TRPM6_HUMAN
ID TRPM6_HUMAN Reviewed; 2022 AA.
AC Q9BX84; Q6VPR8; Q6VPR9; Q6VPS0; Q6VPS1; Q6VPS2;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Transient receptor potential cation channel subfamily M member 6;
DE EC=2.7.11.1;
DE AltName: Full=Channel kinase 2;
DE AltName: Full=Melastatin-related TRP cation channel 6;
GN Name=TRPM6; Synonyms=CHAK2;
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] (ISOFORM TRPM6A), AND CHARACTERIZATION.
RC TISSUE=Kidney;
RX PubMed=11357414;
RA Riazanova L.V., Pavur K.S., Petrov A.N., Dorovkov M.V., Riazanov A.G.;
RT "Novel type of signaling molecules: protein kinases covalently linked to
RT ion channels.";
RL Mol. Biol. (Mosk.) 35:321-332(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRPM6A), AND VARIANT HOMG1 LEU-141.
RC TISSUE=Kidney, and Small intestine;
RX PubMed=12032568; DOI=10.1038/ng889;
RA Schlingmann K.P., Weber S., Peters M., Niemann Nejsum L.N., Vitzthum H.,
RA Klingel K., Kratz M., Haddad E., Ristoff E., Dinour D., Syrrou M.,
RA Nielsen S., Sassen M.C., Waldegger S., Seyberth H.W., Konrad M.;
RT "Hypomagnesemia with secondary hypocalcemia is caused by mutations in
RT TRPM6, a new member of the TRPM gene family.";
RL Nat. Genet. 31:166-170(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS TRPM6A; TRPM6B; TRPM6C; TRPM6T;
RP M6-KINASE 1; M6-KINASE 2 AND M6-KINASE 3), CHARACTERIZATION OF VARIANT
RP HOMG1 LEU-141, AND INTERACTION WITH TRPM7.
RC TISSUE=Lung cancer;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP INTERACTION WITH RACK1, PHOSPHORYLATION AT THR-1851, AND MUTAGENESIS OF
RP LYS-1804 AND THR-1851.
RX PubMed=18258429; DOI=10.1016/j.cub.2007.12.058;
RA Cao G., Thebault S., van der Wijst J., van der Kemp A., Lasonder E.,
RA Bindels R.J., Hoenderop J.G.;
RT "RACK1 inhibits TRPM6 activity via phosphorylation of the fused alpha-
RT kinase domain.";
RL Curr. Biol. 18:168-176(2008).
RN [6]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-75; ILE-338; CYS-1007; ARG-1243;
RP ARG-1274; ILE-1393; GLU-1584; ARG-1663; SER-1673 AND ILE-1724.
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).
RN [7]
RP VARIANTS HOMG1 PRO-708; GLY-872; CYS-1053; PRO-1143 AND ASN-1754, VARIANT
RP ARG-1663, CHARACTERIZATION OF VARIANTS HOMG1 PRO-708; GLY-872; CYS-1053;
RP PRO-1143 AND ASN-1754, CHARACTERIZATION OF VARIANT ARG-1663, AND
RP SUBCELLULAR LOCATION.
RX PubMed=23942199; DOI=10.1038/ejhg.2013.178;
RA Lainez S., Schlingmann K.P., van der Wijst J., Dworniczak B.,
RA van Zeeland F., Konrad M., Bindels R.J., Hoenderop J.G.;
RT "New TRPM6 missense mutations linked to hypomagnesemia with secondary
RT hypocalcemia.";
RL Eur. J. Hum. Genet. 22:497-504(2014).
CC -!- FUNCTION: Essential ion channel and serine/threonine-protein kinase.
CC Crucial for magnesium homeostasis. Has an important role in epithelial
CC magnesium transport and in the active magnesium absorption in the gut
CC and kidney. Isoforms of the type M6-kinase lack the ion channel region.
