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Protein

Transient receptor potential cation channel subfamily M member 7

Gene

TRPM7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Involved in TNF-induced necroptosis downstream of MLKL by mediating calcium influx. 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).3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei1624ATPBy similarity1
Binding sitei1648ATPBy similarity1
Binding sitei1720ATPBy similarity1
Metal bindingi1753ZincBy similarity1
Active sitei1767Proton acceptorBy similarity1
Binding sitei1769ATPBy similarity1
Binding sitei1777ATPBy similarity1
Metal bindingi1810ZincBy similarity1
Metal bindingi1812ZincBy similarity1
Metal bindingi1816ZincBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1794 – 1800ATPBy similarity7

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalcium channel, Ion channel, Kinase, Serine/threonine-protein kinase, Transferase
Biological processCalcium transport, Ion transport, Necrosis, Transport
LigandATP-binding, Calcium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-3295583 TRP channels
SIGNORiQ96QT4

Protein family/group databases

TCDBi1.A.4.5.1 the transient receptor potential ca(2+) channel (trp-cc) family

Names & Taxonomyi

Protein namesi
Recommended name:
Transient receptor potential cation channel subfamily M member 7 (EC:2.7.11.1)
Alternative name(s):
Channel-kinase 1
Long transient receptor potential channel 7
Short name:
LTrpC-7
Short name:
LTrpC7
Gene namesi
Name:TRPM7
Synonyms:CHAK1, LTRPC7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000092439.13
HGNCiHGNC:17994 TRPM7
MIMi605692 gene
neXtProtiNX_Q96QT4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 755CytoplasmicSequence analysisAdd BLAST755
Transmembranei756 – 776HelicalSequence analysisAdd BLAST21
Topological domaini777 – 855ExtracellularSequence analysisAdd BLAST79
Transmembranei856 – 876HelicalSequence analysisAdd BLAST21
Topological domaini877 – 918CytoplasmicSequence analysisAdd BLAST42
Transmembranei919 – 939HelicalSequence analysisAdd BLAST21
Topological domaini940 – 962ExtracellularSequence analysisAdd BLAST23
Transmembranei963 – 983HelicalSequence analysisAdd BLAST21
Topological domaini984 – 995CytoplasmicSequence analysisAdd BLAST12
Transmembranei996 – 1016HelicalSequence analysisAdd BLAST21
Topological domaini1017 – 1035ExtracellularSequence analysisAdd BLAST19
Intramembranei1036 – 1056Pore-formingSequence analysisAdd BLAST21
Topological domaini1057 – 1074ExtracellularSequence analysisAdd BLAST18
Transmembranei1075 – 1095HelicalSequence analysisAdd BLAST21
Topological domaini1096 – 1865CytoplasmicSequence analysisAdd BLAST770

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Amyotrophic lateral sclerosis-parkinsonism/dementia complex 1 (ALS-PDC1)
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder characterized by chronic, progressive and uniformly fatal amyotrophic lateral sclerosis and parkinsonism-dementia. Both diseases are known to occur in the same kindred, the same sibship and even the same individual.
See also OMIM:105500

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1648K → R: Loss of kinase activity. 1 Publication1
Mutagenesisi1799G → D: Loss of kinase activity. 1 Publication1

Keywords - Diseasei

Amyotrophic lateral sclerosis, Neurodegeneration, Parkinsonism

Organism-specific databases

DisGeNETi54822
MalaCardsiTRPM7
MIMi105500 phenotype
OpenTargetsiENSG00000092439
Orphaneti90020 Amyotrophic lateral sclerosis-parkinsonism-dementia complex
PharmGKBiPA38273

Chemistry databases

ChEMBLiCHEMBL1250412
DrugBankiDB04395 Phosphoaminophosphonic Acid-Adenylate Ester
GuidetoPHARMACOLOGYi499

Polymorphism and mutation databases

BioMutaiTRPM7
DMDMi56404941

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153311 – 1865Transient receptor potential cation channel subfamily M member 7Add BLAST1865

