ITB3_HUMAN » Integrin beta-3

ITB3_HUMAN » Integrin beta-3
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
ITB3_HUMAN » Integrin beta-3 » Platelet membrane glycoprotein IIIa;GPIIIa;
Hydrophobic Thickness 34.8 ± 3.8 Å
Tilt Angle 44 ± 1°
ΔGtransfer -34.2 kcal/mol
ΔGfold -27.1 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome
Topology Out
TM Segments 717-748 (717-751)
Pathways

Abciximab Pathway (SMPDB)

Arrhythmogenic right ventricular cardiomyopathy (KEGG)

Developmental Biology (Reactome)

Dilated cardiomyopathy (KEGG)

ECM-receptor interaction (KEGG)

Eptifibatide Pathway (SMPDB)

Extracellular matrix organization (Reactome)

Focal adhesion (KEGG)

Hematopoietic cell lineage (KEGG)

Hemostasis (Reactome)

Hypertrophic cardiomyopathy (KEGG)

Osteoclast differentiation (KEGG)

Phagosome (KEGG)

PI3K-Akt signaling pathway (KEGG)

Proteoglycans in cancer (KEGG)

Regulation of actin cytoskeleton (KEGG)

Signal Transduction (Reactome)

Tirofiban Pathway (SMPDB)

PDB 2rmz (711-753), 2l91 (711-753), 2rn0 (711-753), 2kv9 (739-788), 2ljf (742-788), 2lje (742-788), 2ljd (742-788), 1s4x (742-788), 1mk9 (A/C/E/G=765-776), 1mk7 (A/C=765-775), 1miz (A=765-769), 1tye (B/D/F=27-466), 3fcu (B/D/F=27-487), 3nid (B/D=27-497), 3nif (B/D=27-497), 3nig (B/D=27-497), 3zdz (B/D=27-498), 3zdy (B/D=27-498), 3t3m (B/D=27-498), 3t3p (B/D=27-498), 3zdx (B/D=27-498), 3ze1 (B/D=27-498), 3ze2 (B/D=27-498), 3ze0 (B/D=27-498), 3fcs (B/D=27-716), 2vdr (B=27-487), 2vdq (B=27-487), 2vdp (B=27-487), 2vdo (B=27-487), 2vdn (B=27-487), 2vdm (B=27-487), 2vdl (B=27-487), 2vdk (B=27-487), 2vc2 (B=27-487), 4cak (B=27-716), 4g1e (B=27-717), 4g1m (B=27-718), 4mmx (B=27-718), 4mmy (B=27-718), 4mmz (B=27-718), 1jv2 (B=27-718), 4o02 (B=27-718), 1u8c (B=27-718), 1m1x (B=27-718), 1l5g (B=27-718), 3ije (B=27-721), 2k9j (B=711-753), 2knc (B=715-788), 1kuz (B=742-766), 1kup (B=742-766), 1m8o (B=742-788), 2l1c (B=762-788), 2q6w (C/F=50-61)
OPM 1s4x, 2k9j, 2knc, 2ljd, 2lje, 2ljf, 2rmz, 3ije
Complexes

ITA2B:ITB3_HUMAN

ITA2B:ITB3:IGKC_HUMAN

ITB3:FINC:ITAV_HUMAN

ITB3:ITAV_HUMAN

FIBG:ITA2B:ITB3:IGKC_HUMAN

DRB3:ITB3:DRA_HUMAN

Interactions

CEAM1, Complex: ITB3:CEAM1, PubMed

DRB3, Complex: DRB3:ITB3:DRA, PDBID: 2Q6W

EPHA2, Complex: EPHA2:ITB3

ITA2B, Complex: IGKC:ITA2B:ITB3, PDBID: 2vc2

ITA2, Complex: ITB3:CD9:ITA2, PubMed

ITA5, Complex: ITA5:ITB3:TGM2, PubMed

ITAV, Complex: ITAV:ITB3, PDBID: 1jv2

ITAV, Complex: ITB3:ITAV, PDBID: 1JV2

ITB1, Complex: NID1:ITB3:ITB1, PubMed

JAM1, Complex: ITB3:ITAV:JAM1, PubMed

PECA1, Complex: PECA1:ITB3, PubMed

PGFRA, Complex: ITB3:PGFRA, PubMed

PGFRB, Complex: PGFRB:ITB3, PubMed

PTPRZ, Complex: PTPRZ:ITB3

THY1, Complex: ITB3:THY1, PubMed

VGFR2, Complex: ITB3:VGFR2, PubMed

Domains

AA: 29-76, PDBID: 1TYE, Subunit F, Seq Identity:100%, Integrin plexin domain

AA: 133-381, PDBID: 1JV2, Subunit B, Seq Identity:100%, Integrin beta chain VWA domain

AA: 593-624, PDBID: 1JV2, Subunit B, Seq Identity:100%, EGF-like domain

AA: 634-718, PDBID: 1JV2, Subunit B, Seq Identity:100%, Integrin beta tail domain

AA: 742-786, PDBID: 1KUP, Subunit B, Seq Identity:100%, Integrin beta cytoplasmic domain

UniProt annotation for ITB3_HUMAN » Integrin beta-3
FUNCTION: 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). 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 (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). Integrin ITGAV:ITGB3 interacts with FBLN5 (via N-terminus) (By similarity). Integrin ITGAV:ITGB3 interacts with herpes virus 8/HHV-8 glycoprotein B and acts as a receptor for the virus. Interacts with HIV-1 Tat.

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.

DISEASE: Glanzmann thrombasthenia (GT) OMIM: A 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. mutations affecting the gene represented in this entry.

DISEASE: Bleeding disorder, platelet-type 16 (BDPLT16) OMIM: An 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. mutations affecting the gene represented in this entry.

UniProt features for ITB3_HUMAN » Integrin beta-3
SIGNAL 1 26 Potential.
CHAIN 27 788 Integrin beta-3.
DOMAIN 135 377 VWFA.
REPEAT 463 511 I.
REPEAT 512 553 II.
REPEAT 554 592 III.
REPEAT 593 629 IV.
REGION 463 629 Cysteine-rich tandem repeats.
DISULFID 31 461
DISULFID 39 49
DISULFID 42 75
DISULFID 52 64
DISULFID 203 210
DISULFID 258 299
DISULFID 400 412
DISULFID 432 681
DISULFID 459 463
DISULFID 474 486 Probable.
DISULFID 483 521 Probable.
DISULFID 488 497 Probable.
DISULFID 499 512 Probable.
DISULFID 527 532 Probable.
DISULFID 529 562 Probable.
DISULFID 534 547 Probable.
DISULFID 549 554
DISULFID 568 573 Probable.
DISULFID 570 601 Probable.
DISULFID 575 584 Probable.
DISULFID 586 593 Probable.
DISULFID 607 612 Probable.
DISULFID 609 657 Probable.
DISULFID 614 624 Probable.
DISULFID 627 630 Probable.
DISULFID 634 643 Probable.
DISULFID 640 713 Probable.
DISULFID 661 689
Amino Acid Sequence for ITB3_HUMAN » Integrin beta-3
MRARPRPRPL WATVLALGAL AGVGVGGPNI CTTRGVSSCQ QCLAVSPMCA WCSDEALPLG SPRCDLKENL LKDNCAPESI EFPVSEARVL EDRPLSDKGS GDSSQVTQVS PQRIALRLRP DDSKNFSIQV RQVEDYPVDI YYLMDLSYSM KDDLWSIQNL GTKLATQMRK LTSNLRIGFG AFVDKPVSPY MYISPPEALE NPCYDMKTTC LPMFGYKHVL TLTDQVTRFN EEVKKQSVSR NRDAPEGGFD AIMQATVCDE KIGWRNDASH LLVFTTDAKT HIALDGRLAG IVQPNDGQCH VGSDNHYSAS TTMDYPSLGL MTEKLSQKNI NLIFAVTENV VNLYQNYSEL IPGTTVGVLS MDSSNVLQLI VDAYGKIRSK VELEVRDLPE ELSLSFNATC LNNEVIPGLK SCMGLKIGDT VSFSIEAKVR GCPQEKEKSF TIKPVGFKDS LIVQVTFDCD CACQAQAEPN SHRCNNGNGT FECGVCRCGP GWLGSQCECS EEDYRPSQQD ECSPREGQPV CSQRGECLCG QCVCHSSDFG KITGKYCECD DFSCVRYKGE MCSGHGQCSC GDCLCDSDWT GYYCNCTTRT DTCMSSNGLL CSGRGKCECG SCVCIQPGSY GDTCEKCPTC PDACTFKKEC VECKKFDRGA LHDENTCNRY CRDEIESVKE LKDTGKDAVN CTYKNEDDCV VRFQYYEDSS GKSILYVVEE PECPKGPDIL VVLLSVMGAI LLIGLAALLI WKLLITIHDR KEFAKFEEER ARAKWDTANN PLYKEATSTF TNITYRGT