P14770 (GPIX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Platelet glycoprotein IX
Short name=GP-IX
Short name=GPIX

Alternative name(s):
Glycoprotein 9
CD_antigen=CD42a

Gene names

Name:

GP9

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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 vWF receptor and mediates vWF-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	Two GP-Ib beta are disulfide-linked to one GP-Ib alpha. 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	Bernard-Soulier syndrome (BSS) [MIM:231200]: A coagulation disorder characterized by a prolonged bleeding time, unusually large platelets, thrombocytopenia, and impaired prothrombin consumption. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15
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. Contains 1 LRRCT domain. Contains 1 LRRNT domain.

Ontologies

Keywords
Biological process	Blood coagulation Cell adhesion Hemostasis
Cellular component	Membrane
Disease	Bernard Soulier syndrome Disease mutation
Domain	Leucine-rich repeat Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation, intrinsic pathway Traceable author statement. Source: Reactome cell adhesion Non-traceable author statement Ref.5. Source: ProtInc platelet activation Traceable author statement. Source: Reactome
Cellular_component	integral to plasma membrane Traceable author statement Ref.5. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 16	16	Ref.1 Ref.5 Ref.7 Ref.8
	Chain	17 – 177	161	Platelet glycoprotein IX		PRO_0000021360
Regions
	Topological domain	17 – 147	131	Extracellular Potential
	Transmembrane	148 – 168	21	Helical; Potential
	Topological domain	169 – 177	9	Cytoplasmic Potential
	Domain	17 – 51	35	LRRNT
	Repeat	60 – 83	24	LRR
	Domain	85 – 137	53	LRRCT
Amino acid modifications
	Glycosylation	60	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	7	1	L → P in BSS. Ref.15		VAR_024996
	Natural variant	24	1	C → R in BSS. Ref.13 Corresponds to variant rs28933378 [ dbSNP | Ensembl ].		VAR_024997
	Natural variant	37	1	D → G in BSS. Ref.9		VAR_005263
	Natural variant	56	1	L → P in BSS. Ref.11 Corresponds to variant rs28933377 [ dbSNP | Ensembl ].		VAR_024998
	Natural variant	61	1	N → S in BSS. Ref.9 Corresponds to variant rs5030764 [ dbSNP | Ensembl ].		VAR_005264
	Natural variant	71	1	F → S in BSS. Ref.10		VAR_024999
	Natural variant	113	1	C → Y in BSS. Ref.12		VAR_025008
	Natural variant	156	1	A → T in BSS. Ref.4 Ref.14 Corresponds to variant rs3796130 [ dbSNP | Ensembl ].		VAR_025009
Experimental info
	Sequence conflict	24 – 26	3	CTC → LTT AA sequence Ref.7
	Sequence conflict	125	1	Missing in AAA36809. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P14770 [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

	« Hide 'large scale' referencesShow 'large scale' 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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Liver.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-156. Tissue: Pancreas.
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-177, PROTEIN SEQUENCE OF 17-33 AND 98-109.
[6]	"Corrected DNA sequence of the platelet glycoprotein IX gene." Hayashi T., Suzuki K. Thromb. Haemost. 77:1034-1035(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 58-141.
[7]	"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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 17-33.
[8]	"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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 17-27. Tissue: Platelet.
[9]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS BSS GLY-37 AND SER-61.
[10]	"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] [Europe PMC] [Abstract] Cited for: VARIANT BSS SER-71.
[11]	"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] [Europe PMC] [Abstract] Cited for: VARIANT BSS PRO-56.
[12]	"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] [Europe PMC] [Abstract] Cited for: VARIANT BSS TYR-113.
[13]	"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] [Europe PMC] [Abstract] Cited for: VARIANT BSS ARG-24.
[14]	"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] [Europe PMC] [Abstract] Cited for: VARIANT BSS THR-156.
[15]	"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] [Europe PMC] [Abstract] Cited for: VARIANT BSS PRO-7.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	X52997 mRNA. Translation: CAA37186.1. M80478 Genomic DNA. Translation: AAB40042.1. M25827 mRNA. Translation: AAA36809.1. BC030229 mRNA. Translation: AAH30229.1. D88290 Genomic DNA. Translation: BAA13580.1.
IPI	IPI00027502.
PIR	A46606.
RefSeq	NP_000165.1. NM_000174.3.
UniGene	Hs.1144.
3D structure databases
ProteinModelPortal	P14770.
ModBase	Search...
Protein-protein interaction databases
IntAct	P14770. 3 interactions.
MINT	MINT-6742784.
STRING	9606.ENSP00000303942.
Polymorphism databases
DMDM	2822110.
2D gel databases
OGP	P14770.
Proteomic databases
PaxDb	P14770.
PRIDE	P14770.
Protocols and materials databases
DNASU	2815.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000307395; ENSP00000303942; ENSG00000169704.
GeneID	2815.
KEGG	hsa:2815.
UCSC	uc003elm.2. human.
Organism-specific databases
CTD	2815.
GeneCards	GC03P128779.
HGNC	HGNC:4444. GP9.
MIM	173515. gene. 231200. phenotype.
neXtProt	NX_P14770.
Orphanet	274. Bernard-Soulier syndrome.
PharmGKB	PA28825.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG307904.
HOGENOM	HOG000089943.
HOVERGEN	HBG005898.
InParanoid	P14770.
KO	K06263.
OMA	PPGAFDH.
OrthoDB	EOG4SBF03.
PhylomeDB	P14770.
Enzyme and pathway databases
Reactome	REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	P14770.
Bgee	P14770.
CleanEx	HS_GP9.
Genevestigator	P14770.
GermOnline	ENSG00000169704. Homo sapiens.
Family and domain databases
InterPro	IPR000483. Cys-rich_flank_reg_C. IPR000372. LRR-contain_N. [Graphical view]
Pfam	PF01462. LRRNT. 1 hit. [Graphical view]
SMART	SM00082. LRRCT. 1 hit. SM00013. LRRNT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00468. Quinine.
GenomeRNAi	2815.
NextBio	11097.
SOURCE	Search...

Entry information

Entry name

GPIX_HUMAN

Accession

Primary (citable) accession number: P14770
Secondary accession number(s): Q14445, Q8N1D1, Q92525

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 140 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.