TMC3_HUMAN
ID TMC3_HUMAN Reviewed; 1100 AA.
AC Q7Z5M5; A2RTY2; B2RXJ3; Q7Z405;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 08-MAR-2011, sequence version 3.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Transmembrane channel-like protein 3;
GN Name=TMC3 {ECO:0000312|EMBL:AAP78778.1};
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] {ECO:0000305, ECO:0000312|EMBL:AAP78778.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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] {ECO:0000305, ECO:0000312|EMBL:AAP69868.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
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 GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS TYR-893;
RP LYS-1012 AND ASN-1099.
RC TISSUE=Heart, and Lung;
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).
CC -!- FUNCTION: Probable ion channel. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:12812529};
CC IsoId=Q7Z5M5-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:12906855};
CC IsoId=Q7Z5M5-2; Sequence=VSP_052201, VSP_052202;
CC -!- SIMILARITY: Belongs to the TMC family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP78778.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Due to an insert of 27 undefined residues.; Evidence={ECO:0000305};
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DR EMBL; AY263163; AAP78778.1; ALT_SEQ; mRNA.
DR EMBL; AY236490; AAP69868.1; -; mRNA.
DR EMBL; AC103858; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC132679; AAI32680.1; -; mRNA.
DR EMBL; BC143410; AAI43411.1; -; mRNA.
DR EMBL; BC157874; AAI57875.1; -; mRNA.
DR CCDS; CCDS45324.1; -. [Q7Z5M5-1]
DR RefSeq; NP_001074001.1; NM_001080532.1. [Q7Z5M5-1]
DR AlphaFoldDB; Q7Z5M5; -.
DR SMR; Q7Z5M5; -.
DR BioGRID; 131164; 1.
DR STRING; 9606.ENSP00000352413; -.
DR GlyGen; Q7Z5M5; 1 site.
DR iPTMnet; Q7Z5M5; -.
DR PhosphoSitePlus; Q7Z5M5; -.
DR BioMuta; TMC3; -.
DR DMDM; 325511376; -.
DR EPD; Q7Z5M5; -.
DR MassIVE; Q7Z5M5; -.
DR PaxDb; Q7Z5M5; -.
DR PeptideAtlas; Q7Z5M5; -.
DR PRIDE; Q7Z5M5; -.
DR Antibodypedia; 27981; 15 antibodies from 6 providers.
DR DNASU; 342125; -.
DR Ensembl; ENST00000359440.6; ENSP00000352413.5; ENSG00000188869.13. [Q7Z5M5-1]
DR GeneID; 342125; -.
DR KEGG; hsa:342125; -.
DR MANE-Select; ENST00000359440.6; ENSP00000352413.5; NM_001080532.3; NP_001074001.1.
DR UCSC; uc059mlt.1; human. [Q7Z5M5-1]
DR CTD; 342125; -.
DR DisGeNET; 342125; -.
DR GeneCards; TMC3; -.
DR HGNC; HGNC:22995; TMC3.
DR HPA; ENSG00000188869; Tissue enriched (parathyroid).
DR neXtProt; NX_Q7Z5M5; -.
DR OpenTargets; ENSG00000188869; -.
DR VEuPathDB; HostDB:ENSG00000188869; -.
DR eggNOG; ENOG502QQGX; Eukaryota.
DR GeneTree; ENSGT01050000244942; -.
DR InParanoid; Q7Z5M5; -.
DR OrthoDB; 1048914at2759; -.
DR PhylomeDB; Q7Z5M5; -.
DR TreeFam; TF313462; -.
DR PathwayCommons; Q7Z5M5; -.
DR BioGRID-ORCS; 342125; 7 hits in 1060 CRISPR screens.
DR ChiTaRS; TMC3; human.
DR GenomeRNAi; 342125; -.
DR Pharos; Q7Z5M5; Tdark.
DR PRO; PR:Q7Z5M5; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q7Z5M5; protein.
DR Bgee; ENSG00000188869; Expressed in cortical plate and 64 other tissues.
DR ExpressionAtlas; Q7Z5M5; baseline and differential.
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; 1.
