CAVN4_MOUSE
ID CAVN4_MOUSE Reviewed; 362 AA.
AC A2AMM0; B1PRL4; Q5FW67; Q9CV87; Q9D728;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Caveolae-associated protein 4;
DE AltName: Full=Muscle-related coiled-coil protein;
DE AltName: Full=Muscle-restricted coiled-coil protein;
GN Name=Cavin4; Synonyms=Murc;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
RC STRAIN=C57BL/6J; TISSUE=Heart;
RX PubMed=18332105; DOI=10.1128/mcb.02186-07;
RA Ogata T., Ueyama T., Isodono K., Tagawa M., Takehara N., Kawashima T.,
RA Harada K., Takahashi T., Shioi T., Matsubara H., Oh H.;
RT "MURC, a muscle-restricted coiled-coil protein that modulates the Rho/ROCK
RT pathway, induces cardiac dysfunction and conduction disturbance.";
RL Mol. Cell. Biol. 28:3424-3436(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 [6]
RP IDENTIFICATION IN THE CAVIN COMPLEX, INTERACTION WITH CAVIN1, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=19546242; DOI=10.1083/jcb.200903053;
RA Bastiani M., Liu L., Hill M.M., Jedrychowski M.P., Nixon S.J., Lo H.P.,
RA Abankwa D., Luetterforst R., Fernandez-Rojo M., Breen M.R., Gygi S.P.,
RA Vinten J., Walser P.J., North K.N., Hancock J.F., Pilch P.F., Parton R.G.;
RT "MURC/Cavin-4 and cavin family members form tissue-specific caveolar
RT complexes.";
RL J. Cell Biol. 185:1259-1273(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-324; THR-334 AND SER-353, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=24567387; DOI=10.1073/pnas.1315359111;
RA Ogata T., Naito D., Nakanishi N., Hayashi Y.K., Taniguchi T., Miyagawa K.,
RA Hamaoka T., Maruyama N., Matoba S., Ikeda K., Yamada H., Oh H., Ueyama T.;
RT "MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric
RT cardiac hypertrophy induced by alpha1-adrenergic receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:3811-3816(2014).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26497963; DOI=10.1152/ajpheart.00446.2015;
RA Naito D., Ogata T., Hamaoka T., Nakanishi N., Miyagawa K., Maruyama N.,
RA Kasahara T., Taniguchi T., Nishi M., Matoba S., Ueyama T.;
RT "The coiled-coil domain of MURC/cavin-4 is involved in membrane trafficking
RT of caveolin-3 in cardiomyocytes.";
RL Am. J. Physiol. 309:H2127-H2136(2015).
CC -!- FUNCTION: Modulates the morphology of formed caveolae in
CC cardiomyocytes, but is not required for caveolar formation. Facilitates
CC the recruitment of MAPK1/3 to caveolae within cardiomyocytes and
CC regulates alpha-1 adrenergic receptor-induced hypertrophic responses in
CC cardiomyocytes through MAPK1/3 activation (PubMed:24567387).
CC Contributes to proper membrane localization and stabilization of
CC caveolin-3 (CAV3) in cardiomyocytes (PubMed:26497963). Induces RHOA
CC activation and activates NPPA transcription and myofibrillar
CC organization through the Rho/ROCK signaling pathway (PubMed:18332105).
CC {ECO:0000269|PubMed:18332105, ECO:0000269|PubMed:24567387,
CC ECO:0000269|PubMed:26497963}.
CC -!- SUBUNIT: Component of the CAVIN complex composed of CAVIN1, CAVIN2,
CC CAVIN3 and CAVIN4. Interacts with CAVIN1 (PubMed:19546242). Interacts
CC with CAVIN2; this augments the transactivation of NPPA. Interacts with
CC CAV3, ADRA1A, ADRA1B, MAPK1 and MAPK3 (By similarity).
CC {ECO:0000250|UniProtKB:B1PRL5, ECO:0000250|UniProtKB:Q5BKX8,
CC ECO:0000269|PubMed:19546242}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere
CC {ECO:0000269|PubMed:18332105}. Cytoplasm {ECO:0000269|PubMed:18332105}.
CC Cytoplasm, cytosol {ECO:0000269|PubMed:19546242}. Membrane, caveola
CC {ECO:0000269|PubMed:19546242, ECO:0000269|PubMed:24567387}. Cell
CC membrane, sarcolemma {ECO:0000269|PubMed:19546242}. Cell membrane
CC {ECO:0000269|PubMed:26497963}. Note=In cardiomyocytes, accumulates in
CC the Z-line of the sarcomere. In vascular smooth muscle cells, detected
CC diffusely throughout the cytoplasm (PubMed:18332105). Localizes in the
CC caveolae in a caveolin-dependent manner (PubMed:19546242).
CC {ECO:0000269|PubMed:18332105, ECO:0000269|PubMed:19546242}.
CC -!- TISSUE SPECIFICITY: Abundantly expressed in cardiac and skeletal muscle
CC (at protein level). Weaker expression in aorta and lung. In heart,
CC expressed in cardiomyocytes and vascular smooth muscle cells but not in
CC other surrounding cells including vascular endothelial cells.
CC {ECO:0000269|PubMed:18332105, ECO:0000269|PubMed:19546242}.
CC -!- DEVELOPMENTAL STAGE: Expression increases during development from
CC embryo to adult. {ECO:0000269|PubMed:18332105}.
