LOCUS       NM_152588               5669 bp    mRNA    linear   PRI 04-APR-2024
DEFINITION  Homo sapiens transmembrane O-mannosyltransferase targeting
            cadherins 2 (TMTC2), transcript variant 1, mRNA.
ACCESSION   NM_152588
VERSION     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  (bases 1 to 5669)
  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  (bases 1 to 5669)
  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  (bases 1 to 5669)
  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  (bases 1 to 5669)
  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  (bases 1 to 5669)
  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  (bases 1 to 5669)
  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  (bases 1 to 5669)
  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  (bases 1 to 5669)
  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  (bases 1 to 5669)
  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.
            
            On Nov 22, 2018 this sequence version replaced NM_152588.2.
            
            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##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-249               AC091214.20        63918-64166
            250-5089            AL834509.1         1-4840
            5090-5669           BC071614.1         3352-3931
FEATURES             Location/Qualifiers
     source          1..5669
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q21.31"
     gene            1..5669
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /note="transmembrane O-mannosyltransferase targeting
                     cadherins 2"
                     /db_xref="GeneID:160335"
                     /db_xref="HGNC:HGNC:25440"
                     /db_xref="MIM:615856"
     exon            1..764
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /inference="alignment:Splign:2.1.0"
     CDS             682..3192
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /EC_number="2.4.1.109"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; transmembrane and TPR repeat-containing protein
                     2; transmembrane and tetratricopeptide repeat containing
                     2; protein O-mannosyl-transferase TMTC2"
                     /codon_start=1
                     /product="protein O-mannosyl-transferase TMTC2 isoform 1
                     precursor"
                     /protein_id="NP_689801.1"
                     /db_xref="CCDS:CCDS9025.1"
                     /db_xref="GeneID:160335"
                     /db_xref="HGNC:HGNC:25440"
                     /db_xref="MIM:615856"
                     /translation="MIAELVSSALGLALYLNTLSADFCYDDSRAIKTNQDLLPETPWT
                     HIFYNDFWGTLLTHSGSHKSYRPLCTLSFRLNHAIGGLNPWSYHLVNVLLHAAVTGLF
                     TSFSKILLGDGYWTFMAGLMFASHPIHTEAVAGIVGRADVGASLFFLLSLLCYIKHCS
                     TRGYSARTWGWFLGSGLCAGCSMLWKEQGVTVLAVSAVYDVFVFHRLKIKQILPTIYK
                     RKNLSLFLSISLLIFWGSSLLGARLYWMGNKPPSFSNSDNPAADSDSLLTRTLTFFYL
                     PTKNLWLLLCPDTLSFDWSMDAVPLLKTVCDWRNLHTVAFYTGLLLLAYYGLKSPSVD
                     RECNGKTVTNGKQNANGHSCLSDVEYQNSETKSSFASKVENGIKNDVSQRTQLPSTEN
                     IVVLSLSLLIIPFVPATNLFFYVGFVIAERVLYIPSMGFCLLITVGARALYVKVQKRF
                     LKSLIFYATATLIVFYGLKTAIRNGDWQNEEMLYRSGIKVNPAKAWGNLGNVLKSQSK
                     ISEAESAYRNALYYRSNMADMLYNLGLLLQENSRFAEALHYYKLAIGSRPTLASAYLN
                     TGIILMNQGRTEEARRTFLKCSEIPDENLKDPHAHKSSVTSCLYNLGKLYHEQGHYEE
                     ALSVYKEAIQKMPRQFAPQSLYNMMGEAYMRLSKLPEAEHWYMESLRSKTDHIPAHLT
                     YGKLLALTGRKSEAEKLFLKAIELDPTKGNCYMHYGQFLLEEARLIEAAEMAKKAAEL
                     DSTEFDVVFNAAHMLRQASLNEAAEKYYDLAARLRPNYPAALMNLGAILHLNGRLQKA
                     EANYLRALQLKPDDVITQSNLRKLWNIMEKQGLKTSKT"
     exon            765..1335
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1336..2164
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2165..2279
