TRPM6_MOUSE
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 03-AUG-2022, entry version 132.
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; Q8CIR4; -.
DR PRIDE; Q8CIR4; -.
DR ProteomicsDB; 300025; -.
DR Antibodypedia; 2049; 142 antibodies from 24 providers.
DR DNASU; 225997; -.
DR Ensembl; ENSMUST00000040489; ENSMUSP00000037443; ENSMUSG00000024727.
DR GeneID; 225997; -.
DR KEGG; mmu:225997; -.
DR UCSC; uc008gya.1; mouse.
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; KIHSCSR; -.
DR OrthoDB; 738147at2759; -.
DR PhylomeDB; Q8CIR4; -.
DR TreeFam; TF314204; -.
DR Reactome; R-MMU-3295583; TRP channels.
DR BioGRID-ORCS; 225997; 3 hits in 75 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 67 other tissues.
DR ExpressionAtlas; Q8CIR4; baseline and differential.
DR Genevisible; Q8CIR4; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0031526; C:brush border membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005262; F:calcium channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005261; F:cation channel activity; IDA:MGI.
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:0098655; P:cation transmembrane transport; IBA:GO_Central.
DR GO; GO:0030001; P:metal ion transport; IDA:MGI.
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; ISO:MGI.
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 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
