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Protein

Integrin beta-3

Gene

ITGB3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 (ITGA2B:ITGB3) 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. Fibrinogen binding enhances SELP expression in activated platelets (By similarity). ITGAV:ITGB3 binds to fractalkine (CX3CL1) and acts as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415, PubMed:24789099). ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling (PubMed:18441324). ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling (PubMed:28302677). ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:19578119). ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling (PubMed:29030430). ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). ITGAV:ITGB3 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (PubMed:12807887).2 PublicationsBy similarity12 Publications
(Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Herpes virus 8/HHV-8.1 Publication
(Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Coxsackievirus A9.1 Publication
(Microbial infection) Acts as a receptor for Hantaan virus.1 Publication
(Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Cytomegalovirus/HHV-5.1 Publication
(Microbial infection) Integrin ITGA5:ITGB3 acts as a receptor for Human metapneumovirus.1 Publication
(Microbial infection) Integrin ITGAV:ITGB3 acts aP05556s a receptor for Human parechovirus 1.1 Publication
(Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for West nile virus.1 Publication
(Microbial infection) In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.1 Publication

GO - Molecular functioni

  • cell adhesion molecule binding Source: BHF-UCL
  • coreceptor activity Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • extracellular matrix binding Source: UniProtKB
  • fibronectin binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • integrin binding Source: BHF-UCL
  • platelet-derived growth factor receptor binding Source: BHF-UCL
  • protease binding Source: UniProtKB
  • protein disulfide isomerase activity Source: UniProtKB
  • vascular endothelial growth factor receptor 2 binding Source: BHF-UCL
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionHost cell receptor for virus entry, Integrin, Receptor
Biological processCell adhesion, Host-virus interaction

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-1566948 Elastic fibre formation
R-HSA-210990 PECAM1 interactions
R-HSA-2129379 Molecules associated with elastic fibres
R-HSA-216083 Integrin cell surface interactions
R-HSA-3000170 Syndecan interactions
R-HSA-3000178 ECM proteoglycans
R-HSA-354192 Integrin alphaIIb beta3 signaling
R-HSA-354194 GRB2:SOS provides linkage to MAPK signaling for Integrins
R-HSA-372708 p130Cas linkage to MAPK signaling for integrins
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-445144 Signal transduction by L1
R-HSA-5674135 MAP2K and MAPK activation
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948 Signaling by high-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
SignaLinkiP05106
SIGNORiP05106

Names & Taxonomyi

Protein namesi
Recommended name:
Integrin beta-3
Alternative name(s):
Platelet membrane glycoprotein IIIa
Short name:
GPIIIa
CD_antigen: CD61
Gene namesi
Name:ITGB3
Synonyms:GP3A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000259207.7
HGNCiHGNC:6156 ITGB3
MIMi173470 gene+phenotype
neXtProtiNX_P05106

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini27 – 718ExtracellularSequence analysisAdd BLAST692
Transmembranei719 – 741HelicalSequence analysisAdd BLAST23
Topological domaini742 – 788CytoplasmicSequence analysisAdd BLAST47

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Involvement in diseasei

Glanzmann thrombasthenia (GT)18 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA common inherited disease of platelet aggregation. It is characterized by mucocutaneous bleeding of mild-to-moderate severity. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb-IIIa complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the GPIIb-IIIa complex at reduced levels, have detectable amounts of fibrinogen, and have low or moderate clot retraction capability.
See also OMIM:273800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06992064C → Y in GT; severe type 1 phenotype; the mutation prevents normal ITGA2B/ITGB3 complex expression. 1 PublicationCorresponds to variant dbSNP:rs74554539Ensembl.1
Natural variantiVAR_030473119R → W in GT. 1 PublicationCorresponds to variant dbSNP:rs781062792Ensembl.1
Natural variantiVAR_030474141Y → C in GT. 1 Publication1
Natural variantiVAR_010649143L → W in GT. 1 PublicationCorresponds to variant dbSNP:rs121918452EnsemblClinVar.1
Natural variantiVAR_069921144M → R in GT; severe type 1 phenotype; the mutation prevented normal ITGA2B/ITGB3 complex expression on the cell surface. 1 PublicationCorresponds to variant dbSNP:rs77963874Ensembl.1
Natural variantiVAR_030475145D → N in GT. 1 Publication1
Natural variantiVAR_003998145D → Y in GT; type B. 1 PublicationCorresponds to variant dbSNP:rs121918445EnsemblClinVar.1
Natural variantiVAR_030476150M → V in GT; may confer constitutive activity to the alpha-IIb/(mutated)beta-3 receptor. 1 PublicationCorresponds to variant dbSNP:rs767548512Ensembl.1
Natural variantiVAR_010651188S → L in GT; type II. 1 PublicationCorresponds to variant dbSNP:rs143146734Ensembl.1
Natural variantiVAR_030478222L → P in GT; variant form. 2 PublicationsCorresponds to variant dbSNP:rs79208797Ensembl.1
Natural variantiVAR_003999240R → Q in GT; type B. 1 PublicationCorresponds to variant dbSNP:rs121918444EnsemblClinVar.1
Natural variantiVAR_004000240R → W in GT; variant Strasbourg-1. 1 PublicationCorresponds to variant dbSNP:rs121918446EnsemblClinVar.1
Natural variantiVAR_030479242R → Q in GT. 1 PublicationCorresponds to variant dbSNP:rs377162158Ensembl.1
Natural variantiVAR_030480243D → V in GT. 1 Publication1
Natural variantiVAR_069922247G → D in GT; severe type 1 phenotype; the mutation prevents normal ITGA2B/ITGB3 complex expression on the cell surface; the mutation may interfere with correct folding of the protein. 1 PublicationCorresponds to variant dbSNP:rs79560904EnsemblClinVar.1
Natural variantiVAR_069923279K → M in GT; severe type 1 phenotype; the mutation prevents normal ITGA2B/ITGB3 complex expression on the cell surface; the mutation interupts the interaction of the ITGA2B/ITGB3 complex. 1 PublicationCorresponds to variant dbSNP:rs79775494EnsemblClinVar.1
Natural variantiVAR_030481288L → P in GT. 1 Publication1
Natural variantiVAR_004001306H → P in GT. 2 PublicationsCorresponds to variant dbSNP:rs13306476Ensembl.1
Natural variantiVAR_030482321M → L in GT. 1 Publication1
Natural variantiVAR_030483330I → N in GT; not expressed on the surface and absent inside the transfected cells. 1 Publication1
Natural variantiVAR_004002400C → Y in GT. 1 PublicationCorresponds to variant dbSNP:rs121918449EnsemblClinVar.1
Natural variantiVAR_030484532C → Y in GT. 1 Publication1
Natural variantiVAR_010671568C → R in GT; type I. 1 Publication1
Natural variantiVAR_004003586C → F in GT. 1 Publication1
Natural variantiVAR_030485586C → R in GT; gain-of-function mutation; constitutively binds ligand-induced binding sites antibodies and the fibrinogen-mimetic antibody PAC-1. 1 Publication1
Natural variantiVAR_004004598G → S in GT. 1 Publication1
Natural variantiVAR_030486601C → R in GT. 1 PublicationCorresponds to variant dbSNP:rs747534508Ensembl.1
Natural variantiVAR_010672605G → S in GT; type II. 1 PublicationCorresponds to variant dbSNP:rs144884023Ensembl.1
Natural variantiVAR_004005778S → P in GT; variant Strasbourg-1. 1 PublicationCorresponds to variant dbSNP:rs121918447EnsemblClinVar.1
Bleeding disorder, platelet-type 16 (BDPLT16)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant form of congenital macrothrombocytopenia associated with platelet anisocytosis. It is a disorder of platelet production. Affected individuals may have no or only mildly increased bleeding tendency. In vitro studies show mild platelet functional abnormalities.
See also OMIM:187800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069924749D → H in BDPLT16; the mutant protein is constitutively active. 1 PublicationCorresponds to variant dbSNP:rs398122372EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3690
MalaCardsiITGB3
MIMi173470 gene+phenotype
187800 phenotype
273800 phenotype
OpenTargetsiENSG00000259207
Orphaneti140957 Autosomal dominant macrothrombocytopenia
853 Fetal and neonatal alloimmune thrombocytopenia
849 Glanzmann thrombasthenia
PharmGKBiPA205

Chemistry databases

ChEMBLiCHEMBL3883284
DrugBankiDB00054 Abciximab
DB00098 Anti-thymocyte Globulin (Rabbit)
DB00063 Eptifibatide
DB04863 Lefradafiban
DB05787 LM-609
DB00775 Tirofiban
GuidetoPHARMACOLOGYi2457

Polymorphism and mutation databases

BioMutaiITGB3
DMDMi125987835

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000001634427 – 788Integrin beta-3Add BLAST762

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi31 ↔ 4611 Publication
Disulfide bondi39 ↔ 491 Publication
Disulfide bondi42 ↔ 751 Publication
Disulfide bondi52 ↔ 641 Publication
Glycosylationi125N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi203 ↔ 2101 Publication
Disulfide bondi258 ↔ 2991 Publication
Glycosylationi346N-linked (GlcNAc...) asparagineSequence analysis1 Publication1
Glycosylationi397N-linked (GlcNAc...) asparagineSequence analysis1 Publication1
Disulfide bondi400 ↔ 4121 Publication
Disulfide bondi432 ↔ 6811 Publication
Disulfide bondi459 ↔ 4631 Publication
Disulfide bondi474 ↔ 4861 Publication
Glycosylationi478N-linked (GlcNAc...) asparagine1
Disulfide bondi483 ↔ 5211 Publication
Disulfide bondi488 ↔ 4971 Publication
Disulfide bondi499 ↔ 5121 Publication
Disulfide bondi527 ↔ 5321 Publication
Disulfide bondi529 ↔ 5621 Publication
Disulfide bondi534 ↔ 5471 Publication
Disulfide bondi549 ↔ 5541 Publication
Disulfide bondi568 ↔ 5731 Publication
Disulfide bondi570 ↔ 6011 Publication
Disulfide bondi575 ↔ 5841 Publication
Glycosylationi585N-linked (GlcNAc...) asparagineSequence analysis1 Publication1
Disulfide bondi586 ↔ 5931 Publication
Disulfide bondi607 ↔ 6121 Publication
Disulfide bondi609 ↔ 6571 Publication
Disulfide bondi614 ↔ 6241 Publication
Disulfide bondi627 ↔ 6301 Publication
Disulfide bondi634 ↔ 6431 Publication
Disulfide bondi640 ↔ 7131 Publication
Disulfide bondi661 ↔ 6891 Publication
Glycosylationi680N-linked (GlcNAc...) asparagine2 Publications1
Modified residuei767PhosphothreonineBy similarity1
Modified residuei773PhosphotyrosineCombined sources1
Modified residuei779Phosphothreonine; by PDPK1 and PKB/AKT1; in vitro1 Publication1
Modified residuei785Phosphotyrosine1 Publication1

Post-translational modificationi

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.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP05106
MaxQBiP05106
PaxDbiP05106
PeptideAtlasiP05106
PRIDEiP05106
ProteomicsDBi51790
51791 [P05106-2]
51792 [P05106-3]

PTM databases

GlyConnecti1416
iPTMnetiP05106
PhosphoSitePlusiP05106

Miscellaneous databases

PMAP-CutDBiP05106

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000259207 Expressed in 157 organ(s), highest expression level in left coronary artery
CleanExiHS_ITGB3
ExpressionAtlasiP05106 baseline and differential
GenevisibleiP05106 HS

Organism-specific databases

HPAiHPA027852

Interactioni

Subunit structurei

Heterodimer of an alpha and a beta subunit. Beta-3 (ITGB3) associates with either alpha-IIb (ITGA2B) or alpha-V (ITGAV). Isoform Beta-3C interacts with FLNB. Interacts with COMP. Interacts with PDIA6 following platelet stimulation. Interacts with SYK; upon activation by ITGB3 promotes platelet adhesion. Interacts with MYO10. Interacts with DAB2. Interacts with FERMT2. Interacts with EMP2; regulates the levels of the heterodimer ITGA5:ITGB3 integrin expression on the plasma membrane (PubMed:16216233). Integrin ITGAV:ITGB3 interacts with FBLN5 (via N-terminus) (By similarity). ITGAV:ITGB3 interacts with NOV (PubMed:12695522). ITGAV:ITGB3 is found in a ternary complex with CX3CR1 and CX3CL1 (PubMed:23125415). ITGAV:ITGB3 is found in a ternary complex with NRG1 and ERBB3 (PubMed:20682778). ITGAV:ITGB3 is found in a ternary complex with FGF1 and FGFR1 (PubMed:18441324). ITGAV:ITGB3 interacts with FGF2; it is likely that FGF2 can simultaneously bind ITGAV:ITGB3 and FGF receptors (PubMed:28302677). ITGAV:ITGB3 binds to IL1B (PubMed:29030430). ITGAV:ITGB3 is found in a ternary complex with IGF1 and IGF1R (PubMed:19578119). ITGAV:ITGB3 interacts with IGF2 (PubMed:28873464). ITGAV:ITGB3 interacts with FBN1 (PubMed:12807887). ITGAV:ITGB3 interacts with CD9, CD81 and CD151 (via second extracellular domain) (PubMed:27993971). Interacts (via the allosteric site (site 2)) with CXCL12 in a CXCR4-independent manner (PubMed:29301984).By similarity19 Publications
(Microbial infection) Integrin ITGAV:ITGB3 interacts with herpes virus 8/HHV-8 glycoprotein B.1 Publication
(Microbial infection) Integrin ITGAV:ITGB3 interacts with coxsackievirus A9 capsid proteins.1 Publication
(Microbial infection) Interacts with Hantaan virus glycoprotein G.1 Publication
(Microbial infection) Integrin ITGAV:ITGB3 interacts with cytomegalovirus/HHV-5 gH:gL proteins.1 Publication
(Microbial infection) Integrin ITGA5:ITGB3 interacts with human metapneumovirus fusion protein.1 Publication
(Microbial infection) Integrin ITGAV:ITGB3 interacts with human parechovirus 1 capsid proteins.1 Publication
(Microbial infection) Integrin ITGAV:ITGB3 interacts with west nile virus envelope protein E.1 Publication
(Microbial infection) Interacts with HIV-1 Tat (PubMed:10397733). ITGAV:ITGB3 interacts with AGRA2 (PubMed:16982628).2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109896, 41 interactors
ComplexPortaliCPX-1795 Integrin alphav-beta3 complex
CPX-1799 Integrin alphaIIb-beta3 complex
CORUMiP05106
DIPiDIP-304N
ELMiP05106
IntActiP05106, 29 interactors
MINTiP05106
STRINGi9606.ENSP00000262017

