The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Formin Binding Protein 17; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Formin Binding Protein 17 (FBP17), also called FormiN Binding Protein 1 (FNBP1), is involved in dynamin-mediated endocytosis. It is recruited to clathrin-coated pits late in the endocytosis process and may play a role in the invagination and scission steps. FBP17 binds in vivo to tankyrase, a protein involved in telomere maintenance and mitogen activated protein kinase (MAPK) signaling. 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 1953099425   5 TELWDQFDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLAKKYQPKKNSKEEEEYRYTACKAFLSTLNEMNDYA 84
Cdd:cd07676     1 TELWDQFDNLEKHTQWGIEVLEKYIKFVKERTEIELSYAKQLRNLSKKYQPKKNSKEEEEYKYTSCRAFLMTLNEMNDYA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425  85 GQHEVISENMTSNITVELARYVQELKQERKSYFHDGRKAQQHIEICWKQLESSKRRFERDCKEADRAQQYFEKMDADINV 164
Cdd:cd07676    81 GQHEVISENLASQIIVELTRYVQELKQERKSHFHDGRKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDADINV 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425 165 TKADVEKARQQAQVRHQMAEDSKADYSSILQKFNHEQHEYYHTHIPNIFQKIQEMEERRIVRIGESMKTYAEVDRQVIPI 244
Cdd:cd07676   161 TKADVEKARQQAQIRHQMAEDSKAEYSSYLQKFNKEQHEHYYTHIPNIFQKIQEMEERRIGRVGESMKTYAEVDRQVIPI 240

                         250
                  ....*....|...
gi 1953099425 245 IGKCLDEIVKAAE 257
Cdd:cd07676   241 IGKCLDGITKAAE 253

Src Homology 3 domain of Formin Binding Protein 17; Formin Binding Protein 17 (FBP17), also called FormiN Binding Protein 1 (FNBP1), is involved in dynamin-mediated endocytosis. It is recruited to clathrin-coated pits late in the endocytosis process and may play a role in the invagination and scission steps. FBP17 binds in vivo to tankyrase, a protein involved in telomere maintenance and mitogen activated protein kinase (MAPK) signaling. It contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain, a Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of the related protein, 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1953099425 581 GTCKALYTFEGQNEGTVSVVEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYVEVY 637
Cdd:cd12071     1 GTCKALYPFEGQNEGTISVAEGEMLYVIEEDKGDGWTRIRRNEDEEGYVPTSYIEVY 57

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Formin Binding Protein 17; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Formin Binding Protein 17 (FBP17), also called FormiN Binding Protein 1 (FNBP1), is involved in dynamin-mediated endocytosis. It is recruited to clathrin-coated pits late in the endocytosis process and may play a role in the invagination and scission steps. FBP17 binds in vivo to tankyrase, a protein involved in telomere maintenance and mitogen activated protein kinase (MAPK) signaling. 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 1953099425   5 TELWDQFDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLAKKYQPKKNSKEEEEYRYTACKAFLSTLNEMNDYA 84
Cdd:cd07676     1 TELWDQFDNLEKHTQWGIEVLEKYIKFVKERTEIELSYAKQLRNLSKKYQPKKNSKEEEEYKYTSCRAFLMTLNEMNDYA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425  85 GQHEVISENMTSNITVELARYVQELKQERKSYFHDGRKAQQHIEICWKQLESSKRRFERDCKEADRAQQYFEKMDADINV 164
Cdd:cd07676    81 GQHEVISENLASQIIVELTRYVQELKQERKSHFHDGRKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDADINV 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425 165 TKADVEKARQQAQVRHQMAEDSKADYSSILQKFNHEQHEYYHTHIPNIFQKIQEMEERRIVRIGESMKTYAEVDRQVIPI 244
Cdd:cd07676   161 TKADVEKARQQAQIRHQMAEDSKAEYSSYLQKFNKEQHEHYYTHIPNIFQKIQEMEERRIGRVGESMKTYAEVDRQVIPI 240

