P16671 (CD36_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Platelet glycoprotein 4

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

Gene names

Name:	CD36
Synonyms:	GP3B, GP4

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	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. Receptor for thombospondins, THBS1 AND THBS2, mediating their antiangiogenic efects. Ref.20 Ref.22
Subunit structure	Interacts with THBS1 and THBS2; the interactions mediate the THBS antiangiogenic activity. Ref.12
Subcellular location	Membrane; Multi-pass membrane protein.
Post-translational modification	N-glycosylated and O-glycosylated with a ratio of 2:1. Ref.8 Ref.14 Ref.15 Ref.16
Polymorphism	Genetic variations in CD36 are involved in susceptibility to malaria and influence the severity and outcome of malaria infection [MIM:611162].
Involvement in disease	Defects in CD36 are the cause of platelet glycoprotein IV deficiency (PG4D)[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.17 Ref.21 Genetic variations in CD36 are associated with susceptibility to coronary heart disease type 7 (CHDS7) [MIM:610938]. Ref.23
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 Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cGMP-mediated signaling Inferred from direct assay. Source: BHF-UCL cell adhesion Traceable author statement. Source: ProtInc cholesterol transport Inferred from sequence or structural similarity. Source: BHF-UCL lipid metabolic process Non-traceable author statement. Source: ProtInc lipid storage Inferred from mutant phenotype. Source: BHF-UCL lipoprotein transport Inferred from mutant phenotype. Source: BHF-UCL low-density lipoprotein particle clearance Inferred from mutant phenotype. Source: BHF-UCL nitric oxide mediated signal transduction Inferred from direct assay. Source: BHF-UCL plasma membrane long-chain fatty acid transport Inferred from direct assay. Source: BHF-UCL platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome positive regulation of cell-matrix adhesion Inferred from direct assay. Source: BHF-UCL positive regulation of macrophage derived foam cell differentiation Inferred from mutant phenotype. Source: BHF-UCL
Cellular component	integral to plasma membrane Traceable author statement. Source: BHF-UCL membrane fraction Traceable author statement. Source: ProtInc platelet alpha granule membrane Traceable author statement. Source: Reactome
Molecular function	lipid binding Inferred from direct assay. Source: BHF-UCL low-density lipoprotein particle binding Inferred from direct assay. Source: BHF-UCL low-density lipoprotein receptor activity Inferred from mutant phenotype. Source: BHF-UCL thrombospondin receptor activity Inferred from sequence or structural similarity. Source: BHF-UCL transforming growth factor beta binding Inferred from sequence or structural similarity. Source: BHF-UCL
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	Helical; Potential
	Topological domain	30 – 439	410	Extracellular Potential
	Transmembrane	440 – 461	22	Helical; Potential
	Topological domain	462 – 472	11	Cytoplasmic Potential
	Region	93 – 120	28	Required for interaction with thrombospondins, THBS1 and THBS2
Amino acid modifications
	Lipidation	3	1	S-palmitoyl cysteine Ref.13
	Lipidation	7	1	S-palmitoyl cysteine Ref.13
	Lipidation	464	1	S-palmitoyl cysteine Ref.13
	Lipidation	466	1	S-palmitoyl cysteine Ref.13
	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.16
	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.15
	Glycosylation	417	1	N-linked (GlcNAc...) Ref.14 Ref.16
	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 PG4D; type I; degradation in the cytoplasm due to defects in maturation. Ref.17 Ref.21 Corresponds to variant rs3765187 [ dbSNP | Ensembl ].		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. Ref.22		VAR_019049
	Natural variant	154	1	V → F. Ref.18 Corresponds to variant rs5957 [ dbSNP | Ensembl ].		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 PG4D; type I. Ref.21		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 PG4D; type I. Ref.21		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 in AAA16068. Ref.3
	Sequence conflict	374	1	E → Q AA sequence Ref.11

Sequences

	Sequence		Length	Mass (Da)
	P16671 [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]	"Thrombospondin sequence motif (CSVTCG) is responsible for CD36 binding." Asch A.S., Silbiger S., Heimer E., Nachman R.L. Biochem. Biophys. Res. Commun. 182:1208-1217(1992) [PubMed: 1371676] [Abstract] Cited for: INTERACTION WITH THBS1 AND THBS2.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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 PG4D SER-90.
[18]	"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.
[19]	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)
[20]	"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.
[21]	"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 PG4D SER-90; LEU-254 AND LEU-413.
[22]	"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.
[23]	"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.
[24]	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
EMBL GenBank DDBJ	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. NM_000072.3. NP_001001547.1. NM_001001547.2. NP_001001548.1. NM_001001548.2. NP_001120915.1. NM_001127443.1. NP_001120916.1. NM_001127444.1.
UniGene	Hs.120949.
3D structure databases
ProteinModelPortal	P16671.
ModBase	Search...
Protein-protein interaction databases
IntAct	P16671. 7 interactions.
STRING	P16671.
PTM databases
PhosphoSite	P16671.
Polymorphism databases
DMDM	115982.
Proteomic databases
PRIDE	P16671.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000309881; ENSP00000308165; ENSG00000135218. ENST00000394788; ENSP00000378268; ENSG00000135218. ENST00000432207; ENSP00000411411; ENSG00000135218. ENST00000433696; ENSP00000401863; ENSG00000135218. ENST00000435819; ENSP00000399421; ENSG00000135218. ENST00000447544; ENSP00000415743; ENSG00000135218.
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. 611162. phenotype.
neXtProt	NX_P16671.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG002754.
InParanoid	P16671.
OMA	FLSLVPY.
OrthoDB	EOG4KWJT5.
PhylomeDB	P16671.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_604. Hemostasis. REACT_6900. Immune System.
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]
KO	K06259.
PANTHER	PTHR11923. CD36. 1 hit.
Pfam	PF01130. CD36. 1 hit. [Graphical view]
PRINTS	PR01610. CD36ANTIGEN. PR01609. CD36FAMILY.
ProtoNet	Search...
Other
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:	January 25, 2012
This is version 134 of the entry and version 2 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.