ID   TRPM6_MOUSE             Reviewed;        2028 AA.
AC   Q8CIR4;
DT   07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   24-JAN-2024, entry version 139.
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;
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 [MRNA].
RC   STRAIN=BALB/cJ; TISSUE=Kidney;
RA   Ryazanova L.V., Ryazanov A.G.;
RL   Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Essential ion channel and kinase. Crucial for magnesium
CC       homeostasis. Has an important role in epithelial magnesium transport
CC       and in the active magnesium absorption in the gut and kidney (By
CC       similarity). {ECO:0000250}.
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. Interacts (via kinase domain)
CC       with RACK1 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9BX84};
CC       Multi-pass membrane protein.
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; AY135644; AAN15217.1; -; mRNA.
DR   CCDS; CCDS29691.1; -.
DR   RefSeq; NP_700466.1; NM_153417.1.
DR   AlphaFoldDB; Q8CIR4; -.
DR   SMR; Q8CIR4; -.
DR   BioGRID; 230456; 3.
DR   STRING; 10090.ENSMUSP00000037443; -.
DR   iPTMnet; Q8CIR4; -.
DR   PhosphoSitePlus; Q8CIR4; -.
DR   PaxDb; 10090-ENSMUSP00000037443; -.
DR   ProteomicsDB; 300025; -.
DR   Antibodypedia; 2049; 164 antibodies from 24 providers.
DR   DNASU; 225997; -.
DR   Ensembl; ENSMUST00000040489.9; ENSMUSP00000037443.8; ENSMUSG00000024727.10.
DR   GeneID; 225997; -.
DR   KEGG; mmu:225997; -.
DR   UCSC; uc008gya.1; mouse.
DR   AGR; MGI:2675603; -.
DR   CTD; 140803; -.
DR   MGI; MGI:2675603; Trpm6.
DR   VEuPathDB; HostDB:ENSMUSG00000024727; -.
DR   eggNOG; KOG3614; Eukaryota.
DR   GeneTree; ENSGT00940000158164; -.
DR   HOGENOM; CLU_001390_2_0_1; -.
DR   InParanoid; Q8CIR4; -.
DR   OMA; EVVQTWY; -.
DR   OrthoDB; 201873at2759; -.
DR   PhylomeDB; Q8CIR4; -.
DR   TreeFam; TF314204; -.
DR   Reactome; R-MMU-3295583; TRP channels.
DR   BioGRID-ORCS; 225997; 3 hits in 80 CRISPR screens.
DR   ChiTaRS; Trpm6; mouse.
DR   PRO; PR:Q8CIR4; -.
DR   Proteomes; UP000000589; Chromosome 19.
DR   RNAct; Q8CIR4; Protein.
DR   Bgee; ENSMUSG00000024727; Expressed in conjunctival fornix and 69 other cell types or tissues.
DR   ExpressionAtlas; Q8CIR4; baseline and differential.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR   GO; GO:0031526; C:brush border membrane; IDA:MGI.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0005262; F:calcium channel activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0005261; F:monoatomic cation channel activity; IDA:MGI.
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:0030001; P:metal ion transport; IDA:MGI.
DR   GO; GO:0098655; P:monoatomic cation transmembrane transport; IBA:GO_Central.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0051262; P:protein tetramerization; IEA:InterPro.
DR   GO; GO:0009636; P:response to toxic substance; ISO:MGI.
DR   CDD; cd16972; Alpha_kinase_ChaK2_TRPM6; 1.
DR   Gene3D; 3.20.200.10; MHCK/EF2 kinase; 1.
DR   Gene3D; 1.20.5.1010; TRPM, tetramerisation domain; 1.
DR   InterPro; IPR004166; a-kinase_dom.
DR   InterPro; IPR005821; Ion_trans_dom.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR029597; TRPM6_a-kinase_dom.
DR   InterPro; IPR041491; TRPM_SLOG.
DR   InterPro; IPR032415; TRPM_tetra.
DR   InterPro; IPR037162; TRPM_tetra_sf.
DR   PANTHER; PTHR13800:SF15; TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL SUBFAMILY M MEMBER 6; 1.
DR   PANTHER; PTHR13800; TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL, SUBFAMILY M, MEMBER 6; 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; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS51158; ALPHA_KINASE; 1.
DR   Genevisible; Q8CIR4; MM.
PE   2: Evidence at transcript level;
KW   ATP-binding; Calcium; Calcium channel; Calcium transport; Cell membrane;
KW   Ion channel; Ion transport; Kinase; Membrane; Metal-binding;
KW   Nucleotide-binding; Phosphoprotein; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase; Transmembrane;
KW   Transmembrane helix; Transport; Zinc.
