Reviewed, UniProtKB/Swiss-Prot Q03135 (CAV1_HUMAN)

Names and origin

Protein names

Recommended name:
    Caveolin-1

Gene names

Name:	CAV1
Synonyms:	CAV

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	178 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	May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity By similarity. Involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner.
Subunit structure	Homooligomer. Interacts with GLIPR2, NOSTRIN, SNAP25 and syntaxin. Interacts with rotavirus A NSP4. Interacts (via the N-terminus) with DPP4; the interaction is direct. Ref.8 Ref.12 Ref.13
Subcellular location	Golgi apparatus membrane; Single-pass membrane protein. Cell membrane; Single-pass membrane protein. Membrane › caveola; Single-pass membrane protein. Membrane raft. Note: Colocalized with DPP4 in membrane rafts. Potential hairpin-like structure in the membrane. Membrane protein of caveolae. Ref.6
Tissue specificity	In muscle and lung, less so in liver, brain and kidney.
Post-translational modification	The initiator methionine for isoform Beta is removed during or just after translation. The new N-terminal amino acid is then N-acetylated.
Involvement in disease	Defects in CAV1 are the cause of congenital generalized lipodystrophy type 3 (CGL3) [MIM:612526]; also called Berardinelli-Seip congenital lipodystrophy type 3 (BSCL3). Congenital generalized lipodystrophies are autosomal recessive disorders characterized by a near absence of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes.
Sequence similarities	Belongs to the caveolin family.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cell membrane Golgi apparatus Membrane
Coding sequence diversity	Alternative initiation
Disease	Congenital generalized lipodystrophy Disease mutation
Domain	Transmembrane
PTM	Acetylation Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	T cell costimulation Ref.15 Inferred from direct assay. Source: UniProtKB calcium ion transport Inferred from sequence or structural similarity. Source: UniProtKB caveola assembly Inferred from mutant phenotype. Source: UniProtKB cellular response to starvation Inferred from expression pattern. Source: UniProtKB cholesterol homeostasis Inferred from sequence or structural similarity. Source: UniProtKB cytosolic calcium ion homeostasis Inferred from direct assay. Source: UniProtKB inactivation of MAPK activity Inferred from sequence or structural similarity. Source: UniProtKB interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW lipid storage Inferred from sequence or structural similarity. Source: UniProtKB maintenance of protein location in cell Inferred from sequence or structural similarity. Source: UniProtKB mammary gland involution Inferred from sequence or structural similarity. Source: UniProtKB membrane depolarization Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of BMP signaling pathway Inferred from direct assay. Source: UniProtKB negative regulation of MAPKKK cascade Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of endothelial cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of epithelial cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of nitric oxide biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of peptidyl-serine phosphorylation Inferred from direct assay. Source: UniProtKB nitric oxide homeostasis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of calcium ion transport into cytosol Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of metalloenzyme activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of peptidyl-serine phosphorylation Inferred from direct assay. Source: UniProtKB positive regulation of vasoconstriction Inferred from sequence or structural similarity. Source: UniProtKB protein homooligomerization Inferred from sequence or structural similarity. Source: UniProtKB regulation of blood coagulation Inferred from mutant phenotype. Source: UniProtKB regulation of fatty acid metabolic process Inferred from sequence or structural similarity. Source: UniProtKB regulation of peptidase activity Inferred from sequence or structural similarity. Source: UniProtKB regulation of smooth muscle contraction Inferred from sequence or structural similarity. Source: UniProtKB response to calcium ion Inferred from sequence or structural similarity. Source: UniProtKB response to estrogen stimulus Inferred from direct assay. Source: MGI response to hypoxia Inferred from sequence or structural similarity. Source: UniProtKB response to progesterone stimulus Inferred from direct assay. Source: MGI skeletal muscle tissue development Inferred from sequence or structural similarity. Source: UniProtKB triglyceride metabolic process Inferred from sequence or structural similarity. Source: UniProtKB vasculogenesis Inferred from sequence or structural similarity. Source: UniProtKB vesicle organization Inferred from direct assay. Source: UniProtKB
Cellular component	Golgi membrane Inferred from direct assay. Source: HGNC apical plasma membrane Inferred from direct assay. Source: UniProtKB basolateral plasma membrane Inferred from direct assay. Source: UniProtKB caveola Ref.6 Inferred from direct assay. Source: UniProtKB endoplasmic reticulum Inferred from direct assay. Source: HGNC lipid particle Ref.12 Inferred from Experiment. Source: Reactome perinuclear region of cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	cholesterol binding Traceable author statement. Source: HGNC nitric-oxide synthase binding Inferred from physical interaction. Source: UniProtKB peptidase activator activity Inferred from sequence or structural similarity. Source: UniProtKB protein binding Ref.15 Inferred from physical interaction. Source: UniProtKB protein complex scaffold Traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CAV2	P51636	1	EBI-603614,EBI-603607
FLOT1	O75955	1	EBI-603614,EBI-603643
FLOT2	Q14254	1	EBI-603614,EBI-348613
ID1	P41134	3	EBI-603614,EBI-1215527
SCP2	P22307	1	EBI-603614,EBI-1050999

