P08962 (CD63_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
CD63 antigen

Alternative name(s):
Granulophysin
Lysosomal-associated membrane protein 3
Short name=LAMP-3
Melanoma-associated antigen ME491
OMA81H
Ocular melanoma-associated antigen
Tetraspanin-30
Short name=Tspan-30
CD_antigen=CD63

Gene names

Name:	CD63
Synonyms:	MLA1, TSPAN30

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	238 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	This antigen is associated with early stages of melanoma tumor progression. May play a role in growth regulation.
Subcellular location	Cell membrane; Multi-pass membrane protein. Lysosome membrane; Multi-pass membrane protein. Late endosome membrane; Multi-pass membrane protein. Note: Also found in Weibel-Palade bodies of endothelial cells. Located in platelet dense granules. Ref.3 Ref.12 Ref.14 Ref.16 Ref.17
Tissue specificity	Dysplastic nevi, radial growth phase primary melanomas, hematopoietic cells, tissue macrophages.
Miscellaneous	Lack of expression of CD63 in platelets has been observed in a patient with Hermansky-Pudlak syndrome (HPS). Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous, rare, autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS.
Sequence similarities	Belongs to the tetraspanin (TM4SF) family.

Ontologies

Keywords
Cellular component	Cell membrane Endosome Lysosome Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular protein localization Inferred from direct assay PubMed 15647390. Source: MGI platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome regulation of rubidium ion transport Inferred from direct assay PubMed 15647390. Source: MGI
Cellular_component	cell surface Inferred from direct assay PubMed 15647390. Source: MGI endosome membrane Inferred from direct assay PubMed 15229288. Source: MGI integral to plasma membrane Traceable author statement Ref.3. Source: ProtInc late endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell lysosomal membrane Traceable author statement Ref.3. Source: ProtInc platelet dense granule membrane Traceable author statement. Source: Reactome
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P08962-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P08962-2)

