TRPM6
entrez
140803
canonical
uniprot
Q9BX84
canonical
ensembl
ENSG00000119121
resolver
ensp
ENSP00000354006
resolver
ensp
ENSP00000354962
resolver
ensp
ENSP00000396672
resolver
genesymbol
TRPM6
resolver
genesymbol_syn
CHAK2
resolver
hgnc
HGNC:17995
resolver
uniprot
Q6VPR8
resolver
uniprot
Q6VPR9
resolver
uniprot
Q6VPS0
resolver
uniprot
Q6VPS1
resolver
uniprot
Q6VPS2
resolver
uniprot_entry
TRPM6_HUMAN
resolver
uniprot_sec
Q6VPR8
resolver
uniprot_sec
Q6VPR9
resolver
uniprot_sec
Q6VPS0
resolver
uniprot_sec
Q6VPS1
resolver
uniprot_sec
Q6VPS2
resolver
activity_regulation
ACTIVITY REGULATION: Strongly inhibited by intracellular Mg(2+); unlikely to be active at physiological levels of intracellular Mg(2+) (PubMed:14576148, PubMed:16636202, PubMed:24385424). 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 (By similarity). The kinase activity is controlled through the autophosphorylation of a serine/threonine-rich region located to the N-terminal of the catalytic domain (PubMed:18258429, PubMed:18365021). {ECO:0000250|UniProtKB:Q8CIR4, ECO:0000269|PubMed:14576148, ECO:0000269|PubMed:16636202, ECO:0000269|PubMed:18258429, ECO:0000269|PubMed:18365021, ECO:0000269|PubMed:24385424}.
uniprot
proteins
amino_acid_sequence
MKEQPVLERLQSQKSWIKGVFDKRECSTIIPSSKNPHRCTPVCQVCQNLIRCYCGRLIGDHAGIDYSWTISAAKGKESEQWSVEKHTTKSPTDTFGTINFQDGEHTHHAKYIRTSYDTKLDHLLHLMLKEWKMELPKLVISVHGGIQNFTMPSKFKEIFSQGLVKAAETTGAWIITEGINTGVSKHVGDALKSHSSHSLRKIWTVGIPPWGVIENQRDLIGKDVVCLYQTLDNPLSKLTTLNSMHSHFILSDDGTVGKYGNEMKLRRNLEKYLSLQKIHCRSRQGVPVVGLVVEGGPNVILSVWETVKDKDPVVVCEGTGRAADLLAFTHKHLADEGMLRPQVKEEIICMIQNTFNFSLKQSKHLFQILMECMVHRDCITIFDADSEEQQDLDLAILTALLKGTNLSASEQLNLAMAWDRVDIAKKHILIYEQHWKPDALEQAMSDALVMDRVDFVKLLIEYGVNLHRFLTIPRLEELYNTKQGPTNTLLHHLVQDVKQHTLLSGYRITLIDIGLVVEYLIGRAYRSNYTRKHFRALYNNLYRKYKHQRHSSGNRNESAESTLHSQFIRTAQPYKFKEKSIVLHKSRKKSKEQNVSDDPESTGFLYPYNDLLVWAVLMKRQKMAMFFWQHGEEATVKAVIACILYRAMAHEAKESHMVDDASEELKNYSKQFGQLALDLLEKAFKQNERMAMTLLTYELRNWSNSTCLKLAVSGGLRPFVSHTCTQMLLTDMWMGRLKMRKNSWLKIIISIILPPTILTLEFKSKAEMSHVPQSQDFQFMWYYSDQNASSSKESASVKEYDLERGHDEKLDENQHFGLESGHQHLPWTRKVYEFYSAPIVKFWFYTMAYLAFLMLFTYTVLVEMQPQPSVQEWLVSIYIFTNAIEVVREICISEPGKFTQKVKVWISEYWNLTETVAIGLFSAGFVLRWGDPPFHTAGRLIYCIDIIFWFSRLLDFFAVNQHAGPYVTMIAKMTANMFYIVIIMAIVLLSFGVARKAILSPKEPPSWSLARDIVFEPYWMIYGEVYAGEIDVCSSQPSCPPGSFLTPFLQAVYLFVQYIIMVNLLIAFFNNVYLDMESISNNLWKYNRYRYIMTYHEKPWLPPPLILLSHVGLLLRRLCCHRAPHDQEEGDVGLKLYLSKEDLKKLHDFEEQCVEKYFHEKMEDVNCSCEERIRVTSERVTEMYFQLKEMNEKVSFIKDSLLSLDSQVGHLQDLSALTVDTLKVLSAVDTLQEDEALLAKRKHSTCKKLPHSWSNVICAEVLGSMEIAGEKKYQYYSMPSSLLRSLAGGRHPPRVQRGALLEITNSKREATNVRNDQERQETQSSIVVSGVSPNRQAHSKYGQFLLVPSNLKRVPFSAETVLPLSRPSVPDVLATEQDIQTEVLVHLTGQTPVVSDWASVDEPKEKHEPIAHLLDGQDKAEQVLPTLSCTPEPMTMSSPLSQAKIMQTGGGYVNWAFSEGDETGVFSIKKKWQTCLPSTCDSDSSRSEQHQKQAQDSSLSDNSTRSAQSSECSEVGPWLQPNTSFWINPLRRYRPFARSHSFRFHKEEKLMKICKIKNLSGSSEIGQGAWVKAKMLTKDRRLSKKKKNTQGLQVPIITVNACSQSDQLNPEPGENSISEEEYSKNWFTVSKFSHTGVEPYIHQKMKTKEIGQCAIQISDYLKQSQEDLSKNSLWNSRSTNLNRNSLLKSSIGVDKISASLKSPQEPHHHYSAIERNNLMRLSQTIPFTPVQLFAGEEITVYRLEESSPLNLDKSMSSWSQRGRAAMIQVLSREEMDGGLRKAMRVVSTWSEDDILKPGQVFIVKSFLPEVVRTWHKIFQESTVLHLCLREIQQQRAAQKLIYTFNQVKPQTIPYTPRFLEVFLIYCHSANQWLTIEKYMTGEFRKYNNNNGDEITPTNTLEELMLAFSHWTYEYTRGELLVLDLQGVGENLTDPSVIKPEVKQSRGMVFGPANLGEDAIRNFIAKHHCNSCCRKLKLPDLKRNDYSPERINSTFGLEIKIESAEEPPARETGRNSPEDDMQL
uniprot
proteins
disease_involvement
