Trpm6
entrez
225997
canonical
uniprot
Q8CIR4
canonical
ensembl
ENSMUSG00000024727
resolver
ensp
ENSMUSP00000037443
resolver
enst
ENSMUST00000040489
resolver
genesymbol
Trpm6
resolver
uniprot
A0A1W5LU38
resolver
uniprot_entry
TRPM6_MOUSE
resolver
uniprot_sec
A0A1W5LU38
resolver
activity_regulation
ACTIVITY REGULATION: Strongly inhibited by intracellular Mg(2+); unlikely to be active at physiological levels of intracellular Mg(2+) (PubMed:28821869). In the heteromeric TRPM6-TRPM7 channels complexes, TRPM7 are able to offset the very high sensitivity of TRPM6 to cytosolic Mg(2+) to physiologically relevant concentrations, whereas TRPM6 relieve TRPM7 from the inhibitory action of Mg-ATP. Consequently, the association of TRPM6 with TRPM7 allow for high constitutive activity of TRPM6/7 in the presence of physiological levels of Mg(2+) and Mg-ATP (PubMed:28821869). The kinase activity is controlled through the autophosphorylation of a serine/threonine-rich region located to the N-terminal of the catalytic domain (By similarity). {ECO:0000250|UniProtKB:Q9BX84, ECO:0000269|PubMed:28821869}.
uniprot
proteins
amino_acid_sequence
MQVKKSWIEGVFYKRECNKFIPSSKDPHRCTPGCQICHNLVRCYCGRLIEEHHGLDRAWNLSVTEGHGDEQWSVEKHTVKSPTDTFGTINFQDGEHIHHSKYIRTSWDTKSDHLLHLMLKEWNMELPKLVISVHGGLQNFKISSKLKETFSQGLVKAAETTGAWIITEGINSGVSKHVGDALKAHSSKSLRKIWTVGIPPWGVIENQRELVGKDVVCMYQTLGNPLSKLTTLNCMHSHFILCDDGTVGMYGNEEKLRRNLEKHLSMQKIHTCSRQGVPVVGLVMEGGPNVILWVWETVKNKEPVVVCEGTGRAADLLAFTYKHLEDGGILRPQVKEELFCLIQNMFNFSLRQSKHLFQILMECMVHKDSITIFDADSEEHQDLDLAILTALLKGTSLSISEQLNLAMAWDRMDIAKKHILTYGQHWKPGALEQAMLDALVMDRVDFVKLLIENGVNLHRFLTIPRLEELYNTKQGPTNKFLRHLVQDVKQHTLLSSYRITLIDIGLVIEYLIGGAYRSSYTRKSFRILYNNLYRKHKSVSSFAQGLSQHSLHQRHSLRNRKESSESTLHSQFFRTAQPYKSKEKPEDSQKSKKKSKERQSLSEEPEAAGFIYPYNDLLVWAVLMKRQNMAMFFWQHGEEATVKAVIASILYRAMAREAKESNMVDDTSEELKNYSEQFGQLALDVLEKAFKQNEPMAMKLLTYELKNWSNSTCLKLAVSGGLRPFVSHSCTQMLLTDMWMGRLKMRKNSWLKIIISILLPPMILTLEFKSKAEMSHVPQSQDFQFTWNYSDQGLSNTKESACVKDYDLERGPDEKPDEPLHLDLRNVPQSLPWTRRVYEFYSAPFVKFWFYTMAYLAFLMLFTYTVLVEMQPQPSVHEWLVIIYIFTNAIEKVREICISEPSKFKQKVKMWLSEYWNLMETVAIGLFAVGFGLRWGHPPLQTAGRLIYCIDIIFWFSRLMDFFAVNQHAGPYVTMIAKMAANMFYIVIIMAIVLLSFGVARKAILSPKEPPSWRLARDIVFEPYWMMYGEVYASDIDVCSNETSCPPGSFLTPFLQAVYLFVQYIIMVNLLIACFNNIYLDIKSISNKLWKYNRYRYIMTYHQKPWLPPPFILLNHLCLLLRGLCCRPAPQDQEEGDGGLKLYLTKDDLKKLHDFEEQCVEKYFHEKTEGLNCSFEEQIRMTSERVSEMFFQLKEMNEKVSFIKDSLLSLDSQVGHLQDLSAITVDTLKVLSAVDTLQEDEILLANRKHSTCRKRPHSWTNVICAKVLSDMESCGKKKLQYYSMPPSLLRSLARSQLPPSVQRGALVEVTHSKREASHVREEQEEREMEQRTTASGISHVRQAHSKYGQFLLVPSSGKQVPLSLETPPHLFRSSEEAGIDGLVLEHIHQSDLTTHLPQQTPAASHQALVAEHKDQHEAVTQMSDKPAKAEQDLLAFSGTPAPMTVTSLPSRAISMQDEGGYVNWAFSENDETGVFSFKKKWKTCLASTCNSDSNPGGDYFLHTGGRSGLDNSRRLAQSCECPAGPWTQARRSFWINPLCRDKALIKSHSFRFHKEEKLRKTWKNNSHSKSLETRSTWLKAKLLTKTRSLSKKKRKTQGLQVPVITVNACYQSDQLNAEPGETNTTEEFSKKWLSVSNFSQIGLEPYIYQKMKMKEIKRHTTQASDHLRQPQENRDKTPTWNSGSTSLSRSFLTRSPNEVHKISTSLKSPQEPHHHYSAIERNNLMRLSQTIPFTPIQLFTGEEVTIYKLEESSPLTLDKSMSSWSQHGRAAMIQVLSQEEMDGGLRKAMRVISTWSEDDVLKPGQVFIVKSFLPEVVQTWYKIFQESTVLHLCLREIQQQRAAQKLIYTFNQVKPQTIPYTPRFLEVSLVYCHSANQWLTIEKYMTGEFRKYNNNNGDEIAPTNTLEELMLAFSHWTYEYTRGELLVLDLQGVGENLTDPSVIKPEDKQSRGMVFGPANLGEDAIRSFIAKHRCNSCCGKLRLPDLKRNDYSLSRTHCNLGFGQTIEPTEELPERDKNRSSLEDHTRL
