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Protein

CD63 antigen

Gene

CD63

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functions as cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activation of AKT, FAK/PTK2 and MAP kinases. Promotes cell survival, reorganization of the actin cytoskeleton, cell adhesion, spreading and migration, via its role in the activation of AKT and FAK/PTK2. Plays a role in VEGFA signaling via its role in regulating the internalization of KDR/VEGFR2. Plays a role in intracellular vesicular transport processes, and is required for normal trafficking of the PMEL luminal domain that is essential for the development and maturation of melanocytes. Plays a role in the adhesion of leukocytes onto endothelial cells via its role in the regulation of SELP trafficking. May play a role in mast cell degranulation in response to Ms4a2/FceRI stimulation, but not in mast cell degranulation in response to other stimuli.5 Publications

GO - Biological processi

  • cell-matrix adhesion Source: UniProtKB
  • cell migration Source: UniProtKB
  • cellular protein localization Source: MGI
  • endosome to melanosome transport Source: UniProtKB
  • pigment granule maturation Source: UniProtKB
  • platelet degranulation Source: Reactome
  • positive regulation of integrin-mediated signaling pathway Source: UniProtKB
  • positive regulation of receptor internalization Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • regulation of rubidium ion transport Source: MGI
  • regulation of vascular endothelial growth factor signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000135404-MONOMER.
ReactomeiR-HSA-114608. Platelet degranulation.
R-HSA-6798695. Neutrophil degranulation.

Names & Taxonomyi

Protein namesi
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 namesi
Name:CD63
Synonyms:MLA1, TSPAN30
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:1692. CD63.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 11CytoplasmicSequence analysis10
Transmembranei12 – 32HelicalSequence analysisAdd BLAST21
Topological domaini33 – 51ExtracellularSequence analysisAdd BLAST19
Transmembranei52 – 72HelicalSequence analysisAdd BLAST21
Topological domaini73 – 81CytoplasmicSequence analysis9
Transmembranei82 – 102HelicalSequence analysisAdd BLAST21
Topological domaini103 – 203ExtracellularSequence analysisAdd BLAST101
Transmembranei204 – 224HelicalSequence analysisAdd BLAST21
Topological domaini225 – 238CytoplasmicSequence analysisAdd BLAST14

GO - Cellular componenti

  • cell surface Source: MGI
  • endosome lumen Source: UniProtKB
  • endosome membrane Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular space Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • intrinsic component of plasma membrane Source: UniProtKB
  • late endosome membrane Source: UniProtKB
  • lysosomal membrane Source: UniProtKB
  • melanosome Source: UniProtKB-SubCell
  • multivesicular body, internal vesicle Source: UniProtKB
  • multivesicular body membrane Source: UniProtKB
  • plasma membrane Source: Reactome
  • platelet dense granule membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Lysosome, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi967.
OpenTargetsiENSG00000135404.
PharmGKBiPA26231.

Polymorphism and mutation databases

BioMutaiCD63.
DMDMi116026.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002192162 – 238CD63 antigenAdd BLAST237

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi130N-linked (GlcNAc...)2 Publications1
Glycosylationi150N-linked (GlcNAc...)Sequence analysis1
Glycosylationi172N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Palmitoylated at a low, basal level in unstimulated platelets. The level of palmitoylation increases when platelets are activated by thrombin (in vitro).1 Publication

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

EPDiP08962.
MaxQBiP08962.
PaxDbiP08962.
PeptideAtlasiP08962.
PRIDEiP08962.

PTM databases

iPTMnetiP08962.
PhosphoSitePlusiP08962.
SwissPalmiP08962.

Expressioni

Tissue specificityi

Detected in platelets (at protein level). Dysplastic nevi, radial growth phase primary melanomas, hematopoietic cells, tissue macrophages.1 Publication

Gene expression databases

BgeeiENSG00000135404.
CleanExiHS_CD63.
ExpressionAtlasiP08962. baseline and differential.
GenevisibleiP08962. HS.

Organism-specific databases

HPAiCAB026356.
HPA010088.

