Caveolin 1

Caveolin-1 is a protein that in humans is encoded by the CAV1 gene.[5]

CAV1
Identifiers
Aliases	CAV1, BSCL3, CGL3, LCCNS, MSTP085, PPH3, VIP21, Caveolin 1
External IDs	OMIM: 601047 MGI: 102709 HomoloGene: 1330 GeneCards: CAV1
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q31.2 Start 116,525,001 bp[1] End 116,561,184 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6|6 A2 Start 17,306,335 bp[2] End 17,341,452 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • protein binding, bridging • ion channel binding • structural molecule activity • receptor binding • nitric-oxide synthase binding • patched binding • enzyme binding • peptidase activator activity • Rac GTPase binding • GO:0001948 protein binding • GO:0032947 molecular adaptor activity • protein kinase binding • ATPase binding • cholesterol binding • inward rectifier potassium channel inhibitor activity • identical protein binding • protein heterodimerization activity • GO:0032403 macromolecular complex binding Cellular component • endocytic vesicle membrane • endosome • membrane • focal adhesion • VCP-NPL4-UFD1 AAA ATPase complex • perinuclear region of cytoplasm • caveola • cilium • apical plasma membrane • endoplasmic reticulum • membrane raft • integral component of membrane • Golgi apparatus • early endosome membrane • cell membrane • intracellular • cell cortex • endoplasmic reticulum membrane • Golgi membrane • integral component of plasma membrane • acrosomal membrane • basolateral plasma membrane • cytoplasmic vesicle • lipid droplet • cytoplasm • macromolecular complex • sarcolemma Biological process • caveolin-mediated endocytosis • positive regulation of calcium ion transport into cytosol • vasoconstriction • response to progesterone • inactivation of MAPK activity • negative regulation of protein binding • regulation of peptidase activity • protein localization to plasma membrane raft • mammary gland development • vasculogenesis • negative regulation of pinocytosis • response to ischemia • angiogenesis • apoptotic signaling pathway • positive regulation of extrinsic apoptotic signaling pathway • cholesterol homeostasis • triglyceride metabolic process • negative regulation of canonical Wnt signaling pathway • calcium ion transport • negative regulation of cell proliferation • cellular response to transforming growth factor beta stimulus • positive regulation of toll-like receptor 3 signaling pathway • regulation of cytosolic calcium ion concentration • regulation of smooth muscle contraction • vesicle organization • negative regulation of peptidyl-tyrosine autophosphorylation • regulation of cardiac muscle cell action potential involved in regulation of contraction • negative regulation of transforming growth factor beta receptor signaling pathway • protein localization to basolateral plasma membrane • receptor internalization involved in canonical Wnt signaling pathway • regulation of membrane repolarization during action potential • positive regulation of peptidyl-serine phosphorylation • negative regulation of protein tyrosine kinase activity • regulation of entry of bacterium into host cell • negative regulation of MAP kinase activity • positive regulation of vasoconstriction • negative regulation of potassium ion transmembrane transport • lactation • receptor-mediated endocytosis of virus by host cell • regulation of blood coagulation • regulation of ventricular cardiac muscle cell action potential • protein homooligomerization • GO:0022415 viral process • positive regulation of intrinsic apoptotic signaling pathway • negative regulation of JAK-STAT cascade • mammary gland involution • calcium ion homeostasis • negative regulation of necroptotic process • regulation of the force of heart contraction • lipid storage • nitric oxide homeostasis • membrane depolarization • negative regulation of cytokine-mediated signaling pathway • cellular calcium ion homeostasis • negative regulation of transcription from RNA polymerase II promoter • response to estrogen • response to calcium ion • regulation of fatty acid metabolic process • cellular response to exogenous dsRNA • negative regulation of MAPK cascade • regulation of ruffle assembly • positive regulation of protein binding • positive regulation of protein ubiquitination • negative regulation of anoikis • leukocyte migration • protein localization • positive regulation of cell adhesion molecule production • response to hypoxia • negative regulation of nitric-oxide synthase activity • response to bacterium • caveola assembly • cellular response to hyperoxia • cholesterol transport • cellular response to starvation • T cell costimulation • regulation of nitric-oxide synthase activity • receptor internalization • positive regulation of peptidase activity • positive regulation of ER-associated ubiquitin-dependent protein catabolic process • negative regulation of endothelial cell proliferation • negative regulation of BMP signaling pathway • negative regulation of protein ubiquitination • cellular response to peptide hormone stimulus • positive regulation of gene expression • negative regulation of nitric oxide biosynthetic process • angiotensin-activated signaling pathway involved in heart process • protein oligomerization • negative regulation of peptidyl-serine phosphorylation • posttranscriptional regulation of gene expression • positive regulation of gap junction assembly • maintenance of protein location in cell • negative regulation of signal transduction • regulation of the force of heart contraction by chemical signal • regulation of cell communication by electrical coupling involved in cardiac conduction • regulation of heart rate by cardiac conduction • negative regulation of epithelial cell differentiation • skeletal muscle tissue development • beta-catenin destruction complex disassembly • GO:0048554 positive regulation of catalytic activity • positive regulation of canonical Wnt signaling pathway • negative regulation of tyrosine phosphorylation of STAT protein • negative regulation of inward rectifier potassium channel activity • cell differentiation • positive regulation of cell migration • positive regulation of cold-induced thermogenesis • positive regulation of NF-kappaB transcription factor activity Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	857	12389
Ensembl	ENSG00000105974	ENSMUSG00000007655
UniProt	Q03135	P49817
RefSeq (mRNA)	NM_001753 NM_001172895 NM_001172896 NM_001172897	NM_001243064 NM_007616
RefSeq (protein)	NP_001166366 NP_001166367 NP_001166368 NP_001744	NP_001229993 NP_031642
Location (UCSC)	Chr 7: 116.53 – 116.56 Mb	Chr 6: 17.31 – 17.34 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The scaffolding protein encoded by this gene is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits to the tyrosine kinase FYN, an initiating step in coupling integrins to the Ras-ERK pathway and promoting cell cycle progression. The gene is a tumor suppressor gene candidate and a negative regulator of the Ras-p42/44 MAP kinase cascade. CAV1 and CAV2 are located next to each other on chromosome 7 and express colocalizing proteins that form a stable hetero-oligomeric complex. By using alternative initiation codons in the same reading frame, two isoforms (alpha and beta) are encoded by a single transcript from this gene.[6]

