TMM98_HUMAN
ID TMM98_HUMAN Reviewed; 226 AA.
AC Q9Y2Y6; E1P631; Q9UFK2;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Transmembrane protein 98;
DE AltName: Full=Protein TADA1;
GN Name=TMEM98; ORFNames=UNQ536/PRO1079;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Teramoto T.;
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 [7]
RP TOPOLOGY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=25946230; DOI=10.1089/jir.2014.0110;
RA Fu W., Cheng Y., Zhang Y., Mo X., Li T., Liu Y., Wang P., Pan W., Chen Y.,
RA Xue Y., Ma D., Zhang Y., Han W.;
RT "The Secreted Form of Transmembrane Protein 98 Promotes the Differentiation
RT of T Helper 1 Cells.";
RL J. Interferon Cytokine Res. 35:720-733(2015).
RN [8]
RP TISSUE SPECIFICITY, AND VARIANT NNO4 PRO-193.
RX PubMed=24852644; DOI=10.1001/jamaophthalmol.2014.946;
RA Awadalla M.S., Burdon K.P., Souzeau E., Landers J., Hewitt A.W., Sharma S.,
RA Craig J.E.;
RT "Mutation in TMEM98 in a large white kindred with autosomal dominant
RT nanophthalmos linked to 17p12-q12.";
RL JAMA Ophthalmol. 132:970-977(2014).
RN [9]
RP VARIANT NNO4 PRO-196.
RX PubMed=26392740;
RA Khorram D., Choi M., Roos B.R., Stone E.M., Kopel T., Allen R.,
RA Alward W.L., Scheetz T.E., Fingert J.H.;
RT "Novel TMEM98 mutations in pedigrees with autosomal dominant
RT nanophthalmos.";
RL Mol. Vis. 21:1017-1023(2015).
CC -!- FUNCTION: Functions as a negative regulator of MYRF in oligodendrocyte
CC differentiation and myelination. Interacts with the C-terminal of MYRF
CC inhibiting MYRF self-cleavage and N-fragment nuclear translocation. The
CC secreted form promotes differentiation of T helper 1 cells (Th1).
CC {ECO:0000250|UniProtKB:Q91X86}.
CC -!- SUBUNIT: Interacts (via N-terminal region) with MYRF; the interaction
CC inhibits MYRF self-cleavage. {ECO:0000250|UniProtKB:Q91X86}.
CC -!- INTERACTION:
CC Q9Y2Y6; P54709: ATP1B3; NbExp=3; IntAct=EBI-7333781, EBI-1054481;
CC Q9Y2Y6; P08034: GJB1; NbExp=3; IntAct=EBI-7333781, EBI-17565645;
CC Q9Y2Y6; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-7333781, EBI-712073;
CC Q9Y2Y6; P15941-11: MUC1; NbExp=3; IntAct=EBI-7333781, EBI-17263240;
CC Q9Y2Y6; O43765: SGTA; NbExp=3; IntAct=EBI-7333781, EBI-347996;
CC Q9Y2Y6; P27105: STOM; NbExp=3; IntAct=EBI-7333781, EBI-1211440;
CC Q9Y2Y6; Q96L08: SUSD3; NbExp=3; IntAct=EBI-7333781, EBI-18194029;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25946230};
CC Single-pass type II membrane protein {ECO:0000269|PubMed:25946230}.
CC Secreted {ECO:0000269|PubMed:25946230}. Secreted, extracellular exosome
CC {ECO:0000269|PubMed:25946230}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q91X86}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:25946230}. Note=Secreted by exosomes through a non-
CC classical pathway. {ECO:0000269|PubMed:25946230}.
CC -!- TISSUE SPECIFICITY: Widely expressed with high expression in the ovary,
CC pancreas and prostate (PubMed:25946230). Expressed in the eye,
CC particularly in corneal endothelium, iris, ciliary body, sclera, optic
CC nerve, optic nerve head, and retina (PubMed:24852644). Expressed by
CC activated peripheral blood mononuclear cells (PubMed:25946230).
CC {ECO:0000269|PubMed:24852644, ECO:0000269|PubMed:25946230}.
CC -!- DISEASE: Nanophthalmos 4 (NNO4) [MIM:615972]: A rare disorder of eye
CC development characterized by extreme hyperopia (farsightedness) and
CC small functional eyes. The cornea and lens are normal in size and
CC shape. Hyperopia occurs because insufficient growth along the visual
CC axis places these lensing components too close to the retina.
CC Nanophthalmic eyes show considerable thickening of both the choroidal
CC vascular bed and scleral coat, which provide nutritive and structural
CC support for the retina. {ECO:0000269|PubMed:24852644,
CC ECO:0000269|PubMed:26392740}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TMEM98 family. {ECO:0000305}.
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DR EMBL; AF132000; AAD22105.1; -; mRNA.
DR EMBL; AL117619; CAB56018.1; -; mRNA.
DR EMBL; AY358573; AAQ88936.1; -; mRNA.
DR EMBL; CR457125; CAG33406.1; -; mRNA.
DR EMBL; CH471147; EAW80219.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80220.1; -; Genomic_DNA.
DR EMBL; BC000526; AAH00526.1; -; mRNA.
DR CCDS; CCDS11274.1; -.
DR PIR; T17328; T17328.
DR RefSeq; NP_001028676.1; NM_001033504.1.
DR RefSeq; NP_001288675.1; NM_001301746.1.
DR RefSeq; NP_056359.2; NM_015544.2.
DR AlphaFoldDB; Q9Y2Y6; -.
DR SMR; Q9Y2Y6; -.
DR BioGRID; 117492; 23.
DR IntAct; Q9Y2Y6; 10.
DR MINT; Q9Y2Y6; -.
DR STRING; 9606.ENSP00000463245; -.
DR iPTMnet; Q9Y2Y6; -.
DR PhosphoSitePlus; Q9Y2Y6; -.
DR SwissPalm; Q9Y2Y6; -.
DR BioMuta; TMEM98; -.
DR DMDM; 74735246; -.
DR EPD; Q9Y2Y6; -.
DR jPOST; Q9Y2Y6; -.
DR MassIVE; Q9Y2Y6; -.
DR PaxDb; Q9Y2Y6; -.
DR PeptideAtlas; Q9Y2Y6; -.
DR PRIDE; Q9Y2Y6; -.
DR ProteomicsDB; 85937; -.
DR Antibodypedia; 52106; 46 antibodies from 13 providers.
DR DNASU; 26022; -.
DR Ensembl; ENST00000394642.7; ENSP00000378138.3; ENSG00000006042.12.
DR Ensembl; ENST00000579849.6; ENSP00000463245.1; ENSG00000006042.12.
DR GeneID; 26022; -.
DR KEGG; hsa:26022; -.
DR MANE-Select; ENST00000579849.6; ENSP00000463245.1; NM_015544.3; NP_056359.2.
DR UCSC; uc002hhq.4; human.
DR CTD; 26022; -.
DR DisGeNET; 26022; -.
DR GeneCards; TMEM98; -.
DR HGNC; HGNC:24529; TMEM98.
DR HPA; ENSG00000006042; Low tissue specificity.
DR MalaCards; TMEM98; -.
DR MIM; 615949; gene.
DR MIM; 615972; phenotype.
DR neXtProt; NX_Q9Y2Y6; -.
DR OpenTargets; ENSG00000006042; -.
DR Orphanet; 35612; Nanophthalmos.
DR PharmGKB; PA142670747; -.
DR VEuPathDB; HostDB:ENSG00000006042; -.
DR eggNOG; ENOG502QT8U; Eukaryota.
DR GeneTree; ENSGT00390000012062; -.
DR InParanoid; Q9Y2Y6; -.
DR OMA; RHRYCRP; -.
DR OrthoDB; 1413051at2759; -.
DR PhylomeDB; Q9Y2Y6; -.
DR TreeFam; TF336444; -.
DR PathwayCommons; Q9Y2Y6; -.
DR SignaLink; Q9Y2Y6; -.
DR BioGRID-ORCS; 26022; 9 hits in 1076 CRISPR screens.
DR ChiTaRS; TMEM98; human.
DR GeneWiki; TMEM98; -.
DR GenomeRNAi; 26022; -.
DR Pharos; Q9Y2Y6; Tbio.
DR PRO; PR:Q9Y2Y6; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9Y2Y6; protein.
DR Bgee; ENSG00000006042; Expressed in ileal mucosa and 161 other tissues.
DR ExpressionAtlas; Q9Y2Y6; baseline and differential.
DR Genevisible; Q9Y2Y6; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0031642; P:negative regulation of myelination; ISS:UniProtKB.
DR GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; ISS:UniProtKB.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; IEA:Ensembl.
DR GO; GO:0010955; P:negative regulation of protein processing; IEA:Ensembl.
DR GO; GO:0045063; P:T-helper 1 cell differentiation; ISS:UniProtKB.
DR InterPro; IPR029668; TMEM98.
DR PANTHER; PTHR32510; PTHR32510; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disease variant; Endoplasmic reticulum; Membrane;
KW Reference proteome; Secreted; Transmembrane; Transmembrane helix.
FT CHAIN 1..226
FT /note="Transmembrane protein 98"
FT /id="PRO_0000251711"
FT TOPO_DOM 1..3
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:25946230"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 25..226
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:25946230"
FT REGION 1..88
FT /note="Required for interaction with MYRF"
FT /evidence="ECO:0000250|UniProtKB:Q91X86"
FT REGION 207..226
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 83
FT /note="W -> R (in dbSNP:rs35124349)"
FT /id="VAR_051451"
FT VARIANT 193
FT /note="A -> P (in NNO4; dbSNP:rs587777690)"
FT /evidence="ECO:0000269|PubMed:24852644"
FT /id="VAR_071807"
FT VARIANT 196
FT /note="H -> P (in NNO4; dbSNP:rs869312733)"
FT /evidence="ECO:0000269|PubMed:26392740"
FT /id="VAR_081643"
FT CONFLICT 104
FT /note="L -> P (in Ref. 2; CAB56018)"
FT /evidence="ECO:0000305"
FT CONFLICT 196
FT /note="H -> R (in Ref. 2; CAB56018)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 226 AA; 24611 MW; 4F9997AD8FD3DD0F CRC64;
METVVIVAIG VLATIFLASF AALVLVCRQR YCRPRDLLQR YDSKPIVDLI GAMETQSEPS
ELELDDVVIT NPHIEAILEN EDWIEDASGL MSHCIAILKI CHTLTEKLVA MTMGSGAKMK
TSASVSDIIV VAKRISPRVD DVVKSMYPPL DPKLLDARTT ALLLSVSHLV LVTRNACHLT
GGLDWIDQSL SAAEEHLEVL REAALASEPD KGLPGPEGFL QEQSAI
