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 578817209   5 TELWDQFDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLSKKYQPKKNSKEEEEYKYTSCKAFISNLNEMNDYA 84
Cdd:cd07676    1 TELWDQFDNLEKHTQWGIEVLEKYIKFVKERTEIELSYAKQLRNLSKKYQPKKNSKEEEEYKYTSCRAFLMTLNEMNDYA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209  85 GQHEVISENMASQIIVDLARYVQELKQERKSNFHDGRKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDADINV 164
Cdd:cd07676   81 GQHEVISENLASQIIVELTRYVQELKQERKSHFHDGRKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDADINV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209 165 TKADVEKARQQAQIRHQMAEDSKADYSSILQKFNHEQHEYYHTHIPNIFQKIQEMEERRIVRMGESMKTYAEVDRQVIPI 244
Cdd:cd07676  161 TKADVEKARQQAQIRHQMAEDSKAEYSSYLQKFNKEQHEHYYTHIPNIFQKIQEMEERRIGRVGESMKTYAEVDRQVIPI 240

                        250
                 ....*....|...
gi 578817209 245 IGKCLDGIVKAAE 257
Cdd:cd07676  241 IGKCLDGITKAAE 253

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 578817209 553 GTCKALYTFEGQNEGTISVVEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYVEV 608
Cdd:cd12071    1 GTCKALYPFEGQNEGTISVAEGEMLYVIEEDKGDGWTRIRRNEDEEGYVPTSYIEV 56

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 578817209   5 TELWDQFDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLSKKYQPKKNSKEEEEYKYTSCKAFISNLNEMNDYA 84
Cdd:cd07676    1 TELWDQFDNLEKHTQWGIEVLEKYIKFVKERTEIELSYAKQLRNLSKKYQPKKNSKEEEEYKYTSCRAFLMTLNEMNDYA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209  85 GQHEVISENMASQIIVDLARYVQELKQERKSNFHDGRKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDADINV 164
Cdd:cd07676   81 GQHEVISENLASQIIVELTRYVQELKQERKSHFHDGRKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDADINV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209 165 TKADVEKARQQAQIRHQMAEDSKADYSSILQKFNHEQHEYYHTHIPNIFQKIQEMEERRIVRMGESMKTYAEVDRQVIPI 244
Cdd:cd07676  161 TKADVEKARQQAQIRHQMAEDSKAEYSSYLQKFNKEQHEHYYTHIPNIFQKIQEMEERRIGRVGESMKTYAEVDRQVIPI 240

                        250
                 ....*....|...
gi 578817209 245 IGKCLDGIVKAAE 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 578817209 553 GTCKALYTFEGQNEGTISVVEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYVEV 608
Cdd:cd12071    1 GTCKALYPFEGQNEGTISVAEGEMLYVIEEDKGDGWTRIRRNEDEEGYVPTSYIEV 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 578817209   552 IGTCKALYTFEGQNEGTISVVEGETLYVIEEDkGDGWTRIRRNEDEEGYVPTSYVE 607
Cdd:smart00326   2 GPQVRALYDYTAQDPDELSFKKGDIITVLEKS-DDGWWKGRLGRGKEGLFPSNYVE 56

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 578817209  556 KALYTFEGQNEGTISVVEGETLYVIeEDKGDGWTRIRRNEDEEGYVPT 603
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 578817209   5 TELWDQFDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLSKKYQPKKNSKEEEEYKYTSCKAFISNLNEMNDYA 84
Cdd:cd07676    1 TELWDQFDNLEKHTQWGIEVLEKYIKFVKERTEIELSYAKQLRNLSKKYQPKKNSKEEEEYKYTSCRAFLMTLNEMNDYA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209  85 GQHEVISENMASQIIVDLARYVQELKQERKSNFHDGRKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDADINV 164
Cdd:cd07676   81 GQHEVISENLASQIIVELTRYVQELKQERKSHFHDGRKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDADINV 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209 165 TKADVEKARQQAQIRHQMAEDSKADYSSILQKFNHEQHEYYHTHIPNIFQKIQEMEERRIVRMGESMKTYAEVDRQVIPI 244
Cdd:cd07676  161 TKADVEKARQQAQIRHQMAEDSKAEYSSYLQKFNKEQHEHYYTHIPNIFQKIQEMEERRIGRVGESMKTYAEVDRQVIPI 240