CC -!- INDUCTION: Up-regulated in response to cardiac hypertrophy.
CC {ECO:0000269|PubMed:18332105}.
CC -!- DOMAIN: The coiled coil domain (residues 44-77) is essential for
CC membrane-targeting in cardiomyocytes. {ECO:0000250|UniProtKB:Q5BKX8}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit normal caveolar morphology and
CC cardiac function under physiological conditions, whereas upon alpha-1
CC adrenergic receptor stimulation, show attenuation of cardiac
CC hypertrophy accompanied by suppressed MAPK1/2 activation.
CC {ECO:0000269|PubMed:24567387}.
CC -!- SIMILARITY: Belongs to the CAVIN family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH89601.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAB26442.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; EU487254; ACA62936.1; -; mRNA.
DR EMBL; AK009073; BAB26056.1; -; mRNA.
DR EMBL; AK009691; BAB26442.1; ALT_FRAME; mRNA.
DR EMBL; AL807771; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466565; EDL02328.1; -; Genomic_DNA.
DR EMBL; BC089601; AAH89601.1; ALT_INIT; mRNA.
DR CCDS; CCDS18169.2; -.
DR RefSeq; NP_080785.2; NM_026509.3.
DR AlphaFoldDB; A2AMM0; -.
DR SMR; A2AMM0; -.
DR BioGRID; 212598; 1.
DR IntAct; A2AMM0; 1.
DR STRING; 10090.ENSMUSP00000030033; -.
DR iPTMnet; A2AMM0; -.
DR PhosphoSitePlus; A2AMM0; -.
DR MaxQB; A2AMM0; -.
DR PaxDb; A2AMM0; -.
DR PeptideAtlas; A2AMM0; -.
DR PRIDE; A2AMM0; -.
DR ProteomicsDB; 265278; -.
DR Antibodypedia; 14631; 87 antibodies from 17 providers.
DR DNASU; 68016; -.
DR Ensembl; ENSMUST00000030033; ENSMUSP00000030033; ENSMUSG00000028348.
DR GeneID; 68016; -.
DR KEGG; mmu:68016; -.
DR UCSC; uc012ddz.1; mouse.
DR CTD; 347273; -.
DR MGI; MGI:1915266; Cavin4.
DR VEuPathDB; HostDB:ENSMUSG00000028348; -.
DR eggNOG; ENOG502QQ9A; Eukaryota.
DR GeneTree; ENSGT00950000182910; -.
DR HOGENOM; CLU_065589_1_0_1; -.
DR InParanoid; A2AMM0; -.
DR OMA; YYIEESR; -.
DR OrthoDB; 991901at2759; -.
DR PhylomeDB; A2AMM0; -.
DR TreeFam; TF331031; -.
DR BioGRID-ORCS; 68016; 0 hits in 73 CRISPR screens.
DR PRO; PR:A2AMM0; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; A2AMM0; protein.
DR Bgee; ENSMUSG00000028348; Expressed in interventricular septum and 87 other tissues.
DR Genevisible; A2AMM0; MM.
DR GO; GO:0005901; C:caveola; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell.
DR GO; GO:0016528; C:sarcoplasm; IDA:MGI.
DR GO; GO:0030018; C:Z disc; IDA:MGI.
DR GO; GO:0005096; F:GTPase activator activity; ISO:MGI.
DR GO; GO:0055003; P:cardiac myofibril assembly; ISO:MGI.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0010468; P:regulation of gene expression; ISO:MGI.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IEA:InterPro.
DR GO; GO:0007266; P:Rho protein signal transduction; ISO:MGI.
DR InterPro; IPR033299; Cavin4.
DR InterPro; IPR026752; Cavin_fam.
DR PANTHER; PTHR15240; PTHR15240; 1.
DR PANTHER; PTHR15240:SF4; PTHR15240:SF4; 1.
DR Pfam; PF15237; PTRF_SDPR; 1.
PE 1: Evidence at protein level;
KW Activator; Cell membrane; Coiled coil; Cytoplasm; Developmental protein;
KW Differentiation; Membrane; Myogenesis; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..362
FT /note="Caveolae-associated protein 4"
FT /id="PRO_0000325764"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 230..289
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 305..346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 100..120
FT /evidence="ECO:0000255"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 230..253
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 268..287
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 152
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B1PRL5"
FT MOD_RES 171
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B1PRL5"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B1PRL5"
FT MOD_RES 324
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 334
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 353
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 311
FT /note="E -> D (in Ref. 2; BAB26442)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 362 AA; 41008 MW; 3A3DDAEA43DCF209 CRC64;
MEHNGSASNA GKIHQNRLSS VTEDEDQDAA LTIVTVLDRV ASVVDSVQAS QKRIEERHRE
MGNAIKSVQI DLLKLSQSHS NTGYVVNKLF EKTRKVSAHI KDVKARVEKQ QVRVTKVETK
QEEIMKKNKF RVVIFQEDIP CPASLSVVKD RSLPENQEEA EEVFDPPIEL SSDEEYYVEE
SRSARLRKSG KEHIDHIKKA FSRENMQKTR QTLDKKVSGI RTRIVTPERR ERLRQSGERL
RQSGERLRQS GERFKKSISS AAPSKEAFKI RSLRKAKDPK AEGQEVDRGM GVDIISGSLA
LGPIHEFHSD EFSETEKEVT KGGYSPQEGG DPPTPEPLKV TFKPQVRVED DESLLLELKQ
SS
