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1.A.4.5.8
The intestinal/renal Mg2+ absorption Mg2+ influx channel, Melastatin6 or TRPM6 (5x higher affinity for Mg2+ than Ca2+; regulated by internal Mg2+) (Voets et al., 2004). TRPM6 and its closest homologue TRPM7 (also a Mg2+-permeable cation channel) assemble to form a functional heterooligomeric channel (Chubanov et al., 2004).  Mutations in TRPM6 promotes hypomagnesemia with secondary hypocalcemia (Chubanov et al., 2007). TRPM6 and the closely related TRPM7 are large channel-kinase proteins (Li et al., 2007; Schmitz et al., 2007). TRPM7 also transports protons competitively with Mg2+ and Ca2+ (Numata and Okada, 2008). Intracellular ATP regulates TRPM6 channel activity via its α-kinase domain independently of α-kinase activity (Thébault et al., 2008). Also plays a role in Zn2+ homeostasis and Zn2+- mediated neuronal injury (Inoue et al., 2010).  The protein is cleaved to release a chromatin-modifying kinase (Krapivinsky et al. 2014).  TRPM7 is a Mg2+ sensor and transducer of signaling pathways under stressful environmental conditions. Its kinase can act on its own in chromatin remodeling processes, but TRPM6's kinase activity regulates intracellular trafficking of TRPM7 and TRPM7-dependent cell growth (Cabezas-Bratesco et al. 2015).  Residues involved in cation selectivity have been identified (Topala et al. 2007).

Accession Number:Q9BX84
Protein Name:TRPM6
Length:2022
Molecular Weight:231708.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:8
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Ca2+, Mg2+

Cross database links:

Genevestigator: Q9BX84
HEGENOM: HBG505626
RefSeq: NP_060132.3   
Entrez Gene ID: 140803   
Pfam: PF02816    PF00520   
OMIM: 602014  phenotype
607009  gene
KEGG: hsa:140803   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005524 F:ATP binding
GO:0005262 F:calcium channel activity
GO:0046872 F:metal ion binding
GO:0004674 F:protein serine/threonine kinase activity
GO:0006816 P:calcium ion transport
GO:0006468 P:protein amino acid phosphorylation
GO:0009636 P:response to toxin
GO:0055085 P:transmembrane transport

References (5)

[1] “Novel type of signaling molecules: protein kinases covalently linked to ion channels.”  Riazanova L.V.et.al.   11357414
[2] “Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family.”  Schlingmann K.P.et.al.   12032568
[3] “Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia.”  Chubanov V.et.al.   14976260
[4] “DNA sequence and analysis of human chromosome 9.”  Humphray S.J.et.al.   15164053
[5] “Patterns of somatic mutation in human cancer genomes.”  Greenman C.et.al.   17344846

External Searches:

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  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MKEQPVLERL QSQKSWIKGV FDKRECSTII PSSKNPHRCT PVCQVCQNLI RCYCGRLIGD 
61:	HAGIDYSWTI SAAKGKESEQ WSVEKHTTKS PTDTFGTINF QDGEHTHHAK YIRTSYDTKL 
121:	DHLLHLMLKE WKMELPKLVI SVHGGIQNFT MPSKFKEIFS QGLVKAAETT GAWIITEGIN 
181:	TGVSKHVGDA LKSHSSHSLR KIWTVGIPPW GVIENQRDLI GKDVVCLYQT LDNPLSKLTT 
241:	LNSMHSHFIL SDDGTVGKYG NEMKLRRNLE KYLSLQKIHC RSRQGVPVVG LVVEGGPNVI 
301:	LSVWETVKDK DPVVVCEGTG RAADLLAFTH KHLADEGMLR PQVKEEIICM IQNTFNFSLK 
361:	QSKHLFQILM ECMVHRDCIT IFDADSEEQQ DLDLAILTAL LKGTNLSASE QLNLAMAWDR 
421:	VDIAKKHILI YEQHWKPDAL EQAMSDALVM DRVDFVKLLI EYGVNLHRFL TIPRLEELYN 
481:	TKQGPTNTLL HHLVQDVKQH TLLSGYRITL IDIGLVVEYL IGRAYRSNYT RKHFRALYNN 
541:	LYRKYKHQRH SSGNRNESAE STLHSQFIRT AQPYKFKEKS IVLHKSRKKS KEQNVSDDPE 
601:	STGFLYPYND LLVWAVLMKR QKMAMFFWQH GEEATVKAVI ACILYRAMAH EAKESHMVDD 
661:	ASEELKNYSK QFGQLALDLL EKAFKQNERM AMTLLTYELR NWSNSTCLKL AVSGGLRPFV 
721:	SHTCTQMLLT DMWMGRLKMR KNSWLKIIIS IILPPTILTL EFKSKAEMSH VPQSQDFQFM 
781:	WYYSDQNASS SKESASVKEY DLERGHDEKL DENQHFGLES GHQHLPWTRK VYEFYSAPIV 
841:	KFWFYTMAYL AFLMLFTYTV LVEMQPQPSV QEWLVSIYIF TNAIEVVREI CISEPGKFTQ 
901:	KVKVWISEYW NLTETVAIGL FSAGFVLRWG DPPFHTAGRL IYCIDIIFWF SRLLDFFAVN 
961:	QHAGPYVTMI AKMTANMFYI VIIMAIVLLS FGVARKAILS PKEPPSWSLA RDIVFEPYWM 
1021:	IYGEVYAGEI DVCSSQPSCP PGSFLTPFLQ AVYLFVQYII MVNLLIAFFN NVYLDMESIS 
1081:	NNLWKYNRYR YIMTYHEKPW LPPPLILLSH VGLLLRRLCC HRAPHDQEEG DVGLKLYLSK 
1141:	EDLKKLHDFE EQCVEKYFHE KMEDVNCSCE ERIRVTSERV TEMYFQLKEM NEKVSFIKDS 
1201:	LLSLDSQVGH LQDLSALTVD TLKVLSAVDT LQEDEALLAK RKHSTCKKLP HSWSNVICAE 
1261:	VLGSMEIAGE KKYQYYSMPS SLLRSLAGGR HPPRVQRGAL LEITNSKREA TNVRNDQERQ 
1321:	ETQSSIVVSG VSPNRQAHSK YGQFLLVPSN LKRVPFSAET VLPLSRPSVP DVLATEQDIQ 
1381:	TEVLVHLTGQ TPVVSDWASV DEPKEKHEPI AHLLDGQDKA EQVLPTLSCT PEPMTMSSPL 
1441:	SQAKIMQTGG GYVNWAFSEG DETGVFSIKK KWQTCLPSTC DSDSSRSEQH QKQAQDSSLS 
1501:	DNSTRSAQSS ECSEVGPWLQ PNTSFWINPL RRYRPFARSH SFRFHKEEKL MKICKIKNLS 
1561:	GSSEIGQGAW VKAKMLTKDR RLSKKKKNTQ GLQVPIITVN ACSQSDQLNP EPGENSISEE 
1621:	EYSKNWFTVS KFSHTGVEPY IHQKMKTKEI GQCAIQISDY LKQSQEDLSK NSLWNSRSTN 
1681:	LNRNSLLKSS IGVDKISASL KSPQEPHHHY SAIERNNLMR LSQTIPFTPV QLFAGEEITV 
1741:	YRLEESSPLN LDKSMSSWSQ RGRAAMIQVL SREEMDGGLR KAMRVVSTWS EDDILKPGQV 
1801:	FIVKSFLPEV VRTWHKIFQE STVLHLCLRE IQQQRAAQKL IYTFNQVKPQ TIPYTPRFLE 
1861:	VFLIYCHSAN QWLTIEKYMT GEFRKYNNNN GDEITPTNTL EELMLAFSHW TYEYTRGELL 
1921:	VLDLQGVGEN LTDPSVIKPE VKQSRGMVFG PANLGEDAIR NFIAKHHCNS CCRKLKLPDL 
1981:	KRNDYSPERI NSTFGLEIKI ESAEEPPARE TGRNSPEDDM QL