TRPM7_HUMAN
ID TRPM7_HUMAN Reviewed; 1865 AA.
AC Q96QT4; Q6ZMF5; Q86VJ4; Q8NBW2; Q9BXB2; Q9NXQ2;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Transient receptor potential cation channel subfamily M member 7;
DE EC=2.7.11.1;
DE AltName: Full=Channel-kinase 1;
DE AltName: Full=Long transient receptor potential channel 7;
DE Short=LTrpC-7;
DE Short=LTrpC7;
GN Name=TRPM7; Synonyms=CHAK1, LTRPC7;
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], AND CHARACTERIZATION.
RX PubMed=11385574; DOI=10.1038/35079092;
RA Nadler M.J.S., Hermosura M.C., Inabe K., Perraud A.-L., Zhu Q.,
RA Stokes A.J., Kurosaki T., Kinet J.-P., Penner R., Scharenberg A.M.,
RA Fleig A.;
RT "LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell
RT viability.";
RL Nature 411:590-595(2001).
RN [2]
RP ERRATUM OF PUBMED:11385574.
RA Nadler M.J.S., Hermosura M.C., Inabe K., Perraud A.-L., Zhu Q.,
RA Stokes A.J., Kurosaki T., Kinet J.-P., Penner R., Scharenberg A.M.,
RA Fleig A.;
RL Nature 412:660-660(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RX PubMed=14594813; DOI=10.1074/jbc.m308820200;
RA Ryazanova L.V., Dorovkov M.V., Ansari A., Ryazanov A.G.;
RT "Characterization of the protein kinase activity of TRPM7/ChaK1, a protein
RT kinase fused to the transient receptor potential ion channel.";
RL J. Biol. Chem. 279:3708-3716(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-575 AND 1096-1865, AND VARIANT
RP ILE-1482.
RC TISSUE=Colon, and 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).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 464-998.
RC TISSUE=Liver;
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 FUNCTION, AND MUTAGENESIS OF LYS-1648 AND GLY-1799.
RX PubMed=12887921; DOI=10.1016/s0092-8674(03)00556-7;
RA Schmitz C., Perraud A.-L., Johnson C.O., Inabe K., Smith M.K., Penner R.,
RA Kurosaki T., Fleig A., Scharenberg A.M.;
RT "Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7.";
RL Cell 114:191-200(2003).
RN [7]
RP FUNCTION.
RX PubMed=15485879; DOI=10.1074/jbc.c400441200;
RA Dorovkov M.V., Ryazanov A.G.;
RT "Phosphorylation of annexin I by TRPM7 channel-kinase.";
RL J. Biol. Chem. 279:50643-50646(2004).
RN [8]
RP INTERACTION WITH TRPM6.
RX PubMed=14976260; DOI=10.1073/pnas.0305252101;
RA Chubanov V., Waldegger S., Mederos y Schnitzler M., Vitzthum H.,
RA Sassen M.C., Seyberth H.W., Konrad M., Gudermann T.;
RT "Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6
RT gene causes hypomagnesemia with secondary hypocalcemia.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:2894-2899(2004).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1477, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-101; SER-1387; SER-1390;
RP SER-1395; SER-1404; SER-1477; SER-1527 AND SER-1569, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP FUNCTION.
RX PubMed=24316671; DOI=10.1038/ncb2883;
RA Cai Z., Jitkaew S., Zhao J., Chiang H.C., Choksi S., Liu J., Ward Y.,
RA Wu L.G., Liu Z.G.;
RT "Plasma membrane translocation of trimerized MLKL protein is required for
RT TNF-induced necroptosis.";
RL Nat. Cell Biol. 16:55-65(2014).
RN [14]
RP VARIANT ILE-1482, AND CHARACTERIZATION OF VARIANT ILE-1482.
RX PubMed=16051700; DOI=10.1073/pnas.0505149102;
RA Hermosura M.C., Nayakanti H., Dorovkov M.V., Calderon F.R., Ryazanov A.G.,
RA Haymer D.S., Garruto R.M.;
RT "A TRPM7 variant shows altered sensitivity to magnesium that may contribute
RT to the pathogenesis of two Guamanian neurodegenerative disorders.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:11510-11515(2005).
