CAHM1_MOUSE
ID CAHM1_MOUSE Reviewed; 348 AA.
AC D3Z291;
DT 01-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Calcium homeostasis modulator protein 1;
GN Name=Calhm1 {ECO:0000312|MGI:MGI:3643383};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=22711817; DOI=10.1073/pnas.1204023109;
RA Ma Z., Siebert A.P., Cheung K.H., Lee R.J., Johnson B., Cohen A.S.,
RA Vingtdeux V., Marambaud P., Foskett J.K.;
RT "Calcium homeostasis modulator 1 (CALHM1) is the pore-forming subunit of an
RT ion channel that mediates extracellular Ca2+ regulation of neuronal
RT excitability.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:E1963-E1971(2012).
RN [4]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=22723178; DOI=10.1007/s13238-012-2932-6;
RA Wu J., Peng S., Wu R., Hao Y., Ji G., Yuan Z.;
RT "Generation of Calhm1 knockout mouse and characterization of calhm1 gene
RT expression.";
RL Protein Cell 3:470-480(2012).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=23467090; DOI=10.1038/nature11906;
RA Taruno A., Vingtdeux V., Ohmoto M., Ma Z., Dvoryanchikov G., Li A.,
RA Adrien L., Zhao H., Leung S., Abernethy M., Koppel J., Davies P.,
RA Civan M.M., Chaudhari N., Matsumoto I., Hellekant G., Tordoff M.G.,
RA Marambaud P., Foskett J.K.;
RT "CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter
RT and umami tastes.";
RL Nature 495:223-226(2013).
RN [6]
RP FUNCTION, AND INTERACTION WITH CALHM3.
RX PubMed=29681531; DOI=10.1016/j.neuron.2018.03.043;
RA Ma Z., Taruno A., Ohmoto M., Jyotaki M., Lim J.C., Miyazaki H., Niisato N.,
RA Marunaka Y., Lee R.J., Hoff H., Payne R., Demuro A., Parker I.,
RA Mitchell C.H., Henao-Mejia J., Tanis J.E., Matsumoto I., Tordoff M.G.,
RA Foskett J.K.;
RT "CALHM3 Is Essential for Rapid Ion Channel-Mediated Purinergic
RT Neurotransmission of GPCR-Mediated Tastes.";
RL Neuron 98:547-561(2018).
RN [7]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 76-MET-LEU-77; TYR-222 AND
RP ILE-225.
RX PubMed=30804437; DOI=10.1038/s41598-019-39593-5;
RA Kashio M., Wei-Qi G., Ohsaki Y., Kido M.A., Taruno A.;
RT "CALHM1/CALHM3 channel is intrinsically sorted to the basolateral membrane
RT of epithelial cells including taste cells.";
RL Sci. Rep. 9:2681-2681(2019).
CC -!- FUNCTION: Pore-forming subunit of a voltage-gated ion channel, also
CC permeable to larger molecules including ATP, required for sensory
CC perception of sweet, bitter and umami tastes (PubMed:23467090).
CC Specifically present in type II taste bud cells, where it plays a
CC central role in sweet, bitter and umami taste perception by inducing
CC ATP release from the cell, ATP acting as a neurotransmitter to activate
CC afferent neural gustatory pathways (PubMed:23467090). Together with
CC CALHM3, forms a fast-activating voltage-gated ATP-release channel in
CC type II taste bud cells (TBCs) (PubMed:29681531). Acts both as a
CC voltage-gated and calcium-activated ion channel: mediates neuronal
CC excitability in response to changes in extracellular Ca(2+)
CC concentration (PubMed:22711817). Has poor ion selectivity and forms a
CC wide pore (around 14 Angstroms) that mediates permeation of Ca(2+),
CC Na(+) and K(+), as well as permeation of monovalent anions
CC (PubMed:22711817). Acts as an activator of the ERK1 and ERK2 cascade
CC (By similarity). Triggers endoplasmic reticulum stress by reducing the
CC calcium content of the endoplasmic reticulum (By similarity). May
CC indirectly control amyloid precursor protein (APP) proteolysis and
CC aggregated amyloid-beta (Abeta) peptides levels in a Ca(2+) dependent
CC manner (By similarity). {ECO:0000250|UniProtKB:Q8IU99,
CC ECO:0000269|PubMed:22711817, ECO:0000269|PubMed:23467090,
CC ECO:0000269|PubMed:29681531}.
CC -!- ACTIVITY REGULATION: Inhibited by Gd(3+), Ruthenium Red, and Zn(2+) and
CC partially inhibited by 2-aminoethoxydiphenyl borate.
CC {ECO:0000250|UniProtKB:Q8IU99}.
CC -!- SUBUNIT: Homohexamer (By similarity). Associates with CALHM3 as a pore-
CC forming subunit in an hetero-hexameric channel complex
CC (PubMed:29681531). {ECO:0000250|UniProtKB:Q8IU99,
CC ECO:0000269|PubMed:29681531}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8IU99};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q8IU99}. Endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:Q8IU99}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:Q8IU99}. Basolateral cell membrane
CC {ECO:0000269|PubMed:30804437}; Multi-pass membrane protein.
CC Note=Localizes to the basolateral membrane of epithelial cells
CC including taste cells (PubMed:30804437). Colocalizes with HSPA5 at the
CC endoplasmic reticulum (By similarity). {ECO:0000250|UniProtKB:Q8IU99,
CC ECO:0000269|PubMed:30804437}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in type II taste bud cells.
CC Not expressed in brain. {ECO:0000269|PubMed:22711817,
CC ECO:0000269|PubMed:22723178, ECO:0000269|PubMed:23467090}.
