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 1720414491   43 GHNVVQPTDMEENRTMLFTIGQSEVYLISPDTKKIALEKNFKEISFCSQGIRHVDHFGFICREcsGGGSGGFHFVCYVFQ 122
Cdd:cd01269     48 GPSSVQPTDSEENRTMLFQIGRSELRLISPDTKQVLLEKQFKDISSCSQGIKHVDHFGFICRE--SSEGGGFHFVCYVFK 125

                           90
                   ....*....|....*...
gi 1720414491  123 CTNEALVDEIMMTLKQAF 140
Cdd:cd01269    126 CQSESVVDEIMLTIKQAF 143

phosphodiesterase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720414491  914 KQLQAYEvEYHVLQEELIESSPLSDN----------QRMEKLEKTNSSLRKQNLDLLEQLQVANARIQSLEATVEKLLTS 983
Cdd:PRK12704    58 ALLEAKE-EIHKLRNEFEKELRERRNelqklekrllQKEENLDRKLELLEKREEELEKKEKELEQKQQELEKKEEELEEL 136

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1720414491  984 ESKLKQ-----AALTLEVERSALLQMVE-ELRRQSAR 1014
Cdd:PRK12704   137 IEEQLQeleriSGLTAEEAKEILLEKVEeEARHEAAV 173

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 1720414491   43 GHNVVQPTDMEENRTMLFTIGQSEVYLISPDTKKIALEKNFKEISFCSQGIRHVDHFGFICREcsGGGSGGFHFVCYVFQ 122
Cdd:cd01269     48 GPSSVQPTDSEENRTMLFQIGRSELRLISPDTKQVLLEKQFKDISSCSQGIKHVDHFGFICRE--SSEGGGFHFVCYVFK 125

                           90
                   ....*....|....*...
gi 1720414491  123 CTNEALVDEIMMTLKQAF 140
Cdd:cd01269    126 CQSESVVDEIMLTIKQAF 143

GTPase-activating protein [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720414491  590 ILQQILLLRMEKENQKlqaseNDLLNKRLKLDYEEITPCLkevTTVWEKMLSTPGRSKIKFDMEKVHSAVGQGVPRHHRG 669
Cdd:COG5210    148 KGSSSLNSNPELNKEI-----NELSLKEEPQKLRYYELAA---DKLWISYLDPNPLSFLPVQLSKLRELIRKGIPNELRG 219

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720414491  670 EIWKFLaeqfhLKHPFPSKQQPKDVPYKELLKKLTSQQ-----HAILIDLGRTFPTHPYFSAQLGAGQLSLYNILKAYSL 744
Cdd:COG5210    220 DVWEFL-----LGIGFDLDKNPGLYERLLNLHREAKIPtqeiiSQIEKDLSRTFPDNSLFQTEISIRAENLRRVLKAYSL 294

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720414491  745 LDQEVGYCQGLSFVAGILLLHM-SEEEAFKMLKFLMFDMGLRKQYRPDMIILQIQMYQLSRLLHDYHRDLYNHLEEHEIG 823
Cdd:COG5210    295 YNPEVGYVQGMNFLAAPLLLVLeSEEQAFWCLVKLLKNYGLPGYFLKNLSGLHRDLKVLDDLVEELDPELYEHLLREGVV 374

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720414491  824 PSLYAAPWFLTVFASQFPLGFVARVFDMIFLQGSEVIFKVALSLLGSHKPLILQHENLETIVDFIKN 890
Cdd:COG5210    375 LLMFAFRWFLTLFVREFPLEYALRIWDCLFLEGSSMLFQLALAILKLLRDKLLKLDSDELLDLLLKQ 441

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720414491    48 QPTDMEENRTMLFTIGQSEVYLISPDTKKIALEKNFKEISFCSQGIRHVDHFGFICRECSGGgsggfHFVCYVFQCTNEA 127
Cdd:smart00462   36 QGSEKKEPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGPDDLDVFGYIARDPGSS-----RFACHVFRCEKAA 110

                            90       100
                    ....*....|....*....|....*
gi 1720414491   128 lvDEIMMTLKQAFTVAAVQQTAKAP 152
Cdd:smart00462  111 --EDIALAIGQAFQLAYELKLKARS 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 1720414491   43 GHNVVQPTDMEENRTMLFTIGQSEVYLISPDTKKIALEKNFKEISFCSQGIRHVDHFGFICREcsGGGSGGFHFVCYVFQ 122
Cdd:cd01269     48 GPSSVQPTDSEENRTMLFQIGRSELRLISPDTKQVLLEKQFKDISSCSQGIKHVDHFGFICRE--SSEGGGFHFVCYVFK 125