DISEASE: Hypomagnesemia 1 (HOMG1) [MIM:602014]: A disorder due to a primary defect in intestinal magnesium absorption. It is characterized by low levels of serum magnesium alongside with a normal renal magnesium secretion, secondary hypocalcemia and calcinocis. Affected individuals show neurologic symptoms of hypomagnesemic hypocalcemia, including seizures and muscle spasms, during infancy. Hypocalcemia is secondary to parathyroid failure resulting from magnesium deficiency. Untreated, the disorder may be fatal or may result in neurological damage. {ECO:0000269|PubMed:12032568, ECO:0000269|PubMed:14976260, ECO:0000269|PubMed:16636202, ECO:0000269|PubMed:17197439, ECO:0000269|PubMed:23942199}. Note=The disease is caused by variants affecting the gene represented in this entry.
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:14576148, PubMed:16636202, PubMed:18258429, PubMed:18365021). Crucial for Mg(2+) homeostasis. Has an important role in epithelial Mg(2+) transport and in the active Mg(2+) absorption in the gut and kidney (PubMed:14576148). However, whether TRPM6 forms functional homomeric channels by itself or functions primarily as a subunit of heteromeric TRPM6-TRPM7 channels, is still under debate (PubMed:14576148, PubMed:16636202, PubMed:24385424). {ECO:0000269|PubMed:14576148, ECO:0000269|PubMed:16636202, ECO:0000269|PubMed:18258429, ECO:0000269|PubMed:18365021, ECO:0000269|PubMed:24385424}.; 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:0000269|PubMed:28784805}.
uniprot
proteins
mass_dalton
231708
uniprot
proteins
mutagenesis
MUTAGEN 1063..1065; /note="NLL->FAP: Abolishes channel activity. Abolishes endogenous protein cleavage."; /evidence="ECO:0000269|PubMed:28784805"; MUTAGEN 1804; /note="K->R: Abolishes kinase activity but does not affect expression levels or binding to RACK1."; /evidence="ECO:0000269|PubMed:18258429"; MUTAGEN 1851; /note="T->A: Significantly decreases autophosphorylation. Does not alter binding to RACK1 but prevents inhibition by RACK1."; /evidence="ECO:0000269|PubMed:18258429"; MUTAGEN 1851; /note="T->D: Significantly decreases autophosphorylation. Does not alter binding to RACK1 or inhibition by RACK1."; /evidence="ECO:0000269|PubMed:18258429
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated; autophosphorylation controlls the protein kinase activity of TRPM6 towards their substrates (PubMed:18258429, PubMed:18365021). Autophosphorylation of Thr-1851 in the kinase domain is essential for the inhibitory effect of RACK1 (PubMed:18258429). {ECO:0000269|PubMed:18258429, ECO:0000269|PubMed:18365021}.; 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:0000269|PubMed:28784805}.
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
11357414
uniprot
proteins
pubmed
12032568
uniprot
proteins
pubmed
14576148
uniprot
proteins
pubmed
14976260
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
16636202
uniprot
proteins
pubmed
17197439
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
18258429
uniprot
proteins
pubmed
18365021
uniprot
proteins
pubmed
23942199
uniprot
proteins
pubmed
24385424
uniprot
proteins
pubmed
28784805
uniprot
proteins
sequence_length
2022
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23942199}; Multi-pass membrane protein {ECO:0000305}. Apical cell membrane {ECO:0000269|PubMed:14576148}; Multi-pass membrane protein {ECO:0000305}. Note=TRPM6 requires the presence of TRPM7 to be targeted to the cell membrane (in HEK 293 cells). {ECO:0000269|PubMed:14976260, ECO:0000269|PubMed:17197439}.; SUBCELLULAR LOCATION: [TRPM6 kinase, cleaved form]: Nucleus {ECO:0000269|PubMed:28784805}.
uniprot
proteins
transmembrane_region
TRANSMEM 742..762; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 842..862; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 906..926; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 940..960; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 973..993; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1048..1068; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins