CAHM1_HUMAN
ID CAHM1_HUMAN Reviewed; 346 AA.
AC Q8IU99; Q5W091;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Calcium homeostasis modulator protein 1;
DE AltName: Full=Protein FAM26C;
GN Name=CALHM1 {ECO:0000312|HGNC:HGNC:23494}; Synonyms=FAM26C;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-86.
RC TISSUE=Brain;
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 [3]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION
RP AT ASN-140, VARIANT PRO-86, POLYMORPHISM, AND MUTAGENESIS OF ASN-72; ASN-74
RP AND ASN-140.
RX PubMed=18585350; DOI=10.1016/j.cell.2008.05.048;
RA Dreses-Werringloer U., Lambert J.-C., Vingtdeux V., Zhao H., Vais H.,
RA Siebert A., Jain A., Koppel J., Rovelet-Lecrux A., Hannequin D.,
RA Pasquier F., Galimberti D., Scarpini E., Mann D., Lendon C., Campion D.,
RA Amouyel P., Davies P., Foskett J.K., Campagne F., Marambaud P.;
RT "A polymorphism in CALHM1 influences Ca2+ homeostasis, Abeta levels, and
RT Alzheimer's disease risk.";
RL Cell 133:1149-1161(2008).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=19997627; DOI=10.1371/journal.pone.0007682;
RA Moyer B.D., Hevezi P., Gao N., Lu M., Kalabat D., Soto H., Echeverri F.,
RA Laita B., Yeh S.A., Zoller M., Zlotnik A.;
RT "Expression of genes encoding multi-transmembrane proteins in specific
RT primate taste cell populations.";
RL PLoS ONE 4:E7682-E7682(2009).
RN [5]
RP FUNCTION.
RX PubMed=21574960; DOI=10.1042/bj20110479;
RA Gallego-Sandin S., Alonso M.T., Garcia-Sancho J.;
RT "Calcium homoeostasis modulator 1 (CALHM1) reduces the calcium content of
RT the endoplasmic reticulum (ER) and triggers ER stress.";
RL Biochem. J. 437:469-475(2011).
RN [6]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ASN-72; ASP-121; GLU-163 AND ASP-166.
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 [7]
RP FUNCTION, SUBUNIT, TOPOLOGY, AND SUBCELLULAR LOCATION.
RX PubMed=23300080; DOI=10.1074/jbc.m112.409789;
RA Siebert A.P., Ma Z., Grevet J.D., Demuro A., Parker I., Foskett J.K.;
RT "Structural and functional similarities of calcium homeostasis modulator 1
RT (CALHM1) ion channel with connexins, pannexins, and innexins.";
RL J. Biol. Chem. 288:6140-6153(2013).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF TRP-114 AND ASN-140.
RX PubMed=23345406; DOI=10.1242/jcs.117135;
RA Dreses-Werringloer U., Vingtdeux V., Zhao H., Chandakkar P., Davies P.,
RA Marambaud P.;
RT "CALHM1 controls Ca2+-dependent MEK/ERK/RSK/MSK signaling in neurons.";
RL J. Cell Sci. 126:1199-1206(2013).
RN [9]
RP VARIANT PRO-86.
RX PubMed=19472444; DOI=10.1111/j.1469-1809.2009.00509.x;
RA Beecham G.W., Schnetz-Boutaud N., Haines J.L., Pericak-Vance M.A.;
RT "CALHM1 polymorphism is not associated with late-onset Alzheimer disease.";
RL Ann. Hum. Genet. 73:379-381(2009).
RN [10]
RP VARIANT PRO-86.
RX PubMed=19070563; DOI=10.1016/j.cell.2008.11.030;
RA Bertram L., Schjeide B.M., Hooli B., Mullin K., Hiltunen M., Soininen H.,
RA Ingelsson M., Lannfelt L., Blacker D., Tanzi R.E.;
RT "No association between CALHM1 and Alzheimer's disease risk.";
RL Cell 135:993-994(2008).
RN [11]
RP VARIANT PRO-86.
RX PubMed=19191331; DOI=10.1002/humu.20989;
RA Minster R.L., Demirci F.Y., DeKosky S.T., Kamboh M.I.;
RT "No association between CALHM1 variation and risk of Alzheimer disease.";
RL Hum. Mutat. 30:E566-E569(2009).
