Fe65 N-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 N-terminal PTB domain was shown to interact with a variety of proteins, including the low density lipoprotein receptor-related protein (LRP-1), the ApoEr2 receptor, and the histone acetyltransferase Tip60. 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 327187942 109 KCFAVRSLGWVEMTEEELAPGRSSVAVNNCIRQLSYHKNNLHDPmSGGWGEGKDLLLQLEDETLKLVEPQSQALLHAQPI 188
Cdd:cd01272    2 KRFAVRSLGWVEMAEEDLTPGKSSVAVNNCIRQLSYGRNDIRDT-VGRWGEGKDMLMVLDDDTLKLVDPDDRSVLHSQPI 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 327187942 189 ISIRVWGVGRDSGreRDFAYVARDKLTQMLKCHVFRCEAPAKNIATSLHEICSKIMAERR 248
Cdd:cd01272   81 HSIRVWGVGRDNG--RDFAYVARDKDTRVLKCHVFRCDTPAKAIATALHEICSRIMAERR 138

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

                          10        20
                  ....*....|....*....|...
gi 327187942    3 VQDTSG-TYYWHIPTGTTQWEPP 24
Cdd:pfam00397   8 RWDPDGrVYYYNHETGETQWEKP 30

Fe65 N-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 N-terminal PTB domain was shown to interact with a variety of proteins, including the low density lipoprotein receptor-related protein (LRP-1), the ApoEr2 receptor, and the histone acetyltransferase Tip60. 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 327187942 109 KCFAVRSLGWVEMTEEELAPGRSSVAVNNCIRQLSYHKNNLHDPmSGGWGEGKDLLLQLEDETLKLVEPQSQALLHAQPI 188
Cdd:cd01272    2 KRFAVRSLGWVEMAEEDLTPGKSSVAVNNCIRQLSYGRNDIRDT-VGRWGEGKDMLMVLDDDTLKLVDPDDRSVLHSQPI 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 327187942 189 ISIRVWGVGRDSGreRDFAYVARDKLTQMLKCHVFRCEAPAKNIATSLHEICSKIMAERR 248
Cdd:cd01272   81 HSIRVWGVGRDNG--RDFAYVARDKDTRVLKCHVFRCDTPAKAIATALHEICSRIMAERR 138

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327187942  111 FAVRSLGWVEMTEEeLAPGRS--SVAVNNCIRQLSYHKNNLHDPMSGGWGEGKDLLLQLEDETLKLVEPQSQALLHAQPI 188
Cdd:pfam00640   1 FAVRYLGSVEVPEE-RAPDKNtrMQQAREAIRRVKAAKINKIRGLSGETGPGTKVDLFISTDGLKLLNPDTQELIHDHPL 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 327187942  189 ISIRVWGVGrDSGRERDFAYVARDKLTQMLKCHVFRCEAPAKNIATSLHEICSKI 243
Cdd:pfam00640  80 VSISFCADG-DPDLMRYFAYIARDKATNKFACHVFESEDGAQDIAQSIGQAFALA 133

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 327187942   279 ELVQKFQVYYLGNVPVAKPVGVDVINGALESVLS--SSSREQWTPSHVSVAPATLTILHQQTEAVLGECRVRFLSFLAVG 356
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEARGLQVVQEAIRKLRAaqGSEKKEPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVG 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 327187942   357 R-DVHTFAFIMAAGPAS-FCCHMFWCEPNAASLSEAVQAACMLRYQKCLDARSQ 408
Cdd:smart00462  81 PdDLDVFGYIARDPGSSrFACHVFRCEKAAEDIALAIGQAFQLAYELKLKARSE 134

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
                 ....*....|....*....|....
gi 327187942   2 RVQDTSG-TYYWHIPTGTTQWEPP 24
Cdd:cd00201    6 ERWDPDGrVYYYNHNTKETQWEDP 29

