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 1187610861  16 NIQVEQMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRDWPGIKADDRNDYRSMYPVWKSFLEGTM 95
Cdd:cd07677     1 NIQVEQMTKLQAKHQAECKLLEDEREFSQKIAAIESEYAQKEQKLASQYLKSDWRGMKADERADYRSMYTVWKSFLEGTM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187610861  96 QVAQSRINICENYKNFISEPARTVRSLKEQQLKRCVDQLTKIQTELQETVKDLAKGKKKYFETEQMAHAVREKADIEAKS 175
Cdd:cd07677    81 QVAQSRINICENYKNLISEPARTVRLYKEQQLKRCVDQLTKIQAELQETVKDLAKGKKKYFETEQMAHAVREKADIEAKS 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187610861 176 KLSLFQSRISLQKASVKLKARRSECNSKATHARNDYLLTLAAANAHQDRYYQTDLVNIMKALDGNVYDHLKDYLIAFSRT 255
Cdd:cd07677   161 KLSLFQSRISLQKASVKLKARRSECNSKATHARNDYLLTLAAANAHQDRYYQTDLVNIMKALDGNVYDHLKDYLMAFSRT 240

                         250       260
                  ....*....|....*....|
gi 1187610861 256 ELETCQAVQNTFQFLLETSS 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 1187610861 471 PLTCKVVYSYKASQPDELTIEEHEVLEVIEDGDMEDWVKARNKVGQVGYVPEKYLQF 527
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 1187610861  16 NIQVEQMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRDWPGIKADDRNDYRSMYPVWKSFLEGTM 95
Cdd:cd07677     1 NIQVEQMTKLQAKHQAECKLLEDEREFSQKIAAIESEYAQKEQKLASQYLKSDWRGMKADERADYRSMYTVWKSFLEGTM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187610861  96 QVAQSRINICENYKNFISEPARTVRSLKEQQLKRCVDQLTKIQTELQETVKDLAKGKKKYFETEQMAHAVREKADIEAKS 175
Cdd:cd07677    81 QVAQSRINICENYKNLISEPARTVRLYKEQQLKRCVDQLTKIQAELQETVKDLAKGKKKYFETEQMAHAVREKADIEAKS 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187610861 176 KLSLFQSRISLQKASVKLKARRSECNSKATHARNDYLLTLAAANAHQDRYYQTDLVNIMKALDGNVYDHLKDYLIAFSRT 255
Cdd:cd07677   161 KLSLFQSRISLQKASVKLKARRSECNSKATHARNDYLLTLAAANAHQDRYYQTDLVNIMKALDGNVYDHLKDYLMAFSRT 240

                         250       260
                  ....*....|....*....|
gi 1187610861 256 ELETCQAVQNTFQFLLETSS 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 1187610861 471 PLTCKVVYSYKASQPDELTIEEHEVLEVIEDGDMEDWVKARNKVGQVGYVPEKYLQF 527
Cdd:cd11761     1 PVTCKVLYSYEAQRPDELTITEGEELEVIEDGDGDGWVKARNKSGEVGYVPENYLQF 57

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 1187610861  21 QMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRdwpgiKADDRNDYRSMYPVWKSFLEGTMQVAQS 100
Cdd:pfam00611   1 GFKVLLKRLKQGIKLLEELASFLKERAEIEEEYAKKLQKLAKKFLKK-----KKKPEDDGGTLKKAWDELLTETEQLAKQ 75

                  ...
gi 1187610861 101 RIN 103
Cdd:pfam00611  76 HLK 78

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 1187610861 573 KALYDYEGQTDDELSFPEGAIIRILNKEnqdDDGFWEGEF-SGRIGVFPS 621
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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187610861   19 VEQMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQylkrdWPGiKADDRNDYRSMYPVWKSFLEGTMQVA 98
Cdd:smart00055   8 DDGFEALLSRLKNGLRLLEDLKKFMRERAKIEEEYAKKLQKLSKK-----LRA-VRDTEPEYGSLSKAWEVLLSETDALA 81