                         250
                  ....*....|...
gi 1953099425 245 IGKCLDEIVKAAE 257
Cdd:cd07676   241 IGKCLDGITKAAE 253

Src Homology 3 domain of Formin Binding Protein 17; Formin Binding Protein 17 (FBP17), also called FormiN Binding Protein 1 (FNBP1), is involved in dynamin-mediated endocytosis. It is recruited to clathrin-coated pits late in the endocytosis process and may play a role in the invagination and scission steps. FBP17 binds in vivo to tankyrase, a protein involved in telomere maintenance and mitogen activated protein kinase (MAPK) signaling. It contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain, a Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of the related protein, 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1953099425 581 GTCKALYTFEGQNEGTVSVVEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYVEVY 637
Cdd:cd12071     1 GTCKALYPFEGQNEGTISVAEGEMLYVIEEDKGDGWTRIRRNEDEEGYVPTSYIEVY 57

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 1953099425    1 MSWGTELWDQFDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLAKkyQPKKNSKEEEEYRYTAcKAFLSTLNEM 80
Cdd:smart00055   1 MGFWSELDDGFEALLSRLKNGLRLLEDLKKFMRERAKIEEEYAKKLQKLSK--KLRAVRDTEPEYGSLS-KAWEVLLSET 77

                   ....*...
gi 1953099425   81 NDYAGQHE 88
Cdd:smart00055  78 DALAKQHL 85

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 1953099425 584 KALYTFEGQNEGTVSVVEGETLYVIeEDKGDGWTRIRRNEDEEGYVPT 631
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVL-EKSEDGWWKGRNKGGKEGLIPS 47

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Formin Binding Protein 17; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Formin Binding Protein 17 (FBP17), also called FormiN Binding Protein 1 (FNBP1), is involved in dynamin-mediated endocytosis. It is recruited to clathrin-coated pits late in the endocytosis process and may play a role in the invagination and scission steps. FBP17 binds in vivo to tankyrase, a protein involved in telomere maintenance and mitogen activated protein kinase (MAPK) signaling. 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 1953099425   5 TELWDQFDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLAKKYQPKKNSKEEEEYRYTACKAFLSTLNEMNDYA 84
Cdd:cd07676     1 TELWDQFDNLEKHTQWGIEVLEKYIKFVKERTEIELSYAKQLRNLSKKYQPKKNSKEEEEYKYTSCRAFLMTLNEMNDYA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425  85 GQHEVISENMTSNITVELARYVQELKQERKSYFHDGRKAQQHIEICWKQLESSKRRFERDCKEADRAQQYFEKMDADINV 164
Cdd:cd07676    81 GQHEVISENLASQIIVELTRYVQELKQERKSHFHDGRKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDADINV 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425 165 TKADVEKARQQAQVRHQMAEDSKADYSSILQKFNHEQHEYYHTHIPNIFQKIQEMEERRIVRIGESMKTYAEVDRQVIPI 244
Cdd:cd07676   161 TKADVEKARQQAQIRHQMAEDSKAEYSSYLQKFNKEQHEHYYTHIPNIFQKIQEMEERRIGRVGESMKTYAEVDRQVIPI 240