Interactioni

Subunit structurei

Interacts with TIMP1 and ITGB1 and recruits TIMP1 to ITGB1 (PubMed:16917503, PubMed:24635319). Interacts with CD9. Identified in a complex with CD9 and ITGB3 (PubMed:19640571). Interacts with PMEL (PubMed:21962903). Interacts with KDR/VEGFR2; identified in a complex with ITGB1 and KDR/VEGFR2 and is required to recruit KDR to ITGB1 complexes (PubMed:23632027). Interacts with SYT7 (By similarity).By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
envP045784EBI-762053,EBI-6179711From a different organism.
TIMP1P010335EBI-762053,EBI-712536

Protein-protein interaction databases

BioGridi107405. 23 interactors.
IntActiP08962. 17 interactors.
MINTiMINT-2981823.
STRINGi9606.ENSP00000257857.

Structurei

3D structure databases

ProteinModelPortaliP08962.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi234 – 238Lysosomal targeting motifBy similarity5

Sequence similaritiesi

Belongs to the tetraspanin (TM4SF) family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3882. Eukaryota.
ENOG4111IRY. LUCA.
GeneTreeiENSGT00760000118875.
HOGENOMiHOG000230651.
HOVERGENiHBG107306.
InParanoidiP08962.
KOiK06497.
OMAiWERILTP.
OrthoDBiEOG091G12WV.
PhylomeDBiP08962.
TreeFamiTF316345.

Family and domain databases

InterProiIPR000301. Tetraspanin.
IPR018499. Tetraspanin/Peripherin.
IPR018503. Tetraspanin_CS.
IPR008952. Tetraspanin_EC2.
[Graphical view]
PfamiPF00335. Tetraspannin. 1 hit.
[Graphical view]
PIRSFiPIRSF002419. Tetraspanin. 1 hit.
PRINTSiPR00259. TMFOUR.
SUPFAMiSSF48652. SSF48652. 1 hit.
PROSITEiPS00421. TM4_1. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P08962-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAVEGGMKCV KFLLYVLLLA FCACAVGLIA VGVGAQLVLS QTIIQGATPG
60 70 80 90 100
SLLPVVIIAV GVFLFLVAFV GCCGACKENY CLMITFAIFL SLIMLVEVAA
110 120 130 140 150
AIAGYVFRDK VMSEFNNNFR QQMENYPKNN HTASILDRMQ ADFKCCGAAN
160 170 180 190 200
YTDWEKIPSM SKNRVPDSCC INVTVGCGIN FNEKAIHKEG CVEKIGGWLR
210 220 230
KNVLVVAAAA LGIAFVEVLG IVFACCLVKS IRSGYEVM
Length:238
Mass (Da):25,637
Last modified:January 23, 2007 - v2
Checksum:i85AC8E235C6E425F
GO
Isoform 2 (identifier: P08962-2) [UniParc]FASTAAdd to basket

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

Show »
Length:215
Mass (Da):23,430
Checksum:iC4469E42BCC8C4F7
GO
Isoform 3 (identifier: P08962-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-82: Missing.

Note: Gene prediction based on EST data.
Show »
Length:156
Mass (Da):17,271
Checksum:iD5A714579CDE49EF
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti36Q → E AA sequence (PubMed:7682577).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0469961 – 82Missing in isoform 3. CuratedAdd BLAST82
Alternative sequenceiVSP_04530023 – 45Missing in isoform 2. 1 PublicationAdd BLAST23

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS58242.1. [P08962-3]
CCDS58243.1. [P08962-2]
CCDS8890.1. [P08962-1]
PIRiI38016.
RefSeqiNP_001244318.1. NM_001257389.1. [P08962-1]
NP_001244319.1. NM_001257390.1. [P08962-1]
NP_001244320.1. NM_001257391.1. [P08962-1]
NP_001244321.1. NM_001257392.1. [P08962-2]
NP_001244329.1. NM_001257400.1. [P08962-3]
NP_001244330.1. NM_001257401.1. [P08962-3]
NP_001254627.1. NM_001267698.1. [P08962-1]
NP_001771.1. NM_001780.5. [P08962-1]
UniGeneiHs.445570.

