GPIX_HUMAN
ID GPIX_HUMAN Reviewed; 177 AA.
AC P14770; Q14445; Q8N1D1; Q92525;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 3.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Platelet glycoprotein IX;
DE Short=GP-IX;
DE Short=GPIX;
DE AltName: Full=Glycoprotein 9;
DE AltName: CD_antigen=CD42a;
DE Flags: Precursor;
GN Name=GP9;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 17-33 AND 98-109.
RX PubMed=2253772; DOI=10.1016/0014-5793(90)81361-q;
RA Hickey M.J., Deaven L.L., Roth G.J.;
RT "Human platelet glycoprotein IX. Characterization of cDNA and localization
RT of the gene to chromosome 3.";
RL FEBS Lett. 274:189-192(1990).
RN [2]
RP SEQUENCE REVISION TO 125.
RA Roth G.J.;
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=8429020; DOI=10.1016/s0021-9258(18)53713-3;
RA Hickey M.J., Roth G.J.;
RT "Characterization of the gene encoding human platelet glycoprotein IX.";
RL J. Biol. Chem. 268:3438-3443(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-156.
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 12-177, AND PROTEIN SEQUENCE OF 17-33 AND
RP 98-109.
RX PubMed=2771955; DOI=10.1073/pnas.86.17.6773;
RA Hickey M.J., Williams S.A., Roth G.J.;
RT "Human platelet glycoprotein IX: an adhesive prototype of leucine-rich
RT glycoproteins with flank-center-flank structures.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:6773-6777(1989).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 58-141.
RX PubMed=9184424;
RA Hayashi T., Suzuki K.;
RT "Corrected DNA sequence of the platelet glycoprotein IX gene.";
RL Thromb. Haemost. 77:1034-1035(1997).
RN [7]
RP PROTEIN SEQUENCE OF 17-33.
RX PubMed=3056407; DOI=10.1016/s0006-291x(88)80933-1;
RA Roth G.J., Ozols J., Nugent D.J., Williams S.A.;
RT "Isolation and characterization of human platelet glycoprotein IX.";
RL Biochem. Biophys. Res. Commun. 156:931-939(1988).
RN [8]
RP PROTEIN SEQUENCE OF 17-27.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [9]
RP VARIANTS BSS GLY-37 AND SER-61.
RX PubMed=8481514;
RA Wright S.D., Michaelides K., Johnson D.J., West N.C., Tuddenham E.G.;
RT "Double heterozygosity for mutations in the platelet glycoprotein IX gene
RT in three siblings with Bernard-Soulier syndrome.";
RL Blood 81:2339-2347(1993).
RN [10]
RP VARIANT BSS SER-71.
RX PubMed=9163595; DOI=10.1046/j.1365-2141.1997.582706.x;
RA Noris P., Simsek S., Stibbe J., von dem Borne A.E.G.K.;
RT "A phenylalanine-55 to serine amino-acid substitution in the human
RT glycoprotein IX leucine-rich repeat is associated with Bernard-Soulier
RT syndrome.";
RL Br. J. Haematol. 97:312-320(1997).
RN [11]
RP VARIANT BSS PRO-56.
RX PubMed=9886312; DOI=10.1046/j.1365-2141.1998.01100.x;
RA Noris P., Arbustini E., Spedini P., Belletti S., Balduini C.L.;
RT "A new variant of Bernard-Soulier syndrome characterized by dysfunctional
RT glycoprotein (GP) Ib and severely reduced amounts of GPIX and GPV.";
RL Br. J. Haematol. 103:1004-1013(1998).
RN [12]
RP VARIANT BSS TYR-113.
RX PubMed=10583255; DOI=10.1046/j.1365-2141.1999.01733.x;
RA Kunishima S., Tomiyama Y., Honda S., Kurata Y., Kamiya T., Ozawa K.,
RA Saito H.;
RT "Cys97-->Tyr mutation in the glycoprotein IX gene associated with Bernard-
RT Soulier syndrome.";
RL Br. J. Haematol. 107:539-545(1999).
RN [13]
RP VARIANT BSS ARG-24.
RX PubMed=11167791; DOI=10.1046/j.1365-2141.2001.02529.x;
RA Rivera C.E., Villagra J., Riordan M., Williams S., Lindstrom K.J.,
RA Rick M.E.;
RT "Identification of a new mutation in platelet glycoprotein IX (GPIX) in a
RT patient with Bernard-Soulier syndrome.";
RL Br. J. Haematol. 112:105-108(2001).
RN [14]
RP VARIANT THR-156.
RX PubMed=11758225;
RA Wang Z., Shi J., Han Y.;
RT "A novel point mutation in the transmembrane domain of platelet
RT glycoprotein IX gene identified in a Bernard-Soulier syndrome patient.";
RL Zhonghua Xue Ye Xue Za Zhi 22:464-466(2001).
RN [15]
RP VARIANT BSS PRO-7.
