Reviewed, UniProtKB/Swiss-Prot Q96QT4 (TRPM7_HUMAN)

Names and origin

Protein names

Recommended name:
    Transient receptor potential cation channel subfamily M member 7
    EC=2.7.11.1
Alternative name(s):
    Long transient receptor potential channel 7
      Short name=LTrpC7
    Channel-kinase 1

Gene names

Name:	TRPM7
Synonyms:	CHAK1, LTRPC7

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1865 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Essential ion channel and serine/threonine-protein kinase. Divalent cation channel permeable to calcium and magnesium. Has a central role in magnesium ion homeostasis and in the regulation of anoxic neuronal cell death. The kinase activity is essential for the channel function. May be involved in a fundamental process that adjusts plasma membrane divalent cation fluxes according to the metabolic state of the cell. Phosphorylates annexin A1 (ANXA1). Ref.6 Ref.7
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	Homodimer. Interacts with PLCB1 By similarity. Forms heterodimers with TRPM6.
Subcellular location	Membrane; Multi-pass membrane protein Probable.
Post-translational modification	Autophosphorylated By similarity.
Involvement in disease	Defects in TRPM7 influence susceptibility to amyotrophic lateral sclerosis-parkinsonism/dementia complex type 1 [MIM:105500]; also called amyotrophic lateral sclerosis-parkinsonism/dementia complex of Guam or Guam disease. Amyotrophic lateral sclerosis-parkinsonism/dementia complex type 1 is a neurodegenerative disorder with unusually high incidence among the Chamorro people of the Western Pacific Islands of Guam. Both amyotrophic lateral sclerosis and parkinsonism-dementia are chronic, progressive, and uniformly fatal disorders in this population. Both diseases are known to occur in the same kindred, the same sibship, and even the same individual.
Sequence similarities	In the C-terminal section; belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily. In the N-terminal section; belongs to the transient receptor family. LTrpC subfamily. Contains 1 alpha-type protein kinase domain.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Coiled coil Transmembrane
Ligand	ATP-binding Calcium Metal-binding Nucleotide-binding Zinc
Molecular function	Calcium channel Ionic channel Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	calcium ion transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium channel activity Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1865	1865	Transient receptor potential cation channel subfamily M member 7		PRO_0000215331
Regions
	Topological domain	1 – 755	755	Cytoplasmic Potential
	Transmembrane	756 – 776	21	Potential
	Topological domain	777 – 855	79	Extracellular Potential
	Transmembrane	856 – 876	21	Potential
	Topological domain	877 – 918	42	Cytoplasmic Potential
