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Q9Y210 (TRPC6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Short transient receptor potential channel 6

Short name=TrpC6
Alternative name(s):
Transient receptor protein 6
Short name=TRP-6
Gene names
Name:TRPC6
Synonyms:TRP6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length931 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Interacts with MX1 and RNF24. Ref.7 Ref.8

Subcellular location

Membrane; Multi-pass membrane protein Probable.

Tissue specificity

Expressed primarily in placenta, lung, spleen, ovary and small intestine. Expressed in podocytes and is a component of the glomerular slit diaphragm. Ref.10

Post-translational modification

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

Involvement in disease

Focal segmental glomerulosclerosis 2 (FSGS2) [MIM:603965]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11 Ref.12

Sequence similarities

Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC6 sub-subfamily. [View classification]

Contains 4 ANK repeats.

Ontologies

Keywords
   Biological processCalcium transport
Ion transport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainANK repeat
Repeat
Transmembrane
Transmembrane helix
   LigandCalcium
   Molecular functionCalcium channel
Ion channel
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from electronic annotation. Source: Ensembl

axon guidance

Traceable author statement. Source: Reactome

blood coagulation

Traceable author statement. Source: Reactome

calcium ion transmembrane transport

Traceable author statement. Source: Reactome

cation transport

Traceable author statement Ref.1. Source: ProtInc

cellular response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

cellular response to hypoxia

Inferred from electronic annotation. Source: Ensembl

ion transmembrane transport

Traceable author statement. Source: Reactome

platelet activation

Traceable author statement. Source: Reactome

positive regulation of calcium ion transport

Inferred from direct assay PubMed 10998353. Source: MGI

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of ion transmembrane transporter activity

Inferred from direct assay PubMed 10998353. Source: MGI

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from direct assay PubMed 10998353. Source: MGI

slit diaphragm

Inferred from electronic annotation. Source: Ensembl

   Molecular_functioninositol 1,4,5 trisphosphate binding

Inferred from direct assay PubMed 14505576. Source: BHF-UCL

store-operated calcium channel activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MX1P205914EBI-929362,EBI-929476

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y210-1)

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.
Isoform 2 (identifier: Q9Y210-2)

The sequence of this isoform differs from the canonical sequence as follows:
     316-431: Missing.
Isoform 3 (identifier: Q9Y210-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 931931Short transient receptor potential channel 6
PRO_0000215322

Regions

Topological domain1 – 438438Cytoplasmic Potential
Transmembrane439 – 45921Helical; Potential
Topological domain460 – 48728Extracellular Potential
Transmembrane488 – 50821Helical; Potential
Topological domain509 – 52113Cytoplasmic Potential
Transmembrane522 – 54221Helical; Potential
Topological domain543 – 59250Extracellular Potential
Transmembrane593 – 61321Helical; Potential
Topological domain614 – 63623Cytoplasmic Potential
Transmembrane637 – 65721Helical; Potential
Topological domain658 – 70649Extracellular Potential
Transmembrane707 – 72721Helical; Potential
Topological domain728 – 931204Cytoplasmic Potential
Repeat97 – 12630ANK 1
Repeat132 – 16130ANK 2
Repeat163 – 18927ANK 3
Repeat218 – 24730ANK 4

Amino acid modifications

Modified residue8151Phosphoserine Ref.9
Glycosylation4731N-linked (GlcNAc...) Ref.6
Glycosylation5611N-linked (GlcNAc...) Ref.6

Natural variations

Alternative sequence316 – 431116Missing in isoform 2.
VSP_006572
Alternative sequence377 – 43155Missing in isoform 3.
VSP_006573
Natural variant1121P → Q in FSGS2. Ref.11
VAR_026730
Natural variant1251N → S Found in two siblings with early-onset steroid-resistant nephrotic syndrome. Ref.12
VAR_067247
Natural variant1431N → S in FSGS2. Ref.10
Corresponds to variant rs121434391 [ dbSNP | Ensembl ].
VAR_026731
Natural variant1571N → T.
Corresponds to variant rs35857503 [ dbSNP | Ensembl ].
VAR_038419
Natural variant2181H → L in FSGS2. Ref.12
VAR_067248
Natural variant2701S → T in FSGS2. Ref.10
VAR_026732
Natural variant4041A → V.
Corresponds to variant rs36111323 [ dbSNP | Ensembl ].
VAR_061861
Natural variant8951R → C in FSGS2. Ref.10
VAR_026733
Natural variant8951R → L in a patient with collapsing glomerulosclerosis. Ref.12
VAR_067249
Natural variant8971E → K in FSGS2. Ref.10
VAR_026734

Experimental info

Mutagenesis1251N → A: No effect on RNF24-binding; when associated with A-127; A-128 and A-130. Ref.8
Mutagenesis1271N → A: No effect on RNF24-binding; when associated with A-125; A-128 and A-130. Ref.8
Mutagenesis1281C → A: No effect on RNF24-binding; when associated with A-125; A-127 and A-130. Ref.8
Mutagenesis1301D → A: No effect on RNF24-binding; when associated with A-125; A-127 and A-128. Ref.8
Mutagenesis5611N → Q: Constitutively activates channel. Ref.6
Sequence conflict3361C → R in CAC01686. Ref.3
Sequence conflict5851K → R in CAC06090. Ref.5
Sequence conflict6131I → T in CAC01686. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 7C955C2B0389AC47

