TRPC6_HUMAN
ID TRPC6_HUMAN Reviewed; 931 AA.
AC Q9Y210; Q52M59; Q9HCW3; Q9NQA8; Q9NQA9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Short transient receptor potential channel 6;
DE Short=TrpC6 {ECO:0000303|PubMed:9930701};
DE AltName: Full=Transient receptor protein 6;
DE Short=TRP-6;
GN Name=TRPC6 {ECO:0000303|PubMed:9930701, ECO:0000312|HGNC:HGNC:12338};
GN Synonyms=TRP6 {ECO:0000303|Ref.5};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta, and Testis;
RX PubMed=9930701; DOI=10.1038/16711;
RA Hofmann T., Obukhov A.G., Schaefer M., Harteneck C., Gudermann T.,
RA Schultz G.;
RT "Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol.";
RL Nature 397:259-263(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Teratocarcinoma;
RX PubMed=9925922; DOI=10.1159/000015165;
RA D'Esposito M., Strazzullo M., Cuccurese M., Spalluto C., Rocchi M.,
RA D'Urso M., Ciccodicola A.;
RT "Identification and assignment of the human transient receptor potential
RT channel 6 gene TRPC6 to chromosome 11q21-22.";
RL Cytogenet. Cell Genet. 83:46-47(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Placenta;
RX PubMed=10816590; DOI=10.1074/jbc.m003408200;
RA Philipp S., Trost C., Warnat J., Rautmann J., Himmerkus N., Schroth G.,
RA Kretz O., Nastainczyk W., Cavalie A., Hoth M., Flockerzi V.;
RT "TRP4 (CCE1) protein is part of native calcium release-activated Ca2+-like
RT channels in adrenal cells.";
RL J. Biol. Chem. 275:23965-23972(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 487-643.
RA Fenech C.J., Prestwich S.A., Zholos A.V., Bolton T.B.;
RT "The capacitative calcium entry cation channel Trp6 is expressed in the
RT muscularis externa of the guinea pig ileum and in a human jejunum smooth
RT muscle cell line.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP GLYCOSYLATION AT ASN-473 AND ASN-561, AND MUTAGENESIS OF ASN-561.
RX PubMed=12970363; DOI=10.1074/jbc.m302983200;
RA Dietrich A., Mederos y Schnitzler M., Emmel J., Kalwa H., Hofmann T.,
RA Gudermann T.;
RT "N-linked protein glycosylation is a major determinant for basal TRPC3 and
RT TRPC6 channel activity.";
RL J. Biol. Chem. 278:47842-47852(2003).
RN [7]
RP INTERACTION WITH MX1.
RX PubMed=15757897; DOI=10.1074/jbc.m500391200;
RA Lussier M.P., Cayouette S., Lepage P.K., Bernier C.L., Francoeur N.,
RA St-Hilaire M., Pinard M., Boulay G.;
RT "MxA, a member of the dynamin superfamily, interacts with the ankyrin-like
RT repeat domain of TRPC.";
RL J. Biol. Chem. 280:19393-19400(2005).
RN [8]
RP INTERACTION WITH RNF24, AND MUTAGENESIS OF ASN-125; ASN-127; CYS-128 AND
RP ASP-130.
RX PubMed=17850865; DOI=10.1016/j.ceca.2007.07.009;
RA Lussier M.P., Lepage P.K., Bousquet S.M., Boulay G.;
RT "RNF24, a new TRPC interacting protein, causes the intracellular retention
RT of TRPC.";
RL Cell Calcium 43:432-443(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-815, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [10]
RP VARIANTS FSGS2 SER-143; THR-270; CYS-895 AND LYS-897, AND TISSUE
RP SPECIFICITY.
RX PubMed=15924139; DOI=10.1038/ng1592;
RA Reiser J., Polu K.R., Moller C.C., Kenlan P., Altintas M.M., Wei C.,
RA Faul C., Herbert S., Villegas I., Avila-Casado C., McGee M., Sugimoto H.,
RA Brown D., Kalluri R., Mundel P., Smith P.L., Clapham D.E., Pollak M.R.;
RT "TRPC6 is a glomerular slit diaphragm-associated channel required for
RT normal renal function.";
RL Nat. Genet. 37:739-744(2005).
RN [11]
RP VARIANT FSGS2 GLN-112.