	Transmembrane	919 – 939	21	Potential
	Topological domain	940 – 962	23	Extracellular Potential
	Transmembrane	963 – 983	21	Potential
	Topological domain	984 – 995	12	Cytoplasmic Potential
	Transmembrane	996 – 1016	21	Potential
	Topological domain	1017 – 1035	19	Extracellular Potential
	Topological domain	1036 – 1056	21	Pore forming Potential
	Topological domain	1057 – 1074	18	Extracellular Potential
	Transmembrane	1075 – 1095	21	Potential
	Topological domain	1096 – 1865	770	Cytoplasmic Potential
	Domain	1594 – 1824	231	Alpha-type protein kinase
	Nucleotide binding	1794 – 1800	7	ATP By similarity
	Coiled coil	1198 – 1250	53	By similarity
Sites
	Active site	1767	1	Proton acceptor By similarity
	Metal binding	1753	1	Zinc By similarity
	Metal binding	1810	1	Zinc By similarity
	Metal binding	1812	1	Zinc By similarity
	Metal binding	1816	1	Zinc By similarity
	Binding site	1624	1	ATP By similarity
	Binding site	1648	1	ATP By similarity
	Binding site	1720	1	ATP By similarity
	Binding site	1769	1	ATP By similarity
	Binding site	1777	1	ATP By similarity
Amino acid modifications
	Modified residue	1477	1	Phosphoserine Ref.9
	Modified residue	1493	1	Phosphoserine By similarity
Natural variations
	Natural variant	68	1	G → V Ref.11		VAR_042395
	Natural variant	406	1	S → C in an ovarian serous carcinoma sample; somatic mutation. Ref.11		VAR_042396
	Natural variant	459	1	I → T Ref.11		VAR_042397
	Natural variant	574	1	K → N Ref.11		VAR_042398
	Natural variant	720	1	T → S in a breast infiltrating ductal carcinoma sample; somatic mutation. Ref.11		VAR_042399
	Natural variant	830	1	M → V in a gastric adenocarcinoma sample; somatic mutation. Ref.11		VAR_042400
	Natural variant	949	1	F → Y Ref.11		VAR_042401
	Natural variant	1033	1	A → G: dbSNP rs34530969.		VAR_052381
	Natural variant	1064	1	Q → R Ref.11		VAR_042402
	Natural variant	1145	1	I → V: dbSNP rs34711809.		VAR_052382
	Natural variant	1211	1	I → T Ref.11		VAR_042403
	Natural variant	1254	1	A → V Ref.11		VAR_042404
	Natural variant	1306	1	D → E Ref.11		VAR_042405
	Natural variant	1444	1	R → K Ref.11		VAR_042406
	Natural variant	1482	1	T → I Mutant channels are functional but show increased susceptibility to inhibition by intracellular magnesium concentrations compared to wild-type channels. dbSNP rs8042919. Ref.11 Ref.4 Ref.10		VAR_019967
Experimental info
	Mutagenesis	1648	1	K → R: Loss of kinase activity. Ref.6
	Mutagenesis	1799	1	G → D: Loss of kinase activity. Ref.6
	Sequence conflict	573 – 575	3	EKM → KKK in BAD18773. Ref.4
	Sequence conflict	998	1	A → S Ref.5
	Sequence conflict	1496	1	Missing in AAK19738. Ref.3
	Sequence conflict	1520	1	D → V in AAK19738. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q96QT4-1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: BE732674D52D7485	FASTA	1,865	212,697