                   ....*.
gi 1187610861   99 QSRINI 104
Cdd:smart00055  82 KQHLEL 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 1187610861  16 NIQVEQMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRDWPGIKADDRNDYRSMYPVWKSFLEGTM 95
Cdd:cd07677     1 NIQVEQMTKLQAKHQAECKLLEDEREFSQKIAAIESEYAQKEQKLASQYLKSDWRGMKADERADYRSMYTVWKSFLEGTM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187610861  96 QVAQSRINICENYKNFISEPARTVRSLKEQQLKRCVDQLTKIQTELQETVKDLAKGKKKYFETEQMAHAVREKADIEAKS 175
Cdd:cd07677    81 QVAQSRINICENYKNLISEPARTVRLYKEQQLKRCVDQLTKIQAELQETVKDLAKGKKKYFETEQMAHAVREKADIEAKS 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187610861 176 KLSLFQSRISLQKASVKLKARRSECNSKATHARNDYLLTLAAANAHQDRYYQTDLVNIMKALDGNVYDHLKDYLIAFSRT 255
Cdd:cd07677   161 KLSLFQSRISLQKASVKLKARRSECNSKATHARNDYLLTLAAANAHQDRYYQTDLVNIMKALDGNVYDHLKDYLMAFSRT 240

                         250       260
                  ....*....|....*....|
gi 1187610861 256 ELETCQAVQNTFQFLLETSS 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 1187610861  20 EQMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRDWPGIKADDRNDyRSMYPVWKSFLEGTMQVAQ 99
Cdd:cd07678     5 EQLSILQTKQQRDAELLEDIRSYSKQRAAIEREYGQALQRLASQFLKRDWHRGGNETEMD-RSVRTVWGAWREGTAATGQ 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187610861 100 SRINICENYKNFISEPARTVRSLKEQQLKRCVDQLTKIQTELQETVKDLAKGKKKYFETEQMAHAVREKA-DIEA---KS 175
Cdd:cd07678    84 GRVTRLEAYRRLRDEAGKTGRSAKEQVLKKSTEQLQKAQAELLETVKELSKSKKLYGQLERVSEVAKEKAaDVEArlnKS 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187610861 176 KLSLFQSRISLQKASVKLKARRSECNSKATHARNDYLLTLAAANAHQDRYYQTDLVNIMKALDGNVYDHLKDYLIAFSRT 255
Cdd:cd07678   164 DHGIFHSKASLQKLSAKFSAQSAEYSQQLQAARNEYLLNLVAANAHLDHYYQEELPAIMKALDGDLYERLRDPLTSLSHT 243

                         250       260
                  ....*....|....*....|
gi 1187610861 256 ELETCQAVQNTFQFLLETSS 275
Cdd:cd07678   244 ELEACEVTQEHFHRIEQATS 263

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 1187610861 571 FVKALYDYEGQTDDELSFPEGAIIRILNKENQDDDGFWEGEFSGRIGVFPSVLVEE 626
Cdd:cd11894     1 FVKALYDYEGQTDDELSFPEGAIIRILNKENQDDDGFWEGEFNGRIGVFPSVLVEE 56

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 1187610861 571 FVKALYDYEGQTDDELSFPEGAIIRILNKE-NQDDDGFWEGEFSGRIGVFPSVLVEE 626
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 1187610861  21 QMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRDwpgiKADDRNDYrSMYPVWKSFLEGTMQVAQS 100
Cdd:cd07653     6 QFDNLEKHTQKGIDFLERYGKFVKERAAIEQEYAKKLRKLVKKYLPKK----KEEDEYSF-SSVKAFRSILNEVNDIAGQ 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187610861 101 RINICENYKNFISEPARTVRSLKEQQLKRCVDQLTKIQTELQETVKDLAKGKKKY----FETEQmAHAVREKADIEAKsk 176
Cdd:cd07653    81 HELIAENLNSNVCKELKTLISELRQERKKHLSEGSKLQQKLESSIKQLEKSKKAYekafKEAEK-AKQKYEKADADMN-- 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187610861 177 lslfQSRISLQKASVKLKARRSECNskatHARNDYLLTLAAANAHQDRYYQTDLVNI---MKALDGNVYDHLKDYLIAFS 253
Cdd:cd07653   158 ----LTKADVEKAKANANLKTQAAE----EAKNEYAAQLQKFNKEQRQHYSTDLPQIfdkLQELDEKRINRTVELLLQAA 229

                         250
                  ....*....|..
gi 1187610861 254 RTELETCQAVQN 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 1187610861 572 VKALYDYEGQTDDELSFPEGAIIRILNKENQdDDGFWEGEFSGRIGVFPSVLVEE 626
Cdd:cd11875     2 ARVLFDYEAENEDELTLREGDIVTILSKDCE-DKGWWKGELNGKRGVFPDNFVEP 55