FASTA931106,326
        10         20         30         40         50         60 
MSQSPAFGPR RGSSPRGAAG AAARRNESQD YLLMDSELGE DGCPQAPLPC YGYYPCFRGS 

        70         80         90        100        110        120 
DNRLAHRRQT VLREKGRRLA NRGPAYMFSD RSTSLSIEEE RFLDAAEYGN IPVVRKMLEE 

       130        140        150        160        170        180 
CHSLNVNCVD YMGQNALQLA VANEHLEITE LLLKKENLSR VGDALLLAIS KGYVRIVEAI 

       190        200        210        220        230        240 
LSHPAFAEGK RLATSPSQSE LQQDDFYAYD EDGTRFSHDV TPIILAAHCQ EYEIVHTLLR 

       250        260        270        280        290        300 
KGARIERPHD YFCKCNDCNQ KQKHDSFSHS RSRINAYKGL ASPAYLSLSS EDPVMTALEL 

       310        320        330        340        350        360 
SNELAVLANI EKEFKNDYKK LSMQCKDFVV GLLDLCRNTE EVEAILNGDV ETLQSGDHGR 

       370        380        390        400        410        420 
PNLSRLKLAI KYEVKKFVAH PNCQQQLLSI WYENLSGLRQ QTMAVKFLVV LAVAIGLPFL 

       430        440        450        460        470        480 
ALIYWFAPCS KMGKIMRGPF MKFVAHAASF TIFLGLLVMN AADRFEGTKL LPNETSTDNA 

       490        500        510        520        530        540 
KQLFRMKTSC FSWMEMLIIS WVIGMIWAEC KEIWTQGPKE YLFELWNMLD FGMLAIFAAS 

       550        560        570        580        590        600 
FIARFMAFWH ASKAQSIIDA NDTLKDLTKV TLGDNVKYYN LARIKWDPSD PQIISEGLYA 

       610        620        630        640        650        660 
IAVVLSFSRI AYILPANESF GPLQISLGRT VKDIFKFMVI FIMVFVAFMI GMFNLYSYYI 

       670        680        690        700        710        720 
GAKQNEAFTT VEESFKTLFW AIFGLSEVKS VVINYNHKFI ENIGYVLYGV YNVTMVIVLL 

       730        740        750        760        770        780 
NMLIAMINSS FQEIEDDADV EWKFARAKLW FSYFEEGRTL PVPFNLVPSP KSLFYLLLKL 

       790        800        810        820        830        840 
KKWISELFQG HKKGFQEDAE MNKINEEKKL GILGSHEDLS KLSLDKKQVG HNKQPSIRSS 

       850        860        870        880        890        900 
EDFHLNSFNN PPRQYQKIMK RLIKRYVLQA QIDKESDEVN EGELKEIKQD ISSLRYELLE 

       910        920        930 
EKSQNTEDLA ELIRELGEKL SMEPNQEETN R 

« Hide

Isoform 2 [UniParc].

Checksum: 2E78B50F956CBF0D
Show »

FASTA81593,187
Isoform 3 [UniParc].

Checksum: 8A1F52196619E147
Show »