Interactions

Caveolin 1 has been shown to interact with heterotrimeric G proteins,[7] Src tyrosine kinases (Src, Lyn) and H-Ras,[8] cholesterol,[9] TGF beta receptor 1,[10] endothelial NOS,[11] androgen receptor,[12] amyloid precursor protein,[13] gap junction protein, alpha 1,[14] nitric oxide synthase 2A,[15] epidermal growth factor receptor,[16] endothelin receptor type B,[17] PDGFRB,[18] PDGFRA,[18] PTGS2,[19] TRAF2,[20][21] estrogen receptor alpha,[22] caveolin 2,[23][24] PLD2,[25][26] Bruton's tyrosine kinase[27] and SCP2.[28] All these interactions are through a caveolin-scaffolding domain (CSD) within caveolin-1 molecule.[8] Molecules that interact with caveolin-1 contain caveolin-binding motifs (CBM).[29]

See also

• Caveolin

References

1. GRCh38: Ensembl release 89: ENSG00000105974 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000007655 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Fra AM, Mastroianni N, Mancini M, Pasqualetto E, Sitia R (March 1999). "Human caveolin-1 and caveolin-2 are closely linked genes colocalized with WI-5336 in a region of 7q31 frequently deleted in tumors". Genomics. 56 (3): 355–6. doi:10.1006/geno.1998.5723. PMID 10087206.
6. "Entrez Gene: CAV1 caveolin 1, caveolae protein, 22kDa".
7. Li S, Okamoto T, Chun M, Sargiacomo M, Casanova JE, Hansen SH, Nishimoto I, Lisanti MP (June 1995). "Evidence for a regulated interaction between heterotrimeric G proteins and caveolin". The Journal of Biological Chemistry. 270 (26): 15693–701. doi:10.1074/jbc.270.26.15693. PMID 7797570.
8. Li S, Couet J, Lisanti MP (November 1996). "Src tyrosine kinases, Galpha subunits, and H-Ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases". The Journal of Biological Chemistry. 271 (46): 29182–90. doi:10.1074/jbc.271.46.29182. PMC 6687395. PMID 8910575.
9. Li S, Song KS, Lisanti MP (January 1996). "Expression and characterization of recombinant caveolin. Purification by polyhistidine tagging and cholesterol-dependent incorporation into defined lipid membranes". The Journal of Biological Chemistry. 271 (1): 568–73. doi:10.1074/jbc.271.1.568. PMID 8550621.
10. Razani B, Zhang XL, Bitzer M, von Gersdorff G, Böttinger EP, Lisanti MP (March 2001). "Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor". The Journal of Biological Chemistry. 276 (9): 6727–38. doi:10.1074/jbc.M008340200. PMID 11102446.
11. García-Cardeña G, Fan R, Stern DF, Liu J, Sessa WC (November 1996). "Endothelial nitric oxide synthase is regulated by tyrosine phosphorylation and interacts with caveolin-1". The Journal of Biological Chemistry. 271 (44): 27237–40. doi:10.1074/jbc.271.44.27237. PMID 8910295.
12. Lu ML, Schneider MC, Zheng Y, Zhang X, Richie JP (April 2001). "Caveolin-1 interacts with androgen receptor. A positive modulator of androgen receptor mediated transactivation". The Journal of Biological Chemistry. 276 (16): 13442–51. doi:10.1074/jbc.M006598200. PMID 11278309.
13. Ikezu T, Trapp BD, Song KS, Schlegel A, Lisanti MP, Okamoto T (April 1998). "Caveolae, plasma membrane microdomains for alpha-secretase-mediated processing of the amyloid precursor protein". The Journal of Biological Chemistry. 273 (17): 10485–95. doi:10.1074/jbc.273.17.10485. PMID 9553108.
14. Schubert AL, Schubert W, Spray DC, Lisanti MP (May 2002). "Connexin family members target to lipid raft domains and interact with caveolin-1". Biochemistry. 41 (18): 5754–64. doi:10.1021/bi0121656. PMID 11980479.
15. Felley-Bosco E, Bender FC, Courjault-Gautier F, Bron C, Quest AF (December 2000). "Caveolin-1 down-regulates inducible nitric oxide synthase via the proteasome pathway in human colon carcinoma cells". Proceedings of the National Academy of Sciences of the United States of America. 97 (26): 14334–9. Bibcode:2000PNAS...9714334F. doi:10.1073/pnas.250406797. PMC 18919. PMID 11114180.
16. Couet J, Sargiacomo M, Lisanti MP (November 1997). "Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities". The Journal of Biological Chemistry. 272 (48): 30429–38. doi:10.1074/jbc.272.48.30429. PMID 9374534.
17. Yamaguchi T, Murata Y, Fujiyoshi Y, Doi T (April 2003). "Regulated interaction of endothelin B receptor with caveolin-1". European Journal of Biochemistry. 270 (8): 1816–27. doi:10.1046/j.1432-1033.2003.03544.x. PMID 12694195.
18. Yamamoto M, Toya Y, Jensen RA, Ishikawa Y (March 1999). "Caveolin is an inhibitor of platelet-derived growth factor receptor signaling". Experimental Cell Research. 247 (2): 380–8. doi:10.1006/excr.1998.4379. PMID 10066366.
19. Liou JY, Deng WG, Gilroy DW, Shyue SK, Wu KK (September 2001). "Colocalization and interaction of cyclooxygenase-2 with caveolin-1 in human fibroblasts". The Journal of Biological Chemistry. 276 (37): 34975–82. doi:10.1074/jbc.M105946200. PMID 11432874.
20. Feng X, Gaeta ML, Madge LA, Yang JH, Bradley JR, Pober JS (March 2001). "Caveolin-1 associates with TRAF2 to form a complex that is recruited to tumor necrosis factor receptors". The Journal of Biological Chemistry. 276 (11): 8341–9. doi:10.1074/jbc.M007116200. PMID 11112773.
21. Cao H, Courchesne WE, Mastick CC (March 2002). "A phosphotyrosine-dependent protein interaction screen reveals a role for phosphorylation of caveolin-1 on tyrosine 14: recruitment of C-terminal Src kinase". The Journal of Biological Chemistry. 277 (11): 8771–4. doi:10.1074/jbc.C100661200. PMID 11805080.
22. Schlegel A, Wang C, Pestell RG, Lisanti MP (October 2001). "Ligand-independent activation of oestrogen receptor alpha by caveolin-1". The Biochemical Journal. 359 (Pt 1): 203–10. doi:10.1042/0264-6021:3590203. PMC 1222136. PMID 11563984.
23. Breuza L, Corby S, Arsanto JP, Delgrossi MH, Scheiffele P, Le Bivic A (December 2002). "The scaffolding domain of caveolin 2 is responsible for its Golgi localization in Caco-2 cells". Journal of Cell Science. 115 (Pt 23): 4457–67. doi:10.1242/jcs.00130. PMID 12414992.
24. Scherer PE, Lewis RY, Volonte D, Engelman JA, Galbiati F, Couet J, Kohtz DS, van Donselaar E, Peters P, Lisanti MP (November 1997). "Cell-type and tissue-specific expression of caveolin-2. Caveolins 1 and 2 co-localize and form a stable hetero-oligomeric complex in vivo". The Journal of Biological Chemistry. 272 (46): 29337–46. doi:10.1074/jbc.272.46.29337. PMID 9361015.
25. Zheng X, Bollinger Bollag W (December 2003). "Aquaporin 3 colocates with phospholipase d2 in caveolin-rich membrane microdomains and is downregulated upon keratinocyte differentiation". The Journal of Investigative Dermatology. 121 (6): 1487–95. doi:10.1111/j.1523-1747.2003.12614.x. PMID 14675200.
26. Czarny M, Fiucci G, Lavie Y, Banno Y, Nozawa Y, Liscovitch M (February 2000). "Phospholipase D2: functional interaction with caveolin in low-density membrane microdomains". FEBS Letters. 467 (2–3): 326–32. doi:10.1016/S0014-5793(00)01174-1. PMID 10675563. S2CID 21891748.
27. Vargas L, Nore BF, Berglof A, Heinonen JE, Mattsson PT, Smith CI, Mohamed AJ (March 2002). "Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx". The Journal of Biological Chemistry. 277 (11): 9351–7. doi:10.1074/jbc.M108537200. PMID 11751885.
28. Zhou M, Parr RD, Petrescu AD, Payne HR, Atshaves BP, Kier AB, Ball JM, Schroeder F (June 2004). "Sterol carrier protein-2 directly interacts with caveolin-1 in vitro and in vivo". Biochemistry. 43 (23): 7288–306. doi:10.1021/bi035914n. PMID 15182174.
29. Couet J, Li S, Okamoto T, Ikezu T, Lisanti MP (March 1997). "Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins". The Journal of Biological Chemistry. 272 (10): 6525–33. doi:10.1074/jbc.272.10.6525. PMID 9045678.

Further reading

• Engelman JA, Zhang X, Galbiati F, Volonte D, Sotgia F, Pestell RG, Minetti C, Scherer PE, Okamoto T, Lisanti MP (December 1998). "Molecular genetics of the caveolin gene family: implications for human cancers, diabetes, Alzheimer disease, and muscular dystrophy". American Journal of Human Genetics. 63 (6): 1578–87. doi:10.1086/302172. PMC 1377628. PMID 9837809.
• Razani B, Schlegel A, Liu J, Lisanti MP (August 2001). "Caveolin-1, a putative tumour suppressor gene". Biochemical Society Transactions. 29 (Pt 4): 494–9. doi:10.1042/BST0290494. PMID 11498016.
• Fujimoto T, Kogo H, Nakamura N, Ozeki S (March 2002). "[Microdomains and caveolin]". Tanpakushitsu Kakusan Koso. Protein, Nucleic Acid, Enzyme. 47 (4 Suppl): 326–32. PMID 11915322.
• Shatz M, Liscovitch M (September 2004). "Caveolin-1 and cancer multidrug resistance: coordinate regulation of pro-survival proteins?". Leukemia Research. 28 (9): 907–8. doi:10.1016/j.leukres.2004.03.013. PMID 15234566.
• Frank PG, Lisanti MP (January 2007). "Caveolin-1 and liver regeneration: role in proliferation and lipogenesis". Cell Cycle. 6 (2): 115–6. doi:10.4161/cc.6.2.3722. PMID 17314510.