                           90
                   ....*....|....*...
gi 1720414491  123 CTNEALVDEIMMTLKQAF 140
Cdd:cd01269    126 CQSESVVDEIMLTIKQAF 143

GTPase-activating protein [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720414491  590 ILQQILLLRMEKENQKlqaseNDLLNKRLKLDYEEITPCLkevTTVWEKMLSTPGRSKIKFDMEKVHSAVGQGVPRHHRG 669
Cdd:COG5210    148 KGSSSLNSNPELNKEI-----NELSLKEEPQKLRYYELAA---DKLWISYLDPNPLSFLPVQLSKLRELIRKGIPNELRG 219

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720414491  670 EIWKFLaeqfhLKHPFPSKQQPKDVPYKELLKKLTSQQ-----HAILIDLGRTFPTHPYFSAQLGAGQLSLYNILKAYSL 744
Cdd:COG5210    220 DVWEFL-----LGIGFDLDKNPGLYERLLNLHREAKIPtqeiiSQIEKDLSRTFPDNSLFQTEISIRAENLRRVLKAYSL 294

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720414491  745 LDQEVGYCQGLSFVAGILLLHM-SEEEAFKMLKFLMFDMGLRKQYRPDMIILQIQMYQLSRLLHDYHRDLYNHLEEHEIG 823
Cdd:COG5210    295 YNPEVGYVQGMNFLAAPLLLVLeSEEQAFWCLVKLLKNYGLPGYFLKNLSGLHRDLKVLDDLVEELDPELYEHLLREGVV 374

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720414491  824 PSLYAAPWFLTVFASQFPLGFVARVFDMIFLQGSEVIFKVALSLLGSHKPLILQHENLETIVDFIKN 890
Cdd:COG5210    375 LLMFAFRWFLTLFVREFPLEYALRIWDCLFLEGSSMLFQLALAILKLLRDKLLKLDSDELLDLLLKQ 441

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720414491    48 QPTDMEENRTMLFTIGQSEVYLISPDTKKIALEKNFKEISFCSQGIRHVDHFGFICRECSGGgsggfHFVCYVFQCTNEA 127
Cdd:smart00462   36 QGSEKKEPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGPDDLDVFGYIARDPGSS-----RFACHVFRCEKAA 110

                            90       100
                    ....*....|....*....|....*
gi 1720414491   128 lvDEIMMTLKQAFTVAAVQQTAKAP 152
Cdd:smart00462  111 --EDIALAIGQAFQLAYELKLKARS 133

uncharacterized protein LOC417372 Phosphotyrosine-binding (PTB) PH-like fold; The function of LOC417372 and its related proteins are unknown to date. Members here contain a N-terminal RUN domain, followed by a PDZ domain, and a C-terminal PTB domain. The RUN domain is involved in Ras-like GTPase signaling. The PDZ domain (also called DHR/Dlg homologous region or GLGF after its conserved sequence motif) binds C-terminal polypeptides, internal (non-C-terminal) polypeptides, and lipids. 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 1720414491   54 ENRTMLFTIGQSEVYLISPDTKKIALEKNFKEISFCSQGIRHVDHFGFICRE--CSGGGsggfHFVCYVFQCTNEALVDE 131
Cdd:cd13168     36 TPKEVLLELGEIGVTVWDKSTSEVLFKHSFPEISSCGRRVDDPNYFAYIAGDtpCSLAK----HFVCYVFEAADEEEAET 111

                   ....*....
gi 1720414491  132 IMMTLKQAF 140
Cdd:cd13168    112 ILQGIAQGF 120

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 1720414491   67 VYLISPDTKKIALEKNFKEISFCSQGIRHVDHFGFICRECSGGGSggfhfVCYVFQCTNEAlvDEIMMTLKQAFTVAA 144
Cdd:cd13161     49 IRVVERLTGEVLTNVPIKDISFVTVDPKDKKLFAFISHDPRLGRI-----TCHVFRCKRGA--QEICDTIAEAFKAAA 119

Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold; The null mutations in the LDL receptor adaptor protein 1 (LDLRAP1) gene, which serves as an adaptor for LDLR endocytosis in the liver, causes autosomal recessive hypercholesterolemia (ARH). LDLRAP1 contains a single PTB domain. 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 contains mammals, insects, and sponges.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720414491   61 TIGQSEVYLISPDTKKIALEKNFKEISFCSQGIRHVDHFGFICRECSGGGSggfhfVCYVFQCTNEALVDEIMMTLKQAF 140
Cdd:cd13159     48 TVSPKGIKVTDSATNETILEVSIYRISYCTADANHDKVFAFIATNQDNEKL-----ECHAFLCAKRKMAQAVTLTVAQAF 122

                   .
gi 1720414491  141 T 141
Cdd:cd13159    123 N 123