MCUR1_HUMAN
ID MCUR1_HUMAN Reviewed; 359 AA.
AC Q96AQ8; Q96JS7; Q9H7F8;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Mitochondrial calcium uniporter regulator 1 {ECO:0000303|PubMed:23178883};
DE Short=MCU regulator 1 {ECO:0000303|PubMed:23178883};
DE AltName: Full=Coiled-coil domain-containing protein 90A, mitochondrial {ECO:0000305};
GN Name=MCUR1 {ECO:0000303|PubMed:23178883};
GN Synonyms=C6orf79 {ECO:0000312|HGNC:HGNC:21097},
GN CCDC90A {ECO:0000312|HGNC:HGNC:21097};
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 [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLY-108.
RC TISSUE=Adipose tissue;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, and Ovary;
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 FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, TOPOLOGY, AND
RP INTERACTION WITH MCU.
RX PubMed=23178883; DOI=10.1038/ncb2622;
RA Mallilankaraman K., Cardenas C., Doonan P.J., Chandramoorthy H.C.,
RA Irrinki K.M., Golenar T., Csordas G., Madireddi P., Yang J., Muller M.,
RA Miller R., Kolesar J.E., Molgo J., Kaufman B., Hajnoczky G., Foskett J.K.,
RA Madesh M.;
RT "MCUR1 is an essential component of mitochondrial Ca(2+) uptake that
RT regulates cellular metabolism.";
RL Nat. Cell Biol. 14:1336-1343(2012).
RN [5]
RP INTERACTION WITH MCU.
RX PubMed=26341627; DOI=10.15252/embr.201540436;
RA Lee Y., Min C.K., Kim T.G., Song H.K., Lim Y., Kim D., Shin K., Kang M.,
RA Kang J.Y., Youn H.S., Lee J.G., An J.Y., Park K.R., Lim J.J., Kim J.H.,
RA Kim J.H., Park Z.Y., Kim Y.S., Wang J., Kim D.H., Eom S.H.;
RT "Structure and function of the N-terminal domain of the human mitochondrial
RT calcium uniporter.";
RL EMBO Rep. 16:1318-1333(2015).
RN [6]
RP POSSIBLE FUNCTION IN CYTOCHROME C OXIDASE ASSEMBLY.
RX PubMed=25565209; DOI=10.1016/j.cmet.2014.12.004;
RA Paupe V., Prudent J., Dassa E.P., Rendon O.Z., Shoubridge E.A.;
RT "CCDC90A (MCUR1) is a cytochrome c oxidase assembly factor and not a
RT regulator of the mitochondrial calcium uniporter.";
RL Cell Metab. 21:109-116(2015).
RN [7]
RP FUNCTION.
RX PubMed=26445506; DOI=10.1016/j.cmet.2015.09.015;
RA Vais H., Tanis J.E., Mueller M., Payne R., Mallilankaraman K.,
RA Foskett J.K.;
RT "MCUR1, CCDC90A, is a regulator of the mitochondrial calcium uniporter.";
RL Cell Metab. 22:533-535(2015).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [9]
RP FUNCTION, AND INTERACTION WITH SMDT1/EMRE AND MCU.
RX PubMed=27184846; DOI=10.1016/j.celrep.2016.04.050;
RA Tomar D., Dong Z., Shanmughapriya S., Koch D.A., Thomas T., Hoffman N.E.,
RA Timbalia S.A., Goldman S.J., Breves S.L., Corbally D.P., Nemani N.,
RA Fairweather J.P., Cutri A.R., Zhang X., Song J., Jana F., Huang J.,
RA Barrero C., Rabinowitz J.E., Luongo T.S., Schumacher S.M., Rockman M.E.,
RA Dietrich A., Merali S., Caplan J., Stathopulos P., Ahima R.S., Cheung J.Y.,
RA Houser S.R., Koch W.J., Patel V., Gohil V.M., Elrod J.W., Rajan S.,
RA Madesh M.;
RT "MCUR1 is a scaffold factor for the MCU complex function and promotes
RT mitochondrial bioenergetics.";
RL Cell Rep. 15:1673-1685(2016).
RN [10]
RP FUNCTION, AND INTERACTION WITH MCU AND PPIF.
