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UniProtKB - Q96QT4 (TRPM7_HUMAN)

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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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
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
ProteomicsDBi77898

PTM databases

CarbonylDBiQ96QT4
iPTMnetiQ96QT4
PhosphoSitePlusiQ96QT4

Expressioni

Gene expression databases

BgeeiENSG00000092439
CleanExiHS_TRPM7
ExpressionAtlasiQ96QT4 baseline and differential
GenevisibleiQ96QT4 HS

Organism-specific databases

HPAiHPA052173

Interactioni

Subunit structurei

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

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi120177, 28 interactors
CORUMiQ96QT4
IntActiQ96QT4, 8 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
In the N-terminal section; belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM7 sub-subfamily. [View classification]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:rs8042919EnsemblClinVar.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
ENST00000646667; ENSP00000495860; 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: June 20, 2018
This is version 149 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

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

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