The Bin/Amphiphysin/Rvs (BAR) domain of Amphiphysin I and II; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Amphiphysins function primarily in endocytosis and other membrane remodeling events. They contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin and synaptojanin. They function in synaptic vesicle endocytosis. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. The N-BAR domain of amphiphysin forms a curved dimer with a positively-charged concave face that can drive membrane bending and curvature. Human autoantibodies to amphiphysin-1 hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Mutations in amphiphysin-2 (BIN1) are associated with autosomal recessive centronuclear myopathy.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514  26 QKLGKADETKDEQFEEYVQNFKRQEAEGTRLQRELRGYLAAIKGMQEASMKLTESLHEVYEPDWYGREDVKMVGEKCDVL 105
Cdd:cd07611     1 QKLGKADETKDEQFEEYVQNFKRQETEGTRLQRELRAYLAAIKGMQEASKKLTESLHEVYEPDWYGRDDVKTIGEKCDLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514 106 WEDFHQKLVDGSLLTLDTYLGQFPDIKNRIAKRSRKLVDYDSARHHLEALQSSKRKDESRISKAEEEFQKAQKVFEEFNV 185
Cdd:cd07611    81 WEDFHQKLVDGALLTLDTYLGQFPDIKNRIAKRSRKLVDYDSARHHLEALQTSKRKDEGRIAKAEEEFQKAQKVFEEFNV 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1121947514 186 DLQEELPSLWSRRVGFYVNTFKNVSSLEAKFHKEIAVLCHKLYEVMTKLGD 236
Cdd:cd07611   161 DLQEELPSLWSRRVGFYVNTFKNVSSLEAKFHKEISVLCHKLYEVMTKLGE 211

ORF080 virion core protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514 248 APSDSGPLRIAKTPSP------PEEASPIPSPTASP--NHTLAPAS--PAPVRPRS--PSQTRKGPPVPPLPKVTPTKE- 314
Cdd:PHA02682   83 APSPACAAPAPACPACapaapaPAVTCPAPAPACPPatAPTCPPPAvcPAPARPAPacPPSTRQCPPAPPLPTPKPAPAa 162

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514 315 ----LQQENIINFFEDNFVPEISvTTPSQNEVPEVKKEETLLDLDF---DPFKPEVAAAGSAGVTHSPMSQTLPWDLWTT 387
Cdd:PHA02682  163 kpifLHNQLPPPDYPAASCPTIE-TAPAASPVLEPRIPDKIIDADNddkDLIKKELADIADSVRDLNAESLSLTRDIENA 241

                         170       180
                  ....*....|....*....|....*...
gi 1121947514 388 -STDLAQPTDSSKSLSLCNLIMEETPDS 414
Cdd:PHA02682  242 kSTTQAAIDDLRRLLTGGGVARRDTPSA 269

The Bin/Amphiphysin/Rvs (BAR) domain of Amphiphysin I and II; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Amphiphysins function primarily in endocytosis and other membrane remodeling events. They contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin and synaptojanin. They function in synaptic vesicle endocytosis. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. The N-BAR domain of amphiphysin forms a curved dimer with a positively-charged concave face that can drive membrane bending and curvature. Human autoantibodies to amphiphysin-1 hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Mutations in amphiphysin-2 (BIN1) are associated with autosomal recessive centronuclear myopathy.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514  26 QKLGKADETKDEQFEEYVQNFKRQEAEGTRLQRELRGYLAAIKGMQEASMKLTESLHEVYEPDWYGREDVKMVGEKCDVL 105
Cdd:cd07611     1 QKLGKADETKDEQFEEYVQNFKRQETEGTRLQRELRAYLAAIKGMQEASKKLTESLHEVYEPDWYGRDDVKTIGEKCDLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514 106 WEDFHQKLVDGSLLTLDTYLGQFPDIKNRIAKRSRKLVDYDSARHHLEALQSSKRKDESRISKAEEEFQKAQKVFEEFNV 185
Cdd:cd07611    81 WEDFHQKLVDGALLTLDTYLGQFPDIKNRIAKRSRKLVDYDSARHHLEALQTSKRKDEGRIAKAEEEFQKAQKVFEEFNV 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1121947514 186 DLQEELPSLWSRRVGFYVNTFKNVSSLEAKFHKEIAVLCHKLYEVMTKLGD 236
Cdd:cd07611   161 DLQEELPSLWSRRVGFYVNTFKNVSSLEAKFHKEISVLCHKLYEVMTKLGE 211