Chemistry databases

BindingDBiP05106

Structurei

Secondary structure

1788
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP05106
SMRiP05106
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05106

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini135 – 377VWFAAdd BLAST243
Repeati463 – 511IAdd BLAST49
Repeati512 – 553IIAdd BLAST42
Repeati554 – 592IIIAdd BLAST39
Repeati593 – 629IVAdd BLAST37

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni203 – 210Involved in CX3CL1-, NRG1-, FGF1- and IGF1-binding4 Publications8
Regioni293 – 313CX3CL1-binding1 PublicationAdd BLAST21
Regioni463 – 629Cysteine-rich tandem repeatsAdd BLAST167

Sequence similaritiesi

Belongs to the integrin beta chain family.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1226 Eukaryota
ENOG410XP60 LUCA
GeneTreeiENSGT00760000119064
HOVERGENiHBG006190
InParanoidiP05106
KOiK06493
OMAiPRCNLKE
OrthoDBiEOG091G029W
PhylomeDBiP05106
TreeFamiTF105392

Family and domain databases

Gene3Di3.40.50.410, 1 hit
InterProiView protein in InterPro
IPR013111 EGF_extracell
IPR027068 Integrin_beta-3
IPR033760 Integrin_beta_N
IPR015812 Integrin_bsu
IPR014836 Integrin_bsu_cyt_dom
IPR012896 Integrin_bsu_tail
IPR036349 Integrin_bsu_tail_dom_sf
IPR002369 Integrin_bsu_VWA
IPR032695 Integrin_dom_sf
IPR016201 PSI
IPR036465 vWFA_dom_sf
PANTHERiPTHR10082 PTHR10082, 1 hit
PTHR10082:SF25 PTHR10082:SF25, 1 hit
PfamiView protein in Pfam
PF07974 EGF_2, 1 hit
PF08725 Integrin_b_cyt, 1 hit
PF07965 Integrin_B_tail, 1 hit
PF00362 Integrin_beta, 1 hit
PF17205 PSI_integrin, 1 hit
PIRSFiPIRSF002512 Integrin_B, 1 hit
PRINTSiPR01186 INTEGRINB
SMARTiView protein in SMART
SM00187 INB, 1 hit
SM01241 Integrin_b_cyt, 1 hit
SM01242 Integrin_B_tail, 1 hit
SM00423 PSI, 1 hit
SUPFAMiSSF53300 SSF53300, 1 hit
SSF69179 SSF69179, 1 hit
SSF69687 SSF69687, 1 hit
PROSITEiView protein in PROSITE
PS00022 EGF_1, 2 hits
PS01186 EGF_2, 1 hit
PS00243 INTEGRIN_BETA, 3 hits

Sequences (3+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform Beta-3A (identifier: P05106-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MRARPRPRPL WATVLALGAL AGVGVGGPNI CTTRGVSSCQ QCLAVSPMCA
60 70 80 90 100
WCSDEALPLG SPRCDLKENL LKDNCAPESI EFPVSEARVL EDRPLSDKGS
110 120 130 140 150
GDSSQVTQVS PQRIALRLRP DDSKNFSIQV RQVEDYPVDI YYLMDLSYSM
160 170 180 190 200
KDDLWSIQNL GTKLATQMRK LTSNLRIGFG AFVDKPVSPY MYISPPEALE
210 220 230 240 250
NPCYDMKTTC LPMFGYKHVL TLTDQVTRFN EEVKKQSVSR NRDAPEGGFD
260 270 280 290 300
AIMQATVCDE KIGWRNDASH LLVFTTDAKT HIALDGRLAG IVQPNDGQCH
310 320 330 340 350
VGSDNHYSAS TTMDYPSLGL MTEKLSQKNI NLIFAVTENV VNLYQNYSEL
360 370 380 390 400
IPGTTVGVLS MDSSNVLQLI VDAYGKIRSK VELEVRDLPE ELSLSFNATC
410 420 430 440 450
LNNEVIPGLK SCMGLKIGDT VSFSIEAKVR GCPQEKEKSF TIKPVGFKDS
460 470 480 490 500
LIVQVTFDCD CACQAQAEPN SHRCNNGNGT FECGVCRCGP GWLGSQCECS
510 520 530 540 550
EEDYRPSQQD ECSPREGQPV CSQRGECLCG QCVCHSSDFG KITGKYCECD
560 570 580 590 600
DFSCVRYKGE MCSGHGQCSC GDCLCDSDWT GYYCNCTTRT DTCMSSNGLL
610 620 630 640 650
CSGRGKCECG SCVCIQPGSY GDTCEKCPTC PDACTFKKEC VECKKFDRGA
660 670 680 690 700
LHDENTCNRY CRDEIESVKE LKDTGKDAVN CTYKNEDDCV VRFQYYEDSS
710 720 730 740 750
GKSILYVVEE PECPKGPDIL VVLLSVMGAI LLIGLAALLI WKLLITIHDR
760 770 780
KEFAKFEEER ARAKWDTANN PLYKEATSTF TNITYRGT
Length:788
Mass (Da):87,058
Last modified:February 6, 2007 - v2
Checksum:iF246623608E05F9E
GO
Isoform Beta-3B (identifier: P05106-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     768-788: ANNPLYKEATSTFTNITYRGT → VRDGAGRFLKSLV