RX PubMed=12100158; DOI=10.1046/j.1365-2141.2002.03544.x;
RA Lanza F., de la Salle C., Baas M.-J., Schwartz A., Boval B.,
RA Cazenave J.-P., Caen J.P.;
RT "A Leu7-to-Pro mutation in the signal peptide of platelet glycoprotein
RT (GP)IX in a case of Bernard-Soulier syndrome abolishes surface expression
RT of the GPIb-V-IX complex.";
RL Br. J. Haematol. 118:260-266(2002).
CC -!- FUNCTION: The GPIb-V-IX complex functions as the vWF receptor and
CC mediates vWF-dependent platelet adhesion to blood vessels. The adhesion
CC of platelets to injured vascular surfaces in the arterial circulation
CC is a critical initiating event in hemostasis. GP-IX may provide for
CC membrane insertion and orientation of GP-Ib.
CC -!- SUBUNIT: Two GP-Ib beta are disulfide-linked to one GP-Ib alpha. GP-IX
CC is complexed with the GP-Ib heterodimer via a non covalent linkage.
CC -!- INTERACTION:
CC P14770; P40197: GP5; NbExp=2; IntAct=EBI-1754109, EBI-10891395;
CC P14770; P49639: HOXA1; NbExp=4; IntAct=EBI-1754109, EBI-740785;
CC P14770; O43597: SPRY2; NbExp=3; IntAct=EBI-1754109, EBI-742487;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- DISEASE: Bernard-Soulier syndrome (BSS) [MIM:231200]: A coagulation
CC disorder characterized by a prolonged bleeding time, unusually large
CC platelets, thrombocytopenia, and impaired prothrombin consumption.
CC {ECO:0000269|PubMed:10583255, ECO:0000269|PubMed:11167791,
CC ECO:0000269|PubMed:11758225, ECO:0000269|PubMed:12100158,
CC ECO:0000269|PubMed:8481514, ECO:0000269|PubMed:9163595,
CC ECO:0000269|PubMed:9886312}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Platelet activation apparently involves disruption of
CC the macromolecular complex of GP-Ib with the platelet glycoprotein IX
CC (GP-IX) and dissociation of GP-Ib from the actin-binding protein.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X52997; CAA37186.1; -; mRNA.
DR EMBL; M80478; AAB40042.1; -; Genomic_DNA.
DR EMBL; M25827; AAA36809.1; -; mRNA.
DR EMBL; BC030229; AAH30229.1; -; mRNA.
DR EMBL; D88290; BAA13580.1; -; Genomic_DNA.
DR CCDS; CCDS3055.1; -.
DR PIR; A46606; A46606.
DR RefSeq; NP_000165.1; NM_000174.4.
DR RefSeq; XP_005247431.1; XM_005247374.3.
DR RefSeq; XP_011511003.1; XM_011512701.1.
DR RefSeq; XP_011511004.1; XM_011512702.1.
DR PDB; 3REZ; X-ray; 2.35 A; A/B/C/D=45-52, A/B/C/D=65-76, A/B/C/D=92-102.
DR PDBsum; 3REZ; -.
DR AlphaFoldDB; P14770; -.
DR SMR; P14770; -.
DR BioGRID; 109077; 110.
DR ComplexPortal; CPX-114; Glycoprotein Ib-IX-V complex.
DR ComplexPortal; CPX-117; Glycoprotein Ib-IX-V-Filamin-A complex.
DR IntAct; P14770; 8.
DR MINT; P14770; -.
DR STRING; 9606.ENSP00000303942; -.
DR DrugBank; DB00468; Quinine.
DR GlyGen; P14770; 1 site.
DR iPTMnet; P14770; -.
DR PhosphoSitePlus; P14770; -.
DR BioMuta; GP9; -.
DR DMDM; 2822110; -.
DR OGP; P14770; -.
DR MassIVE; P14770; -.
DR PaxDb; P14770; -.
DR PeptideAtlas; P14770; -.
DR PRIDE; P14770; -.
DR ProteomicsDB; 53080; -.
DR Antibodypedia; 17356; 517 antibodies from 38 providers.
DR DNASU; 2815; -.
DR Ensembl; ENST00000307395.5; ENSP00000303942.4; ENSG00000169704.5.
DR GeneID; 2815; -.
DR KEGG; hsa:2815; -.
DR MANE-Select; ENST00000307395.5; ENSP00000303942.4; NM_000174.5; NP_000165.1.
DR UCSC; uc003elm.3; human.
DR CTD; 2815; -.
DR DisGeNET; 2815; -.
DR GeneCards; GP9; -.
DR HGNC; HGNC:4444; GP9.
DR HPA; ENSG00000169704; Tissue enhanced (bone marrow, lung, lymphoid tissue).
DR MalaCards; GP9; -.
DR MIM; 173515; gene.
DR MIM; 231200; phenotype.
DR neXtProt; NX_P14770; -.
DR OpenTargets; ENSG00000169704; -.
DR Orphanet; 274; Bernard-Soulier syndrome.