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 1187610861 572 VKALYDYEGQTDDELSFPEGAIIRILNKenqDDDGFWEGEFSGRIGVFPSVLVE 625
Cdd:cd11826     2 VVALYDYTADKDDELSFQEGDIIYVTKK---NDDGWYEGVLNGVTGLFPGNYVE 52

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 1187610861  21 QMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRdwpgiKADDRNDYRSMYPVWKSFLEGTMQVAQS 100
Cdd:pfam00611   1 GFKVLLKRLKQGIKLLEELASFLKERAEIEEEYAKKLQKLAKKFLKK-----KKKPEDDGGTLKKAWDELLTETEQLAKQ 75

                  ...
gi 1187610861 101 RIN 103
Cdd:pfam00611  76 HLK 78

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 1187610861 572 VKALYDYEGQTDDELSFPEGAIIRILNKEnqdDDGFWEGEFSGRIGVFPSVLVEE 626
Cdd:cd11877     2 VRAKFNFEGTNEDELSFDKGDIITVTQVV---EGGWWEGTLNGKTGWFPSNYVKE 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 1187610861 572 VKALYDYEGQTDDELSFPEGAIirILNKENQDDDgFWEGEFSGRIGVFPSVLVEE 626
Cdd:cd11961     2 AKALYDYDAAEDNELSFFENDK--IINIEFVDDD-WWLGECHGSRGLFPSNYVEL 53

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Slit-Robo GTPase Activating Protein 2; 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. srGAP2 is expressed in zones of neuronal differentiation. It plays a role in the regeneration of neurons and axons. srGAP2 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 1187610861  19 VEQMTKLQAKHQAECDLLEDMRTFSQKKAAIEREYAQGIQKLASQYLKRDWPGIKADDRNDYRSMYPV--WKSFLEGTMQ 96
Cdd:cd07682     4 VEQLKCLDQQCELRVQLLQDLQDFFRKKAEIEMDYSRNLEKLAERFLAKTRSTKDQQFKKDQNVLSPVncWNLLLNQVKR 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187610861  97 VAQSRINICENYKNFI--------SEPARTVRSLKE--QQLKrcvDQLTKIQTELQETVK-------DLAKGKKKYFETE 159
Cdd:cd07682    84 ESRDHATLSDIYLNNIiprfvqisEDSGRLFKKSKEvgLQLQ---EDLMKVLNELYTVMKtyhmynaDSISAQSKLKEAE 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187610861 160 -----QMAHAVREKADIEAKSKLSLFQSRIS-----------LQKASVKLKARRSECNSKATHARNDYLLTLAAANAHQD 223
Cdd:cd07682   161 kqeekQMSRSVRQEDRQTPRSPDSTTNIRIEekhvrrssvkkIEKMKEKRQAKYTENKLKAIKARNEYLLALEATNASVF 240

                         250
                  ....*....|....*
gi 1187610861 224 RYYQTDLVNIMKALD 238
Cdd:cd07682   241 KYYIHDLSDLIDCCD 255

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 1187610861 570 CFVKALYDYEGQTDDELSFPEGAIIRILNKENQDddgFWEGEFSGRIGVFPSVLVE 625
Cdd:cd11995     1 CQVIGMYDYTAQNDDELAFSKGQIINVLNKEDPD---WWKGELNGQVGLFPSNYVK 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 1187610861 573 KALYDYEGQTDDELSFPEGAIIRILNKEnqdDDGFWEGEF-SGRIGVFPS 621
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKS---EDGWWKGRNkGGKEGLIPS 47

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain 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 1187610861 571 FVKALYDYEGQTDDELSFPEGAIIRILnkENQDDDGFWEGEFSGRIGVFPSVLVE 625
Cdd:cd11843     1 PVRALYDYEGQESDELSFKAGDILTKL--EEEDEQGWCKGRLDGRVGLYPANYVE 53

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 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 1187610861 573 KALYDYEGQTDDELSFPEGAIIRILNKENQDDdGFWEGEFSGRIGVFPSVLVE 625
Cdd:cd12142     3 RVLFDYNPVAPDELALKKGDVIEVISKETEDE-GWWEGELNGRRGFFPDNFVM 54

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.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1187610861 473 TCKVVYSYKASQPDELTIEEHEVLEVIEDGDmEDWVKARNKVGQVGYVPEKY 524
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLEKDD-DGWWEGELNGGREGLFPANY 51

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 1187610861 572 VKALYDYEGQTDDELSFPEGAIIRILNKENQDddgFWEGEFSGRIGVFPSVLVEE 626
Cdd:cd12046     2 VVALFSYEASQPEDLEFQKGDVILVLSKVNED---WLEGQCKGKIGIFPSAFVED 53

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) 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. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also 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 1187610861 572 VKALYDYEGQTDDELSFPEGAIIRILNKenqDDDGFWEGEFSGRIGVFPSVLVEE 626
Cdd:cd11873     2 VIVEFDYDAEEPDELTLKVGDIITNVKK---MEEGWWEGTLNGKRGMFPDNFVKV 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
                  ....*....|....*....|....*....|....*....|....*..
gi 1187610861 475 KVVYSYKASQPDELTIEEHEVLEVIEDGDmEDWVKARNKVGQVGYVP 521
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKSE-DGWWKGRNKGGKEGLIP 46

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP 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 CD2AP. 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 1187610861 571 FVKALYDYEGQTDDELSFPEGAIIRILNKENqDDDGFWEGEFSGRIGVFP 620
Cdd:cd12056     3 YCKALFHYEGTNEDELDFKEGEIILIISKDT-GEPGWWKGELNGKEGVFP 51

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 1187610861 570 CFVkALYDYEGQT--------DDELSFPEGAIIRILnkENQDDDGFWEGEFSGRIGVFPSVLVEE 626
Cdd:cd12012     1 LFV-ALFDYDPLTmspnpdaaEEELPFKEGQLIKVY--GDKDADGFYLGEINGRRGLVPCNMVSE 62

Src Homology 3 domain of Cdc42-Interacting Protein 4; 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. It functions downstream of Cdc42 in PDGF-dependent actin reorganization and cell migration, and also regulates the activity of PDGFRbeta. It uses Src as a substrate in regulating the invasiveness of breast tumor cells. CIP4 may also play a role in the pathogenesis of Huntington's disease. Members of this subfamily typically contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain, a central Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of CIP4 associates with Gapex-5, a Rab31 GEF. 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 1187610861 473 TCKVVYSYKASQPDELTIEEHEVLEVIEDGDMEDWVKARNKVGQVGYVPEKYLQF 527
Cdd:cd11911     1 TCTALYDFDGTSEGTLSMEEGEILLVLEEDGGDGWTRVRKNNGDEGYVPTSYIEV 55

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. 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 1187610861 573 KALYDYEGQTDDELSFPEGAIIRILNKENqdDDGFWEGEFSGRIGVFPSVLVEE 626
Cdd:cd11830     3 KARYDFCARDMRELSLKEGDVVKIYNKKG--QQGWWRGEINGRIGWFPSTYVEE 54

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.

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gi 1187610861 474 CKVVYSYKASQPDELTIEEHEVLEVIEDGDMEDWVKARNKVGQVGYVPEKYLQ 526
Cdd:cd11763     2 VRALYDFDSQPSGELSLRAGEVLTITRQDVGDGWLEGRNSRGEVGLFPSSYVE 54

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically 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 1187610861 571 FVKALYDYEGQTDDELSFPEGAIIRILNKENQDddgFWEGEFSGRIGVFPSVLVEE 626
Cdd:cd11805     1 RVQALYDFNPQEPGELEFRRGDIITVLDSSDPD---WWKGELRGRVGIFPANYVQP 53

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.

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gi 1187610861 478 YSYKASQPDELTIEEHEVLEVIED-GDMEDWVKARNKVGQVGYVPEKYLQ 526
Cdd:cd11767     6 YPFTGENDEELSFEKGERLEIIEKpEDDPDWWKARNALGTTGLVPRNYVE 55

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. 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. 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.

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gi 1187610861 572 VKALYDYEGQTDDELSFPEGAIIRILNKenqDDDGFWEGEFSGRIGVFPSVLVEELS 628
Cdd:cd11972     5 VVAIYDYTKDKEDELSFQEGAIIYVIKK---NDDGWYEGVMNGVTGLFPGNYVESIM 58

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. 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 1187610861 572 VKALYDYEGQTDDELSFPEGAIIRILNKENQDddgFWEGEFSG---RIGVFPS 621
Cdd:cd11821     2 VRALYDCQADNDDELTFSEGEIIVVTGEEDDE---WWEGHIEGdpsRRGVFPV 51

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), 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. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains 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 1187610861 574 ALYDYEGQTDDELSFPEGAIIRILNKEN--QDDDGFWEGEFSGRIGVFPS 621
Cdd:cd12058     4 ALYDYEASGEDELSLRRGDVVEVLSQDAavSGDDGWWAGKIRHRLGIFPA 53