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0  structures 100  species 0  interactions 305  sequences 1  architecture

Family: Caveolin (PF01146)

Summary: Caveolin

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Caveolin Edit Wikipedia article

Caveolin
Identifiers
Symbol Caveolin
Pfam PF01146
InterPro IPR001612
PROSITE PDOC00930
Caveolin 1, caveolae protein, 22kDa
Identifiers
Symbol CAV1
Alt. symbols CAV
Entrez 857
HUGO 1527
OMIM 601047
RefSeq NM_001753
UniProt Q03135
Other data
Locus Chr. 7 q31
Caveolin 2
Identifiers
Symbol CAV2
Entrez 858
HUGO 1528
OMIM 601048
RefSeq NM_001233
UniProt P51636
Other data
Locus Chr. 7 q31
Caveolin 3
Identifiers
Symbol CAV3
Entrez 859
HUGO 1529
OMIM 601253
RefSeq NM_001234
UniProt P56539
Other data
Locus Chr. 3 p25

Caveolins are a family of integral membrane proteins that are the principal components of caveolae membranes and involved in receptor-independent endocytosis.[1][2][3] Caveolins may act as scaffolding proteins within caveolar membranes by compartmentalizing and concentrating signaling molecules. Various classes of signaling molecules, including G-protein subunits, receptor and non-receptor tyrosine kinases, endothelial nitric oxide synthase (eNOS), and small GTPases, bind Cav-1 through its 'caveolin-scaffolding domain'.

The caveolin gene family has three members in vertebrates: CAV1, CAV2, and CAV3, coding for the proteins caveolin-1, caveolin-2, and caveolin-3, respectively. All three members are membrane proteins with similar structure. Caveolin forms oligomers and associates with cholesterol and sphingolipids in certain areas of the cell membrane, leading to the formation of caveolae.

Structure and expression[edit]

The caveolins are similar in structure. They all form hairpin loops that are inserted into the cell membrane. Both the C-terminus and the N-terminus face the cytoplasmic side of the membrane. There are two isoforms of caveolin-1: caveolin-1α and caveolin-1β, the latter lacking a part of the N-terminus.

Caveolins are found in the majority of adherent, mammalian cells.

Function[edit]

The functions of caveolins are still under intensive investigation. They are best known for their role in the formation of 50-nanometer-size invaginations of the plasma membrane, called caveolae. Oligomers of caveolin form the coat of these domains. Cells that lack caveolins also lack caveolae. Many functions are ascribed to these domains, ranging from endocytosis and transcytosis to signal transduction.

Caveolin-1 has also been shown to play a role in the integrin signaling. The tyrosine phosphorylated form of caveolin-1 colocalizes with focal adhesions, suggesting a role for caveolin-1 in migration. Indeed, downregulation of caveolin-1 leads to less efficient migration in vitro.

Genetically engineered mice that lack caveolin-1 and caveolin-2 are viable and fertile, showing that neither the caveolins nor the caveolae are essential in embryonic development or reproduction of these animals. However, knock-out animals do develop abnormal, hypertrophic lungs, and cardiac myopathy, leading to a reduction in lifespan. Mice lacking caveolins also suffer from impaired angiogenic responses as well as abnormal responses to vasoconstrictive stimuli. In zebrafish, lack of caveolins leads to embryonic lethality, suggesting that higher vertebrates (as exemplified by mice) have developed compensation or redundancy for the functions of caveolins.

Role in disease[edit]

Cancer[edit]

Caveolins have a paradoxical role in the development of this disease. They have been implicated in both tumor suppression and oncogenesis.[4] High expression of caveolins leads to inhibition of cancer-related pathways, such as growth factor signaling pathways. However, certain cancer cells that express caveolins have been shown to be more aggressive and metastatic, because of a potential for anchorage-independent growth.

Cardiovascular diseases[edit]

Caveolins are thought to play an important role during the development of atherosclerosis.[5] Furthermore, caveolin-3 has been associated with Long QT syndrome.[6]

Muscular dystrophy[edit]

Caveolin-3 has been implicated in the development of certain types of muscular dystrophy (Limb-girdle muscular dystrophy).[7]

References[edit]

  1. ^ Tang Z, Scherer PE, Okamoto T, Song K, Chu C, Kohtz DS, Nishimoto I, Lodish HF, Lisanti MP (January 1996). "Molecular cloning of caveolin-3, a novel member of the caveolin gene family expressed predominantly in muscle". J. Biol. Chem. 271 (4): 2255–61. doi:10.1074/jbc.271.4.2255. PMID 8567687. 
  2. ^ Scherer PE, Okamoto T, Chun M, Nishimoto I, Lodish HF, Lisanti MP (January 1996). "Identification, sequence, and expression of caveolin-2 defines a caveolin gene family". Proc. Natl. Acad. Sci. U.S.A. 93 (1): 131–5. doi:10.1073/pnas.93.1.131. PMC 40192. PMID 8552590. 
  3. ^ Williams TM, Lisanti MP (2004). "The caveolin proteins". Genome Biol. 5 (3): 214. doi:10.1186/gb-2004-5-3-214. PMC 395759. PMID 15003112. 
  4. ^ Shatz M, Liscovitch M (March 2008). "Caveolin-1: a tumor-promoting role in human cancer". Int. J. Radiat. Biol. 84 (3): 177–89. doi:10.1080/09553000701745293. PMID 18300018. 
  5. ^ Williams TM, Lisanti MP (2004). "The Caveolin genes: from cell biology to medicine". Ann. Med. 36 (8): 584–95. doi:10.1080/07853890410018899. PMID 15768830. 
  6. ^ Vatta M, Ackerman MJ, Ye B, Makielski JC, Ughanze EE, Taylor EW, Tester DJ, Balijepalli RC, Foell JD, Li Z, Kamp TJ, Towbin JA (November 2006). "Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome". Circulation 114 (20): 2104–12. doi:10.1161/CIRCULATIONAHA.106.635268. PMID 17060380. 
  7. ^ Galbiati F, Razani B, Lisanti MP (October 2001). "Caveolae and caveolin-3 in muscular dystrophy". Trends Mol Med 7 (10): 435–41. doi:10.1016/S1471-4914(01)02105-0. PMID 11597517. 

External links[edit]

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Caveolin Provide feedback

All three known Caveolin forms have the FEDVIAEP caveolin 'signature motif' within their hydrophilic N-terminal domain. Caveolin 2 (Cav-2) is co-localised and co-expressed with Cav-1/VIP21, forms heterodimers with it and needs Cav-1 for proper membrane localisation. Cav-3 has greater protein sequence similarity to Cav-1 than to Cav-2. Cellular processes caveolins are involved in include vesicular transport, cholesterol homeostasis, signal transduction, and tumour suppression [1].

Literature references

  1. Williams TM, Lisanti MP; , Genome Biol 2004;5:214.: The caveolin proteins. PUBMED:15003112 EPMC:15003112


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001612

Caveolins [PUBMED:8567687, PUBMED:8552590, PUBMED:15003112] are a family of integral membrane proteins which are the principal components of caveolae membranes. Cavoleae are flask-shaped plasma membrane invaginations whose exact cellular function is not yet clear. Caveolins may act as scaffolding proteins within caveolar membranes by compartmentalizing and concentrating signalling molecules. Various classes of signalling molecules, including G-protein subunits, receptor and non-receptor tyrosine kinases, endothelial nitric oxide synthase (eNOS), and small GTPases, bind Cav-1 through its 'caveolin-scaffolding domain'.

Currently, three different forms of caveolins are known: caveolin-1 (or VIP21), caveolin-2 and caveolin-3 (or M-caveolin).

Caveolins are proteins of about 20 Kd, they form high molecular mass homo-oligomers. Structurally they seem to have N-terminal and C-terminal hydrophilic segments and a long central transmembrane domain that probably forms a hairpin in the membrane. Both extremities are known to face the cytoplasm. Caveolae are enriched with cholesterol and Cav-1 is one of the few proteins that binds cholesterol tightly and specifically.

Domain organisation

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Alignments

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  Seed
(21)
Full
(305)
Representative proteomes NCBI
(266)
Meta
(0)
RP15
(40)
RP35
(53)
RP55
(98)
RP75
(153)
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  Seed
(21)
Full
(305)
Representative proteomes NCBI
(266)
Meta
(0)
RP15
(40)
RP35
(53)
RP55
(98)
RP75
(153)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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Curation and family details

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Seed source: Prosite
Previous IDs: none
Type: Family
Author: Finn RD, Bateman A
Number in seed: 21
Number in full: 305
Average length of the domain: 143.40 aa
Average identity of full alignment: 45 %
Average coverage of the sequence by the domain: 85.68 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 25.6 25.6
Noise cut-off 21.6 21.5
Model length: 148
Family (HMM) version: 12
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