RX PubMed=15879175; DOI=10.1126/science.1106215;
RA Winn M.P., Conlon P.J., Lynn K.L., Farrington M.K., Creazzo T.,
RA Hawkins A.F., Daskalakis N., Kwan S.Y., Ebersviller S., Burchette J.L.,
RA Pericak-Vance M.A., Howell D.N., Vance J.M., Rosenberg P.B.;
RT "A mutation in the TRPC6 cation channel causes familial focal segmental
RT glomerulosclerosis.";
RL Science 308:1801-1804(2005).
RN [12]
RP VARIANT SER-15, AND MUTAGENESIS OF GLN-889.
RX PubMed=19124028; DOI=10.1016/j.mrfmmm.2008.11.021;
RA Zhu B., Chen N., Wang Z.H., Pan X.X., Ren H., Zhang W., Wang W.M.;
RT "Identification and functional analysis of a novel TRPC6 mutation
RT associated with late onset familial focal segmental glomerulosclerosis in
RT Chinese patients.";
RL Mutat. Res. 664:84-90(2009).
RN [13]
RP VARIANTS FSGS2 SER-109; SER-125 AND PRO-780.
RX PubMed=19458060; DOI=10.1093/ndt/gfp229;
RG FSGS Study Group;
RA Santin S., Ars E., Rossetti S., Salido E., Silva I., Garcia-Maset R.,
RA Gimenez I., Ruiz P., Mendizabal S., Luciano Nieto J., Pena A.,
RA Camacho J.A., Fraga G., Cobo M.A., Bernis C., Ortiz A., de Pablos A.L.,
RA Sanchez-Moreno A., Pintos G., Mirapeix E., Fernandez-Llama P., Ballarin J.,
RA Torra R., Zamora I., Lopez-Hellin J., Madrid A., Ventura C., Vilalta R.,
RA Espinosa L., Garcia C., Melgosa M., Navarro M., Gimenez A., Cots J.V.,
RA Alexandra S., Caramelo C., Egido J., San Jose M.D., de la Cerda F.,
RA Sala P., Raspall F., Vila A., Daza A.M., Vazquez M., Ecija J.L.,
RA Espinosa M., Justa M.L., Poveda R., Aparicio C., Rosell J., Muley R.,
RA Montenegro J., Gonzalez D., Hidalgo E., de Frutos D.B., Trillo E.,
RA Gracia S., de los Rios F.J.;
RT "TRPC6 mutational analysis in a large cohort of patients with focal
RT segmental glomerulosclerosis.";
RL Nephrol. Dial. Transplant. 24:3089-3096(2009).
RN [14]
RP VARIANTS SER-15 AND VAL-404, VARIANTS FSGS2 SER-143; THR-270 AND
RP 874-LYS--ARG-931 DEL, CHARACTERIZATION OF VARIANT FSGS2 SER-143,
RP MUTAGENESIS OF MET-132, AND FUNCTION.
RX PubMed=19936226; DOI=10.1371/journal.pone.0007771;
RA Heeringa S.F., Moeller C.C., Du J., Yue L., Hinkes B., Chernin G.,
RA Vlangos C.N., Hoyer P.F., Reiser J., Hildebrandt F.;
RT "A novel TRPC6 mutation that causes childhood FSGS.";
RL PLoS ONE 4:E7771-E7771(2009).
RN [15]
RP VARIANTS FSGS2 ALA-TYR-MET-PHE-88 INS AND ASP-757.
RX PubMed=20798252; DOI=10.2215/cjn.01190210;
RA Buescher A.K., Kranz B., Buescher R., Hildebrandt F., Dworniczak B.,
RA Pennekamp P., Kuwertz-Broeking E., Wingen A.M., John U., Kemper M.,
RA Monnens L., Hoyer P.F., Weber S., Konrad M.;
RT "Immunosuppression and renal outcome in congenital and pediatric steroid-
RT resistant nephrotic syndrome.";
RL Clin. J. Am. Soc. Nephrol. 5:2075-2084(2010).
RN [16]
RP VARIANTS FSGS2 SER-125 AND LEU-218, AND VARIANT LEU-895.
RX PubMed=21734084; DOI=10.2215/cjn.07830910;
RA Gigante M., Caridi G., Montemurno E., Soccio M., d'Apolito M., Cerullo G.,
RA Aucella F., Schirinzi A., Emma F., Massella L., Messina G., De Palo T.,
RA Ranieri E., Ghiggeri G.M., Gesualdo L.;
RT "TRPC6 mutations in children with steroid-resistant nephrotic syndrome and
RT atypical phenotype.";
RL Clin. J. Am. Soc. Nephrol. 6:1626-1634(2011).
RN [17]
RP VARIANT FSGS2 HIS-360.
