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Protein

Short transient receptor potential channel 6

Gene

TRPC6

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

Functioni

Thought to form a receptor-activated non-selective calcium permeant cation channel (PubMed:19936226, PubMed:23291369). Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Activated by diacylglycerol (DAG) in a membrane-delimited fashion, independently of protein kinase C (PubMed:26892346). Seems not to be activated by intracellular calcium store depletion.3 Publications

GO - Molecular functioni

  • actin binding Source: Ensembl
  • actinin binding Source: Ensembl
  • calcium channel activity Source: Reactome
  • cation channel activity Source: UniProtKB
  • clathrin binding Source: Ensembl
  • inositol 1,4,5 trisphosphate binding Source: BHF-UCL
  • protein homodimerization activity Source: UniProtKB
  • store-operated calcium channel activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionCalcium channel, Ion channel
Biological processCalcium transport, Ion transport, Transport
LigandCalcium

Enzyme and pathway databases

ReactomeiR-HSA-114508 Effects of PIP2 hydrolysis
R-HSA-139853 Elevation of cytosolic Ca2+ levels
R-HSA-3295583 TRP channels
R-HSA-418890 Role of second messengers in netrin-1 signaling
SIGNORiQ9Y210

Protein family/group databases

TCDBi1.A.4.1.5 the transient receptor potential ca(2+) channel (trp-cc) family

Names & Taxonomyi

Protein namesi
Recommended name:
Short transient receptor potential channel 6
Short name:
TrpC61 Publication
Alternative name(s):
Transient receptor protein 6
Short name:
TRP-6
Gene namesi
Name:TRPC61 PublicationImported
Synonyms:TRP61 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000137672.12
HGNCiHGNC:12338 TRPC6
MIMi603652 gene
neXtProtiNX_Q9Y210

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 – 438CytoplasmicSequence analysisAdd BLAST438
Transmembranei439 – 459HelicalSequence analysisAdd BLAST21
Topological domaini460 – 487ExtracellularSequence analysisAdd BLAST28
Transmembranei488 – 508HelicalSequence analysisAdd BLAST21
Topological domaini509 – 521CytoplasmicSequence analysisAdd BLAST13
Transmembranei522 – 542HelicalSequence analysisAdd BLAST21
Topological domaini543 – 592ExtracellularSequence analysisAdd BLAST50
Transmembranei593 – 613HelicalSequence analysisAdd BLAST21
Topological domaini614 – 636CytoplasmicSequence analysisAdd BLAST23
Transmembranei637 – 657HelicalSequence analysisAdd BLAST21
Topological domaini658 – 706ExtracellularSequence analysisAdd BLAST49
Transmembranei707 – 727HelicalSequence analysisAdd BLAST21
Topological domaini728 – 931CytoplasmicSequence analysisAdd BLAST204

