ID:ITB3_HUMAN DESCRIPTION: RecName: Full=Integrin beta-3; AltName: Full=Platelet membrane glycoprotein IIIa; Short=GPIIIa; AltName: CD_antigen=CD61; Flags: Precursor; FUNCTION: Integrin alpha-V/beta-3 is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha- IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. SUBUNIT: Heterodimer of an alpha and a beta subunit. Beta-3 associates with either alpha-IIb or alpha-V. Isoform Beta-3C interacts with FLNB. Interacts with COMP. Interacts with HIV-1 Tat. Interacts with PDIA6 following platelet stimulation. Interacts with SYK; upon activation by ITGB3 promotes platelet adhesion. Interacts with MYO10. Interacts with DAB2. INTERACTION: Self; NbExp=4; IntAct=EBI-702847, EBI-702847; P06935:- (xeno); NbExp=4; IntAct=EBI-702847, EBI-981051; P05094:ACTN1 (xeno); NbExp=2; IntAct=EBI-702847, EBI-5847257; P08514:ITGA2B; NbExp=3; IntAct=EBI-702847, EBI-702693; P06756:ITGAV; NbExp=9; IntAct=EBI-702847, EBI-298282; P05480:Src (xeno); NbExp=5; IntAct=EBI-702847, EBI-298680; P54939:TLN1 (xeno); NbExp=2; IntAct=EBI-702847, EBI-1035421; P26039:Tln1 (xeno); NbExp=3; IntAct=EBI-702847, EBI-1039593; SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. TISSUE SPECIFICITY: Isoform beta-3A and isoform beta-3C are widely expressed. Isoform beta-3A is specifically expressed in osteoblast cells; isoform beta-3C is specifically expressed in prostate and testis. PTM: Phosphorylated on tyrosine residues in response to thrombin- induced platelet aggregation. Probably involved in outside-in signaling. A peptide (AA 740-762) is capable of binding GRB2 only when both Tyr-773 and Tyr-785 are phosphorylated. Phosphorylation of Thr-779 inhibits SHC binding. POLYMORPHISM: Position 59 is associated with platelet-specific alloantigen HPA-1 (ZW or PL(A)). HPA-1A/ZW(A)/PL(A1) has Leu-59 and HPA-1B/ZW(B)/PL(A2) has Pro-59. HPA-1A is involved in fetal- maternal alloimmune thromobocytopenia (FMAIT) as well as in neonatal alloimmune thrombocytopenia (NAIT). POLYMORPHISM: Position 169 is associated with platelet-specific alloantigen HPA-4 (PEN or YUK). HPA-4A/PEN(A)/YUK(A) has Arg-169 and HPA-4B/PEN(B)/YUK(B) has Gln-169. HPA-4B is involved in neonatal alloimmune thrombocytopenia (NAIT or NATP). POLYMORPHISM: Position 433 is associated with platelet-specific alloantigen MO. MO(-) has Pro-433 and MO(+) has Ala-433. MO(+) is involved in NAIT. POLYMORPHISM: Position 515 is associated with platelet-specific alloantigen CA/TU. CA(-)/TU(-) has Arg-515 and CA(+)/TU(+) has Gln-515. CA(+) is involved in NAIT. POLYMORPHISM: Position 662 is associated with platelet-specific alloantigen SR(A). SR(A)(-) has Arg-662 and SR(A)(+) has Cys-662. DISEASE: Defects in ITGB3 are a cause of Glanzmann thrombasthenia (GT) [MIM:273800]; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. It is an autosomal recessive disorder characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors. SIMILARITY: Belongs to the integrin beta chain family. SIMILARITY: Contains 1 VWFA domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ITGB3"; WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=ITGB3";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P05106
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BioCarta from NCI Cancer Genome Anatomy Project h_edg1Pathway - Phospholipids as signalling intermediaries h_ucalpainPathway - uCalpain and friends in Cell spread
