Full text data of TMCO1
TMCO1
(TMCC4)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Transmembrane and coiled-coil domain-containing protein 1 (Transmembrane and coiled-coil domains protein 4; Xenogeneic cross-immune protein PCIA3)
Transmembrane and coiled-coil domain-containing protein 1 (Transmembrane and coiled-coil domains protein 4; Xenogeneic cross-immune protein PCIA3)
UniProt
Q9UM00
ID TMCO1_HUMAN Reviewed; 188 AA.
AC Q9UM00; B2REA0; O75545; Q9BZS3; Q9BZU8;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-2000, sequence version 1.
DT 22-JAN-2014, entry version 106.
DE RecName: Full=Transmembrane and coiled-coil domain-containing protein 1;
DE AltName: Full=Transmembrane and coiled-coil domains protein 4;
DE AltName: Full=Xenogeneic cross-immune protein PCIA3;
GN Name=TMCO1; Synonyms=TMCC4; ORFNames=PNAS-10, PNAS-136, UNQ151/PRO177;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Gastric adenocarcinoma;
RX PubMed=10393320;
RA Iwamuro S., Saeki M., Kato S.;
RT "Multi-ubiquitination of a nascent membrane protein produced in a
RT rabbit reticulocyte lysate.";
RL J. Biochem. 126:48-53(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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
RT xenogeneic antibody screening.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (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 1 AND 2).
RC TISSUE=Promyelocytic leukemia;
RA Yu W.-Q., Sun B.-Z., Chai Y.-B., Zhu F., Liu X.-S., Li Z., Lu F.,
RA Yan W., 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 1).
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.,
RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale
RT effort to identify novel human secreted and transmembrane proteins: a
RT bioinformatics assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA 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.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA 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.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA 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 MRNA] (ISOFORM 1).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188, AND MASS
RP SPECTROMETRY.
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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60 AND SER-188, AND MASS
RP SPECTROMETRY.
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 [12]
RP INVOLVEMENT IN CFSMR, AND TISSUE SPECIFICITY.
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
RT retardation.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:258-263(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60 AND SER-188, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein. Golgi apparatus membrane; Multi-pass membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UM00-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UM00-2; Sequence=VSP_019505;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed in adult and fetal tissues,
CC with higher levels in thymus, prostate, testis and small intestine
CC and lower levels in brain, placenta, lung and kidney.
CC -!- DISEASE: Craniofacial dysmorphism, skeletal anomalies and mental
CC retardation syndrome (CFSMR) [MIM:614132]: A disorder
CC characterized by craniofacial and skeletal anomalies, associated
CC with mental retardation. Typical craniofacial dysmorphism include
CC brachycephaly, highly arched bushy eyebrows, synophrys, long
CC eyelashes, low-set ears, microdontism of primary teeth, and
CC generalized gingival hyperplasia, whereas Sprengel deformity of
CC scapula, fusion of spine, rib abnormities, pectus excavatum, and
CC pes planus represent skeletal anomalies. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TMCO1 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC25388.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=AAK07514.1; Type=Frameshift; Positions=Several;
CC Sequence=AAK07549.1; Type=Frameshift; Positions=Several;
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DR EMBL; AB020980; BAA86974.1; -; mRNA.
DR EMBL; AY763589; AAV34755.1; -; mRNA.
DR EMBL; AF070626; AAC25388.1; ALT_INIT; 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; CAH74064.1; -; Genomic_DNA.
DR EMBL; BC000104; AAH00104.1; -; mRNA.
DR RefSeq; NP_061899.2; NM_019026.4.
DR UniGene; Hs.31498; -.
DR ProteinModelPortal; Q9UM00; -.
DR IntAct; Q9UM00; 2.
DR STRING; 9606.ENSP00000356856; -.
DR PhosphoSite; Q9UM00; -.
DR DMDM; 74753399; -.
DR PaxDb; Q9UM00; -.
DR PRIDE; Q9UM00; -.
DR DNASU; 54499; -.
DR Ensembl; ENST00000392129; ENSP00000375975; ENSG00000143183.
DR GeneID; 54499; -.
DR KEGG; hsa:54499; -.
DR CTD; 54499; -.
DR GeneCards; GC01M165693; -.
DR HGNC; HGNC:18188; TMCO1.
DR HPA; HPA038775; -.
DR MIM; 614123; gene.
DR MIM; 614132; phenotype.
DR neXtProt; NX_Q9UM00; -.
DR Orphanet; 228407; TMCO1 defect syndrome.
DR PharmGKB; PA142670792; -.
DR eggNOG; NOG301636; -.
DR HOGENOM; HOG000240371; -.
DR HOVERGEN; HBG054437; -.
DR InParanoid; Q9UM00; -.
DR OrthoDB; EOG78WKTD; -.
DR PhylomeDB; Q9UM00; -.
DR GeneWiki; TMCO1; -.
DR GenomeRNAi; 54499; -.
DR NextBio; 56846; -.
DR PRO; PR:Q9UM00; -.
DR ArrayExpress; Q9UM00; -.
DR Bgee; Q9UM00; -.
DR CleanEx; HS_TMCO1; -.
DR Genevestigator; Q9UM00; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR InterPro; IPR002809; DUF106_TM.
DR InterPro; IPR008559; UCP023322_TM_euk.
