TMCO1_HUMAN
ID TMCO1_HUMAN Reviewed; 239 AA.
AC Q9UM00; B2REA0; J9JIE6; O75545; Q9BZS3; Q9BZU8;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Calcium load-activated calcium channel {ECO:0000305|PubMed:27212239};
DE Short=CLAC channel {ECO:0000305|PubMed:27212239};
DE AltName: Full=Transmembrane and coiled-coil domain-containing protein 1 {ECO:0000305};
DE AltName: Full=Transmembrane and coiled-coil domains protein 4 {ECO:0000305};
DE AltName: Full=Xenogeneic cross-immune protein PCIA3 {ECO:0000303|Ref.2};
GN Name=TMCO1 {ECO:0000312|HGNC:HGNC:18188};
GN Synonyms=TMCC4 {ECO:0000312|HGNC:HGNC:18188};
GN ORFNames=PNAS-10 {ECO:0000303|Ref.4}, PNAS-136 {ECO:0000303|Ref.4},
GN UNQ151/PRO177 {ECO:0000303|PubMed:12975309};
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] (ISOFORM 3), TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Gastric adenocarcinoma;
RX PubMed=10393320; DOI=10.1093/oxfordjournals.jbchem.a022435;
RA Iwamuro S., Saeki M., Kato S.;
RT "Multi-ubiquitination of a nascent membrane protein produced in a rabbit
RT reticulocyte lysate.";
RL J. Biochem. 126:48-53(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Placenta;
RA Deng H.-X., Wei Y.-Q., Zhao X., Yang H.-S., Wang R., Yang J.-L.;
RT "Identification of angiogenesis-related genes from placenta by xenogeneic
RT antibody screening.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 10-239 (ISOFORM 1).
RC TISSUE=Brain;
RA Yu W., Gibbs R.A.;
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Promyelocytic leukemia;
RA Yu W.-Q., Sun B.-Z., Chai Y.-B., Zhu F., Liu X.-S., Li Z., Lu F., Yan W.,
RA Yang H., Zhao Z.-L.;
RT "Human acute promyelocytic leukemia cell line NB4's
RT apoptosis/differentiation related genes.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Trachea;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Placenta;
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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-111 AND SER-239, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP INVOLVEMENT IN CFSMR, TISSUE SPECIFICITY, AND VARIANT CFSMR 98-SER--SER-239
RP DEL.
RX PubMed=20018682; DOI=10.1073/pnas.0908457107;
RA Xin B., Puffenberger E.G., Turben S., Tan H., Zhou A., Wang H.;
RT "Homozygous frameshift mutation in TMCO1 causes a syndrome with
RT craniofacial dysmorphism, skeletal anomalies, and mental retardation.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:258-263(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-111 AND SER-239, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP INVOLVEMENT IN POAG.
RX PubMed=21532571; DOI=10.1038/ng.824;
RA Burdon K.P., Macgregor S., Hewitt A.W., Sharma S., Chidlow G., Mills R.A.,
RA Danoy P., Casson R., Viswanathan A.C., Liu J.Z., Landers J., Henders A.K.,
RA Wood J., Souzeau E., Crawford A., Leo P., Wang J.J., Rochtchina E.,
RA Nyholt D.R., Martin N.G., Montgomery G.W., Mitchell P., Brown M.A.,
RA Mackey D.A., Craig J.E.;
RT "Genome-wide association study identifies susceptibility loci for open
RT angle glaucoma at TMCO1 and CDKN2B-AS1.";
RL Nat. Genet. 43:574-578(2011).
RN [17]
RP INVOLVEMENT IN POAG, AND TISSUE SPECIFICITY.
RX PubMed=22714896; DOI=10.1167/iovs.11-9047;
RA Sharma S., Burdon K.P., Chidlow G., Klebe S., Crawford A., Dimasi D.P.,
RA Dave A., Martin S., Javadiyan S., Wood J.P., Casson R., Danoy P.,
RA Griggs K., Hewitt A.W., Landers J., Mitchell P., Mackey D.A., Craig J.E.;
RT "Association of genetic variants in the TMCO1 gene with clinical parameters
RT related to glaucoma and characterization of the protein in the eye.";
RL Invest. Ophthalmol. Vis. Sci. 53:4917-4925(2012).
RN [18]
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 [19]
RP VARIANT CFSMR 138-ARG--SER-239 DEL.
RX PubMed=23320496; DOI=10.1111/cge.12088;
RA Caglayan A.O., Per H., Akgumus G., Gumus H., Baranoski J., Canpolat M.,
RA Calik M., Yikilmaz A., Bilguvar K., Kumandas S., Gunel M.;
RT "Whole-exome sequencing identified a patient with TMCO1 defect syndrome and
RT expands the phenotic spectrum.";
RL Clin. Genet. 84:394-395(2013).
RN [20]
RP VARIANT CFSMR 138-ARG--SER-239 DEL.
RX PubMed=24194475; DOI=10.1002/ajmg.a.36248;
RA Alanay Y., Erguener B., Utine E., Hacariz O., Kiper P.O., Taskiran E.Z.,
RA Percin F., Uz E., Sagiroglu M.S., Yuksel B., Boduroglu K., Akarsu N.A.;
RT "TMCO1 deficiency causes autosomal recessive cerebrofaciothoracic
RT dysplasia.";
RL Am. J. Med. Genet. A 164A:291-304(2014).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, TOPOLOGY, AND MUTAGENESIS OF
RP ASP-191.
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).
RN [22]
RP FUNCTION, AND INTERACTION WITH CCDC47; NCLN; NOMO; TMEM147; SEC61A1; SEC61B
RP AND SEC61G.
RX PubMed=32820719; DOI=10.7554/elife.56889;
RA McGilvray P.T., Anghel S.A., Sundaram A., Zhong F., Trnka M.J.,
RA Fuller J.R., Hu H., Burlingame A.L., Keenan R.J.;
RT "An ER translocon for multi-pass membrane protein biogenesis.";
RL Elife 9:0-0(2020).
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
CC (PubMed:32820719). Together with SEC61 and TMEM147, forms the lipid-
CC filled cavity at the center of the translocon where TMEM147 may insert
CC hydrophobic segments of mutli-pass membrane proteins from the lumen
CC into de central membrane cavity in a process gated by SEC61, and TMCO1
CC may insert hydrophobic segments of nascent chains from the cytosol into
CC the cavity (PubMed:32820719). {ECO:0000269|PubMed:27212239,
CC ECO:0000269|PubMed:32820719}.
CC -!- SUBUNIT: Homodimer and homotetramer (PubMed:27212239). Homodimer under
CC resting conditions; forms homotetramers following and ER calcium
CC overload (PubMed:27212239). The ribosome-associated ER translocon
CC complex includes SEC61A1, SEC61B, SEC61G, TMCO1, CCDC47, NCLN/Nicalin,
CC NOMO and TMEM147; in the absence of ribosomes, only the complex forms
CC with NCLN/Nicalin, NOMO and TMEM147 remains intact (PubMed:32820719).
CC {ECO:0000269|PubMed:27212239, ECO:0000269|PubMed:32820719}.
CC -!- INTERACTION:
CC Q9UM00-1; Q7Z3Y9: KRT26; NbExp=3; IntAct=EBI-11614122, EBI-12084444;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10393320, ECO:0000269|PubMed:27212239}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:10393320,
CC ECO:0000269|PubMed:27212239}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:10393320}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:10393320}. Note=The first transmembrane region is
CC required for localization to the endoplasmic reticulum
CC (PubMed:27212239). A publication reported localization in cytoplasm and
CC nucleus (PubMed:22714896). Nuclear localization is however in
CC contradiction with two other reports (PubMed:10393320,
CC PubMed:27212239). {ECO:0000269|PubMed:10393320,
CC ECO:0000269|PubMed:22714896, ECO:0000269|PubMed:27212239}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=3;
CC Name=1;
CC IsoId=Q9UM00-3; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UM00-2; Sequence=VSP_019505;
CC Name=3;
CC IsoId=Q9UM00-1; Sequence=VSP_060086;
CC -!- TISSUE SPECIFICITY: Widely expressed in adult and fetal tissues, with
CC higher levels in thymus, prostate, testis and small intestine and lower
CC levels in brain, placenta, lung and kidney (PubMed:10393320,
CC PubMed:20018682). Present in most tissues in the eye, including the
CC trabecular meshwork and retina (at protein level) (PubMed:22714896).
CC {ECO:0000269|PubMed:10393320, ECO:0000269|PubMed:20018682,
CC ECO:0000269|PubMed:22714896}.
