TMCO1_MOUSE
ID TMCO1_MOUSE Reviewed; 188 AA.
AC Q921L3; Q3TS11;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Calcium load-activated calcium channel {ECO:0000250|UniProtKB:Q9UM00};
DE Short=CLAC channel {ECO:0000250|UniProtKB:Q9UM00};
DE AltName: Full=Transmembrane and coiled-coil domain-containing protein 1 {ECO:0000305};
GN Name=Tmco1 {ECO:0000312|MGI:MGI:1921173};
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Epididymis, and Thymus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II, FVB/N, and FVB/N-3; TISSUE=Mammary tumor;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27212239; DOI=10.1016/j.cell.2016.04.051;
RA Wang Q.C., Zheng Q., Tan H., Zhang B., Li X., Yang Y., Yu J., Liu Y.,
RA Chai H., Wang X., Sun Z., Wang J.Q., Zhu S., Wang F., Yang M., Guo C.,
RA Wang H., Zheng Q., Li Y., Chen Q., Zhou A., Tang T.S.;
RT "TMCO1 is an ER Ca(2+) load-activated Ca(2+) channel.";
RL Cell 165:1454-1466(2016).
CC -!- FUNCTION: Calcium-selective channel required to prevent calcium stores
CC from overfilling, thereby playing a key role in calcium homeostasis
CC (PubMed:27212239). In response to endoplasmic reticulum (ER)
CC overloading, assembles into a homotetramer, forming a functional
CC calcium-selective channel, regulating the calcium content in
CC endoplasmic reticulum store (PubMed:27212239). Component of a ribosome-
CC associated ER translocon complex involved in multi-pass membrane
CC protein transport into the ER membrane and biogenesis. Together with
CC SEC61 and TMEM147, forms the lipid-filled cavity at the center of the
CC translocon where TMEM147 may insert hydrophobic segments of mutli-pass
CC membrane proteins from the lumen into de central membrane cavity in a
CC process gated by SEC61, and TMCO1 may insert hydrophobic segments of
CC nascent chains from the cytosol into the cavity (By similarity).
CC {ECO:0000250|UniProtKB:Q9UM00, ECO:0000269|PubMed:27212239}.
CC -!- SUBUNIT: Homodimer and homotetramer. Homodimer under resting
CC conditions; forms homotetramers following and ER calcium overload. The
CC ribosome-associated ER translocon complex includes SEC61A1, SEC61B,
CC SEC61G, TMCO1, CCDC47, NCLN/Nicalin, NOMO and TMEM147; in the absence
CC of ribosomes, only the complex forms with NCLN/Nicalin, NOMO and
CC TMEM147 remains intact. {ECO:0000250|UniProtKB:Q9UM00}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9UM00}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9UM00}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q9UM00}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9UM00}. Note=The first transmembrane region is
CC required for localization to the endoplasmic reticulum.
CC {ECO:0000250|UniProtKB:Q9UM00}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at a much lower rate than predicted
CC by the Mendelian ratio. Surviving mice show a reduced body size, low
CC survival rate and delayed osteogenesis. Adult mice display craniofacial
CC dysmorphism such as open cranial sutures, flattened faces with shorten
CC nasal bones and skull anomalies. Moreover, magnetic resonance imaging
CC (MRI) of brain shows significantly enlarged brain ventricles. Adult
CC mice show defects in spatial recognition memory in a Y-maze task assay
CC and a significant deficiency in motor coordination in rotarod
CC assessments. Defects are probably due to calcium overload, calcium
CC imaging results revealing a significant overload of endoplasmic
CC reticulum calcium in osteoblasts. {ECO:0000269|PubMed:27212239}.
CC -!- SIMILARITY: Belongs to the TMCO1 family. {ECO:0000305}.
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DR EMBL; AK037709; BAC29856.1; -; mRNA.
DR EMBL; AK162344; BAE36865.1; -; mRNA.
DR EMBL; BC011457; AAH11457.1; -; mRNA.
DR EMBL; BC019761; AAH19761.1; -; mRNA.