DR PANTHER; PTHR20917; PTHR20917; 1.
DR Pfam; PF01956; DUF106; 1.
DR PIRSF; PIRSF023322; DUF841_euk; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Complete proteome;
KW Endoplasmic reticulum; Golgi apparatus; Membrane; Mental retardation;
KW Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1 188 Transmembrane and coiled-coil domain-
FT containing protein 1.
FT /FTId=PRO_0000244076.
FT TRANSMEM 10 30 Helical; (Potential).
FT TRANSMEM 91 111 Helical; (Potential).
FT COILED 32 89 Potential.
FT COMPBIAS 180 183 Poly-Pro.
FT MOD_RES 60 60 Phosphoserine.
FT MOD_RES 188 188 Phosphoserine.
FT VAR_SEQ 64 82 Missing (in isoform 2).
FT /FTId=VSP_019505.
FT CONFLICT 129 129 S -> P (in Ref. 4; AAK07514/AAK07549).
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
//
ID TMCO1_HUMAN Reviewed; 188 AA.
AC Q9UM00; B2REA0; O75545; Q9BZS3; Q9BZU8;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-2000, sequence version 1.
DT 22-JAN-2014, entry version 106.
DE RecName: Full=Transmembrane and coiled-coil domain-containing protein 1;
DE AltName: Full=Transmembrane and coiled-coil domains protein 4;
DE AltName: Full=Xenogeneic cross-immune protein PCIA3;
GN Name=TMCO1; Synonyms=TMCC4; ORFNames=PNAS-10, PNAS-136, UNQ151/PRO177;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Gastric adenocarcinoma;
RX PubMed=10393320;
RA Iwamuro S., Saeki M., Kato S.;
RT "Multi-ubiquitination of a nascent membrane protein produced in a
RT rabbit reticulocyte lysate.";
RL J. Biochem. 126:48-53(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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
RT xenogeneic antibody screening.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (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 1 AND 2).
RC TISSUE=Promyelocytic leukemia;
RA Yu W.-Q., Sun B.-Z., Chai Y.-B., Zhu F., Liu X.-S., Li Z., Lu F.,
RA Yan W., 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 1).
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.,
RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale
RT effort to identify novel human secreted and transmembrane proteins: a
RT bioinformatics assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA 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.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA 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.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA 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 MRNA] (ISOFORM 1).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188, AND MASS
RP SPECTROMETRY.
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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60 AND SER-188, AND MASS
RP SPECTROMETRY.
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 [12]
RP INVOLVEMENT IN CFSMR, AND TISSUE SPECIFICITY.
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
RT retardation.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:258-263(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60 AND SER-188, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein. Golgi apparatus membrane; Multi-pass membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UM00-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UM00-2; Sequence=VSP_019505;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed in adult and fetal tissues,
CC with higher levels in thymus, prostate, testis and small intestine
CC and lower levels in brain, placenta, lung and kidney.
CC -!- DISEASE: Craniofacial dysmorphism, skeletal anomalies and mental
CC retardation syndrome (CFSMR) [MIM:614132]: A disorder
CC characterized by craniofacial and skeletal anomalies, associated
CC with mental retardation. Typical craniofacial dysmorphism include
CC brachycephaly, highly arched bushy eyebrows, synophrys, long
CC eyelashes, low-set ears, microdontism of primary teeth, and
CC generalized gingival hyperplasia, whereas Sprengel deformity of
CC scapula, fusion of spine, rib abnormities, pectus excavatum, and
CC pes planus represent skeletal anomalies. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TMCO1 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC25388.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=AAK07514.1; Type=Frameshift; Positions=Several;
CC Sequence=AAK07549.1; Type=Frameshift; Positions=Several;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AB020980; BAA86974.1; -; mRNA.
DR EMBL; AY763589; AAV34755.1; -; mRNA.
DR EMBL; AF070626; AAC25388.1; ALT_INIT; 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; CAH74064.1; -; Genomic_DNA.
DR EMBL; BC000104; AAH00104.1; -; mRNA.
DR RefSeq; NP_061899.2; NM_019026.4.
DR UniGene; Hs.31498; -.
DR ProteinModelPortal; Q9UM00; -.
DR IntAct; Q9UM00; 2.
DR STRING; 9606.ENSP00000356856; -.
DR PhosphoSite; Q9UM00; -.
DR DMDM; 74753399; -.
DR PaxDb; Q9UM00; -.
DR PRIDE; Q9UM00; -.
DR DNASU; 54499; -.
DR Ensembl; ENST00000392129; ENSP00000375975; ENSG00000143183.
DR GeneID; 54499; -.
DR KEGG; hsa:54499; -.
DR CTD; 54499; -.
DR GeneCards; GC01M165693; -.
DR HGNC; HGNC:18188; TMCO1.
DR HPA; HPA038775; -.
DR MIM; 614123; gene.
DR MIM; 614132; phenotype.
DR neXtProt; NX_Q9UM00; -.
DR Orphanet; 228407; TMCO1 defect syndrome.
DR PharmGKB; PA142670792; -.
DR eggNOG; NOG301636; -.
DR HOGENOM; HOG000240371; -.
DR HOVERGEN; HBG054437; -.
DR InParanoid; Q9UM00; -.