Reactome (by CSHL, EBI, and GO)
Protein P05106 (Reactome details) participates in the following event(s):
R-HSA-114560 Adhesion of integrin alphaIIbbeta3 to fibrin network R-HSA-216072 Interaction of integrin alphaIIbbeta3 with von Willebrand factor R-HSA-349593 Interaction of integrin alphaIIbbeta3 with Fibronectin R-HSA-349603 Interaction of integrin alphaIIb beta 3 with THBS1 (Thrombospondin-1) R-HSA-432110 Integrin alpha IIb beta3 T779 phosphorylation blocks SHC binding R-HSA-210304 Interaction of integrin alphaVbeta3 with PECAM1 R-HSA-265423 Interaction of integrin alphaVbeta3 with Fibrillin R-HSA-265425 Interaction of integrin alphaVbeta3 with von Willbrand Factor R-HSA-265426 Interaction of integrin alphaVbeta3 with Tenascin R-HSA-265427 Interaction of integrin alphaVbeta3 with IPSP (Bone sialoprotein 2) R-NUL-2731085 Syndecan-1 binds integrin alphaVbeta3 R-HSA-2731123 Syndecan-1 binds Integrin alphaVbeta3 R-HSA-4086200 Dentin matrix protein 1 binds integrin alphaVbeta3 R-HSA-4088218 Tetrastatin binds integrin alphaVbeta3 R-HSA-5218818 Integrin alphaVbeta3 binds p-6Y-VEGFR2 R-HSA-354077 Integrin alphaIIb beta3 activation R-HSA-377641 Clustering of Integrin alphaIIb beta3 complexes R-HSA-374686 L1 interaction with Integrins R-HSA-481044 Surface deployment of platelet alpha granule membrane components R-HSA-2426471 VTN binds integrins alphaVbeta1, alphaVbeta3, alpha3beta5, alphaIIBbeta3 R-HSA-5218836 PTK2beta binds alphaVbeta3 R-HSA-2395320 Latent TGF-beta-1 binds integrins R-HSA-2328037 Fibrillin-1 binds integrins R-HSA-2396029 Latent TGF-beta-3 binds integrins R-HSA-2426259 COMP binds Integrin alpha5beta1, Integrin alphaVbeta3, CD47 R-HSA-2681667 TNC binds Integrin alphaVbeta3, alphaVbeta6, alpha2beta1, alpha7beta1, alpha8beta1, alpha9beta1, alphaXbeta1 R-HSA-2731074 Syndecan-1 binds Integrins alpha2beta1, (alpha6beta4) R-HSA-2752125 SPP1 (osteopontin) binds integrins alphaVbeta1, alphaVbeta3, alphaVbeta5 R-HSA-4085083 Tumstatin binds integrin alphaVbeta 3, alpha3beta1 R-HSA-4085087 Canstatin binds integrins alphaVbeta3, alphaVbeta5 R-HSA-4088264 Endostatin binds integrin alphaVbeta3, alphaVbeta5, alpha3beta1, alpha5beta1 R-HSA-216050 Integrins alpha4beta1, alpha8beta1, alphaVbeta1, alphaVbeta3, alphaVbeta6 bind Fibronectin matrix R-HSA-216076 VTN (vitronectin) binds Integrin alphaVbeta3, alphaVbeta5, alphaVbeta8 R-HSA-354149 Interaction of integrin alphaIIb beta3 with Fibrinogen R-HSA-432096 Activated integrin alphaIIb beta3 binds SHC1 R-HSA-377644 Release of CSK from SRC R-HSA-377643 Dephosphorylation of inactive SRC by PTPB1 R-HSA-354066 Translocation of FADK1 to Focal complexes R-HSA-429415 SYK binds to integrin alphaIIb beta3 R-HSA-377640 Autophosphorylation of SRC R-HSA-5218830 SRC-1 phosphorylates PTK2-beta R-HSA-354087 Recruitment of GRB2 to p-FADK1 R-HSA-372705 Recruitment of p130Cas to FADK1 R-HSA-354124 Phosphorylation of pFADK1 by SRC R-HSA-354073 Autophosphorylation of FADK1 at Y397 R-HSA-429441 SYK activation by SRC R-HSA-5218851 p-Y402-PTK2B phosphorylates p-5Y,S732-PTK2 on Y407 R-HSA-354165 Interaction of SOS with GRB2 bound to FADK1 R-HSA-372697 Crk binding to p130cas R-HSA-372693 Phosphorylation of p130Cas by SRC-FADK1 complex R-HSA-5672972 MAP2Ks and MAPKs bind to the