CAV2_RAT
ID CAV2_RAT Reviewed; 162 AA.
AC Q2IBC5; Q6P6R8; Q8VIK7;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Caveolin-2;
GN Name=Cav2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=11883949; DOI=10.1006/bbrc.2002.6603;
RA Magga J.M., Kay J.G., Davy A., Poulton N.P., Robbins S.M., Braun J.E.A.;
RT "ATP dependence of the SNARE/caveolin 1 interaction in the hippocampus.";
RL Biochem. Biophys. Res. Commun. 291:1232-1238(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12917688; DOI=10.1038/nature01858;
RA Thomas J.W., Touchman J.W., Blakesley R.W., Bouffard G.G.,
RA Beckstrom-Sternberg S.M., Margulies E.H., Blanchette M., Siepel A.C.,
RA Thomas P.J., McDowell J.C., Maskeri B., Hansen N.F., Schwartz M.S.,
RA Weber R.J., Kent W.J., Karolchik D., Bruen T.C., Bevan R., Cutler D.J.,
RA Schwartz S., Elnitski L., Idol J.R., Prasad A.B., Lee-Lin S.-Q.,
RA Maduro V.V.B., Summers T.J., Portnoy M.E., Dietrich N.L., Akhter N.,
RA Ayele K., Benjamin B., Cariaga K., Brinkley C.P., Brooks S.Y., Granite S.,
RA Guan X., Gupta J., Haghighi P., Ho S.-L., Huang M.C., Karlins E.,
RA Laric P.L., Legaspi R., Lim M.J., Maduro Q.L., Masiello C.A.,
RA Mastrian S.D., McCloskey J.C., Pearson R., Stantripop S., Tiongson E.E.,
RA Tran J.T., Tsurgeon C., Vogt J.L., Walker M.A., Wetherby K.D.,
RA Wiggins L.S., Young A.C., Zhang L.-H., Osoegawa K., Zhu B., Zhao B.,
RA Shu C.L., De Jong P.J., Lawrence C.E., Smit A.F., Chakravarti A.,
RA Haussler D., Green P., Miller W., Green E.D.;
RT "Comparative analyses of multi-species sequences from targeted genomic
RT regions.";
RL Nature 424:788-793(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=16645331; DOI=10.4142/jvs.2006.7.2.101;
RA Kim H., Lee T., Lee J., Ahn M., Moon C., Wie M.B., Shin T.;
RT "Immunohistochemical study of caveolin-1 and -2 in the rat retina.";
RL J. Vet. Sci. 7:101-104(2006).
RN [5]
RP PHOSPHORYLATION AT TYR-19, INTERACTION WITH MAPK1 AND INSR, FUNCTION,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-19.
RX PubMed=19778377; DOI=10.1111/j.1582-4934.2009.00391.x;
RA Kwon H., Jeong K., Pak Y.;
RT "Identification of pY19-caveolin-2 as a positive regulator of insulin-
RT stimulated actin cytoskeleton-dependent mitogenesis.";
RL J. Cell. Mol. Med. 13:1549-1564(2009).
RN [6]
RP PHOSPHORYLATION AT TYR-19 AND TYR-27, INTERACTION WITH MAPK1 AND STAT3,
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-19 AND TYR-27.
RX PubMed=19427337; DOI=10.1016/j.bbamcr.2009.04.015;
RA Kwon H., Jeong K., Hwang E.M., Park J.-Y., Hong S.-G., Choi W.-S., Pak Y.;
RT "Caveolin-2 regulation of STAT3 transcriptional activation in response to
RT insulin.";
RL Biochim. Biophys. Acta 1793:1325-1333(2009).
CC -!- FUNCTION: May act as a scaffolding protein within caveolar membranes.
CC Interacts directly with G-protein alpha subunits and can functionally
CC regulate their activity. Acts as an accessory protein in conjunction
CC with CAV1 in targeting to lipid rafts and driving caveolae formation.
CC The Ser-36 phosphorylated form has a role in modulating mitosis in
CC endothelial cells. Positive regulator of cellular mitogenesis of the
CC MAPK signaling pathway. Required for the insulin-stimulated nuclear
CC translocation and activation of MAPK1 and STAT3, and the subsequent
CC regulation of cell cycle progression. {ECO:0000269|PubMed:19427337,
CC ECO:0000269|PubMed:19778377}.
CC -!- SUBUNIT: Monomer or homodimer (By similarity). Interacts with CAV1; the
CC interaction forms a stable heterooligomeric complex that is required
CC for targeting to lipid rafts and for caveolae formation. Tyrosine
CC phosphorylated forms do not form heterooligomers with the Tyr-19-
CC phosphorylated form existing as a monomer or dimer and the Tyr-27-form
CC as a monomer only. Interacts (tyrosine phosphorylated form) with the
CC SH2 domain-containing proteins, RASA1, NCK1 and SRC. Interacts
CC (tyrosine phosphorylated form) with INSR; the interaction (Tyr-27-
CC phosphorylated form) is increased on insulin stimulation. Interacts
CC (Tyr-19-phosphorylated form) with MAPK1 (phosphorylated form); the
CC interaction, promoted by insulin, leads to nuclear location and MAPK1
CC activation. Interacts with STAT3; the interaction is increased on
CC insulin-induced tyrosine phosphorylation leading to STAT activation.
CC {ECO:0000250, ECO:0000269|PubMed:19427337,
CC ECO:0000269|PubMed:19778377}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Golgi apparatus membrane;
CC Peripheral membrane protein. Cell membrane; Peripheral membrane
CC protein. Membrane, caveola; Peripheral membrane protein. Note=Potential
CC hairpin-like structure in the membrane. Membrane protein of caveolae.
CC Tyr-19-phosphorylated form is enriched at sites of cell-cell contact
CC and, in response to insulin, is translocated to the nucleus in complex
CC with MAPK1. Tyr-27-phosphorylated form is located both in the cytoplasm
CC and plasma membrane. The CAV1-mediated Ser-23-phosphorylated form
CC locates to the plasma membrane. The Ser-36-phosphorylated form resides
CC in intracellular compartments (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: In the retina, mainly expressed in vessels, but
CC also diffuse expression in the inner and outer plexiform layers and in
CC the inner nuclear layer. {ECO:0000269|PubMed:16645331}.
CC -!- PTM: Phosphorylated on serine and tyrosine residues. CAV1 promotes
CC phosphorylation on Ser-23 which targets the complex to the plasma
CC membrane, lipid rafts and caveolae. Phosphorylation on Ser-36 appears
CC to modulate mitosis in endothelial cells (By similarity).
CC Phosphorylation on both Tyr-19 and Tyr-27 is required for insulin-
CC induced 'Ser-727' phosphorylation of STAT3 and its activation.
CC Phosphorylation on Tyr-19 is required for insulin-induced
CC phosphorylation of MAPK1 and DNA binding of STAT3. Tyrosine
CC phosphorylation is induced by both EGF and insulin. {ECO:0000250,
CC ECO:0000269|PubMed:19427337, ECO:0000269|PubMed:19778377}.
CC -!- SIMILARITY: Belongs to the caveolin family. {ECO:0000305}.
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DR EMBL; AF439780; AAL33581.1; -; mRNA.
DR EMBL; DP000027; AAR16307.1; -; Genomic_DNA.
DR EMBL; BC062059; AAH62059.1; -; mRNA.
DR RefSeq; NP_571989.2; NM_131914.2.
DR AlphaFoldDB; Q2IBC5; -.
DR BioGRID; 264175; 4.
DR CORUM; Q2IBC5; -.
DR IntAct; Q2IBC5; 1.
DR STRING; 10116.ENSRNOP00000008722; -.
DR iPTMnet; Q2IBC5; -.
DR PhosphoSitePlus; Q2IBC5; -.
DR PaxDb; Q2IBC5; -.
DR PRIDE; Q2IBC5; -.
DR GeneID; 363425; -.
DR KEGG; rno:363425; -.
DR UCSC; RGD:620348; rat.
DR CTD; 858; -.
DR RGD; 620348; Cav2.
DR eggNOG; ENOG502RZYX; Eukaryota.
DR InParanoid; Q2IBC5; -.
DR OrthoDB; 1468974at2759; -.
DR PhylomeDB; Q2IBC5; -.
DR TreeFam; TF315736; -.
DR Reactome; R-RNO-9009391; Extra-nuclear estrogen signaling.
DR PRO; PR:Q2IBC5; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0002080; C:acrosomal membrane; ISO:RGD.
DR GO; GO:0005901; C:caveola; IDA:RGD.
DR GO; GO:0002095; C:caveolar macromolecular signaling complex; ISO:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:BHF-UCL.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0005811; C:lipid droplet; IDA:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:BHF-UCL.
DR GO; GO:0005635; C:nuclear envelope; IDA:BHF-UCL.
DR GO; GO:0005637; C:nuclear inner membrane; IDA:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0031748; F:D1 dopamine receptor binding; ISS:UniProtKB.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI:BHF-UCL.
DR GO; GO:0060090; F:molecular adaptor activity; ISO:RGD.
DR GO; GO:0051219; F:phosphoprotein binding; IPI:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:RGD.
DR GO; GO:0097110; F:scaffold protein binding; ISO:RGD.
DR GO; GO:0000149; F:SNARE binding; IDA:RGD.
DR GO; GO:0019905; F:syntaxin binding; IDA:RGD.
DR GO; GO:0071711; P:basement membrane organization; ISO:RGD.
DR GO; GO:0070836; P:caveola assembly; ISS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0007268; P:chemical synaptic transmission; IDA:RGD.
DR GO; GO:0007029; P:endoplasmic reticulum organization; ISS:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0007005; P:mitochondrion organization; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IMP:RGD.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0044794; P:positive regulation by host of viral process; ISO:RGD.
DR GO; GO:0060161; P:positive regulation of dopamine receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:RGD.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:BHF-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IDA:BHF-UCL.
DR GO; GO:0019065; P:receptor-mediated endocytosis of virus by host cell; ISO:RGD.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR GO; GO:0007088; P:regulation of mitotic nuclear division; ISO:RGD.
DR GO; GO:0048741; P:skeletal muscle fiber development; ISS:UniProtKB.
DR GO; GO:0048278; P:vesicle docking; ISS:UniProtKB.
DR GO; GO:0006906; P:vesicle fusion; ISS:UniProtKB.
DR GO; GO:0016050; P:vesicle organization; ISO:RGD.
DR GO; GO:0019076; P:viral release from host cell; ISO:RGD.
DR InterPro; IPR033306; CAV-2.
DR InterPro; IPR001612; Caveolin.
DR InterPro; IPR018361; Caveolin_CS.
DR PANTHER; PTHR10844; PTHR10844; 1.
DR PANTHER; PTHR10844:SF3; PTHR10844:SF3; 1.
DR Pfam; PF01146; Caveolin; 1.
DR PROSITE; PS01210; CAVEOLIN; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Golgi apparatus; Membrane; Nucleus;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..162
FT /note="Caveolin-2"
FT /id="PRO_0000385179"
FT TOPO_DOM 1..86
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 87..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 108..162
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 19
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:19427337,
FT ECO:0000269|PubMed:19778377"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WVC3"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51636"
FT MOD_RES 27
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:19427337"
FT MOD_RES 36
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51636"
FT MUTAGEN 19
FT /note="Y->A: Abolishes phosphorylation, insulin-stimulated
FT interaction with phosphorylated MAPK1, MAPK1 nuclear
FT translocation and activation, reduction of insulin-induced
FT DNA binding of STAT3 but no effect on 'S-727'
FT phosphorylation of STAT3. Completely abolishes
FT phosphorylation, decreases insulin-induced DNA binding and
FT impairs nuclear location of STAT3, inhibits insulin-induced
FT 'S-727' phosphorylation of STAT3, and eliminates binding to
FT RASA1, SRC and NCK1; when associated with A-27."
FT /evidence="ECO:0000269|PubMed:19427337,
FT ECO:0000269|PubMed:19778377"
FT MUTAGEN 27
FT /note="Y->A: Abolishes phosphorylation and insulin-induced
FT nuclear location, but no effect on insulin-induced 'S-727'
FT phosphorylation of STAT3 nor on MAPK1 phosphorylation.
FT Completely abolishes insulin-induced phosphorylation,
FT nuclear location, nuclear translocation of MAPK1 and STAT3
FT and 'S-727' phosphorylation of STAT3 and MAPK1
FT phosphorylation; when associated with A-19."
FT /evidence="ECO:0000269|PubMed:19427337"
FT CONFLICT 28
FT /note="T -> A (in Ref. 2; AAR16307)"
FT /evidence="ECO:0000305"
FT CONFLICT 29
FT /note="D -> G (in Ref. 1; AAL33581)"
FT /evidence="ECO:0000305"
FT CONFLICT 124
FT /note="M -> V (in Ref. 1; AAL33581)"
FT /evidence="ECO:0000305"
FT CONFLICT 162
FT /note="D -> N (in Ref. 1; AAL33581)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 162 AA; 18266 MW; 7F8423C6B42F2F55 CRC64;
MGLETEKADV QLFMADDAYS HHSVVDYTDP EKYVDSSQDR DPHQLNSHLK LGFEDLIAEP
PTTHSFDKVW ICSHALFEIS KYVIYKFLTV FLAIPLAFIA GILFATLSCL HIWILMPFVK
TCLMVLPSVQ TIWKSVTDVV IGPLCTSVGR IFSSVSMQLS HD