BAR domain; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different protein families. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysin, endophilin, BRAP and Nadrin. BAR domains are also frequently found alongside domains that determine lipid specificity, like pfam00169 and pfam00787 domains in beta centaurins and sorting nexins respectively.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514  13 VQKRLNRAQEKVLQKLGKADETK-DEQFEEYVQNFKRQEAEGTRLQRELRGYLAAIKGMQEASM-------KLTESLHEV 84
Cdd:pfam03114   1 LKKQFNRASQLLGEKVGGAEKTKlDEDFEELERRFDTTEKEIKKLQKDTKGYLQPNPGARAKQTvleqpeeLLAESMIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514  85 YEPDWYGR------EDVKMVGEKCDVLWEDFHQKLVDGSLLTLDTYLGQFPDIKNRIAKRSRKLVDYDSARHHLEALQSS 158
Cdd:pfam03114  81 GKDLGEDSsfgkalEDYGEALKRLAQLLEQLDDRVETNFLDPLRNLLKEFKEIQKHRKKLERKRLDYDAAKTRVKKAKKK 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1121947514 159 KRKDESRISKAEEEFQKAQKVFEEFNVDLQEELPSLWSRRVGFYVNTFKNVSSLEAKFHKEIAVLCHKLYEVMTK 233
Cdd:pfam03114 161 KSSKAKDESQAEEELRKAQAKFEESNEQLKALLPNLLSLEVEFVVNQLVAFVEAQLDFHRQCYQLLEQLQQQLGK 235

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
                   ....*....|....*....|....*....|....*....|..
gi 1121947514  789 YKVEALHDFEAANADELTLQRGDVVLVVpSDSEADQVKAEVG 830
Cdd:smart00326   3 PQVRALYDYTAQDPDELSFKKGDIITVL-EKSDDGWWKGRLG 43

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
                  ....*....|....*....|....*....|....*.
gi 1121947514 793 ALHDFEAANADELTLQRGDVVLVVpSDSEADQVKAE 828
Cdd:pfam00018   2 ALYDYTAQEPDELSFKKGDIIIVL-EKSEDGWWKGR 36

The Bin/Amphiphysin/Rvs (BAR) domain of Amphiphysin I and II; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Amphiphysins function primarily in endocytosis and other membrane remodeling events. They contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin and synaptojanin. They function in synaptic vesicle endocytosis. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. The N-BAR domain of amphiphysin forms a curved dimer with a positively-charged concave face that can drive membrane bending and curvature. Human autoantibodies to amphiphysin-1 hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Mutations in amphiphysin-2 (BIN1) are associated with autosomal recessive centronuclear myopathy.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514  26 QKLGKADETKDEQFEEYVQNFKRQEAEGTRLQRELRGYLAAIKGMQEASMKLTESLHEVYEPDWYGREDVKMVGEKCDVL 105
Cdd:cd07611     1 QKLGKADETKDEQFEEYVQNFKRQETEGTRLQRELRAYLAAIKGMQEASKKLTESLHEVYEPDWYGRDDVKTIGEKCDLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514 106 WEDFHQKLVDGSLLTLDTYLGQFPDIKNRIAKRSRKLVDYDSARHHLEALQSSKRKDESRISKAEEEFQKAQKVFEEFNV 185
Cdd:cd07611    81 WEDFHQKLVDGALLTLDTYLGQFPDIKNRIAKRSRKLVDYDSARHHLEALQTSKRKDEGRIAKAEEEFQKAQKVFEEFNV 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1121947514 186 DLQEELPSLWSRRVGFYVNTFKNVSSLEAKFHKEIAVLCHKLYEVMTKLGD 236
Cdd:cd07611   161 DLQEELPSLWSRRVGFYVNTFKNVSSLEAKFHKEISVLCHKLYEVMTKLGE 211

