TM231_HUMAN
ID TM231_HUMAN Reviewed; 316 AA.
AC Q9H6L2; A0JLU1; A6NDZ6; B3KU85; G5E9E3; Q6P450; Q6UWW5;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Transmembrane protein 231;
GN Name=TMEM231; ORFNames=UNQ870/PRO1886;
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] (ISOFORM 1), AND VARIANT VAL-6.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP VAL-6.
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain, Lymph, and Ovary;
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 [6]
RP IDENTIFICATION IN THE TECTONIC-LIKE COMPLEX, AND INTERACTION WITH TMEM107.
RX PubMed=26595381; DOI=10.1038/ncb3273;
RA Lambacher N.J., Bruel A.L., van Dam T.J., Szymanska K., Slaats G.G.,
RA Kuhns S., McManus G.J., Kennedy J.E., Gaff K., Wu K.M., van der Lee R.,
RA Burglen L., Doummar D., Riviere J.B., Faivre L., Attie-Bitach T.,
RA Saunier S., Curd A., Peckham M., Giles R.H., Johnson C.A., Huynen M.A.,
RA Thauvin-Robinet C., Blacque O.E.;
RT "TMEM107 recruits ciliopathy proteins to subdomains of the ciliary
RT transition zone and causes Joubert syndrome.";
RL Nat. Cell Biol. 18:122-131(2016).
RN [7]
RP VARIANT JBTS20 ASN-209.
RX PubMed=23012439; DOI=10.1136/jmedgenet-2012-101132;
RG FORGE Canada Consortium;
RA Srour M., Hamdan F.F., Schwartzentruber J.A., Patry L., Ospina L.H.,
RA Shevell M.I., Desilets V., Dobrzeniecka S., Mathonnet G., Lemyre E.,
RA Massicotte C., Labuda D., Amrom D., Andermann E., Sebire G., Maranda B.,
RA Rouleau G.A., Majewski J., Michaud J.L.;
RT "Mutations in TMEM231 cause Joubert syndrome in French Canadians.";
RL J. Med. Genet. 49:636-641(2012).
RN [8]
RP VARIANT MKS11 PRO-272.
RX PubMed=23349226; DOI=10.1136/jmedgenet-2012-101431;
RA Shaheen R., Ansari S., Mardawi E.A., Alshammari M.J., Alkuraya F.S.;
RT "Mutations in TMEM231 cause Meckel-Gruber syndrome.";
RL J. Med. Genet. 50:160-162(2013).
RN [9]
RP VARIANT JBTS20 ASN-209.
RX PubMed=26477546; DOI=10.1016/j.ajhg.2015.09.009;
RG Care4Rare Canada Consortium;
RA Srour M., Hamdan F.F., McKnight D., Davis E., Mandel H.,
RA Schwartzentruber J., Martin B., Patry L., Nassif C., Dionne-Laporte A.,
RA Ospina L.H., Lemyre E., Massicotte C., Laframboise R., Maranda B.,
RA Labuda D., Decarie J.C., Rypens F., Goldsher D., Fallet-Bianco C.,
RA Soucy J.F., Laberge A.M., Maftei C., Boycott K., Brais B., Boucher R.M.,
RA Rouleau G.A., Katsanis N., Majewski J., Elpeleg O., Kukolich M.K.,
RA Shalev S., Michaud J.L.;
RT "Joubert Syndrome in French Canadians and Identification of Mutations in
RT CEP104.";
RL Am. J. Hum. Genet. 97:744-753(2015).
CC -!- FUNCTION: Transmembrane component of the tectonic-like complex, a
CC complex localized at the transition zone of primary cilia and acting as
CC a barrier that prevents diffusion of transmembrane proteins between the
CC cilia and plasma membranes. Required for ciliogenesis and sonic
CC hedgehog/SHH signaling (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Part of the tectonic-like complex (also named B9 complex).
CC Interacts with TMEM107. {ECO:0000269|PubMed:26595381}.
CC -!- INTERACTION:
CC Q9H6L2; Q15323: KRT31; NbExp=3; IntAct=EBI-10307654, EBI-948001;
CC Q9H6L2; Q6A162: KRT40; NbExp=3; IntAct=EBI-10307654, EBI-10171697;
CC Q9H6L2; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-10307654, EBI-945833;
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium membrane {ECO:0000250};
CC Multi-pass membrane protein {ECO:0000250}. Note=Localizes to the
CC transition zone of primary cilia; SEPT2 is required for localization to
CC the transition zone. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9H6L2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H6L2-2; Sequence=VSP_042388;
CC Name=3;
CC IsoId=Q9H6L2-3; Sequence=VSP_042387;
CC -!- DISEASE: Joubert syndrome 20 (JBTS20) [MIM:614970]: A disorder
CC presenting with cerebellar ataxia, oculomotor apraxia, hypotonia,
CC neonatal breathing abnormalities and psychomotor delay.