                        250
                 ....*....|...
gi 578817209 245 IGKCLDGIVKAAE 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 578817209   5 TELWDQFDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLSKKYQPKKNSKEEEEyKYTSCKAFISNLNEMNDYA 84
Cdd:cd07675    1 TELWDQFDNLDKHTQWGIDFLERYAKFVKERLEIEQNYAKQLRNLVKKYCPKRSSKDEEP-RFTSCLSFYNILNELNDYA 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209  85 GQHEVISENMASQIIVDLARYVQELKQERKSNFHDGRKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDADINV 164
Cdd:cd07675   80 GQREVVAEEMGHRVYGELMRYSHDLKGERKMHLQEGRKAQQYLDMCWKQMDNSKKKFERECREAEKAQQSYERLDNDTNA 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209 165 TKADVEKARQQAQIRHQMAEDSKADYSSILQKFNHEQHEYYHTHIPNIFQKIQEMEERRIVRMGESMKTYAEVDRQVIPI 244
Cdd:cd07675  160 TKSDVEKAKQQLNLRTHMADESKNEYAAQLQNFNGEQHKHFYIVIPQIYKQLQEMDERRTVKLSECYRGFADSERKVIPI 239

                        250
                 ....*....|...
gi 578817209 245 IGKCLDGIVKAAE 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 578817209 405 PPEQRRKKLQQKVDELNKEIQKEMDQRDAITKMKDVYLKNPQMGDPASLDHKLAEVSQNIEKLRVETQKFEAWLAEVEGR 484
Cdd:cd11628    1 PPEQRRKRLQQKIDELSRELQKEMDQSEALMKMKDVYEKNPQMGDPASLQPQIAETASNIDRLRGELHKYEAWLAEAEGR 80

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 578817209  10 QFDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLSKKYQPKKnskeeeEYKYTSCKAFISNLNEMNDYAGQHEV 89
Cdd:cd07610    1 GFELLEKRTELGLDLLKDLREFLKKRAAIEEEYAKNLQKLAKKFSKKP------ESGKTSLGTSWNSLREETESAATVHE 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209  90 ISENMASQIIVDLARYVQEL-KQERKSNFHDGRKAQQHIETCWKQLESSKrrferdckeadraqqyfekmdadinvtkad 168
Cdd:cd07610   75 ELSEKLSQLIREPLEKVKEDkEQARKKELAEGEKLKKKLQELWAKLAKKA------------------------------ 124

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209 169 vekarqqaqirhqmaedsKADYSSILQKFNHEQHEYYHTHIPNIfQKIQEMEERRIVRMGESMKTYAEVDRQVIPIIGKC 248
Cdd:cd07610  125 ------------------DEEYREQVEKLNPAQSEYEEEKLNKI-QAEQEREEERLEILKDNLKNYINAIKEIPQKIQQE 185

                 ....*.
gi 578817209 249 LDGIVK 254
Cdd:cd07610  186 LEQSIN 191

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578817209 554 TCKALYTFEGQNEGTISVVEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYVEV 608
Cdd:cd11911    1 TCTALYDFDGTSEGTLSMEEGEILLVLEEDGGDGWTRVRKNNGDEGYVPTSYIEV 55

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 578817209 555 CKALYTFEGQNEGTISVVEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYVEV 608
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 578817209   10 QFDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLSKKYQPKKNSKEEEEykYTSCKAFISNLNEMNDYAGQHE 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 578817209 553 GTCKALYTFEGQNEGTISVVEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYVE 607
Cdd:cd11761    2 VTCKVLYSYEAQRPDELTITEGEELEVIEDGDGDGWVKARNKSGEVGYVPENYLQ 56

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Proline-Serine-Threonine Phosphatase-Interacting Proteins; F-BAR domains are dimerization modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganization. Vetebrates contain two Proline-Serine-Threonine Phosphatase-Interacting Proteins (PSTPIPs), PSTPIP1 and PSTPIP2. PSTPIPs are mainly expressed in hematopoietic cells and are involved in the regulation of cell adhesion and motility. Mutations in PSTPIPs have been shown to cause autoinflammatory disorders. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain, while PSTPIP2 contains only the N-terminal F-BAR 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 578817209  11 FDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLSKKYQPKKnskeeeeyKYTSCKAFISNLNEMNDYAGQHEVi 90
Cdd:cd07647    7 FDTLLQRLKEGKKMCKELEDFLKQRAKAEEDYGKALLKLSKSAGPGD--------EIGTLKSSWDSLRKETENVANAHI- 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209  91 seNMAsQIIVDLARYVQEL----KQERKSNFHDGRKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDAdiNVTK 166
Cdd:cd07647   78 --QLA-QSLREEAEKLEEFrekqKEERKKTEDIMKRSQKNKKELYKKTMKAKKSYEQKCREKDKAEQAYEKSSS--GAQP 152

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578817209 167 ADVEKARQQAQIRHQMAEDSKADYSS---ILQKfNHEQHEYYHTHIPNIFQKiqeMEERRI 224
Cdd:cd07647  153 KEAEKLKKKAAQCKTSAEEADSAYKSsigCLED-ARVEWESEHATACQVFQN---MEEERI 209