DR EMBL; BC020098; AAH20098.1; -; mRNA.
DR CCDS; CCDS15456.1; -.
DR RefSeq; NP_001034572.1; NM_001039483.1.
DR AlphaFoldDB; Q921L3; -.
DR SMR; Q921L3; -.
DR BioGRID; 213130; 5.
DR STRING; 10090.ENSMUSP00000095081; -.
DR iPTMnet; Q921L3; -.
DR PhosphoSitePlus; Q921L3; -.
DR SwissPalm; Q921L3; -.
DR EPD; Q921L3; -.
DR jPOST; Q921L3; -.
DR MaxQB; Q921L3; -.
DR PaxDb; Q921L3; -.
DR PRIDE; Q921L3; -.
DR ProteomicsDB; 259473; -.
DR Antibodypedia; 34332; 57 antibodies from 17 providers.
DR Ensembl; ENSMUST00000097473; ENSMUSP00000095081; ENSMUSG00000052428.
DR Ensembl; ENSMUST00000195015; ENSMUSP00000142042; ENSMUSG00000052428.
DR GeneID; 68944; -.
DR KEGG; mmu:68944; -.
DR UCSC; uc007dkv.1; mouse.
DR CTD; 54499; -.
DR MGI; MGI:1921173; Tmco1.
DR VEuPathDB; HostDB:ENSMUSG00000052428; -.
DR eggNOG; KOG3312; Eukaryota.
DR GeneTree; ENSGT00390000002659; -.
DR HOGENOM; CLU_081121_0_0_1; -.
DR InParanoid; Q921L3; -.
DR OMA; WADTLLI; -.
DR OrthoDB; 1506634at2759; -.
DR PhylomeDB; Q921L3; -.
DR TreeFam; TF315045; -.
DR BioGRID-ORCS; 68944; 4 hits in 71 CRISPR screens.
DR ChiTaRS; Tmco1; mouse.
DR PRO; PR:Q921L3; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q921L3; protein.
DR Bgee; ENSMUSG00000052428; Expressed in right kidney and 262 other tissues.
DR ExpressionAtlas; Q921L3; baseline and differential.
DR Genevisible; Q921L3; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005262; F:calcium channel activity; ISS:UniProtKB.
DR GO; GO:0043022; F:ribosome binding; ISS:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IMP:UniProtKB.
DR GO; GO:0006983; P:ER overload response; ISS:UniProtKB.
DR InterPro; IPR002809; EMC3/TMCO1.
DR InterPro; IPR008559; TMCO1.
DR PANTHER; PTHR20917; PTHR20917; 1.
DR Pfam; PF01956; EMC3_TMCO1; 1.
DR PIRSF; PIRSF023322; DUF841_euk; 1.
DR SMART; SM01415; DUF106; 1.
PE 1: Evidence at protein level;
KW Calcium; Calcium channel; Calcium transport; Coiled coil;
KW Endoplasmic reticulum; Golgi apparatus; Ion channel; Ion transport;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..188
FT /note="Calcium load-activated calcium channel"
FT /id="PRO_0000244077"
FT TOPO_DOM 1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9UM00"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..90
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9UM00"
FT TRANSMEM 91..111
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 112..137
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9UM00"
FT INTRAMEM 138..154
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:Q9UM00"
FT TOPO_DOM 155..188
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9UM00"
FT COILED 32..89
FT /evidence="ECO:0000255"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UM00"
FT MOD_RES 188
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UM00"
SQ SEQUENCE 188 AA; 21175 MW; FB77BFC4F0629EB1 CRC64;
MSTMFADTLL IVFISVCTAL LAEGITWVLV YRTDKYKRLK AEVEKQSKKL EKKKETITES
AGRQQKKKIE RQEEKLKNNN RDLSMVRMKS MFAIGFCFTA LMGMFNSIFD GRVVAKLPFT
PLSYIQGLSH RNLLGDDTTD CSFIFLYILC TMSIRQNIQK ILGLAPSRAA TKQAGGFLGP
PPPSGKFS