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 -!- SUBUNIT: Forms heterodimers with TRPM7. TRPM6 requires the presence of
CC TRPM7 to be targeted to the cell membrane (in HEK 293 cells). Interacts
CC (via kinase domain) with RACK1. {ECO:0000269|PubMed:14976260,
CC ECO:0000269|PubMed:18258429}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23942199};
CC Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=TRPM6a;
CC IsoId=Q9BX84-1; Sequence=Displayed;
CC Name=TRPM6b;
CC IsoId=Q9BX84-2; Sequence=VSP_012069;
CC Name=TRPM6c;
CC IsoId=Q9BX84-3; Sequence=VSP_012070;
CC Name=TRPM6t;
CC IsoId=Q9BX84-4; Sequence=VSP_012075, VSP_012076;
CC Name=M6-kinase 1;
CC IsoId=Q9BX84-5; Sequence=VSP_012074;
CC Name=M6-kinase 2;
CC IsoId=Q9BX84-6; Sequence=VSP_012073;
CC Name=M6-kinase 3;
CC IsoId=Q9BX84-7; Sequence=VSP_012071, VSP_012072;
CC -!- TISSUE SPECIFICITY: Highly expressed in kidney and colon. Isoform
CC TRPM6a and isoform TRPM6b, are coexpressed with TRPM7 in kidney, and
CC testis, and are also found in several cell lines of lung origin.
CC Isoform TRPM6c is detected only in testis and in NCI-H510A small cell
CC lung carcinoma cells.
CC -!- DISEASE: Hypomagnesemia 1 (HOMG1) [MIM:602014]: A disorder due to a
CC primary defect in intestinal magnesium absorption. It is characterized
CC by low levels of serum magnesium alongside with a normal renal
CC magnesium secretion, secondary hypocalcemia and calcinocis. Affected
CC individuals show neurologic symptoms of hypomagnesemic hypocalcemia,
CC including seizures and muscle spasms, during infancy. Hypocalcemia is
CC secondary to parathyroid failure resulting from magnesium deficiency.
CC Untreated, the disorder may be fatal or may result in neurological
CC damage. {ECO:0000269|PubMed:12032568, ECO:0000269|PubMed:14976260,
CC ECO:0000269|PubMed:23942199}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform M6-kinase 1]: Lacks the ion channel region.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform M6-kinase 2]: Lacks the ion channel region.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform M6-kinase 3]: Lacks the ion channel region.
CC {ECO:0000305}.
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. TRPM6 sub-subfamily.
CC {ECO:0000305}.
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DR EMBL; AF350881; AAK31202.2; -; mRNA.
DR EMBL; AF448232; AAM21562.1; -; mRNA.
DR EMBL; AY333282; AAR03487.1; -; mRNA.
DR EMBL; AY333283; AAR03488.1; -; mRNA.
DR EMBL; AY333284; AAR03489.1; -; mRNA.
DR EMBL; AY333285; AAR03490.1; -; mRNA.
DR EMBL; AY333286; AAR03491.1; -; mRNA.
DR EMBL; AY333287; AAR03492.1; -; mRNA.
DR EMBL; AY333288; AAR03493.1; -; mRNA.
DR EMBL; AL354795; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS55318.1; -. [Q9BX84-3]
DR CCDS; CCDS55319.1; -. [Q9BX84-2]
DR CCDS; CCDS6647.1; -. [Q9BX84-1]
DR RefSeq; NP_001170781.1; NM_001177310.1. [Q9BX84-2]
DR RefSeq; NP_001170782.1; NM_001177311.1. [Q9BX84-3]
DR RefSeq; NP_060132.3; NM_017662.4. [Q9BX84-1]
DR AlphaFoldDB; Q9BX84; -.
DR SMR; Q9BX84; -.
DR BioGRID; 126713; 1.
DR CORUM; Q9BX84; -.
DR IntAct; Q9BX84; 3.
DR MINT; Q9BX84; -.
DR STRING; 9606.ENSP00000354006; -.
DR BindingDB; Q9BX84; -.
DR ChEMBL; CHEMBL1628470; -.