FASTA876100,106

References

« Hide 'large scale' references
[1]"Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol."
Hofmann T., Obukhov A.G., Schaefer M., Harteneck C., Gudermann T., Schultz G.
Nature 397:259-263(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Placenta and Testis.
[2]"Identification and assignment of the human transient receptor potential channel 6 gene TRPC6 to chromosome 11q21-22."
D'Esposito M., Strazzullo M., Cuccurese M., Spalluto C., Rocchi M., D'Urso M., Ciccodicola A.
Cytogenet. Cell Genet. 83:46-47(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Teratocarcinoma.
[3]"TRP4 (CCE1) protein is part of native calcium release-activated Ca2+-like channels in adrenal cells."
Philipp S., Trost C., Warnat J., Rautmann J., Himmerkus N., Schroth G., Kretz O., Nastainczyk W., Cavalie A., Hoth M., Flockerzi V.
J. Biol. Chem. 275:23965-23972(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
Tissue: Placenta.
[4]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]"The capacitative calcium entry cation channel Trp6 is expressed in the muscularis externa of the guinea pig ileum and in a human jejunum smooth muscle cell line."
Fenech C.J., Prestwich S.A., Zholos A.V., Bolton T.B.
Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 487-643.
[6]"N-linked protein glycosylation is a major determinant for basal TRPC3 and TRPC6 channel activity."
Dietrich A., Mederos y Schnitzler M., Emmel J., Kalwa H., Hofmann T., Gudermann T.
J. Biol. Chem. 278:47842-47852(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-473 AND ASN-561, MUTAGENESIS OF ASN-561.
[7]"MxA, a member of the dynamin superfamily, interacts with the ankyrin-like repeat domain of TRPC."
Lussier M.P., Cayouette S., Lepage P.K., Bernier C.L., Francoeur N., St-Hilaire M., Pinard M., Boulay G.
J. Biol. Chem. 280:19393-19400(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MX1.
[8]"RNF24, a new TRPC interacting protein, causes the intracellular retention of TRPC."
Lussier M.P., Lepage P.K., Bousquet S.M., Boulay G.
Cell Calcium 43:432-443(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RNF24, MUTAGENESIS OF ASN-125; ASN-127; CYS-128 AND ASP-130.
[9]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-815, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[10]"TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function."
Reiser J., Polu K.R., Moller C.C., Kenlan P., Altintas M.M., Wei C., Faul C., Herbert S., Villegas I., Avila-Casado C., McGee M., Sugimoto H., Brown D., Kalluri R., Mundel P., Smith P.L., Clapham D.E., Pollak M.R.
Nat. Genet. 37:739-744(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS FSGS2 SER-143; THR-270; CYS-895 AND LYS-897, TISSUE SPECIFICITY.
[11]"A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis."
Winn M.P., Conlon P.J., Lynn K.L., Farrington M.K., Creazzo T., Hawkins A.F., Daskalakis N., Kwan S.Y., Ebersviller S., Burchette J.L., Pericak-Vance M.A., Howell D.N., Vance J.M., Rosenberg P.B.
Science 308:1801-1804(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FSGS2 GLN-112.
[12]"TRPC6 mutations in children with steroid-resistant nephrotic syndrome and atypical phenotype."
Gigante M., Caridi G., Montemurno E., Soccio M., d'Apolito M., Cerullo G., Aucella F., Schirinzi A., Emma F., Massella L., Messina G., De Palo T., Ranieri E., Ghiggeri G.M., Gesualdo L.
Clin. J. Am. Soc. Nephrol. 6:1626-1634(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FSGS2 LEU-218, VARIANTS SER-125 AND LEU-895.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_004612.2. NM_004621.5.
UniGeneHs.159003.

3D structure databases

ProteinModelPortalQ9Y210.
SMRQ9Y210. Positions 68-254.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113076. 12 interactions.
IntActQ9Y210. 2 interactions.
STRING9606.ENSP00000340913.

Chemistry

GuidetoPHARMACOLOGY491.

Protein family/group databases

TCDB1.A.4.1.5. the transient receptor potential ca(2+) channel (trp-cc) family.

PTM databases

PhosphoSiteQ9Y210.

Polymorphism databases

DMDM6686048.

Proteomic databases

PaxDbQ9Y210.
PRIDEQ9Y210.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000344327; ENSP00000340913; ENSG00000137672. [Q9Y210-1]
ENST00000348423; ENSP00000343672; ENSG00000137672. [Q9Y210-2]
ENST00000360497; ENSP00000353687; ENSG00000137672. [Q9Y210-3]
GeneID7225.
KEGGhsa:7225.
UCSCuc001pgk.4. human. [Q9Y210-1]
uc009ywy.3. human. [Q9Y210-2]
uc009ywz.1. human. [Q9Y210-3]

Organism-specific databases

CTD7225.
GeneCardsGC11M101322.
HGNCHGNC:12338. TRPC6.
HPAHPA045098.
MIM603652. gene.
603965. phenotype.
neXtProtNX_Q9Y210.
Orphanet93213. Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis.
PharmGKBPA37011.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG254238.
HOGENOMHOG000020590.
HOVERGENHBG068337.
InParanoidQ9Y210.
KOK04969.
OMANRGPAYM.
OrthoDBEOG77HDD1.
PhylomeDBQ9Y210.
TreeFamTF313147.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_15518. Transmembrane transport of small molecules.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressQ9Y210.
BgeeQ9Y210.
CleanExHS_TRPC6.
GenevestigatorQ9Y210.

Family and domain databases

Gene3D1.25.40.20. 1 hit.
InterProIPR002110. 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]
PANTHERPTHR10117. PTHR10117. 1 hit.
PTHR10117:SF7. PTHR10117:SF7. 1 hit.
PfamPF12796. Ank_2. 1 hit.
PF00520. Ion_trans. 1 hit.
PF08344. TRP_2. 1 hit.
[Graphical view]
PRINTSPR01097. TRNSRECEPTRP.
PR01647. TRPCHANNEL6.
SMARTSM00248. ANK. 3 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
TIGRFAMsTIGR00870. trp. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 2 hits.
PS50088. ANK_REPEAT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTRPC6. human.
GeneWikiTRPC6.
GenomeRNAi7225.
NextBio28295.
PROQ9Y210.
SOURCESearch...

Entry information

Entry nameTRPC6_HUMAN
AccessionPrimary (citable) accession number: Q9Y210
Secondary accession number(s): Q52M59 expand/collapse secondary AC list , Q9HCW3, Q9NQA8, Q9NQA9
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1999
Last modified: April 16, 2014
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM