TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain; The TBC1D1-like members here include TBC1D1, TBC1D4 (also called Akt substrate of 160 kDa or AS160), and pollux (PLX), a calmodulin-binding protein, and are thought to have a role in regulating cell growth and differentiation. These proteins are thought to function as GTPase-activating protein for Rab family protein(s). They may play a role in the cell cycle and differentiation of various tissues. They all contain an N-terminal PTB domain, a calmodulin CBD domain, and a C-terminal TBC domain which is thought to be a GTPase activator protein of Rab-like small GTPases. Recently, TBC1D1 and TBC1D4 were recognized to potentially link the proximal signalling of insulin and/or exercise with GLUT4. TBC1D4 is thought to be involved in contraction-stimulated glucose uptake, but TBC1D4-independent mechanisms (potentially involving TBC1D1) are likely to be essential for most of the contraction's effect. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034639040  164 EFDDTFSKKFEVLFCGRVTVAHKKAPPALIDECIEKFNHVSGSRGSesprpnpphaaptgsqepvrrpmrksfsqpglrs 243
Cdd:cd01269      1 DISPSNSQFFEVLYCGKIKVSHKKVPPTFIDDCLEKFRLHELEKSR---------------------------------- 46

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034639040  244 lafrkelqdgglrssgffssfeesdienhliSGHNIVQPTDIEENRTMLFTIGQSEVYLISPDTKKIALEKNFKEISFCS 323
Cdd:cd01269     47 -------------------------------SGPSSVQPTDSEENRTMLFQIGRSELRLISPDTKQVLLEKQFKDISSCS 95

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1034639040  324 QGIRHVDHFGFICRESSGGGGFHFVCYVFQCTNEALVDEIMMTLKQAF 371
Cdd:cd01269     96 QGIKHVDHFGFICRESSEGGGFHFVCYVFKCQSESVVDEIMLTIKQAF 143

Domain of unknown function (DUF3350); This domain is functionally uncharacterized and is found in eukaryotic proteins, such as TBC1 domain family members 1 and 4. This presumed domain is typically between 50 to 64 amino acids in length. TBC domain proteins may act as GTPase-activating proteins for RAB2A, RAB8A, RAB10 and RAB14.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034639040  703 ELPPRSPLEPVCEDGP-------FGPPPEEKKRTSRELRELWQKAILQQILLLRMEKENQKLQ 758
Cdd:pfam11830    1 ELLPLSPLAPGGEEDPagllsseDSPVGEKKKRTSEELRELWRKAIHQQILLLRMEKENQKLE 63

Cell division protein ZapB, interacts with FtsZ [Cell cycle control, cell division, chromosome partitioning];

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034639040 1107 NLDLLEQL----QVANGRIQSLEATIEKLLSSESKLKQAMLTLELERSALLQTVEELRRRSAEPSDR 1169
Cdd:COG3074      2 SLELLEELeakvQQAVDTIELLQMEVEELKEKNEELEQENEELQSENEELQSENEQLKTENAEWQER 68

TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain; The TBC1D1-like members here include TBC1D1, TBC1D4 (also called Akt substrate of 160 kDa or AS160), and pollux (PLX), a calmodulin-binding protein, and are thought to have a role in regulating cell growth and differentiation. These proteins are thought to function as GTPase-activating protein for Rab family protein(s). They may play a role in the cell cycle and differentiation of various tissues. They all contain an N-terminal PTB domain, a calmodulin CBD domain, and a C-terminal TBC domain which is thought to be a GTPase activator protein of Rab-like small GTPases. Recently, TBC1D1 and TBC1D4 were recognized to potentially link the proximal signalling of insulin and/or exercise with GLUT4. TBC1D4 is thought to be involved in contraction-stimulated glucose uptake, but TBC1D4-independent mechanisms (potentially involving TBC1D1) are likely to be essential for most of the contraction's effect. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034639040  164 EFDDTFSKKFEVLFCGRVTVAHKKAPPALIDECIEKFNHVSGSRGSesprpnpphaaptgsqepvrrpmrksfsqpglrs 243
Cdd:cd01269      1 DISPSNSQFFEVLYCGKIKVSHKKVPPTFIDDCLEKFRLHELEKSR---------------------------------- 46