The sequence of this isoform differs from the canonical sequence as follows:
     23-45: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.12 Ref.13
	Chain	2 – 238	237	CD63 antigen		PRO_0000219216
Regions
	Topological domain	2 – 11	10	Cytoplasmic Potential
	Transmembrane	12 – 32	21	Helical; Potential
	Topological domain	33 – 51	19	Extracellular Potential
	Transmembrane	52 – 72	21	Helical; Potential
	Topological domain	73 – 81	9	Cytoplasmic Potential
	Transmembrane	82 – 102	21	Helical; Potential
	Topological domain	103 – 203	101	Extracellular Potential
	Transmembrane	204 – 224	21	Helical; Potential
	Topological domain	225 – 238	14	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	130	1	N-linked (GlcNAc...) Ref.15 Ref.18
	Glycosylation	150	1	N-linked (GlcNAc...) Potential
	Glycosylation	172	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	23 – 45	23	Missing in isoform 2.		VSP_045300
Experimental info
	Sequence conflict	36	1	Q → E AA sequence Ref.12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 85AC8E235C6E425F	FASTA	238	25,637
	10 20 30 40 50 60 MAVEGGMKCV KFLLYVLLLA FCACAVGLIA VGVGAQLVLS QTIIQGATPG SLLPVVIIAV 70 80 90 100 110 120 GVFLFLVAFV GCCGACKENY CLMITFAIFL SLIMLVEVAA AIAGYVFRDK VMSEFNNNFR 130 140 150 160 170 180 QQMENYPKNN HTASILDRMQ ADFKCCGAAN YTDWEKIPSM SKNRVPDSCC INVTVGCGIN 190 200 210 220 230 FNEKAIHKEG CVEKIGGWLR KNVLVVAAAA LGIAFVEVLG IVFACCLVKS IRSGYEVM
	Isoform 2 [UniParc]. Checksum: C4469E42BCC8C4F7	FASTA	215	23,430
	10 20 30 40 50 60 MAVEGGMKCV KFLLYVLLLA FCGATPGSLL PVVIIAVGVF LFLVAFVGCC GACKENYCLM 70 80 90 100 110 120 ITFAIFLSLI MLVEVAAAIA GYVFRDKVMS EFNNNFRQQM ENYPKNNHTA SILDRMQADF 130 140 150 160 170 180 KCCGAANYTD WEKIPSMSKN RVPDSCCINV TVGCGINFNE KAIHKEGCVE KIGGWLRKNV 190 200 210 LVVAAAALGI AFVEVLGIVF ACCLVKSIRS GYEVM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of an antigen associated with early stages of melanoma tumor progression." Hotta H., Ross A.H., Huebner K., Isobe M., Wendeborn S., Chao M.V., Ricciardi R.P., Tsujimoto Y., Croce C.M., Koprowski H. Cancer Res. 48:2955-2962(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Characterization of three abundant mRNAs from human ovarian granulosa cells." Rapp G., Freudenstein J., Klaudiny J., Mucha J., Wempe F., Zimmer M., Scheit K.H. DNA Cell Biol. 9:479-485(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Ovary.
[3]	"CD63 antigen. A novel lysosomal membrane glycoprotein, cloned by a screening procedure for intracellular antigens in eukaryotic cells." Metzelaar M.J., Wigngaard P.L., Peters P.J., Sixma J.J., Nieuwenhuis H.K., Clevers H.C. J. Biol. Chem. 266:3239-3245(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION.
[4]	"An ocular melanoma-associated antigen. Molecular characterization." Wang M.X., Earley J.J. Jr., Shields J.A., Donoso L.A. Arch. Ophthalmol. 110:399-404(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	"Genomic structure of the ME491/CD63 antigen gene and functional analysis of the 5'-flanking regulatory sequences." Hotta H., Miyamoto H., Hara I., Takahashi N., Homma M. Biochem. Biophys. Res. Commun. 185:436-442(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Melanocyte variant of lysosome-associated membrane protein-3 (LAMP3; also CD63 and melanoma associated antigen ME419) mRNA." Ancans J., Suzuki I., Thody A.J. Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Skin.
[7]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Skeletal muscle.
[8]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[9]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[10]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	"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] (ISOFORM 1). Tissue: Lung and Muscle.
[12]	"The protein CD63 is in platelet dense granules, is deficient in a patient with Hermansky-Pudlak syndrome, and appears identical to granulophysin." Nishibori M., Cham B., McNicol A., Shalev A., Jain N., Gerrard J.M. J. Clin. Invest. 91:1775-1782(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-38, SUBCELLULAR LOCATION, LACK OF EXPRESSION IN HERMANSKY-PUDLAK SYNDROME. Tissue: Platelet.
[13]	"Isolation and amino terminal sequencing of a novel melanoma-associated antigen." Ross A.H., Dietzschold B., Jackson D.M., Earley J.J., Ghrist B.F.D., Atkinson B., Koprowski H. Arch. Biochem. Biophys. 242:540-548(1985) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-21.
[14]	"The tetraspanin CD63/lamp3 cycles between endocytic and secretory compartments in human endothelial cells." Kobayashi T., Vischer U.M., Rosnoblet C., Lebrand C., Lindsay M., Parton R.G., Kruithof E.K.O., Gruenberg J. Mol. Biol. Cell 11:1829-1843(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[15]	"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry." Zhang H., Li X.-J., Martin D.B., Aebersold R. Nat. Biotechnol. 21:660-666(2003) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-130.
[16]	"LAMP-1 and LAMP-2, but not LAMP-3, are reliable markers for activation-induced secretion of human mast cells." Gruetzkau A., Smorodchenko A., Lippert U., Kirchhof L., Artuc M., Henz B.M. Cytometry 61:62-68(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[17]	"Integral and associated lysosomal membrane proteins." Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H., Elsaesser H.-P., Mann M., Hasilik A. Traffic 8:1676-1686(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Placenta.
[18]	"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] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-130, MASS SPECTROMETRY. Tissue: Liver.
[19]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X07982 mRNA. Translation: CAA30792.1. M59907 mRNA. Translation: AAA63235.1. M58485 mRNA. No translation available. S93788 mRNA. Translation: AAB21617.1. X62654 Genomic DNA. Translation: CAA44519.1. AF508304 mRNA. Translation: AAM34259.1. AK311893 mRNA. Translation: BAG34834.1. CR542096 mRNA. Translation: CAG46893.1. BT007073 mRNA. Translation: AAP35736.1. BT020137 mRNA. Translation: AAV38939.1. BT020138 mRNA. Translation: AAV38940.1. AC009779 Genomic DNA. No translation available. CH471054 Genomic DNA. Translation: EAW96827.1. BC002349 mRNA. Translation: AAH02349.1. BC013017 mRNA. Translation: AAH13017.1.
IPI	IPI00215998.
PIR	I38016.
RefSeq	NP_001244318.1. NM_001257389.1. NP_001244319.1. NM_001257390.1. NP_001244320.1. NM_001257391.1. NP_001244321.1. NM_001257392.1. NP_001244329.1. NM_001257400.1. NP_001254627.1. NM_001267698.1. NP_001771.1. NM_001780.5.
UniGene	Hs.445570.
3D structure databases
ProteinModelPortal	P08962.
ModBase	Search...
Protein-protein interaction databases
IntAct	P08962. 9 interactions.
MINT	MINT-2981823.
STRING	9606.ENSP00000257857.
PTM databases
PhosphoSite	P08962.
Polymorphism databases
DMDM	116026.
Proteomic databases
PaxDb	P08962.
PRIDE	P08962.
Protocols and materials databases
DNASU	967.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000257857; ENSP00000257857; ENSG00000135404. ENST00000549117; ENSP00000447730; ENSG00000135404. ENST00000552692; ENSP00000449337; ENSG00000135404. ENST00000552754; ENSP00000446807; ENSG00000135404.
GeneID	967.
KEGG	hsa:967.
UCSC	uc001shn.3. human. uc009znz.3. human.
Organism-specific databases
CTD	967.
GeneCards	GC12M056119.
HGNC	HGNC:1692. CD63.
HPA	CAB026356. HPA010088.
MIM	155740. gene.
neXtProt	NX_P08962.
PharmGKB	PA26231.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG268658.
HOGENOM	HOG000230651.
HOVERGEN	HBG107306.
InParanoid	P08962.
KO	K06497.
OMA	FNKDFRQ.
OrthoDB	EOG4HX51Z.
PhylomeDB	P08962.
Enzyme and pathway databases
Reactome	REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	P08962.
Bgee	P08962.
CleanEx	HS_CD63.
Genevestigator	P08962.
GermOnline	ENSG00000135404. Homo sapiens.
Family and domain databases
InterPro	IPR000301. Tetraspanin. IPR018499. Tetraspanin/Peripherin. IPR018503. Tetraspanin_CS. IPR008952. Tetraspanin_EC2. [Graphical view]
Pfam	PF00335. Tetraspannin. 1 hit. [Graphical view]
PIRSF	PIRSF002419. Tetraspanin. 1 hit.
PRINTS	PR00259. TMFOUR.
SUPFAM	SSF48652. Tetraspanin. 1 hit.
PROSITE	PS00421. TM4_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CD63. human.
GenomeRNAi	967.
NextBio	4044.
SOURCE	Search...

Entry information

Entry name

CD63_HUMAN

Accession

Primary (citable) accession number: P08962
Secondary accession number(s): Q5TZP3, Q8N6Z9, Q9UCG6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	January 23, 2007
Last modified:	May 29, 2013
This is version 137 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.