                         250
                  ....*....|...
gi 1953099425 245 IGKCLDEIVKAAE 257
Cdd:cd07676   241 IGKCLDGITKAAE 253

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Formin Binding Protein 1-Like; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. FormiN Binding Protein 1-Like (FNBP1L), also known as Toca-1 (Transducer of Cdc42-dependent actin assembly), forms a complex with neural Wiskott-Aldrich syndrome protein (N-WASP). The FNBP1L/N-WASP complex induces the formation of filopodia and endocytic vesicles. FNBP1L is required for Cdc42-induced actin assembly and is essential for autophagy of intracellular pathogens. It contains an N-terminal F-BAR domain, a central Cdc42-binding HR1 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 1953099425   5 TELWDQFDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLAKKYQPKKNSKEEEEyRYTACKAFLSTLNEMNDYA 84
Cdd:cd07675     1 TELWDQFDNLDKHTQWGIDFLERYAKFVKERLEIEQNYAKQLRNLVKKYCPKRSSKDEEP-RFTSCLSFYNILNELNDYA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425  85 GQHEVISENMTSNITVELARYVQELKQERKSYFHDGRKAQQHIEICWKQLESSKRRFERDCKEADRAQQYFEKMDADINV 164
Cdd:cd07675    80 GQREVVAEEMGHRVYGELMRYSHDLKGERKMHLQEGRKAQQYLDMCWKQMDNSKKKFERECREAEKAQQSYERLDNDTNA 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425 165 TKADVEKARQQAQVRHQMAEDSKADYSSILQKFNHEQHEYYHTHIPNIFQKIQEMEERRIVRIGESMKTYAEVDRQVIPI 244
Cdd:cd07675   160 TKSDVEKAKQQLNLRTHMADESKNEYAAQLQNFNGEQHKHFYIVIPQIYKQLQEMDERRTVKLSECYRGFADSERKVIPI 239

                         250
                  ....*....|...
gi 1953099425 245 IGKCLDEIVKAAE 257
Cdd:cd07675   240 ISKCLEGMVLAAK 252

Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of vertebrate Cdc42-Interacting Protein 4 and FormiN Binding Protein 1-Like; CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. FNBP1L, also called Toca-1 (Transducer of Cdc42-dependent actin assembly 1), forms a complex with neural WASP; the complex induces the formation of filopodia and endocytic vesicles. FNBP1L is required for Cdc42-induced actin assembly and is essential for autophagy of intracellular pathogens. 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. CIP4 and FNBP1L contain an N-terminal F-BAR domain, a central HR1 domain, and a C-terminal SH3 domain. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family; the HR1 domain of CIP4 binds Cdc42 and TC10. Translocation of CIP4 is facilitated by its binding to TC10 at the plasma membrane.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425 433 PPEQRRKKLQQKVDELNKEIQKEMDQRDAITKMKDVYLKNPQMGDPASLDHKLAEVSQNIEKLRLEAQKFEAWLAEVEGR 512
Cdd:cd11628     1 PPEQRRKRLQQKIDELSRELQKEMDQSEALMKMKDVYEKNPQMGDPASLQPQIAETASNIDRLRGELHKYEAWLAEAEGR 80

Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Cdc42-Interacting Protein 4 and similar proteins; 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, central HR1 domain, and a C-terminal SH3 domain. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family; the HR1 domain of CIP4 binds Cdc42 and TC10. Translocation of CIP4 is facilitated by its binding to TC10 at the plasma membrane.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1953099425 434 PEQRRKKLQQKVDELNKEIQKEMDQRDAITKMKDVYLKNPQMGDPASLDHKLAEVSQNIEKLRLEAQKFEAWLAEVE 510
Cdd:cd11619     1 PEQRRKKLQQKIDELEKEIEKETKSRDGLMKMKGVYEQNPQLGDPASVEGQLAEYAKKLDKLREELQKYQGYLAEAE 77

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 1953099425  10 QFDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLAKKYQPKKNSKeeeeyrYTACKAFLSTLNEMNDYAGQHEV 89
Cdd:cd07610     1 GFELLEKRTELGLDLLKDLREFLKKRAAIEEEYAKNLQKLAKKFSKKPESG------KTSLGTSWNSLREETESAATVHE 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425  90 ISENMTSNITVELARYVQEL-KQERKSYFHDGRKAQQHIEICWKQLESSKrrferdckeadraqqyfekmdadinvtkad 168
Cdd:cd07610    75 ELSEKLSQLIREPLEKVKEDkEQARKKELAEGEKLKKKLQELWAKLAKKA------------------------------ 124

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425 169 vekarqqaqvrhqmaedsKADYSSILQKFNHEQHEYYHTHIPNIfQKIQEMEERRIVRIGESMKTYAEVDRQVIPIIGKC 248
Cdd:cd07610   125 ------------------DEEYREQVEKLNPAQSEYEEEKLNKI-QAEQEREEERLEILKDNLKNYINAIKEIPQKIQQE 185