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034639040  244 lafrkelqdgglrssgffssfeesdienhliSGHNIVQPTDIEENRTMLFTIGQSEVYLISPDTKKIALEKNFKEISFCS 323
Cdd:cd01269     47 -------------------------------SGPSSVQPTDSEENRTMLFQIGRSELRLISPDTKQVLLEKQFKDISSCS 95

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1034639040  324 QGIRHVDHFGFICRESSGGGGFHFVCYVFQCTNEALVDEIMMTLKQAF 371
Cdd:cd01269     96 QGIKHVDHFGFICRESSEGGGFHFVCYVFKCQSESVVDEIMLTIKQAF 143

Rab-GTPase-TBC domain; Identification of a TBC domain in GYP6_YEAST and GYP7_YEAST, which are GTPase activator proteins of yeast Ypt6 and Ypt7, implies that these domains are GTPase activator proteins of Rab-like small GTPases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034639040  858 QHAILIDLGRTFPTHPYFsaQLGAGQLSLYNILKAYSLLDQEVGYCQGLSFVAGILLL-HMSEEEAFKMLKFLMFDMGLR 936
Cdd:pfam00566    9 PEQIEKDVPRTFPHSFFF--DNGPGQNSLRRILKAYSIYNPDVGYCQGMNFIAAPLLLvYLDEEDAFWCFVSLLENYLLR 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034639040  937 KQYRPDMIILQIQMYQLSRLLHDYHRDLYNHLEEHEIGPSLYAAPWFLTMFASQFPLGFVARVFDMIFLQGTEV-IFKVA 1015
Cdd:pfam00566   87 DFYTPDFPGLKRDLYVFEELLKKKLPKLYKHLKELGLDPDLFASQWFLTLFAREFPLSTVLRIWDYFFLEGEKFvLFRVA 166

                          170
                   ....*....|..
gi 1034639040 1016 LSLLGSHKPLIL 1027
Cdd:pfam00566  167 LAILKRFREELL 178

Domain of unknown function (DUF3350); This domain is functionally uncharacterized and is found in eukaryotic proteins, such as TBC1 domain family members 1 and 4. This presumed domain is typically between 50 to 64 amino acids in length. TBC domain proteins may act as GTPase-activating proteins for RAB2A, RAB8A, RAB10 and RAB14.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034639040  703 ELPPRSPLEPVCEDGP-------FGPPPEEKKRTSRELRELWQKAILQQILLLRMEKENQKLQ 758
Cdd:pfam11830    1 ELLPLSPLAPGGEEDPagllsseDSPVGEKKKRTSEELRELWRKAIHQQILLLRMEKENQKLE 63

Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to bind peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034639040   21 FGLQLVGSLPVHSLTTMPMlpwVVAEVRRLSRQSTRKEPVTKQVRLCVSPSGLRCEpEPGRSQQWDPLIYSSIFECkpqr 100
Cdd:cd00934      3 FQVKYLGSVEVGSSRGVDV---VEEALKALAAALKSSKRKPGPVLLEVSSKGVKLL-DLDTKELLLRHPLHRISYC---- 74

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1034639040  101 vhklIHNSHDPSYFACLIKEDAVhRQSICYVFKADDQTKVPEIISSIRQA 150
Cdd:cd00934     75 ----GRDPDNPNVFAFIAGEEGG-SGFRCHVFQCEDEEEAEEILQAIGQA 119

Cell division protein ZapB, interacts with FtsZ [Cell cycle control, cell division, chromosome partitioning];