CC Neuroradiologically, it is characterized by cerebellar vermian
CC hypoplasia/aplasia, thickened and reoriented superior cerebellar
CC peduncles, and an abnormally large interpeduncular fossa, giving the
CC appearance of a molar tooth on transaxial slices (molar tooth sign).
CC Additional variable features include retinal dystrophy and renal
CC disease. {ECO:0000269|PubMed:23012439, ECO:0000269|PubMed:26477546}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Meckel syndrome 11 (MKS11) [MIM:615397]: A disorder
CC characterized by a combination of renal cysts and variably associated
CC features including developmental anomalies of the central nervous
CC system (typically encephalocele), hepatic ductal dysplasia and cysts,
CC and polydactyly. {ECO:0000269|PubMed:23349226}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TMEM231 family. {ECO:0000305}.
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DR EMBL; AY358612; AAQ88975.1; -; mRNA.
DR EMBL; AK025820; BAB15244.1; -; mRNA.
DR EMBL; AK096650; BAG53347.1; -; mRNA.
DR EMBL; AK290483; BAF83172.1; -; mRNA.
DR EMBL; AC009163; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC025287; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471114; EAW95632.1; -; Genomic_DNA.
DR EMBL; CH471114; EAW95633.1; -; Genomic_DNA.
DR EMBL; BC010609; AAH10609.1; -; mRNA.
DR EMBL; BC016401; AAH16401.1; -; mRNA.
DR EMBL; BC063677; AAH63677.1; -; mRNA.
DR CCDS; CCDS45530.1; -. [Q9H6L2-1]
DR RefSeq; NP_001070884.2; NM_001077416.2.
DR RefSeq; NP_001070886.1; NM_001077418.2. [Q9H6L2-1]
DR AlphaFoldDB; Q9H6L2; -.
DR BioGRID; 311393; 78.
DR DIP; DIP-61994N; -.
DR IntAct; Q9H6L2; 29.
DR MINT; Q9H6L2; -.
DR STRING; 9606.ENSP00000258173; -.
DR GlyConnect; 1852; 1 N-Linked glycan (1 site).
DR GlyGen; Q9H6L2; 3 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q9H6L2; -.
DR PhosphoSitePlus; Q9H6L2; -.
DR SwissPalm; Q9H6L2; -.
DR BioMuta; TMEM231; -.
DR DMDM; 74733611; -.
DR EPD; Q9H6L2; -.
DR jPOST; Q9H6L2; -.
DR MassIVE; Q9H6L2; -.
DR MaxQB; Q9H6L2; -.
DR PeptideAtlas; Q9H6L2; -.
DR PRIDE; Q9H6L2; -.
DR ProteomicsDB; 80998; -. [Q9H6L2-1]
DR ProteomicsDB; 80999; -. [Q9H6L2-2]
DR ProteomicsDB; 81000; -. [Q9H6L2-3]
DR Antibodypedia; 8257; 53 antibodies from 20 providers.
DR DNASU; 79583; -.
DR Ensembl; ENST00000258173.11; ENSP00000258173.5; ENSG00000205084.12. [Q9H6L2-1]
DR Ensembl; ENST00000568377.5; ENSP00000476267.1; ENSG00000205084.12. [Q9H6L2-2]
DR Ensembl; ENST00000692689.1; ENSP00000509732.1; ENSG00000205084.12. [Q9H6L2-3]
DR GeneID; 79583; -.
DR KEGG; hsa:79583; -.
DR MANE-Select; ENST00000258173.11; ENSP00000258173.5; NM_001077418.3; NP_001070886.1.
DR UCSC; uc002fem.5; human. [Q9H6L2-1]
DR CTD; 79583; -.
DR DisGeNET; 79583; -.
DR GeneCards; TMEM231; -.
DR GeneReviews; TMEM231; -.
DR HGNC; HGNC:37234; TMEM231.
DR HPA; ENSG00000205084; Tissue enriched (fallopian).
DR MalaCards; TMEM231; -.
DR MIM; 614949; gene.
DR MIM; 614970; phenotype.
DR MIM; 615397; phenotype.
DR neXtProt; NX_Q9H6L2; -.
DR OpenTargets; ENSG00000205084; -.
DR Orphanet; 2318; Joubert syndrome with oculorenal defect.
DR Orphanet; 564; Meckel syndrome.
DR Orphanet; 2752; Orofaciodigital syndrome type 3.
DR PharmGKB; PA165450754; -.
DR VEuPathDB; HostDB:ENSG00000205084; -.
DR eggNOG; KOG4838; Eukaryota.
DR GeneTree; ENSGT00390000015366; -.
DR InParanoid; Q9H6L2; -.
DR OMA; QLPARYH; -.
DR OrthoDB; 1247968at2759; -.
DR PhylomeDB; Q9H6L2; -.
DR TreeFam; TF312969; -.
DR PathwayCommons; Q9H6L2; -.
DR SignaLink; Q9H6L2; -.
DR BioGRID-ORCS; 79583; 10 hits in 1083 CRISPR screens.
DR ChiTaRS; TMEM231; human.
DR GenomeRNAi; 79583; -.
DR Pharos; Q9H6L2; Tbio.
DR PRO; PR:Q9H6L2; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9H6L2; protein.
DR Bgee; ENSG00000205084; Expressed in bronchial epithelial cell and 172 other tissues.
DR ExpressionAtlas; Q9H6L2; baseline and differential.
DR Genevisible; Q9H6L2; HS.
DR GO; GO:0060170; C:ciliary membrane; ISS:UniProtKB.
DR GO; GO:0035869; C:ciliary transition zone; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0036038; C:MKS complex; ISS:UniProtKB.
DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl.
DR GO; GO:0060271; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0060563; P:neuroepithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0032880; P:regulation of protein localization; IBA:GO_Central.
DR GO; GO:0007224; P:smoothened signaling pathway; ISS:UniProtKB.
DR GO; GO:0001944; P:vasculature development; IEA:Ensembl.
DR InterPro; IPR019306; TMEM231.
DR PANTHER; PTHR14605; PTHR14605; 1.
DR Pfam; PF10149; TM231; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Ciliopathy; Cilium;
KW Cilium biogenesis/degradation; Disease variant; Glycoprotein;
KW Joubert syndrome; Meckel syndrome; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..316
FT /note="Transmembrane protein 231"
FT /id="PRO_0000317520"
FT TRANSMEM 23..43
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..282
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 194
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 221
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..116
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_042387"
FT VAR_SEQ 1..46
FT /note="MALYELFSHPVERSYRAGLCSKAALFLLLAAALTYIPPLLVAFRSH -> MS
FT SSLTRSSAVTARGSAPKPRCSCCWPLRSRTSRRCWWPSGATVSLPRPLCHEAPRARSAR
FT AGLPNRLPTALFNS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042388"
FT VARIANT 6
FT /note="L -> V (in dbSNP:rs3743601)"
FT /evidence="ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:14702039"
FT /id="VAR_038543"
FT VARIANT 209
FT /note="D -> N (in JBTS20; dbSNP:rs200799769)"
FT /evidence="ECO:0000269|PubMed:23012439,
FT ECO:0000269|PubMed:26477546"
FT /id="VAR_069044"
FT VARIANT 272
FT /note="Q -> P (in MKS11; dbSNP:rs397514754)"
FT /evidence="ECO:0000269|PubMed:23349226"
FT /id="VAR_070456"
FT CONFLICT 125
FT /note="P -> S (in Ref. 5; AAH63677)"
FT /evidence="ECO:0000305"
FT CONFLICT Q9H6L2-2:2
FT /note="S -> R (in Ref. 2; BAG53347)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 316 AA; 36059 MW; 11EE554E49B21B84 CRC64;
MALYELFSHP VERSYRAGLC SKAALFLLLA AALTYIPPLL VAFRSHGFWL KRSSYEEQPT
VRFQHQVLLV ALLGPESDGF LAWSTFPAFN RLQGDRLRVP LVSTREEDRN QDGKTDMLHF
KLELPLQSTE HVLGVQLILT FSYRLHRMAT LVMQSMAFLQ SSFPVPGSQL YVNGDLRLQQ
KQPLSCGGLD ARYNISVING TSPFAYDYDL THIVAAYQER NVTTVLNDPN PIWLVGRAAD
APFVINAIIR YPVEVISYQP GFWEMVKFAW VQYVSILLIF LWVFERIKIF VFQNQVVTTI
PVTVTPRGDL CKEHLS
