Reviewed, UniProtKB/Swiss-Prot P16671 (CD36_HUMAN)

Names and origin

Protein names

Recommended name:
    Platelet glycoprotein 4
Alternative name(s):
    Platelet glycoprotein IV
      Short name=GPIV
    Glycoprotein IIIb
      Short name=GPIIIB
    Leukocyte differentiation antigen CD36
    PAS IV
    PAS-4
    Platelet collagen receptor
    Fatty acid translocase
      Short name=FAT
    Thrombospondin receptor
    CD_antigen=CD36

Gene names

Name:	CD36
Synonyms:	GP3B, GP4

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	472 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	Seems to have numerous potential physiological functions. Binds to collagen, thrombospondin, anionic phospholipids and oxidized LDL. May function as a cell adhesion molecule. Directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes. Binds long chain fatty acids and may function in the transport and/or as a regulator of fatty acid transport. Ref.19 Ref.21
Subcellular location	Membrane; Multi-pass membrane protein.
Post-translational modification	N-glycosylated and O-glycosylated with a ratio of 2:1. Ref.8 Ref.13 Ref.14 Ref.15
Polymorphism	Genetic variation in CD36 influences the severity and outcome of malaria infection.
Involvement in disease	Defects in CD36 are the cause of platelet glycoprotein IV deficiency [MIM:608404]; also known as CD36 deficiency. Platelet glycoprotein IV deficiency can be divided into 2 subgroups. The type I phenotype is characterized by platelets and monocytes/macrophages exhibiting complete CD36 deficiency. The type II phenotype lacks the surface expression of CD36 in platelets, but expression in monocytes/macrophages is near normal. Ref.16 Ref.20 Genetic variations in CD36 are associated with susceptibility to coronary heart disease type 7 (CHDS7) [MIM:610938]. Ref.22
Sequence similarities	Belongs to the CD36 family.
Sequence caution	The sequence AAM14636.2 differs from that shown. Reason: Frameshift at position 53.

Ontologies

Keywords
Biological process	Cell adhesion Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	blood coagulation Traceable author statement. Source: ProtInc cGMP-mediated signaling Inferred from direct assay. Source: UniProtKB cell adhesion Traceable author statement. Source: ProtInc cholesterol transport Inferred from sequence or structural similarity. Source: UniProtKB lipid metabolic process Ref.5 Non-traceable author statement. Source: ProtInc lipid storage Inferred from mutant phenotype. Source: UniProtKB lipoprotein catabolic process Inferred from mutant phenotype. Source: UniProtKB lipoprotein particle clearance Inferred from sequence or structural similarity. Source: UniProtKB lipoprotein transport Inferred from mutant phenotype. Source: UniProtKB nitric oxide mediated signal transduction Inferred from direct assay. Source: UniProtKB plasma membrane long-chain fatty acid transport Inferred from direct assay. Source: UniProtKB positive regulation of cell-matrix adhesion Inferred from direct assay. Source: UniProtKB positive regulation of macrophage derived foam cell differentiation Inferred from mutant phenotype. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA cell surface Inferred from direct assay. Source: UniProtKB integral to plasma membrane Ref.8 Traceable author statement. Source: UniProtKB membrane fraction Ref.8 Traceable author statement. Source: ProtInc platelet alpha granule membrane Inferred from Experiment. Source: Reactome
Molecular function	lipid binding Inferred from direct assay. Source: UniProtKB low-density lipoprotein receptor activity Inferred from mutant phenotype. Source: UniProtKB thrombospondin receptor activity Inferred from sequence or structural similarity. Source: UniProtKB transforming growth factor beta binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.8
	Chain	2 – 472	471	Platelet glycoprotein 4		PRO_0000144151
Regions
	Topological domain	2 – 7	6	Cytoplasmic Potential
	Transmembrane	8 – 29	22	Potential
	Topological domain	30 – 439	410	Extracellular Potential
	Transmembrane	440 – 461	22	Potential
	Topological domain	462 – 472	11	Cytoplasmic Potential
Amino acid modifications
	Lipidation	3	1	S-palmitoyl cysteine Ref.12
	Lipidation	7	1	S-palmitoyl cysteine Ref.12
	Lipidation	464	1	S-palmitoyl cysteine Ref.12
	Lipidation	466	1	S-palmitoyl cysteine Ref.12
	Glycosylation	79	1	N-linked (GlcNAc...) Potential
	Glycosylation	102	1	N-linked (GlcNAc...) Potential
	Glycosylation	134	1	N-linked (GlcNAc...) Potential
	Glycosylation	163	1	N-linked (GlcNAc...) Potential
	Glycosylation	205	1	N-linked (GlcNAc...) Ref.15
	Glycosylation	220	1	N-linked (GlcNAc...) Potential
	Glycosylation	235	1	N-linked (GlcNAc...) Potential
	Glycosylation	247	1	N-linked (GlcNAc...) Potential
	Glycosylation	321	1	N-linked (GlcNAc...) Ref.14
	Glycosylation	417	1	N-linked (GlcNAc...) Ref.13 Ref.15
	Disulfide bond	243 ↔ 311		By similarity
	Disulfide bond	272 ↔ 333		By similarity
	Disulfide bond	313 ↔ 322		By similarity
Natural variations
	Natural variant	90	1	P → S in platelet glycoprotein IV deficiency; type I; degradation in the cytoplasm due to defects in maturation. dbSNP rs3765187. Ref.16 Ref.20		VAR_017913
	Natural variant	123	1	E → K in individuals from a malaria endemic area in West Africa. Ref.9		VAR_017914
	Natural variant	127	1	S → L		VAR_019049
	Natural variant	154	1	V → F: dbSNP rs5957. Ref.17		VAR_013918
	Natural variant	174	1	T → A in individuals from a malaria endemic area in West Africa. Ref.9		VAR_017915
	Natural variant	232	1	G → GN in individuals from a malaria endemic area in West Africa. Ref.9		VAR_017916
	Natural variant	254	1	F → L in platelet glycoprotein IV deficiency; type I. Ref.20		VAR_017917
	Natural variant	271	1	I → T in individuals from a malaria endemic area in West Africa. Ref.9		VAR_017918
	Natural variant	413	1	I → L in platelet glycoprotein IV deficiency; type I. Ref.20		VAR_017919
Experimental info
	Sequence conflict	44	1	L → R in AAD13993. Ref.4
	Sequence conflict	238	1	Y → D in AAD13993. Ref.4
	Sequence conflict	374	1	E → Q Ref.3
	Sequence conflict	374	1	E → Q Ref.11