DR DrugBank; DB14513; Magnesium.
DR DrugBank; DB09481; Magnesium carbonate.
DR GuidetoPHARMACOLOGY; 498; -.
DR TCDB; 1.A.4.5.8; the transient receptor potential ca(2+) channel (trp-cc) family.
DR iPTMnet; Q9BX84; -.
DR PhosphoSitePlus; Q9BX84; -.
DR BioMuta; TRPM6; -.
DR DMDM; 56404951; -.
DR EPD; Q9BX84; -.
DR MassIVE; Q9BX84; -.
DR MaxQB; Q9BX84; -.
DR PaxDb; Q9BX84; -.
DR PeptideAtlas; Q9BX84; -.
DR PRIDE; Q9BX84; -.
DR ProteomicsDB; 79380; -. [Q9BX84-1]
DR ProteomicsDB; 79381; -. [Q9BX84-2]
DR ProteomicsDB; 79382; -. [Q9BX84-3]
DR ProteomicsDB; 79383; -. [Q9BX84-4]
DR ProteomicsDB; 79384; -. [Q9BX84-5]
DR ProteomicsDB; 79385; -. [Q9BX84-6]
DR ProteomicsDB; 79386; -. [Q9BX84-7]
DR ABCD; Q9BX84; 1 sequenced antibody.
DR Antibodypedia; 2049; 142 antibodies from 24 providers.
DR DNASU; 140803; -.
DR Ensembl; ENST00000360774.6; ENSP00000354006.1; ENSG00000119121.22. [Q9BX84-1]
DR Ensembl; ENST00000361255.7; ENSP00000354962.3; ENSG00000119121.22. [Q9BX84-3]
DR Ensembl; ENST00000449912.6; ENSP00000396672.2; ENSG00000119121.22. [Q9BX84-2]
DR GeneID; 140803; -.
DR KEGG; hsa:140803; -.
DR MANE-Select; ENST00000360774.6; ENSP00000354006.1; NM_017662.5; NP_060132.3.
DR UCSC; uc004ajk.1; human. [Q9BX84-1]
DR CTD; 140803; -.
DR DisGeNET; 140803; -.
DR GeneCards; TRPM6; -.
DR HGNC; HGNC:17995; TRPM6.
DR HPA; ENSG00000119121; Group enriched (brain, intestine).
DR MalaCards; TRPM6; -.
DR MIM; 602014; phenotype.
DR MIM; 607009; gene.
DR neXtProt; NX_Q9BX84; -.
DR OpenTargets; ENSG00000119121; -.
DR Orphanet; 30924; Primary hypomagnesemia with secondary hypocalcemia.
DR PharmGKB; PA38479; -.
DR VEuPathDB; HostDB:ENSG00000119121; -.
DR eggNOG; KOG3614; Eukaryota.
DR GeneTree; ENSGT00940000158164; -.
DR HOGENOM; CLU_001390_2_0_1; -.
DR InParanoid; Q9BX84; -.
DR OMA; KIHSCSR; -.
DR OrthoDB; 738147at2759; -.
DR PhylomeDB; Q9BX84; -.
DR TreeFam; TF314204; -.
DR PathwayCommons; Q9BX84; -.
DR Reactome; R-HSA-3295583; TRP channels.
DR SignaLink; Q9BX84; -.
DR SIGNOR; Q9BX84; -.
DR BioGRID-ORCS; 140803; 7 hits in 1104 CRISPR screens.
DR ChiTaRS; TRPM6; human.
DR GeneWiki; TRPM6; -.
DR GenomeRNAi; 140803; -.
DR Pharos; Q9BX84; Tchem.
DR PRO; PR:Q9BX84; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9BX84; protein.
DR Bgee; ENSG00000119121; Expressed in colonic mucosa and 124 other tissues.
DR ExpressionAtlas; Q9BX84; baseline and differential.
DR Genevisible; Q9BX84; HS.
DR GO; GO:0016324; C:apical plasma membrane; IBA:GO_Central.
DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl.