RN [12]
RP VARIANT PRO-86.
RX PubMed=19191332; DOI=10.1002/humu.20990;
RA Sleegers K., Brouwers N., Bettens K., Engelborghs S., van Miegroet H.,
RA De Deyn P.P., Van Broeckhoven C.;
RT "No association between CALHM1 and risk for Alzheimer dementia in a Belgian
RT population.";
RL Hum. Mutat. 30:E570-E574(2009).
RN [13]
RP VARIANT PRO-86.
RX PubMed=19545933; DOI=10.1016/j.neurobiolaging.2009.05.008;
RA Tan E.K., Ho P., Cheng S.Y., Yih Y., Li H.H., Fook-Chong S., Lee W.L.,
RA Zhao Y.;
RT "CALHM1 variant is not associated with Alzheimer's disease among Asians.";
RL Neurobiol. Aging 32:546.E11-546.E12(2011).
RN [14]
RP VARIANT PRO-86.
RX PubMed=19655363; DOI=10.1002/ajmg.b.31014;
RA Inoue K., Tanaka N., Yamashita F., Sawano Y., Asada T., Goto Y.;
RT "The P86L common allele of CALHM1 does not influence risk for Alzheimer
RT disease in Japanese cohorts.";
RL Am. J. Med. Genet. B Neuropsychiatr. Genet. 153:532-535(2010).
RN [15]
RP VARIANT PRO-86.
RX PubMed=20061624; DOI=10.3233/jad-2010-1207;
RA Cui P.J., Zheng L., Cao L., Wang Y., Deng Y.L., Wang G., Xu W., Tang H.D.,
RA Ma J.F., Zhang T., Ding J.Q., Cheng Q., Chen S.D.;
RT "CALHM1 P86L polymorphism is a risk factor for Alzheimer's disease in the
RT Chinese population.";
RL J. Alzheimers Dis. 19:31-35(2010).
RN [16]
RP VARIANT PRO-86.
RX PubMed=20164592; DOI=10.3233/jad-2010-1357;
RA Boada M., Antunez C., Lopez-Arrieta J., Galan J.J., Moron F.J.,
RA Hernandez I., Marin J., Martinez-Lage P., Alegret M., Carrasco J.M.,
RA Moreno C., Real L.M., Gonzalez-Perez A., Tarraga L., Ruiz A.;
RT "CALHM1 P86L polymorphism is associated with late-onset Alzheimer's disease
RT in a recessive model.";
RL J. Alzheimers Dis. 20:247-251(2010).
RN [17]
RP VARIANT PRO-86.
RX PubMed=20847397; DOI=10.3233/jad-2010-100933;
RA Lambert J.C., Sleegers K., Gonzalez-Perez A., Ingelsson M., Beecham G.W.,
RA Hiltunen M., Combarros O., Bullido M.J., Brouwers N., Bettens K., Berr C.,
RA Pasquier F., Richard F., Dekosky S.T., Hannequin D., Haines J.L.,
RA Tognoni G., Fievet N., Dartigues J.F., Tzourio C., Engelborghs S.,
RA Arosio B., Coto E., De Deyn P., Del Zompo M., Mateo I., Boada M.,
RA Antunez C., Lopez-Arrieta J., Epelbaum J., Schjeide B.M., Frank-Garcia A.,
RA Giedraitis V., Helisalmi S., Porcellini E., Pilotto A., Forti P., Ferri R.,
RA Delepine M., Zelenika D., Lathrop M., Scarpini E., Siciliano G.,
RA Solfrizzi V., Sorbi S., Spalletta G., Ravaglia G., Valdivieso F.,
RA Vepsalainen S., Alvarez V., Bosco P., Mancuso M., Panza F., Nacmias B.,
RA Bossu P., Hanon O., Piccardi P., Annoni G., Mann D., Marambaud P.,
RA Seripa D., Galimberti D., Tanzi R.E., Bertram L., Lendon C., Lannfelt L.,
RA Licastro F., Campion D., Pericak-Vance M.A., Soininen H.,
RA Van Broeckhoven C., Alperovitch A., Ruiz A., Kamboh M.I., Amouyel P.;
RT "The CALHM1 P86L polymorphism is a genetic modifier of age at onset in
RT Alzheimer's disease: a meta-analysis study.";
RL J. Alzheimers Dis. 22:247-255(2010).
RN [18]
RP VARIANT PRO-86.
RX PubMed=21378601; DOI=10.1097/ypg.0b013e3283457bcc;
RA Feher A., Juhasz A., Rimanoczy A., Pakaski M., Kalman J., Janka Z.;
RT "No association between CALHM1 polymorphism and Alzheimer's disease risk in
RT a Hungarian population.";
RL Psychiatr. Genet. 21:249-252(2011).
CC -!- FUNCTION: Pore-forming subunit of a voltage-gated ion channel required
CC for sensory perception of sweet, bitter and umami tastes (By
CC similarity). Specifically present in type II taste bud cells, where it
CC plays a central role in sweet, bitter and umami taste perception by
CC inducing ATP release from the cell, ATP acting as a neurotransmitter to
CC activate afferent neural gustatory pathways (By similarity). Together
CC with CALHM3, forms a fast-activating voltage-gated ATP-release channel
CC in type II taste bud cells (TBCs) (By similarity). 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, PubMed:23300080). Has poor ion
CC selectivity and forms a wide pore (around 14 Angstroms) that mediates
CC permeation of Ca(2+), Na(+) and K(+), as well as permeation of
CC monovalent anions (PubMed:22711817). Acts as an activator of the ERK1
CC and ERK2 cascade (PubMed:23345406). Triggers endoplasmic reticulum
CC stress by reducing the calcium content of the endoplasmic reticulum
CC (PubMed:21574960). May indirectly control amyloid precursor protein
CC (APP) proteolysis and aggregated amyloid-beta (Abeta) peptides levels
CC in a Ca(2+) dependent manner (PubMed:18585350).
CC {ECO:0000250|UniProtKB:D3Z291, ECO:0000269|PubMed:18585350,
CC ECO:0000269|PubMed:21574960, ECO:0000269|PubMed:22711817,
CC ECO:0000269|PubMed:23300080, ECO:0000269|PubMed:23345406}.
CC -!- ACTIVITY REGULATION: Inhibited by Gd(3+), Ruthenium Red, and Zn(2+) and
CC partially inhibited by 2-aminoethoxydiphenyl borate.
CC {ECO:0000269|PubMed:22711817}.
CC -!- SUBUNIT: Homohexamer. Associates with CALHM3 as a pore-forming subunit
CC in an hetero-hexameric channel complex (By similarity).
CC {ECO:0000250|UniProtKB:D3Z291, ECO:0000269|PubMed:18585350,
CC ECO:0000269|PubMed:23300080}.
CC -!- INTERACTION:
CC Q8IU99; P05067: APP; NbExp=3; IntAct=EBI-1790341, EBI-77613;
CC Q8IU99; Q8IU99: CALHM1; NbExp=3; IntAct=EBI-1790341, EBI-1790341;
CC Q8IU99; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-1790341, EBI-9087876;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein
CC {ECO:0000269|PubMed:18585350, ECO:0000269|PubMed:22711817,
CC ECO:0000269|PubMed:23300080}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:18585350}; Multi-pass membrane protein. Basolateral
CC cell membrane; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:D3Z291}. Note=Colocalizes with HSPA5 at the
CC endoplasmic reticulum (PubMed:18585350). Localizes to the basolateral
CC membrane of epithelial cells including taste cells (By similarity).
CC {ECO:0000250|UniProtKB:D3Z291, ECO:0000269|PubMed:18585350}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in adult brain. Detected
CC also in retinoic acid-differentiated SH-SY5Y cells. Specifically
CC expressed in circumvallate taste bud cells.
CC {ECO:0000269|PubMed:18585350, ECO:0000269|PubMed:19997627}.
