ID   TRPM5_HUMAN             Reviewed;        1165 AA.
AC   Q9NZQ8; A6NHS0; Q52LU2; Q9NY34;
DT   08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   27-MAR-2024, entry version 151.
DE   RecName: Full=Transient receptor potential cation channel subfamily M member 5;
DE   AltName: Full=Long transient receptor potential channel 5;
DE            Short=LTrpC-5;
DE            Short=LTrpC5;
DE   AltName: Full=MLSN1- and TRP-related gene 1 protein;
GN   Name=TRPM5 {ECO:0000312|HGNC:HGNC:14323};
GN   Synonyms=LTRPC5 {ECO:0000312|EMBL:CAB66342.1}, MTR1
GN   {ECO:0000312|EMBL:AAF26288.1};
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:AAF26288.1}
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORM 3),
RP   AND TISSUE SPECIFICITY.
RX   PubMed=10607831; DOI=10.1093/hmg/9.2.203;
RA   Prawitt D., Enklaar T., Klemm G., Gaertner B., Spangenberg C.,
RA   Winterpacht A., Higgins M., Pelletier J., Zabel B.;
RT   "Identification and characterization of MTR1, a novel gene with homology to
RT   melastatin (MLSN1) and the trp gene family located in the BWS-WT2 critical
RT   region on chromosome 11p15.5 and showing allele-specific expression.";
RL   Hum. Mol. Genet. 9:203-216(2000).
RN   [2] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [3] {ECO:0000305, ECO:0000312|EMBL:AAH93787.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-254.
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   [4] {ECO:0000305, ECO:0000312|EMBL:CAB66342.1}
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 9-1165 (ISOFORM 2).
RA   Paulsen M., El-Maarri O., Engemann S., Franck O., Stroedicke M.,
RA   Davies K.R., Bowden L.M., Reinhardt R., Reik W., Harteneck C., Walter J.;
RT   "Comparative sequence analysis and characterization of the imprinting
RT   cluster on the human chromosome 11p15.5 and distal mouse chromosome 7.";
RL   Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [5] {ECO:0000305}
RP   FUNCTION.
RX   PubMed=14634208; DOI=10.1073/pnas.2334624100;
RA   Prawitt D., Monteilh-Zoller M.K., Brixel L., Spangenberg C., Zabel B.,
RA   Fleig A., Penner R.;
RT   "TRPM5 is a transient Ca2+-activated cation channel responding to rapid
RT   changes in [Ca2+]i.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:15166-15171(2003).
CC   -!- FUNCTION: Voltage-modulated Ca(2+)-activated, monovalent cation channel
CC       (VCAM) that mediates a transient membrane depolarization and plays a
CC       central role in taste transduction. Monovalent-specific, non-selective
CC       cation channel that mediates the transport of Na(+), K(+) and Cs(+)
CC       ions equally well. Activated directly by increases in intracellular
CC       Ca(2+), but is impermeable to it. Gating is voltage-dependent and
CC       displays rapid activation and deactivation kinetics upon channel
CC       stimulation even during sustained elevations in Ca(2+). Also activated
CC       by a fast intracellular Ca(2+) increase in response to inositol 1,4,5-
CC       triphosphate-producing receptor agonists. The channel is blocked by
CC       extracellular acidification. External acidification has 2 effects, a
CC       fast reversible block of the current and a slower irreversible
CC       enhancement of current inactivation. Is a highly temperature-sensitive,
CC       heat activated channel showing a steep increase of inward currents at
CC       temperatures between 15 and 35 degrees Celsius. Heat activation is due
CC       to a shift of the voltage-dependent activation curve to negative
CC       potentials. Activated by arachidonic acid in vitro. May be involved in
CC       perception of bitter, sweet and umami tastes. May also be involved in
CC       sensing semiochemicals. {ECO:0000269|PubMed:14634208}.
CC   -!- INTERACTION:
CC       Q9NZQ8; Q9UM19: HPCAL4; NbExp=3; IntAct=EBI-18161658, EBI-744820;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000250|UniProtKB:Q8TD43, ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1 {ECO:0000269|PubMed:10607831, ECO:0000269|PubMed:15489334,
CC       ECO:0000269|PubMed:16554811};
CC         IsoId=Q9NZQ8-1; Sequence=Displayed;
CC       Name=2 {ECO:0000269|Ref.4};
CC         IsoId=Q9NZQ8-2; Sequence=VSP_052741;
CC       Name=3 {ECO:0000269|PubMed:10607831};
CC         IsoId=Q9NZQ8-3; Sequence=VSP_052742, VSP_052743;
CC   -!- TISSUE SPECIFICITY: Strongly expressed in fetal brain, liver and
CC       kidney, and in adult prostate, testis, ovary, colon and peripheral
CC       blood leukocytes. Also expressed in a large proportion of Wilms' tumors
CC       and rhabdomyosarcomas. In monochromosomal cell lines shows exclusive
CC       paternal expression. {ECO:0000269|PubMed:10607831}.
CC   -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. LTrpC
CC       subfamily. TRPM5 sub-subfamily. {ECO:0000305}.
