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   27-MAR-2024, entry version 215.
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.
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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   GlyCosmos; P14770; 1 site, No reported glycans.
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; 9606-ENSP00000303942; -.
DR   PeptideAtlas; P14770; -.
DR   ProteomicsDB; 53080; -.
DR   Antibodypedia; 17356; 538 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   AGR; HGNC:4444; -.
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; 5356136at2759; -.
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; 13 hits in 1147 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 cell types or tissues.
DR   GO; GO:1990779; C:glycoprotein Ib-IX-V complex; IPI:ComplexPortal.
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; ISO: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; Ribonuclease Inhibitor; 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   PANTHER; PTHR22650; GLYCOPROTEIN IB BETA; 1.
DR   PANTHER; PTHR22650:SF6; PLATELET GLYCOPROTEIN IX; 1.
DR   Pfam; PF13855; LRR_8; 1.
DR   Pfam; PF01462; LRRNT; 1.
DR   SMART; SM00082; LRRCT; 1.
DR   SMART; SM00013; LRRNT; 1.
DR   SUPFAM; SSF52058; L domain-like; 1.
DR   Genevisible; P14770; HS.
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
//