CC -!- POLYMORPHISM: Leu-86 causes a dysregulation of Ca(2+) homeostasis and
CC amyloid precursor protein (APP) metabolism and has been suggested to be
CC a risk factor for the development of Alzheimer disease
CC (PubMed:18585350, PubMed:20061624, PubMed:20164592). However, this
CC association with Alzheimer disease could not be confirmed in a number
CC of studies performed in different populations (PubMed:19472444,
CC PubMed:19070563, PubMed:19191331, PubMed:19191332, PubMed:19545933,
CC PubMed:19655363, PubMed:21378601). According to a meta-analysis study,
CC Leu-86 is likely not a genetic determinant of Alzheimer disease but may
CC modulate age of onset by interacting with the effect of the APOE*4
CC allele of the APOE gene (PubMed:20847397).
CC {ECO:0000269|PubMed:18585350, ECO:0000269|PubMed:19070563,
CC ECO:0000269|PubMed:19191331, ECO:0000269|PubMed:19191332,
CC ECO:0000269|PubMed:19472444, ECO:0000269|PubMed:19545933,
CC ECO:0000269|PubMed:19655363, ECO:0000269|PubMed:20061624,
CC ECO:0000269|PubMed:20164592, ECO:0000269|PubMed:20847397,
CC ECO:0000269|PubMed:21378601}.
CC -!- SIMILARITY: Belongs to the CALHM family. {ECO:0000305}.
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DR EMBL; AL139339; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036193; AAH36193.1; -; mRNA.
DR EMBL; BC036208; AAH36208.1; -; mRNA.
DR CCDS; CCDS7550.1; -.
DR RefSeq; NP_001001412.3; NM_001001412.3.
DR AlphaFoldDB; Q8IU99; -.
DR SMR; Q8IU99; -.
DR IntAct; Q8IU99; 3.
DR STRING; 9606.ENSP00000329926; -.
DR TCDB; 1.A.84.1.1; the calcium homeostasis modulator ca(2+) channel (calhm-c) family.
DR GlyGen; Q8IU99; 1 site.
DR iPTMnet; Q8IU99; -.
DR PhosphoSitePlus; Q8IU99; -.
DR BioMuta; CALHM1; -.
DR DMDM; 68565595; -.
DR PaxDb; Q8IU99; -.
DR PeptideAtlas; Q8IU99; -.
DR PRIDE; Q8IU99; -.
DR ProteomicsDB; 70525; -.
DR Antibodypedia; 3119; 160 antibodies from 29 providers.
DR DNASU; 255022; -.
DR Ensembl; ENST00000329905.6; ENSP00000329926.6; ENSG00000185933.7.
DR GeneID; 255022; -.
DR KEGG; hsa:255022; -.
DR MANE-Select; ENST00000329905.6; ENSP00000329926.6; NM_001001412.4; NP_001001412.3.
DR UCSC; uc001kxe.3; human.
DR CTD; 255022; -.
DR DisGeNET; 255022; -.
DR GeneCards; CALHM1; -.
DR HGNC; HGNC:23494; CALHM1.
DR HPA; ENSG00000185933; Tissue enhanced (brain).
DR MIM; 612234; gene.
DR neXtProt; NX_Q8IU99; -.
DR OpenTargets; ENSG00000185933; -.
DR PharmGKB; PA162380954; -.
DR VEuPathDB; HostDB:ENSG00000185933; -.
DR eggNOG; ENOG502RCIV; Eukaryota.
DR GeneTree; ENSGT01030000234610; -.
DR HOGENOM; CLU_069286_0_0_1; -.
DR InParanoid; Q8IU99; -.
DR OMA; WHRCKPP; -.
DR OrthoDB; 960393at2759; -.
DR PhylomeDB; Q8IU99; -.
DR TreeFam; TF329085; -.
DR PathwayCommons; Q8IU99; -.
DR Reactome; R-HSA-9717207; Sensory perception of sweet, bitter, and umami (glutamate) taste.
DR Reactome; R-HSA-9730628; Sensory perception of salty taste.
DR SignaLink; Q8IU99; -.
DR BioGRID-ORCS; 255022; 11 hits in 1069 CRISPR screens.
DR GenomeRNAi; 255022; -.
DR Pharos; Q8IU99; Tbio.
DR PRO; PR:Q8IU99; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q8IU99; protein.
DR Bgee; ENSG00000185933; Expressed in endothelial cell and 34 other tissues.