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei101PhosphoserineCombined sources1
Modified residuei1224PhosphoserineBy similarity1
Modified residuei1255PhosphoserineBy similarity1
Modified residuei1301PhosphoserineBy similarity1
Modified residuei1386PhosphoserineBy similarity1
Modified residuei1387PhosphoserineCombined sources1
Modified residuei1390PhosphoserineCombined sources1
Modified residuei1395PhosphoserineCombined sources1
Modified residuei1404PhosphoserineCombined sources1
Modified residuei1405PhosphothreonineBy similarity1
Modified residuei1446PhosphoserineBy similarity1
Modified residuei1467PhosphothreonineBy similarity1
Modified residuei1477PhosphoserineCombined sources1
Modified residuei1500PhosphoserineBy similarity1
Modified residuei1504PhosphoserineBy similarity1
Modified residuei1527PhosphoserineCombined sources1
Modified residuei1569PhosphoserineCombined sources1
Modified residuei1851PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ96QT4
MaxQBiQ96QT4
PaxDbiQ96QT4
PeptideAtlasiQ96QT4
PRIDEiQ96QT4

PTM databases

CarbonylDBiQ96QT4
iPTMnetiQ96QT4
PhosphoSitePlusiQ96QT4

Expressioni

Gene expression databases

BgeeiENSG00000092439
CleanExiHS_TRPM7
ExpressionAtlasiQ96QT4 baseline and differential
GenevisibleiQ96QT4 HS

Organism-specific databases

HPAiHPA035523
HPA052173

Interactioni

Subunit structurei

Homodimer. Interacts with PLCB1 (By similarity). Forms heterodimers with TRPM6.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi120177, 28 interactors
CORUMiQ96QT4
IntActiQ96QT4, 5 interactors
MINTiQ96QT4
STRINGi9606.ENSP00000320239

Structurei

3D structure databases

ProteinModelPortaliQ96QT4
SMRiQ96QT4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1594 – 1824Alpha-type protein kinasePROSITE-ProRule annotationAdd BLAST231

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili1198 – 1250By similarityAdd BLAST53

Sequence similaritiesi

In the C-terminal section; belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily.Curated

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3614 Eukaryota
ENOG410XR5B LUCA
GeneTreeiENSGT00760000119127
HOGENOMiHOG000230920
HOVERGENiHBG055663
InParanoidiQ96QT4
KOiK04982
OMAiKQGPTNP
OrthoDBiEOG091G0DHL
PhylomeDBiQ96QT4
TreeFamiTF314204

Family and domain databases

Gene3Di1.20.5.1010, 1 hit
InterProiView protein in InterPro
IPR005821 Ion_trans_dom
IPR011009 Kinase-like_dom_sf
IPR004166 MHCK_EF2_kinase
IPR029601 TRPM7
IPR032415 TRPM_tetra
IPR037162 TRPM_tetra_sf
PANTHERiPTHR13800:SF8 PTHR13800:SF8, 1 hit
PfamiView protein in Pfam
PF02816 Alpha_kinase, 1 hit
PF00520 Ion_trans, 1 hit
PF16519 TRPM_tetra, 1 hit
SMARTiView protein in SMART
SM00811 Alpha_kinase, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51158 ALPHA_KINASE, 1 hit

Sequencei

Sequence statusi: Complete.

Q96QT4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSQKSWIEST LTKRECVYII PSSKDPHRCL PGCQICQQLV RCFCGRLVKQ
60 70 80 90 100
HACFTASLAM KYSDVKLGDH FNQAIEEWSV EKHTEQSPTD AYGVINFQGG
110 120 130 140 150
SHSYRAKYVR LSYDTKPEVI LQLLLKEWQM ELPKLVISVH GGMQKFELHP
160 170 180 190 200
RIKQLLGKGL IKAAVTTGAW ILTGGVNTGV AKHVGDALKE HASRSSRKIC
210 220 230 240 250
TIGIAPWGVI ENRNDLVGRD VVAPYQTLLN PLSKLNVLNN LHSHFILVDD
260 270 280 290 300
GTVGKYGAEV RLRRELEKTI NQQRIHARIG QGVPVVALIF EGGPNVILTV
310 320 330 340 350
LEYLQESPPV PVVVCEGTGR AADLLAYIHK QTEEGGNLPD AAEPDIISTI
360 370 380 390 400
KKTFNFGQNE ALHLFQTLME CMKRKELITV FHIGSDEHQD IDVAILTALL
410 420 430 440 450
KGTNASAFDQ LILTLAWDRV DIAKNHVFVY GQQWLVGSLE QAMLDALVMD
460 470 480 490 500
RVAFVKLLIE NGVSMHKFLT IPRLEELYNT KQGPTNPMLF HLVRDVKQGN
510 520 530 540 550
LPPGYKITLI DIGLVIEYLM GGTYRCTYTR KRFRLIYNSL GGNNRRSGRN
560 570 580 590 600
TSSSTPQLRK SHESFGNRAD KKEKMRHNHF IKTAQPYRPK IDTVMEEGKK
610 620 630 640 650
KRTKDEIVDI DDPETKRFPY PLNELLIWAC LMKRQVMARF LWQHGEESMA
660 670 680 690 700
KALVACKIYR SMAYEAKQSD LVDDTSEELK QYSNDFGQLA VELLEQSFRQ
710 720 730 740 750
DETMAMKLLT YELKNWSNST CLKLAVSSRL RPFVAHTCTQ MLLSDMWMGR
760 770 780 790 800
LNMRKNSWYK VILSILVPPA ILLLEYKTKA EMSHIPQSQD AHQMTMDDSE
810 820 830 840 850
NNFQNITEEI PMEVFKEVRI LDSNEGKNEM EIQMKSKKLP ITRKFYAFYH
860 870 880 890 900
APIVKFWFNT LAYLGFLMLY TFVVLVQMEQ LPSVQEWIVI AYIFTYAIEK
910 920 930 940 950
VREIFMSEAG KVNQKIKVWF SDYFNISDTI AIISFFIGFG LRFGAKWNFA
960 970 980 990 1000
NAYDNHVFVA GRLIYCLNII FWYVRLLDFL AVNQQAGPYV MMIGKMVANM
1010 1020 1030 1040 1050
FYIVVIMALV LLSFGVPRKA ILYPHEAPSW TLAKDIVFHP YWMIFGEVYA
1060 1070 1080 1090 1100
YEIDVCANDS VIPQICGPGT WLTPFLQAVY LFVQYIIMVN LLIAFFNNVY
1110 1120 1130 1140 1150
LQVKAISNIV WKYQRYHFIM AYHEKPVLPP PLIILSHIVS LFCCICKRRK
1160 1170 1180 1190 1200
KDKTSDGPKL FLTEEDQKKL HDFEEQCVEM YFNEKDDKFH SGSEERIRVT
1210 1220 1230 1240 1250
FERVEQMCIQ IKEVGDRVNY IKRSLQSLDS QIGHLQDLSA LTVDTLKTLT
1260 1270 1280 1290 1300
AQKASEASKV HNEITRELSI SKHLAQNLID DGPVRPSVWK KHGVVNTLSS
1310 1320 1330 1340 1350
SLPQGDLESN NPFHCNILMK DDKDPQCNIF GQDLPAVPQR KEFNFPEAGS
1360 1370 1380 1390 1400
SSGALFPSAV SPPELRQRLH GVELLKIFNK NQKLGSSSTS IPHLSSPPTK
1410 1420 1430 1440 1450
FFVSTPSQPS CKSHLETGTK DQETVCSKAT EGDNTEFGAF VGHRDSMDLQ
1460 1470 1480 1490 1500
RFKETSNKIK ILSNNNTSEN TLKRVSSLAG FTDCHRTSIP VHSKQAEKIS
1510 1520 1530 1540 1550
RRPSTEDTHE VDSKAALIPD WLQDRPSNRE MPSEEGTLNG LTSPFKPAMD
1560 1570 1580 1590 1600
TNYYYSAVER NNLMRLSQSI PFTPVPPRGE PVTVYRLEES SPNILNNSMS
1610 1620 1630 1640 1650
SWSQLGLCAK IEFLSKEEMG GGLRRAVKVQ CTWSEHDILK SGHLYIIKSF
1660 1670 1680 1690 1700
LPEVVNTWSS IYKEDTVLHL CLREIQQQRA AQKLTFAFNQ MKPKSIPYSP
1710 1720 1730 1740 1750
RFLEVFLLYC HSAGQWFAVE ECMTGEFRKY NNNNGDEIIP TNTLEEIMLA
1760 1770 1780 1790 1800
FSHWTYEYTR GELLVLDLQG VGENLTDPSV IKAEEKRSCD MVFGPANLGE
1810 1820 1830 1840 1850
DAIKNFRAKH HCNSCCRKLK LPDLKRNDYT PDKIIFPQDE PSDLNLQPGN
1860
STKESESTNS VRLML
Length:1,865
Mass (Da):212,697
Last modified:December 1, 2001 - v1
Checksum:iBE732674D52D7485
GO