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Focal segmental glomerulosclerosis 2 (FSGS2)11 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.
See also OMIM:603965
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07978588F → FAYMF in FSGS2; unknown pathological significance. 1 Publication1
Natural variantiVAR_079786109G → S in FSGS2; increases calcium ion transport. 2 Publications1
Natural variantiVAR_026730112P → Q in FSGS2; increases calcium ion transport. 2 PublicationsCorresponds to variant dbSNP:rs121434390EnsemblClinVar.1
Natural variantiVAR_067247125N → S in FSGS2; unknown pathological significance; decreases calcium ion transport. 3 PublicationsCorresponds to variant dbSNP:rs146776939Ensembl.1
Natural variantiVAR_026731143N → S in FSGS2; increases cation channel activity; does not change the outward peak current; increases significantly the inward peak current amplitude; increases calcium ion transport. 3 PublicationsCorresponds to variant dbSNP:rs121434391EnsemblClinVar.1
Natural variantiVAR_079787175R → Q in FSGS2; increases cation channel activity; does not change plasma membrane expression; increases calcium ion transport. 2 Publications1
Natural variantiVAR_067248218H → L in FSGS2; increases calcium ion transport. 2 PublicationsCorresponds to variant dbSNP:rs779430565Ensembl.1
Natural variantiVAR_026732270S → T in FSGS2. 3 PublicationsCorresponds to variant dbSNP:rs121434392EnsemblClinVar.1
Natural variantiVAR_079788360R → H in FSGS2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs777715086Ensembl.1
Natural variantiVAR_079789395L → A in FSGS2; unknown pathological significance; requires 2 nucleotide substitutions; decreases calcium ion transport. 2 Publications1
Natural variantiVAR_079790757G → D in FSGS2; decreases calcium ion transport; does not change localization at cell membrane; does not affect homodimer formation. 2 Publications1
Natural variantiVAR_079791780L → P in FSGS2; unknown pathological significance; decreases calcium ion transport. 2 PublicationsCorresponds to variant dbSNP:rs771594597Ensembl.1
Natural variantiVAR_079792874 – 931Missing in FSGS2. 1 PublicationAdd BLAST58
Natural variantiVAR_026733895R → C in FSGS2; increases cation channel activity; does not change plasma membrane expression; significantly reduces the ratio of cell-surface to total expression; increases calcium ion transport. 4 PublicationsCorresponds to variant dbSNP:rs121434394EnsemblClinVar.1
Natural variantiVAR_067249895R → L in FSGS2; decreases calcium ion transport. 2 Publications1
Natural variantiVAR_026734897E → K in FSGS2; increases calcium ion transport. 3 PublicationsCorresponds to variant dbSNP:rs121434395EnsemblClinVar.1
Natural variantiVAR_079793897Missing in FSGS2. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi110N → H: Increases calcium ion transport. 1 Publication1
Mutagenesisi125N → A: No effect on RNF24-binding; when associated with A-127; A-128 and A-130. 1 Publication1
Mutagenesisi127N → A: No effect on RNF24-binding; when associated with A-125; A-128 and A-130. 1 Publication1
Mutagenesisi128C → A: No effect on RNF24-binding; when associated with A-125; A-127 and A-130. 1 Publication1
Mutagenesisi130D → A: No effect on RNF24-binding; when associated with A-125; A-127 and A-128. 1 Publication1
Mutagenesisi132M → T: Increases cation channel activity. Increases significantly inward and outward currents and does not show channel inactivation. Increases calcium ion transport. 2 Publications1
Mutagenesisi561N → Q: Constitutively activates channel. 1 Publication1
Mutagenesisi755 – 757EEG → KKR: Decreases calcium ion transport. 1 Publication3
Mutagenesisi755 – 756EE → KK: Increases calcium ion transport. 1 Publication2
Mutagenesisi826 – 827KK → EE: Decreases calcium ion transport. 1 Publication2
Mutagenesisi889Q → K: Increases calcium transport. Increases calcium ion transport. 2 Publications1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi7225
MalaCardsiTRPC6
MIMi603965 phenotype
OpenTargetsiENSG00000137672
Orphaneti93213 Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis
PharmGKBiPA37011

Chemistry databases

ChEMBLiCHEMBL2417347
GuidetoPHARMACOLOGYi491

Polymorphism and mutation databases

BioMutaiTRPC6
DMDMi6686048

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153221 – 931Short transient receptor potential channel 6Add BLAST931

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi473N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi561N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei815PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by FYN, leading to an increase of TRPC6 channel activity.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9Y210
PaxDbiQ9Y210
PeptideAtlasiQ9Y210
PRIDEiQ9Y210

PTM databases

iPTMnetiQ9Y210
PhosphoSitePlusiQ9Y210

Expressioni

Tissue specificityi

Expressed primarily in placenta, lung, spleen, ovary and small intestine. Expressed in podocytes and is a component of the glomerular slit diaphragm.1 Publication

Gene expression databases

BgeeiENSG00000137672
CleanExiHS_TRPC6
ExpressionAtlasiQ9Y210 baseline and differential
GenevisibleiQ9Y210 HS

Organism-specific databases

HPAiHPA045098
HPA062164

Interactioni

Subunit structurei

Homodimer; forms channel complex (PubMed:26892346). Interacts with MX1 and RNF24 (PubMed:15757897, PubMed:17850865).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MX1P205914EBI-929362,EBI-929476

GO - Molecular functioni

  • actin binding Source: Ensembl
  • actinin binding Source: Ensembl
  • clathrin binding Source: Ensembl
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi113076, 12 interactors
IntActiQ9Y210, 2 interactors
STRINGi9606.ENSP00000340913

Chemistry databases

BindingDBiQ9Y210

Structurei

3D structure databases

ProteinModelPortaliQ9Y210
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati97 – 126ANK 1Add BLAST30
Repeati132 – 161ANK 2Add BLAST30
Repeati163 – 189ANK 3Add BLAST27
Repeati218 – 247ANK 4Add BLAST30

Sequence similaritiesi

Keywords - Domaini

ANK repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3609 Eukaryota
ENOG410XQ0Y LUCA
GeneTreeiENSGT00760000119180
HOGENOMiHOG000020590
HOVERGENiHBG068337
InParanoidiQ9Y210
KOiK04969
OMAiNRGPAYM
OrthoDBiEOG091G01FB
PhylomeDBiQ9Y210
TreeFamiTF313147

