LOCUS       NP_689801                836 aa            linear   PRI 27-APR-2025
DEFINITION  protein O-mannosyl-transferase TMTC2 isoform 1 precursor [Homo
            sapiens].
ACCESSION   NP_689801
VERSION     NP_689801.1
DBSOURCE    REFSEQ: accession NM_152588.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 836)
  AUTHORS   Eisenhaber,B., Sinha,S., Jadalanki,C.K., Shitov,V.A., Tan,Q.W.,
            Sirota,F.L. and Eisenhaber,F.
  TITLE     Conserved sequence motifs in human TMTC1, TMTC2, TMTC3, and TMTC4,
            new O-mannosyltransferases from the GT-C/PMT clan, are rationalized
            as ligand binding sites
  JOURNAL   Biol Direct 16 (1), 4 (2021)
   PUBMED   33436046
  REMARK    GeneRIF: Conserved sequence motifs in human TMTC1, TMTC2, TMTC3,
            and TMTC4, new O-mannosyltransferases from the GT-C/PMT clan, are
            rationalized as ligand binding sites.
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 836)
  AUTHORS   Wasserman,J.K., Dickson,B.C., Smith,A., Swanson,D., Purgina,B.M.
            and Weinreb,I.
  TITLE     Metastasizing Pleomorphic Adenoma: Recurrent PLAG1/HMGA2
            Rearrangements and Identification of a Novel HMGA2-TMTC2 Fusion
  JOURNAL   Am J Surg Pathol 43 (8), 1145-1151 (2019)
   PUBMED   31094927
  REMARK    GeneRIF: Metastasizing pleomorphic adenomas with recurrent
            PLAG1/HMGA2 gene rearrangements and a novel HMGA2-TMTC2 fusion.
REFERENCE   3  (residues 1 to 836)
  AUTHORS   Kondkar,A.A., Azad,T.A., Almobarak,F.A., Abu-Amero,K.K. and
            Al-Obeidan,S.A.
  TITLE     Polymorphism rs7961953 in TMTC2 gene is not associated with primary
            open-angle glaucoma in a Saudi cohort
  JOURNAL   Ophthalmic Genet 40 (1), 74-76 (2019)
   PUBMED   30729851
  REMARK    GeneRIF: Polymorphism rs7961953 in TMTC2 gene is not associated
            with primary open-angle glaucoma.
REFERENCE   4  (residues 1 to 836)
  AUTHORS   Larsen,I.S.B., Narimatsu,Y., Joshi,H.J., Siukstaite,L.,
            Harrison,O.J., Brasch,J., Goodman,K.M., Hansen,L., Shapiro,L.,
            Honig,B., Vakhrushev,S.Y., Clausen,H. and Halim,A.
  TITLE     Discovery of an O-mannosylation pathway selectively serving
            cadherins and protocadherins
  JOURNAL   Proc Natl Acad Sci U S A 114 (42), 11163-11168 (2017)
   PUBMED   28973932
REFERENCE   5  (residues 1 to 836)
  AUTHORS   Runge,C.L., Indap,A., Zhou,Y., Kent,J.W. Jr., King,E., Erbe,C.B.,
            Cole,R., Littrell,J., Merath,K., James,R., Ruschendorf,F.,
            Kerschner,J.E., Marth,G., Hubner,N., Goring,H.H., Friedland,D.R.,
            Kwok,W.M. and Olivier,M.
  TITLE     Association of TMTC2 With Human Nonsyndromic Sensorineural Hearing
            Loss
  JOURNAL   JAMA Otolaryngol Head Neck Surg 142 (9), 866-872 (2016)
   PUBMED   27311106
  REMARK    GeneRIF: A previously uncharacterized gene, TMTC2, has been
            identified as a candidate for causing progressive sensorineural
            hearing loss in humans. This finding identifies a novel locus that
            causes autosomal dominant SNHL.
REFERENCE   6  (residues 1 to 836)
  AUTHORS   Sunryd,J.C., Cheon,B., Graham,J.B., Giorda,K.M., Fissore,R.A. and
            Hebert,D.N.
  TITLE     TMTC1 and TMTC2 are novel endoplasmic reticulum tetratricopeptide
            repeat-containing adapter proteins involved in calcium homeostasis
  JOURNAL   J Biol Chem 289 (23), 16085-16099 (2014)
   PUBMED   24764305
  REMARK    GeneRIF: findings provide an important link between aneuploidy and
            the stress pathways activated by Aurora B inhibition and also
            support the use of Aurora B inhibitors in combination therapy for
            treatment of cancer.
