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   27-MAR-2024, entry version 136.
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   GlyGen; Q5BKX8; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q5BKX8; -.
DR   PhosphoSitePlus; Q5BKX8; -.
DR   BioMuta; CAVIN4; -.
DR   DMDM; 172045939; -.
DR   MassIVE; Q5BKX8; -.
DR   PaxDb; 9606-ENSP00000418668; -.
DR   PeptideAtlas; Q5BKX8; -.
DR   ProteomicsDB; 62708; -.
DR   Antibodypedia; 14631; 99 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   AGR; HGNC:33742; -.
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; GPIHEFH; -.
DR   OrthoDB; 5351866at2759; -.
DR   PhylomeDB; Q5BKX8; -.
DR   TreeFam; TF331031; -.
DR   PathwayCommons; Q5BKX8; -.
DR   SignaLink; Q5BKX8; -.
DR   BioGRID-ORCS; 347273; 10 hits in 1145 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 116 other cell types or tissues.
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   InterPro; IPR026752; Cavin_fam.
DR   PANTHER; PTHR15240:SF4; CAVEOLAE-ASSOCIATED PROTEIN 4; 1.
DR   PANTHER; PTHR15240; CAVIN; 1.
DR   Pfam; PF15237; PTRF_SDPR; 1.
DR   Genevisible; Q5BKX8; HS.
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
//