Reviewed, UniProtKB/Swiss-Prot P14770 (GPIX_HUMAN)

Names and origin

Protein names

Recommended name:
    Platelet glycoprotein IX
      Short name=GPIX
Alternative name(s):
    CD_antigen=CD42a

Gene names

Name:

GP9

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	177 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	The GPIb-V-IX complex functions as the von Willebrand factor receptor and mediates von willebrand factor-dependent platelet adhesion to blood vessels. The adhesion of platelets to injured vascular surfaces in the arterial circulation is a critical initiating event in hemostasis. GP-IX may provide for membrane insertion and orientation of GP-Ib.
Subunit structure	GP-Ib alpha and beta are disulfide linked. GP-IX is complexed with the GP-Ib heterodimer via a non covalent linkage.
Subcellular location	Membrane; Single-pass type I membrane protein.
Involvement in disease	Defects in GP9 are a cause of Bernard-Soulier syndrome (BSS) [MIM:231200]; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.
Miscellaneous	Platelet activation apparently involves disruption of the macromolecular complex of GP-Ib with the platelet glycoprotein IX (GP-IX) and dissociation of GP-Ib from the actin-binding protein.
Sequence similarities	Contains 1 LRR (leucine-rich) repeat.

Ontologies

Keywords
Biological process	Blood coagulation Cell adhesion Hemostasis
Cellular component	Membrane
Disease	Bernard Soulier syndrome Disease mutation
Domain	Leucine-rich repeat Signal Transmembrane
PTM	Glycoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	blood coagulation Traceable author statement. Source: ProtInc cell adhesion Ref.4 Non-traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.4 Traceable author statement. Source: ProtInc platelet alpha granule membrane Inferred from Experiment. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Signal peptide	1 – 16	16
	Chain	17 – 177	161	Platelet glycoprotein IX
Regions
	Topological domain	17 – 151	135	Extracellular Potential
	Transmembrane	152 – 171	20	Potential
	Topological domain	172 – 177	6	Cytoplasmic Potential
	Repeat	56 – 79	24	LRR
Amino acid modifications
	Glycosylation	60	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	7	1	L → P in BSS.
	Natural variant	24	1	C → R in BSS.
	Natural variant	37	1	D → G in BSS.
	Natural variant	56	1	L → P in BSS.
	Natural variant	61	1	N → S in BSS. dbSNP rs5030764.
	Natural variant	71	1	F → S in BSS.
	Natural variant	113	1	C → Y in BSS.
	Natural variant	156	1	A → T in BSS.
Experimental info
	Sequence conflict	24 – 26	3	CTC → LTT AA sequence Ref.6
	Sequence conflict	125	1	Missing in AAA36809. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P14770-1 [UniParc]. Last modified November 1, 1997. Version 3. Checksum: 6A023B96C7854D59	FASTA	177	19,046
	10 20 30 40 50 60 MPAWGALFLL WATAEATKDC PSPCTCRALE TMGLWVDCRG HGLTALPALP ARTRHLLLAN 70 80 90 100 110 120 NSLQSVPPGA FDHLPQLQTL DVTQNPWHCD CSLTYLRLWL EDRTPEALLQ VRCASPSLAA 130 140 150 160 170 HGPLGRLTGY QLGSCGWQLQ ASWVRPGVLW DVALVAVAAL GLALLAGLLC ATTEALD