DR OrthoDB; EOG78WKTD; -.
DR PhylomeDB; Q9UM00; -.
DR GeneWiki; TMCO1; -.
DR GenomeRNAi; 54499; -.
DR NextBio; 56846; -.
DR PRO; PR:Q9UM00; -.
DR ArrayExpress; Q9UM00; -.
DR Bgee; Q9UM00; -.
DR CleanEx; HS_TMCO1; -.
DR Genevestigator; Q9UM00; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR InterPro; IPR002809; DUF106_TM.
DR InterPro; IPR008559; UCP023322_TM_euk.
DR PANTHER; PTHR20917; PTHR20917; 1.
DR Pfam; PF01956; DUF106; 1.
DR PIRSF; PIRSF023322; DUF841_euk; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Complete proteome;
KW Endoplasmic reticulum; Golgi apparatus; Membrane; Mental retardation;
KW Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1 188 Transmembrane and coiled-coil domain-
FT containing protein 1.
FT /FTId=PRO_0000244076.
FT TRANSMEM 10 30 Helical; (Potential).
FT TRANSMEM 91 111 Helical; (Potential).
FT COILED 32 89 Potential.
FT COMPBIAS 180 183 Poly-Pro.
FT MOD_RES 60 60 Phosphoserine.
FT MOD_RES 188 188 Phosphoserine.
FT VAR_SEQ 64 82 Missing (in isoform 2).
FT /FTId=VSP_019505.
FT CONFLICT 129 129 S -> P (in Ref. 4; AAK07514/AAK07549).
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
//
MIM
614123
*RECORD*
*FIELD* NO
614123
*FIELD* TI
*614123 TRANSMEMBRANE AND COILED-COIL DOMAINS PROTEIN 1; TMCO1
*FIELD* TX
CLONING
read more
By sequencing clones obtained from a TH-1080 human fibroblast cDNA
library, Iwamuro et al. (1999) identified TMCO1, which they designated
HP10122. The deduced 188-amino acid protein has a calculated molecular
mass of 21.2 kD. It contains 3 putative hydrophobic regions, including
an N-terminal transmembrane helix. Northern blot analysis detected
variable expression of a 1.5-kb TMCO1 transcript in all tissues
examined. Expression was highest in thymus, prostate, testis, and small
intestine and weakest in brain, placenta, lung, and kidney.
Fluorescence-tagged TMCO1 was expressed in the endoplasmic reticulum and
Golgi perinuclear region of transfected COS-7 cells. In vitro
translation resulted in a major protein with an apparent molecular mass
of 23 kD. Iwamuro et al. (1999) also observed protein ladder bands
between 28 and 64 kD that represented polyubiquitinated TMCO1 produced
cotranslationally.
Zhang et al. (2010) cloned porcine Tmco1, which encodes a deduced
188-amino acid single-pass transmembrane protein that is 100% identical
to human TMCO1. Immunohistochemical analysis revealed that endogenous
Tmco1 localized to mitochondria in PK-15 porcine kidney cells.
Xin et al. (2010) reported ubiquitous expression of the TMCO1 gene in 16
adult human and 8 fetal human tissues, with relatively higher expression
in adult thymus, prostate, and testes.
Using RT-PCR, Burdon et al. (2011) demonstrated expression of TMCO1 in
human ocular tissues, including in the iris, ciliary body, retina, and
optic nerve.
GENE STRUCTURE
The TMCO1 gene contains 7 exons (Xin et al., 2010).
MAPPING
Zhang et al. (2010) stated that the TMCO1 gene maps to chromosome
1q22-q25.
Xin et al. (2010) noted that the TMCO1 gene maps to chromosome
1q23.3-q24.1.
MOLECULAR GENETICS
By genomewide homozygosity mapping followed by candidate gene
sequencing, Xin et al. (2010) identified homozygosity for a 2-bp
deletion in the TMCO1 gene (614123.0001) in 9 Ohio Amish patients with a
syndrome characterized by craniofacial dysmorphism, skeletal anomalies,
and mental retardation (CFSMR; 614132). Further analysis of the
Pennsylvania Amish population identified 6 patients with a similar
phenotype who were also homozygous for the 2-bp deletion. Two patients
from Somerset County, Pennsylvania, were on the same haplotype as the
Ohio Amish patients, and 3 patients from Lancaster County, Pennsylvania,
were on a different haplotype. Xin et al. (2010) proposed the
designation 'TMCO1 defect syndrome.'
For discussion of a possible association between variation near the
TMCO1 gene and open-angle glaucoma, see 137760.
In a 7-year-old Turkish boy with severe neurodevelopmental delay and
craniofacial and skeletal anomalies, Caglayan et al. (2013) identified
homozygosity for a nonsense mutation in the TMCO1 gene (R87X;
614123.0002).
*FIELD* AV
.0001
CRANIOFACIAL DYSMORPHISM, SKELETAL ANOMALIES, AND MENTAL RETARDATION
SYNDROME
TMCO1, 2-BP DEL, 139AG
In 9 Amish patients from northeastern Ohio with craniofacial
dysmorphism, skeletal anomalies, and mental retardation (CFSMR; 614132),
Xin et al. (2010) identified a homozygous 2-bp deletion (139delAG) in
exon 2 of the TMCO1 gene, resulting in a frameshift and premature
truncation at codon 47. Screening of ethnically matched controls from
the same community showed a carrier frequency of 0.7%. Screening of
Amish from southeastern Pennsylvania yielded a carrier frequency of
6.6%. Further analysis identified 6 homozygous carriers from
Pennsylvania who had a similar phenotype.
.0002
CRANIOFACIAL DYSMORPHISM, SKELETAL ANOMALIES, AND MENTAL RETARDATION
SYNDROME
TMCO1, ARG87TER
In a 7-year-old Turkish boy with severe neurodevelopmental delay and
craniofacial and skeletal anomalies (CFSMR; 614132), Caglayan et al.
(2013) identified homozygosity for a G-to-A transition in exon 5 of the
TMOC1 gene, resulting in an arg87-to-ter (R87X) substitution. The
mutation was found in heterozygosity in the available parent.
*FIELD* RF
1. Burdon, K. P.; Macgregor, S.; Hewitt, A. W.; Sharma, S.; Chidlow,
G.; Mills, R. A.; Danoy, P.; Casson, R.; Viswanathan, A. C.; Liu,
J. Z.; Landers, J.; Henders, A. K.; and 13 others: Genome-wide
association study identifies susceptibility loci for open angle glaucoma
at TMCO1 and CDKN2B-AS1. Nature Genet. 43: 574-578, 2011.
2. Caglayan, A. O.; Per, H.; Akgumus, G.; Gumus, H.; Baranoski, J.;
Canpolat, M.; Calik, M.; Yikilmaz, A.; Bilguvar, K.; Kumandas, S.;
Gunel, M.: Whole-exome sequencing identified a patient with TMCO1
defect syndrome and expands the phenotic (sic) spectrum. (Letter) Clin.
Genet. 84: 394-395, 2013.
3. Iwamuro, S.; Saeki, M.; Kato, S.: Multi-ubiquitination of a nascent
membrane protein produced in a rabbit reticulocyte lysate. J. Biochem. 126:
48-53, 1999.
4. Xin, B.; Puffenberger, E. G.; Turben, S.; Tan, H.; Zhou, A.; Wang,
H.: Homozygous frameshift mutation in TMCO1 causes a syndrome with
craniofacial dysmorphism, skeletal anomalies, and mental retardation. Proc.
Nat. Acad. Sci. 107: 258-263, 2010.
5. Zhang, Z.; Mo, D.; Cong, P.; He, Z.; Ling, F.; Li, A.; Niu, Y.;
Zhao, X.; Zhou, C.; Chen, Y.: Molecular cloning, expression patterns
and subcellular localization of porcine TMCO1 gene. Molec. Biol.
Rep. 37: 1611-1618, 2010.
*FIELD* CN
Marla J. F. O'Neill - updated: 11/7/2013
Marla J. F. O'Neill - updated: 12/6/2011
Cassandra L. Kniffin - updated: 8/1/2011
*FIELD* CD
Patricia A. Hartz: 7/26/2011
*FIELD* ED
alopez: 11/08/2013
mcolton: 11/7/2013
alopez: 12/7/2011
terry: 12/6/2011
wwang: 8/3/2011
ckniffin: 8/1/2011
mgross: 7/26/2011
*RECORD*
*FIELD* NO
614123
*FIELD* TI
*614123 TRANSMEMBRANE AND COILED-COIL DOMAINS PROTEIN 1; TMCO1
*FIELD* TX
CLONING
read more
By sequencing clones obtained from a TH-1080 human fibroblast cDNA
library, Iwamuro et al. (1999) identified TMCO1, which they designated
HP10122. The deduced 188-amino acid protein has a calculated molecular
mass of 21.2 kD. It contains 3 putative hydrophobic regions, including
an N-terminal transmembrane helix. Northern blot analysis detected
variable expression of a 1.5-kb TMCO1 transcript in all tissues
examined. Expression was highest in thymus, prostate, testis, and small
intestine and weakest in brain, placenta, lung, and kidney.
Fluorescence-tagged TMCO1 was expressed in the endoplasmic reticulum and
Golgi perinuclear region of transfected COS-7 cells. In vitro
translation resulted in a major protein with an apparent molecular mass
of 23 kD. Iwamuro et al. (1999) also observed protein ladder bands
between 28 and 64 kD that represented polyubiquitinated TMCO1 produced
cotranslationally.
Zhang et al. (2010) cloned porcine Tmco1, which encodes a deduced
188-amino acid single-pass transmembrane protein that is 100% identical
to human TMCO1. Immunohistochemical analysis revealed that endogenous
Tmco1 localized to mitochondria in PK-15 porcine kidney cells.
Xin et al. (2010) reported ubiquitous expression of the TMCO1 gene in 16
adult human and 8 fetal human tissues, with relatively higher expression
in adult thymus, prostate, and testes.
Using RT-PCR, Burdon et al. (2011) demonstrated expression of TMCO1 in
human ocular tissues, including in the iris, ciliary body, retina, and
optic nerve.
GENE STRUCTURE
The TMCO1 gene contains 7 exons (Xin et al., 2010).
MAPPING
Zhang et al. (2010) stated that the TMCO1 gene maps to chromosome
1q22-q25.
Xin et al. (2010) noted that the TMCO1 gene maps to chromosome
1q23.3-q24.1.
