE---DGWWEGINTGRTGLVPANYVE 49

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 1958645935 499 KVVYSYKASQPDELTIEEHEVLEVIEDGDmEDWVKARNKVGQVGYVP 545
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKSE-DGWWKGRNKGGKEGLIP 46

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. 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 1958645935 596 VKALYDYEGQTDDELSFPEGAIIRIVNKENQDddgFWEGEFSGRIGVFPSVLVEE 650
Cdd:cd12046     2 VVALFSYEASQPEDLEFQKGDVILVLSKVNED---WLEGQCKGKIGIFPSAFVED 53

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Slit-Robo GTPase Activating Protein 1; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs. srGAP1, also called Rho GTPase-Activating Protein 13 (ARHGAP13), is a Cdc42- and RhoA-specific GAP and is expressed later in the development of CNS (central nervous system) tissues. It is an important downstream signaling molecule of Robo1. srGAP1 contains an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. 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 1958645935  20 EQMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRDWpgiKTDDRNDYRS----MYPV--WKSFLEA 93
Cdd:cd07683     5 EQQKCLEQQTEMRVQLLQDLQDFFRKKAEIESEYSRNLEKLAERFMAKTR---STKDHQQYKKdqnlLSPVncWYLLLNQ 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935  94 TMQVAQSRINICENYKNFISEPARAVRSLKEQQLKRCVDQLTKIQTELQETVKDLVKGKKKY--FETE------QMAHAV 165
Cdd:cd07683    82 VRRESKDHATLSDIYLNNVIMRFMQISEDSTRMFKKSKEIAFQLHEDLMKVLNELYTVMKTYhmYHTEsisaesKLKEAE 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958645935 166 REKADIEAKSKLSLFQSRIS-----------LQKASVKLKARRTECNTKATHARNDYLLTLAAANAHQDRYYQTDLLNIM 234
Cdd:cd07683   162 KQEEKQIGRSGDPVFHIRLEdrhqrrssvkkIEKMKEKRQAKYSENKLKSIKARNEYLLTLEATNASVFKYYIHDLSDLI 241

                  ....
gi 1958645935 235 KALD 238
Cdd:cd07683   242 DCCD 245

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958645935 596 VKALYDYEGQTDDELSFPEGAIIRIVNKENQDDDgFWEGEFSGRIGVFPS 645
Cdd:cd11841     2 VTALYSFEGQQPCDLSFQAGDRITVLTRTDSQFD-WWEGRLRGRVGIFPA 50

Second Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958645935 594 CFVkALYDYEGQT--------DDELSFPEGAIIRIVnkENQDDDGFWEGEFSGRIGVFPSVLVEE 650
Cdd:cd12012     1 LFV-ALFDYDPLTmspnpdaaEEELPFKEGQLIKVY--GDKDADGFYLGEINGRRGLVPCNMVSE 62

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 1958645935 498 CKVVYSYKASQPDELTIEEHEVLEVIEDGDMEDWVKARNKVGQVGYVPEKYLQ 550
Cdd:cd11763     2 VRALYDFDSQPSGELSLRAGEVLTITRQDVGDGWLEGRNSRGEVGLFPSSYVE 54

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958645935 596 VKALYDYEGQTDDELSFPEGAIIRIVNKENqddDGFWEGEFSGRIG-VFPSVLVEEL 651
Cdd:cd11969     2 VKALYDYRAKRSDELSFCKGALIHNVSKET---GGWWKGDYGGKVQhYFPSNYVEDV 55

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958645935 597 KALYDYEGQTDDELSFPEGAIIRIVNKENQDddGFWEGEFSGRIGVFPSVLVEE 650
Cdd:cd11976     3 KARYDFCARDRSELSLKEGDIIKILNKKGQQ--GWWRGEIYGRVGWFPANYVEE 54

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. 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 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. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958645935 502 YSYKASQPDELTIEEHEVLEVIED-GDMEDWVKARNKVGQVGYVPEKYLQ 550
Cdd:cd11767     6 YPFTGENDEELSFEKGERLEIIEKpEDDPDWWKARNALGTTGLVPRNYVE 55