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: Bifunctional protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain (PubMed:27991852, PubMed:28821869). Crucial for Mg(2+) homeostasis. Has an important role in epithelial magnesium transport and in the active Mg(2+) absorption in the gut and kidney (PubMed:27991852). However, whether TRPM6 forms functional homomeric channels by itself or functions primarily as a subunit of heteromeric TRPM6-TRPM7 channels, is still under debate (By similarity). {ECO:0000250|UniProtKB:Q9BX84, ECO:0000269|PubMed:27991852, ECO:0000269|PubMed:28821869}.; FUNCTION: [TRPM6 kinase, cleaved form]: The C-terminal kinase domain can be cleaved from the channel segment in a cell-type-specific fashion. The cleaved kinase fragments can translocate to the nucleus, and bind chromatin-remodeling complex proteins to ultimately phosphorylate specific Ser/Thr residues of histones known to be functionally important for cell differentiation and development. {ECO:0000250|UniProtKB:Q9BX84}.
uniprot
proteins
mass_dalton
232888
uniprot
proteins
mutagenesis
MUTAGEN 1810; /note="K->R: Abolishes protein kinase activity."; /evidence="ECO:0000269|PubMed:28821869
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated; autophosphorylation controls the protein kinase activity of TRPM6 towards their substrates. Autophosphorylation of Thr-1857 in the kinase domain is essential for the inhibitory effect of RACK1. {ECO:0000250|UniProtKB:Q9BX84}.; PTM: The C-terminus of TRPM6 is proteolytically cleaved in vivo, in a cell type-specific fashion, releasing the kinase module from the transmembrane domain. The cleaved kinase fragments are translocated to the nucleus to phosphorylate histones and regulate gene expression. {ECO:0000250|UniProtKB:Q9BX84}.
uniprot
proteins
protein_family
ALPK subfamily; Transient receptor (TC 1.A.4) family
uniprot
proteins
protein_family
Alpha-type protein kinase family
uniprot
proteins
protein_family
LTrpC subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
TRPM6 sub-subfamily
uniprot
proteins
pubmed
19692351
uniprot
proteins
pubmed
27991852
uniprot
proteins
pubmed
28821869
uniprot
proteins
sequence_length
2028
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9BX84}; Multi-pass membrane protein {ECO:0000305}. Apical cell membrane {ECO:0000250|UniProtKB:Q9BX84}; Multi-pass membrane protein {ECO:0000305}. Note=TRPM6 requires the presence of TRPM7 to be targeted to the cell membrane. {ECO:0000250|UniProtKB:Q9BX84}.; SUBCELLULAR LOCATION: [TRPM6 kinase, cleaved form]: Nucleus {ECO:0000250|UniProtKB:Q9BX84}.
uniprot
proteins
transmembrane_region
TRANSMEM 748..768; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 848..868; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 911..931; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 946..966; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 979..999; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1054..1074; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins