Fe65 C-terminal Phosphotyrosine-binding (PTB) domain; The neuronal adaptor protein Fe65 is involved in brain development, Alzheimer disease amyloid precursor protein (APP) signaling, and proteolytic processing of APP. It contains three protein-protein interaction domains, one WW domain, and a unique tandem array of phosphotyrosine-binding (PTB) domains. The C-terminal PTB domain is responsible for APP binding. 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 95147540 283 AVSQAAQKYEALYMGTLPVTKAMGMDVLNEAIGTLTARGDRNAWVPTMLSVSDSLMTAHPIQAEasteEEPLWQCPVRLV 362
Cdd:cd01271   1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKDE----EEVLVECRVRFL 76

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 95147540 363 TFIGVGRDPHTFGLIADLGRQSFQCAAFWCQPHAGGLSEAVQAACMVQYQK 413
Cdd:cd01271  77 SFMGIGKDVHTFAFIMDTGPQLFQCHVFWCEPNAGALSEAVQAACMLRYQK 127

Fe65 C-terminal Phosphotyrosine-binding (PTB) domain; The neuronal adaptor protein Fe65 is involved in brain development, Alzheimer disease amyloid precursor protein (APP) signaling, and proteolytic processing of APP. It contains three protein-protein interaction domains, one WW domain, and a unique tandem array of phosphotyrosine-binding (PTB) domains. The C-terminal PTB domain is responsible for APP binding. 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 95147540 283 AVSQAAQKYEALYMGTLPVTKAMGMDVLNEAIGTLTARGDRNAWVPTMLSVSDSLMTAHPIQAEasteEEPLWQCPVRLV 362
Cdd:cd01271   1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKDE----EEVLVECRVRFL 76

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 95147540 363 TFIGVGRDPHTFGLIADLGRQSFQCAAFWCQPHAGGLSEAVQAACMVQYQK 413
Cdd:cd01271  77 SFMGIGKDVHTFAFIMDTGPQLFQCHVFWCEPNAGALSEAVQAACMLRYQK 127

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 95147540    114 PGAKCFAVRSLGWVEVPEEDlapgkSSIAVNNCIQQLAQTRSrsqppdGAWGEGQNMLMILKKDAMSLVNPLDHSLIHCQ 193
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEAR-----GLQVVQEAIRKLRAAQG------SEKKEPQKVILSISSRGVKLIDEDTKAVLHEH 69

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 95147540    194 PLVHIRVWGVGSSkgRDRDFAFVASDKDSCMLKCHVFCCDVPAKAIASALHGLCAQILSER 254
Cdd:smart00462  70 PLRRISFCAVGPD--DLDVFGYIARDPGSSRFACHVFRCEKAAEDIALAIGQAFQLAYELK 128

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.

                           10        20        30
                   ....*....|....*....|....*....|...
gi 95147540     30 GLPPGWRKIHDAAG-TYYWHVPSGSTQWQRPTW 61
Cdd:smart00456   1 PLPPGWEERKDPDGrPYYYNHETKETQWEKPRE 33

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

                        10        20        30
                ....*....|....*....|....*....|.
gi 95147540  32 PPGWRKIHDAAG-TYYWHVPSGSTQWQRPTW 61
Cdd:cd00201   1 PPGWEERWDPDGrVYYYNHNTKETQWEDPRE 31

Fe65 C-terminal Phosphotyrosine-binding (PTB) domain; The neuronal adaptor protein Fe65 is involved in brain development, Alzheimer disease amyloid precursor protein (APP) signaling, and proteolytic processing of APP. It contains three protein-protein interaction domains, one WW domain, and a unique tandem array of phosphotyrosine-binding (PTB) domains. The C-terminal PTB domain is responsible for APP binding. 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 95147540 283 AVSQAAQKYEALYMGTLPVTKAMGMDVLNEAIGTLTARGDRNAWVPTMLSVSDSLMTAHPIQAEasteEEPLWQCPVRLV 362
Cdd:cd01271   1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKDE----EEVLVECRVRFL 76

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 95147540 363 TFIGVGRDPHTFGLIADLGRQSFQCAAFWCQPHAGGLSEAVQAACMVQYQK 413
Cdd:cd01271  77 SFMGIGKDVHTFAFIMDTGPQLFQCHVFWCEPNAGALSEAVQAACMLRYQK 127

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 95147540    114 PGAKCFAVRSLGWVEVPEEDlapgkSSIAVNNCIQQLAQTRSrsqppdGAWGEGQNMLMILKKDAMSLVNPLDHSLIHCQ 193
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEAR-----GLQVVQEAIRKLRAAQG------SEKKEPQKVILSISSRGVKLIDEDTKAVLHEH 69

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 95147540    194 PLVHIRVWGVGSSkgRDRDFAFVASDKDSCMLKCHVFCCDVPAKAIASALHGLCAQILSER 254
Cdd:smart00462  70 PLRRISFCAVGPD--DLDVFGYIARDPGSSRFACHVFRCEKAAEDIALAIGQAFQLAYELK 128

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 95147540 118 CFAVRSLGWVEVPEEDlapGKSSIAVNNCIQQLAQTRSRSQPpdgawgegQNMLMILKKDAMSLVNPLDHSLIHCQPLVH 197
Cdd:cd00934   2 SFQVKYLGSVEVGSSR---GVDVVEEALKALAAALKSSKRKP--------GPVLLEVSSKGVKLLDLDTKELLLRHPLHR 70

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 95147540 198 IRVWGVGSSkgRDRDFAFVASDKDSCMLKCHVFCCD--VPAKAIASALH 244
Cdd:cd00934  71 ISYCGRDPD--NPNVFAFIAGEEGGSGFRCHVFQCEdeEEAEEILQAIG 117

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.

                          10        20        30
                  ....*....|....*....|....*....|
gi 95147540    31 LPPGWRKIHDAAG-TYYWHVPSGSTQWQRP 59
Cdd:pfam00397   1 LPPGWEERWDPDGrVYYYNHETGETQWEKP 30

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 95147540 118 CFAVRSLGWVEVPEedlapGKSSIAVNNCIQQLaqtRSRSQPPDGAwgegqnmLMILKKDAMSLVNPLDHSLIHCQPLVH 197
Cdd:cd13161   3 VFEAKYLGSVPVKE-----PKGNDVVMAAVKRL---KDLKLKPKPV-------VLVVSSEGIRVVERLTGEVLTNVPIKD 67

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 95147540 198 IRVWGVGsskGRDRD-FAFVASDKDSCMLKCHVFCCDVPAKAIASA 242
Cdd:cd13161  68 ISFVTVD---PKDKKlFAFISHDPRLGRITCHVFRCKRGAQEICDT 110

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 95147540 291 YEALYMGTLPVTKAMGMDVLNEAIGTLTARGdrNAWVPTMLSVSDSLMTAhpiqAEASTeEEPLWQCPVRLVTFIGV-GR 369
Cdd:cd13161   4 FEAKYLGSVPVKEPKGNDVVMAAVKRLKDLK--LKPKPVVLVVSSEGIRV----VERLT-GEVLTNVPIKDISFVTVdPK 76

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 95147540 370 DPHTFGLIA---DLGRQSfqCAAFWCQPHAGGLSEAVQAA 406
Cdd:cd13161  77 DKKLFAFIShdpRLGRIT--CHVFRCKRGAQEICDTIAEA 114

GTPase activating protein for Rab 6 Phosphotyrosine-binding (PTB) domain; GAPCenA is a centrosome-associated GTPase activating protein (GAP) for Rab 6. It consists of an N-terminal PTB domain and a C-terminal TBC 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 is part of the Dab-like subgroup.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 95147540 181 LVNPLDHSLIHCQPLVHIRVWGVGSSKGRDRD-FAFVASDKDSCMLKCHVFCCDVP 235
Cdd:cd01211  54 LYDPTSNTEIASYPIYRILFCARGPDGTSESDcFAFTWSHGETAIFQCHVFRCEIP 109