TMTC2_HUMAN
ID TMTC2_HUMAN Reviewed; 836 AA.
AC Q8N394; B2RCU7; Q8N2K8;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Protein O-mannosyl-transferase TMTC2 {ECO:0000305};
DE EC=2.4.1.109 {ECO:0000269|PubMed:28973932};
DE AltName: Full=Transmembrane and TPR repeat-containing protein 2 {ECO:0000312|HGNC:HGNC:25440};
GN Name=TMTC2 {ECO:0000312|HGNC:HGNC:25440};
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].
RC TISSUE=Brain, and Embryo;
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 MRNA].
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=28973932; DOI=10.1073/pnas.1708319114;
RA Larsen I.S.B., Narimatsu Y., Joshi H.J., Siukstaite L., Harrison O.J.,
RA Brasch J., Goodman K.M., Hansen L., Shapiro L., Honig B., Vakhrushev S.Y.,
RA Clausen H., Halim A.;
RT "Discovery of an O-mannosylation pathway selectively serving cadherins and
RT protocadherins.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:11163-11168(2017).
CC -!- FUNCTION: Transfers mannosyl residues to the hydroxyl group of serine
CC or threonine residues. The 4 members of the TMTC family are O-mannosyl-
CC transferases dedicated primarily to the cadherin superfamily, each
CC member seems to have a distinct role in decorating the cadherin domains
CC with O-linked mannose glycans at specific regions. Also acts as O-
CC mannosyl-transferase on other proteins such as PDIA3.
CC {ECO:0000269|PubMed:28973932}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a dolichyl beta-D-mannosyl phosphate + L-seryl-[protein] = 3-
CC O-(alpha-D-mannosyl)-L-seryl-[protein] + a dolichyl phosphate + H(+);
CC Xref=Rhea:RHEA:17377, Rhea:RHEA-COMP:9517, Rhea:RHEA-COMP:9527,
CC Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:13546, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29999, ChEBI:CHEBI:57683, ChEBI:CHEBI:58211,
CC ChEBI:CHEBI:137321; EC=2.4.1.109;
CC Evidence={ECO:0000269|PubMed:28973932};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17378;
CC Evidence={ECO:0000269|PubMed:28973932};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a dolichyl beta-D-mannosyl phosphate + L-threonyl-[protein] =
CC 3-O-(alpha-D-mannosyl)-L-threonyl-[protein] + a dolichyl phosphate +
CC H(+); Xref=Rhea:RHEA:53396, Rhea:RHEA-COMP:9517, Rhea:RHEA-COMP:9527,
CC Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:13547, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:57683, ChEBI:CHEBI:58211,
CC ChEBI:CHEBI:137323; EC=2.4.1.109;
CC Evidence={ECO:0000269|PubMed:28973932};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53397;
CC Evidence={ECO:0000269|PubMed:28973932};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000269|PubMed:28973932}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Endoplasmic reticulum {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the TMTC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC11102.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK074634; BAC11102.1; ALT_INIT; mRNA.
DR EMBL; AK315285; BAG37694.1; -; mRNA.
DR EMBL; AL834509; CAD39165.1; -; mRNA.
DR EMBL; CH471054; EAW97384.1; -; Genomic_DNA.
DR EMBL; BC093852; AAH93852.1; -; mRNA.
DR EMBL; BC093854; AAH93854.1; -; mRNA.
DR CCDS; CCDS9025.1; -.
DR RefSeq; NP_001307250.1; NM_001320321.1.
DR RefSeq; NP_689801.1; NM_152588.2.
DR AlphaFoldDB; Q8N394; -.
DR SMR; Q8N394; -.
DR BioGRID; 127753; 84.
DR IntAct; Q8N394; 5.
DR MINT; Q8N394; -.
DR STRING; 9606.ENSP00000322300; -.
DR GlyGen; Q8N394; 1 site.
DR iPTMnet; Q8N394; -.
DR PhosphoSitePlus; Q8N394; -.
DR BioMuta; TMTC2; -.
DR DMDM; 74759843; -.
DR EPD; Q8N394; -.
DR jPOST; Q8N394; -.
DR MassIVE; Q8N394; -.
DR MaxQB; Q8N394; -.
DR PaxDb; Q8N394; -.
DR PeptideAtlas; Q8N394; -.
DR PRIDE; Q8N394; -.
DR ProteomicsDB; 71782; -.
DR Antibodypedia; 29839; 51 antibodies from 16 providers.
DR DNASU; 160335; -.
DR Ensembl; ENST00000321196.8; ENSP00000322300.3; ENSG00000179104.9.
DR GeneID; 160335; -.
DR KEGG; hsa:160335; -.
DR MANE-Select; ENST00000321196.8; ENSP00000322300.3; NM_152588.3; NP_689801.1.
DR UCSC; uc001szt.5; human.
DR CTD; 160335; -.
DR DisGeNET; 160335; -.
DR GeneCards; TMTC2; -.
DR HGNC; HGNC:25440; TMTC2.
DR HPA; ENSG00000179104; Tissue enriched (brain).
DR MIM; 615856; gene.
DR neXtProt; NX_Q8N394; -.
DR OpenTargets; ENSG00000179104; -.
DR PharmGKB; PA142670719; -.
DR VEuPathDB; HostDB:ENSG00000179104; -.