Show »
Length:780
Mass (Da):86,113
Checksum:iC21A1B7814080CD7
GO
Isoform Beta-3C (identifier: P05106-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     768-788: ANNPLYKEATSTFTNITYRGT → HYAQSLRKWNQPVSIDG

Show »
Length:784
Mass (Da):86,694
Checksum:iB8A9F2A7F3C39247
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
I3L4X8I3L4X8_HUMAN
Integrin beta
ITGB3
443Annotation score:
Q16157Q16157_HUMAN
Integrin beta-3
ITGB3 integrin beta 3
35Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti12A → V in AAA52589 (PubMed:3494014).Curated1
Sequence conflicti12A → V in AAA35927 (PubMed:2345548).Curated1
Sequence conflicti151K → P in AAA67537 (PubMed:2341395).Curated1
Sequence conflicti151K → P in AAB23689 (PubMed:1382574).Curated1
Sequence conflicti205D → EY in AAA67537 (PubMed:2341395).Curated1
Sequence conflicti649 – 653GALHD → EPYMT in AAA52589 (PubMed:3494014).Curated5
Sequence conflicti649 – 653GALHD → EPYMT in AAA60122 (PubMed:2452834).Curated5
Sequence conflicti649 – 653GALHD → EPYMT in AAB71380 (PubMed:9195946).Curated5
Sequence conflicti716G → H (PubMed:3165296).Curated1
Sequence conflicti737 – 741ALLIW → PCSSG in AAA67537 (PubMed:2341395).Curated5