REFERENCE   7  (residues 1 to 836)
  AUTHORS   Nakano,M., Ikeda,Y., Taniguchi,T., Yagi,T., Fuwa,M., Omi,N.,
            Tokuda,Y., Tanaka,M., Yoshii,K., Kageyama,M., Naruse,S.,
            Matsuda,A., Mori,K., Kinoshita,S. and Tashiro,K.
  TITLE     Three susceptible loci associated with primary open-angle glaucoma
            identified by genome-wide association study in a Japanese
            population
  JOURNAL   Proc Natl Acad Sci U S A 106 (31), 12838-12842 (2009)
   PUBMED   19625618
  REMARK    GeneRIF: Observational study and genome-wide association study of
            gene-disease association. (HuGE Navigator)
REFERENCE   8  (residues 1 to 836)
  AUTHORS   Mole,D.R., Blancher,C., Copley,R.R., Pollard,P.J., Gleadle,J.M.,
            Ragoussis,J. and Ratcliffe,P.J.
  TITLE     Genome-wide association of hypoxia-inducible factor (HIF)-1alpha
            and HIF-2alpha DNA binding with expression profiling of
            hypoxia-inducible transcripts
  JOURNAL   J Biol Chem 284 (25), 16767-16775 (2009)
   PUBMED   19386601
  REMARK    GeneRIF: TMTC2 expression induced by HIF-2alpha.
REFERENCE   9  (residues 1 to 836)
  AUTHORS   Uhl,G.R., Liu,Q.R., Drgon,T., Johnson,C., Walther,D., Rose,J.E.,
            David,S.P., Niaura,R. and Lerman,C.
  TITLE     Molecular genetics of successful smoking cessation: convergent
            genome-wide association study results
  JOURNAL   Arch Gen Psychiatry 65 (6), 683-693 (2008)
   PUBMED   18519826
  REMARK    GeneRIF: Clinical trial and genome-wide association study of
            gene-disease association, gene-environment interaction, and
            pharmacogenomic / toxicogenomic. (HuGE Navigator)
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC091214.20, AL834509.1 and
            BC071614.1.
            
            Summary: The protein encoded by this gene is an integral membrane
            protein localized to the endoplasmic reticulum (ER). The encoded
            protein contains many tetratricopeptide repeats, sequences known
            for being involved in protein-protein interactions. This protein
            binds both the calcium uptake pump SERCA2B and the
            carbohydrate-binding chaperone calnexin, and it appears to play a
            role in calcium homeostasis in the ER. Multiple transcript variants
            encoding different isoforms have been found for this gene.
            [provided by RefSeq, Feb 2016].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1).
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1803614.136354.1,
                                           SRR1803615.89632.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1968189
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000321196.8/ ENSP00000322300.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..836
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q21.31"
     Protein         1..836
                     /product="protein O-mannosyl-transferase TMTC2 isoform 1
                     precursor"
                     /EC_number="2.4.1.109"
                     /note="transmembrane and TPR repeat-containing protein 2;
                     transmembrane and tetratricopeptide repeat containing 2;
                     protein O-mannosyl-transferase TMTC2"
                     /calculated_mol_wt=91998
     sig_peptide     1..21
                     /inference="COORDINATES: ab initio prediction:SignalP:6.0"
                     /calculated_mol_wt=2151
     Site            1..21
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Region          <78..>198
                     /region_name="ArnT"
                     /note="PMT family glycosyltransferase ArnT/Agl22, involved
                     in glycosylation of proteins and lipid IVA [Cell
                     wall/membrane/envelope biogenesis]; COG1807"
                     /db_xref="CDD:441412"
     Site            85..105
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Site            108..128
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Site            133..153
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Site            163..184
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Site            185..204
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Site            221..241
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Region          247..318
                     /region_name="TMTC_DUF1736"
                     /note="Protein O-mannosyl-transferase TMTC, DUF1736;
                     pfam08409"
                     /db_xref="CDD:462468"
     Site            313..333
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Site            400..420
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Site            423..443
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Site            450..470
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Region          488..727
                     /region_name="TPR"
                     /note="Tetratricopeptide (TPR) repeat [General function
                     prediction only]; COG0457"
                     /db_xref="CDD:440225"
     Region          493..526
