ID TMC5_HUMAN Reviewed; 1006 AA. AC Q6UXY8; Q68DK8; Q8IY20; Q8NHV6; Q9H8I7; DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 3. DT 02-SEP-2026, entry version 149. DE RecName: Full=Transmembrane channel-like protein 5; GN Name=TMC5 {ECO:0000312|HGNC:HGNC:22999}; ORFNames=UNQ8238/PRO33604; 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] (ISOFORM 3). RX PubMed=12812529; DOI=10.1186/1471-2164-4-24; RA Keresztes G., Mutai H., Heller S.; RT "TMC and EVER genes belong to a larger novel family, the TMC gene family RT encoding transmembrane proteins."; RL BMC Genomics 4:24-24(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RX PubMed=12906855; DOI=10.1016/s0888-7543(03)00154-x; RA Kurima K., Yang Y., Sorber K., Griffith A.J.; RT "Characterization of the transmembrane channel-like (TMC) gene family: RT functional clues from hearing loss and epidermodysplasia verruciformis."; RL Genomics 82:300-308(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4). RC TISSUE=Testis; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 200-1006 (ISOFORM 1). RC TISSUE=Rectum tumor; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 667-1006. RC TISSUE=Placenta; 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). CC -!- FUNCTION: Probable component of an ion channel (Probable). Molecular CC function hasn't been characterized yet (Probable). {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane CC protein {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q6UXY8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6UXY8-2; Sequence=VSP_026046; CC Name=3; CC IsoId=Q6UXY8-3; Sequence=VSP_026044, VSP_026045; CC Name=4; CC IsoId=Q6UXY8-4; Sequence=VSP_026043; CC -!- SIMILARITY: Belongs to the TMC family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB14629.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY263164; AAP78779.1; -; mRNA. DR EMBL; AY236494; AAP69872.1; -; mRNA. DR EMBL; AY358155; AAQ88522.1; -; mRNA. DR EMBL; AC130456; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC027602; AAH27602.1; -; mRNA. DR EMBL; BC038118; AAH38118.1; -; mRNA. DR EMBL; CR749359; CAH18212.1; -; mRNA. DR EMBL; AK023655; BAB14629.1; ALT_INIT; mRNA. DR CCDS; CCDS10577.1; -. [Q6UXY8-3] DR CCDS; CCDS42126.1; -. [Q6UXY8-2] DR CCDS; CCDS45431.1; -. [Q6UXY8-1] DR RefSeq; NP_001098718.1; NM_001105248.1. [Q6UXY8-1] DR RefSeq; NP_001098719.1; NM_001105249.1. [Q6UXY8-2] DR RefSeq; NP_001248770.1; NM_001261841.2. [Q6UXY8-1] DR RefSeq; NP_001295090.1; NM_001308161.1. DR RefSeq; NP_079056.2; NM_024780.5. [Q6UXY8-3] DR AlphaFoldDB; Q6UXY8; -. DR SMR; Q6UXY8; -. DR BioGRID; 122929; 59. DR FunCoup; Q6UXY8; 84. DR IntAct; Q6UXY8; 2. DR STRING; 9606.ENSP00000379531; -. DR TCDB; 1.A.17.4.16; the calcium-dependent chloride channel (ca-clc) family. DR GlyGen; Q6UXY8; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q6UXY8; -. DR PhosphoSitePlus; Q6UXY8; -. DR SwissPalm; Q6UXY8; -. DR BioMuta; TMC5; -. DR DMDM; 313104276; -. DR jPOST; Q6UXY8; -. DR MassIVE; Q6UXY8; -. DR PaxDb; 9606-ENSP00000379531; -. DR PeptideAtlas; Q6UXY8; -. DR ProteomicsDB; 67677; -. [Q6UXY8-1] DR ProteomicsDB; 67678; -. [Q6UXY8-2] DR ProteomicsDB; 67679; -. [Q6UXY8-3] DR ProteomicsDB; 67680; -. [Q6UXY8-4] DR Antibodypedia; 25361; 81 antibodies from 16 providers. DR DNASU; 79838; -. DR Ensembl; ENST00000219821.9; ENSP00000219821.5; ENSG00000103534.18. [Q6UXY8-3] DR Ensembl; ENST00000381414.8; ENSP00000370822.4; ENSG00000103534.18. [Q6UXY8-2] DR Ensembl; ENST00000396229.6; ENSP00000379531.2; ENSG00000103534.18. [Q6UXY8-1] DR Ensembl; ENST00000542583.7; ENSP00000446274.2; ENSG00000103534.18. [Q6UXY8-1] DR Ensembl; ENST00000561503.5; ENSP00000456148.1; ENSG00000103534.18. [Q6UXY8-4] DR Ensembl; ENST00000856996.1; ENSP00000527055.1; ENSG00000103534.18. [Q6UXY8-1] DR Ensembl; ENST00000856999.1; ENSP00000527058.1; ENSG00000103534.18. [Q6UXY8-1] DR Ensembl; ENST00000857001.1; ENSP00000527060.1; ENSG00000103534.18. [Q6UXY8-1] DR Ensembl; ENST00000949094.1; ENSP00000619153.1; ENSG00000103534.18. [Q6UXY8-1] DR GeneID; 79838; -. DR KEGG; hsa:79838; -. DR MANE-Select; ENST00000542583.7; ENSP00000446274.2; NM_001261841.2; NP_001248770.1. DR UCSC; uc002dgb.5; human. [Q6UXY8-1] DR AGR; HGNC:22999; -. DR ClinPGx; PA134923498; -. DR CTD; 79838; -. DR DisGeNET; 79838; -. DR GeneCards; TMC5; -. DR HGNC; HGNC:22999; TMC5. DR HPA; ENSG00000103534; Tissue enhanced (intestine, stomach). DR OpenTargets; ENSG00000103534; -. DR VEuPathDB; HostDB:ENSG00000103534; -. DR eggNOG; ENOG502QQB2; Eukaryota. DR GeneTree; ENSGT01050000244894; -. DR HOGENOM; CLU_013958_0_2_1; -. DR InParanoid; Q6UXY8; -. DR OMA; SLPHAYF; -. DR OrthoDB; 1936208at2759; -. DR PAN-GO; Q6UXY8; 1 GO annotation based on evolutionary models. DR PhylomeDB; Q6UXY8; -. DR PathwayCommons; Q6UXY8; -. DR SignaLink; Q6UXY8; -. DR Agora; ENSG00000103534; -. DR BioGRID-ORCS; 79838; 10 hits in 1145 CRISPR screens. DR ChiTaRS; TMC5; human. DR GenomeRNAi; 79838; -. DR Pharos; Q6UXY8; Tbio. DR PRO; PR:Q6UXY8; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q6UXY8; protein. DR Bgee; ENSG00000103534; Expressed in pancreatic ductal cell and 160 other cell types or tissues. DR ExpressionAtlas; Q6UXY8; baseline and differential. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0008381; F:mechanosensitive monoatomic ion channel activity; IBA:GO_Central. DR InterPro; IPR038900; TMC. DR InterPro; IPR012496; TMC_dom. DR PANTHER; PTHR23302:SF5; TRANSMEMBRANE CHANNEL-LIKE PROTEIN 5; 1. DR PANTHER; PTHR23302; TRANSMEMBRANE CHANNEL-RELATED; 1. DR Pfam; PF07810; TMC; 1. PE 1: Evidence at protein level; KW Alternative splicing; Membrane; Proteomics identification; KW Reference proteome; Transmembrane; Transmembrane helix. FT CHAIN 1..1006 FT /note="Transmembrane channel-like protein 5" FT /id="PRO_0000289966" FT TOPO_DOM 1..458 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 459..479 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 480..485 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 486..508 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 509..525 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 526..546 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 547..619 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 620..640 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 641..654 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 655..675 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 676..698 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 