Sequences

	Sequence		Length	Mass (Da)
	P16671-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 543E748259A094FA	FASTA	472	53,053
	10 20 30 40 50 60 MGCDRNCGLI AGAVIGAVLA VFGGILMPVG DLLIQKTIKK QVVLEEGTIA FKNWVKTGTE 70 80 90 100 110 120 VYRQFWIFDV QNPQEVMMNS SNIQVKQRGP YTYRVRFLAK ENVTQDAEDN TVSFLQPNGA 130 140 150 160 170 180 IFEPSLSVGT EADNFTVLNL AVAAASHIYQ NQFVQMILNS LINKSKSSMF QVRTLRELLW 190 200 210 220 230 240 GYRDPFLSLV PYPVTTTVGL FYPYNNTADG VYKVFNGKDN ISKVAIIDTY KGKRNLSYWE 250 260 270 280 290 300 SHCDMINGTD AASFPPFVEK SQVLQFFSSD ICRSIYAVFE SDVNLKGIPV YRFVLPSKAF 310 320 330 340 350 360 ASPVENPDNY CFCTEKIISK NCTSYGVLDI SKCKEGRPVY ISLPHFLYAS PDVSEPIDGL 370 380 390 400 410 420 NPNEEEHRTY LDIEPITGFT LQFAKRLQVN LLVKPSEKIQ VLKNLKRNYI VPILWLNETG 430 440 450 460 470 TIGDEKANMF RSQVTGKINL LGLIEMILLS VGVVMFVAFM ISYCACRSKT IK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"CD36 directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes." Oquendo P., Hundt E., Lawler J., Seed B. Cell 58:95-101(1989) [PubMed: 2473841] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	Sugimoto Y., Tsuruo T. Submitted (AUG-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Characterization of two alternatively spliced 5'-untranslated exons of the human CD36 gene in different cell types." Taylor K.T., Tang Y., Sobieski D.A., Lipsky R.H. Gene 133:205-212(1993) [PubMed: 7693552] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Cloning of the cDNA encoding human platelet CD36: comparison to PCR amplified fragments of monocyte, endothelial and HEL cells." Wyler B., Daviet L., Bortkiewicz H., Bordet J.C., McGregor J.L. Thromb. Haemost. 70:500-505(1993) [PubMed: 7505064] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Platelet.
[5]	"Structural organization of the gene for human CD36 glycoprotein." Armesilla A.L., Vega M.A. J. Biol. Chem. 269:18985-18991(1994) [PubMed: 7518447] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	SeattleSNPs variation discovery resource Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skeletal muscle.
[8]	"Isolation and characterization of platelet glycoprotein IV (CD36)." Tandon N.N., Lipsky R.H., Burgess W.H., Jamieson G.A. J. Biol. Chem. 264:7570-7575(1989) [PubMed: 2468669] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-37, GLYCOSYLATION. Tissue: Platelet.
[9]	"Variability of the CD36 gene in West Africa." Gelhaus A., Scheding A., Browne E., Burchard G.D., Horstmann R.D. Hum. Mutat. 18:444-450(2001) [PubMed: 11668637] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 41-203; 274-375 AND 419-472, VARIANTS LYS-123; ALA-174; ASN-232 INS AND THR-271.
[10]	"Gene encoding the collagen type I and thrombospondin receptor CD36 is located on chromosome 7q11.2." Fernandez-Ruiz E., Armesilla A.L., Sanchez-Madrid F., Vega M.A. Genomics 17:759-761(1993) [PubMed: 7503937] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 144-203.
[11]	"Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes." Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V. Biochem. J. 383:237-248(2004) [PubMed: 15242332] [Abstract] Cited for: PROTEIN SEQUENCE OF 261-273 AND 369-385. Tissue: Adipocyte.
[12]	"CD36 is palmitoylated on both N- and C-terminal cytoplasmic tails." Tao N., Wagner S.J., Lublin D.M. J. Biol. Chem. 271:22315-22320(1996) [PubMed: 8798390] [Abstract] Cited for: PALMITOYLATION AT CYS-3; CYS-7; CYS-464 AND CYS-466.
[13]	"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach." Lewandrowski U., Moebius J., Walter U., Sickmann A. Mol. Cell. Proteomics 5:226-233(2006) [PubMed: 16263699] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-417, MASS SPECTROMETRY. Tissue: Platelet.
[14]	"Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry." Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F. Proteomics 8:3833-3847(2008) [PubMed: 18780401] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-321, MASS SPECTROMETRY. Tissue: Milk.
[15]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-205 AND ASN-417, MASS SPECTROMETRY. Tissue: Liver.
[16]	"Molecular basis of CD36 deficiency. Evidence that a 478C-->T substitution (proline90-->serine) in CD36 cDNA accounts for CD36 deficiency." Kashiwagi H., Tomiyama Y., Honda S., Kosugi S., Shiraga M., Nagao N., Sekiguchi S., Kanayama Y., Kurata Y., Matsuzawa Y. J. Clin. Invest. 95:1040-1046(1995) [PubMed: 7533783] [Abstract] Cited for: VARIANT PLATELET GLYCOPROTEIN IV DEFICIENCY SER-90.
[17]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed: 10391209] [Abstract] Cited for: VARIANT PHE-154.
[18]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
[19]	"Malaria susceptibility and CD36 mutation." Aitman T.J., Cooper L.D., Norsworthy P.J., Wahid F.N., Gray J.K., Curtis B.R., McKeigue P.M., Kwiatkowski D., Greenwood B.M., Snow R.W., Hill A.V., Scott J. Nature 405:1015-1016(2000) [PubMed: 10890433] [Abstract] Cited for: ROLE IN MALARIA INFECTION.
[20]	"Identification of cryptic splice site, exon skipping, and novel point mutations in type I CD36 deficiency." Hanawa H., Watanabe K., Nakamura T., Ogawa Y., Toba K., Fuse I., Kodama M., Kato K., Fuse K., Aizawa Y. J. Med. Genet. 39:286-291(2002) [PubMed: 11950861] [Abstract] Cited for: VARIANTS PLATELET GLYCOPROTEIN IV DEFICIENCY SER-90; LEU-254 AND LEU-413.
[21]	"CD36 polymorphism is associated with protection from cerebral malaria." Omi K., Ohashi J., Patarapotikul J., Hananantachai H., Naka I., Looareesuwan S., Tokunaga K. Am. J. Hum. Genet. 72:364-374(2003) [PubMed: 12506336] [Abstract] Cited for: VARIANT LEU-127, ROLE IN MALARIA INFECTION.
[22]	"A common haplotype at the CD36 locus is associated with high free fatty acid levels and increased cardiovascular risk in Caucasians." Ma X., Bacci S., Mlynarski W., Gottardo L., Soccio T., Menzaghi C., Iori E., Lager R.A., Shroff A.R., Gervino E.V., Nesto R.W., Johnstone M.T., Abumrad N.A., Avogaro A., Trischitta V., Doria A. Hum. Mol. Genet. 13:2197-2205(2004) [PubMed: 15282206] [Abstract] Cited for: INVOLVEMENT IN CHDS7.
[23]	Erratum Ma X., Bacci S., Mlynarski W., Gottardo L., Soccio T., Menzaghi C., Iori E., Lager R.A., Shroff A.R., Gervino E.V., Nesto R.W., Johnstone M.T., Abumrad N.A., Avogaro A., Trischitta V., Doria A. Hum. Mol. Genet. 14:3973-3973(2005)
+	Additional computationally mapped references.

Web resources

Wikipedia

CD36 entry

GeneReviews

SeattleSNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	M24795 mRNA. Translation: AAA35534.1. M98398 mRNA. Translation: AAA58412.1. M98399 mRNA. Translation: AAA58413.1. L06850 mRNA. Translation: AAA16068.1. S67532 mRNA. Translation: AAD13993.1. Z32770 , Z32754, Z32755, Z32756, Z32757, Z32758, Z32759, Z32760, Z32761, Z32762, Z32763, Z32764 Genomic DNA. Translation: CAA83662.1. AY095373 Genomic DNA. Translation: AAM14636.2. Frameshift. BC008406 mRNA. Translation: AAH08406.1. AF300626 Genomic DNA. Translation: AAG60625.1. AF300627 Genomic DNA. Translation: AAG60626.1. AF300628 Genomic DNA. Translation: AAG60627.1. AF300633 Genomic DNA. Translation: AAG60632.1. AF300634 Genomic DNA. Translation: AAG60633.1. AF300635 Genomic DNA. Translation: AAG60634.1. AF300639 Genomic DNA. Translation: AAG60638.1. AF300640 Genomic DNA. Translation: AAG60639.1. S67044 mRNA. Translation: AAB28992.1. Z22924 Genomic DNA. Translation: CAA80504.1.
IPI	IPI00418495.
PIR	A54870.
RefSeq	NP_000063.2. NP_001001547.1. NP_001001548.1. NP_001120915.1. NP_001120916.1.
UniGene	Hs.120949
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	P16671.
PTM databases
PhosphoSite	P16671.
Proteomic databases
PRIDE	P16671.
Genome annotation databases
Ensembl	ENST00000309881; ENSP00000308165; ENSG00000135218; Homo sapiens. [Genome view] ENST00000394788; ENSP00000378268; ENSG00000135218; Homo sapiens. [Genome view] ENST00000394791; ENSP00000378271; ENSG00000135218; Homo sapiens. [Genome view] ENST00000432207; ENSP00000411411; ENSG00000135218; Homo sapiens. [Genome view] ENST00000433696; ENSP00000401863; ENSG00000135218; Homo sapiens. [Genome view] ENST00000435819; ENSP00000399421; ENSG00000135218; Homo sapiens. [Genome view] ENST00000447544; ENSP00000415743; ENSG00000135218; Homo sapiens. [Genome view]
GeneID	948.
KEGG	hsa:948.
UCSC	uc003uhc.1. human.
Organism-specific databases
CTD	948.
GeneCards	GC07P080069.
H-InvDB	HIX0006805.
HGNC	HGNC:1663. CD36.
HPA	CAB025866. HPA002018.
MIM	173510. gene. 248310. phenotype. 608404. phenotype. 610938. phenotype.
Orphanet	73271. Bleeding diathesis due to glycoprotein VI deficiency or integrin alpha2-beta1 deficiency.
PharmGKB	PA26212.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P16671.
OMA	FLSLVPY
OrthoDB	EOG9HB151
Enzyme and pathway databases
Reactome	REACT_602. Metabolism of lipids and lipoproteins. REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	P16671.
Bgee	P16671.
Genevestigator	P16671.
GermOnline	ENSG00000135218. Homo sapiens.
Family and domain databases
InterPro	IPR002159. CD36. IPR005428. CD36_antigen. [Graphical view]
PANTHER	PTHR11923. CD36. 1 hit.
Pfam	PF01130. CD36. 1 hit. [Graphical view]
PRINTS	PR01610. CD36ANTIGEN. PR01609. CD36FAMILY.
ProtoNet	Search...
Other Resources
NextBio	3938.
SOURCE	Search...

Entry information

Entry name

CD36_HUMAN

Accession

Primary (citable) accession number: P16671
Secondary accession number(s): Q13966 , Q16093, Q8TCV7, Q9BPZ8, Q9BQC2, Q9BZM8, Q9BZN3, Q9BZN4, Q9BZN5

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	January 23, 2007
Last modified:	November 24, 2009
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.