Polymorphismi

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).
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).
Position 433 is associated with platelet-specific alloantigen MO. MO- has Pro-433 and MO+ has Ala-433. MO+ is involved in NAIT.
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.
Position 662 is associated with platelet-specific alloantigen SR(A). SR(A)- has Arg-662 and SR(A)+ has Cys-662.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00399359L → P in alloantigen HPA-1B. 3 PublicationsCorresponds to variant dbSNP:rs5918EnsemblClinVar.1
Natural variantiVAR_06992064C → Y in GT; severe type 1 phenotype; the mutation prevents normal ITGA2B/ITGB3 complex expression. 1 PublicationCorresponds to variant dbSNP:rs74554539Ensembl.1
Natural variantiVAR_04963366L → R1 PublicationCorresponds to variant dbSNP:rs36080296Ensembl.1
Natural variantiVAR_030473119R → W in GT. 1 PublicationCorresponds to variant dbSNP:rs781062792Ensembl.1
Natural variantiVAR_030474141Y → C in GT. 1 Publication1
Natural variantiVAR_010649143L → W in GT. 1 PublicationCorresponds to variant dbSNP:rs121918452EnsemblClinVar.1
Natural variantiVAR_069921144M → R in GT; severe type 1 phenotype; the mutation prevented normal ITGA2B/ITGB3 complex expression on the cell surface. 1 PublicationCorresponds to variant dbSNP:rs77963874Ensembl.1
Natural variantiVAR_030475145D → N in GT. 1 Publication1
Natural variantiVAR_003998145D → Y in GT; type B. 1 PublicationCorresponds to variant dbSNP:rs121918445EnsemblClinVar.1
Natural variantiVAR_030476150M → V in GT; may confer constitutive activity to the alpha-IIb/(mutated)beta-3 receptor. 1 PublicationCorresponds to variant dbSNP:rs767548512Ensembl.1
Natural variantiVAR_030477166T → I Associated with neonatal thrombocytopenia; alloantigen Duv(a+); does not affect significantly the integrin function. 1 PublicationCorresponds to variant dbSNP:rs74708909Ensembl.1
Natural variantiVAR_003994169R → Q in alloantigen HPA-4B. 2 PublicationsCorresponds to variant dbSNP:rs5917EnsemblClinVar.1
Natural variantiVAR_010651188S → L in GT; type II. 1 PublicationCorresponds to variant dbSNP:rs143146734Ensembl.1
Natural variantiVAR_030478222L → P in GT; variant form. 2 PublicationsCorresponds to variant dbSNP:rs79208797Ensembl.1
Natural variantiVAR_003999240R → Q in GT; type B. 1 PublicationCorresponds to variant dbSNP:rs121918444EnsemblClinVar.1
Natural variantiVAR_004000240R → W in GT; variant Strasbourg-1. 1 PublicationCorresponds to variant dbSNP:rs121918446EnsemblClinVar.1
Natural variantiVAR_030479242R → Q in GT. 1 PublicationCorresponds to variant dbSNP:rs377162158Ensembl.1
Natural variantiVAR_030480243D → V in GT. 1 Publication1
Natural variantiVAR_069922247G → D in GT; severe type 1 phenotype; the mutation prevents normal ITGA2B/ITGB3 complex expression on the cell surface; the mutation may interfere with correct folding of the protein. 1 PublicationCorresponds to variant dbSNP:rs79560904EnsemblClinVar.1
Natural variantiVAR_069923279K → M in GT; severe type 1 phenotype; the mutation prevents normal ITGA2B/ITGB3 complex expression on the cell surface; the mutation interupts the interaction of the ITGA2B/ITGB3 complex. 1 PublicationCorresponds to variant dbSNP:rs79775494EnsemblClinVar.1
Natural variantiVAR_030481288L → P in GT. 1 Publication1
Natural variantiVAR_004001306H → P in GT. 2 PublicationsCorresponds to variant dbSNP:rs13306476Ensembl.1
Natural variantiVAR_030482321M → L in GT. 1 Publication1
Natural variantiVAR_030483330I → N in GT; not expressed on the surface and absent inside the transfected cells. 1 Publication1
Natural variantiVAR_004002400C → Y in GT. 1 PublicationCorresponds to variant dbSNP:rs121918449EnsemblClinVar.1
Natural variantiVAR_003995433P → A in alloantigen MO(+); in a case of neonatal alloimmune thrombocytopenia. 1 PublicationCorresponds to variant dbSNP:rs121918448EnsemblClinVar.1
Natural variantiVAR_014178453V → I1 PublicationCorresponds to variant dbSNP:rs5921Ensembl.1
Natural variantiVAR_003996515R → Q in alloantigen CA(+)/TU(+). 1 PublicationCorresponds to variant dbSNP:rs13306487EnsemblClinVar.1
Natural variantiVAR_030484532C → Y in GT. 1 Publication1
Natural variantiVAR_010671568C → R in GT; type I. 1 Publication1
Natural variantiVAR_004003586C → F in GT. 1 Publication1
Natural variantiVAR_030485586C → R in GT; gain-of-function mutation; constitutively binds ligand-induced binding sites antibodies and the fibrinogen-mimetic antibody PAC-1. 1 Publication1
Natural variantiVAR_004004598G → S in GT. 1 Publication1
Natural variantiVAR_030486601C → R in GT. 1 PublicationCorresponds to variant dbSNP:rs747534508Ensembl.1
Natural variantiVAR_010672605G → S in GT; type II. 1 PublicationCorresponds to variant dbSNP:rs144884023Ensembl.1
Natural variantiVAR_003997662R → C in alloantigen SR(A). 1 PublicationCorresponds to variant dbSNP:rs151219882Ensembl.1
Natural variantiVAR_069924749D → H in BDPLT16; the mutant protein is constitutively active. 1 PublicationCorresponds to variant dbSNP:rs398122372EnsemblClinVar.1
Natural variantiVAR_004005778S → P in GT; variant Strasbourg-1. 1 PublicationCorresponds to variant dbSNP:rs121918447EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002745768 – 788ANNPL…TYRGT → VRDGAGRFLKSLV in isoform Beta-3B. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_002746768 – 788ANNPL…TYRGT → HYAQSLRKWNQPVSIDG in isoform Beta-3C. 1 PublicationAdd BLAST21

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02703 mRNA Translation: AAA52589.1
M20311 mRNA Translation: AAA60122.1
M35999 mRNA Translation: AAA35927.1
U95204 mRNA Translation: AAB71380.1
CH471231 Genomic DNA Translation: EAW57682.1
BC127666 mRNA Translation: AAI27667.1
BC127667 mRNA Translation: AAI27668.1
L28832 Genomic DNA Translation: AAA20880.2
M32686
, M32667, M32672, M32673, M32674, M32675, M32680, M32681, M32682, M32685 Genomic DNA Translation: AAA67537.1
M57494
, M57481, M57482, M57483, M57484, M57485, M57486, M57487, M57488, M57489, M57490, M57491, M57492, M57493 Genomic DNA Translation: AAA52600.1
U03881 Genomic DNA Translation: AAA16076.1
S49379 Genomic DNA Translation: AAB23689.2
M25108 mRNA Translation: AAA36121.1
CCDSiCCDS11511.1 [P05106-1]
PIRiA26547
A60798
B36268
I77349
S14324
RefSeqiNP_000203.2, NM_000212.2 [P05106-1]
UniGeneiHs.218040

Genome annotation databases

EnsembliENST00000559488; ENSP00000452786; ENSG00000259207 [P05106-1]
GeneIDi3690
KEGGihsa:3690
UCSCiuc002ilj.4 human [P05106-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