                     /region_name="TPR 1.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00339"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Region          493..521
                     /region_name="TPR repeat"
                     /note="TPR repeat [structural motif]"
                     /db_xref="CDD:276809"
     Region          527..560
                     /region_name="TPR 2.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00339"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Region          527..555
                     /region_name="TPR repeat"
                     /note="TPR repeat [structural motif]"
                     /db_xref="CDD:276809"
     Site            order(528,531..532,535..536,538,562,565..566,569..570,
                     572..573,596,610..611,614..615,618)
                     /site_type="other"
                     /note="putative protein binding surface [polypeptide
                     binding]"
                     /db_xref="CDD:276809"
     Region          560..590
                     /region_name="TPR repeat"
                     /note="TPR repeat [structural motif]"
                     /db_xref="CDD:276809"
     Region          561..594
                     /region_name="TPR 3.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00339"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Region          595..634
                     /region_name="TPR repeat"
                     /note="TPR repeat [structural motif]"
                     /db_xref="CDD:276809"
     Region          606..639
                     /region_name="TPR 4.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00339"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Region          642..671
                     /region_name="TPR repeat"
                     /note="TPR repeat [structural motif]"
                     /db_xref="CDD:276809"
     Region          643..676
                     /region_name="TPR 5.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00339"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Region          646..>819
                     /region_name="TPR"
                     /note="Tetratricopeptide (TPR) repeat [General function
                     prediction only]; COG0457"
                     /db_xref="CDD:440225"
     Region          677..710
                     /region_name="TPR 6.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00339"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Region          679..705
                     /region_name="TPR repeat"
                     /note="TPR repeat [structural motif]"
                     /db_xref="CDD:276809"
     Site            order(681..682,685..686,688,712,715..716,719..720,
                     722..723,780,783..784,787..788,791)
                     /site_type="other"
                     /note="putative protein binding surface [polypeptide
                     binding]"
                     /db_xref="CDD:276809"
     Region          710..774
                     /region_name="TPR repeat"
                     /note="TPR repeat [structural motif]"
                     /db_xref="CDD:276809"
     Region          711..744
                     /region_name="TPR 7.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00339"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Region          745..778
                     /region_name="TPR 8.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00339"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Region          779..812
                     /region_name="TPR 9.
                     /evidence=ECO:0000255|PROSITE-ProRule:PRU00339"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8N394.1)"
     Region          779..807
                     /region_name="TPR repeat"
                     /note="TPR repeat [structural motif]"
                     /db_xref="CDD:276809"
     CDS             1..836
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /coded_by="NM_152588.3:682..3192"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1"
                     /db_xref="CCDS:CCDS9025.1"
                     /db_xref="GeneID:160335"
                     /db_xref="HGNC:HGNC:25440"
                     /db_xref="MIM:615856"
ORIGIN      
        1 miaelvssal glalylntls adfcyddsra iktnqdllpe tpwthifynd fwgtllthsg
       61 shksyrplct lsfrlnhaig glnpwsyhlv nvllhaavtg lftsfskill gdgywtfmag
      121 lmfashpiht eavagivgra dvgaslffll sllcyikhcs trgysartwg wflgsglcag
      181 csmlwkeqgv tvlavsavyd vfvfhrlkik qilptiykrk nlslflsisl lifwgssllg
      241 arlywmgnkp psfsnsdnpa adsdslltrt ltffylptkn lwlllcpdtl sfdwsmdavp
      301 llktvcdwrn lhtvafytgl lllayyglks psvdrecngk tvtngkqnan ghsclsdvey
      361 qnsetkssfa skvengiknd vsqrtqlpst enivvlslsl liipfvpatn lffyvgfvia
      421 ervlyipsmg fcllitvgar alyvkvqkrf lkslifyata tlivfyglkt airngdwqne
      481 emlyrsgikv npakawgnlg nvlksqskis eaesayrnal yyrsnmadml ynlglllqen
      541 srfaealhyy klaigsrptl asaylntgii lmnqgrteea rrtflkcsei pdenlkdpha
      601 hkssvtscly nlgklyheqg hyeealsvyk eaiqkmprqf apqslynmmg eaymrlsklp
      661 eaehwymesl rsktdhipah ltygkllalt grkseaeklf lkaieldptk gncymhygqf
      721 lleearliea aemakkaael dstefdvvfn aahmlrqasl neaaekyydl aarlrpnypa
      781 almnlgailh lngrlqkaea nylralqlkp ddvitqsnlr klwnimekqg lktskt
//