                  ....*.
gi 1953099425 249 LDEIVK 254
Cdd:cd07610   186 LEQSIN 191

Src Homology 3 domain of Cdc42-Interacting Protein 4, Bzz1 and similar domains; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4) and similar proteins such as Formin Binding Protein 17 (FBP17) and FormiN Binding Protein 1-Like (FNBP1L), as well as yeast Bzz1 (or Bzz1p). 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. Bzz1 is also a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Members of this subfamily contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain as well as at least one C-terminal SH3 domain. Bzz1 contains a second SH3 domain at the C-terminus. 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 1953099425 583 CKALYTFEGQNEGTVSVVEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYVEV 636
Cdd:cd11777     2 CKALYAFVGSSEGTISMTEGEKLSLVEEDKGDGWTRVRRDTGEEGYVPTSYIRI 55

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1953099425  10 QFDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLAKKYQPKKNSKEEEEyrYTACKAFLSTLNEMNDYAGQHE 88
Cdd:pfam00611   1 GFKVLLKRLKQGIKLLEELASFLKERAEIEEEYAKKLQKLAKKFLKKKKKPEDDG--GTLKKAWDELLTETEQLAKQHL 77

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 1953099425 581 GTCKALYTFEGQNEGTVSVVEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYVE 635
Cdd:cd11761     2 VTCKVLYSYEAQRPDELTITEGEELEVIEDGDGDGWVKARNKSGEVGYVPENYLQ 56

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1953099425  580 IGTCKALYTFEGQNEGTVSVVEGETLYVIEEDkGDGWTRIRRNEDEEGYVPTSYVE 635
Cdd:smart00326   2 GPQVRALYDYTAQDPDELSFKKGDIITVLEKS-DDGWWKGRLGRGKEGLFPSNYVE 56

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1953099425 582 TCKALYTFEGQNEGTVSVVEGETLYVIEEDkGDGWTRIRRNEDEEGYVPTSY 633
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLEKD-DDGWWEGELNGGREGLFPANY 51

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. 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 1953099425 585 ALYTFEGQNEGTVSVVEGETLYVIEEDKGdGWTRIrRNEDEEGYVPTSYVE 635
Cdd:cd11856     4 AIADYEAQGDDEISLQEGEVVEVLEKNDS-GWWYV-RKGDKEGWVPASYLE 52

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins, 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. 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 1953099425  28 YIKFVKERTEIELSYAKQLRNLAKKYQPKKNSKEEEEyryTACKAFLSTLNEMNDYAGQHEVISENMTSNItvelaryVQ 107
Cdd:cd07655    24 LMKMVQERAEIEKAYAKKLKEWAKKWRDLIEKGPEYG---TLETAWKGLLSEAERLSELHLSIRDKLLNDV-------VE 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425 108 ELKQERKSYFH--------------DG-RKAQQHIEICWKQLESSKRRFERDCKEADRAQQYFEKMDADINVTKADVEKA 172
Cdd:cd07655    94 EVKTWQKENYHksmmggfketkeaeDGfAKAQKPWAKLLKKVEKAKKAYHAACKAEKSAQKQENNAKSDTSLSPDQVKKL 173

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1953099425 173 RQQAQVRHQMAEDSKADYSSILQKFNHEQHEYYHThIPNIFQKIQEMEERRIVRIGESMKTY 234
Cdd:cd07655   174 QDKVEKCKQEVSKTKDKYEKALEDLNKYNPRYMED-MEQVFDKCQEFEEKRLDFFKEILLSY 234