The Bin/Amphiphysin/Rvs (BAR) domain of Bridging integrator 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Bridging integrator 2 (Bin2) is a BAR domain containing protein that is mainly expressed in hematopoietic cells. It is upregulated during granulocyte differentiation and is thought to function primarily in this lineage. The BAR domain of Bin2 is closely related to the BAR domains of amphiphysins, which function primarily in endocytosis and other membrane remodeling events. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. Unlike amphiphysins, Bin2 does not appear to contain a C-terminal SH3 domain. Amphiphysin I proteins, enriched in the brain and nervous system, function in synaptic vesicle endocytosis. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), function in intracellular vessicle trafficking. Bin2 can form a stable complex with Bin1 in cells but cannot replace the function of Bin1, and thus, appears to harbor a nonredundant function. The N-BAR domain of amphiphysin forms a curved dimer with a positively-charged concave face that can drive membrane bending and curvature.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514  26 QKLGKADETKDEQFEEYVQNFKRQEAEGTRLQRELRGYLAAIKGMQEASMKLTESLHEVYEPDWYGREDVKMVGEKCDVL 105
Cdd:cd07612     1 QKLGKTVETKDEQFEQCAMNLNMQQSDGNRLYKDLKAYLNAVKVMHESSKRLSQTLQDIYEPDWDGHEDLGAIVEGEDLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514 106 WEDFHQKLVDGSLLTLDTYLGQFPDIKNRIAKRSRKLVDYDSARHHLEALQSSKRKDESRISKAEEEFQKAQKVFEEFNV 185
Cdd:cd07612    81 WNDYEAKLHDQALRTMESYMAQFPDVKERVAKRGRKLVDYDSARHHLEALQNAKKKDDAKIAKAEEEFNRAQVVFEDINR 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1121947514 186 DLQEELPSLWSRRVGFYVNTFKNVSSLEAKFHKEIAVLCHKLYEVMTKLGD 236
Cdd:cd07612   161 ELREELPILYDSRIGCYVTVFQNISNLRDTFYKEMSKLNHDLYNVMKKLED 211

BAR domain; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different protein families. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysin, endophilin, BRAP and Nadrin. BAR domains are also frequently found alongside domains that determine lipid specificity, like pfam00169 and pfam00787 domains in beta centaurins and sorting nexins respectively.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514  13 VQKRLNRAQEKVLQKLGKADETK-DEQFEEYVQNFKRQEAEGTRLQRELRGYLAAIKGMQEASM-------KLTESLHEV 84
Cdd:pfam03114   1 LKKQFNRASQLLGEKVGGAEKTKlDEDFEELERRFDTTEKEIKKLQKDTKGYLQPNPGARAKQTvleqpeeLLAESMIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514  85 YEPDWYGR------EDVKMVGEKCDVLWEDFHQKLVDGSLLTLDTYLGQFPDIKNRIAKRSRKLVDYDSARHHLEALQSS 158
Cdd:pfam03114  81 GKDLGEDSsfgkalEDYGEALKRLAQLLEQLDDRVETNFLDPLRNLLKEFKEIQKHRKKLERKRLDYDAAKTRVKKAKKK 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1121947514 159 KRKDESRISKAEEEFQKAQKVFEEFNVDLQEELPSLWSRRVGFYVNTFKNVSSLEAKFHKEIAVLCHKLYEVMTK 233
Cdd:pfam03114 161 KSSKAKDESQAEEELRKAQAKFEESNEQLKALLPNLLSLEVEFVVNQLVAFVEAQLDFHRQCYQLLEQLQQQLGK 235

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514  45 NFKRQEAEGTRLQRELRGYLAAIKGMQEASMKLTESLHEVYE-----PDWYGREDVKMVGEKCDVL---WEDFHQKLVDG 116
Cdd:cd07307     1 KLDELEKLLKKLIKDTKKLLDSLKELPAAAEKLSEALQELGKelpdlSNTDLGEALEKFGKIQKELeefRDQLEQKLENK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514 117 SLLTLDTYL-GQFPDIKNRIAKRSRKLVDYDSARHHLEALQSsKRKDESRISKAEEEFQKAQKVFEEFNVDLQEELPSLW 195
Cdd:cd07307    81 VIEPLKEYLkKDLKEIKKRRKKLDKARLDYDAAREKLKKLRK-KKKDSSKLAEAEEELQEAKEKYEELREELIEDLNKLE 159

                         170       180
                  ....*....|....*....|....*.
gi 1121947514 196 SRRVGFYVNTFKNVSSLEAKFHKEIA 221
Cdd:cd07307   160 EKRKELFLSLLLSFIEAQSEFFKEVL 185

The Bin/Amphiphysin/Rvs (BAR) domain of Saccharomyces cerevisiae Reduced viability upon starvation protein 167 and similar proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of fungal proteins with similarity to Saccharomyces cerevisiae Reduced viability upon starvation protein 167 (Rvs167p) and Schizosaccharomyces pombe Hob1 (homolog of Bin1). S. cerevisiae Rvs167p plays a role in regulation of the actin cytoskeleton, endocytosis, and sporulation. It forms a heterodimer with another BAR domain protein Rvs161p. Rvs161p and Rvs167p share common functions but are not interchangeable. Their BAR domains cannot be replaced with each other and the overexpression of one cannot suppress the mutant phenotypes of the other. Rvs167p also interacts with the GTPase activating protein (GAP) Gyp5p, which is involved in ER to Golgi vesicle trafficking. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514  36 DEQFEEYVQNFKRQEAEGTRLQRELRGYLAAIKGMQEASMKLTESLHEVYEPdwygredvkMVGEKCDVL---------- 105
Cdd:cd07599     1 DEQFEELEKDFKSLEKSLKKLIEQSKAFRDSWRSILTHQIAFAKEFAELYDP---------IVGPKESVGshpapestla 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514 106 ----WEDFHQKLVDGSLLTLDTY-----------LGQFPDIKNRIAKRSRKLVDYDSARHHLEALQSSKR----KDESRI 166
Cdd:cd07599    72 rlsrYVKALEELKKELLEELEFFeervilpakelKKYIKKIRKTIKKRDHKKLDYDKLQNKLNKLLQKKKelslKDEKQL 151