DR PharmGKB; PA28825; -.
DR VEuPathDB; HostDB:ENSG00000169704; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00530000064244; -.
DR HOGENOM; CLU_094615_1_1_1; -.
DR InParanoid; P14770; -.
DR OMA; GYELGSC; -.
DR OrthoDB; 1366218at2759; -.
DR PhylomeDB; P14770; -.
DR PathwayCommons; P14770; -.
DR Reactome; R-HSA-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR Reactome; R-HSA-430116; GP1b-IX-V activation signalling.
DR Reactome; R-HSA-75892; Platelet Adhesion to exposed collagen.
DR Reactome; R-HSA-76009; Platelet Aggregation (Plug Formation).
DR Reactome; R-HSA-9673221; Defective F9 activation.
DR SignaLink; P14770; -.
DR SIGNOR; P14770; -.
DR BioGRID-ORCS; 2815; 8 hits in 1068 CRISPR screens.
DR GeneWiki; Glycoprotein_IX; -.
DR GenomeRNAi; 2815; -.
DR Pharos; P14770; Tbio.
DR PRO; PR:P14770; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P14770; protein.
DR Bgee; ENSG00000169704; Expressed in monocyte and 70 other tissues.
DR Genevisible; P14770; HS.
DR GO; GO:1990779; C:glycoprotein Ib-IX-V complex; IPI:ComplexPortal.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0007596; P:blood coagulation; TAS:ProtInc.
DR GO; GO:0007597; P:blood coagulation, intrinsic pathway; IPI:ComplexPortal.
DR GO; GO:0007155; P:cell adhesion; NAS:ProtInc.
DR GO; GO:0035855; P:megakaryocyte development; IC:ComplexPortal.
DR GO; GO:0010572; P:positive regulation of platelet activation; IDA:ComplexPortal.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IDA:ComplexPortal.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000372; LRRNT.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF01462; LRRNT; 1.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00013; LRRNT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Bernard Soulier syndrome; Blood coagulation; Cell adhesion;
KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein;
KW Hemostasis; Leucine-rich repeat; Membrane; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0000269|PubMed:2253772, ECO:0000269|PubMed:2771955,
FT ECO:0000269|PubMed:3056407"
FT CHAIN 17..177
FT /note="Platelet glycoprotein IX"
FT /id="PRO_0000021360"
FT TOPO_DOM 17..147
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..168
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 169..177
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 17..51
FT /note="LRRNT"
FT REPEAT 60..83
FT /note="LRR"
FT DOMAIN 85..137
FT /note="LRRCT"
FT CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 7
FT /note="L -> P (in BSS; dbSNP:rs121918038)"
FT /evidence="ECO:0000269|PubMed:12100158"
FT /id="VAR_024996"
FT VARIANT 24
FT /note="C -> R (in BSS; dbSNP:rs28933378)"
FT /evidence="ECO:0000269|PubMed:11167791"
FT /id="VAR_024997"
FT VARIANT 37
FT /note="D -> G (in BSS; dbSNP:rs121918036)"
FT /evidence="ECO:0000269|PubMed:8481514"
FT /id="VAR_005263"
FT VARIANT 56
FT /note="L -> P (in BSS; dbSNP:rs28933377)"
FT /evidence="ECO:0000269|PubMed:9886312"
FT /id="VAR_024998"
FT VARIANT 61
FT /note="N -> S (in BSS; dbSNP:rs5030764)"
FT /evidence="ECO:0000269|PubMed:8481514"
FT /id="VAR_005264"
FT VARIANT 71
FT /note="F -> S (in BSS; dbSNP:rs121918037)"
FT /evidence="ECO:0000269|PubMed:9163595"
FT /id="VAR_024999"
FT VARIANT 113
FT /note="C -> Y (in BSS)"
FT /evidence="ECO:0000269|PubMed:10583255"
FT /id="VAR_025008"
FT VARIANT 156
FT /note="A -> T (in dbSNP:rs3796130)"
FT /evidence="ECO:0000269|PubMed:11758225,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_025009"
FT CONFLICT 24..26
FT /note="CTC -> LTT (in Ref. 7; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 125
FT /note="Missing (in Ref. 2; AAA36809)"
FT /evidence="ECO:0000305"
FT TURN 68..73
FT /evidence="ECO:0007829|PDB:3REZ"
FT HELIX 94..101
FT /evidence="ECO:0007829|PDB:3REZ"
SQ SEQUENCE 177 AA; 19046 MW; 6A023B96C7854D59 CRC64;
MPAWGALFLL WATAEATKDC PSPCTCRALE TMGLWVDCRG HGLTALPALP ARTRHLLLAN
NSLQSVPPGA FDHLPQLQTL DVTQNPWHCD CSLTYLRLWL EDRTPEALLQ VRCASPSLAA
HGPLGRLTGY QLGSCGWQLQ ASWVRPGVLW DVALVAVAAL GLALLAGLLC ATTEALD