Alternative products

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

Isoform Alpha (identifier: Q03135-1)

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 Beta (identifier: Q03135-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-31: Missing.

Note: Initiator Met-1 is removed. Contains a N-acetylalanine at position 2.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.6
	Chain	2 – 178	177	Caveolin-1		PRO_0000004764
Regions
	Topological domain	2 – 104	103	Cytoplasmic Potential
	Transmembrane	105 – 125	21	Potential
	Topological domain	126 – 178	53	Cytoplasmic Potential
Amino acid modifications
	Modified residue	2	1	N-acetylserine Ref.6
	Modified residue	5	1	N6-acetyllysine Ref.20
	Modified residue	6	1	Phosphotyrosine Ref.9 Ref.18
	Modified residue	14	1	Phosphotyrosine Ref.9 Ref.18 Ref.10 Ref.14
	Modified residue	25	1	Phosphotyrosine Ref.9 Ref.18
	Modified residue	37	1	Phosphoserine Ref.11 Ref.16 Ref.17
	Modified residue	42	1	Phosphotyrosine Ref.18
	Lipidation	133	1	S-palmitoyl cysteine By similarity
	Lipidation	143	1	S-palmitoyl cysteine By similarity
	Lipidation	156	1	S-palmitoyl cysteine By similarity
Natural variations
	Alternative sequence	1 – 31	31	Missing in isoform Beta.		VSP_018692
	Natural variant	132	1	P → L in breast cancer; seems to form misfolded oligomers that are retained within the Golgi complex and are not targeted to caveolae or the plasma membrane. Ref.21		VAR_015103
Experimental info
	Sequence conflict	82	1	D → H in CAA79476. Ref.1
	Sequence conflict	144	1	I → T in CAA79476. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 2424DE9B5E6521D5	FASTA	178	20,472
	10 20 30 40 50 60 MSGGKYVDSE GHLYTVPIRE QGNIYKPNNK AMADELSEKQ VYDAHTKEID LVNRDPKHLN 70 80 90 100 110 120 DDVVKIDFED VIAEPEGTHS FDGIWKASFT TFTVTKYWFY RLLSALFGIP MALIWGIYFA 130 140 150 160 170 ILSFLHIWAV VPCIKSFLIE IQCISRVYSI YVHTVCDPLF EAVGKIFSNV RINLQKEI
	Isoform Beta. Checksum: 1A7D806312F72A47	FASTA	147	17,023
	10 20 30 40 50 60 MADELSEKQV YDAHTKEIDL VNRDPKHLND DVVKIDFEDV IAEPEGTHSF DGIWKASFTT 70 80 90 100 110 120 FTVTKYWFYR LLSALFGIPM ALIWGIYFAI LSFLHIWAVV PCIKSFLIEI QCISRVYSIY 130 140 VHTVCDPLFE AVGKIFSNVR INLQKEI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The sequence of human caveolin reveals identity with VIP21, a component of transport vesicles." Glenney J.R. Jr. FEBS Lett. 314:45-48(1992) [PubMed: 1360410] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[2]	"Analysis of the CAVEOLIN-1 gene at human chromosome 7q31.1 in primary tumours and tumour-derived cell lines." Hurlstone A.F., Reid G., Reeves J.R., Fraser J., Strathdee G., Rahilly M., Parkinson E.K., Black D.M. Oncogene 18:1881-1890(1999) [PubMed: 10086342] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Sequence and detailed organization of the human caveolin-1 and -2 genes located near the D7S522 locus (7q31.1). Methylation of a CpG island in the 5' promoter region of the caveolin-1 gene in human breast cancer cell lines." Engelman J.A., Zhang X.L., Lisanti M.P. FEBS Lett. 448:221-230(1999) [PubMed: 10218480] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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 (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"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: Brain and Lung.
[6]	"N-terminal processing and modifications of caveolin-1 in caveolae from human adipocytes." Vainonen J.P., Aboulaich N., Turkina M.V., Stralfors P., Vener A.V. Biochem. Biophys. Res. Commun. 320:480-486(2004) [PubMed: 15219854] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-66, SUBCELLULAR LOCATION, ACETYLATION AT SER-2, PHOSPHORYLATION. Tissue: Adipose tissue.
[7]	"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 58-65. Tissue: Adipocyte.
[8]	"Identification and characterization of a novel human plant pathogenesis-related protein that localizes to lipid-enriched microdomains in the Golgi complex." Eberle H.B., Serrano R.L., Fuellekrug J., Schlosser A., Lehmann W.D., Lottspeich F., Kaloyanova D., Wieland F.T., Helms J.B. J. Cell Sci. 115:827-838(2002) [PubMed: 11865038] [Abstract] Cited for: INTERACTION WITH GLIPR2. Tissue: Brain.
[9]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-6; TYR-14 AND TYR-25, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-14, MASS SPECTROMETRY.
[11]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, MASS SPECTROMETRY. Tissue: Epithelium.
[12]	"Translocation of endothelial nitric-oxide synthase involves a ternary complex with caveolin-1 and NOSTRIN." Schilling K., Opitz N., Wiesenthal A., Oess S., Tikkanen R., Mueller-Esterl W., Icking A. Mol. Biol. Cell 17:3870-3880(2006) [PubMed: 16807357] [Abstract] Cited for: INTERACTION WITH NOSTRIN.
[13]	"The rotavirus enterotoxin NSP4 directly interacts with the caveolar structural protein caveolin-1." Parr R.D., Storey S.M., Mitchell D.M., McIntosh A.L., Zhou M., Mir K.D., Ball J.M. J. Virol. 80:2842-2854(2006) [PubMed: 16501093] [Abstract] Cited for: INTERACTION WITH ROTAVIRUS A NSP4.
[14]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-14, MASS SPECTROMETRY.
[15]	"Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1." Ohnuma K., Uchiyama M., Yamochi T., Nishibashi K., Hosono O., Takahashi N., Kina S., Tanaka H., Lin X., Dang N.H., Morimoto C. J. Biol. Chem. 282:10117-10131(2007) [PubMed: 17287217] [Abstract] Cited for: FUNCTION, INTERACTION WITH DPP4, SUBCELLULAR LOCATION.
[16]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, MASS SPECTROMETRY.
[17]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, MASS SPECTROMETRY.
[18]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-6; TYR-14; TYR-25 AND TYR-42, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[19]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, MASS SPECTROMETRY.
[20]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-5, MASS SPECTROMETRY.
[21]	"Caveolin-1 mutations (P132L and null) and the pathogenesis of breast cancer: caveolin-1 (P132L) behaves in a dominant-negative manner and caveolin-1 (-/-) null mice show mammary epithelial cell hyperplasia." Lee H., Park D.S., Razani B., Russell R.G., Pestell R.G., Lisanti M.P. Am. J. Pathol. 161:1357-1369(2002) [PubMed: 12368209] [Abstract] Cited for: VARIANT LEU-132.
[22]	"Association of a homozygous nonsense caveolin-1 mutation with Berardinelli-Seip congenital lipodystrophy." Kim C.A., Delepine M., Boutet E., El Mourabit H., Le Lay S., Meier M., Nemani M., Bridel E., Leite C.C., Bertola D.R., Semple R.K., O'Rahilly S., Dugail I., Capeau J., Lathrop M., Magre J. J. Clin. Endocrinol. Metab. 93:1129-1134(2008) [PubMed: 18211975] [Abstract] Cited for: INVOLVEMENT IN CONGENITAL GENERALIZED LIPODYSTROPHY TYPE 3.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Wikipedia