699..719 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 720..732 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 733..753 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 754..786 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 787..807 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 808..835 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 836..856 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 857..900 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 901..921 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 922..1006 FT /note="Extracellular" FT /evidence="ECO:0000255" FT REGION 1..289 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 20..30 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 50..59 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 76..101 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 138..149 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 239..250 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 1..359 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_026043" FT VAR_SEQ 1..246 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12812529, FT ECO:0000303|PubMed:12906855, ECO:0000303|PubMed:15489334" FT /id="VSP_026044" FT VAR_SEQ 247..348 FT /note="ENGHDYGSSETPKMTRGVLSRTSSIQPSFRHRSDDPVGSLWGENDYPEGIEM FT ASMEMANSYGHSLPGAPGSGYVNPAYVGESGPVHAYGNPPLSECDWHKSP -> MLSDD FT HVNEIIIQVENVSSGVQSHPSSNQIFQEKVLLDSSINMVLSISDIDVIDSQTVSKRNDQ FT KGNQVLRFSTSLNESMSQTLHSLECMGIDTPGSSHETV (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12812529, FT ECO:0000303|PubMed:12906855, ECO:0000303|PubMed:15489334" FT /id="VSP_026045" FT VAR_SEQ 859..916 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12975309" FT /id="VSP_026046" FT VARIANT 328 FT /note="S -> N (in dbSNP:rs16972013)" FT /id="VAR_057285" FT VARIANT 355 FT /note="A -> T (in dbSNP:rs36019638)" FT /id="VAR_061850" FT CONFLICT 419 FT /note="N -> D (in Ref. 5; CAH18212)" FT /evidence="ECO:0000305" FT CONFLICT 547 FT /note="M -> T (in Ref. 5; AAH38118)" FT /evidence="ECO:0000305" SQ SEQUENCE 1006 AA; 114797 MW; 7132E259B2FAF2EC CRC64; MSAYYRNNWS EEDPDYPDYS GSQNRTQGYL KTQGYPDVPG PLNNPDYPGT RSNPYSVASR TRPDYPGSLA EPNYPRSLSN PDYSGTRSNA YSAASRTSPD HPTSLPEPDY SEFQSHPYHR ASSRQPDYPG SQRNPDFAGS SSSGNYAGSR THPDHFGSLE PDYPGAQSNS DHPGPRANLN HPGSRKNLEH TSFRINPYAD SLGKPDYPGA DIQPNSPPFF GEPDYPSAED NQNLPSTWRE PDYSDAENGH DYGSSETPKM TRGVLSRTSS IQPSFRHRSD DPVGSLWGEN DYPEGIEMAS MEMANSYGHS LPGAPGSGYV NPAYVGESGP VHAYGNPPLS ECDWHKSPQG QKLIASLIPM TSRDRIKAIR NQPRTMEEKR NLRKIVDKEK SKQTHRILQL NCCIQCLNSI SRAYRRSKNS LSEILNSISL WQKTLKIIGG KFGTSVLSYF NFLRWLLKFN IFSFILNFSF IIIPQFTVAK KNTLQFTGLE FFTGVGYFRD TVMYYGFYTN STIQHGNSGA SYNMQLAYIF TIGACLTTCF FSLLFSMAKY FRNNFINPHI YSGGITKLIF CWDFTVTHEK AVKLKQKNLS TEIRENLSEL RQENSKLTFN QLLTRFSAYM VAWVVSTGVA IACCAAVYYL AEYNLEFLKT HSNPGAVLLL PFVVSCINLA VPCIYSMFRL VERYEMPRHE VYVLLIRNIF LKISIIGILC YYWLNTVALS GEECWETLIG QDIYRLLLMD FVFSLVNSFL GEFLRRIIGM QLITSLGLQE FDIARNVLEL IYAQTLVWIG IFFCPLLPFI QMIMLFIMFY SKNISLMMNF QPPSKAWRAS QMMTFFIFLL FFPSFTGVLC TLAITIWRLK PSADCGPFRG LPLFIHSIYS WIDTLSTRPG YLWVVWIYRN LIGSVHFFFI LTLIVLIITY LYWQITEGRK IMIRLLHEQI INEGKDKMFL IEKLIKLQDM EKKANPSSLV LERREVEQQG FLHLGEHDGS LDLRSRRSVQ EGNPRA //