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034639040 1107 NLDLLEQL----QVANGRIQSLEATIEKLLSSESKLKQAMLTLELERSALLQTVEELRRRSAEPSDR 1169
Cdd:COG3074      2 SLELLEELeakvQQAVDTIELLQMEVEELKEKNEELEQENEELQSENEELQSENEQLKTENAEWQER 68

TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain; The TBC1D1-like members here include TBC1D1, TBC1D4 (also called Akt substrate of 160 kDa or AS160), and pollux (PLX), a calmodulin-binding protein, and are thought to have a role in regulating cell growth and differentiation. These proteins are thought to function as GTPase-activating protein for Rab family protein(s). They may play a role in the cell cycle and differentiation of various tissues. They all contain an N-terminal PTB domain, a calmodulin CBD domain, and a C-terminal TBC domain which is thought to be a GTPase activator protein of Rab-like small GTPases. Recently, TBC1D1 and TBC1D4 were recognized to potentially link the proximal signalling of insulin and/or exercise with GLUT4. TBC1D4 is thought to be involved in contraction-stimulated glucose uptake, but TBC1D4-independent mechanisms (potentially involving TBC1D1) are likely to be essential for most of the contraction's effect. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034639040  164 EFDDTFSKKFEVLFCGRVTVAHKKAPPALIDECIEKFNHVSGSRGSesprpnpphaaptgsqepvrrpmrksfsqpglrs 243
Cdd:cd01269      1 DISPSNSQFFEVLYCGKIKVSHKKVPPTFIDDCLEKFRLHELEKSR---------------------------------- 46

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034639040  244 lafrkelqdgglrssgffssfeesdienhliSGHNIVQPTDIEENRTMLFTIGQSEVYLISPDTKKIALEKNFKEISFCS 323
Cdd:cd01269     47 -------------------------------SGPSSVQPTDSEENRTMLFQIGRSELRLISPDTKQVLLEKQFKDISSCS 95

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1034639040  324 QGIRHVDHFGFICRESSGGGGFHFVCYVFQCTNEALVDEIMMTLKQAF 371
Cdd:cd01269     96 QGIKHVDHFGFICRESSEGGGFHFVCYVFKCQSESVVDEIMLTIKQAF 143

Rab-GTPase-TBC domain; Identification of a TBC domain in GYP6_YEAST and GYP7_YEAST, which are GTPase activator proteins of yeast Ypt6 and Ypt7, implies that these domains are GTPase activator proteins of Rab-like small GTPases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034639040  858 QHAILIDLGRTFPTHPYFsaQLGAGQLSLYNILKAYSLLDQEVGYCQGLSFVAGILLL-HMSEEEAFKMLKFLMFDMGLR 936
Cdd:pfam00566    9 PEQIEKDVPRTFPHSFFF--DNGPGQNSLRRILKAYSIYNPDVGYCQGMNFIAAPLLLvYLDEEDAFWCFVSLLENYLLR 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034639040  937 KQYRPDMIILQIQMYQLSRLLHDYHRDLYNHLEEHEIGPSLYAAPWFLTMFASQFPLGFVARVFDMIFLQGTEV-IFKVA 1015
Cdd:pfam00566   87 DFYTPDFPGLKRDLYVFEELLKKKLPKLYKHLKELGLDPDLFASQWFLTLFAREFPLSTVLRIWDYFFLEGEKFvLFRVA 166

                          170
                   ....*....|..
gi 1034639040 1016 LSLLGSHKPLIL 1027
Cdd:pfam00566  167 LAILKRFREELL 178

Domain of unknown function (DUF3350); This domain is functionally uncharacterized and is found in eukaryotic proteins, such as TBC1 domain family members 1 and 4. This presumed domain is typically between 50 to 64 amino acids in length. TBC domain proteins may act as GTPase-activating proteins for RAB2A, RAB8A, RAB10 and RAB14.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034639040  703 ELPPRSPLEPVCEDGP-------FGPPPEEKKRTSRELRELWQKAILQQILLLRMEKENQKLQ 758
Cdd:pfam11830    1 ELLPLSPLAPGGEEDPagllsseDSPVGEKKKRTSEELRELWRKAIHQQILLLRMEKENQKLE 63

Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to bind peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034639040  286 EENRTMLFTIGQSEVYLISPDTKKIALEKNFKEISFCSQGIRHVDHFGFICRESsggGGFHFVCYVFQCTNEALVDEIMM 365
Cdd:cd00934     38 RKPGPVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRDPDNPNVFAFIAGEE---GGSGFRCHVFQCEDEEEAEEILQ 114

                   ....*.
gi 1034639040  366 TLKQAF 371
Cdd:cd00934    115 AIGQAF 120

Ankyrin repeat and sterile alpha motif (SAM) domain-containing (Anks) protein family Phosphotyrosine-binding (PTB) domain; Both AIDA-1b (AbetaPP intracellular domain-associated protein 1b) and Odin (also known as ankyrin repeat and sterile alpha motif domain-containing 1A; ANKS1A) belong to the Anks protein family. Both of these family members interacts with the EphA8 receptor. Ank members consists of ankyrin repeats, a SAM domain and a C-terminal PTB domain which is crucial for interaction with the juxtamembrane (JM) region of EphA8. PTB domains are classified into three groups, namely, phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains of which the Anks PTB is a member. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034639040  300 VYLISPDTKKIALEKNFKEISFCSQGIRHVDHFGFICRESSGGggfHFVCYVFQCTNEALVDEIMMTLKQAFTVA 374
Cdd:cd01274     65 VKFIDATTKNLICEHEIRNISCACQDPEDLNTFAYITKDLKTD---HHYCHVFCVLTVDLATEIILTLGQAFEVA 136

Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to bind peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034639040   21 FGLQLVGSLPVHSLTTMPMlpwVVAEVRRLSRQSTRKEPVTKQVRLCVSPSGLRCEpEPGRSQQWDPLIYSSIFECkpqr 100
Cdd:cd00934      3 FQVKYLGSVEVGSSRGVDV---VEEALKALAAALKSSKRKPGPVLLEVSSKGVKLL-DLDTKELLLRHPLHRISYC---- 74

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1034639040  101 vhklIHNSHDPSYFACLIKEDAVhRQSICYVFKADDQTKVPEIISSIRQA 150
Cdd:cd00934     75 ----GRDPDNPNVFAFIAGEEGG-SGFRCHVFQCEDEEEAEEILQAIGQA 119

Cell death protein 6 homolog (CED-6/GULP1) Phosphotyrosine-binding (PTB) domain; CED6 (also known as GULP1: engulfment adaptor PTB domain containing 1) is an adaptor protein involved in the specific recognition and engulfment of apoptotic cells. CED6 has been shown to interact with the cytoplasmic tail of another protein involved in the engulfment of apoptotic cells, CED1. CED6 has a C-terminal PTB domain, which can bind to NPXY motifs. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034639040  300 VYLISPDTKKIALEKNFKEISFCSQGIRHVDHFGFICRESSGGGgfHFvCYVFQCtnEALVDEIMMTLKQAFTVA 374
Cdd:cd01273     66 VKIQDPKTKVIMHQFPLHRISFCADDKTDKRIFSFIAKDSESEK--HL-CFVFDS--EKLAEEITLTIGQAFDLA 135

Cell division protein ZapB, interacts with FtsZ [Cell cycle control, cell division, chromosome partitioning];

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034639040 1107 NLDLLEQL----QVANGRIQSLEATIEKLLSSESKLKQAMLTLELERSALLQTVEELRRRSAEPSDR 1169
Cdd:COG3074      2 SLELLEELeakvQQAVDTIELLQMEVEELKEKNEELEQENEELQSENEELQSENEQLKTENAEWQER 68