RN [15]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-68; CYS-406; THR-459; ASN-574; SER-720;
RP VAL-830; TYR-949; ARG-1064; THR-1211; VAL-1254; GLU-1306; LYS-1444 AND
RP ILE-1482.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Essential ion channel and serine/threonine-protein kinase.
CC Divalent cation channel permeable to calcium and magnesium. Has a
CC central role in magnesium ion homeostasis and in the regulation of
CC anoxic neuronal cell death. Involved in TNF-induced necroptosis
CC downstream of MLKL by mediating calcium influx. The kinase activity is
CC essential for the channel function. May be involved in a fundamental
CC process that adjusts plasma membrane divalent cation fluxes according
CC to the metabolic state of the cell. Phosphorylates annexin A1 (ANXA1).
CC {ECO:0000269|PubMed:12887921, ECO:0000269|PubMed:15485879,
CC ECO:0000269|PubMed:24316671}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Homodimer. Interacts with PLCB1 (By similarity). Forms
CC heterodimers with TRPM6. {ECO:0000250, ECO:0000269|PubMed:14976260}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- PTM: Autophosphorylated. {ECO:0000250}.
CC -!- DISEASE: Amyotrophic lateral sclerosis-parkinsonism/dementia complex 1
CC (ALS-PDC1) [MIM:105500]: A neurodegenerative disorder characterized by
CC chronic, progressive and uniformly fatal amyotrophic lateral sclerosis
CC and parkinsonism-dementia. Both diseases are known to occur in the same
CC kindred, the same sibship and even the same individual. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: In the C-terminal section; belongs to the protein kinase
CC superfamily. Alpha-type protein kinase family. ALPK subfamily.
CC {ECO:0000305}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the transient
CC receptor (TC 1.A.4) family. LTrpC subfamily. TRPM7 sub-subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC11462.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAD18773.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY032950; AAK44211.1; -; mRNA.
DR EMBL; AF346629; AAK19738.2; -; mRNA.
DR EMBL; AK000124; BAA90958.1; -; mRNA.
DR EMBL; AK172800; BAD18773.1; ALT_INIT; mRNA.
DR EMBL; AK075193; BAC11462.1; ALT_INIT; mRNA.
DR EMBL; BC051024; AAH51024.1; -; mRNA.
DR CCDS; CCDS42035.1; -.
DR RefSeq; NP_001288141.1; NM_001301212.1.
DR RefSeq; NP_060142.3; NM_017672.5.
DR AlphaFoldDB; Q96QT4; -.
DR SMR; Q96QT4; -.
DR BioGRID; 120177; 131.
DR CORUM; Q96QT4; -.
DR IntAct; Q96QT4; 16.
DR MINT; Q96QT4; -.
DR STRING; 9606.ENSP00000320239; -.
DR BindingDB; Q96QT4; -.
DR ChEMBL; CHEMBL1250412; -.
DR DrugBank; DB04447; 1,4-Dithiothreitol.
DR DrugBank; DB14513; Magnesium.
DR DrugBank; DB09481; Magnesium carbonate.
DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester.
DR GuidetoPHARMACOLOGY; 499; -.
DR TCDB; 1.A.4.5.1; the transient receptor potential ca(2+) channel (trp-cc) family.
DR CarbonylDB; Q96QT4; -.
DR iPTMnet; Q96QT4; -.
DR PhosphoSitePlus; Q96QT4; -.
DR BioMuta; TRPM7; -.
DR DMDM; 56404941; -.
DR EPD; Q96QT4; -.
DR jPOST; Q96QT4; -.
DR MassIVE; Q96QT4; -.
DR MaxQB; Q96QT4; -.
DR PaxDb; Q96QT4; -.
DR PeptideAtlas; Q96QT4; -.
DR PRIDE; Q96QT4; -.
DR ProteomicsDB; 77898; -.
DR Antibodypedia; 24755; 470 antibodies from 40 providers.
DR DNASU; 54822; -.
DR Ensembl; ENST00000646667.1; ENSP00000495860.1; ENSG00000092439.16.
DR GeneID; 54822; -.
DR KEGG; hsa:54822; -.
DR MANE-Select; ENST00000646667.1; ENSP00000495860.1; NM_017672.6; NP_060142.3.
DR UCSC; uc001zyt.5; human.
DR CTD; 54822; -.
DR DisGeNET; 54822; -.
DR GeneCards; TRPM7; -.
DR HGNC; HGNC:17994; TRPM7.
DR HPA; ENSG00000092439; Tissue enriched (parathyroid).
DR MalaCards; TRPM7; -.
DR MIM; 105500; phenotype.
DR MIM; 605692; gene.
DR neXtProt; NX_Q96QT4; -.
DR OpenTargets; ENSG00000092439; -.
DR Orphanet; 140957; Autosomal dominant macrothrombocytopenia.
DR Orphanet; 90020; Parkinson-dementia complex of Guam.
DR PharmGKB; PA38273; -.
DR VEuPathDB; HostDB:ENSG00000092439; -.
DR eggNOG; KOG3614; Eukaryota.
DR GeneTree; ENSGT00940000157091; -.
DR InParanoid; Q96QT4; -.
DR OMA; ENNFQTA; -.
DR OrthoDB; 738147at2759; -.
DR PhylomeDB; Q96QT4; -.
DR TreeFam; TF314204; -.
DR PathwayCommons; Q96QT4; -.
DR Reactome; R-HSA-3295583; TRP channels.
DR SignaLink; Q96QT4; -.
DR SIGNOR; Q96QT4; -.
DR BioGRID-ORCS; 54822; 391 hits in 1114 CRISPR screens.
DR ChiTaRS; TRPM7; human.
DR GeneWiki; TRPM7; -.
DR GenomeRNAi; 54822; -.
DR Pharos; Q96QT4; Tchem.
DR PRO; PR:Q96QT4; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q96QT4; protein.
DR Bgee; ENSG00000092439; Expressed in left ventricle myocardium and 177 other tissues.
DR ExpressionAtlas; Q96QT4; baseline and differential.
DR Genevisible; Q96QT4; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0001726; C:ruffle; IEA:Ensembl.
DR GO; GO:0003779; F:actin binding; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005262; F:calcium channel activity; IBA:GO_Central.
DR GO; GO:0005261; F:cation channel activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017022; F:myosin binding; IEA:Ensembl.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0031032; P:actomyosin structure organization; IEA:Ensembl.
DR GO; GO:0070588; P:calcium ion transmembrane transport; TAS:Reactome.
DR GO; GO:0006816; P:calcium ion transport; IBA:GO_Central.
DR GO; GO:0016340; P:calcium-dependent cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:0098655; P:cation transmembrane transport; IBA:GO_Central.
DR GO; GO:0010961; P:cellular magnesium ion homeostasis; IEA:InterPro.
DR GO; GO:0072507; P:divalent inorganic cation homeostasis; IBA:GO_Central.
DR GO; GO:0070266; P:necroptotic process; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0051262; P:protein tetramerization; IEA:InterPro.
DR Gene3D; 1.20.5.1010; -; 1.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR004166; MHCK_EF2_kinase.
DR InterPro; IPR029601; TRPM7.
DR InterPro; IPR041491; TRPM_SLOG.
DR InterPro; IPR032415; TRPM_tetra.
DR InterPro; IPR037162; TRPM_tetra_sf.
DR PANTHER; PTHR13800:SF8; PTHR13800:SF8; 1.
DR Pfam; PF02816; Alpha_kinase; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF18139; LSDAT_euk; 1.
DR Pfam; PF16519; TRPM_tetra; 1.
DR SMART; SM00811; Alpha_kinase; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51158; ALPHA_KINASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Amyotrophic lateral sclerosis; ATP-binding; Calcium;
KW Calcium channel; Calcium transport; Coiled coil; Ion channel;
KW Ion transport; Kinase; Membrane; Metal-binding; Necrosis;
KW Neurodegeneration; Nucleotide-binding; Parkinsonism; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Transmembrane; Transmembrane helix; Transport; Zinc.
FT CHAIN 1..1865
FT /note="Transient receptor potential cation channel
FT subfamily M member 7"
FT /id="PRO_0000215331"
FT TOPO_DOM 1..755
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 756..776
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 777..855
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 856..876
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 877..918
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 919..939
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 940..962
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 963..983
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 984..995
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 996..1016
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1017..1035
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 1036..1056
FT /note="Pore-forming"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1057..1074
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1075..1095
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1096..1865
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1594..1824
FT /note="Alpha-type protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00501"
FT REGION 544..575
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1386..1407
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1492..1511
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1524..1543
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1836..1865
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1198..1250
FT /evidence="ECO:0000250"
FT COMPBIAS 544..562
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1843..1865
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1767
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 1624
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 1648
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 1720
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 1753
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 1769
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 1777
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 1794..1800
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 1810
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 1812
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 1816
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 101
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1224
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q923J1"
FT MOD_RES 1255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q923J1"
FT MOD_RES 1301
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q923J1"
FT MOD_RES 1386
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q923J1"
FT MOD_RES 1387
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1390
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1395
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1404
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1405
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q923J1"
FT MOD_RES 1446
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q923J1"
FT MOD_RES 1467
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q923J1"
FT MOD_RES 1477
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1500
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q923J1"
FT MOD_RES 1504
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q923J1"
FT MOD_RES 1527
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1569
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1851
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q923J1"
FT VARIANT 68
FT /note="G -> V (in dbSNP:rs56064201)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042395"
FT VARIANT 406
FT /note="S -> C (in an ovarian serous carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042396"
FT VARIANT 459
FT /note="I -> T (in dbSNP:rs55924090)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042397"
FT VARIANT 574
FT /note="K -> N (in dbSNP:rs56040619)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042398"
FT VARIANT 720
FT /note="T -> S (in a breast infiltrating ductal carcinoma
FT sample; somatic mutation; dbSNP:rs1040254222)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042399"
FT VARIANT 830
FT /note="M -> V (in a gastric adenocarcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042400"
FT VARIANT 949
FT /note="F -> Y (in dbSNP:rs55681028)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042401"
FT VARIANT 1033
FT /note="A -> G (in dbSNP:rs34530969)"
FT /id="VAR_052381"
FT VARIANT 1064
FT /note="Q -> R (in dbSNP:rs56298128)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042402"
FT VARIANT 1145
FT /note="I -> V (in dbSNP:rs34711809)"
FT /id="VAR_052382"
FT VARIANT 1211
FT /note="I -> T (in dbSNP:rs56090496)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042403"
FT VARIANT 1254
FT /note="A -> V (in dbSNP:rs56288221)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042404"
FT VARIANT 1306
FT /note="D -> E (in dbSNP:rs55970334)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042405"
FT VARIANT 1444
FT /note="R -> K (in dbSNP:rs55840070)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042406"
FT VARIANT 1482
FT /note="T -> I (mutant channels are functional but show
FT increased susceptibility to inhibition by intracellular
FT magnesium concentrations compared to wild-type channels;
FT dbSNP:rs8042919)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:16051700, ECO:0000269|PubMed:17344846"
FT /id="VAR_019967"
FT MUTAGEN 1648
FT /note="K->R: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:12887921"
FT MUTAGEN 1799
FT /note="G->D: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:12887921"
FT CONFLICT 573..575
FT /note="EKM -> KKK (in Ref. 4; BAD18773)"
FT /evidence="ECO:0000305"
FT CONFLICT 998
FT /note="A -> S (in Ref. 5)"
FT /evidence="ECO:0000305"
FT CONFLICT 1496
FT /note="Missing (in Ref. 3; AAK19738)"
FT /evidence="ECO:0000305"
FT CONFLICT 1520
FT /note="D -> V (in Ref. 3; AAK19738)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1865 AA; 212697 MW; BE732674D52D7485 CRC64;
MSQKSWIEST LTKRECVYII PSSKDPHRCL PGCQICQQLV RCFCGRLVKQ HACFTASLAM
KYSDVKLGDH FNQAIEEWSV EKHTEQSPTD AYGVINFQGG SHSYRAKYVR LSYDTKPEVI
LQLLLKEWQM ELPKLVISVH GGMQKFELHP RIKQLLGKGL IKAAVTTGAW ILTGGVNTGV
AKHVGDALKE HASRSSRKIC TIGIAPWGVI ENRNDLVGRD VVAPYQTLLN PLSKLNVLNN
LHSHFILVDD GTVGKYGAEV RLRRELEKTI NQQRIHARIG QGVPVVALIF EGGPNVILTV
LEYLQESPPV PVVVCEGTGR AADLLAYIHK QTEEGGNLPD AAEPDIISTI KKTFNFGQNE
ALHLFQTLME CMKRKELITV FHIGSDEHQD IDVAILTALL KGTNASAFDQ LILTLAWDRV
DIAKNHVFVY GQQWLVGSLE QAMLDALVMD RVAFVKLLIE NGVSMHKFLT IPRLEELYNT
KQGPTNPMLF HLVRDVKQGN LPPGYKITLI DIGLVIEYLM GGTYRCTYTR KRFRLIYNSL
GGNNRRSGRN TSSSTPQLRK SHESFGNRAD KKEKMRHNHF IKTAQPYRPK IDTVMEEGKK
KRTKDEIVDI DDPETKRFPY PLNELLIWAC LMKRQVMARF LWQHGEESMA KALVACKIYR
SMAYEAKQSD LVDDTSEELK QYSNDFGQLA VELLEQSFRQ DETMAMKLLT YELKNWSNST
CLKLAVSSRL RPFVAHTCTQ MLLSDMWMGR LNMRKNSWYK VILSILVPPA ILLLEYKTKA
EMSHIPQSQD AHQMTMDDSE NNFQNITEEI PMEVFKEVRI LDSNEGKNEM EIQMKSKKLP
ITRKFYAFYH APIVKFWFNT LAYLGFLMLY TFVVLVQMEQ LPSVQEWIVI AYIFTYAIEK
VREIFMSEAG KVNQKIKVWF SDYFNISDTI AIISFFIGFG LRFGAKWNFA NAYDNHVFVA
GRLIYCLNII FWYVRLLDFL AVNQQAGPYV MMIGKMVANM FYIVVIMALV LLSFGVPRKA
ILYPHEAPSW TLAKDIVFHP YWMIFGEVYA YEIDVCANDS VIPQICGPGT WLTPFLQAVY
LFVQYIIMVN LLIAFFNNVY LQVKAISNIV WKYQRYHFIM AYHEKPVLPP PLIILSHIVS
LFCCICKRRK KDKTSDGPKL FLTEEDQKKL HDFEEQCVEM YFNEKDDKFH SGSEERIRVT
FERVEQMCIQ IKEVGDRVNY IKRSLQSLDS QIGHLQDLSA LTVDTLKTLT AQKASEASKV
HNEITRELSI SKHLAQNLID DGPVRPSVWK KHGVVNTLSS SLPQGDLESN NPFHCNILMK
DDKDPQCNIF GQDLPAVPQR KEFNFPEAGS SSGALFPSAV SPPELRQRLH GVELLKIFNK
NQKLGSSSTS IPHLSSPPTK FFVSTPSQPS CKSHLETGTK DQETVCSKAT EGDNTEFGAF
VGHRDSMDLQ RFKETSNKIK ILSNNNTSEN TLKRVSSLAG FTDCHRTSIP VHSKQAEKIS
RRPSTEDTHE VDSKAALIPD WLQDRPSNRE MPSEEGTLNG LTSPFKPAMD TNYYYSAVER
NNLMRLSQSI PFTPVPPRGE PVTVYRLEES SPNILNNSMS SWSQLGLCAK IEFLSKEEMG
GGLRRAVKVQ CTWSEHDILK SGHLYIIKSF LPEVVNTWSS IYKEDTVLHL CLREIQQQRA
AQKLTFAFNQ MKPKSIPYSP RFLEVFLLYC HSAGQWFAVE ECMTGEFRKY NNNNGDEIIP
TNTLEEIMLA FSHWTYEYTR GELLVLDLQG VGENLTDPSV IKAEEKRSCD MVFGPANLGE
DAIKNFRAKH HCNSCCRKLK LPDLKRNDYT PDKIIFPQDE PSDLNLQPGN STKESESTNS
VRLML
