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 2462538520   35 EDAFYNSQKFEVLYCGKVTVTHKKAPSSLIDDCMEKFSLHEQQRLKiqgeqrgpdpgedladlevvvpgspgdclpeead 114
Cdd:cd01269      1 DISPSNSQFFEVLYCGKIKVSHKKVPPTFIDDCLEKFRLHELEKSR---------------------------------- 46

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538520  115 gtdthlglpagasqpaltssrvcfperiledsgfdeqqefrsrcssvtgvqrrvhegsqksqprrrhaSAPSHVQPSDSE 194
Cdd:cd01269     47 --------------------------------------------------------------------SGPSSVQPTDSE 58

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538520  195 KNRTMLFQVGRFEINLISPDTKSVVLEKNFKDISSCSQGIKHVDHFGFICRESPEPGLSQYICYVFQCASESLVDEVMLT 274
Cdd:cd01269     59 ENRTMLFQIGRSELRLISPDTKQVLLEKQFKDISSCSQGIKHVDHFGFICRESSEGGGFHFVCYVFKCQSESVVDEIMLT 138

                   ....*
gi 2462538520  275 LKQAF 279
Cdd:cd01269    139 IKQAF 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 2462538520  643 ELLPLSPLSPTMEEEPlVVFLSGEDDPEKIEERKKSKELRSLWRKAIHQQILLLRMEKENQKLE 706
Cdd:pfam11830    1 ELLPLSPLAPGGEEDP-AGLLSSEDSPVGEKKKRTSEELRELWRKAIHQQILLLRMEKENQKLE 63

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 2462538520   35 EDAFYNSQKFEVLYCGKVTVTHKKAPSSLIDDCMEKFSLHEQQRLKiqgeqrgpdpgedladlevvvpgspgdclpeead 114
Cdd:cd01269      1 DISPSNSQFFEVLYCGKIKVSHKKVPPTFIDDCLEKFRLHELEKSR---------------------------------- 46

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538520  115 gtdthlglpagasqpaltssrvcfperiledsgfdeqqefrsrcssvtgvqrrvhegsqksqprrrhaSAPSHVQPSDSE 194
Cdd:cd01269     47 --------------------------------------------------------------------SGPSSVQPTDSE 58

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538520  195 KNRTMLFQVGRFEINLISPDTKSVVLEKNFKDISSCSQGIKHVDHFGFICRESPEPGLSQYICYVFQCASESLVDEVMLT 274
Cdd:cd01269     59 ENRTMLFQIGRSELRLISPDTKQVLLEKQFKDISSCSQGIKHVDHFGFICRESSEGGGFHFVCYVFKCQSESVVDEIMLT 138

                   ....*
gi 2462538520  275 LKQAF 279
Cdd:cd01269    139 IKQAF 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 2462538520  805 QHAILVDLGRTFPTHPYFsvQLGPGQLSLFNLLKAYSLLDKEVGYCQGISFVAGVLLL-HMSEEQAFEMLKFLMYDLGFR 883
Cdd:pfam00566    9 PEQIEKDVPRTFPHSFFF--DNGPGQNSLRRILKAYSIYNPDVGYCQGMNFIAAPLLLvYLDEEDAFWCFVSLLENYLLR 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538520  884 KQYRPDMMSLQIQMYQLSRLLHDYHRDLYNHLEENEISPSLYAAPWFLTLFASQFSLGFVARVFDIIFLQGTEV-IFKVA 962
Cdd:pfam00566   87 DFYTPDFPGLKRDLYVFEELLKKKLPKLYKHLKELGLDPDLFASQWFLTLFAREFPLSTVLRIWDYFFLEGEKFvLFRVA 166

                          170
                   ....*....|..
gi 2462538520  963 LSLLSSQETLIM 974
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 2462538520  643 ELLPLSPLSPTMEEEPlVVFLSGEDDPEKIEERKKSKELRSLWRKAIHQQILLLRMEKENQKLE 706
Cdd:pfam11830    1 ELLPLSPLAPGGEEDP-AGLLSSEDSPVGEKKKRTSEELRELWRKAIHQQILLLRMEKENQKLE 63

Phosphotyrosine interaction domain (PTB/PID);

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538520  166 RRVHEgsqksQPRRRHASAPSHVQPSDSeknrtMLFQVGRFEINLISPDTKSVVLEKNFKDISSCSQG-IKHVDHFGFIC 244
Cdd:pfam00640   31 RRVKA-----AKINKIRGLSGETGPGTK-----VDLFISTDGLKLLNPDTQELIHDHPLVSISFCADGdPDLMRYFAYIA 100

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2462538520  245 RESPepgLSQYICYVFQCasESLVDEVMLTLKQAFSTA 282
Cdd:pfam00640  101 RDKA---TNKFACHVFES--EDGAQDIAQSIGQAFALA 133

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 2462538520   35 EDAFYNSQKFEVLYCGKVTVTHKKAPSSLIDDCMEKFSLHEQQRLKiqgeqrgpdpgedladlevvvpgspgdclpeead 114
Cdd:cd01269      1 DISPSNSQFFEVLYCGKIKVSHKKVPPTFIDDCLEKFRLHELEKSR---------------------------------- 46

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538520  115 gtdthlglpagasqpaltssrvcfperiledsgfdeqqefrsrcssvtgvqrrvhegsqksqprrrhaSAPSHVQPSDSE 194
Cdd:cd01269     47 --------------------------------------------------------------------SGPSSVQPTDSE 58

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538520  195 KNRTMLFQVGRFEINLISPDTKSVVLEKNFKDISSCSQGIKHVDHFGFICRESPEPGLSQYICYVFQCASESLVDEVMLT 274
Cdd:cd01269     59 ENRTMLFQIGRSELRLISPDTKQVLLEKQFKDISSCSQGIKHVDHFGFICRESSEGGGFHFVCYVFKCQSESVVDEIMLT 138

                   ....*
gi 2462538520  275 LKQAF 279
Cdd:cd01269    139 IKQAF 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 2462538520  805 QHAILVDLGRTFPTHPYFsvQLGPGQLSLFNLLKAYSLLDKEVGYCQGISFVAGVLLL-HMSEEQAFEMLKFLMYDLGFR 883
Cdd:pfam00566    9 PEQIEKDVPRTFPHSFFF--DNGPGQNSLRRILKAYSIYNPDVGYCQGMNFIAAPLLLvYLDEEDAFWCFVSLLENYLLR 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538520  884 KQYRPDMMSLQIQMYQLSRLLHDYHRDLYNHLEENEISPSLYAAPWFLTLFASQFSLGFVARVFDIIFLQGTEV-IFKVA 962
Cdd:pfam00566   87 DFYTPDFPGLKRDLYVFEELLKKKLPKLYKHLKELGLDPDLFASQWFLTLFAREFPLSTVLRIWDYFFLEGEKFvLFRVA 166

                          170
                   ....*....|..
gi 2462538520  963 LSLLSSQETLIM 974
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 2462538520  643 ELLPLSPLSPTMEEEPlVVFLSGEDDPEKIEERKKSKELRSLWRKAIHQQILLLRMEKENQKLE 706
Cdd:pfam11830    1 ELLPLSPLAPGGEEDP-AGLLSSEDSPVGEKKKRTSEELRELWRKAIHQQILLLRMEKENQKLE 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 2462538520  160 SVTGVQRRVHEGSQKSQPRRRHASAPSHvqpsdsEKNRTMLFQVGRFEINLISPDTKSVVLEKNFKDISSCSQGIKHVDH 239
Cdd:cd00934     10 SVEVGSSRGVDVVEEALKALAAALKSSK------RKPGPVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRDPDNPNV 83

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 2462538520  240 FGFICRespEPGLSQYICYVFQCASESLVDEVMLTLKQAF 279
Cdd:cd00934     84 FAFIAG---EEGGSGFRCHVFQCEDEEEAEEILQAIGQAF 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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538520  208 INLISPDTKSVVLEKNFKDISSCSQGIKHVDHFGFICRESPEpglSQYICYVFQCASESLVDEVMLTLKQAFSTA--AAL 285
Cdd:cd01274     65 VKFIDATTKNLICEHEIRNISCACQDPEDLNTFAYITKDLKT---DHHYCHVFCVLTVDLATEIILTLGQAFEVAyqLAL 141

                   ....*
gi 2462538520  286 QSAKT 290
Cdd:cd01274    142 RAQKS 146

Tyrosine-specific kinase/HM-motif TK (TM/HMTK) Phosphotyrosine-binding (PTB) PH-like fold; TK kinases catalyzes the transfer of the terminal phosphate of ATP to a specific tyrosine residue on its target protein. TK kinases play significant roles in development and cell division. Tyrosine-protein kinases can be divided into two subfamilies: receptor tyrosine kinases, which have an intracellular tyrosine kinase domain, a transmembrane domain and an extracellular ligand-binding domain; and non-receptor (cytoplasmic) tyrosine kinases, which are soluble, cytoplasmic kinases. In HMTK the conserved His-Arg-Asp sequence within the catalytic loop is replaced by a His-Met sequence. TM/HMTK have are 2-3 N-terminal PTB domains. PTB domains in TKs are thought to function analogously to the membrane targeting (PH, myristoylation) and pTyr binding (SH2) domains of Src subgroup kinases. 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 2462538520  208 INLISPDTKSVVLEKNFKDISSCSQGIKHVDHFGFICRespEPGLSQYICYVFQCASESlvDEVMLTLKQAFSTAAA 284
Cdd:cd13161     49 IRVVERLTGEVLTNVPIKDISFVTVDPKDKKLFAFISH---DPRLGRITCHVFRCKRGA--QEICDTIAEAFKAAAE 120

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462538520  187 HVQPSDSEKNRTMLFQVGRFEINLISPDTKSVVLEKNFKDISSCS--QGIKHVdhFGFICRESPEpglSQYICYVFQcaS 264
Cdd:cd01273     45 QLKKSEGAKLPKVELQISIDGVKIQDPKTKVIMHQFPLHRISFCAddKTDKRI--FSFIAKDSES---EKHLCFVFD--S 117

                           90
                   ....*....|....*...
gi 2462538520  265 ESLVDEVMLTLKQAFSTA 282
Cdd:cd01273    118 EKLAEEITLTIGQAFDLA 135