Genome annotation databases

EnsembliENST00000257857; ENSP00000257857; ENSG00000135404. [P08962-1]
ENST00000420846; ENSP00000393502; ENSG00000135404. [P08962-1]
ENST00000546939; ENSP00000447356; ENSG00000135404. [P08962-3]
ENST00000549117; ENSP00000447730; ENSG00000135404. [P08962-1]
ENST00000550776; ENSP00000448091; ENSG00000135404. [P08962-3]
ENST00000552692; ENSP00000449337; ENSG00000135404. [P08962-1]
ENST00000552754; ENSP00000446807; ENSG00000135404. [P08962-2]
GeneIDi967.
KEGGihsa:967.
UCSCiuc001shn.5. human. [P08962-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS58242.1. [P08962-3]
CCDS58243.1. [P08962-2]
CCDS8890.1. [P08962-1]
PIRiI38016.
RefSeqiNP_001244318.1. NM_001257389.1. [P08962-1]
NP_001244319.1. NM_001257390.1. [P08962-1]
NP_001244320.1. NM_001257391.1. [P08962-1]
NP_001244321.1. NM_001257392.1. [P08962-2]
NP_001244329.1. NM_001257400.1. [P08962-3]
NP_001244330.1. NM_001257401.1. [P08962-3]
NP_001254627.1. NM_001267698.1. [P08962-1]
NP_001771.1. NM_001780.5. [P08962-1]
UniGeneiHs.445570.

3D structure databases

ProteinModelPortaliP08962.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107405. 23 interactors.
IntActiP08962. 17 interactors.
MINTiMINT-2981823.
STRINGi9606.ENSP00000257857.

PTM databases

iPTMnetiP08962.
PhosphoSitePlusiP08962.
SwissPalmiP08962.

Polymorphism and mutation databases

BioMutaiCD63.
DMDMi116026.

Proteomic databases

EPDiP08962.
MaxQBiP08962.
PaxDbiP08962.
PeptideAtlasiP08962.
PRIDEiP08962.

Protocols and materials databases

DNASUi967.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000257857; ENSP00000257857; ENSG00000135404. [P08962-1]
ENST00000420846; ENSP00000393502; ENSG00000135404. [P08962-1]
ENST00000546939; ENSP00000447356; ENSG00000135404. [P08962-3]
ENST00000549117; ENSP00000447730; ENSG00000135404. [P08962-1]
ENST00000550776; ENSP00000448091; ENSG00000135404. [P08962-3]
ENST00000552692; ENSP00000449337; ENSG00000135404. [P08962-1]
ENST00000552754; ENSP00000446807; ENSG00000135404. [P08962-2]
GeneIDi967.
KEGGihsa:967.
UCSCiuc001shn.5. human. [P08962-1]

Organism-specific databases

CTDi967.
DisGeNETi967.
GeneCardsiCD63.
HGNCiHGNC:1692. CD63.
HPAiCAB026356.
HPA010088.
MIMi155740. gene.
neXtProtiNX_P08962.
OpenTargetsiENSG00000135404.
PharmGKBiPA26231.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3882. Eukaryota.
ENOG4111IRY. LUCA.
GeneTreeiENSGT00760000118875.
HOGENOMiHOG000230651.
HOVERGENiHBG107306.
InParanoidiP08962.
KOiK06497.
OMAiWERILTP.
OrthoDBiEOG091G12WV.
PhylomeDBiP08962.
TreeFamiTF316345.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000135404-MONOMER.
ReactomeiR-HSA-114608. Platelet degranulation.
R-HSA-6798695. Neutrophil degranulation.

Miscellaneous databases

ChiTaRSiCD63. human.
GeneWikiiCD63.
GenomeRNAii967.
PROiP08962.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135404.
CleanExiHS_CD63.
ExpressionAtlasiP08962. baseline and differential.
GenevisibleiP08962. HS.

Family and domain databases

InterProiIPR000301. Tetraspanin.
IPR018499. Tetraspanin/Peripherin.
IPR018503. Tetraspanin_CS.
IPR008952. Tetraspanin_EC2.
[Graphical view]
PfamiPF00335. Tetraspannin. 1 hit.
[Graphical view]
PIRSFiPIRSF002419. Tetraspanin. 1 hit.
PRINTSiPR00259. TMFOUR.
SUPFAMiSSF48652. SSF48652. 1 hit.
PROSITEiPS00421. TM4_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCD63_HUMAN
AccessioniPrimary (citable) accession number: P08962
Secondary accession number(s): F8VZE2
, Q5TZP3, Q8N6Z9, Q9UCG6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 173 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

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.
This antigen is associated with early stages of melanoma tumor progression.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.