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of FCH domain Only 2 protein; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. The specific function of FCH domain Only 2 (FCHO2) is still unknown. It contains an N-terminal F-BAR domain and a C-terminal domain of unknown function named SAFF which is also present in FCHO1 and endophilin interacting protein 1. 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 1953099425  31 FVKERTEIELSYAKQLRNLAKKyqpkknskeeeeyrytackafLSTLNEMNDYAGQHEVI--SENMTSNITVELARYVQE 108
Cdd:cd07673    34 FIRERATIEEAYSRSMTKLAKS---------------------ASNYSQLGTFAPVWDVFktSTEKLANCHLELVRKLQE 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425 109 LKQERKSYFHDGRK--------------AQQHIEICWKQLESSKRRFERDCKEADRAQQYfekmdadiNVTKADVEKArq 174
Cdd:cd07673    93 LIKEVQKYGEEQVKshkktkeevagtleAVQNIQSITQALQKSKENYNAKCLEQERLKKE--------GATQREIEKA-- 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425 175 qaQVRHQMAEDSkadYSSILQKFNHEQHEYyHTHIPNIFQKIQEMEERRIVRIGESMKTYAEVDRQVIPIIGKCLDEIVK 254
Cdd:cd07673   163 --AVKSKKATES---YKLYVEKYALAKADF-EQKMTETAQKFQDIEETHLIRIKEIIGSYSNSVKEIHIQIGQVHEEFIN 236

                         250       260       270
                  ....*....|....*....|....*....|..
gi 1953099425 255 AAESIDQKNDSQLVIEAYKSGFEPPGDIEFED 286
Cdd:cd07673   237 NMANTTVESLIQKFAESKGTGKERPGPIEFEE 268

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1); F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSIN 1 or Syndapin I is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. It contains an N-terminal F-BAR 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 1953099425  32 VKERTEIELSYAKQLRNLAKKYQ------PKKNSKEeeeyrytacKAFLSTLNEMNDYAGQHEVISENMtsnitveLARY 105
Cdd:cd07680    28 VQERAKIEKAYGQQLTDWAKRWRqliekgPQYGSLE---------RAWGAIMTEADKVSELHQEVKNNL-------LNED 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425 106 VQELKQERKSYFH--------------DG-RKAQQHIEICWKQLESSKRRFERDCKEADRAQQYFEKMDADINVTKADVE 170
Cdd:cd07680    92 LEKVKNWQKDAYHkqimggfketkeaeDGfRKAQKPWAKKMKELEAAKKAYHLACKEEKLAMTREANSKAEQSVTPEQQK 171

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1953099425 171 KARQQAQVRHQMAEDSKADYSSILQKFNHEQHEYYHThIPNIFQKIQEMEERRIVRIGE 229
Cdd:cd07680   172 KLQDKVDKCKQDVQKTQEKYEKVLDDVGKTTPQYMEN-MEQVFEQCQQFEEKRLVFLKE 229

Src Homology 3 domain of Sorting Nexin 33; SNX33 interacts with Wiskott-Aldrich syndrome protein (WASP) and plays a role in the maintenance of cell shape and cell cycle progression. It modulates the shedding and endocytosis of cellular prion protein (PrP(c)) and amyloid precursor protein (APP). SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX33 also contains BAR and SH3 domains. 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 1953099425 584 KALYTFEGQNEGTVSVVEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYVEV 636
Cdd:cd11896     3 RALYSFQSENKEEINIQENEELVIFSENSLDGWLQGQNSRGETGLFPASYVEI 55

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR and SH3 domains. 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 1953099425 584 KALYTFEGQNEGTVSVVEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYVEV 636
Cdd:cd11897     3 RALYDFRSENPGEISLREHEVLSLCSEQDIEGWLEGVNSRGDRGLFPASYVEV 55

Src Homology 3 domain of Sorting nexin 9; Sorting nexin 9 (SNX9), also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX9 also contains BAR and SH3 domains. 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 1953099425 584 KALYTFE---GQNEGTVSvvEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYVEV 636
Cdd:cd11898     3 RVLYDFAaepGNNELTVK--EGEIITVTNPNVGGGWIEAKNSQGERGLVPTDYVEI 56

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. 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 1953099425 584 KALYTFEGQNEGTVSVVEGETLYVIEEDKGDGWTRIRRNED-EEGYVPTSYVEV 636
Cdd:cd11775     4 KVLYDFDAQSDDELTVKEGDVVYILDDKKSKDWWMVENVSTgKEGVVPASYIEI 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 1953099425   9 DQFDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLAKKYQ----PKKNSKEEEEYR--YTACKAFLSTLNEMnd 82
Cdd:cd07677     5 EQMTKLQAKHQAECKLLEDEREFSQKIAAIESEYAQKEQKLASQYLksdwRGMKADERADYRsmYTVWKSFLEGTMQV-- 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425  83 yAGQHEVISENMtSNITVELARYVQELK-QERKSYFHDGRKAQQHIEICWKQLESSKRRFerdcKEADR-AQQYFEKMDA 160
Cdd:cd07677    83 -AQSRINICENY-KNLISEPARTVRLYKeQQLKRCVDQLTKIQAELQETVKDLAKGKKKY----FETEQmAHAVREKADI 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1953099425 161 D-----------INVTKADVE-KARQQAQvrHQMAEDSKADYSSILQKFNHEQHEYYHTHIPNIFQKI 216
Cdd:cd07677   157 EaksklslfqsrISLQKASVKlKARRSEC--NSKATHARNDYLLTLAAANAHQDRYYQTDLVNIMKAL 222

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Proline-Serine-Threonine Phosphatase-Interacting 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. Proline-Serine-Threonine Phosphatase-Interacting Protein 1 (PSTPIP1), also known as CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. 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 1953099425  32 VKERTEIELSYAKQLRNLAKKY--QPKKNSkeeeeyrytaCKAFLSTLNEMNDYAGQHEVISENMTSNITVELARYVQEL 109
Cdd:cd07671    28 LKQRAQAEERYGKELVQIARKAggQTEINT----------LKASFDQLKQQIENIGNSHIQLAGMLREELKSLEEFRERQ 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953099425 110 KQERKSYFHDGRKAQQHIEICWKQLESSKRRFERDCKEADRAQQYFEKMDAdiNVTKADVEKARQQAQVRHQMAEDSKAD 189
Cdd:cd07671    98 KEQRKKYEAVMERVQKSKVSLYKKTMESKKTYEQRCREADEAEQTFERSSS--TGNPKQSEKSQNKAKQCRDAATEAERV 175

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1953099425 190 YSSILQKFNHEQHEYYHTHIpNIFQKIQEMEERRI 224
Cdd:cd07671   176 YKQNIEQLDKARTEWETEHI-LTCEVFQLQEDDRI 209

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. 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 1953099425 583 CKALYTFEGQNEGTVSVVEGETLYVIEEdKGDGWTRIRRNEDEEGYVPTSYVEV 636
Cdd:cd11770     2 YEALSDFQAEQEGDLSFKKGEVLRIISK-RADGWWLAENSKGNRGLVPKTYLKV 54

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. 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 1953099425 583 CKALYTFEGQNEGTVSVVEGETLYVIEEDKGDGWT-RIRRN----EDEEGYVPTSY 633
Cdd:cd11773     2 YKALYDYEPQTEDELTIQEDDILYLLEKSDDDWWKvKLKVNssddDEPVGLVPATY 57

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1953099425 585 ALYTFEGQNEGTVSVVEGETLYVIEEDkGDGWTRIRRNEdEEGYVPTSYVE 635
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIEES-EDGWWEGINTG-RTGLVPANYVE 49

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, 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 1953099425 583 CKALYTFEGQNEGTVSVVEGETLYVIEE-DkgDGWTRIRRNeDEEGYVPTSYVEV 636
Cdd:cd11803     3 CRALYDFEPENEGELGFKEGDIITLTNQiD--ENWYEGMVN-GQSGFFPVNYVEV 54

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. 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 1953099425 584 KALYTFEGQNEGTVSVVEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYVE 635
Cdd:cd11998     4 RALYDYDGQEQDELSFKAGDELTKLEDEDEQGWCKGRLDSGQVGLYPANYVE 55

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) 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 1953099425 584 KALYTFEGQNEGTVSVVEGETLYVIEEDKGDGWTRIRRNeDEEGYVPTSYVE 635
Cdd:cd11849     3 RALYDFKSAEPNTLSFSEGETFLLLERSNAHWWLVTNHS-GETGYVPANYVK 53