	10 20 30 40 50 60 MSQKSWIEST LTKRECVYII PSSKDPHRCL PGCQICQQLV RCFCGRLVKQ HACFTASLAM 70 80 90 100 110 120 KYSDVKLGDH FNQAIEEWSV EKHTEQSPTD AYGVINFQGG SHSYRAKYVR LSYDTKPEVI 130 140 150 160 170 180 LQLLLKEWQM ELPKLVISVH GGMQKFELHP RIKQLLGKGL IKAAVTTGAW ILTGGVNTGV 190 200 210 220 230 240 AKHVGDALKE HASRSSRKIC TIGIAPWGVI ENRNDLVGRD VVAPYQTLLN PLSKLNVLNN 250 260 270 280 290 300 LHSHFILVDD GTVGKYGAEV RLRRELEKTI NQQRIHARIG QGVPVVALIF EGGPNVILTV 310 320 330 340 350 360 LEYLQESPPV PVVVCEGTGR AADLLAYIHK QTEEGGNLPD AAEPDIISTI KKTFNFGQNE 370 380 390 400 410 420 ALHLFQTLME CMKRKELITV FHIGSDEHQD IDVAILTALL KGTNASAFDQ LILTLAWDRV 430 440 450 460 470 480 DIAKNHVFVY GQQWLVGSLE QAMLDALVMD RVAFVKLLIE NGVSMHKFLT IPRLEELYNT 490 500 510 520 530 540 KQGPTNPMLF HLVRDVKQGN LPPGYKITLI DIGLVIEYLM GGTYRCTYTR KRFRLIYNSL 550 560 570 580 590 600 GGNNRRSGRN TSSSTPQLRK SHESFGNRAD KKEKMRHNHF IKTAQPYRPK IDTVMEEGKK 610 620 630 640 650 660 KRTKDEIVDI DDPETKRFPY PLNELLIWAC LMKRQVMARF LWQHGEESMA KALVACKIYR 670 680 690 700 710 720 SMAYEAKQSD LVDDTSEELK QYSNDFGQLA VELLEQSFRQ DETMAMKLLT YELKNWSNST 730 740 750 760 770 780 CLKLAVSSRL RPFVAHTCTQ MLLSDMWMGR LNMRKNSWYK VILSILVPPA ILLLEYKTKA 790 800 810 820 830 840 EMSHIPQSQD AHQMTMDDSE NNFQNITEEI PMEVFKEVRI LDSNEGKNEM EIQMKSKKLP 850 860 870 880 890 900 ITRKFYAFYH APIVKFWFNT LAYLGFLMLY TFVVLVQMEQ LPSVQEWIVI AYIFTYAIEK 910 920 930 940 950 960 VREIFMSEAG KVNQKIKVWF SDYFNISDTI AIISFFIGFG LRFGAKWNFA NAYDNHVFVA 970 980 990 1000 1010 1020 GRLIYCLNII FWYVRLLDFL AVNQQAGPYV MMIGKMVANM FYIVVIMALV LLSFGVPRKA 1030 1040 1050 1060 1070 1080 ILYPHEAPSW TLAKDIVFHP YWMIFGEVYA YEIDVCANDS VIPQICGPGT WLTPFLQAVY 1090 1100 1110 1120 1130 1140 LFVQYIIMVN LLIAFFNNVY LQVKAISNIV WKYQRYHFIM AYHEKPVLPP PLIILSHIVS 1150 1160 1170 1180 1190 1200 LFCCICKRRK KDKTSDGPKL FLTEEDQKKL HDFEEQCVEM YFNEKDDKFH SGSEERIRVT 1210 1220 1230 1240 1250 1260 FERVEQMCIQ IKEVGDRVNY IKRSLQSLDS QIGHLQDLSA LTVDTLKTLT AQKASEASKV 1270 1280 1290 1300 1310 1320 HNEITRELSI SKHLAQNLID DGPVRPSVWK KHGVVNTLSS SLPQGDLESN NPFHCNILMK 1330 1340 1350 1360 1370 1380 DDKDPQCNIF GQDLPAVPQR KEFNFPEAGS SSGALFPSAV SPPELRQRLH GVELLKIFNK 1390 1400 1410 1420 1430 1440 NQKLGSSSTS IPHLSSPPTK FFVSTPSQPS CKSHLETGTK DQETVCSKAT EGDNTEFGAF 1450 1460 1470 1480 1490 1500 VGHRDSMDLQ RFKETSNKIK ILSNNNTSEN TLKRVSSLAG FTDCHRTSIP VHSKQAEKIS 1510 1520 1530 1540 1550 1560 RRPSTEDTHE VDSKAALIPD WLQDRPSNRE MPSEEGTLNG LTSPFKPAMD TNYYYSAVER 1570 1580 1590 1600 1610 1620 NNLMRLSQSI PFTPVPPRGE PVTVYRLEES SPNILNNSMS SWSQLGLCAK IEFLSKEEMG 1630 1640 1650 1660 1670 1680 GGLRRAVKVQ CTWSEHDILK SGHLYIIKSF LPEVVNTWSS IYKEDTVLHL CLREIQQQRA 1690 1700 1710 1720 1730 1740 AQKLTFAFNQ MKPKSIPYSP RFLEVFLLYC HSAGQWFAVE ECMTGEFRKY NNNNGDEIIP 1750 1760 1770 1780 1790 1800 TNTLEEIMLA FSHWTYEYTR GELLVLDLQG VGENLTDPSV IKAEEKRSCD MVFGPANLGE 1810 1820 1830 1840 1850 1860 DAIKNFRAKH HCNSCCRKLK LPDLKRNDYT PDKIIFPQDE PSDLNLQPGN STKESESTNS VRLML

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell viability." Nadler M.J.S., Hermosura M.C., Inabe K., Perraud A.-L., Zhu Q., Stokes A.J., Kurosaki T., Kinet J.-P., Penner R., Scharenberg A.M., Fleig A. Nature 411:590-595(2001) [PubMed: 11385574] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
[2]	Erratum Nadler M.J.S., Hermosura M.C., Inabe K., Perraud A.-L., Zhu Q., Stokes A.J., Kurosaki T., Kinet J.-P., Penner R., Scharenberg A.M., Fleig A. Nature 412:660-660(2001)
[3]	"Characterization of the protein kinase activity of TRPM7/ChaK1, a protein kinase fused to the transient receptor potential ion channel." Ryazanova L.V., Dorovkov M.V., Ansari A., Ryazanov A.G. J. Biol. Chem. 279:3708-3716(2004) [PubMed: 14594813] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-575 AND 1096-1865, VARIANT ILE-1482. Tissue: Colon and Placenta.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 464-998. Tissue: Liver.
[6]	"Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7." Schmitz C., Perraud A.-L., Johnson C.O., Inabe K., Smith M.K., Penner R., Kurosaki T., Fleig A., Scharenberg A.M. Cell 114:191-200(2003) [PubMed: 12887921] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-1648 AND GLY-1799.
[7]	"Phosphorylation of annexin I by TRPM7 channel-kinase." Dorovkov M.V., Ryazanov A.G. J. Biol. Chem. 279:50643-50646(2004) [PubMed: 15485879] [Abstract] Cited for: FUNCTION.
[8]	"Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia." Chubanov V., Waldegger S., Mederos y Schnitzler M., Vitzthum H., Sassen M.C., Seyberth H.W., Konrad M., Gudermann T. Proc. Natl. Acad. Sci. U.S.A. 101:2894-2899(2004) [PubMed: 14976260] [Abstract] Cited for: INTERACTION WITH TRPM6.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1477, MASS SPECTROMETRY.
[10]	"A TRPM7 variant shows altered sensitivity to magnesium that may contribute to the pathogenesis of two Guamanian neurodegenerative disorders." Hermosura M.C., Nayakanti H., Dorovkov M.V., Calderon F.R., Ryazanov A.G., Haymer D.S., Garruto R.M. Proc. Natl. Acad. Sci. U.S.A. 102:11510-11515(2005) [PubMed: 16051700] [Abstract] Cited for: VARIANT ILE-1482, CHARACTERIZATION OF VARIANT ILE-1482.
[11]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-68; CYS-406; THR-459; ASN-574; SER-720; VAL-830; TYR-949; ARG-1064; THR-1211; VAL-1254; GLU-1306; LYS-1444 AND ILE-1482.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY032950 mRNA. Translation: AAK44211.1. AF346629 mRNA. Translation: AAK19738.2. AK000124 mRNA. Translation: BAA90958.1. AK172800 mRNA. Translation: BAD18773.1. Different initiation. AK075193 mRNA. Translation: BAC11462.1. Different initiation. BC051024 mRNA. Translation: AAH51024.1.
IPI	IPI00290032.
RefSeq	NP_060142.3.
UniGene	Hs.512894
3D structure databases
HSSP	HSSP built from PDB template 1IA9 based on UniProtKB Q9JLQ1.
SMR	Q96QT4. Positions 1551-1830.
ModBase	Search...
Protein family/group databases
TCDB	1.A.4.5.6. transient receptor potential Ca2+ channel (TRP-CC) family.
PTM databases
PhosphoSite	Q96QT4.
Proteomic databases
PRIDE	Q96QT4.
Genome annotation databases
Ensembl	ENSG00000092439. Homo sapiens. [Contig view]
GeneID	54822.
KEGG	hsa:54822.
Organism-specific databases
GeneCards	GC15M048639.
H-InvDB	HIX0012237.
HGNC	HGNC:17994. TRPM7.
MIM	105500. phenotype. 605692. gene.
Orphanet	90020. Amyotrophic lateral sclerosis-parkinsonism-dementia complex.
PharmGKB	PA38273.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q96QT4.
HOVERGEN	Q96QT4.
OMA	Q96QT4. MRHNHFI.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Gene expression databases
ArrayExpress	Q96QT4.
Bgee	Q96QT4.
CleanEx	HS_TRPM7.
GermOnline	ENSG00000092439. Homo sapiens.
Family and domain databases
InterPro	IPR005821. Ion_trans. IPR004166. MHCK_EF2_kinase. [Graphical view]
Pfam	PF02816. Alpha_kinase. 1 hit. PF00520. Ion_trans. 1 hit. [Graphical view]
SMART	SM00811. Alpha_kinase. 1 hit. [Graphical view]
PROSITE	PS51158. ALPHA_KINASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	57577.
SOURCE	Search...

Entry information

Entry name

TRPM7_HUMAN

Accession

Primary (citable) accession number: Q96QT4
Secondary accession number(s): Q6ZMF5 , Q86VJ4, Q8NBW2, Q9BXB2, Q9NXQ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 7, 2004
Last sequence update:	December 1, 2001
Last modified:	June 16, 2009
This is version 64 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)