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Protein

Caveolin-2

Gene

CAV2

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

Functioni

May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. Acts as an accessory protein in conjunction with CAV1 in targeting to lipid rafts and driving caveolae formation. The Ser-36 phosphorylated form has a role in modulating mitosis in endothelial cells. Positive regulator of cellular mitogenesis of the MAPK signaling pathway. Required for the insulin-stimulated nuclear translocation and activation of MAPK1 and STAT3, and the subsequent regulation of cell cycle progression (By similarity).By similarity2 Publications

GO - Molecular functioni

GO - Biological processi

  • caveola assembly Source: BHF-UCL
  • endoplasmic reticulum organization Source: UniProtKB
  • insulin receptor signaling pathway Source: BHF-UCL
  • mitochondrion organization Source: UniProtKB
  • negative regulation of endothelial cell proliferation Source: UniProtKB
  • negative regulation of transforming growth factor beta receptor signaling pathway Source: Ensembl
  • positive regulation by host of viral process Source: AgBase
  • positive regulation by host of viral release from host cell Source: AgBase
  • positive regulation of dopamine receptor signaling pathway Source: BHF-UCL
  • positive regulation of endothelial cell proliferation Source: Ensembl
  • positive regulation of GTPase activity Source: BHF-UCL
  • positive regulation of MAPK cascade Source: BHF-UCL
  • protein oligomerization Source: Ensembl
  • receptor-mediated endocytosis of virus by host cell Source: CACAO
  • regulation of mitotic nuclear division Source: BHF-UCL
  • skeletal muscle fiber development Source: UniProtKB
  • vesicle docking Source: BHF-UCL
  • vesicle fusion Source: BHF-UCL
  • vesicle organization Source: BHF-UCL

Enzyme and pathway databases

SignaLinkiP51636
SIGNORiP51636

Names & Taxonomyi

Protein namesi
Recommended name:
Caveolin-2
Gene namesi
Name:CAV2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000105971.14
HGNCiHGNC:1528 CAV2
MIMi601048 gene
neXtProtiNX_P51636

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 86CytoplasmicSequence analysisAdd BLAST86
Intramembranei87 – 107HelicalSequence analysisAdd BLAST21
Topological domaini108 – 162CytoplasmicSequence analysisAdd BLAST55

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Golgi apparatus, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi19Y → A: Greatly reduced Src-mediated phosphorylation and binding of RASA1, SRC and NCK1. Completely eliminates Src-mediated tyrosine phosphorylation and binding to RASA1, SRC and NCK1; when associated with A-27. 1 Publication1
Mutagenesisi23S → A: Abolishes phosphorylation. 1 Publication1
Mutagenesisi27Y → A: Greatly reduced Src-mediated phosphorylation and binding of RASA1, SRC and NCK1. Completely eliminates Src-mediated phosphorylation and binding of RASA1, SRC and NCK1; when associated with A-19. 1 Publication1
Mutagenesisi36S → A: Abolishes phosphorylation. 1 Publication1

Organism-specific databases

DisGeNETi858
OpenTargetsiENSG00000105971
PharmGKBiPA26108

Polymorphism and mutation databases

BioMutaiCAV2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000047721 – 162Caveolin-2Add BLAST162

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19Phosphotyrosine; by SRC2 Publications1
Modified residuei20PhosphoserineBy similarity1
Modified residuei23Phosphoserine1 Publication1
Modified residuei27Phosphotyrosine; by SRC1 Publication1
Modified residuei36Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylated on serine and tyrosine residues. CAV1 promotes phosphorylation on Ser-23 which then targets the complex to the plasma membrane, lipid rafts and caveolae. Phosphorylation on Ser-36 appears to modulate mitosis in endothelial cells (By similarity). Phosphorylation on both Tyr-19 and Tyr-27 is required for insulin-induced 'Ser-727' phosphorylation of STAT3 and its activation. Phosphorylation on Tyr-19 is required for insulin-induced phosphorylation of MAPK1 and DNA binding of STAT3. Tyrosine phosphorylation is induced by both EGF and insulin (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP51636
PeptideAtlasiP51636
PRIDEiP51636

PTM databases

iPTMnetiP51636
PhosphoSitePlusiP51636
SwissPalmiP51636

Expressioni

Tissue specificityi

Expressed in endothelial cells, smooth muscle cells, skeletal myoblasts and fibroblasts.1 Publication

Gene expression databases

BgeeiENSG00000105971
CleanExiHS_CAV2
ExpressionAtlasiP51636 baseline and differential
GenevisibleiP51636 HS

Organism-specific databases

HPAiCAB013488
HPA044810

Interactioni

Subunit structurei

Monomer or homodimer. Interacts with CAV1; the interaction forms a stable heterooligomeric complex that is required for targeting to lipid rafts and for caveolae formation. Tyrosine phosphorylated forms do not form heterooligomers with the Tyr-19-phosphorylated form existing as a monomer or dimer, and the Tyr-27-form as a monomer only. Interacts (tyrosine phosphorylated form) with the SH2 domain-containing proteins, RASA1, NCK1 and SRC. Interacts (tyrosine phosphorylated form) with INSR, the interaction (Tyr-27-phosphorylated form) is increased on insulin stimulation. Interacts (Tyr-19 phosphorylated form) with MAPK1 (phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation. Interacts with STAT3; the interaction is increased on insulin-induced tyrosine phosphorylation leading to STAT activation (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CAV1Q031352EBI-603607,EBI-603614

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107306, 11 interactors
DIPiDIP-34929N
IntActiP51636, 7 interactors
MINTiP51636
STRINGi9606.ENSP00000222693

Structurei

3D structure databases

ProteinModelPortaliP51636
SMRiP51636
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the caveolin family.Curated

Phylogenomic databases

eggNOGiENOG410IFFB Eukaryota
ENOG4111STF LUCA
GeneTreeiENSGT00390000014924
HOGENOMiHOG000036550
HOVERGENiHBG003422
InParanoidiP51636
KOiK12958
OMAiHLKVGFE
OrthoDBiEOG091G0M1R
PhylomeDBiP51636
TreeFamiTF315736

Family and domain databases

InterProiView protein in InterPro
IPR033306 CAV-2
IPR001612 Caveolin
IPR018361 Caveolin_CS
PANTHERiPTHR10844 PTHR10844, 1 hit
PTHR10844:SF3 PTHR10844:SF3, 1 hit
PfamiView protein in Pfam
PF01146 Caveolin, 1 hit
PROSITEiView protein in PROSITE
PS01210 CAVEOLIN, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

Isoform Alpha (identifier: P51636-1) [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
MGLETEKADV QLFMDDDSYS HHSGLEYADP EKFADSDQDR DPHRLNSHLK
60 70 80 90 100
LGFEDVIAEP VTTHSFDKVW ICSHALFEIS KYVMYKFLTV FLAIPLAFIA
110 120 130 140 150
GILFATLSCL HIWILMPFVK TCLMVLPSVQ TIWKSVTDVI IAPLCTSVGR
160
CFSSVSLQLS QD
Length:162
Mass (Da):18,291
Last modified:July 15, 1999 - v2
Checksum:i89FDEDA861330B87
GO
Isoform Beta (identifier: P51636-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-13: Missing.

Note: Produced by alternative initiation.
Show »
Length:149
Mass (Da):16,829
Checksum:i0706B574F5E1AAD8
GO
Isoform C (identifier: P51636-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     51-112: LGFEDVIAEP...LFATLSCLHI → DFNAFCKDLP...WTPGLEIGIL
     113-162: Missing.

Note: Produced by alternative splicing.
Show »
Length:112
Mass (Da):12,780
Checksum:i7C60DC5ABD6B0105
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_012071130Q → E. Corresponds to variant dbSNP:rs8940Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0186961 – 13Missing in isoform Beta. CuratedAdd BLAST13
Alternative sequenceiVSP_03811451 – 112LGFED…SCLHI → DFNAFCKDLPNGSAFSADNM EECDRCYHCSIVYERRTMLL FCQPATEPGLNTWTPGLEIG IL in isoform C. 1 PublicationAdd BLAST62
Alternative sequenceiVSP_038115113 – 162Missing in isoform C. 1 PublicationAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF035752 mRNA Translation: AAB88492.1
AJ133269 Genomic DNA Translation: CAB63653.1
BT007051 mRNA Translation: AAP35700.1
BC005256 mRNA Translation: AAH05256.1
AJ242718 Genomic DNA Translation: CAB65090.1
AK310786 mRNA No translation available.
CH236947 Genomic DNA Translation: EAL24361.1
CCDSiCCDS5765.1 [P51636-3]
CCDS5766.1 [P51636-1]
RefSeqiNP_001193676.1, NM_001206747.1 [P51636-2]
NP_001193677.1, NM_001206748.1
NP_001224.1, NM_001233.4 [P51636-1]
NP_937855.1, NM_198212.2 [P51636-3]
UniGeneiHs.212332
Hs.603096

Genome annotation databases

EnsembliENST00000222693; ENSP00000222693; ENSG00000105971 [P51636-1]
ENST00000343213; ENSP00000345679; ENSG00000105971 [P51636-3]
GeneIDi858
KEGGihsa:858
UCSCiuc003vie.4 human [P51636-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCAV2_HUMAN
AccessioniPrimary (citable) accession number: P51636
Secondary accession number(s): A4D0U2, Q9UGM7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 15, 1999
Last modified: April 25, 2018
This is version 172 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health