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 578817209 554 TCKALYTFEGQNEGTISVVEGETLYVIEEDkGDGWTRIRRNEDEEGYVPTSY 605
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 578817209 557 ALYTFEGQNEGTISVVEGETLYVIEEDKGdGWTRIrRNEDEEGYVPTSYVE 607
Cdd:cd11856    4 AIADYEAQGDDEISLQEGEVVEVLEKNDS-GWWYV-RKGDKEGWVPASYLE 52

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 578817209 557 ALYTFEGQNEGTISVVEGETLYVIEEDKGD-GWTRIRRNEDEEGYVPTSYVEV 608
Cdd:cd11767    4 ALYPFTGENDEELSFEKGERLEIIEKPEDDpDWWKARNALGTTGLVPRNYVEV 56

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 578817209  28 YIKFVKERTEIELSYAKQLRNLSKKYQPKKNSKEEEEYKYTSCKAFISnlnEMNDYAGQHEVISENMASQIivdlaryVQ 107
Cdd:cd07655   24 LMKMVQERAEIEKAYAKKLKEWAKKWRDLIEKGPEYGTLETAWKGLLS---EAERLSELHLSIRDKLLNDV-------VE 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209 108 ELKQERKSNFH--------------DG-RKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDADINVTKADVEKA 172
Cdd:cd07655   94 EVKTWQKENYHksmmggfketkeaeDGfAKAQKPWAKLLKKVEKAKKAYHAACKAEKSAQKQENNAKSDTSLSPDQVKKL 173

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209 173 RQQAQIRHQMAEDSKADYSSILQKFNHEQHEYYHThIPNIFQKIQEMEERRIVRMGESMKTYaevdrqvipiiGKCLDGI 252
Cdd:cd07655  174 QDKVEKCKQEVSKTKDKYEKALEDLNKYNPRYMED-MEQVFDKCQEFEEKRLDFFKEILLSY-----------HRHLDLS 241

                 ...
gi 578817209 253 VKA 255
Cdd:cd07655  242 TNP 244

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 578817209  32 VKERTEIELSYAKQLRNLSKKYQpkknSKEEEEYKYTSC-KAFISNLNEMNDYAGQHEVISENMASQiivDLaryvQELK 110
Cdd:cd07680   28 VQERAKIEKAYGQQLTDWAKRWR----QLIEKGPQYGSLeRAWGAIMTEADKVSELHQEVKNNLLNE---DL----EKVK 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209 111 QERKSNFH--------------DG-RKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDADINVTKADVEKARQQ 175
Cdd:cd07680   97 NWQKDAYHkqimggfketkeaeDGfRKAQKPWAKKMKELEAAKKAYHLACKEEKLAMTREANSKAEQSVTPEQQKKLQDK 176

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 578817209 176 AQIRHQMAEDSKADYSSILQKFNHEQHEYYHThIPNIFQKIQEMEERRIVRMGE 229
Cdd:cd07680  177 VDKCKQDVQKTQEKYEKVLDDVGKTTPQYMEN-MEQVFEQCQQFEEKRLVFLKE 229

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 578817209 556 KALYTFEGQNEGTISVVEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYVEV 608
Cdd:cd11897    3 RALYDFRSENPGEISLREHEVLSLCSEQDIEGWLEGVNSRGDRGLFPASYVEV 55

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. 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 578817209 556 KALYTFEGQNEGTISVVEGETLYVIEEDKGDGWTriRRNEDEEGYVPTSYVE 607
Cdd:cd11772    3 RALYDYEAQHPDELSFEEGDLLYISDKSDPNWWK--ATCGGKTGLIPSNYVE 52

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. 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 578817209 557 ALYTFEGQNEGTISVVEGETlYVIEEDKGDGWTRIRRNEDEEGYVPTSYVE 607
Cdd:cd11768    4 ALYDFQPIEPGDLPLEKGEE-YVVLDDSNEHWWRARDKNGNEGYIPSNYVT 53

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578817209 554 TCKALYTFEGQNEGTISVVEGETLYVIEEDKGDGWT-RIRRnedEEGYVPTSYVE 607
Cdd:cd11827    1 QCKALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTgRLRG---KEGLFPGNYVE 52

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 578817209 556 KALYTFEGQNEGTISVVEGETLYVIEEDKGDGWTRIRRNED-EEGYVPTSYVEV 608
Cdd:cd11775    4 KVLYDFDAQSDDELTVKEGDVVYILDDKKSKDWWMVENVSTgKEGVVPASYIEI 57