Sequence cautioni

The sequence BAC11462 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAD18773 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti573 – 575EKM → KKK in BAD18773 (PubMed:14702039).Curated3
Sequence conflicti998A → S (PubMed:15489334).Curated1
Sequence conflicti1496Missing in AAK19738 (PubMed:14594813).Curated1
Sequence conflicti1520D → V in AAK19738 (PubMed:14594813).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04239568G → V1 PublicationCorresponds to variant dbSNP:rs56064201Ensembl.1
Natural variantiVAR_042396406S → C in an ovarian serous carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_042397459I → T1 PublicationCorresponds to variant dbSNP:rs55924090Ensembl.1
Natural variantiVAR_042398574K → N1 PublicationCorresponds to variant dbSNP:rs56040619Ensembl.1
Natural variantiVAR_042399720T → S in a breast infiltrating ductal carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1040254222Ensembl.1
Natural variantiVAR_042400830M → V in a gastric adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_042401949F → Y1 PublicationCorresponds to variant dbSNP:rs55681028Ensembl.1
Natural variantiVAR_0523811033A → G. Corresponds to variant dbSNP:rs34530969Ensembl.1
Natural variantiVAR_0424021064Q → R1 PublicationCorresponds to variant dbSNP:rs56298128Ensembl.1
Natural variantiVAR_0523821145I → V. Corresponds to variant dbSNP:rs34711809Ensembl.1
Natural variantiVAR_0424031211I → T1 PublicationCorresponds to variant dbSNP:rs56090496Ensembl.1
Natural variantiVAR_0424041254A → V1 PublicationCorresponds to variant dbSNP:rs56288221Ensembl.1
Natural variantiVAR_0424051306D → E1 PublicationCorresponds to variant dbSNP:rs55970334Ensembl.1
Natural variantiVAR_0424061444R → K1 PublicationCorresponds to variant dbSNP:rs55840070Ensembl.1
Natural variantiVAR_0199671482T → I Mutant channels are functional but show increased susceptibility to inhibition by intracellular magnesium concentrations compared to wild-type channels. 3 PublicationsCorresponds to variant dbSNP:rs8042919Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS42035.1
RefSeqiNP_001288141.1, NM_001301212.1
NP_060142.3, NM_017672.5
UniGeneiHs.512894

Genome annotation databases

EnsembliENST00000313478; ENSP00000320239; ENSG00000092439
GeneIDi54822
KEGGihsa:54822
UCSCiuc001zyt.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTRPM7_HUMAN
AccessioniPrimary (citable) accession number: Q96QT4
Secondary accession number(s): Q6ZMF5
, Q86VJ4, Q8NBW2, Q9BXB2, Q9NXQ2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: December 1, 2001
Last modified: April 25, 2018
This is version 147 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health