RX PubMed=22732337; DOI=10.5414/cn107320;
RA Buescher A.K., Konrad M., Nagel M., Witzke O., Kribben A., Hoyer P.F.,
RA Weber S.;
RT "Mutations in podocyte genes are a rare cause of primary FSGS associated
RT with ESRD in adult patients.";
RL Clin. Nephrol. 78:47-53(2012).
RN [18]
RP VARIANT FSGS2 ALA-395, AND VARIANT VAL-404.
RX PubMed=21511817; DOI=10.1093/ndt/gfr202;
RA Mir S., Yavascan O., Berdeli A., Sozeri B.;
RT "TRPC6 gene variants in Turkish children with steroid-resistant nephrotic
RT syndrome.";
RL Nephrol. Dial. Transplant. 27:205-209(2012).
RN [19]
RP VARIANTS FSGS2 THR-270; CYS-895; GLU-897 DEL AND LYS-897.
RX PubMed=23014460; DOI=10.1038/ki.2012.349;
RA Barua M., Brown E.J., Charoonratana V.T., Genovese G., Sun H., Pollak M.R.;
RT "Mutations in the INF2 gene account for a significant proportion of
RT familial but not sporadic focal and segmental glomerulosclerosis.";
RL Kidney Int. 83:316-322(2013).
RN [20]
RP VARIANTS FSGS2 GLN-175 AND CYS-895, CHARACTERIZATION OF VARIANTS FSGS2
RP GLN-175 AND CYS-895, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23291369; DOI=10.1093/ndt/gfs572;
RA Hofstra J.M., Lainez S., van Kuijk W.H., Schoots J., Baltissen M.P.,
RA Hoefsloot L.H., Knoers N.V., Berden J.H., Bindels R.J., van der Vlag J.,
RA Hoenderop J.G., Wetzels J.F., Nijenhuis T.;
RT "New TRPC6 gain-of-function mutation in a non-consanguineous Dutch family
RT with late-onset focal segmental glomerulosclerosis.";
RL Nephrol. Dial. Transplant. 28:1830-1838(2013).
RN [21]
RP MUTAGENESIS OF ASN-110; MET-132; 755-GLU--GLY-757; 755-GLU-GLU-756;
RP 826-LYS-LYS-827 AND GLN-889, VARIANTS FSGS2 SER-109; GLN-112; SER-125;
RP SER-143; GLN-175; LEU-218; ALA-395; ASP-757; PRO-780; CYS-895; LEU-895 AND
RP LYS-897, CHARACTERIZATION OF VARIANTS FSGS2 SER-109; GLN-112; SER-125;
RP SER-143; GLN-175; LEU-218; ALA-395; ASP-757; PRO-780; CYS-895; LEU-895 AND
RP LYS-897, VARIANT VAL-404, CHARACTERIZATION OF VARIANT VAL-404, FUNCTION,
RP SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=26892346; DOI=10.1681/asn.2015030318;
RA Riehle M., Buescher A.K., Gohlke B.O., Kassmann M., Kolatsi-Joannou M.,
RA Braesen J.H., Nagel M., Becker J.U., Winyard P., Hoyer P.F., Preissner R.,
RA Krautwurst D., Gollasch M., Weber S., Harteneck C.;
RT "TRPC6 G757D Loss-of-Function Mutation Associates with FSGS.";
RL J. Am. Soc. Nephrol. 27:2771-2783(2016).
CC -!- FUNCTION: Thought to form a receptor-activated non-selective calcium
CC permeant cation channel (PubMed:19936226, PubMed:23291369). Probably is
CC operated by a phosphatidylinositol second messenger system activated by
CC receptor tyrosine kinases or G-protein coupled receptors. Activated by
CC diacylglycerol (DAG) in a membrane-delimited fashion, independently of
CC protein kinase C (PubMed:26892346). Seems not to be activated by
CC intracellular calcium store depletion. {ECO:0000269|PubMed:19936226,
CC ECO:0000269|PubMed:23291369, ECO:0000269|PubMed:26892346}.
CC -!- SUBUNIT: Homodimer; forms channel complex (PubMed:26892346). Interacts
CC with MX1 and RNF24 (PubMed:15757897, PubMed:17850865).
CC {ECO:0000269|PubMed:15757897, ECO:0000269|PubMed:17850865,
CC ECO:0000269|PubMed:26892346}.
CC -!- INTERACTION:
CC Q9Y210; P20591: MX1; NbExp=4; IntAct=EBI-929362, EBI-929476;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23291369,
CC ECO:0000269|PubMed:26892346}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Y210-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y210-2; Sequence=VSP_006572;
CC Name=3;
CC IsoId=Q9Y210-3; Sequence=VSP_006573;
CC -!- TISSUE SPECIFICITY: Expressed primarily in placenta, lung, spleen,
CC ovary and small intestine. Expressed in podocytes and is a component of
CC the glomerular slit diaphragm. {ECO:0000269|PubMed:15924139}.
CC -!- PTM: Phosphorylated by FYN, leading to an increase of TRPC6 channel
CC activity. {ECO:0000250|UniProtKB:Q61143}.
CC -!- DISEASE: Focal segmental glomerulosclerosis 2 (FSGS2) [MIM:603965]: A
CC renal pathology defined by the presence of segmental sclerosis in
CC glomeruli and resulting in proteinuria, reduced glomerular filtration
CC rate and progressive decline in renal function. Renal insufficiency
CC often progresses to end-stage renal disease, a highly morbid state
CC requiring either dialysis therapy or kidney transplantation.
CC {ECO:0000269|PubMed:15879175, ECO:0000269|PubMed:15924139,
CC ECO:0000269|PubMed:19458060, ECO:0000269|PubMed:19936226,
CC ECO:0000269|PubMed:20798252, ECO:0000269|PubMed:21511817,
CC ECO:0000269|PubMed:21734084, ECO:0000269|PubMed:22732337,
CC ECO:0000269|PubMed:23014460, ECO:0000269|PubMed:23291369,
CC ECO:0000269|PubMed:26892346}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. STrpC
CC subfamily. TRPC6 sub-subfamily. {ECO:0000305}.
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DR EMBL; AF080394; AAC63289.2; -; mRNA.
DR EMBL; AJ006276; CAA06943.1; -; mRNA.
DR EMBL; AJ271066; CAC01684.1; -; mRNA.
DR EMBL; AJ271067; CAC01685.1; -; mRNA.
DR EMBL; AJ271068; CAC01686.1; -; mRNA.
DR EMBL; BC093658; AAH93658.1; -; mRNA.
DR EMBL; BC093660; AAH93660.1; -; mRNA.
DR EMBL; AJ007018; CAC06090.1; -; mRNA.
DR CCDS; CCDS8311.1; -. [Q9Y210-1]
DR RefSeq; NP_004612.2; NM_004621.5. [Q9Y210-1]
DR RefSeq; XP_016873710.1; XM_017018221.1. [Q9Y210-2]
DR PDB; 5YX9; EM; 3.80 A; A/B/C/D=1-931.
DR PDB; 6UZ8; EM; 2.84 A; A/B/C/D=85-931.
DR PDB; 6UZA; EM; 3.08 A; A/B/C/D=85-931.
DR PDB; 7A6U; EM; 3.62 A; A/B/C/D=1-931.
DR PDB; 7DXF; EM; 2.90 A; A/B/C/D=1-931.
DR PDB; 7DXG; EM; 2.90 A; A/B/C/D=1-931.
DR PDBsum; 5YX9; -.
DR PDBsum; 6UZ8; -.
DR PDBsum; 6UZA; -.
DR PDBsum; 7A6U; -.
DR PDBsum; 7DXF; -.
DR PDBsum; 7DXG; -.
DR AlphaFoldDB; Q9Y210; -.
DR SMR; Q9Y210; -.
DR BioGRID; 113076; 77.
DR IntAct; Q9Y210; 2.
DR STRING; 9606.ENSP00000340913; -.
DR BindingDB; Q9Y210; -.
DR ChEMBL; CHEMBL2417347; -.
DR GuidetoPHARMACOLOGY; 491; -.
DR TCDB; 1.A.4.1.5; the transient receptor potential ca(2+) channel (trp-cc) family.
DR GlyConnect; 2074; 2 N-Linked glycans (1 site).
DR GlyGen; Q9Y210; 2 sites, 4 N-linked glycans (1 site).
DR iPTMnet; Q9Y210; -.
DR PhosphoSitePlus; Q9Y210; -.
DR BioMuta; TRPC6; -.
DR DMDM; 6686048; -.
DR EPD; Q9Y210; -.
DR jPOST; Q9Y210; -.
DR MassIVE; Q9Y210; -.
DR PaxDb; Q9Y210; -.
DR PeptideAtlas; Q9Y210; -.
DR PRIDE; Q9Y210; -.
DR ProteomicsDB; 85580; -. [Q9Y210-1]
DR ProteomicsDB; 85581; -. [Q9Y210-2]
DR ProteomicsDB; 85582; -. [Q9Y210-3]
DR ABCD; Q9Y210; 1 sequenced antibody.
DR Antibodypedia; 17956; 424 antibodies from 40 providers.
DR DNASU; 7225; -.
DR Ensembl; ENST00000344327.8; ENSP00000340913.3; ENSG00000137672.13. [Q9Y210-1]
DR Ensembl; ENST00000348423.8; ENSP00000343672.4; ENSG00000137672.13. [Q9Y210-2]
DR Ensembl; ENST00000360497.4; ENSP00000353687.4; ENSG00000137672.13. [Q9Y210-3]
DR GeneID; 7225; -.
DR KEGG; hsa:7225; -.
DR MANE-Select; ENST00000344327.8; ENSP00000340913.3; NM_004621.6; NP_004612.2.
DR UCSC; uc001pgk.4; human. [Q9Y210-1]
DR CTD; 7225; -.
DR DisGeNET; 7225; -.
DR GeneCards; TRPC6; -.
DR HGNC; HGNC:12338; TRPC6.
DR HPA; ENSG00000137672; Tissue enhanced (lung, placenta).
DR MalaCards; TRPC6; -.
DR MIM; 603652; gene.
DR MIM; 603965; phenotype.
DR neXtProt; NX_Q9Y210; -.
DR OpenTargets; ENSG00000137672; -.
DR Orphanet; 656; Genetic steroid-resistant nephrotic syndrome.
DR PharmGKB; PA37011; -.
DR VEuPathDB; HostDB:ENSG00000137672; -.
DR eggNOG; KOG3609; Eukaryota.
DR GeneTree; ENSGT01050000244831; -.
DR InParanoid; Q9Y210; -.
DR OMA; WISELFW; -.
DR OrthoDB; 1018075at2759; -.
DR PhylomeDB; Q9Y210; -.
DR TreeFam; TF313147; -.
DR PathwayCommons; Q9Y210; -.
DR Reactome; R-HSA-114508; Effects of PIP2 hydrolysis.
DR Reactome; R-HSA-139853; Elevation of cytosolic Ca2+ levels.
DR Reactome; R-HSA-3295583; TRP channels.
DR Reactome; R-HSA-418890; Role of second messengers in netrin-1 signaling.
DR SABIO-RK; Q9Y210; -.
DR SignaLink; Q9Y210; -.
DR SIGNOR; Q9Y210; -.
DR BioGRID-ORCS; 7225; 15 hits in 1059 CRISPR screens.
DR ChiTaRS; TRPC6; human.
DR GeneWiki; TRPC6; -.
DR GenomeRNAi; 7225; -.
DR Pharos; Q9Y210; Tchem.
DR PRO; PR:Q9Y210; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9Y210; protein.
DR Bgee; ENSG00000137672; Expressed in right lung and 108 other tissues.
DR ExpressionAtlas; Q9Y210; baseline and differential.
DR Genevisible; Q9Y210; HS.
DR GO; GO:0034703; C:cation channel complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0036057; C:slit diaphragm; IEA:Ensembl.
DR GO; GO:0005262; F:calcium channel activity; TAS:Reactome.
DR GO; GO:0005261; F:cation channel activity; IDA:UniProtKB.
DR GO; GO:0070679; F:inositol 1,4,5 trisphosphate binding; IDA:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0015279; F:store-operated calcium channel activity; IBA:GO_Central.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006812; P:cation transport; TAS:ProtInc.
DR GO; GO:0006828; P:manganese ion transport; IBA:GO_Central.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; IDA:MGI.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR GO; GO:0032414; P:positive regulation of ion transmembrane transporter activity; IDA:MGI.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR GO; GO:0007338; P:single fertilization; IBA:GO_Central.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR013555; TRP_dom.
DR InterPro; IPR005462; TRPC6_channel.
DR InterPro; IPR002153; TRPC_channel.
DR PANTHER; PTHR10117; PTHR10117; 1.
DR PANTHER; PTHR10117:SF7; PTHR10117:SF7; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF08344; TRP_2; 1.
DR PRINTS; PR01097; TRNSRECEPTRP.
DR PRINTS; PR01647; TRPCHANNEL6.
DR SMART; SM00248; ANK; 3.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 2.
DR PROSITE; PS50088; ANK_REPEAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ANK repeat; Calcium; Calcium channel;
KW Calcium transport; Cell membrane; Disease variant; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..931
FT /note="Short transient receptor potential channel 6"
FT /id="PRO_0000215322"
FT TOPO_DOM 1..438
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 439..459
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 460..487
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 488..508
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 509..521
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 522..542
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 543..592
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 593..613
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 614..636
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 637..657
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 658..706
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 707..727
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 728..931
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 97..126
FT /note="ANK 1"
FT REPEAT 132..161
FT /note="ANK 2"
FT REPEAT 163..189
FT /note="ANK 3"
FT REPEAT 218..247
FT /note="ANK 4"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 815
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087"
FT CARBOHYD 473
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12970363"
FT CARBOHYD 561
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12970363"
FT VAR_SEQ 316..431
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10816590"
FT /id="VSP_006572"
FT VAR_SEQ 377..431
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10816590"
FT /id="VSP_006573"
FT VARIANT 15
FT /note="P -> S (in dbSNP:rs3802829)"
FT /evidence="ECO:0000269|PubMed:19124028,
FT ECO:0000269|PubMed:19936226"
FT /id="VAR_079784"
FT VARIANT 88
FT /note="F -> FAYMF (in FSGS2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:20798252"
FT /id="VAR_079785"
FT VARIANT 109
FT /note="G -> S (in FSGS2; increases calcium ion transport)"
FT /evidence="ECO:0000269|PubMed:19458060,
FT ECO:0000269|PubMed:26892346"
FT /id="VAR_079786"
FT VARIANT 112
FT /note="P -> Q (in FSGS2; increases calcium ion transport;
FT dbSNP:rs121434390)"
FT /evidence="ECO:0000269|PubMed:15879175,
FT ECO:0000269|PubMed:26892346"
FT /id="VAR_026730"
FT VARIANT 125
FT /note="N -> S (in FSGS2; unknown pathological significance;
FT decreases calcium ion transport; dbSNP:rs146776939)"
FT /evidence="ECO:0000269|PubMed:19458060,
FT ECO:0000269|PubMed:21734084, ECO:0000269|PubMed:26892346"
FT /id="VAR_067247"
FT VARIANT 143
FT /note="N -> S (in FSGS2; increases cation channel activity;
FT does not change the outward peak current; increases
FT significantly the inward peak current amplitude; increases
FT calcium ion transport; dbSNP:rs121434391)"
FT /evidence="ECO:0000269|PubMed:15924139,
FT ECO:0000269|PubMed:19936226, ECO:0000269|PubMed:26892346"
FT /id="VAR_026731"
FT VARIANT 157
FT /note="N -> T (in dbSNP:rs35857503)"
FT /id="VAR_038419"
FT VARIANT 175
FT /note="R -> Q (in FSGS2; increases cation channel activity;
FT does not change plasma membrane expression; increases
FT calcium ion transport; dbSNP:rs1451194842)"
FT /evidence="ECO:0000269|PubMed:23291369,
FT ECO:0000269|PubMed:26892346"
FT /id="VAR_079787"
FT VARIANT 218
FT /note="H -> L (in FSGS2; increases calcium ion transport;
FT dbSNP:rs779430565)"
FT /evidence="ECO:0000269|PubMed:21734084,
FT ECO:0000269|PubMed:26892346"
FT /id="VAR_067248"
FT VARIANT 270
FT /note="S -> T (in FSGS2; dbSNP:rs121434392)"
FT /evidence="ECO:0000269|PubMed:15924139,
FT ECO:0000269|PubMed:19936226, ECO:0000269|PubMed:23014460"
FT /id="VAR_026732"
FT VARIANT 360
FT /note="R -> H (in FSGS2; unknown pathological significance;
FT dbSNP:rs777715086)"
FT /evidence="ECO:0000269|PubMed:22732337"
FT /id="VAR_079788"
FT VARIANT 395
FT /note="L -> A (in FSGS2; unknown pathological significance;
FT requires 2 nucleotide substitutions; decreases calcium ion
FT transport)"
FT /evidence="ECO:0000269|PubMed:21511817,
FT ECO:0000269|PubMed:26892346"
FT /id="VAR_079789"
FT VARIANT 404
FT /note="A -> V (increases calcium ion transport;
FT dbSNP:rs36111323)"
FT /evidence="ECO:0000269|PubMed:19936226,
FT ECO:0000269|PubMed:21511817, ECO:0000269|PubMed:26892346"
FT /id="VAR_061861"
FT VARIANT 757
FT /note="G -> D (in FSGS2; decreases calcium ion transport;
FT does not change localization at cell membrane; does not
FT affect homodimer formation)"
FT /evidence="ECO:0000269|PubMed:20798252,
FT ECO:0000269|PubMed:26892346"
FT /id="VAR_079790"
FT VARIANT 780
FT /note="L -> P (in FSGS2; unknown pathological significance;
FT decreases calcium ion transport; dbSNP:rs771594597)"
FT /evidence="ECO:0000269|PubMed:19458060,
FT ECO:0000269|PubMed:26892346"
FT /id="VAR_079791"
FT VARIANT 874..931
FT /note="Missing (in FSGS2)"
FT /evidence="ECO:0000269|PubMed:19936226"
FT /id="VAR_079792"
FT VARIANT 895
FT /note="R -> C (in FSGS2; increases cation channel activity;
FT does not change plasma membrane expression; significantly
FT reduces the ratio of cell-surface to total expression;
FT increases calcium ion transport; dbSNP:rs121434394)"
FT /evidence="ECO:0000269|PubMed:15924139,
FT ECO:0000269|PubMed:23014460, ECO:0000269|PubMed:23291369,
FT ECO:0000269|PubMed:26892346"
FT /id="VAR_026733"
FT VARIANT 895
FT /note="R -> L (in FSGS2; decreases calcium ion transport)"
FT /evidence="ECO:0000269|PubMed:21734084,
FT ECO:0000269|PubMed:26892346"
FT /id="VAR_067249"
FT VARIANT 897
FT /note="E -> K (in FSGS2; increases calcium ion transport;
FT dbSNP:rs121434395)"
FT /evidence="ECO:0000269|PubMed:15924139,
FT ECO:0000269|PubMed:23014460, ECO:0000269|PubMed:26892346"
FT /id="VAR_026734"
FT VARIANT 897
FT /note="Missing (in FSGS2)"
FT /evidence="ECO:0000269|PubMed:23014460"
FT /id="VAR_079793"
FT MUTAGEN 110
FT /note="N->H: Increases calcium ion transport."
FT /evidence="ECO:0000269|PubMed:26892346"
FT MUTAGEN 125
FT /note="N->A: No effect on RNF24-binding; when associated
FT with A-127; A-128 and A-130."
FT /evidence="ECO:0000269|PubMed:17850865"
FT MUTAGEN 127
FT /note="N->A: No effect on RNF24-binding; when associated
FT with A-125; A-128 and A-130."
FT /evidence="ECO:0000269|PubMed:17850865"
FT MUTAGEN 128
FT /note="C->A: No effect on RNF24-binding; when associated
FT with A-125; A-127 and A-130."
FT /evidence="ECO:0000269|PubMed:17850865"
FT MUTAGEN 130
FT /note="D->A: No effect on RNF24-binding; when associated
FT with A-125; A-127 and A-128."
FT /evidence="ECO:0000269|PubMed:17850865"
FT MUTAGEN 132
FT /note="M->T: Increases cation channel activity. Increases
FT significantly inward and outward currents and does not show
FT channel inactivation. Increases calcium ion transport."
FT /evidence="ECO:0000269|PubMed:19936226,
FT ECO:0000269|PubMed:26892346"
FT MUTAGEN 561
FT /note="N->Q: Constitutively activates channel."
FT /evidence="ECO:0000269|PubMed:12970363"
FT MUTAGEN 755..757
FT /note="EEG->KKR: Decreases calcium ion transport."
FT /evidence="ECO:0000269|PubMed:26892346"
FT MUTAGEN 755..756
FT /note="EE->KK: Increases calcium ion transport."
FT /evidence="ECO:0000269|PubMed:26892346"
FT MUTAGEN 826..827
FT /note="KK->EE: Decreases calcium ion transport."
FT /evidence="ECO:0000269|PubMed:26892346"
FT MUTAGEN 889
FT /note="Q->K: Increases calcium transport. Increases calcium
FT ion transport."