DR eggNOG; KOG1124; Eukaryota.
DR GeneTree; ENSGT00940000156144; -.
DR HOGENOM; CLU_011615_4_0_1; -.
DR InParanoid; Q8N394; -.
DR OMA; DYTCLFC; -.
DR OrthoDB; 1320023at2759; -.
DR PhylomeDB; Q8N394; -.
DR TreeFam; TF328339; -.
DR PathwayCommons; Q8N394; -.
DR SignaLink; Q8N394; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 160335; 8 hits in 1078 CRISPR screens.
DR ChiTaRS; TMTC2; human.
DR GeneWiki; TMTC2; -.
DR GenomeRNAi; 160335; -.
DR Pharos; Q8N394; Tbio.
DR PRO; PR:Q8N394; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q8N394; protein.
DR Bgee; ENSG00000179104; Expressed in ventricular zone and 169 other tissues.
DR ExpressionAtlas; Q8N394; baseline and differential.
DR Genevisible; Q8N394; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004169; F:dolichyl-phosphate-mannose-protein mannosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0000030; F:mannosyltransferase activity; IMP:UniProtKB.
DR GO; GO:0055074; P:calcium ion homeostasis; IMP:UniProtKB.
DR GO; GO:0035269; P:protein O-linked mannosylation; IMP:UniProtKB.
DR Gene3D; 1.25.40.10; -; 3.
DR InterPro; IPR013618; TMTC_DUF1736.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR001440; TPR_1.
DR InterPro; IPR019734; TPR_repeat.
DR Pfam; PF08409; DUF1736; 1.
DR Pfam; PF00515; TPR_1; 1.
DR Pfam; PF13181; TPR_8; 1.
DR SMART; SM00028; TPR; 8.
DR SUPFAM; SSF48452; SSF48452; 2.
DR PROSITE; PS50005; TPR; 9.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Membrane; Reference proteome; Repeat;
KW TPR repeat; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..836
FT /note="Protein O-mannosyl-transferase TMTC2"
FT /id="PRO_0000280290"
FT TRANSMEM 85..105
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 108..128
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 133..153
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 163..183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 184..204
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 222..241
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 313..333
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 400..420
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 423..443
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 450..470
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REPEAT 462..492
FT /note="TPR 1"
FT REPEAT 493..526
FT /note="TPR 2"
FT REPEAT 527..560
FT /note="TPR 3"
FT REPEAT 562..594
FT /note="TPR 4"
FT REPEAT 606..639
FT /note="TPR 5"
FT REPEAT 643..676
FT /note="TPR 6"
FT REPEAT 677..710
FT /note="TPR 7"
FT REPEAT 712..744
FT /note="TPR 8"
FT REPEAT 746..778
FT /note="TPR 9"
FT REPEAT 779..812
FT /note="TPR 10"
FT CARBOHYD 221
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 315
FT /note="A -> T (in dbSNP:rs1201791)"
FT /id="VAR_031113"
FT VARIANT 443
FT /note="Y -> S (in dbSNP:rs17010106)"
FT /id="VAR_031114"
FT VARIANT 741
FT /note="D -> Y (in dbSNP:rs428398)"
FT /id="VAR_053852"
SQ SEQUENCE 836 AA; 94130 MW; C61517F1B39B3A28 CRC64;
MIAELVSSAL GLALYLNTLS ADFCYDDSRA IKTNQDLLPE TPWTHIFYND FWGTLLTHSG
SHKSYRPLCT LSFRLNHAIG GLNPWSYHLV NVLLHAAVTG LFTSFSKILL GDGYWTFMAG
LMFASHPIHT EAVAGIVGRA DVGASLFFLL SLLCYIKHCS TRGYSARTWG WFLGSGLCAG
CSMLWKEQGV TVLAVSAVYD VFVFHRLKIK QILPTIYKRK NLSLFLSISL LIFWGSSLLG
ARLYWMGNKP PSFSNSDNPA ADSDSLLTRT LTFFYLPTKN LWLLLCPDTL SFDWSMDAVP
LLKTVCDWRN LHTVAFYTGL LLLAYYGLKS PSVDRECNGK TVTNGKQNAN GHSCLSDVEY
QNSETKSSFA SKVENGIKND VSQRTQLPST ENIVVLSLSL LIIPFVPATN LFFYVGFVIA
ERVLYIPSMG FCLLITVGAR ALYVKVQKRF LKSLIFYATA TLIVFYGLKT AIRNGDWQNE
EMLYRSGIKV NPAKAWGNLG NVLKSQSKIS EAESAYRNAL YYRSNMADML YNLGLLLQEN
SRFAEALHYY KLAIGSRPTL ASAYLNTGII LMNQGRTEEA RRTFLKCSEI PDENLKDPHA
HKSSVTSCLY NLGKLYHEQG HYEEALSVYK EAIQKMPRQF APQSLYNMMG EAYMRLSKLP
EAEHWYMESL RSKTDHIPAH LTYGKLLALT GRKSEAEKLF LKAIELDPTK GNCYMHYGQF
LLEEARLIEA AEMAKKAAEL DSTEFDVVFN AAHMLRQASL NEAAEKYYDL AARLRPNYPA
ALMNLGAILH LNGRLQKAEA NYLRALQLKP DDVITQSNLR KLWNIMEKQG LKTSKT
