Tensin-related Phosphotyrosine-binding (PTB) domain; Tensin plays critical roles in renal function, muscle regeneration, and cell migration. It binds to actin filaments and interacts with the cytoplasmic tails of beta-integrin via its PTB domain, allowing tensin to link actin filaments to integrin receptors. Tensin functions as a platform for assembly and disassembly of signaling complexes at focal adhesions by recruiting tyrosine-phosphorylated signaling molecules, and also by providing interaction sites for other proteins. In addition to its PTB domain, it contains a C-terminal SH2 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904331  23 CITKFAQYVGSFPVDDLDTQESVWLVQQQLWALKDC-PRRRAVILKFSLQGLKIYSGEGEVLLMAHALRRILYSTWCPAD 101
Cdd:cd13157    1 TVSRNAQYIGSFPVSGLDVADRADSVRKQLESLKESgSRGRPVILSVSLSGIKICSEDGKVVLMAHALRRVSYSTCRPAH 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 767904331 102 CQFAFMARNPRSPASKLFCHLFVGSQPGEVQILHLLLCRSFQLAYLLQH 150
Cdd:cd13157   81 AQFAFVARNPGGPTNRQYCHVFVTRSPREAQELNLLLCRAFQLAYLKQH 129

Tensin-related Phosphotyrosine-binding (PTB) domain; Tensin plays critical roles in renal function, muscle regeneration, and cell migration. It binds to actin filaments and interacts with the cytoplasmic tails of beta-integrin via its PTB domain, allowing tensin to link actin filaments to integrin receptors. Tensin functions as a platform for assembly and disassembly of signaling complexes at focal adhesions by recruiting tyrosine-phosphorylated signaling molecules, and also by providing interaction sites for other proteins. In addition to its PTB domain, it contains a C-terminal SH2 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904331  23 CITKFAQYVGSFPVDDLDTQESVWLVQQQLWALKDC-PRRRAVILKFSLQGLKIYSGEGEVLLMAHALRRILYSTWCPAD 101
Cdd:cd13157    1 TVSRNAQYIGSFPVSGLDVADRADSVRKQLESLKESgSRGRPVILSVSLSGIKICSEDGKVVLMAHALRRVSYSTCRPAH 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 767904331 102 CQFAFMARNPRSPASKLFCHLFVGSQPGEVQILHLLLCRSFQLAYLLQH 150
Cdd:cd13157   81 AQFAFVARNPGGPTNRQYCHVFVTRSPREAQELNLLLCRAFQLAYLKQH 129

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767904331 296 WAFAGISRPCALALLRRDVLGAFLLWPELGASGQWCLSVRTQCGVVPH-QVFRNHLGRYCLEHLPAEFPSLEALVENH 372
Cdd:cd00173    2 WFHGSISREEAERLLRGKPDGTFLVRESSSEPGDYVLSVRSGDGKVKHyLIERNEGGYYLLGGSGRTFPSLPELVEHY 79

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767904331   64 VILKFSLQGLKIYSGEGEVLLMAHALRRIlySTWCPAD----CQFAFMARNPRSPasKLFCHLFVGSQPGE 130
Cdd:pfam00640  54 VDLFISTDGLKLLNPDTQELIHDHPLVSI--SFCADGDpdlmRYFAYIARDKATN--KFACHVFESEDGAQ 120

Tensin-related Phosphotyrosine-binding (PTB) domain; Tensin plays critical roles in renal function, muscle regeneration, and cell migration. It binds to actin filaments and interacts with the cytoplasmic tails of beta-integrin via its PTB domain, allowing tensin to link actin filaments to integrin receptors. Tensin functions as a platform for assembly and disassembly of signaling complexes at focal adhesions by recruiting tyrosine-phosphorylated signaling molecules, and also by providing interaction sites for other proteins. In addition to its PTB domain, it contains a C-terminal SH2 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904331  23 CITKFAQYVGSFPVDDLDTQESVWLVQQQLWALKDC-PRRRAVILKFSLQGLKIYSGEGEVLLMAHALRRILYSTWCPAD 101
Cdd:cd13157    1 TVSRNAQYIGSFPVSGLDVADRADSVRKQLESLKESgSRGRPVILSVSLSGIKICSEDGKVVLMAHALRRVSYSTCRPAH 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 767904331 102 CQFAFMARNPRSPASKLFCHLFVGSQPGEVQILHLLLCRSFQLAYLLQH 150
Cdd:cd13157   81 AQFAFVARNPGGPTNRQYCHVFVTRSPREAQELNLLLCRAFQLAYLKQH 129

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 767904331  28 AQYVGSFPVDDLDTQESVWLVQQQLWALKDCPRRRA--VILKFSLQGLKIYSGEGEVLLMAHALRRILYSTWCPAD-CQF 104
Cdd:cd00934    5 VKYLGSVEVGSSRGVDVVEEALKALAAALKSSKRKPgpVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRDPDNpNVF 84

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 767904331 105 AFMARNPrsPASKLFCHLFVGSQPGEVQILHLLLCRSF 142
Cdd:cd00934   85 AFIAGEE--GGSGFRCHVFQCEDEEEAEEILQAIGQAF 120

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 767904331  24 ITKFAQYVGSFPVDDLDTQE-SVWLVQQQLWALKDCPRR-RAVILKFSLQGLKIYSGEGEVLLMAHALRRILYstwCPAD 101
Cdd:cd13159    3 VTFYLKYLGSTLVEKPKGEGaTAEAVKTIIAMAKASGKKlQKVTLTVSPKGIKVTDSATNETILEVSIYRISY---CTAD 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 767904331 102 CQ----FAFMARNPRSpaSKLFCHLFVGSQPGEVQILHLLLCRSFQ 143
Cdd:cd13159   80 ANhdkvFAFIATNQDN--EKLECHAFLCAKRKMAQAVTLTVAQAFN 123

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904331 294 NIWAFAGISRPCALALLRRDVLGAFLLWPELGASGQWCLSVRTQcGVVPHqvFRNHLGRYCLEHLPAE--FPSLEALVEN 371
Cdd:cd09935    3 HSWYHGPISRNAAEYLLSSGINGSFLVRESESSPGQYSISLRYD-GRVYH--YRISEDSDGKVYVTQEhrFNTLAELVHH 79

                         90
                 ....*....|..
gi 767904331 372 HAVTERSLFCPL 383
Cdd:cd09935   80 HSKNADGLITTL 91

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767904331   64 VILKFSLQGLKIYSGEGEVLLMAHALRRIlySTWCPAD----CQFAFMARNPRSPasKLFCHLFVGSQPGE 130
Cdd:pfam00640  54 VDLFISTDGLKLLNPDTQELIHDHPLVSI--SFCADGDpdlmRYFAYIARDKATN--KFACHVFESEDGAQ 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904331  28 AQYVGSFPVDDLdTQESVwlVQQQLWALKDCPRR-RAVILKFSLQGLKIYSGE-GEVlLMAHALRRILYSTWCPAD-CQF 104
Cdd:cd13161    6 AKYLGSVPVKEP-KGNDV--VMAAVKRLKDLKLKpKPVVLVVSSEGIRVVERLtGEV-LTNVPIKDISFVTVDPKDkKLF 81

                         90
                 ....*....|....*....
gi 767904331 105 AFMARNPRspASKLFCHLF 123
Cdd:cd13161   82 AFISHDPR--LGRITCHVF 98