FT /evidence="ECO:0000269|PubMed:19124028,
FT ECO:0000269|PubMed:26892346"
FT CONFLICT 336
FT /note="C -> R (in Ref. 3; CAC01686)"
FT /evidence="ECO:0000305"
FT CONFLICT 585
FT /note="K -> R (in Ref. 5; CAC06090)"
FT /evidence="ECO:0000305"
FT CONFLICT 613
FT /note="I -> T (in Ref. 3; CAC01686)"
FT /evidence="ECO:0000305"
FT HELIX 97..108
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 111..119
FT /evidence="ECO:0007829|PDB:6UZ8"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 136..142
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 146..152
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 161..171
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 174..180
FT /evidence="ECO:0007829|PDB:6UZ8"
FT STRAND 205..212
FT /evidence="ECO:0007829|PDB:6UZ8"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 222..228
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 232..240
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 258..264
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 268..280
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 283..289
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 293..310
FT /evidence="ECO:0007829|PDB:6UZ8"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 315..334
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 339..346
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:6UZA"
FT STRAND 357..360
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 364..371
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 375..378
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 381..392
FT /evidence="ECO:0007829|PDB:6UZ8"
FT TURN 397..399
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 405..415
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 417..426
FT /evidence="ECO:0007829|PDB:6UZ8"
FT TURN 431..437
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 439..459
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 460..464
FT /evidence="ECO:0007829|PDB:6UZ8"
FT STRAND 478..482
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 484..487
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 493..520
FT /evidence="ECO:0007829|PDB:6UZ8"
FT TURN 521..523
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 526..557
FT /evidence="ECO:0007829|PDB:6UZ8"
FT STRAND 576..580
FT /evidence="ECO:0007829|PDB:6UZA"
FT HELIX 583..585
FT /evidence="ECO:0007829|PDB:6UZA"
FT HELIX 591..605
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 606..612
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 614..616
FT /evidence="ECO:0007829|PDB:6UZ8"
FT TURN 618..620
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 621..630
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 631..633
FT /evidence="ECO:0007829|PDB:6UZ8"
FT TURN 634..636
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 637..656
FT /evidence="ECO:0007829|PDB:6UZ8"
FT STRAND 660..666
FT /evidence="ECO:0007829|PDB:6UZ8"
FT STRAND 668..670
FT /evidence="ECO:0007829|PDB:6UZA"
FT HELIX 671..680
FT /evidence="ECO:0007829|PDB:6UZ8"
FT TURN 681..684
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 688..691
FT /evidence="ECO:0007829|PDB:6UZ8"
FT STRAND 693..696
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 698..731
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 737..751
FT /evidence="ECO:0007829|PDB:6UZ8"
FT STRAND 754..757
FT /evidence="ECO:0007829|PDB:6UZ8"
FT TURN 762..766
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 854..875
FT /evidence="ECO:0007829|PDB:6UZ8"
FT HELIX 881..917
FT /evidence="ECO:0007829|PDB:6UZ8"
SQ SEQUENCE 931 AA; 106326 MW; 7C955C2B0389AC47 CRC64;
MSQSPAFGPR RGSSPRGAAG AAARRNESQD YLLMDSELGE DGCPQAPLPC YGYYPCFRGS
DNRLAHRRQT VLREKGRRLA NRGPAYMFSD RSTSLSIEEE RFLDAAEYGN IPVVRKMLEE
CHSLNVNCVD YMGQNALQLA VANEHLEITE LLLKKENLSR VGDALLLAIS KGYVRIVEAI
LSHPAFAEGK RLATSPSQSE LQQDDFYAYD EDGTRFSHDV TPIILAAHCQ EYEIVHTLLR
KGARIERPHD YFCKCNDCNQ KQKHDSFSHS RSRINAYKGL ASPAYLSLSS EDPVMTALEL
SNELAVLANI EKEFKNDYKK LSMQCKDFVV GLLDLCRNTE EVEAILNGDV ETLQSGDHGR
PNLSRLKLAI KYEVKKFVAH PNCQQQLLSI WYENLSGLRQ QTMAVKFLVV LAVAIGLPFL
ALIYWFAPCS KMGKIMRGPF MKFVAHAASF TIFLGLLVMN AADRFEGTKL LPNETSTDNA
KQLFRMKTSC FSWMEMLIIS WVIGMIWAEC KEIWTQGPKE YLFELWNMLD FGMLAIFAAS
FIARFMAFWH ASKAQSIIDA NDTLKDLTKV TLGDNVKYYN LARIKWDPSD PQIISEGLYA
IAVVLSFSRI AYILPANESF GPLQISLGRT VKDIFKFMVI FIMVFVAFMI GMFNLYSYYI
GAKQNEAFTT VEESFKTLFW AIFGLSEVKS VVINYNHKFI ENIGYVLYGV YNVTMVIVLL
NMLIAMINSS FQEIEDDADV EWKFARAKLW FSYFEEGRTL PVPFNLVPSP KSLFYLLLKL
KKWISELFQG HKKGFQEDAE MNKINEEKKL GILGSHEDLS KLSLDKKQVG HNKQPSIRSS
EDFHLNSFNN PPRQYQKIMK RLIKRYVLQA QIDKESDEVN EGELKEIKQD ISSLRYELLE
EKSQNTEDLA ELIRELGEKL SMEPNQEETN R
