Description: Homo sapiens integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) (ITGB3), mRNA. RefSeq Summary (NM_000212): The ITGB3 protein product is the integrin beta chain beta 3. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain. A given chain may combine with multiple partners resulting in different integrins. Integrin beta 3 is found along with the alpha IIb chain in platelets. Integrins are known to participate in cell adhesion as well as cell-surface mediated signalling. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr17:45,331,208-45,390,077 Size: 58,870 Total Exon Count: 15 Strand: + Coding Region Position: hg19 chr17:45,331,228-45,387,570 Size: 56,343 Coding Exon Count: 15
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";
aspirin resistance Macchi, L. et al. 2003, Resistance in vitro to low-dose aspirin is associated with platelet PlA1 (GP IIIa) polymorphism but not with C807T(GP Ia/IIa) and C-5T Kozak (GP Ibalpha) polymorphisms., Journal of the American College of Cardiology. 2003 Sep;42(6):1115-9.
[PubMed 13678940]
Platelets homozygous for the Pl(A1) allele appear to be less sensitive to inhibitory action of low-dose aspirin. This differential sensitivity to aspirin may have potential clinical implications whereby specific antiplatelet therapy may be best tailored according to the patient's Pl(A) genotype.
asthma IgE wheezing Thompson, E. E. et al. 2007, Integrin beta3 genotype influences asthma and allergy phenotypes in the first 6 years of life, J Allergy Clin Immunol 2007 119(6) 1423-9.
[PubMed 17556058]
Our results suggest that genetic variation in ITGB3 contributes to asthma susceptibility and allergic sensitization, and that the effects of this gene begin early in life.
asthma; allergy Weiss, L. A. et al. 2005, Variation in ITGB3 is associated with asthma and sensitization to mold allergen in four populations., American journal of respiratory and critical care medicine. 2005 Jul;172(1):67-73.
[PubMed 15817799]
This study provides evidence that ITGB3 plays a role in the pathogenesis of asthma and sensitization to mold allergens.
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
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
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
US Server