Family and domain databases

CDDicd00204 ANK, 1 hit
Gene3Di1.25.40.20, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR005821 Ion_trans_dom
IPR004729 TRP_channel
IPR013555 TRP_dom
IPR005462 TRPC6_channel
IPR002153 TRPC_channel
PANTHERiPTHR10117 PTHR10117, 1 hit
PTHR10117:SF7 PTHR10117:SF7, 1 hit
PfamiView protein in Pfam
PF12796 Ank_2, 1 hit
PF00520 Ion_trans, 1 hit
PF08344 TRP_2, 1 hit
PRINTSiPR01097 TRNSRECEPTRP
PR01647 TRPCHANNEL6
SMARTiView protein in SMART
SM00248 ANK, 3 hits
SUPFAMiSSF48403 SSF48403, 1 hit
TIGRFAMsiTIGR00870 trp, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 2 hits
PS50088 ANK_REPEAT, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y210-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSQSPAFGPR RGSSPRGAAG AAARRNESQD YLLMDSELGE DGCPQAPLPC
60 70 80 90 100
YGYYPCFRGS DNRLAHRRQT VLREKGRRLA NRGPAYMFSD RSTSLSIEEE
110 120 130 140 150
RFLDAAEYGN IPVVRKMLEE CHSLNVNCVD YMGQNALQLA VANEHLEITE
160 170 180 190 200
LLLKKENLSR VGDALLLAIS KGYVRIVEAI LSHPAFAEGK RLATSPSQSE
210 220 230 240 250
LQQDDFYAYD EDGTRFSHDV TPIILAAHCQ EYEIVHTLLR KGARIERPHD
260 270 280 290 300
YFCKCNDCNQ KQKHDSFSHS RSRINAYKGL ASPAYLSLSS EDPVMTALEL
310 320 330 340 350
SNELAVLANI EKEFKNDYKK LSMQCKDFVV GLLDLCRNTE EVEAILNGDV
360 370 380 390 400
ETLQSGDHGR PNLSRLKLAI KYEVKKFVAH PNCQQQLLSI WYENLSGLRQ
410 420 430 440 450
QTMAVKFLVV LAVAIGLPFL ALIYWFAPCS KMGKIMRGPF MKFVAHAASF
460 470 480 490 500
TIFLGLLVMN AADRFEGTKL LPNETSTDNA KQLFRMKTSC FSWMEMLIIS
510 520 530 540 550
WVIGMIWAEC KEIWTQGPKE YLFELWNMLD FGMLAIFAAS FIARFMAFWH
560 570 580 590 600
ASKAQSIIDA NDTLKDLTKV TLGDNVKYYN LARIKWDPSD PQIISEGLYA
610 620 630 640 650
IAVVLSFSRI AYILPANESF GPLQISLGRT VKDIFKFMVI FIMVFVAFMI
660 670 680 690 700
GMFNLYSYYI GAKQNEAFTT VEESFKTLFW AIFGLSEVKS VVINYNHKFI
710 720 730 740 750
ENIGYVLYGV YNVTMVIVLL NMLIAMINSS FQEIEDDADV EWKFARAKLW
760 770 780 790 800
FSYFEEGRTL PVPFNLVPSP KSLFYLLLKL KKWISELFQG HKKGFQEDAE
810 820 830 840 850
MNKINEEKKL GILGSHEDLS KLSLDKKQVG HNKQPSIRSS EDFHLNSFNN
860 870 880 890 900
PPRQYQKIMK RLIKRYVLQA QIDKESDEVN EGELKEIKQD ISSLRYELLE
910 920 930
EKSQNTEDLA ELIRELGEKL SMEPNQEETN R
Length:931
Mass (Da):106,326
Last modified:November 1, 1999 - v1
Checksum:i7C955C2B0389AC47
GO
Isoform 2 (identifier: Q9Y210-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     316-431: Missing.

Show »
Length:815
Mass (Da):93,187
Checksum:i2E78B50F956CBF0D
GO
Isoform 3 (identifier: Q9Y210-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     377-431: Missing.

Show »
Length:876
Mass (Da):100,106
Checksum:i8A1F52196619E147
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti336C → R in CAC01686 (PubMed:10816590).Curated1
Sequence conflicti585K → R in CAC06090 (Ref. 5) Curated1
Sequence conflicti613I → T in CAC01686 (PubMed:10816590).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07978415P → S Polymorphism. 2 PublicationsCorresponds to variant dbSNP:rs3802829EnsemblClinVar.1
Natural variantiVAR_07978588F → FAYMF in FSGS2; unknown pathological significance. 1 Publication1
Natural variantiVAR_079786109G → S in FSGS2; increases calcium ion transport. 2 Publications1
Natural variantiVAR_026730112P → Q in FSGS2; increases calcium ion transport. 2 PublicationsCorresponds to variant dbSNP:rs121434390EnsemblClinVar.1
Natural variantiVAR_067247125N → S in FSGS2; unknown pathological significance; decreases calcium ion transport. 3 PublicationsCorresponds to variant dbSNP:rs146776939Ensembl.1
Natural variantiVAR_026731143N → S in FSGS2; increases cation channel activity; does not change the outward peak current; increases significantly the inward peak current amplitude; increases calcium ion transport. 3 PublicationsCorresponds to variant dbSNP:rs121434391EnsemblClinVar.1
Natural variantiVAR_038419157N → T. Corresponds to variant dbSNP:rs35857503Ensembl.1
Natural variantiVAR_079787175R → Q in FSGS2; increases cation channel activity; does not change plasma membrane expression; increases calcium ion transport. 2 Publications1
Natural variantiVAR_067248218H → L in FSGS2; increases calcium ion transport. 2 PublicationsCorresponds to variant dbSNP:rs779430565Ensembl.1
Natural variantiVAR_026732270S → T in FSGS2. 3 PublicationsCorresponds to variant dbSNP:rs121434392EnsemblClinVar.1
Natural variantiVAR_079788360R → H in FSGS2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs777715086Ensembl.1
Natural variantiVAR_079789395L → A in FSGS2; unknown pathological significance; requires 2 nucleotide substitutions; decreases calcium ion transport. 2 Publications1
Natural variantiVAR_061861404A → V Polymorphism; increases calcium ion transport. 3 PublicationsCorresponds to variant dbSNP:rs36111323EnsemblClinVar.1
Natural variantiVAR_079790757G → D in FSGS2; decreases calcium ion transport; does not change localization at cell membrane; does not affect homodimer formation. 2 Publications1
Natural variantiVAR_079791780L → P in FSGS2; unknown pathological significance; decreases calcium ion transport. 2 PublicationsCorresponds to variant dbSNP:rs771594597Ensembl.1
Natural variantiVAR_079792874 – 931Missing in FSGS2. 1 PublicationAdd BLAST58
Natural variantiVAR_026733895R → C in FSGS2; increases cation channel activity; does not change plasma membrane expression; significantly reduces the ratio of cell-surface to total expression; increases calcium ion transport. 4 PublicationsCorresponds to variant dbSNP:rs121434394EnsemblClinVar.1
Natural variantiVAR_067249895R → L in FSGS2; decreases calcium ion transport. 2 Publications1
Natural variantiVAR_026734897E → K in FSGS2; increases calcium ion transport. 3 PublicationsCorresponds to variant dbSNP:rs121434395EnsemblClinVar.1
Natural variantiVAR_079793897Missing in FSGS2. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_006572316 – 431Missing in isoform 2. 1 PublicationAdd BLAST116
Alternative sequenceiVSP_006573377 – 431Missing in isoform 3. 1 PublicationAdd BLAST55

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF080394 mRNA Translation: AAC63289.2
AJ006276 mRNA Translation: CAA06943.1
AJ271066 mRNA Translation: CAC01684.1
AJ271067 mRNA Translation: CAC01685.1
AJ271068 mRNA Translation: CAC01686.1
BC093658 mRNA Translation: AAH93658.1
BC093660 mRNA Translation: AAH93660.1
AJ007018 mRNA Translation: CAC06090.1
CCDSiCCDS8311.1 [Q9Y210-1]
RefSeqiNP_004612.2, NM_004621.5 [Q9Y210-1]
XP_016873710.1, XM_017018221.1 [Q9Y210-2]
UniGeneiHs.159003

Genome annotation databases

EnsembliENST00000344327; ENSP00000340913; ENSG00000137672 [Q9Y210-1]
ENST00000348423; ENSP00000343672; ENSG00000137672 [Q9Y210-2]
ENST00000360497; ENSP00000353687; ENSG00000137672 [Q9Y210-3]
GeneIDi7225
KEGGihsa:7225
UCSCiuc001pgk.4 human [Q9Y210-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTRPC6_HUMAN
AccessioniPrimary (citable) accession number: Q9Y210
Secondary accession number(s): Q52M59
, Q9HCW3, Q9NQA8, Q9NQA9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1999
Last modified: May 23, 2018
This is version 168 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 11
    Human chromosome 11: 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. SIMILARITY comments
    Index of protein domains and families

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