SHMPD

The Singapore human mutation and polymorphism database

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02703 mRNA Translation: AAA52589.1
M20311 mRNA Translation: AAA60122.1
M35999 mRNA Translation: AAA35927.1
U95204 mRNA Translation: AAB71380.1
CH471231 Genomic DNA Translation: EAW57682.1
BC127666 mRNA Translation: AAI27667.1
BC127667 mRNA Translation: AAI27668.1
L28832 Genomic DNA Translation: AAA20880.2
M32686
, M32667, M32672, M32673, M32674, M32675, M32680, M32681, M32682, M32685 Genomic DNA Translation: AAA67537.1
M57494
, M57481, M57482, M57483, M57484, M57485, M57486, M57487, M57488, M57489, M57490, M57491, M57492, M57493 Genomic DNA Translation: AAA52600.1
U03881 Genomic DNA Translation: AAA16076.1
S49379 Genomic DNA Translation: AAB23689.2
M25108 mRNA Translation: AAA36121.1
CCDSiCCDS11511.1 [P05106-1]
PIRiA26547
A60798
B36268
I77349
S14324
RefSeqiNP_000203.2, NM_000212.2 [P05106-1]
UniGeneiHs.218040

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JV2X-ray3.10B27-718[»]
1KUPNMR-B742-766[»]
1KUZNMR-B742-766[»]
1L5GX-ray3.20B27-718[»]
1M1XX-ray3.30B27-718[»]
1M8ONMR-B742-788[»]
1MIZX-ray1.90A765-769[»]
1MK7X-ray2.20A/C765-775[»]
1MK9X-ray2.80A/C/E/G765-776[»]
1RN0model-B135-378[»]
1S4XNMR-A742-788[»]
1TYEX-ray2.90B/D/F27-466[»]
1U8CX-ray3.10B27-718[»]
2INImodel-B81-460[»]
B558-716[»]
2K9JNMR-B711-753[»]
2KNCNMR-B715-788[»]
2KV9NMR-B739-788[»]
2L1CNMR-B762-788[»]
2L91NMR-A711-753[»]
2LJDNMR-A742-788[»]
2LJENMR-A742-788[»]
2LJFNMR-A742-788[»]
2MTPNMR-C742-788[»]
2N9YNMR-B712-753[»]
2Q6WX-ray2.25C/F50-61[»]
2RMZNMR-A711-753[»]
2RN0NMR-A711-753[»]
2VC2X-ray3.10B27-487[»]
2VDKX-ray2.80B27-487[»]
2VDLX-ray2.75B27-487[»]
2VDMX-ray2.90B27-487[»]
2VDNX-ray2.90B27-487[»]
2VDOX-ray2.51B27-487[»]
2VDPX-ray2.80B27-487[»]
2VDQX-ray2.59B27-487[»]
2VDRX-ray2.40B27-487[»]
3FCSX-ray2.55B/D27-716[»]
3FCUX-ray2.90B/D/F27-487[»]
3IJEX-ray2.90B27-721[»]
3NIDX-ray2.30B/D27-497[»]
3NIFX-ray2.40B/D27-497[»]
3NIGX-ray2.25B/D27-497[»]
3T3MX-ray2.60B/D27-498[»]
3T3PX-ray2.20B/D27-498[»]
3ZDXX-ray2.45B/D27-498[»]
3ZDYX-ray2.45B/D27-498[»]
3ZDZX-ray2.75B/D27-498[»]
3ZE0X-ray2.95B/D27-498[»]
3ZE1X-ray3.00B/D27-498[»]
3ZE2X-ray2.35B/D27-498[»]
4CAKelectron microscopy20.50B27-716[»]
4G1EX-ray3.00B27-717[»]
4G1MX-ray2.90B27-718[»]
4MMXX-ray3.32B27-718[»]
4MMYX-ray3.18B27-718[»]
4MMZX-ray3.10B27-718[»]
4O02X-ray3.60B27-718[»]
4Z7NX-ray2.60B/D29-497[»]
4Z7OX-ray2.85B/D29-497[»]
4Z7QX-ray2.70B/D27-497[»]
5HDBX-ray2.70B/D27-497[»]
6AVQelectron microscopy35.00B27-718[»]
6AVRelectron microscopy35.00B27-718[»]
6AVUelectron microscopy35.00B27-718[»]
6BXBX-ray2.39A/B27-135[»]
A/B378-548[»]
6BXFX-ray3.20A/B27-135[»]
A/B378-548[»]
6CKBX-ray2.80A/B27-135[»]
A/B378-548[»]
ProteinModelPortaliP05106
SMRiP05106
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109896, 41 interactors
ComplexPortaliCPX-1795 Integrin alphav-beta3 complex
CPX-1799 Integrin alphaIIb-beta3 complex
CORUMiP05106
DIPiDIP-304N
ELMiP05106
IntActiP05106, 29 interactors
MINTiP05106
STRINGi9606.ENSP00000262017