                         170       180
                  ....*....|....*....|....*...
gi 1121947514 167 SKAEEEFQKAQKVFEEFNVDLQEELPSL 194
Cdd:cd07599   152 AKLERKLEEAKEEYEALNELLKSELPKL 179

The Bin/Amphiphysin/Rvs (BAR) domain of Dynamin Binding Protein; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. DyNamin Binding Protein (DNMBP), also called Tuba, is a Cdc42-specific Guanine nucleotide Exchange Factor (GEF) that binds dynamin and various actin regulatory proteins. It serves as a link between dynamin function, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. DNMBP contains BAR and SH3 domains as well as a Dbl Homology domain (DH domain), which harbors GEF activity. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of DNMBP may be involved in binding to membranes. The gene encoding DNMBP is a candidate gene for late onset Alzheimer's disease.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514  33 ETKDEQFEEYVQNFKRQEAEGTRLQRELRGYLAAIKGMQEASMKLTESLHEVYEPD--------WYGREDVKMVGEKcdv 104
Cdd:cd07589     1 QTKDKEFDELEKKFGSLEKQVQLVVRNVELYLQHVQESVLVKVLALEVVLDLYPSNhprleskwERFRRVVRGISSK--- 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514 105 LWEDFH---QKLVdgsLLTLDTYLGQFPDIKNRIAKRSRKLVDYDSARhhlealqssKRKDESRisKAEEEFQKAQKVFE 181
Cdd:cd07589    78 ALPEFKsrvRKLV---IEPLSSLLKLFSGPQKLIQKRYDKLLDYERYK---------EKKERGG--KVDEELEEAANQYE 143

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1121947514 182 EFNVDLQEELPSLWSRRVGFYVNTFKNVSSLEAKFHKEI 220
Cdd:cd07589   144 ALNAQLKEELPKFNQLTAQLLETCLKSFVELQRDLYDTL 182

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
                   ....*....|....*....|....*....|....*....|..
gi 1121947514  789 YKVEALHDFEAANADELTLQRGDVVLVVpSDSEADQVKAEVG 830
Cdd:smart00326   3 PQVRALYDYTAQDPDELSFKKGDIITVL-EKSDDGWWKGRLG 43

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1121947514 793 ALHDFEAANADELTLQRGDVVLVVPSDSEadqVKAEVGMW 832
Cdd:cd11876     4 ALFDYDARGEDELTLRRGQPVEVLSKDAA---VSGDEGWW 40

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
                  ....*....|....*....|....*....|....*.
gi 1121947514 793 ALHDFEAANADELTLQRGDVVLVVpSDSEADQVKAE 828
Cdd:pfam00018   2 ALYDYTAQEPDELSFKKGDIIIVL-EKSEDGWWKGR 36

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), 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
                  ....*....|....*....|....*....|....*....
gi 1121947514 790 KVEALHDFEAANADELTLQRGDVVLVVpSDSEADQVKAE 828
Cdd:cd11963     3 KVRALYDFEAVEDNELTFKHGEIIIVL-DDSDANWWKGE 40

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1121947514 793 ALHDFEAANADELTLQRGDVVLVVPSDSeadQVKAEVGMW 832
Cdd:cd12059     4 AVFDYEASAEDELTLRRGDRVEVLSKDS---AVSGDEGWW 40

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1121947514 793 ALHDFEAANADELTLQRGDVVLVVPSDSeadQVKAEVGMW 832
Cdd:cd12058     4 ALYDYEASGEDELSLRRGDVVEVLSQDA---AVSGDDGWW 40

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH 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
                  ....*....|....*....|....*
gi 1121947514 791 VEALHDFEAANADELTLQRGDVVLV 815
Cdd:cd11793     2 VQCVHAYTAQQPDELTLEEGDVVNV 26