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:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005262; F:calcium channel activity; TAS:Reactome.
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:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0070588; P:calcium ion transmembrane transport; TAS:Reactome.
DR GO; GO:0098655; P:cation transmembrane transport; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0051262; P:protein tetramerization; IEA:InterPro.
DR GO; GO:0009636; P:response to toxic substance; IDA:UniProtKB.
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; IPR029597; TRPM6.
DR InterPro; IPR041491; TRPM_SLOG.
DR InterPro; IPR032415; TRPM_tetra.
DR InterPro; IPR037162; TRPM_tetra_sf.
DR PANTHER; PTHR13800:SF15; PTHR13800:SF15; 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 Alternative splicing; ATP-binding; Calcium; Calcium channel;
KW Calcium transport; Cell membrane; Disease variant; Ion channel;
KW Ion transport; Kinase; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Primary hypomagnesemia; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Transmembrane;
KW Transmembrane helix; Transport; Zinc.
FT CHAIN 1..2022
FT /note="Transient receptor potential cation channel
FT subfamily M member 6"
FT /id="PRO_0000215329"
FT TOPO_DOM 1..741
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 742..762
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 763..841
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 842..862
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 863..905
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 906..926
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 927..939
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 940..960
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 961..972
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 973..993
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 994..1012
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 1013..1033
FT /note="Pore-forming"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1034..1047
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1048..1068
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1069..2022
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1750..1980
FT /note="Alpha-type protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00501"
FT REGION 1479..1516
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1997..2022
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1491..1516
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2002..2022
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1923
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 1780
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 1804
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 1876
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 1909
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 1925
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 1933
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 1950..1956
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 1966
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 1968
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 1972
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 1851
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:18258429"
FT VAR_SEQ 1..11
FT /note="MKEQPVLERLQ -> MIILSK (in isoform TRPM6b)"
FT /evidence="ECO:0000303|PubMed:14976260"
FT /id="VSP_012069"
FT VAR_SEQ 1..11
FT /note="MKEQPVLERLQ -> MTAPVT (in isoform TRPM6c)"
FT /evidence="ECO:0000303|PubMed:14976260"
FT /id="VSP_012070"
FT VAR_SEQ 281
FT /note="R -> P (in isoform M6-kinase 3)"
FT /evidence="ECO:0000303|PubMed:14976260"