Caveolin entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z18951 mRNA. Translation: CAA79476.1. AF095593, AF095591, AF095592 Genomic DNA. Translation: AAD23745.1. AJ133269 Genomic DNA. Translation: CAB63654.1. AF125348 Genomic DNA. Translation: AAD34722.1. BT007143 mRNA. Translation: AAP35807.1. BC009685 mRNA. Translation: AAH09685.1. BC082246 mRNA. Translation: AAH82246.1.
IPI	IPI00009236. IPI00759683.
PIR	S26884.
RefSeq	NP_001744.2.
UniGene	Hs.74034
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-5960N.
IntAct	Q03135. 16 interactions.
STRING	Q03135.
PTM databases
PhosphoSite	Q03135.
Proteomic databases
PeptideAtlas	Q03135.
PRIDE	Q03135.
Genome annotation databases
Ensembl	ENST00000341049; ENSP00000339191; ENSG00000105974; Homo sapiens. [Genome view]
GeneID	857.
KEGG	hsa:857.
UCSC	uc003vif.1. human. uc003vih.2. human.
Organism-specific databases
CTD	857.
GeneCards	GC07P115952.
H-InvDB	HIX0007018.
HGNC	HGNC:1527. CAV1.
HPA	CAB003791.
MIM	601047. gene. 612526. phenotype.
Orphanet	528. Lipodystrophy, Berardinelli type.
PharmGKB	PA26107.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11341.
HOVERGEN	Q03135.
InParanoid	Q03135.
OMA	IYVHTFC.
PhylomeDB	Q03135.
Enzyme and pathway databases
Pathway_Interaction_DB	insulin_pathway. Insulin Pathway. pdgfrapathway. PDGFR-alpha signaling pathway. ptp1bpathway. Signaling events mediated by PTP1B. vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2. tgfbrpathway. TGF-beta receptor signaling. tnfpathway. TNF receptor signaling pathway. vegfr1_pathway. VEGFR1 specific signals.
Reactome	REACT_12508. Metabolism of nitric oxide. REACT_604. Hemostasis. REACT_6900. Signaling in Immune system.
Gene expression databases
ArrayExpress	Q03135.
Bgee	Q03135.
CleanEx	HS_CAV1.
Genevestigator	Q03135.
GermOnline	ENSG00000105974. Homo sapiens.
Family and domain databases
InterPro	IPR001612. Caveolin. IPR015504. Caveolin_1. IPR018361. Caveolin_CS. [Graphical view]
PANTHER	PTHR10844. Caveolin. 1 hit. PTHR10844:SF5. Caveolin_1. 1 hit.
Pfam	PF01146. Caveolin. 1 hit. [Graphical view]
PROSITE	PS01210. CAVEOLIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	3556.
SOURCE	Search...

Entry information

Entry name

CAV1_HUMAN

Accession

Primary (citable) accession number: Q03135
Secondary accession number(s): Q9UGP1, Q9UNG1, Q9UQH6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 115 of the entry and version 4 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.