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2280..2365
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2366..2550
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2551..2629
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2630..2751
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2752..2833
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2834..2948
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2949..3012
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /inference="alignment:Splign:2.1.0"
     exon            3013..5669
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5650..5655
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /note="hexamer: AATAAA"
     polyA_site      5669
                     /gene="TMTC2"
                     /gene_synonym="IBDBP1"
                     /note="major polyA site"
ORIGIN      
        1 gagaacccca cgcgggagct tctggagtct ccagccaccg cttctcactt cactggagaa
       61 gggagctggg gctggggctg gggctggggc tgggagggag ctaataaaca ttgaatgtgc
      121 agcagctgcc ttggcggccg gagtccgccc gagcgacacc ggagcagtgc gcccgggagg
      181 cggcgagggg aggcggttcg ccttgtccct cccacccgcg cctctttctc tctcttcctc
      241 cagctggtcc cagagcccgg cttggtccgg tccctctgcc cccatcccgc acccttccac
      301 ctcctccgag tcccactcct cacctaggac gccccaaact gccatgggtt agggtgggga
      361 tcgcgacccg cgcgaaagac cagccctgcg cttccgccgg gggacgcgga gcccaaacgc
      421 cgctcaccgc ttgcgggcgc cgggcatggg gagtgtggtg tgagcccgca cccggggagg
      481 acgcaggagc tgcggagacg ggcgcgagga ggaggagagg agtcgtggat tggaaggacc
      541 cgagggaggg agggtgggga agcgagggaa aagtgaagct gggaggagaa ggcggcggaa
      601 ggtggagatt gatgcttctg ttttttgttg ccgctgctgc cctcgcgctg ggagccgagc
      661 cggagggaag gcggtggaga gatgattgca gagttggtga gcagcgctct ggggctcgcc
      721 ttgtatctca acaccctgag tgcggatttc tgctatgatg acagccgtgc tatcaagact
      781 aatcaggacc ttctcccaga aactccatgg acgcacattt tctacaatga tttttggggg
      841 actcttctaa cccacagtgg cagccacaag tcctaccggc cactctgcac tctttctttt
      901 cgcctgaacc atgccattgg agggttgaat ccctggagct accatcttgt caatgtcctg
      961 ttgcatgcag cagtcactgg tctcttcaca agcttctcca agatcctcct tggtgatgga
     1021 tactggacat tcatggctgg cttgatgttt gcttctcacc ccattcacac ggaggcagtg
     1081 gcaggaatcg tgggacgagc cgatgtcggg gccagtctct tctttctcct ctccttgctc
     1141 tgctacatta aacactgttc tacaagaggc tactcagcca gaacctgggg ctggttcctg
     1201 gggtcaggac tgtgcgcagg atgcagcatg ttgtggaagg aacaaggagt gactgttctc
     1261 gcagtttcag cagtttatga tgtctttgtc tttcacaggc tgaaaataaa acagatatta
     1321 cctaccattt acaaaaggaa gaacttgtcg cttttcctaa gcattagttt gttaattttc
     1381 tggggttcct cccttttggg tgcccggtta tactggatgg gaaacaaacc accaagcttt
     1441 tccaactcgg acaaccccgc tgctgattcg gacagcctcc tcacccgcac tctcaccttc
     1501 ttctacttgc caaccaagaa cctctggctg ttgctatgtc cagataccct cagttttgat
     1561 tggtcaatgg atgctgtgcc tctgctcaaa acagtttgtg actggagaaa cctacacact
     1621 gtggccttct atactggact ccttctcctt gcctactatg gtttgaagag cccgagcgta
     1681 gacagagaat gcaatgggaa aactgtaaca aatggcaagc agaatgcaaa tggacatagc
     1741 tgcctttcag atgtggagta ccagaactca gagactaagt ccagctttgc atccaaagta
     1801 gaaaatggca ttaaaaacga tgtatcacag agaacccagc ttccttctac ggagaacatt
     1861 gttgttctgt ctttatcttt gttaatcata ccctttgttc ctgccacgaa cctgtttttc
     1921 tatgtcggct ttgtaattgc agagcgagta ttatatattc ctagtatggg cttctgccta
     1981 ctgattacag tgggtgctag agccctttat gtcaaagtcc aaaagcggtt cctcaagagc
     2041 ttgatttttt atgctacagc tacactaatt gttttttatg gactcaagac tgcgatcagg
     2101 aatggagact ggcagaatga ggaaatgctt tatagatcag ggataaaagt aaacccagct
     2161 aaagcatggg gtaaccttgg aaatgttctg aagagtcaga gcaaaatttc tgaagctgaa
     2221 agcgcctata gaaatgcttt gtactaccgc agcaacatgg ctgacatgct ttataattta
     2281 gggctacttc tccaggagaa cagcaggttt gcagaagcac tacattatta taaattggcc
     2341 attgggagca ggcctaccct ggcttctgca tatttaaata ccggtattat tctaatgaac
     2401 caaggaagga cggaagaagc ccgacggaca ttcttaaagt gttcggagat cccagatgaa
     2461 aacctaaagg accctcatgc acacaagagc tctgttacca gttgtttgta caacctagga