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
                  ....*....|....*....|....*.
gi 1121947514 790 KVEALHDFEAANADELTLQRGDVVLV 815
Cdd:cd11836     1 KYRALYAFEARNPDEISFQPGDIIQV 26

ribonuclease E; Reviewed

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514  599 APPAEPKAEEPPATVTPAVGLDAGLDTRAEEPVEEAV-----IMPGSDADVTVETlvsAEEGSPVEEAETEKAALPTVEE 673
Cdd:PRK10811   888 VEAVAEVVEEPVVVAEPQPEEVVVVETTHPEVIAAPVteqpqVITESDVAVAQEV---AEHAEPVVEPQDETADIEEAAE 964

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1121947514  674 VglegPKIDTAATEVVDGDRSQPEGTEAAARQEKAIPSVVIEPASNNEGEGEHETA 729
Cdd:PRK10811   965 T----AEVVVAEPEVVAQPAAPVVAEVAAEVETVTAVEPEVAPAQVPEATVEHNHA 1016

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20
                  ....*....|....*....|....*..
gi 1121947514 790 KVEALHDFEAANADELTLQRGDVVLVV 816
Cdd:cd11877     1 LVRAKFNFEGTNEDELSFDKGDIITVT 27

Src Homology 3 domain of fungal BOI-like proteins; This subfamily includes the Saccharomyces cerevisiae proteins BOI1 and BOI2, and similar proteins. They contain an N-terminal SH3 domain, a Sterile alpha motif (SAM), and a Pleckstrin homology (PH) domain at the C-terminus. BOI1 and BOI2 interact with the SH3 domain of Bem1p, a protein involved in bud formation. They promote polarized cell growth and participates in the NoCut signaling pathway, which is involved in the control of cytokinesis. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1121947514 791 VEALHDFEAANADELTLQRGDVVLVVPSDSE 821
Cdd:cd11886     2 LIVIHDFNARSEDELTLKPGDKIELIEDDEE 32

DNA polymerase III subunit gamma/tau;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514 599 APPAEPKAEEPPATVTPAVGLDAGLDTRAEEPVEEAvimPGSDADVTVEtlvSAEEGSPVEEAETEKAALPTVEEVGLEG 678
Cdd:PRK07003  396 VPAVTAVTGAAGAALAPKAAAAAAATRAEAPPAAPA---PPATADRGDD---AADGDAPVPAKANARASADSRCDERDAQ 469

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1121947514 679 PKIDTAATEVVDGDrsqpegTEAAARQEKAIPSVVIEPASNNeGEGEHETAAGAESKEATKDAALPGPTSETAEPA 754
Cdd:PRK07003  470 PPADSGSASAPASD------APPDAAFEPAPRAAAPSAATPA-AVPDARAPAAASREDAPAAAAPPAPEARPPTPA 538

Fifth Src homology 3 domain (or SH3E) 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 fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1121947514 790 KVEALHDFEAANADELTLQRGDVVLVVPSDsEADQVKAEVG 830
Cdd:cd11840     1 QVIALFPYTAQNEDELSFQKGDIINVLSKD-DPDWWRGELN 40

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. 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
                  ....*....|....*....|....*....|....*..
gi 1121947514 793 ALHDFEAANADELTLQRGDVVLVVPSDSEADQVKAEV 829
Cdd:cd11948     4 ALYSFQATESDELPFQKGDILKILNMEDDQNWYKAEL 40

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They 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, Brk 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. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. 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
                  ....*....|....*....|....*....|....*.
gi 1121947514 793 ALHDFEAANADELTLQRGDVVLVVpSDSEADQVKAE 828
Cdd:cd11845     4 ALYDYEARTDDDLSFKKGDRLQIL-DDSDGDWWLAR 38

DNA polymerase III subunit gamma/tau;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514 599 APPAEPKAEEPPATVTPAVGLDAGLDTRAEEPVEEAvimpgsdadVTVETLVSAEEGSPVEEAETEKAALPTVEEVGLEG 678
Cdd:PRK12323  397 PAPAAPPAAPAAAPAAAAAARAVAAAPARRSPAPEA---------LAAARQASARGPGGAPAPAPAPAAAPAAAARPAAA 467

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1121947514 679 PKIDTAATEVVDGDRSQPEGTEAAARQE----KAIPSVVIEPASNNEGEGEHETAAGAESKEATKDAALPGPTSETAePA 754
Cdd:PRK12323  468 GPRPVAAAAAAAPARAAPAAAPAPADDDpppwEELPPEFASPAPAQPDAAPAGWVAESIPDPATADPDDAFETLAPA-PA 546

                         170       180
                  ....*....|....*....|....*..
gi 1121947514 755 TEQKTTEQTTEDPQPAPSAPSTSEASL 781
Cdd:PRK12323  547 AAPAPRAAAATEPVVAPRPPRASASGL 573