CC -!- DISEASE: Craniofacial dysmorphism, skeletal anomalies and intellectual
CC disability syndrome (CFSMR) [MIM:213980]: A disorder characterized by
CC craniofacial and skeletal anomalies, associated with intellectual
CC disability. Typical craniofacial dysmorphism include brachycephaly,
CC highly arched bushy eyebrows, synophrys, long eyelashes, low-set ears,
CC microdontism of primary teeth, and generalized gingival hyperplasia,
CC whereas Sprengel deformity of scapula, fusion of spine, rib
CC abnormities, pectus excavatum, and pes planus represent skeletal
CC anomalies. {ECO:0000269|PubMed:20018682, ECO:0000269|PubMed:23320496,
CC ECO:0000269|PubMed:24194475}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Glaucoma, primary open angle (POAG) [MIM:137760]: A complex
CC and genetically heterogeneous ocular disorder characterized by a
CC specific pattern of optic nerve and visual field defects. The angle of
CC the anterior chamber of the eye is open, and usually the intraocular
CC pressure is increased. However, glaucoma can occur at any intraocular
CC pressure. The disease is generally asymptomatic until the late stages,
CC by which time significant and irreversible optic nerve damage has
CC already taken place. In some cases, POAG shows digenic inheritance
CC involving mutations in CYP1B1 and MYOC genes.
CC {ECO:0000269|PubMed:21532571, ECO:0000269|PubMed:22714896}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TMCO1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK07514.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAK07549.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB020980; BAA86974.1; -; mRNA.
DR EMBL; AY763589; AAV34755.1; -; mRNA.
DR EMBL; AF070626; AAC25388.1; -; mRNA.
DR EMBL; AF274935; AAK07514.1; ALT_FRAME; mRNA.
DR EMBL; AF277194; AAK07549.1; ALT_FRAME; mRNA.
DR EMBL; AY359027; AAQ89386.1; -; mRNA.
DR EMBL; AK316610; BAG38197.1; -; mRNA.
DR EMBL; AL451074; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW90763.1; -; Genomic_DNA.
DR EMBL; BC000104; AAH00104.1; -; mRNA.
DR CCDS; CCDS1251.2; -. [Q9UM00-1]
DR RefSeq; NP_061899.2; NM_019026.4. [Q9UM00-1]
DR PDB; 6W6L; EM; 3.84 A; 6=52-239.
DR PDBsum; 6W6L; -.
DR AlphaFoldDB; Q9UM00; -.
DR SMR; Q9UM00; -.
DR BioGRID; 119995; 171.
DR IntAct; Q9UM00; 39.
DR MINT; Q9UM00; -.
DR STRING; 9606.ENSP00000480514; -.
DR TCDB; 1.A.106.1.1; the calcium load-activated calcium channel (clac) family.
DR iPTMnet; Q9UM00; -.
DR PhosphoSitePlus; Q9UM00; -.
DR SwissPalm; Q9UM00; -.
DR BioMuta; TMCO1; -.
DR DMDM; 74753399; -.
DR EPD; Q9UM00; -.
DR jPOST; Q9UM00; -.
DR MassIVE; Q9UM00; -.
DR MaxQB; Q9UM00; -.
DR PaxDb; Q9UM00; -.
DR PeptideAtlas; Q9UM00; -.
DR PRIDE; Q9UM00; -.
DR ProteomicsDB; 85163; -. [Q9UM00-1]
DR ProteomicsDB; 85164; -. [Q9UM00-2]
DR TopDownProteomics; Q9UM00-1; -. [Q9UM00-1]
DR Antibodypedia; 34332; 57 antibodies from 17 providers.
DR DNASU; 54499; -.
DR Ensembl; ENST00000367881.11; ENSP00000356856.6; ENSG00000143183.18. [Q9UM00-1]
DR Ensembl; ENST00000612311.4; ENSP00000480514.1; ENSG00000143183.18. [Q9UM00-3]
DR GeneID; 54499; -.
DR KEGG; hsa:54499; -.
DR MANE-Select; ENST00000367881.11; ENSP00000356856.6; NM_019026.6; NP_061899.3. [Q9UM00-1]
DR UCSC; uc001gdj.6; human.
DR UCSC; uc057mzb.1; human. [Q9UM00-3]
DR CTD; 54499; -.
DR DisGeNET; 54499; -.
DR GeneCards; TMCO1; -.
DR HGNC; HGNC:18188; TMCO1.
DR HPA; ENSG00000143183; Low tissue specificity.
DR MalaCards; TMCO1; -.