FT /id="VSP_012071"
FT VAR_SEQ 282..1734
FT /note="Missing (in isoform M6-kinase 3)"
FT /evidence="ECO:0000303|PubMed:14976260"
FT /id="VSP_012072"
FT VAR_SEQ 500..1666
FT /note="Missing (in isoform M6-kinase 2)"
FT /evidence="ECO:0000303|PubMed:14976260"
FT /id="VSP_012073"
FT VAR_SEQ 547..1595
FT /note="Missing (in isoform M6-kinase 1)"
FT /evidence="ECO:0000303|PubMed:14976260"
FT /id="VSP_012074"
FT VAR_SEQ 1926..1943
FT /note="GVGENLTDPSVIKPEVKQ -> ALWFWDSMLKARLGGWRM (in isoform
FT TRPM6t)"
FT /evidence="ECO:0000303|PubMed:14976260"
FT /id="VSP_012075"
FT VAR_SEQ 1944..2022
FT /note="Missing (in isoform TRPM6t)"
FT /evidence="ECO:0000303|PubMed:14976260"
FT /id="VSP_012076"
FT VARIANT 75
FT /note="G -> V (in a lung adenocarcinoma sample; somatic
FT mutation; dbSNP:rs1193127627)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042387"
FT VARIANT 141
FT /note="S -> L (in HOMG1; impairs heterodimer formation
FT resulting in intracellular retention; dbSNP:rs121912625)"
FT /evidence="ECO:0000269|PubMed:12032568,
FT ECO:0000269|PubMed:14976260"
FT /id="VAR_019963"
FT VARIANT 338
FT /note="M -> I (in dbSNP:rs56155062)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042388"
FT VARIANT 708
FT /note="L -> P (in HOMG1; loss of function; no effect on
FT cell membrane localization)"
FT /evidence="ECO:0000269|PubMed:23942199"
FT /id="VAR_071480"
FT VARIANT 872
FT /note="E -> G (in HOMG1; loss of function; no effect on
FT cell membrane localization)"
FT /evidence="ECO:0000269|PubMed:23942199"
FT /id="VAR_071481"
FT VARIANT 948
FT /note="F -> L (in dbSNP:rs13290391)"
FT /id="VAR_052380"
FT VARIANT 1007
FT /note="W -> C (in a lung large cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042389"
FT VARIANT 1053
FT /note="Y -> C (in HOMG1; loss of function; no effect on
FT cell membrane localization)"
FT /evidence="ECO:0000269|PubMed:23942199"
FT /id="VAR_071482"
FT VARIANT 1071
FT /note="N -> D (in dbSNP:rs2274922)"
FT /id="VAR_019964"
FT VARIANT 1143
FT /note="L -> P (in HOMG1; loss of function; no effect on
FT cell membrane localization)"
FT /evidence="ECO:0000269|PubMed:23942199"
FT /id="VAR_071483"
FT VARIANT 1243
FT /note="H -> R (in dbSNP:rs55694430)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042390"
FT VARIANT 1274
FT /note="Q -> R (in dbSNP:rs34608911)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042391"
FT VARIANT 1393
FT /note="V -> I (in dbSNP:rs3750425)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_019965"
FT VARIANT 1584
FT /note="K -> E (in dbSNP:rs2274924)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_019966"
FT VARIANT 1663
FT /note="Q -> R (no effect on function or cell membrane
FT localization; dbSNP:rs55679040)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:23942199"
FT /id="VAR_042392"
FT VARIANT 1673
FT /note="L -> S (in dbSNP:rs56254742)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042393"
FT VARIANT 1724
FT /note="T -> I (in dbSNP:rs56290308)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042394"
FT VARIANT 1754
FT /note="S -> N (in HOMG1; loss of function; no effect on
FT cell membrane localization)"
FT /evidence="ECO:0000269|PubMed:23942199"
FT /id="VAR_071484"
FT MUTAGEN 1804
FT /note="K->R: Abolishes kinase activity but does not affect
FT expression levels or binding to RACK1."
FT /evidence="ECO:0000269|PubMed:18258429"
FT MUTAGEN 1851
FT /note="T->A: Significantly decreases autophosphorylation.
FT Does not alter binding to RACK1 but prevents inhibition by
FT RACK1."
FT /evidence="ECO:0000269|PubMed:18258429"
FT MUTAGEN 1851
FT /note="T->D: Significantly decreases autophosphorylation.
FT Does not alter binding to RACK1 or inhibition by RACK1."