FT   CHAIN           1..2028
FT                   /note="Transient receptor potential cation channel
FT                   subfamily M member 6"
FT                   /id="PRO_0000215330"
FT   TOPO_DOM        1..747
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        748..768
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        769..847
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        848..868
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        869..910
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        911..931
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        932..945
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        946..966
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        967..978
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        979..999
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1000..1018
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        1019..1039
FT                   /note="Pore-forming"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1040..1053
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1054..1074
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1075..2028
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          1756..1986
FT                   /note="Alpha-type protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00501"
FT   REGION          577..601
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1313..1339
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1658..1694
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2009..2028
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        579..601
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1313..1332
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1658..1673
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1674..1694
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1929
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         1786
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         1810
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         1882
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         1915
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         1931
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         1939
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         1956..1962
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         1972
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         1974
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         1978
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         1857
FT                   /note="Phosphothreonine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BX84"
SQ   SEQUENCE   2028 AA;  232888 MW;  3060C1D70DC9A20E CRC64;
     MQVKKSWIEG VFYKRECNKF IPSSKDPHRC TPGCQICHNL VRCYCGRLIE EHHGLDRAWN
     LSVTEGHGDE QWSVEKHTVK SPTDTFGTIN FQDGEHIHHS KYIRTSWDTK SDHLLHLMLK
     EWNMELPKLV ISVHGGLQNF KISSKLKETF SQGLVKAAET TGAWIITEGI NSGVSKHVGD
     ALKAHSSKSL RKIWTVGIPP WGVIENQREL VGKDVVCMYQ TLGNPLSKLT TLNCMHSHFI
     LCDDGTVGMY GNEEKLRRNL EKHLSMQKIH TCSRQGVPVV GLVMEGGPNV ILWVWETVKN
     KEPVVVCEGT GRAADLLAFT YKHLEDGGIL RPQVKEELFC LIQNMFNFSL RQSKHLFQIL
     MECMVHKDSI TIFDADSEEH QDLDLAILTA LLKGTSLSIS EQLNLAMAWD RMDIAKKHIL
     TYGQHWKPGA LEQAMLDALV MDRVDFVKLL IENGVNLHRF LTIPRLEELY NTKQGPTNKF
     LRHLVQDVKQ HTLLSSYRIT LIDIGLVIEY LIGGAYRSSY TRKSFRILYN NLYRKHKSVS
     SFAQGLSQHS LHQRHSLRNR KESSESTLHS QFFRTAQPYK SKEKPEDSQK SKKKSKERQS
     LSEEPEAAGF IYPYNDLLVW AVLMKRQNMA MFFWQHGEEA TVKAVIASIL YRAMAREAKE
     SNMVDDTSEE LKNYSEQFGQ LALDVLEKAF KQNEPMAMKL LTYELKNWSN STCLKLAVSG
     GLRPFVSHSC TQMLLTDMWM GRLKMRKNSW LKIIISILLP PMILTLEFKS KAEMSHVPQS
     QDFQFTWNYS DQGLSNTKES ACVKDYDLER GPDEKPDEPL HLDLRNVPQS LPWTRRVYEF
     YSAPFVKFWF YTMAYLAFLM LFTYTVLVEM QPQPSVHEWL VIIYIFTNAI EKVREICISE
     PSKFKQKVKM WLSEYWNLME TVAIGLFAVG FGLRWGHPPL QTAGRLIYCI DIIFWFSRLM
     DFFAVNQHAG PYVTMIAKMA ANMFYIVIIM AIVLLSFGVA RKAILSPKEP PSWRLARDIV
     FEPYWMMYGE VYASDIDVCS NETSCPPGSF LTPFLQAVYL FVQYIIMVNL LIACFNNIYL
     DIKSISNKLW KYNRYRYIMT YHQKPWLPPP FILLNHLCLL LRGLCCRPAP QDQEEGDGGL
     KLYLTKDDLK KLHDFEEQCV EKYFHEKTEG LNCSFEEQIR MTSERVSEMF FQLKEMNEKV
     SFIKDSLLSL DSQVGHLQDL SAITVDTLKV LSAVDTLQED EILLANRKHS TCRKRPHSWT
     NVICAKVLSD MESCGKKKLQ YYSMPPSLLR SLARSQLPPS VQRGALVEVT HSKREASHVR
     EEQEEREMEQ RTTASGISHV RQAHSKYGQF LLVPSSGKQV PLSLETPPHL FRSSEEAGID
     GLVLEHIHQS DLTTHLPQQT PAASHQALVA EHKDQHEAVT QMSDKPAKAE QDLLAFSGTP
     APMTVTSLPS RAISMQDEGG YVNWAFSEND ETGVFSFKKK WKTCLASTCN SDSNPGGDYF
     LHTGGRSGLD NSRRLAQSCE CPAGPWTQAR RSFWINPLCR DKALIKSHSF RFHKEEKLRK
     TWKNNSHSKS LETRSTWLKA KLLTKTRSLS KKKRKTQGLQ VPVITVNACY QSDQLNAEPG
     ETNTTEEFSK KWLSVSNFSQ IGLEPYIYQK MKMKEIKRHT TQASDHLRQP QENRDKTPTW
     NSGSTSLSRS FLTRSPNEVH KISTSLKSPQ EPHHHYSAIE RNNLMRLSQT IPFTPIQLFT
     GEEVTIYKLE ESSPLTLDKS MSSWSQHGRA AMIQVLSQEE MDGGLRKAMR VISTWSEDDV
     LKPGQVFIVK SFLPEVVQTW YKIFQESTVL HLCLREIQQQ RAAQKLIYTF NQVKPQTIPY
     TPRFLEVSLV YCHSANQWLT IEKYMTGEFR KYNNNNGDEI APTNTLEELM LAFSHWTYEY
     TRGELLVLDL QGVGENLTDP SVIKPEDKQS RGMVFGPANL GEDAIRSFIA KHRCNSCCGK
     LRLPDLKRND YSLSRTHCNL GFGQTIEPTE ELPERDKNRS SLEDHTRL
//