DR MIM; 137760; phenotype.
DR MIM; 213980; phenotype.
DR MIM; 614123; gene.
DR neXtProt; NX_Q9UM00; -.
DR OpenTargets; ENSG00000143183; -.
DR Orphanet; 1394; Cerebrofaciothoracic dysplasia.
DR PharmGKB; PA142670792; -.
DR VEuPathDB; HostDB:ENSG00000143183; -.
DR eggNOG; KOG3312; Eukaryota.
DR GeneTree; ENSGT00390000002659; -.
DR HOGENOM; CLU_081121_0_0_1; -.
DR InParanoid; Q9UM00; -.
DR OrthoDB; 1506634at2759; -.
DR PhylomeDB; Q9UM00; -.
DR TreeFam; TF315045; -.
DR PathwayCommons; Q9UM00; -.
DR SignaLink; Q9UM00; -.
DR BioGRID-ORCS; 54499; 9 hits in 1081 CRISPR screens.
DR ChiTaRS; TMCO1; human.
DR GeneWiki; TMCO1; -.
DR GenomeRNAi; 54499; -.
DR Pharos; Q9UM00; Tbio.
DR PRO; PR:Q9UM00; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9UM00; protein.
DR Bgee; ENSG00000143183; Expressed in calcaneal tendon and 202 other tissues.
DR ExpressionAtlas; Q9UM00; baseline and differential.
DR Genevisible; Q9UM00; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005262; F:calcium channel activity; IDA:UniProtKB.
DR GO; GO:0043022; F:ribosome binding; IDA:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IDA:UniProtKB.
DR GO; GO:0006983; P:ER overload response; IDA:UniProtKB.
DR InterPro; IPR002809; EMC3/TMCO1.
DR InterPro; IPR008559; TMCO1.
DR PANTHER; PTHR20917; PTHR20917; 1.
DR Pfam; PF01956; EMC3_TMCO1; 1.
DR SMART; SM01415; DUF106; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Alternative splicing; Calcium;
KW Calcium channel; Calcium transport; Coiled coil; Disease variant;
KW Endoplasmic reticulum; Glaucoma; Golgi apparatus; Intellectual disability;
KW Ion channel; Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..239
FT /note="Calcium load-activated calcium channel"
FT /id="PRO_0000244076"
FT TOPO_DOM 1..60
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:27212239"
FT TRANSMEM 61..81
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 82..141
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:27212239"
FT TRANSMEM 142..162
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 163..188
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:27212239"
FT INTRAMEM 189..205
FT /note="Pore-forming"
FT /evidence="ECO:0000305|PubMed:27212239"
FT TOPO_DOM 206..239
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:27212239"
FT COILED 83..140
FT /evidence="ECO:0000255"
FT MOD_RES 111
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 239
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231"
FT VAR_SEQ 1..51
FT /note="Missing (in isoform 3)"
FT /id="VSP_060086"
FT VAR_SEQ 115..133
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_019505"
FT VARIANT 98..239
FT /note="Missing (in CFSMR)"
FT /evidence="ECO:0000269|PubMed:20018682"
FT /id="VAR_076652"
FT VARIANT 138..239
FT /note="Missing (in CFSMR)"
FT /evidence="ECO:0000269|PubMed:23320496,
FT ECO:0000269|PubMed:24194475"
FT /id="VAR_076653"
FT MUTAGEN 191
FT /note="D->A: Abolishes the calcium channel activity."
FT /evidence="ECO:0000269|PubMed:27212239"
FT MUTAGEN 191
FT /note="D->E: Retains some of the calcium channel activity."
FT /evidence="ECO:0000269|PubMed:27212239"
FT CONFLICT 180
FT /note="S -> P (in Ref. 4; AAK07514/AAK07549)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 239 AA; 27079 MW; 8364C78CCA2DA982 CRC64;
MPRKRKCDLR AVRVGLLLGG GGVYGSRFRF TFPGCRALSP WRVRVQRRRC EMSTMFADTL
LIVFISVCTA LLAEGITWVL VYRTDKYKRL KAEVEKQSKK LEKKKETITE SAGRQQKKKI
ERQEEKLKNN NRDLSMVRMK SMFAIGFCFT ALMGMFNSIF DGRVVAKLPF TPLSYIQGLS
HRNLLGDDTT DCSFIFLYIL CTMSIRQNIQ KILGLAPSRA ATKQAGGFLG PPPPSGKFS