DR Pfam; PF07810; TMC; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1100
FT /note="Transmembrane channel-like protein 3"
FT /id="PRO_0000259602"
FT TOPO_DOM 1..148
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 149..169
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 170..192
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 193..213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 214..225
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 226..246
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 247..319
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 320..340
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 341..361
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 362..382
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 383..393
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 394..414
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 415..508
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 509..529
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 530..569
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 570..590
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 591..618
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 619..639
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 640..679
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 680..700
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 701..1100
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 738..812
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 929..956
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1005..1090
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 749..797
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 940..954
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1038..1083
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 722..724
FT /note="RSE -> SIS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12906855"
FT /id="VSP_052201"
FT VAR_SEQ 725..1100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12906855"
FT /id="VSP_052202"
FT VARIANT 196
FT /note="V -> I (in dbSNP:rs7497202)"
FT /id="VAR_066557"
FT VARIANT 893
FT /note="C -> Y (in dbSNP:rs11636318)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_066558"
FT VARIANT 1012
FT /note="R -> K (in dbSNP:rs8031046)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_066559"
FT VARIANT 1099
FT /note="D -> N (in dbSNP:rs4417518)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_066560"
FT CONFLICT 30
FT /note="Missing (in Ref. 1; AAP78778)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="L -> V (in Ref. 1; AAP78778)"
FT /evidence="ECO:0000305"
FT CONFLICT 248
FT /note="K -> R (in Ref. 1; AAP78778)"
FT /evidence="ECO:0000305"
FT CONFLICT 734
FT /note="E -> EGK (in Ref. 1; AAP78778)"
FT /evidence="ECO:0000305"
FT CONFLICT 735
FT /note="A -> AA (in Ref. 1; AAP78778)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1100 AA; 125685 MW; 727B3B1B766FF6EA CRC64;
MKTSKASQRY RGIRRNASQC YLYQESLLLS NLDDSFSADE TGDSNDPEQI FQNIQFQKDL
MANIRCRPWT MGQKLRALRQ AKNIVLKFEG RLTRTRGYQA AGAELWRKFA RLACNFVVIF
IPWEMRIKKI ESHFGSGVAS YFIFLRWLFG INIVLTIMTG AFIVIPELIA GQPFGSTARK
TIPKEQVSSA QDLDTVWSLG GYLQYSVLFY GYYGRERKIG RAGYRLPLAY FLVGMAVFAY
SFIILLKKMA KNSRTSLASA SNENYTFCWR VFCAWDYLIG NPEAAESKTA AIVNSIREAI
LEEQEKKKSK NLAVTICLRI IANILVLLSL AGSIYLIYFV VDRSQKLEQS KKELTLWEKN
EVSVVVSLVT MIAPSAFDLI AALEMYHPRT TLRFQLARVL VLYLGNLYSL IIALLDKVNS
MSIEEMATKN NTSHWIDSTT FFATRTAPEE EKWSTSRPGM GLRRNNTWAL EETSISAYTM
PLIKANKTSL HTQSPQDQCW ETYVGQEMLK LSIIDMLFTV ASILLIDFFR GLFVRYLSDY
WCWDLESKFP EYGEFKIAEN VLHLVYNQGM IWMGAFFSPC LPAFNVLKLI GLMYLRSWAV
LTCNVPHQQV FRASRSNNFY LAMLLFMLFL CMLPTIFAIV RYKPSLNCGP FSGQEKIYDI
VSETIEKDFP VWFGSVVGHI SSPVVILPAV LLLFMLIYYL QSIARSLKLS NHQLKMQIQN
ARSEDKKKVA QMVEARIQTQ EESTKKLPND SDLTSQLSSA HSGTPQNNGN VAHFDSGSSK
SGRIETVAQS MPQSPRPGDR APSSPLPGVP KSRLEHETNR YLHGLCASTS DLHRNRSRTP
MTFTTHIEDV HSEPLFRKDF QQINPPHRGP QASTLLAQGP RPHAPRYYVI NECDSYKKKH
LNVWPERHFK IDASGDIVEL YPRNVRQYAS RVPRQPPSPQ LSEEEEETPS RDWIKRSLPP
RSLIDLRRAP HFYIGERSES QTRDPEHQGR VHYKSWNEDF EGHLERPAYV PRKPRSRNFQ
YPQPPLKPRG KPRFEPSLTE SDSVSAASSS DQQNSSADQY LQVTHSQGRF PRSVGQPSRR
KAKSGQELTV DLDDLICSDV