DR Genevisible; Q8IU99; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005227; F:calcium activated cation channel activity; IDA:UniProtKB.
DR GO; GO:0005261; F:cation channel activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IEA:Ensembl.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IDA:UniProtKB.
DR GO; GO:0015867; P:ATP transport; ISS:UniProtKB.
DR GO; GO:0006812; P:cation transport; IDA:UniProtKB.
DR GO; GO:0051291; P:protein heterooligomerization; IEA:Ensembl.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0050913; P:sensory perception of bitter taste; ISS:UniProtKB.
DR GO; GO:0050916; P:sensory perception of sweet taste; ISS:UniProtKB.
DR GO; GO:0050917; P:sensory perception of umami taste; ISS: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..346
FT /note="Calcium homeostasis modulator protein 1"
FT /id="PRO_0000186723"
FT TOPO_DOM 1..17
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 18..38
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 39..50
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 51..71
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 72..108
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 109..129
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 130..181
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 182..202
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 203..346
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 313..346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 74
FT /note="Not glycosylated"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:18585350"
FT VARIANT 86
FT /note="L -> P (in dbSNP:rs2986017)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:18585350, ECO:0000269|PubMed:19070563,
FT ECO:0000269|PubMed:19191331, ECO:0000269|PubMed:19191332,
FT ECO:0000269|PubMed:19472444, ECO:0000269|PubMed:19545933,
FT ECO:0000269|PubMed:19655363, ECO:0000269|PubMed:20061624,
FT ECO:0000269|PubMed:20164592, ECO:0000269|PubMed:20847397,
FT ECO:0000269|PubMed:21378601"
FT /id="VAR_023095"
FT MUTAGEN 72
FT /note="N->G: Significant inhibition on the control of
FT cytosolic Ca(2+) levels. Does not affect ion channel
FT activity."
FT /evidence="ECO:0000269|PubMed:18585350,
FT ECO:0000269|PubMed:22711817"
FT MUTAGEN 74
FT /note="N->A: Has no effect on glycosylation."
FT /evidence="ECO:0000269|PubMed:18585350"
FT MUTAGEN 114
FT /note="W->A: Impairs ability to activate the ERK1 and ERK2
FT cascade."
FT /evidence="ECO:0000269|PubMed:23345406"
FT MUTAGEN 121
FT /note="D->C: Impaired ion channel activity in response to
FT change in extracellular Ca(2+) concentration."
FT /evidence="ECO:0000269|PubMed:22711817"
FT MUTAGEN 121
FT /note="D->E: No effect."
FT /evidence="ECO:0000269|PubMed:22711817"
FT MUTAGEN 140
FT /note="N->A: Prevents glycosylation and impairs ability to
FT activate the ERK1 and ERK2 cascade."
FT /evidence="ECO:0000269|PubMed:18585350,
FT ECO:0000269|PubMed:23345406"
FT MUTAGEN 163
FT /note="E->A: No effect."
FT /evidence="ECO:0000269|PubMed:22711817"
FT MUTAGEN 166
FT /note="D->R: No effect."
FT /evidence="ECO:0000269|PubMed:22711817"
FT CONFLICT 264
FT /note="H -> N (in Ref. 2; AAH36193/AAH36208)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 346 AA; 38264 MW; 13A1FBA6592A9EC1 CRC64;
MMDKFRMIFQ FLQSNQESFM NGICGIMALA SAQMYSAFDF NCPCLPGYNA AYSAGILLAP
PLVLFLLGLV MNNNVSMLAE EWKRPLGRRA KDPAVLRYMF CSMAQRALIA PVVWVAVTLL
DGKCFLCAFC TAVPVSALGN GSLAPGLPAP ELARLLARVP CPEIYDGDWL LAREVAVRYL
RCISQALGWS FVLLTTLLAF VVRSVRPCFT QAAFLKSKYW SHYIDIERKL FDETCTEHAK
AFAKVCIQQF FEAMNHDLEL GHTHGTLATA PASAAAPTTP DGAEEEREKL RGITDQGTMN
RLLTSWHKCK PPLRLGQEEP PLMGNGWAGG GPRPPRKEVA TYFSKV