FT /evidence="ECO:0000269|PubMed:18258429"
SQ SEQUENCE 2022 AA; 231708 MW; 59346B3BE3300466 CRC64;
MKEQPVLERL QSQKSWIKGV FDKRECSTII PSSKNPHRCT PVCQVCQNLI RCYCGRLIGD
HAGIDYSWTI SAAKGKESEQ WSVEKHTTKS PTDTFGTINF QDGEHTHHAK YIRTSYDTKL
DHLLHLMLKE WKMELPKLVI SVHGGIQNFT MPSKFKEIFS QGLVKAAETT GAWIITEGIN
TGVSKHVGDA LKSHSSHSLR KIWTVGIPPW GVIENQRDLI GKDVVCLYQT LDNPLSKLTT
LNSMHSHFIL SDDGTVGKYG NEMKLRRNLE KYLSLQKIHC RSRQGVPVVG LVVEGGPNVI
LSVWETVKDK DPVVVCEGTG RAADLLAFTH KHLADEGMLR PQVKEEIICM IQNTFNFSLK
QSKHLFQILM ECMVHRDCIT IFDADSEEQQ DLDLAILTAL LKGTNLSASE QLNLAMAWDR
VDIAKKHILI YEQHWKPDAL EQAMSDALVM DRVDFVKLLI EYGVNLHRFL TIPRLEELYN
TKQGPTNTLL HHLVQDVKQH TLLSGYRITL IDIGLVVEYL IGRAYRSNYT RKHFRALYNN
LYRKYKHQRH SSGNRNESAE STLHSQFIRT AQPYKFKEKS IVLHKSRKKS KEQNVSDDPE
STGFLYPYND LLVWAVLMKR QKMAMFFWQH GEEATVKAVI ACILYRAMAH EAKESHMVDD
ASEELKNYSK QFGQLALDLL EKAFKQNERM AMTLLTYELR NWSNSTCLKL AVSGGLRPFV
SHTCTQMLLT DMWMGRLKMR KNSWLKIIIS IILPPTILTL EFKSKAEMSH VPQSQDFQFM
WYYSDQNASS SKESASVKEY DLERGHDEKL DENQHFGLES GHQHLPWTRK VYEFYSAPIV
KFWFYTMAYL AFLMLFTYTV LVEMQPQPSV QEWLVSIYIF TNAIEVVREI CISEPGKFTQ
KVKVWISEYW NLTETVAIGL FSAGFVLRWG DPPFHTAGRL IYCIDIIFWF SRLLDFFAVN
QHAGPYVTMI AKMTANMFYI VIIMAIVLLS FGVARKAILS PKEPPSWSLA RDIVFEPYWM
IYGEVYAGEI DVCSSQPSCP PGSFLTPFLQ AVYLFVQYII MVNLLIAFFN NVYLDMESIS
NNLWKYNRYR YIMTYHEKPW LPPPLILLSH VGLLLRRLCC HRAPHDQEEG DVGLKLYLSK
EDLKKLHDFE EQCVEKYFHE KMEDVNCSCE ERIRVTSERV TEMYFQLKEM NEKVSFIKDS
LLSLDSQVGH LQDLSALTVD TLKVLSAVDT LQEDEALLAK RKHSTCKKLP HSWSNVICAE
VLGSMEIAGE KKYQYYSMPS SLLRSLAGGR HPPRVQRGAL LEITNSKREA TNVRNDQERQ
ETQSSIVVSG VSPNRQAHSK YGQFLLVPSN LKRVPFSAET VLPLSRPSVP DVLATEQDIQ
TEVLVHLTGQ TPVVSDWASV DEPKEKHEPI AHLLDGQDKA EQVLPTLSCT PEPMTMSSPL
SQAKIMQTGG GYVNWAFSEG DETGVFSIKK KWQTCLPSTC DSDSSRSEQH QKQAQDSSLS
DNSTRSAQSS ECSEVGPWLQ PNTSFWINPL RRYRPFARSH SFRFHKEEKL MKICKIKNLS
GSSEIGQGAW VKAKMLTKDR RLSKKKKNTQ GLQVPIITVN ACSQSDQLNP EPGENSISEE
EYSKNWFTVS KFSHTGVEPY IHQKMKTKEI GQCAIQISDY LKQSQEDLSK NSLWNSRSTN
LNRNSLLKSS IGVDKISASL KSPQEPHHHY SAIERNNLMR LSQTIPFTPV QLFAGEEITV
YRLEESSPLN LDKSMSSWSQ RGRAAMIQVL SREEMDGGLR KAMRVVSTWS EDDILKPGQV
FIVKSFLPEV VRTWHKIFQE STVLHLCLRE IQQQRAAQKL IYTFNQVKPQ TIPYTPRFLE
VFLIYCHSAN QWLTIEKYMT GEFRKYNNNN GDEITPTNTL EELMLAFSHW TYEYTRGELL
VLDLQGVGEN LTDPSVIKPE VKQSRGMVFG PANLGEDAIR NFIAKHHCNS CCRKLKLPDL
KRNDYSPERI NSTFGLEIKI ESAEEPPARE TGRNSPEDDM QL