CC -!- DISRUPTION PHENOTYPE: Impaired perceptions of sweet, bitter and umami
CC compounds. Mice are viable and fertile, with no visible morphological
CC abnormalities in their taste buds or any altered expression of taste-
CC related marker genes. They do however display a loss of both preference
CC for sweet and umami compounds and for avoidance of bitter compounds.
CC Perceptions of sour and salty tastes are unaffected. Reduced voltage-
CC gated currents in type II cells and taste-evoked ATP release from taste
CC buds without affecting the excitability of taste cells by taste
CC stimuli. Elderly males and females do not show defects in spatial
CC learning and memory retrieving. {ECO:0000269|PubMed:22723178,
CC ECO:0000269|PubMed:23467090}.
CC -!- SIMILARITY: Belongs to the CALHM family. {ECO:0000305}.
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DR EMBL; AC124724; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466534; EDL42030.1; -; Genomic_DNA.
DR CCDS; CCDS38015.1; -.
DR RefSeq; NP_001074740.1; NM_001081271.1.
DR AlphaFoldDB; D3Z291; -.
DR SMR; D3Z291; -.
DR STRING; 10090.ENSMUSP00000107444; -.
DR GlyGen; D3Z291; 1 site.
DR iPTMnet; D3Z291; -.
DR PhosphoSitePlus; D3Z291; -.
DR SwissPalm; D3Z291; -.
DR PaxDb; D3Z291; -.
DR PRIDE; D3Z291; -.
DR Antibodypedia; 3119; 160 antibodies from 29 providers.
DR Ensembl; ENSMUST00000111813; ENSMUSP00000107444; ENSMUSG00000079258.
DR GeneID; 546729; -.
DR KEGG; mmu:546729; -.
DR UCSC; uc008hus.1; mouse.
DR CTD; 255022; -.
DR MGI; MGI:3643383; Calhm1.
DR VEuPathDB; HostDB:ENSMUSG00000079258; -.
DR eggNOG; ENOG502RCIV; Eukaryota.
DR GeneTree; ENSGT01030000234610; -.
DR HOGENOM; CLU_069286_0_0_1; -.
DR InParanoid; D3Z291; -.
DR OMA; WHRCKPP; -.
DR OrthoDB; 960393at2759; -.
DR PhylomeDB; D3Z291; -.
DR TreeFam; TF329085; -.
DR BioGRID-ORCS; 546729; 3 hits in 72 CRISPR screens.
DR PRO; PR:D3Z291; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; D3Z291; protein.
DR ExpressionAtlas; D3Z291; baseline and differential.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005227; F:calcium activated cation channel activity; ISS:UniProtKB.
DR GO; GO:0005261; F:cation channel activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:CACAO.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IMP:UniProtKB.
DR GO; GO:0015867; P:ATP transport; IMP:UniProtKB.
DR GO; GO:0006812; P:cation transport; ISS:UniProtKB.
DR GO; GO:0051291; P:protein heterooligomerization; IDA:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0050913; P:sensory perception of bitter taste; IMP:UniProtKB.
DR GO; GO:0050916; P:sensory perception of sweet taste; IMP:UniProtKB.
DR GO; GO:0050909; P:sensory perception of taste; IMP:CACAO.
DR GO; GO:0050917; P:sensory perception of umami taste; IMP:UniProtKB.
DR InterPro; IPR029569; CALHM.
DR InterPro; IPR029568; CALHM1.
DR PANTHER; PTHR32261; PTHR32261; 1.
DR PANTHER; PTHR32261:SF2; PTHR32261:SF2; 1.
DR Pfam; PF14798; Ca_hom_mod; 1.
PE 1: Evidence at protein level;
KW Calcium; Calcium channel; Calcium transport; Cell membrane;
KW Endoplasmic reticulum; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Reference proteome; Sensory transduction; Taste; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..348
FT /note="Calcium homeostasis modulator protein 1"
FT /id="PRO_0000422239"
FT TOPO_DOM 1..16
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..48
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 49..69
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 70..107
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 108..128
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 129..180
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..201
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 202..348
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 324..348
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 139
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 76..77
FT /note="ML->AA: Affects basolateral membrane sorting in
FT vitro but not in vivo; when associated with A-222 and A-
FT 225."
FT /evidence="ECO:0000269|PubMed:30804437"
FT MUTAGEN 222
FT /note="Y->A: Affects basolateral membrane sorting in vitro
FT but not in vivo; when associated with 76-A-A-77 and A-225."
FT /evidence="ECO:0000269|PubMed:30804437"
FT MUTAGEN 225
FT /note="I->A: Affects basolateral membrane sorting in vitro
FT but not in vivo; when associated with 76-A-A-77 and A-222."
FT /evidence="ECO:0000269|PubMed:30804437"
SQ SEQUENCE 348 AA; 38827 MW; 338717B7C1F8C354 CRC64;
MDKFRMIFQF LQSNQESFMN GICGIMALAS AQMYSAFDFN CPCLPGYNVV YSLGILLTPP
LVLFLLGLVM NNNISMLAEE WKRPAGRRAK DPAVLRYMFC SMAQRALIAP VVWVAVTLLD
GKCFLCAFCT AVPVATLGNG SLVPGLPAPE LARLLARVPC PEIYDGNWLL AREVAVRYLR
CISQALGWSF VLLTTLLAFV VRSVRPCFTQ VAFLKSKYWS HYIDIERKLF DETCTEHAKA
FAKVCIQQFF EAMNHDLELG HTHGVLATAT ATATATEAVQ SPSDRTEEER EKLRGITDQG
TMNRLLTSWH KCKPPLRLGQ EAPLMSNGWA GGEPRPPRKE VATYFSKV