MOLECULAR GENETICS
By genomewide homozygosity mapping followed by candidate gene
sequencing, Xin et al. (2010) identified homozygosity for a 2-bp
deletion in the TMCO1 gene (614123.0001) in 9 Ohio Amish patients with a
syndrome characterized by craniofacial dysmorphism, skeletal anomalies,
and mental retardation (CFSMR; 614132). Further analysis of the
Pennsylvania Amish population identified 6 patients with a similar
phenotype who were also homozygous for the 2-bp deletion. Two patients
from Somerset County, Pennsylvania, were on the same haplotype as the
Ohio Amish patients, and 3 patients from Lancaster County, Pennsylvania,
were on a different haplotype. Xin et al. (2010) proposed the
designation 'TMCO1 defect syndrome.'
For discussion of a possible association between variation near the
TMCO1 gene and open-angle glaucoma, see 137760.
In a 7-year-old Turkish boy with severe neurodevelopmental delay and
craniofacial and skeletal anomalies, Caglayan et al. (2013) identified
homozygosity for a nonsense mutation in the TMCO1 gene (R87X;
614123.0002).
*FIELD* AV
.0001
CRANIOFACIAL DYSMORPHISM, SKELETAL ANOMALIES, AND MENTAL RETARDATION
SYNDROME
TMCO1, 2-BP DEL, 139AG
In 9 Amish patients from northeastern Ohio with craniofacial
dysmorphism, skeletal anomalies, and mental retardation (CFSMR; 614132),
Xin et al. (2010) identified a homozygous 2-bp deletion (139delAG) in
exon 2 of the TMCO1 gene, resulting in a frameshift and premature
truncation at codon 47. Screening of ethnically matched controls from
the same community showed a carrier frequency of 0.7%. Screening of
Amish from southeastern Pennsylvania yielded a carrier frequency of
6.6%. Further analysis identified 6 homozygous carriers from
Pennsylvania who had a similar phenotype.
.0002
CRANIOFACIAL DYSMORPHISM, SKELETAL ANOMALIES, AND MENTAL RETARDATION
SYNDROME
TMCO1, ARG87TER
In a 7-year-old Turkish boy with severe neurodevelopmental delay and
craniofacial and skeletal anomalies (CFSMR; 614132), Caglayan et al.
(2013) identified homozygosity for a G-to-A transition in exon 5 of the
TMOC1 gene, resulting in an arg87-to-ter (R87X) substitution. The
mutation was found in heterozygosity in the available parent.
*FIELD* RF
1. Burdon, K. P.; Macgregor, S.; Hewitt, A. W.; Sharma, S.; Chidlow,
G.; Mills, R. A.; Danoy, P.; Casson, R.; Viswanathan, A. C.; Liu,
J. Z.; Landers, J.; Henders, A. K.; and 13 others: Genome-wide
association study identifies susceptibility loci for open angle glaucoma
at TMCO1 and CDKN2B-AS1. Nature Genet. 43: 574-578, 2011.
2. Caglayan, A. O.; Per, H.; Akgumus, G.; Gumus, H.; Baranoski, J.;
Canpolat, M.; Calik, M.; Yikilmaz, A.; Bilguvar, K.; Kumandas, S.;
Gunel, M.: Whole-exome sequencing identified a patient with TMCO1
defect syndrome and expands the phenotic (sic) spectrum. (Letter) Clin.
Genet. 84: 394-395, 2013.
3. Iwamuro, S.; Saeki, M.; Kato, S.: Multi-ubiquitination of a nascent
membrane protein produced in a rabbit reticulocyte lysate. J. Biochem. 126:
48-53, 1999.
4. Xin, B.; Puffenberger, E. G.; Turben, S.; Tan, H.; Zhou, A.; Wang,
H.: Homozygous frameshift mutation in TMCO1 causes a syndrome with
craniofacial dysmorphism, skeletal anomalies, and mental retardation. Proc.
Nat. Acad. Sci. 107: 258-263, 2010.
5. Zhang, Z.; Mo, D.; Cong, P.; He, Z.; Ling, F.; Li, A.; Niu, Y.;
Zhao, X.; Zhou, C.; Chen, Y.: Molecular cloning, expression patterns
and subcellular localization of porcine TMCO1 gene. Molec. Biol.
Rep. 37: 1611-1618, 2010.
*FIELD* CN
Marla J. F. O'Neill - updated: 11/7/2013
Marla J. F. O'Neill - updated: 12/6/2011
Cassandra L. Kniffin - updated: 8/1/2011
*FIELD* CD
Patricia A. Hartz: 7/26/2011
*FIELD* ED
alopez: 11/08/2013
mcolton: 11/7/2013
alopez: 12/7/2011
terry: 12/6/2011
wwang: 8/3/2011
ckniffin: 8/1/2011
mgross: 7/26/2011
MIM
614132
*RECORD*
*FIELD* NO
614132
*FIELD* TI
#614132 CRANIOFACIAL DYSMORPHISM, SKELETAL ANOMALIES, AND MENTAL RETARDATION
SYNDROME; CFSMR
read more;;TMCO1 DEFECT SYNDROME
*FIELD* TX
A number sign (#) is used with this entry because this syndrome,
characterized by craniofacial dysmorphism, skeletal anomalies, and
mental retardation (CFSMR), is caused by homozygous mutation in the
TMCO1 gene (614123) on chromosome 1q23.3-q24.1.
CLINICAL FEATURES
Xin et al. (2010) described a mental retardation syndrome in 11 patients
from the Old Order Amish population of Geauga County in northeastern
Ohio. Some abnormalities, such as cleft lip and palate and
ventriculomegaly, could be observed from the prenatal period, although
not all patients had prenatal ultrasound. Features at birth included
hypotonia, poor feeding, and craniofacial dysmorphisms, including
brachycephaly, flat face, low hairline, low-set ears, high-arched
palate, and cleft lip and palate. Features that appeared later included
highly arched bushy eyebrows, synophrys, hypertelorism, long eyelashes,
wide nasal bridge, short nose with anteverted nares, microdontism, and
gingival hyperplasia. Skeletal dysmorphisms tended to involve the axial
skeleton, with pectus excavatum, scoliosis, vertebral fusion, and rib
anomalies. Two patients had tall stature, whereas 3 had short stature.
All had global developmental delay. Neurologic examination showed
hyporeflexia, unsteady gait, and intention tremor in some older
patients. Some had variable genitourinary anomalies, such as renal
agenesis, hydronephrosis, vesicoureteral reflux, and undescended testes.
First trimester spontaneous abortions occurred in 22% of pregnancies.
Caglayan et al. (2013) reported a 7-year-old Turkish boy, born of
first-cousin parents, who was hypotonic at birth and had feeding
difficulties, hypothyroidism, and significant neurodevelopmental delay.
His family reported that he was anxious and exhibited self-mutilating
behavior such as chewing his fingers. Examination at 7 years of age
revealed dysmorphic features including short neck, low hairline, low-set
ears, synophrys, hypertelorism, anteverted nares, high-arched palate,
prognathism, hyperextensible fingers, pectus carinatum, scoliosis, and
genu varus. He was awake but unable to speak, walk, or feed himself.
Brain MRI showed dysgenesis of the corpus callosum and cerebellar
herniation.
INHERITANCE
The transmission pattern in the families reported by Xin et al. (2010)
was consistent with autosomal recessive inheritance, since affected
individuals were of Old Order Amish descent, and genealogic analysis
revealed multiple lines of common descent between all parents of
affected children.
MOLECULAR GENETICS
By genomewide homozygosity mapping followed by candidate gene
sequencing, Xin et al. (2010) identified homozygosity for a 2-bp
deletion in the TMCO1 gene (614123.0001) in 9 of 11 northeastern Ohio
Amish patients with a mental retardation syndrome and skeletal
anomalies. Two patients were deceased, and their genotype was not
confirmed. Screening of ethnically matched controls from the same
community showed a carrier frequency of 0.7%. Screening of Old Order
Amish from southeastern Pennsylvania yielded a carrier frequency of
6.6%. Further analysis identified 6 more patients from Pennsylvania with
a similar phenotype who were also homozygous for the 2-bp deletion. Two
patients from Somerset County, Pennsylvania, were on the same haplotype
as the Ohio Amish patients, and 3 patients from Lancaster County,
Pennsylvania, were on a different haplotype. Xin et al. (2010) proposed
the designation 'TMCO1 defect syndrome.'
In a 7-year-old Turkish boy with mental retardation and craniofacial and
skeletal anomalies, Caglayan et al. (2013) performed homozygosity
mapping followed by exome sequencing and identified homozygosity for a
nonsense mutation in the TMCO1 gene (R87X; 614123.0002). The mutation
was found in heterozygosity in the available parent. In contrast to
patients previously described with TMOC1 deficiency, Caglayan et al.
(2013) noted that this patient had more profound developmental
impairment and did not show craniosynostosis or spinal fusion, which
occurred in 18% and 55% of the original cases, respectively.
*FIELD* RF
1. Caglayan, A. O.; Per, H.; Akgumus, G.; Gumus, H.; Baranoski, J.;
Canpolat, M.; Calik, M.; Yikilmaz, A.; Bilguvar, K.; Kumandas, S.;
Gunel, M.: Whole-exome sequencing identified a patient with TMCO1
defect syndrome and expands the phenotic (sic) spectrum. (Letter) Clin.
Genet. 84: 394-395, 2013.
2. Xin, B.; Puffenberger, E. G.; Turben, S.; Tan, H.; Zhou, A.; Wang,
H.: Homozygous frameshift mutation in TMCO1 causes a syndrome with
craniofacial dysmorphism, skeletal anomalies, and mental retardation. Proc.
Nat. Acad. Sci. 107: 258-263, 2010.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Tall stature;
Short stature
HEAD AND NECK:
[Head];
Brachycephaly;
Macrocephalic appearance (90%);
[Face];
Flat face;
[Ears];
Low-set ears;
[Eyes];
Hypertelorism;
Strabismus (45%);
High arched eyebrows;
Bushy eyebrows;
Synophrys;
Long eyelashes;
[Nose];
Wide nasal bridge;
Short nose;
Anteverted nares;
[Mouth];
High arched palate;
Cleft lip (27%);
Cleft palate (27%);
Gingival hyperplasia;
[Teeth];
Microdontism of primary teeth;
[Neck];
Short neck (55%)
CHEST:
[External features];
Pectus excavatum (82%);
Pectus carinatum (in some patients);
[Ribs, sternum, clavicles, and scapulae];
Rib abnormalities (55%);
Rib fusion;
Sprengel anomaly (80%)
ABDOMEN:
[Gastrointestinal];
Poor feeding;
Constipation (64%)
GENITOURINARY:
Urogenital abnormalities (45%)
SKELETAL:
[Skull];
Craniosynostosis (18%);
[Spine];
Vertebral fusion (55%);
Scoliosis (64%);
[Limbs];
Genu varus (in some patients);
[Hands];
Long, hyperextensible fingers (55%);
[Feet];
Pes planus;
Club feet (27%)
SKIN, NAILS, HAIR:
[Hair];
Low hairline;
Hypertrichosis (64%);
Bushy eyebrows;
Synophrys;
Long eyelashes
MUSCLE, SOFT TISSUE:
Hypotonia
NEUROLOGIC:
[Central nervous system];
Delayed psychomotor development;
Mental retardation;
Lack of speech development (45%);
Hypotonia;
Unstable gait;
Intention tremor (55%);
Enlarged ventricles (57%);
Dysgenesis of corpus callosum (in some patients);
Cerebellar herniation (in some patients);
[Peripheral nervous system];
Hyporeflexia (90%);
[Behavioral/psychiatric manifestations];
Anxiety (64%);
Self-mutilating behavior (in some patients)
PRENATAL MANIFESTATIONS:
[Movement];
Decreased fetal movements (36%);
[Amniotic fluid];
Polyhydramnios (36%)
MISCELLANEOUS:
Onset at prenatally or at birth;
Variable phenotype;
Patients from Old Order Amish community and Turkey have been reported
MOLECULAR BASIS:
Caused by mutation in the transmembrane and coiled-coil domains protein
1 gene (TMCO1, 614123.0001)
*FIELD* CN
Marla J. F. O'Neill - updated: 12/09/2013
*FIELD* CD
Cassandra L. Kniffin: 7/28/2011
*FIELD* ED
joanna: 12/09/2013
joanna: 12/29/2011
ckniffin: 8/1/2011
*FIELD* CN
Marla J. F. O'Neill - updated: 11/7/2013
*FIELD* CD
Cassandra L. Kniffin: 7/28/2011
*FIELD* ED
alopez: 11/08/2013
mcolton: 11/7/2013
wwang: 8/3/2011
ckniffin: 8/1/2011
*RECORD*
*FIELD* NO
614132
*FIELD* TI
#614132 CRANIOFACIAL DYSMORPHISM, SKELETAL ANOMALIES, AND MENTAL RETARDATION
SYNDROME; CFSMR
read more;;TMCO1 DEFECT SYNDROME
*FIELD* TX
A number sign (#) is used with this entry because this syndrome,
characterized by craniofacial dysmorphism, skeletal anomalies, and
mental retardation (CFSMR), is caused by homozygous mutation in the
TMCO1 gene (614123) on chromosome 1q23.3-q24.1.
CLINICAL FEATURES
Xin et al. (2010) described a mental retardation syndrome in 11 patients
from the Old Order Amish population of Geauga County in northeastern
Ohio. Some abnormalities, such as cleft lip and palate and
ventriculomegaly, could be observed from the prenatal period, although
not all patients had prenatal ultrasound. Features at birth included
hypotonia, poor feeding, and craniofacial dysmorphisms, including
brachycephaly, flat face, low hairline, low-set ears, high-arched
palate, and cleft lip and palate. Features that appeared later included
highly arched bushy eyebrows, synophrys, hypertelorism, long eyelashes,
wide nasal bridge, short nose with anteverted nares, microdontism, and
gingival hyperplasia. Skeletal dysmorphisms tended to involve the axial
skeleton, with pectus excavatum, scoliosis, vertebral fusion, and rib
anomalies. Two patients had tall stature, whereas 3 had short stature.
All had global developmental delay. Neurologic examination showed
hyporeflexia, unsteady gait, and intention tremor in some older
patients. Some had variable genitourinary anomalies, such as renal
agenesis, hydronephrosis, vesicoureteral reflux, and undescended testes.
First trimester spontaneous abortions occurred in 22% of pregnancies.
Caglayan et al. (2013) reported a 7-year-old Turkish boy, born of
first-cousin parents, who was hypotonic at birth and had feeding
difficulties, hypothyroidism, and significant neurodevelopmental delay.
His family reported that he was anxious and exhibited self-mutilating
behavior such as chewing his fingers. Examination at 7 years of age
revealed dysmorphic features including short neck, low hairline, low-set
ears, synophrys, hypertelorism, anteverted nares, high-arched palate,
prognathism, hyperextensible fingers, pectus carinatum, scoliosis, and
genu varus. He was awake but unable to speak, walk, or feed himself.
Brain MRI showed dysgenesis of the corpus callosum and cerebellar
herniation.
INHERITANCE
The transmission pattern in the families reported by Xin et al. (2010)
was consistent with autosomal recessive inheritance, since affected
individuals were of Old Order Amish descent, and genealogic analysis
revealed multiple lines of common descent between all parents of
affected children.