     2521 aagctgtatc atgagcaggg acactatgag gaagccctta gtgtatacaa ggaagcaatt
     2581 cagaaaatgc caaggcagtt tgccccacag agcttgtaca acatgatggg tgaagcatat
     2641 atgcgtttaa gcaaactccc cgaagcagag cattggtata tggaatcact gagatccaag
     2701 actgaccaca tccctgctca tctcacctat gggaagctgc tagctctaac aggtcgtaag
     2761 agtgaggctg aaaagctctt cttgaaggct attgagctgg atcccaccaa aggaaactgt
     2821 tacatgcatt atggtcagtt tcttctggaa gaagctcgtc tcatagaagc agctgagatg
     2881 gcaaaaaaag cagctgaact agacagcaca gagtttgatg ttgtcttcaa tgctgcccac
     2941 atgctcagac aggctagcct caatgaagca gctgagaagt attatgatct ggcagccagg
     3001 ctgaggccta attatccggc tgctttgatg aacctgggag ccattctgca cctcaatggc
     3061 agactccaga aggccgaggc caactacctg cgggccctgc agctcaagcc agacgatgtc
     3121 atcacacagt ccaatctccg caaactgtgg aacatcatgg aaaaacaagg cttaaagact
     3181 tctaagacct gacacaggag gcagaagccc atcctcctcc atttttaaaa gctggcttcc
     3241 ttagcagaca gaacttccca gcagtgctat gacaagagct ggtgttagac ttcaagacca
     3301 gggcagaggt cattgaggtc actaccgctt ctggaagaat ccactttgct gtaggcacag
     3361 ctgttaacac caaaaagggg aaagccggaa acctcctgga ggatgtcatt gttacccata
     3421 gactgtaaac cagagcactt aaaacagaac cttttggcat tcttaaaaag ggaggggtgg
     3481 gtgtgtaagt cacagatttt gttcattttc tgaaagctaa tttcaaaatt atgttgttcc
     3541 ttaaacactg tgagaggaag tcagagtgtc cattcaggca tggcaaacaa ttagggttaa
     3601 gtgttacgag ggagtgataa acacgtagtg tgagtcccag tgagccgccg gttgtcctaa
     3661 cgctgctgtc ttccctgttt gggacagcct gcttatcaat ttctgaagct tagaacactt
     3721 tttttaatac tgtgtcaaga tctgtcagaa tctgctatgt ttcttgacca gtgcacataa
     3781 tgttttatga tttggatgtc agaggcttca ttcttttgga catcatttgc tttttatgtt
     3841 ctgaaaagga tatggagagt agagctaacc atacttcaca ctcgagttgt atgagggact
     3901 ggggaggcct tatatgtgtc aggcaggcat tttttaaatt ttaatatcgt caatattttc
     3961 ccccaaactg cccagtagaa ttcattgtat taattctttt gaaattacct ttgaaaatag
     4021 ctattcctgg agaatgtgca agcttacata aggataaagg acaggggagg agtttgtaag
     4081 ccttgcagtt ccaataacta accaacaggt tattagacaa aagggaaggt gttttgtgct
     4141 tctcagatgt tgctggttta ggagtgtgtg atgatgcttg ccagtgattt tgtgttttgg
     4201 aaagggtagg tatcgaatgt taatcacttt ctaatgggta cctaaacagc aatgctgata
     4261 aatgttcaag gaattatttt catcttagtt tgttcttctc aaaaggcatc aaaaacaact
     4321 tatttgaagc tgcaatagag tgtagcatta gcctgcatgt ttctaggtct tctgccaagt
     4381 gcttttctca gttgaaaact atttttcact agcaaaattg gtattttatt tcattacctg
     4441 ttagtaacta cttcaatgat catttcacaa gaaaaagact ataaattaag tagagaacaa
     4501 catttttatt gaacattttt ggcttgcaat caaactttgc cactaaaaat taacttcata
     4561 aaacactagt ccgttatcaa cttcttcaca gagaaagtag ctatactata ccctacatat
     4621 ttatttattt attattctac tatagcagaa taacaaaact tgatgcatta agccagttct
     4681 ttgcaactga aaattacctg tttctccttc cctttcacac tccatgtata tatgatcagc
     4741 ctctccatta aaaagaagct ggacatgcaa atacatcata ttatgttttc tccatatttt
     4801 atgtttttct atgtatctga atacagtggg ataaataatt gaaagtagtg ttcctatggc
     4861 attagtgttt ttgtgagaag ggtaaatgta gtgagaaagg ttttttcatg gcattaataa
     4921 gaaagccctt ctgtaatata tatattattt tgtaaacatt tcactgaagg gccaaaagtt
     4981 aaattataac taaatcactg tgttttcaga atgatattta acaacaaacc cgtggtcaaa
     5041 ccaaaatagt gggttgaagt gtattattca tcttttagtg cattggcaat tgcaaaaaaa
     5101 aaaaaggaat ttaatataag gctatagaga ttaattcagt gtctaacatt tgtatttatt
     5161 taaatagtta ttgacctatg atgactttct agtcttaaca ttttatcttt ttattgttgt
     5221 tgttcttcct ttcaaagatg tggttcttaa taggttcact gaatgcacag ttgaggcact
     5281 tcttgtgaca ccagttccca agtagcgtta ataattgggc ctgtgtcata aaatgcacgg
     5341 atcattaata actaaatgtc cctgacactt ttcactacag ggctggactt agtaactgac
     5401 caacttcggg gggagggttg gggcaagggg gggtgggcgt tagaacatga tcaaaaaatg
     5461 tctccgctca gggatttatg gtggattatt gcagacagtg ctaaaaatat agagcacaag
     5521 acaagtttac taaattaaaa ttttattttt tgagaaactg ttatttgtat aaattatcaa
     5581 gatttgtagg ctttcctttt gtagaaataa ttgttttatg tgccagagaa tttcaatttt
     5641 gttttcaaca ataaagcatt gataagaaa
//