Chemistry databases

BindingDBiP05106
ChEMBLiCHEMBL3883284
DrugBankiDB00054 Abciximab
DB00098 Anti-thymocyte Globulin (Rabbit)
DB00063 Eptifibatide
DB04863 Lefradafiban
DB05787 LM-609
DB00775 Tirofiban
GuidetoPHARMACOLOGYi2457

PTM databases

GlyConnecti1416
iPTMnetiP05106
PhosphoSitePlusiP05106

Polymorphism and mutation databases

BioMutaiITGB3
DMDMi125987835

Proteomic databases

EPDiP05106
MaxQBiP05106
PaxDbiP05106
PeptideAtlasiP05106
PRIDEiP05106
ProteomicsDBi51790
51791 [P05106-2]
51792 [P05106-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000559488; ENSP00000452786; ENSG00000259207 [P05106-1]
GeneIDi3690
KEGGihsa:3690
UCSCiuc002ilj.4 human [P05106-1]

Organism-specific databases

CTDi3690
DisGeNETi3690
EuPathDBiHostDB:ENSG00000259207.7
GeneCardsiITGB3
HGNCiHGNC:6156 ITGB3
HPAiHPA027852
MalaCardsiITGB3
MIMi173470 gene+phenotype
187800 phenotype
273800 phenotype
neXtProtiNX_P05106
OpenTargetsiENSG00000259207
Orphaneti140957 Autosomal dominant macrothrombocytopenia
853 Fetal and neonatal alloimmune thrombocytopenia
849 Glanzmann thrombasthenia
PharmGKBiPA205
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1226 Eukaryota
ENOG410XP60 LUCA
GeneTreeiENSGT00760000119064
HOVERGENiHBG006190
InParanoidiP05106
KOiK06493
OMAiPRCNLKE
OrthoDBiEOG091G029W
PhylomeDBiP05106
TreeFamiTF105392

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-1566948 Elastic fibre formation
R-HSA-210990 PECAM1 interactions
R-HSA-2129379 Molecules associated with elastic fibres
R-HSA-216083 Integrin cell surface interactions
R-HSA-3000170 Syndecan interactions
R-HSA-3000178 ECM proteoglycans
R-HSA-354192 Integrin alphaIIb beta3 signaling
R-HSA-354194 GRB2:SOS provides linkage to MAPK signaling for Integrins
R-HSA-372708 p130Cas linkage to MAPK signaling for integrins
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-445144 Signal transduction by L1
R-HSA-5674135 MAP2K and MAPK activation
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948 Signaling by high-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
SignaLinkiP05106
SIGNORiP05106

Miscellaneous databases

ChiTaRSiITGB3 human
EvolutionaryTraceiP05106
GeneWikiiCD61
GenomeRNAii3690
PMAP-CutDBiP05106
PROiPR:P05106
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000259207 Expressed in 157 organ(s), highest expression level in left coronary artery
CleanExiHS_ITGB3
ExpressionAtlasiP05106 baseline and differential
GenevisibleiP05106 HS

Family and domain databases

Gene3Di3.40.50.410, 1 hit
InterProiView protein in InterPro
IPR013111 EGF_extracell
IPR027068 Integrin_beta-3
IPR033760 Integrin_beta_N
IPR015812 Integrin_bsu
IPR014836 Integrin_bsu_cyt_dom
IPR012896 Integrin_bsu_tail
IPR036349 Integrin_bsu_tail_dom_sf
IPR002369 Integrin_bsu_VWA
IPR032695 Integrin_dom_sf
IPR016201 PSI
IPR036465 vWFA_dom_sf
PANTHERiPTHR10082 PTHR10082, 1 hit
PTHR10082:SF25 PTHR10082:SF25, 1 hit
PfamiView protein in Pfam
PF07974 EGF_2, 1 hit
PF08725 Integrin_b_cyt, 1 hit
PF07965 Integrin_B_tail, 1 hit
PF00362 Integrin_beta, 1 hit
PF17205 PSI_integrin, 1 hit
PIRSFiPIRSF002512 Integrin_B, 1 hit
PRINTSiPR01186 INTEGRINB
SMARTiView protein in SMART
SM00187 INB, 1 hit
SM01241 Integrin_b_cyt, 1 hit
SM01242 Integrin_B_tail, 1 hit
SM00423 PSI, 1 hit
SUPFAMiSSF53300 SSF53300, 1 hit
SSF69179 SSF69179, 1 hit
SSF69687 SSF69687, 1 hit
PROSITEiView protein in PROSITE
PS00022 EGF_1, 2 hits
PS01186 EGF_2, 1 hit
PS00243 INTEGRIN_BETA, 3 hits
ProtoNetiSearch...

Entry informationi

Entry nameiITB3_HUMAN
AccessioniPrimary (citable) accession number: P05106
Secondary accession number(s): A0PJW2
, D3DXJ8, O15495, Q12806, Q13413, Q14648, Q16499
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: February 6, 2007
Last modified: November 7, 2018
This is version 253 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Metallothioneins
    Classification of metallothioneins and list of entries
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  8. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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