MOLECULAR GENETICS
By genomewide homozygosity mapping followed by candidate gene
sequencing, Xin et al. (2010) identified homozygosity for a 2-bp
deletion in the TMCO1 gene (614123.0001) in 9 of 11 northeastern Ohio
Amish patients with a mental retardation syndrome and skeletal
anomalies. Two patients were deceased, and their genotype was not
confirmed. Screening of ethnically matched controls from the same
community showed a carrier frequency of 0.7%. Screening of Old Order
Amish from southeastern Pennsylvania yielded a carrier frequency of
6.6%. Further analysis identified 6 more patients from Pennsylvania with
a similar phenotype who were also homozygous for the 2-bp deletion. Two
patients from Somerset County, Pennsylvania, were on the same haplotype
as the Ohio Amish patients, and 3 patients from Lancaster County,
Pennsylvania, were on a different haplotype. Xin et al. (2010) proposed
the designation 'TMCO1 defect syndrome.'
In a 7-year-old Turkish boy with mental retardation and craniofacial and
skeletal anomalies, Caglayan et al. (2013) performed homozygosity
mapping followed by exome sequencing and identified homozygosity for a
nonsense mutation in the TMCO1 gene (R87X; 614123.0002). The mutation
was found in heterozygosity in the available parent. In contrast to
patients previously described with TMOC1 deficiency, Caglayan et al.
(2013) noted that this patient had more profound developmental
impairment and did not show craniosynostosis or spinal fusion, which
occurred in 18% and 55% of the original cases, respectively.
*FIELD* RF
1. Caglayan, A. O.; Per, H.; Akgumus, G.; Gumus, H.; Baranoski, J.;
Canpolat, M.; Calik, M.; Yikilmaz, A.; Bilguvar, K.; Kumandas, S.;
Gunel, M.: Whole-exome sequencing identified a patient with TMCO1
defect syndrome and expands the phenotic (sic) spectrum. (Letter) Clin.
Genet. 84: 394-395, 2013.
2. Xin, B.; Puffenberger, E. G.; Turben, S.; Tan, H.; Zhou, A.; Wang,
H.: Homozygous frameshift mutation in TMCO1 causes a syndrome with
craniofacial dysmorphism, skeletal anomalies, and mental retardation. Proc.
Nat. Acad. Sci. 107: 258-263, 2010.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Tall stature;
Short stature
HEAD AND NECK:
[Head];
Brachycephaly;
Macrocephalic appearance (90%);
[Face];
Flat face;
[Ears];
Low-set ears;
[Eyes];
Hypertelorism;
Strabismus (45%);
High arched eyebrows;
Bushy eyebrows;
Synophrys;
Long eyelashes;
[Nose];
Wide nasal bridge;
Short nose;
Anteverted nares;
[Mouth];
High arched palate;
Cleft lip (27%);
Cleft palate (27%);
Gingival hyperplasia;
[Teeth];
Microdontism of primary teeth;
[Neck];
Short neck (55%)
CHEST:
[External features];
Pectus excavatum (82%);
Pectus carinatum (in some patients);
[Ribs, sternum, clavicles, and scapulae];
Rib abnormalities (55%);
Rib fusion;
Sprengel anomaly (80%)
ABDOMEN:
[Gastrointestinal];
Poor feeding;
Constipation (64%)
GENITOURINARY:
Urogenital abnormalities (45%)
SKELETAL:
[Skull];
Craniosynostosis (18%);
[Spine];
Vertebral fusion (55%);
Scoliosis (64%);
[Limbs];
Genu varus (in some patients);
[Hands];
Long, hyperextensible fingers (55%);
[Feet];
Pes planus;
Club feet (27%)
SKIN, NAILS, HAIR:
[Hair];
Low hairline;
Hypertrichosis (64%);
Bushy eyebrows;
Synophrys;
Long eyelashes
MUSCLE, SOFT TISSUE:
Hypotonia
NEUROLOGIC:
[Central nervous system];
Delayed psychomotor development;
Mental retardation;
Lack of speech development (45%);
Hypotonia;
Unstable gait;
Intention tremor (55%);
Enlarged ventricles (57%);
Dysgenesis of corpus callosum (in some patients);
Cerebellar herniation (in some patients);
[Peripheral nervous system];
Hyporeflexia (90%);
[Behavioral/psychiatric manifestations];
Anxiety (64%);
Self-mutilating behavior (in some patients)
PRENATAL MANIFESTATIONS:
[Movement];
Decreased fetal movements (36%);
[Amniotic fluid];
Polyhydramnios (36%)
MISCELLANEOUS:
Onset at prenatally or at birth;
Variable phenotype;
Patients from Old Order Amish community and Turkey have been reported
MOLECULAR BASIS:
Caused by mutation in the transmembrane and coiled-coil domains protein
1 gene (TMCO1, 614123.0001)
*FIELD* CN
Marla J. F. O'Neill - updated: 12/09/2013
*FIELD* CD
Cassandra L. Kniffin: 7/28/2011
*FIELD* ED
joanna: 12/09/2013
joanna: 12/29/2011
ckniffin: 8/1/2011
*FIELD* CN
Marla J. F. O'Neill - updated: 11/7/2013
*FIELD* CD
Cassandra L. Kniffin: 7/28/2011
*FIELD* ED
alopez: 11/08/2013
mcolton: 11/7/2013
wwang: 8/3/2011
ckniffin: 8/1/2011