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DR   EMBL; AF177473; AAF26288.1; -; mRNA.
DR   EMBL; AC124057; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC093787; AAH93787.1; -; mRNA.
DR   EMBL; BC093789; AAH93789.1; -; mRNA.
DR   EMBL; AJ270996; CAB66342.1; -; mRNA.
DR   CCDS; CCDS31340.1; -. [Q9NZQ8-1]
DR   RefSeq; NP_055370.1; NM_014555.3. [Q9NZQ8-1]
DR   AlphaFoldDB; Q9NZQ8; -.
DR   SMR; Q9NZQ8; -.
DR   BioGRID; 118932; 2.
DR   IntAct; Q9NZQ8; 2.
DR   STRING; 9606.ENSP00000155858; -.
DR   BindingDB; Q9NZQ8; -.
DR   ChEMBL; CHEMBL1628468; -.
DR   DrugCentral; Q9NZQ8; -.
DR   GuidetoPHARMACOLOGY; 497; -.
DR   TCDB; 1.A.4.5.3; the transient receptor potential ca2+/cation channel (trp-cc) family.
DR   iPTMnet; Q9NZQ8; -.
DR   PhosphoSitePlus; Q9NZQ8; -.
DR   BioMuta; TRPM5; -.
DR   DMDM; 74753086; -.
DR   MassIVE; Q9NZQ8; -.
DR   PaxDb; 9606-ENSP00000155858; -.
DR   PeptideAtlas; Q9NZQ8; -.
DR   ProteomicsDB; 83486; -. [Q9NZQ8-1]
DR   ProteomicsDB; 83487; -. [Q9NZQ8-2]
DR   ProteomicsDB; 83488; -. [Q9NZQ8-3]
DR   TopDownProteomics; Q9NZQ8-3; -. [Q9NZQ8-3]
DR   Antibodypedia; 23152; 209 antibodies from 30 providers.
DR   DNASU; 29850; -.
DR   Ensembl; ENST00000696290.1; ENSP00000512529.1; ENSG00000070985.14. [Q9NZQ8-1]
DR   GeneID; 29850; -.
DR   KEGG; hsa:29850; -.
DR   MANE-Select; ENST00000696290.1; ENSP00000512529.1; NM_014555.4; NP_055370.1.
DR   UCSC; uc001lwm.5; human. [Q9NZQ8-1]
DR   AGR; HGNC:14323; -.
DR   CTD; 29850; -.
DR   DisGeNET; 29850; -.
DR   GeneCards; TRPM5; -.
DR   HGNC; HGNC:14323; TRPM5.
DR   HPA; ENSG00000070985; Tissue enhanced (epididymis, intestine, pancreas).
DR   MIM; 604600; gene.
DR   neXtProt; NX_Q9NZQ8; -.
DR   OpenTargets; ENSG00000070985; -.
DR   PharmGKB; PA37869; -.
DR   VEuPathDB; HostDB:ENSG00000070985; -.
DR   eggNOG; KOG3614; Eukaryota.
DR   GeneTree; ENSGT00940000160588; -.
DR   InParanoid; Q9NZQ8; -.
DR   OMA; CYCTAVI; -.
DR   OrthoDB; 201873at2759; -.
DR   PhylomeDB; Q9NZQ8; -.
DR   TreeFam; TF314204; -.
DR   PathwayCommons; Q9NZQ8; -.
DR   Reactome; R-HSA-3295583; TRP channels.
DR   Reactome; R-HSA-9717207; Sensory perception of sweet, bitter, and umami (glutamate) taste.
DR   SignaLink; Q9NZQ8; -.
DR   BioGRID-ORCS; 29850; 13 hits in 1147 CRISPR screens.
DR   GeneWiki; TRPM5; -.
DR   GenomeRNAi; 29850; -.
DR   Pharos; Q9NZQ8; Tchem.
DR   PRO; PR:Q9NZQ8; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q9NZQ8; Protein.
DR   Bgee; ENSG00000070985; Expressed in mucosa of transverse colon and 35 other cell types or tissues.
DR   ExpressionAtlas; Q9NZQ8; baseline and differential.
DR   GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR   GO; GO:0016020; C:membrane; TAS:ProtInc.
DR   GO; GO:0034702; C:monoatomic ion channel complex; IEA:UniProtKB-KW.
DR   GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0005227; F:calcium-activated cation channel activity; IBA:GO_Central.
DR   GO; GO:0099604; F:ligand-gated calcium channel activity; IBA:GO_Central.
DR   GO; GO:0005216; F:monoatomic ion channel activity; TAS:ProtInc.
DR   GO; GO:0005267; F:potassium channel activity; IEA:Ensembl.
DR   GO; GO:0005272; F:sodium channel activity; TAS:Reactome.
DR   GO; GO:0070588; P:calcium ion transmembrane transport; IBA:GO_Central.
DR   InterPro; IPR005821; Ion_trans_dom.
DR   InterPro; IPR041491; TRPM_SLOG.
DR   PANTHER; PTHR13800:SF5; TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL SUBFAMILY M MEMBER 5; 1.
DR   PANTHER; PTHR13800; TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL, SUBFAMILY M, MEMBER 6; 1.
DR   Pfam; PF00520; Ion_trans; 1.
DR   Pfam; PF18139; LSDAT_euk; 1.
DR   Genevisible; Q9NZQ8; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Coiled coil; Ion channel;
KW   Ion transport; Ligand-gated ion channel; Membrane; Receptor;
KW   Reference proteome; Transmembrane; Transmembrane helix; Transport;
KW   Voltage-gated channel.
FT   CHAIN           1..1165
FT                   /note="Transient receptor potential cation channel
FT                   subfamily M member 5"
FT                   /id="PRO_0000328933"
FT   TOPO_DOM        1..646
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        647..667
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        668..733
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        734..754
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        755..811
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        812..832
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        833..835
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        836..856
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        857..872
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        873..893
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        894..954
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        955..975
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        976..1165
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          481..505
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1126..1165
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          553..581
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        483..499
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         155
FT                   /note="Q -> QVH (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.4"
FT                   /id="VSP_052741"
FT   VAR_SEQ         870..872
FT                   /note="MKD -> KPV (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:10607831"
FT                   /id="VSP_052742"
FT   VAR_SEQ         873..1165
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:10607831"
FT                   /id="VSP_052743"
FT   VARIANT         235
FT                   /note="N -> S (in dbSNP:rs886277)"
FT                   /id="VAR_052377"
FT   VARIANT         254
FT                   /note="V -> A (in dbSNP:rs3986599)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_042578"
FT   VARIANT         335
FT                   /note="V -> L (in dbSNP:rs34350821)"
FT                   /id="VAR_052378"
FT   VARIANT         456
FT                   /note="A -> T (in dbSNP:rs34551253)"
FT                   /id="VAR_052379"
FT   VARIANT         578
FT                   /note="R -> Q (in dbSNP:rs4929982)"
FT                   /id="VAR_059836"
SQ   SEQUENCE   1165 AA;  131451 MW;  C4AD5BAA866BE73B CRC64;
     MQDVQGPRPG SPGDAEDRRE LGLHRGEVNF GGSGKKRGKF VRVPSGVAPS VLFDLLLAEW
     HLPAPNLVVS LVGEEQPFAM KSWLRDVLRK GLVKAAQSTG AWILTSALRV GLARHVGQAV
     RDHSLASTST KVRVVAVGMA SLGRVLHRRI LEEAQEDFPV HYPEDDGGSQ GPLCSLDSNL
     SHFILVEPGP PGKGDGLTEL RLRLEKHISE QRAGYGGTGS IEIPVLCLLV NGDPNTLERI
     SRAVEQAAPW LILVGSGGIA DVLAALVNQP HLLVPKVAEK QFKEKFPSKH FSWEDIVRWT
     KLLQNITSHQ HLLTVYDFEQ EGSEELDTVI LKALVKACKS HSQEPQDYLD ELKLAVAWDR
     VDIAKSEIFN GDVEWKSCDL EEVMVDALVS NKPEFVRLFV DNGADVADFL TYGRLQELYR
     SVSRKSLLFD LLQRKQEEAR LTLAGLGTQQ AREPPAGPPA FSLHEVSRVL KDFLQDACRG
     FYQDGRPGDR RRAEKGPAKR PTGQKWLLDL NQKSENPWRD LFLWAVLQNR HEMATYFWAM
     GQEGVAAALA ACKILKEMSH LETEAEAARA TREAKYERLA LDLFSECYSN SEARAFALLV
     RRNRCWSKTT CLHLATEADA KAFFAHDGVQ AFLTRIWWGD MAAGTPILRL LGAFLCPALV
     YTNLITFSEE APLRTGLEDL QDLDSLDTEK SPLYGLQSRV EELVEAPRAQ GDRGPRAVFL
     LTRWRKFWGA PVTVFLGNVV MYFAFLFLFT YVLLVDFRPP PQGPSGPEVT LYFWVFTLVL
     EEIRQGFFTD EDTHLVKKFT LYVGDNWNKC DMVAIFLFIV GVTCRMLPSA FEAGRTVLAM
     DFMVFTLRLI HIFAIHKQLG PKIIVVERMM KDVFFFLFFL SVWLVAYGVT TQALLHPHDG
     RLEWIFRRVL YRPYLQIFGQ IPLDEIDEAR VNCSTHPLLL EDSPSCPSLY ANWLVILLLV
     TFLLVTNVLL MNLLIAMFSY TFQVVQGNAD MFWKFQRYNL IVEYHERPAL APPFILLSHL
     SLTLRRVFKK EAEHKREHLE RDLPDPLDQK VVTWETVQKE NFLSKMEKRR RDSEGEVLRK
     TAHRVDFIAK YLGGLREQEK RIKCLESQIN YCSVLVSSVA DVLAQGGGPR SSQHCGEGSQ
     LVAADHRGGL DGWEQPGAGQ PPSDT
//