MCUB_HUMAN
ID MCUB_HUMAN Reviewed; 336 AA.
AC Q9NWR8; A8K4Y3; Q6IAC1;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Calcium uniporter regulatory subunit MCUb, mitochondrial {ECO:0000305};
DE Short=MCUb {ECO:0000250|UniProtKB:Q810S1};
DE AltName: Full=Coiled-coil domain-containing protein 109B {ECO:0000305};
DE Flags: Precursor;
GN Name=MCUB {ECO:0000303|PubMed:24231807, ECO:0000312|HGNC:HGNC:26076};
GN Synonyms=CCDC109B {ECO:0000312|HGNC:HGNC:26076};
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].
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].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 89-336, AND VARIANT VAL-255.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE UNIPLEX COMPLEX.
RX PubMed=24231807; DOI=10.1126/science.1242993;
RA Sancak Y., Markhard A.L., Kitami T., Kovacs-Bogdan E., Kamer K.J.,
RA Udeshi N.D., Carr S.A., Chaudhuri D., Clapham D.E., Li A.A., Calvo S.E.,
RA Goldberger O., Mootha V.K.;
RT "EMRE is an essential component of the mitochondrial calcium uniporter
RT complex.";
RL Science 342:1379-1382(2013).
CC -!- FUNCTION: Negatively regulates the activity of MCU, the mitochondrial
CC inner membrane calcium uniporter, and thereby modulates calcium uptake
CC into the mitochondrion. Does not form functional calcium channels by
CC itself. Mitochondrial calcium homeostasis plays key roles in cellular
CC physiology and regulates cell bioenergetics, cytoplasmic calcium
CC signals and activation of cell death pathways.
CC {ECO:0000250|UniProtKB:Q810S1}.
CC -!- SUBUNIT: Heterooligomer with MCU; this reduces MCU channel activity.
CC Homooligomer (By similarity). Component of the uniplex complex,
CC composed of MCU, MCUB, MICU1, MICU2 and EMRE/SMDT1.
CC {ECO:0000250|UniProtKB:Q810S1, ECO:0000269|PubMed:24231807}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:24231807}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:24231807}.
CC -!- SIMILARITY: Belongs to the MCU (TC 1.A.77) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH02633.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAA91309.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK000654; BAA91309.1; ALT_INIT; mRNA.
DR EMBL; AK291098; BAF83787.1; -; mRNA.
DR EMBL; CH471057; EAX06242.1; -; Genomic_DNA.
DR EMBL; BC002633; AAH02633.1; ALT_INIT; mRNA.
DR EMBL; CR457234; CAG33515.1; -; mRNA.
DR CCDS; CCDS3683.2; -.
DR RefSeq; NP_060388.2; NM_017918.4.
DR AlphaFoldDB; Q9NWR8; -.
DR SMR; Q9NWR8; -.
DR BioGRID; 120345; 171.
DR ComplexPortal; CPX-5966; Mitochondrial calcium uniporter complex, MICUB variant.
DR CORUM; Q9NWR8; -.
DR IntAct; Q9NWR8; 11.
DR STRING; 9606.ENSP00000378145; -.
DR TCDB; 1.A.77.1.12; the mg(2+)/ca(2+) uniporter (mcu) family.
DR GlyGen; Q9NWR8; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NWR8; -.
DR PhosphoSitePlus; Q9NWR8; -.
DR BioMuta; MCUB; -.
DR DMDM; 143955289; -.
DR EPD; Q9NWR8; -.
DR jPOST; Q9NWR8; -.
DR MassIVE; Q9NWR8; -.
DR MaxQB; Q9NWR8; -.
DR PaxDb; Q9NWR8; -.
DR PeptideAtlas; Q9NWR8; -.
DR PRIDE; Q9NWR8; -.
DR ProteomicsDB; 82963; -.
DR Antibodypedia; 62656; 83 antibodies from 18 providers.
DR DNASU; 55013; -.
DR Ensembl; ENST00000394650.7; ENSP00000378145.4; ENSG00000005059.16.
DR GeneID; 55013; -.
DR KEGG; hsa:55013; -.
DR MANE-Select; ENST00000394650.7; ENSP00000378145.4; NM_017918.5; NP_060388.2.
DR UCSC; uc011cfs.3; human.
DR CTD; 55013; -.