RX PubMed=26976564; DOI=10.1073/pnas.1602264113;
RA Chaudhuri D., Artiga D.J., Abiria S.A., Clapham D.E.;
RT "Mitochondrial calcium uniporter regulator 1 (MCUR1) regulates the calcium
RT threshold for the mitochondrial permeability transition.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:E1872-E1880(2016).
CC -!- FUNCTION: Key regulator of mitochondrial calcium uniporter (MCU)
CC required for calcium entry into mitochondrion (PubMed:23178883,
CC PubMed:26445506, PubMed:27184846, PubMed:26976564). Plays a direct role
CC in uniporter-mediated calcium uptake via a direct interaction with MCU
CC (PubMed:23178883). Probably involved in the assembly of the membrane
CC components of the uniporter complex (uniplex) (PubMed:27184846).
CC {ECO:0000269|PubMed:23178883, ECO:0000269|PubMed:26445506,
CC ECO:0000269|PubMed:26976564, ECO:0000269|PubMed:27184846}.
CC -!- SUBUNIT: Interacts (via coiled coil regions) with MCU; the interaction
CC is direct (PubMed:23178883, PubMed:26341627, PubMed:27184846,
CC PubMed:26976564). Interacts with SMDT1/EMRE; the interaction is direct
CC (PubMed:27184846). Interacts with PPIF (PubMed:26976564).
CC {ECO:0000269|PubMed:23178883, ECO:0000269|PubMed:26341627,
CC ECO:0000269|PubMed:26976564, ECO:0000269|PubMed:27184846}.
CC -!- INTERACTION:
CC Q96AQ8; Q8NE86-1: MCU; NbExp=4; IntAct=EBI-14404755, EBI-15932889;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:23178883}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:23178883}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96AQ8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96AQ8-2; Sequence=VSP_026998, VSP_026999;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:23178883}.
CC -!- SIMILARITY: Belongs to the CCDC90 family. {ECO:0000305}.
CC -!- CAUTION: A paper reported that MCUR1 has an indirect role as a
CC regulator of mitochondrial calcium uniporter (MCU) and is involved in
CC cytochrome c oxidase (COX) assembly instead (PubMed:25565209).
CC Subsequent publications however confirmed the function of MCUR1 as a
CC regulator of MCU (PubMed:26445506, PubMed:27184846).
CC {ECO:0000269|PubMed:25565209, ECO:0000269|PubMed:26445506,
CC ECO:0000269|PubMed:27184846}.
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DR EMBL; AK024611; BAB14934.1; -; mRNA.
DR EMBL; AL023583; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008234; AAH08234.1; -; mRNA.
DR EMBL; BC016850; AAH16850.1; -; mRNA.
DR CCDS; CCDS35495.1; -. [Q96AQ8-1]
DR RefSeq; NP_001026883.1; NM_001031713.3. [Q96AQ8-1]
DR AlphaFoldDB; Q96AQ8; -.
DR SMR; Q96AQ8; -.
DR BioGRID; 122001; 188.
DR DIP; DIP-61861N; -.
DR IntAct; Q96AQ8; 5.
DR STRING; 9606.ENSP00000368468; -.
DR iPTMnet; Q96AQ8; -.
DR PhosphoSitePlus; Q96AQ8; -.
DR BioMuta; MCUR1; -.
DR DMDM; 74751750; -.
DR EPD; Q96AQ8; -.
DR jPOST; Q96AQ8; -.
DR MassIVE; Q96AQ8; -.
DR MaxQB; Q96AQ8; -.
DR PaxDb; Q96AQ8; -.
DR PeptideAtlas; Q96AQ8; -.
DR PRIDE; Q96AQ8; -.
DR ProteomicsDB; 75993; -. [Q96AQ8-1]
DR ProteomicsDB; 75994; -. [Q96AQ8-2]
DR TopDownProteomics; Q96AQ8-1; -. [Q96AQ8-1]
DR Antibodypedia; 25007; 77 antibodies from 20 providers.
DR DNASU; 63933; -.
DR Ensembl; ENST00000379170.9; ENSP00000368468.3; ENSG00000050393.12. [Q96AQ8-1]
DR Ensembl; ENST00000488770.1; ENSP00000476162.1; ENSG00000050393.12. [Q96AQ8-2]
DR GeneID; 63933; -.
DR KEGG; hsa:63933; -.
DR MANE-Select; ENST00000379170.9; ENSP00000368468.3; NM_001031713.4; NP_001026883.1.
DR UCSC; uc003nbc.3; human. [Q96AQ8-1]
DR CTD; 63933; -.
DR DisGeNET; 63933; -.
DR GeneCards; MCUR1; -.
DR HGNC; HGNC:21097; MCUR1.
DR HPA; ENSG00000050393; Tissue enhanced (retina).
DR MIM; 616952; gene.
DR neXtProt; NX_Q96AQ8; -.
DR OpenTargets; ENSG00000050393; -.
DR PharmGKB; PA162381944; -.
DR VEuPathDB; HostDB:ENSG00000050393; -.
DR eggNOG; KOG3156; Eukaryota.
DR GeneTree; ENSGT00940000158957; -.
DR HOGENOM; CLU_791208_0_0_1; -.
DR InParanoid; Q96AQ8; -.
DR OMA; MSHITAV; -.
DR OrthoDB; 1252164at2759; -.
DR PhylomeDB; Q96AQ8; -.
DR TreeFam; TF331442; -.
DR PathwayCommons; Q96AQ8; -.
DR SignaLink; Q96AQ8; -.
DR BioGRID-ORCS; 63933; 16 hits in 1076 CRISPR screens.
DR ChiTaRS; MCUR1; human.
DR GenomeRNAi; 63933; -.
DR Pharos; Q96AQ8; Tbio.
DR PRO; PR:Q96AQ8; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q96AQ8; protein.
DR Bgee; ENSG00000050393; Expressed in jejunal mucosa and 204 other tissues.
DR ExpressionAtlas; Q96AQ8; baseline and differential.
DR Genevisible; Q96AQ8; HS.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0036444; P:calcium import into the mitochondrion; IMP:UniProtKB.
DR GO; GO:0070509; P:calcium ion import; IMP:UniProtKB.
DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0051561; P:positive regulation of mitochondrial calcium ion concentration; IMP:UniProtKB.
DR InterPro; IPR024461; CCDC90-like.
DR InterPro; IPR012439; MCUR1.
DR PANTHER; PTHR14360; PTHR14360; 1.
DR PANTHER; PTHR14360:SF11; PTHR14360:SF11; 1.
DR Pfam; PF07798; DUF1640; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Calcium transport; Coiled coil;
KW Ion transport; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..359
FT /note="Mitochondrial calcium uniporter regulator 1"
FT /id="PRO_0000295692"
FT TOPO_DOM 1..68
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:23178883"
FT TRANSMEM 69..85
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 86..338
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:23178883"
FT TRANSMEM 339..358
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:23178883"
FT COILED 235..310
FT /evidence="ECO:0000255"
FT VAR_SEQ 179..257
FT /note="GFATQQAEIIVSALVKILEANMDIVYKDMVTKMQQEITFQQVMSQIANVKKD
FT MIILEKSEFSALRAENEKIKLELHQLK -> ESHSFIQAGVQWHSLGLLQPPPPGFKRS
FT SHLILLSSWDYRHAPPHLDNFSVFLLETGFHHVGQAGLKLLTSSDPPTLAS (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_026998"
FT VAR_SEQ 258..359
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_026999"
FT VARIANT 108
FT /note="S -> G (in dbSNP:rs1204145)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_033320"
FT VARIANT 216
FT /note="T -> A (in dbSNP:rs3180196)"
FT /id="VAR_033321"
FT CONFLICT 42
FT /note="L -> P (in Ref. 1; BAB14934)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="R -> W (in Ref. 3; AAH08234)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 359 AA; 39694 MW; 488A2ABECFA2780B CRC64;
MDCGSVGGQR TQRLPGRQRL LFLPVGLSGR PGGSETSARR CLSALSDGLG ALRPRAPAAR
GGVSRASPLL LLLLVPSPRL AAAAPRRQLG DWERSRLGYA APPAGRSSAW RCSPGVAAAA
GALPQYHGPA PALVSCRREL SLSAGSLQLE RKRRDFTSSG SRKLYFDTHA LVCLLEDNGF
ATQQAEIIVS ALVKILEANM DIVYKDMVTK MQQEITFQQV MSQIANVKKD MIILEKSEFS
ALRAENEKIK LELHQLKQQV MDEVIKVRTD TKLDFNLEKS RVKELYSLNE KKLLELRTEI
VALHAQQDRA LTQTDRKIET EVAGLKTMLE SHKLDNIKYL AGSIFTCLTV ALGFYRLWI