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 578817209 555 CKALYTFEGQNEGTISVVEGETLYVIEEdKGDGWTRIRRNEDEEGYVPTSYVEV 608
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 578817209 555 CKALYTFEGQNEGTISVVEGETLYVIEEDKGDGWT-RIRRN----EDEEGYVPTSY 605
Cdd:cd11773    2 YKALYDYEPQTEDELTIQEDDILYLLEKSDDDWWKvKLKVNssddDEPVGLVPATY 57

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. 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 578817209 554 TCKALYTFEGQNEGTISVVEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYVEV 608
Cdd:cd11769    3 ECIAKYNFNGASEEDLPFKKGDILTIVAVTKDPNWYKAKNKDGREGMIPANYVQK 57

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 578817209 556 KALYTFEGQNEGTISVVEGETLYVIEEDKGDGWTRIRRNeDEEGYVPTSYVE 607
Cdd:cd11849    3 RALYDFKSAEPNTLSFSEGETFLLLERSNAHWWLVTNHS-GETGYVPANYVK 53

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 578817209  32 VKERTEIELSYAKQLRNLSKKyqpkknskEEEEYKYTSCKAFISNLNEMNDYAGQHEVISENMASQIIVDLARYVQELKQ 111
Cdd:cd07671   28 LKQRAQAEERYGKELVQIARK--------AGGQTEINTLKASFDQLKQQIENIGNSHIQLAGMLREELKSLEEFRERQKE 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209 112 ERKSNFHDGRKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDAdiNVTKADVEKARQQAQIRHQMAEDSKADYS 191
Cdd:cd07671  100 QRKKYEAVMERVQKSKVSLYKKTMESKKTYEQRCREADEAEQTFERSSS--TGNPKQSEKSQNKAKQCRDAATEAERVYK 177

                        170       180       190
                 ....*....|....*....|....*....|...
gi 578817209 192 SILQKFNHEQHEYYHTHIpNIFQKIQEMEERRI 224
Cdd:cd07671  178 QNIEQLDKARTEWETEHI-LTCEVFQLQEDDRI 209

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 578817209 555 CKALYTFEGQNEGTISVVEGETLYVIEEDKGD-GWTRIRRNEdEEGYVPTSYVE 607
Cdd:cd11836    2 YRALYAFEARNPDEISFQPGDIIQVDESQVAEpGWLAGELKG-KTGWFPANYVE 54

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Protein kinase C and Casein kinase Substrate in Neurons 2 (PACSIN2); 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 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. PACSIN 2 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 578817209  32 VKERTEIELSYAKQLRNLSKKYqpkKNSKEEEEYKYTSCKAFISNLNEMNDYAGQH-EVISENMASQIivdlaryvQELK 110
Cdd:cd07679   28 LHERARIEKVYAQQLTEWAKRW---RQLVEKGPQYGTVEKAWCALMSEAEKVSELHlEVKASLMNEDF--------EKIK 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209 111 QERKSNFH--------------DG-RKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDADINVTKADVEKARQQ 175
Cdd:cd07679   97 NWQKEAFHkqmmggfketkeaeDGfRKAQKPWAKKLKEVEAAKKAYHTACKEEKLATSREANSKADPALNPEQLKKLQDK 176

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 578817209 176 AQIRHQMAEDSKADYSSILQKFNHEQHEYYHtHIPNIFQKIQEMEERRI 224
Cdd:cd07679  177 VEKCKQDVLKTKEKYEKSLKELDQTTPQYME-NMEQVFEQCQQFEEKRL 224

The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); 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 3 or Syndapin III is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSIN 3 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 578817209  33 KERTEIELSYAKQLRNLSKKYqpkKNSKEEEEYKYTSCKAFISNLNEMNDYAGQHEVISENMASQIIVDLARYVQEL--K 110
Cdd:cd07681   29 QERAKIEKGYAQQLSDWARKW---RGIVEKGPQYGTLEKAWHAFLTAAERLSEIHLELRENLVGEDSEKVRAWQKEAfhK 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578817209 111 Q------ERKSNFHDGRKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDADINVTKADVEKARQQAQIRHQMAE 184
Cdd:cd07681  106 QmiggfrESKEAEEGFRKAQKPWVKKLKEVESSKKGYHAARKDERTAQTRETHAKADSTVSQEQLRKLQDRVEKCTQEAE 185

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 578817209 185 DSKADYSSILQKFNHEQHEYYHThIPNIFQKIQEMEERRI 224
Cdd:cd07681  186 KAKEQYEKALEELNRYNPRYMED-MEQAFEICQEAERKRL 224

Src homology 3 domain of Srms Protein Tyrosine Kinase; Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (Srms) is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Srms lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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 578817209 557 ALYTFEGQNEGTISVVEGETLYVIEEDKGDGWTRIRRNEDEEGYVPTSYV 606
Cdd:cd11846    4 ALYDFTARSTHELSVEQGDKLCVIEEEGDYIFARKLTGNPESGLVPASYV 53