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Protein

Short transient receptor potential channel 6

Gene

TRPC6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Thought to form a receptor-activated non-selective calcium permeant cation channel. 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. Seems not to be activated by intracellular calcium store depletion.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Calcium channel, Ion channel

Keywords - Biological processi

Calcium transport, Ion transport, Transport

Keywords - Ligandi

Calcium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000137672-MONOMER.
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.

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:
TrpC6
Alternative name(s):
Transient receptor protein 6
Short name:
TRP-6
Gene namesi
Name:TRPC6
Synonyms:TRP6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:12338. TRPC6.

Subcellular locationi

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

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • integral component of plasma membrane Source: GO_Central
  • membrane Source: UniProtKB
  • plasma membrane Source: MGI
  • slit diaphragm Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Focal segmental glomerulosclerosis 2 (FSGS2)3 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_026730112P → Q in FSGS2. 1 PublicationCorresponds to variant rs121434390dbSNPEnsembl.1
Natural variantiVAR_026731143N → S in FSGS2. 1 PublicationCorresponds to variant rs121434391dbSNPEnsembl.1
Natural variantiVAR_067248218H → L in FSGS2. 1 PublicationCorresponds to variant rs779430565dbSNPEnsembl.1
Natural variantiVAR_026732270S → T in FSGS2. 1 PublicationCorresponds to variant rs121434392dbSNPEnsembl.1
Natural variantiVAR_026733895R → C in FSGS2. 1 PublicationCorresponds to variant rs121434394dbSNPEnsembl.1
Natural variantiVAR_026734897E → K in FSGS2. 1 PublicationCorresponds to variant rs121434395dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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
Mutagenesisi561N → Q: Constitutively activates channel. 1 Publication1

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...)1 Publication1
Glycosylationi561N-linked (GlcNAc...)1 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.

Interactioni

Subunit structurei

Interacts with MX1 and RNF24.2 Publications

Binary interactionsi

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

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

Contains 4 ANK repeats.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR005821. Ion_trans_dom.
IPR004729. TRP_channel.
IPR013555. TRP_dom.
IPR005462. TRPC6_channel.
IPR002153. TRPC_channel.
[Graphical view]
PANTHERiPTHR10117. PTHR10117. 2 hits.
PTHR10117:SF7. PTHR10117:SF7. 2 hits.
PfamiPF12796. Ank_2. 1 hit.
PF00520. Ion_trans. 1 hit.
PF08344. TRP_2. 1 hit.
[Graphical view]
PRINTSiPR01097. TRNSRECEPTRP.
PR01647. TRPCHANNEL6.
SMARTiSM00248. ANK. 3 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
TIGRFAMsiTIGR00870. trp. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 2 hits.
PS50088. ANK_REPEAT. 1 hit.
[Graphical view]

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_026730112P → Q in FSGS2. 1 PublicationCorresponds to variant rs121434390dbSNPEnsembl.1
Natural variantiVAR_067247125N → S Found in two siblings with early-onset steroid-resistant nephrotic syndrome. 1 PublicationCorresponds to variant rs146776939dbSNPEnsembl.1
Natural variantiVAR_026731143N → S in FSGS2. 1 PublicationCorresponds to variant rs121434391dbSNPEnsembl.1
Natural variantiVAR_038419157N → T.Corresponds to variant rs35857503dbSNPEnsembl.1
Natural variantiVAR_067248218H → L in FSGS2. 1 PublicationCorresponds to variant rs779430565dbSNPEnsembl.1
Natural variantiVAR_026732270S → T in FSGS2. 1 PublicationCorresponds to variant rs121434392dbSNPEnsembl.1
Natural variantiVAR_061861404A → V.Corresponds to variant rs36111323dbSNPEnsembl.1
Natural variantiVAR_026733895R → C in FSGS2. 1 PublicationCorresponds to variant rs121434394dbSNPEnsembl.1
Natural variantiVAR_067249895R → L in a patient with collapsing glomerulosclerosis. 1 Publication1
Natural variantiVAR_026734897E → K in FSGS2. 1 PublicationCorresponds to variant rs121434395dbSNPEnsembl.1

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ9Y210.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113076. 12 interactors.
IntActiQ9Y210. 2 interactors.
STRINGi9606.ENSP00000340913.

Chemistry databases

BindingDBiQ9Y210.
ChEMBLiCHEMBL2417347.
GuidetoPHARMACOLOGYi491.

Protein family/group databases

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

PTM databases

iPTMnetiQ9Y210.
PhosphoSitePlusiQ9Y210.

Polymorphism and mutation databases

BioMutaiTRPC6.
DMDMi6686048.

Proteomic databases

EPDiQ9Y210.
PaxDbiQ9Y210.
PeptideAtlasiQ9Y210.
PRIDEiQ9Y210.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi7225.
DisGeNETi7225.
GeneCardsiTRPC6.
HGNCiHGNC:12338. TRPC6.
HPAiHPA045098.
MalaCardsiTRPC6.
MIMi603652. gene.
603965. phenotype.
neXtProtiNX_Q9Y210.
OpenTargetsiENSG00000137672.
Orphaneti93213. Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis.
PharmGKBiPA37011.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000137672-MONOMER.
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.

Miscellaneous databases

ChiTaRSiTRPC6. human.
GeneWikiiTRPC6.
GenomeRNAii7225.
PROiQ9Y210.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137672.
CleanExiHS_TRPC6.
ExpressionAtlasiQ9Y210. baseline and differential.
GenevisibleiQ9Y210. HS.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR005821. Ion_trans_dom.
IPR004729. TRP_channel.
IPR013555. TRP_dom.
IPR005462. TRPC6_channel.
IPR002153. TRPC_channel.
[Graphical view]
PANTHERiPTHR10117. PTHR10117. 2 hits.
PTHR10117:SF7. PTHR10117:SF7. 2 hits.
PfamiPF12796. Ank_2. 1 hit.
PF00520. Ion_trans. 1 hit.
PF08344. TRP_2. 1 hit.
[Graphical view]
PRINTSiPR01097. TRNSRECEPTRP.
PR01647. TRPCHANNEL6.
SMARTiSM00248. ANK. 3 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
TIGRFAMsiTIGR00870. trp. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 2 hits.
PS50088. ANK_REPEAT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTRPC6_HUMAN
AccessioniPrimary (citable) accession number: Q9Y210
Secondary accession number(s): Q52M59
, Q9HCW3, Q9NQA8, Q9NQA9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1999
Last modified: November 2, 2016
This is version 158 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.