Fe65 N-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 N-terminal PTB domain was shown to interact with a variety of proteins, including the low density lipoprotein receptor-related protein (LRP-1), the ApoEr2 receptor, and the histone acetyltransferase Tip60. 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 327187942 109 KCFAVRSLGWVEMTEEELAPGRSSVAVNNCIRQLSYHKNNLHDPmSGGWGEGKDLLLQLEDETLKLVEPQSQALLHAQPI 188
Cdd:cd01272    2 KRFAVRSLGWVEMAEEDLTPGKSSVAVNNCIRQLSYGRNDIRDT-VGRWGEGKDMLMVLDDDTLKLVDPDDRSVLHSQPI 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 327187942 189 ISIRVWGVGRDSGreRDFAYVARDKLTQMLKCHVFRCEAPAKNIATSLHEICSKIMAERR 248
Cdd:cd01272   81 HSIRVWGVGRDNG--RDFAYVARDKDTRVLKCHVFRCDTPAKAIATALHEICSRIMAERR 138

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327187942  111 FAVRSLGWVEMTEEeLAPGRS--SVAVNNCIRQLSYHKNNLHDPMSGGWGEGKDLLLQLEDETLKLVEPQSQALLHAQPI 188
Cdd:pfam00640   1 FAVRYLGSVEVPEE-RAPDKNtrMQQAREAIRRVKAAKINKIRGLSGETGPGTKVDLFISTDGLKLLNPDTQELIHDHPL 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 327187942  189 ISIRVWGVGrDSGRERDFAYVARDKLTQMLKCHVFRCEAPAKNIATSLHEICSKI 243
Cdd:pfam00640  80 VSISFCADG-DPDLMRYFAYIARDKATNKFACHVFESEDGAQDIAQSIGQAFALA 133

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 327187942   279 ELVQKFQVYYLGNVPVAKPVGVDVINGALESVLS--SSSREQWTPSHVSVAPATLTILHQQTEAVLGECRVRFLSFLAVG 356
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEARGLQVVQEAIRKLRAaqGSEKKEPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVG 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 327187942   357 R-DVHTFAFIMAAGPAS-FCCHMFWCEPNAASLSEAVQAACMLRYQKCLDARSQ 408
Cdd:smart00462  81 PdDLDVFGYIARDPGSSrFACHVFRCEKAAEDIALAIGQAFQLAYELKLKARSE 134

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 327187942 110 CFAVRSLGWVEMTEEELAPgRSSVAVNNCIRQLSYHKNnlhdpmsggwgEGKDLLLQLEDETLKLVEPQSQALLHAQPII 189
Cdd:cd00934    2 SFQVKYLGSVEVGSSRGVD-VVEEALKALAAALKSSKR-----------KPGPVLLEVSSKGVKLLDLDTKELLLRHPLH 69

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 327187942 190 SIRVwgVGRDSGRERDFAYVARDKLTQMLKCHVFRC--EAPAKNIATSLHEIC 240
Cdd:cd00934   70 RISY--CGRDPDNPNVFAFIAGEEGGSGFRCHVFQCedEEEAEEILQAIGQAF 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 327187942 165 LQLEDETLKLVEPQSQALLHAQPIISIrVWgVGRDSGRERDFAYVARDKLTQMLKCHVFRCEAPAKNIAT 234
Cdd:cd13161   42 LVVSSEGIRVVERLTGEVLTNVPIKDI-SF-VTVDPKDKKLFAFISHDPRLGRITCHVFRCKRGAQEICD 109

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 327187942 171 TLKLVEPQSQALLHAQPIISIRVWGVGRDSGRERD-FAYVARDKLTQMLKCHVFRCEAPakniatslhEICSKIM----- 244
Cdd:cd01211   51 SVRLYDPTSNTEIASYPIYRILFCARGPDGTSESDcFAFTWSHGETAIFQCHVFRCEIP---------EAVSKVLysfak 121

                 ....*..
gi 327187942 245 AERRNAR 251
Cdd:cd01211  122 AFRRVPK 128

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
                 ....*....|....*....|....
gi 327187942   2 RVQDTSG-TYYWHIPTGTTQWEPP 24
Cdd:cd00201    6 ERWDPDGrVYYYNHNTKETQWEDP 29

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
                 ....*....|....*....|....*..
gi 327187942 199 DSGRERDFAYVARDKLTQMLKCHVFRC 225
Cdd:cd13159   79 DANHDKVFAFIATNQDNEKLECHAFLC 105