CAVN4_HUMAN
ID CAVN4_HUMAN Reviewed; 364 AA.
AC Q5BKX8; B1PRL3; B4DT88;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Caveolae-associated protein 4 {ECO:0000312|HGNC:HGNC:33742};
DE AltName: Full=Muscle-related coiled-coil protein;
DE AltName: Full=Muscle-restricted coiled-coil protein;
GN Name=CAVIN4 {ECO:0000312|HGNC:HGNC:33742}; Synonyms=MURC;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH CAVIN2.
RC 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 TISSUE=Pericardium;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 7-364.
RC TISSUE=Muscle;
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 [5]
RP SUBCELLULAR LOCATION.
RX PubMed=19525939; DOI=10.1038/ncb1887;
RA Hansen C.G., Bright N.A., Howard G., Nichols B.J.;
RT "SDPR induces membrane curvature and functions in the formation of
RT caveolae.";
RL Nat. Cell Biol. 11:807-814(2009).
RN [6]
RP INTERACTION WITH ADRA1A; ADRA1B; CAVIN1; CAVIN2 AND CAV3.
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 [7]
RP INTERACTION WITH CAV3, SUBCELLULAR LOCATION, AND DOMAIN COILED-COIL.
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).
RN [8]
RP REVIEW.
RX PubMed=26614875; DOI=10.1016/bs.ircmb.2015.07.009;
RA Nassar Z.D., Parat M.O.;
RT "Cavin family: new players in the biology of caveolae.";
RL Int. Rev. Cell Mol. Biol. 320:235-305(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. Contributes to proper
CC membrane localization and stabilization of caveolin-3 (CAV3) in
CC cardiomyocytes (By similarity). Induces RHOA activation and activates
CC NPPA transcription and myofibrillar organization through the Rho/ROCK
CC signaling pathway (PubMed:18332105). {ECO:0000250|UniProtKB:A2AMM0,
CC ECO:0000269|PubMed:18332105}.
CC -!- SUBUNIT: Component of the CAVIN complex composed of CAVIN1, CAVIN2,
CC CAVIN3 and CAVIN4 (By similarity). Interacts with CAVIN1, ADRA1A and
CC ADRA1B (PubMed:24567387). Interacts with CAVIN2; this augments the
CC transactivation of NPPA (PubMed:18332105, PubMed:24567387). Interacts
CC with CAV3 (PubMed:26497963, PubMed:24567387). Interacts with MAPK1 and
CC MAPK3 (By similarity). {ECO:0000250|UniProtKB:A2AMM0,
CC ECO:0000250|UniProtKB:B1PRL5, ECO:0000269|PubMed:18332105,
CC ECO:0000269|PubMed:24567387, ECO:0000269|PubMed:26497963}.
CC -!- INTERACTION:
CC Q5BKX8; Q13895: BYSL; NbExp=3; IntAct=EBI-12836558, EBI-358049;
CC Q5BKX8; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-12836558, EBI-741158;
CC Q5BKX8; Q8N5A5-2: ZGPAT; NbExp=3; IntAct=EBI-12836558, EBI-10183064;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere
CC {ECO:0000250|UniProtKB:A2AMM0}. Cytoplasm
CC {ECO:0000250|UniProtKB:A2AMM0}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:A2AMM0}. Cell membrane, sarcolemma
CC {ECO:0000250|UniProtKB:A2AMM0}. Membrane, caveola
CC {ECO:0000269|PubMed:19525939}. 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. Localizes in the caveolae in a
CC caveolin-dependent manner. {ECO:0000250|UniProtKB:A2AMM0}.
CC -!- DOMAIN: The coiled coil domain (residues 44-77) is essential for
CC membrane-targeting in cardiomyocytes. {ECO:0000269|PubMed:26497963}.
CC -!- SIMILARITY: Belongs to the CAVIN family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH90888.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; EU487253; ACA62935.1; -; mRNA.
DR EMBL; AK300099; BAG61900.1; -; mRNA.
DR EMBL; AL354917; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC090888; AAH90888.1; ALT_INIT; mRNA.
DR CCDS; CCDS35083.1; -.
DR RefSeq; NP_001018126.1; NM_001018116.2.
DR AlphaFoldDB; Q5BKX8; -.
DR SMR; Q5BKX8; -.
DR BioGRID; 131419; 7.
DR IntAct; Q5BKX8; 5.
DR STRING; 9606.ENSP00000418668; -.
DR iPTMnet; Q5BKX8; -.
DR PhosphoSitePlus; Q5BKX8; -.
DR BioMuta; CAVIN4; -.
DR DMDM; 172045939; -.
DR MassIVE; Q5BKX8; -.
DR PaxDb; Q5BKX8; -.
DR PeptideAtlas; Q5BKX8; -.
DR PRIDE; Q5BKX8; -.
DR ProteomicsDB; 62708; -.
DR Antibodypedia; 14631; 87 antibodies from 17 providers.
DR DNASU; 347273; -.
DR Ensembl; ENST00000307584.6; ENSP00000418668.1; ENSG00000170681.7.
DR GeneID; 347273; -.
DR KEGG; hsa:347273; -.
DR MANE-Select; ENST00000307584.6; ENSP00000418668.1; NM_001018116.2; NP_001018126.1.
DR UCSC; uc004bba.5; human.
DR CTD; 347273; -.
DR DisGeNET; 347273; -.
DR GeneCards; CAVIN4; -.
DR HGNC; HGNC:33742; CAVIN4.
DR HPA; ENSG00000170681; Group enriched (skeletal muscle, tongue).
DR MIM; 617714; gene.
DR neXtProt; NX_Q5BKX8; -.
DR OpenTargets; ENSG00000170681; -.
DR PharmGKB; PA164723237; -.
DR VEuPathDB; HostDB:ENSG00000170681; -.
DR eggNOG; ENOG502QQ9A; Eukaryota.
DR GeneTree; ENSGT00950000182910; -.
DR HOGENOM; CLU_065589_1_0_1; -.
DR InParanoid; Q5BKX8; -.
DR OMA; YYIEESR; -.
DR OrthoDB; 991901at2759; -.
DR PhylomeDB; Q5BKX8; -.
DR TreeFam; TF331031; -.
DR PathwayCommons; Q5BKX8; -.
DR SignaLink; Q5BKX8; -.
DR BioGRID-ORCS; 347273; 10 hits in 1067 CRISPR screens.
DR ChiTaRS; MURC; human.
DR GenomeRNAi; 347273; -.
DR Pharos; Q5BKX8; Tbio.
DR PRO; PR:Q5BKX8; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q5BKX8; protein.
DR Bgee; ENSG00000170681; Expressed in quadriceps femoris and 114 other tissues.
DR Genevisible; Q5BKX8; HS.
DR GO; GO:0005901; C:caveola; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:0030018; C:Z disc; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0010468; P:regulation of gene expression; IMP:CACAO.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IEA:InterPro.
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..364
FT /note="Caveolae-associated protein 4"
FT /id="PRO_0000325763"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 231..283
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 311..339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 44..77
FT /evidence="ECO:0000255"
FT COILED 202..226
FT /evidence="ECO:0000255"
FT COMPBIAS 1..16
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 231..254
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 269..283
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 312..327
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B1PRL5"
FT MOD_RES 173
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B1PRL5"
FT MOD_RES 326
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:A2AMM0"
FT MOD_RES 336
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:A2AMM0"
FT MOD_RES 355
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A2AMM0"
FT CONFLICT 34
FT /note="V -> A (in Ref. 2; BAG61900)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 364 AA; 41899 MW; 5EF86C58E970FC29 CRC64;
MEHNGSASNA DKIHQNRLSS VTEDEDQDAA LTIVTVLDKV ASIVDSVQAS QKRIEERHRE
MENAIKSVQI DLLKLSQSHS NTGHIINKLF EKTRKVSAHI KDVKARVEKQ QIHVKKVEVK
QEEIMKKNKF RVVIFQEKFR CPTSLSVVKD RNLTENQEED DDDIFDPPVD LSSDEEYYVE
ESRSARLRKS GKEHIDNIKK AFSKENMQKT RQNLDKKVNR IRTRIVTPER RERLRQSGER
LRQSGERLRQ SGERFKKSIS NAAPSKEAFK MRSLRKGKDR TVAEGEECAR EMGVDIIARS
ESLGPISELY SDELSEPEHE AARPVYPPHE GREIPTPEPL KVTFKSQVKV EDDESLLLDL
KHSS
