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 568933681 564 PKTELVQKFRVQYLGMLPVDRPVGMDTLNSAIENLMTSSSKEDWPSVNMNVADATVTVISEKNEEEVLVECRVRFLSFMG 643
Cdd:cd01271    1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKDEEEVLVECRVRFLSFMG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 568933681 644 VGKDVHTFAFIMDTGNQRFECHVFWCEPNAANVSEAVQAACMLRYQK 690
Cdd:cd01271   81 IGKDVHTFAFIMDTGPQLFQCHVFWCEPNAGALSEAVQAACMLRYQK 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 568933681 564 PKTELVQKFRVQYLGMLPVDRPVGMDTLNSAIENLMTSSSKEDWPSVNMNVADATVTVISEKNEEEVLVECRVRFLSFMG 643
Cdd:cd01271    1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKDEEEVLVECRVRFLSFMG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 568933681 644 VGKDVHTFAFIMDTGNQRFECHVFWCEPNAANVSEAVQAACMLRYQK 690
Cdd:cd01271   81 IGKDVHTFAFIMDTGPQLFQCHVFWCEPNAGALSEAVQAACMLRYQK 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 568933681   567 ELVQKFRVQYLGMLPVDRPVGMDTLNSAIENL--MTSSSKEDWPSVNMNVADATVTVISEKNEEeVLVECRVRFLSFMGV 644
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEARGLQVVQEAIRKLraAQGSEKKEPQKVILSISSRGVKLIDEDTKA-VLHEHPLRRISFCAV 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 568933681   645 G-KDVHTFAFIM-DTGNQRFECHVFWCEPNAANVSEAVQAACMLRYQKCLVARPP 697
Cdd:smart00462  80 GpDDLDVFGYIArDPGSSRFACHVFRCEKAAEDIALAIGQAFQLAYELKLKARSE 134

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 568933681  293 LPPGWKRVNDIAG-TYYWHIPTGTTQWERP 321
Cdd:pfam00397   1 LPPGWEERWDPDGrVYYYNHETGETQWEKP 30

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 568933681 294 PPGWKRVNDIAG-TYYWHIPTGTTQWERPV 322
Cdd:cd00201    1 PPGWEERWDPDGrVYYYNHNTKETQWEDPR 30

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 568933681 564 PKTELVQKFRVQYLGMLPVDRPVGMDTLNSAIENLMTSSSKEDWPSVNMNVADATVTVISEKNEEEVLVECRVRFLSFMG 643
Cdd:cd01271    1 PKEEPVQKLKALYLGSTPVSKPTGMDVLNEAIDTLLSSVPKEQWTPVNVSVAPSTVTILSQKDEEEVLVECRVRFLSFMG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 568933681 644 VGKDVHTFAFIMDTGNQRFECHVFWCEPNAANVSEAVQAACMLRYQK 690
Cdd:cd01271   81 IGKDVHTFAFIMDTGPQLFQCHVFWCEPNAGALSEAVQAACMLRYQK 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 568933681   567 ELVQKFRVQYLGMLPVDRPVGMDTLNSAIENL--MTSSSKEDWPSVNMNVADATVTVISEKNEEeVLVECRVRFLSFMGV 644
Cdd:smart00462   1 GSGVSFRVKYLGSVEVPEARGLQVVQEAIRKLraAQGSEKKEPQKVILSISSRGVKLIDEDTKA-VLHEHPLRRISFCAV 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 568933681   645 G-KDVHTFAFIM-DTGNQRFECHVFWCEPNAANVSEAVQAACMLRYQKCLVARPP 697
Cdd:smart00462  80 GpDDLDVFGYIArDPGSSRFACHVFRCEKAAEDIALAIGQAFQLAYELKLKARSE 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 568933681 570 QKFRVQYLGMLPVDRPVGMDTLNSAIENLMT--SSSKEDWPSVNMNVADATVTVIsEKNEEEVLVECRVRFLSFMGVGKD 647
Cdd:cd00934    1 ASFQVKYLGSVEVGSSRGVDVVEEALKALAAalKSSKRKPGPVLLEVSSKGVKLL-DLDTKELLLRHPLHRISYCGRDPD 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 568933681 648 V-HTFAFI-MDTGNQRFECHVFWCEPN--AANVSEAVQAAC 684
Cdd:cd00934   80 NpNVFAFIaGEEGGSGFRCHVFQCEDEeeAEEILQAIGQAF 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 568933681 572 FRVQYLGMLPVDRPVGMDTLNSAIENLmtSSSKEDWPSVNMNVADATVTVIsEKNEEEVLVECRVRFLSFMGV-GKDVHT 650
Cdd:cd13161    4 FEAKYLGSVPVKEPKGNDVVMAAVKRL--KDLKLKPKPVVLVVSSEGIRVV-ERLTGEVLTNVPIKDISFVTVdPKDKKL 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 568933681 651 FAFIM-DTGNQRFECHVFWCEPNAANVSEAVQAA 683
Cdd:cd13161   81 FAFIShDPRLGRITCHVFRCKRGAQEICDTIAEA 114

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 568933681  293 LPPGWKRVNDIAG-TYYWHIPTGTTQWERP 321
Cdd:pfam00397   1 LPPGWEERWDPDGrVYYYNHETGETQWEKP 30

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 568933681 294 PPGWKRVNDIAG-TYYWHIPTGTTQWERPV 322
Cdd:cd00201    1 PPGWEERWDPDGrVYYYNHNTKETQWEDPR 30

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 568933681 572 FRVQYLGMLPVDRPVGMDTLNSAIENL--MTSSSKEDWPSVNMNVADATVTVISEKNEEEVLVECRVRfLSFMGVGK-DV 648
Cdd:cd13159    5 FYLKYLGSTLVEKPKGEGATAEAVKTIiaMAKASGKKLQKVTLTVSPKGIKVTDSATNETILEVSIYR-ISYCTADAnHD 83

                         90       100
                 ....*....|....*....|..
gi 568933681 649 HTFAFIMDTG-NQRFECHVFWC 669
Cdd:cd13159   84 KVFAFIATNQdNEKLECHAFLC 105

Phosphotyrosine-binding domain; The phosphotyrosine-binding domain (PTB, also phosphotyrosine-interaction or PI domain) in the protein tensin tends to be found at the C-terminus. Tensin is a multi-domain protein that binds to actin filaments and functions as a focal-adhesion molecule (focal adhesions are regions of plasma membrane through which cells attach to the extracellular matrix). Human tensin has actin-binding sites, an SH2 (pfam00017) domain and a region similar to the tumour suppressor PTEN. The PTB domain interacts with the cytoplasmic tails of beta integrin by binding to an NPXY motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568933681  422 AVNNCIRQLSYCKNDIRdtvgIWGEgkDMYLSLENDMLSLVDPMDRSVLHSQPIVNIRVWGVGRDNGRERD-FAYVARDK 500
Cdd:pfam08416  20 AVEDAIRKLQLLDAQGR----VWTQ--EMLLQVSDQGITLTDNETKEELESYPLDSISHCQAVLNDGRYNSiLALVCQEP 93

                          90       100       110
                  ....*....|....*....|....*....|
gi 568933681  501 DTRILKCHVFRC-----DTPAKAIATSLHE 525
Cdd:pfam08416  94 GQSKPDVHLFQCdelgaELIAEDIESALSD 123