References

[1]	"Human platelet glycoprotein IX. Characterization of cDNA and localization of the gene to chromosome 3." Hickey M.J., Deaven L.L., Roth G.J. FEBS Lett. 274:189-192(1990) [PubMed: 2253772] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 17-33 AND 98-109.
[2]	Roth G.J. Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 125.
[3]	"Characterization of the gene encoding human platelet glycoprotein IX." Hickey M.J., Roth G.J. J. Biol. Chem. 268:3438-3443(1993) [PubMed: 8429020] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Liver.
[4]	"Human platelet glycoprotein IX: an adhesive prototype of leucine-rich glycoproteins with flank-center-flank structures." Hickey M.J., Williams S.A., Roth G.J. Proc. Natl. Acad. Sci. U.S.A. 86:6773-6777(1989) [PubMed: 2771955] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-177, PROTEIN SEQUENCE OF 17-33 AND 98-109.
[5]	"Corrected DNA sequence of the platelet glycoprotein IX gene." Hayashi T., Suzuki K. Thromb. Haemost. 77:1034-1035(1997) [PubMed: 9184424] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 58-141.
[6]	"Isolation and characterization of human platelet glycoprotein IX." Roth G.J., Ozols J., Nugent D.J., Williams S.A. Biochem. Biophys. Res. Commun. 156:931-939(1988) [PubMed: 3056407] [Abstract] Cited for: PROTEIN SEQUENCE OF 17-33.
[7]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 17-27. Tissue: Platelet.
[8]	"Double heterozygosity for mutations in the platelet glycoprotein IX gene in three siblings with Bernard-Soulier syndrome." Wright S.D., Michaelides K., Johnson D.J., West N.C., Tuddenham E.G. Blood 81:2339-2347(1993) [PubMed: 8481514] [Abstract] Cited for: VARIANTS BSS GLY-37 AND SER-61.
[9]	"A phenylalanine-55 to serine amino-acid substitution in the human glycoprotein IX leucine-rich repeat is associated with Bernard-Soulier syndrome." Noris P., Simsek S., Stibbe J., von dem Borne A.E.G.K. Br. J. Haematol. 97:312-320(1997) [PubMed: 9163595] [Abstract] Cited for: VARIANT BSS SER-71.
[10]	"A new variant of Bernard-Soulier syndrome characterized by dysfunctional glycoprotein (GP) Ib and severely reduced amounts of GPIX and GPV." Noris P., Arbustini E., Spedini P., Belletti S., Balduini C.L. Br. J. Haematol. 103:1004-1013(1998) [PubMed: 9886312] [Abstract] Cited for: VARIANT BSS PRO-56.
[11]	"Cys97-->Tyr mutation in the glycoprotein IX gene associated with Bernard-Soulier syndrome." Kunishima S., Tomiyama Y., Honda S., Kurata Y., Kamiya T., Ozawa K., Saito H. Br. J. Haematol. 107:539-545(1999) [PubMed: 10583255] [Abstract] Cited for: VARIANT BSS TYR-113.
[12]	"Identification of a new mutation in platelet glycoprotein IX (GPIX) in a patient with Bernard-Soulier syndrome." Rivera C.E., Villagra J., Riordan M., Williams S., Lindstrom K.J., Rick M.E. Br. J. Haematol. 112:105-108(2001) [PubMed: 11167791] [Abstract] Cited for: VARIANT BSS ARG-24.
[13]	"A novel point mutation in the transmembrane domain of platelet glycoprotein IX gene identified in a Bernard-Soulier syndrome patient." Wang Z., Shi J., Han Y. Zhonghua Xue Ye Xue Za Zhi 22:464-466(2001) [PubMed: 11758225] [Abstract] Cited for: VARIANT BSS THR-156.
[14]	"A Leu7-to-Pro mutation in the signal peptide of platelet glycoprotein (GP)IX in a case of Bernard-Soulier syndrome abolishes surface expression of the GPIb-V-IX complex." Lanza F., de la Salle C., Baas M.-J., Schwartz A., Boval B., Cazenave J.-P., Caen J.P. Br. J. Haematol. 118:260-266(2002) [PubMed: 12100158] [Abstract] Cited for: VARIANT BSS PRO-7.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	X52997 mRNA. Translation: CAA37186.1. M80478 Genomic DNA. Translation: AAB40042.1. M25827 mRNA. Translation: AAA36809.1. D88290 Genomic DNA. Translation: BAA13580.1.
PIR	A46606.
RefSeq	NP_000165.1.
UniGene	Hs.1144
3D structure databases
HSSP	HSSP built from PDB template 1M0Z based on UniProtKB P07359.
ModBase	Search...
2-D gel databases
OGP	P14770.
Genome annotation databases
Ensembl	ENSG00000169704. Homo sapiens. [Contig view]
GeneID	2815.
KEGG	hsa:2815.
Organism-specific databases
H-InvDB	HIX0003662.
HGNC	HGNC:4444. GP9.
MIM	173515. gene. 231200. phenotype.
Orphanet	274. Bernard-Soulier syndrome.
PharmGKB	PA24478.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P14770.
HOVERGEN	P14770.
Enzyme and pathway databases
Reactome	REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	P14770.
CleanEx	HS_GP9.
GermOnline	ENSG00000169704. Homo sapiens.
Family and domain databases
InterPro	IPR001611. LRR. IPR000483. LRR_C. IPR000372. LRR_cys_N. [Graphical view]
Pfam	PF01463. LRRCT. 1 hit. PF01462. LRRNT. 1 hit. [Graphical view]
PRINTS	PR00019. LEURICHRPT.
SMART	SM00082. LRRCT. 1 hit. SM00013. LRRNT. 1 hit. [Graphical view]
ProDom	P14770. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
DrugBank	DB00468. Quinine.
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

GPIX_HUMAN

Accession

Primary (citable) accession number: P14770
Secondary accession number(s): Q14445, Q92525

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	November 1, 1997
Last modified:	July 22, 2008
This is version 94 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)