DR DisGeNET; 55013; -.
DR GeneCards; MCUB; -.
DR HGNC; HGNC:26076; MCUB.
DR HPA; ENSG00000005059; Tissue enhanced (lymphoid).
DR neXtProt; NX_Q9NWR8; -.
DR OpenTargets; ENSG00000005059; -.
DR PharmGKB; PA145008731; -.
DR VEuPathDB; HostDB:ENSG00000005059; -.
DR eggNOG; KOG2966; Eukaryota.
DR GeneTree; ENSGT00940000158059; -.
DR HOGENOM; CLU_056554_0_1_1; -.
DR InParanoid; Q9NWR8; -.
DR OMA; HAMELED; -.
DR OrthoDB; 1076768at2759; -.
DR PhylomeDB; Q9NWR8; -.
DR TreeFam; TF314435; -.
DR PathwayCommons; Q9NWR8; -.
DR Reactome; R-HSA-8949215; Mitochondrial calcium ion transport.
DR Reactome; R-HSA-8949664; Processing of SMDT1.
DR SignaLink; Q9NWR8; -.
DR BioGRID-ORCS; 55013; 13 hits in 1077 CRISPR screens.
DR ChiTaRS; MCUB; human.
DR GenomeRNAi; 55013; -.
DR Pharos; Q9NWR8; Tbio.
DR PRO; PR:Q9NWR8; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9NWR8; protein.
DR Bgee; ENSG00000005059; Expressed in monocyte and 175 other tissues.
DR Genevisible; Q9NWR8; HS.
DR GO; GO:0034704; C:calcium channel complex; ISS:UniProtKB.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0031224; C:intrinsic component of membrane; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:1990246; C:uniplex complex; IDA:UniProtKB.
DR GO; GO:0019855; F:calcium channel inhibitor activity; ISS:UniProtKB.
DR GO; GO:0036444; P:calcium import into the mitochondrion; IBA:GO_Central.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; ISS:UniProtKB.
DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; ISS:UniProtKB.
DR InterPro; IPR006769; MCU_C.
DR InterPro; IPR039055; MCU_fam.
DR PANTHER; PTHR13462; PTHR13462; 1.
DR Pfam; PF04678; MCU; 1.
PE 1: Evidence at protein level;
KW Calcium; Calcium transport; Coiled coil; Ion transport; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Reference proteome;
KW Transit peptide; Transmembrane; Transmembrane helix; Transport.
FT TRANSIT 1..35
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 36..336
FT /note="Calcium uniporter regulatory subunit MCUb,
FT mitochondrial"
FT /id="PRO_0000282980"
FT TRANSMEM 220..240
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..270
FT /note="Helical"
FT /evidence="ECO:0000255"
FT COILED 179..210
FT /evidence="ECO:0000255"
FT COILED 297..323
FT /evidence="ECO:0000255"
FT VARIANT 63
FT /note="I -> N (in dbSNP:rs4698744)"
FT /id="VAR_060149"
FT VARIANT 253
FT /note="Y -> F (in dbSNP:rs13846)"
FT /id="VAR_031443"
FT VARIANT 255
FT /note="I -> V (in dbSNP:rs1053680)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_031444"
FT CONFLICT 193
FT /note="D -> G (in Ref. 4; CAG33515)"
FT /evidence="ECO:0000305"
FT CONFLICT 214
FT /note="E -> G (in Ref. 4; CAG33515)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 336 AA; 39082 MW; 90C4BEBD5B1EFFD9 CRC64;
MLQRGLWPWR TRLLPTPGTW RPARPWPLPP PPQVLRVKLC GNVKYYQSHH YSTVVPPDEI
TVIYRHGLPL VTLTLPSRKE RCQFVVKPML STVGSFLQDL QNEDKGIKTA AIFTADGNMI
SASTLMDILL MNDFKLVINK IAYDVQCPKR EKPSNEHTAE MEHMKSLVHR LFTILHLEES
QKKREHHLLE KIDHLKEQLQ PLEQVKAGIE AHSEAKTSGL LWAGLALLSI QGGALAWLTW
WVYSWDIMEP VTYFITFANS MVFFAYFIVT RQDYTYSAVK SRQFLQFFHK KSKQQHFDVQ
QYNKLKEDLA KAKESLKQAR HSLCLQMQVE ELNEKN
