TMC5_HUMAN
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 03-AUG-2022, entry version 131.
DE RecName: Full=Transmembrane channel-like protein 5;
GN Name=TMC5; 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 ion channel. {ECO:0000250}.
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};
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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_001261841.1. [Q6UXY8-1]
DR RefSeq; NP_001295090.1; NM_001308161.1.
DR RefSeq; NP_079056.2; NM_024780.4. [Q6UXY8-3]
DR AlphaFoldDB; Q6UXY8; -.
DR BioGRID; 122929; 58.
DR IntAct; Q6UXY8; 1.
DR STRING; 9606.ENSP00000379531; -.
DR TCDB; 1.A.17.4.16; the calcium-dependent chloride channel (ca-clc) family.
DR iPTMnet; Q6UXY8; -.
DR PhosphoSitePlus; Q6UXY8; -.
DR BioMuta; TMC5; -.
DR DMDM; 313104276; -.
DR EPD; Q6UXY8; -.
DR jPOST; Q6UXY8; -.
DR MassIVE; Q6UXY8; -.
DR PaxDb; Q6UXY8; -.
DR PeptideAtlas; Q6UXY8; -.
DR PRIDE; Q6UXY8; -.
DR ProteomicsDB; 67677; -. [Q6UXY8-1]
DR ProteomicsDB; 67678; -. [Q6UXY8-2]
DR ProteomicsDB; 67679; -. [Q6UXY8-3]
DR ProteomicsDB; 67680; -. [Q6UXY8-4]
DR Antibodypedia; 25361; 78 antibodies from 15 providers.
DR DNASU; 79838; -.
DR Ensembl; ENST00000219821.9; ENSP00000219821.5; ENSG00000103534.17. [Q6UXY8-3]
DR Ensembl; ENST00000381414.8; ENSP00000370822.4; ENSG00000103534.17. [Q6UXY8-2]
DR Ensembl; ENST00000396229.6; ENSP00000379531.2; ENSG00000103534.17. [Q6UXY8-1]
DR Ensembl; ENST00000542583.7; ENSP00000446274.2; ENSG00000103534.17. [Q6UXY8-1]
DR Ensembl; ENST00000561503.5; ENSP00000456148.1; ENSG00000103534.17. [Q6UXY8-4]
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 CTD; 79838; -.
DR DisGeNET; 79838; -.
DR GeneCards; TMC5; -.
DR HGNC; HGNC:22999; TMC5.
DR HPA; ENSG00000103534; Tissue enhanced (intestine, stomach).
DR neXtProt; NX_Q6UXY8; -.
DR OpenTargets; ENSG00000103534; -.
DR PharmGKB; PA134923498; -.
DR VEuPathDB; HostDB:ENSG00000103534; -.
DR eggNOG; ENOG502QQB2; Eukaryota.
DR GeneTree; ENSGT01050000244894; -.
DR HOGENOM; CLU_013958_0_2_1; -.
DR InParanoid; Q6UXY8; -.
DR OMA; FSCWESM; -.
DR OrthoDB; 1048914at2759; -.
DR PhylomeDB; Q6UXY8; -.
DR TreeFam; TF313462; -.
DR PathwayCommons; Q6UXY8; -.
DR SignaLink; Q6UXY8; -.
DR BioGRID-ORCS; 79838; 10 hits in 1069 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 158 other tissues.
DR ExpressionAtlas; Q6UXY8; baseline and differential.
DR Genevisible; Q6UXY8; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0008381; F:mechanosensitive ion channel activity; IBA:GO_Central.
DR InterPro; IPR038900; TMC.
DR InterPro; IPR012496; TMC_dom.
DR PANTHER; PTHR23302; PTHR23302; 2.
DR Pfam; PF07810; TMC; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Ion channel; Ion transport; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
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 17..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 73..149
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 250..276
FT /note="Polar 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