activated RAF complex R-HSA-6802912 High kinase activity BRAF mutants bind MAP2Ks and MAPKs R-HSA-6802914 RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs R-HSA-6802925 Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs R-HSA-6802934 p-BRAF and RAF fusion dimers bind MAP2Ks and MAPKs R-HSA-6802942 RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs R-HSA-5672980 Dissociation of RAS:RAF complex R-HSA-6802932 Dissociation of BRAF/RAF fusion complex R-HSA-6803227 Dissociation of high activity BRAF complexes R-HSA-6803230 Dissociation of moderate activity BRAF complexes R-HSA-6803233 Dissociation of oncogenic RAS:RAF complex R-HSA-6803234 Dissociation of paradoxically activated RAS:BRAF complexes R-HSA-5672978 RAF phosphorylates MAP2K dimer R-HSA-5672973 MAP2Ks phosphorylate MAPKs R-HSA-6802918 Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants R-HSA-6802943 RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks R-HSA-6802919 RAS:GTP:moderate kinase activity p-RAF complexes phosphorylate MAP2Ks R-HSA-6802921 Activated MAP2Ks phosphorylate MAPKs downstream of moderate kinase activity BRAF mutants R-HSA-6802911 High kinase activity BRAF complexes phosphorylate MAP2Ks R-HSA-6802910 Activated MAP2Ks phosphorylate MAPKs downstream of high kinase activity BRAF mutants R-HSA-6802926 Mutant RAS:p-RAF complexes phosphorylate MAP2Ks R-HSA-6802922 Activated MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS R-HSA-6802933 p-BRAF and RAF fusion dimers phosphorylate MAP2Ks R-HSA-6802935 MAPKs are phosphorylated downstream of BRAF and RAF fusion dimers R-HSA-216083 Integrin cell surface interactions R-HSA-354192 Integrin alphaIIb beta3 signaling R-HSA-210990 PECAM1 interactions R-HSA-3000170 Syndecan interactions R-HSA-3000178 ECM proteoglycans R-HSA-4420097 VEGFA-VEGFR2 Pathway R-HSA-445144 Signal transduction by L1 R-HSA-114608 Platelet degranulation R-HSA-1474244 Extracellular matrix organization R-HSA-76009 Platelet Aggregation (Plug Formation) R-HSA-9006921 Integrin signaling R-HSA-2129379 Molecules associated with elastic fibres R-HSA-1566948 Elastic fibre formation R-HSA-202733 Cell surface interactions at the vascular wall R-HSA-3000171 Non-integrin membrane-ECM interactions R-HSA-194138 Signaling by VEGF R-HSA-373760 L1CAM interactions R-HSA-76005 Response to elevated platelet cytosolic Ca2+ R-HSA-76002 Platelet activation, signaling and aggregation R-HSA-162582 Signal Transduction R-HSA-109582 Hemostasis R-HSA-9006934 Signaling by Receptor Tyrosine Kinases R-HSA-354194 GRB2:SOS provides linkage to MAPK signaling for Integrins R-HSA-372708 p130Cas linkage to MAPK signaling for integrins R-HSA-422475 Axon guidance R-HSA-1266738 Developmental Biology R-HSA-5674135 MAP2K and MAPK activation R-HSA-6802948 Signaling by high-kinase activity BRAF mutants R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants R-HSA-6802949 Signaling by RAS mutants R-HSA-6802952 Signaling by BRAF and RAF fusions R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF R-HSA-5673001 RAF/MAP kinase cascade R-HSA-6802957 Oncogenic MAPK signaling R-HSA-5684996 MAPK1/MAPK3 signaling R-HSA-5663202 Diseases of signal transduction R-HSA-5683057 MAPK family signaling cascades R-HSA-1643685 Disease
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Common Gene Haplotype Alleles 
