TRPC4_HUMAN
ID TRPC4_HUMAN Reviewed; 977 AA.
AC Q9UBN4; B1ALE0; B1ALE1; B1ALE2; Q15721; Q3SWS6; Q96P03; Q96P04; Q96P05;
AC Q9UIB0; Q9UIB1; Q9UIB2;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Short transient receptor potential channel 4;
DE Short=TrpC4;
DE AltName: Full=Trp-related protein 4;
DE Short=hTrp-4;
DE Short=hTrp4;
GN Name=TRPC4;
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 ALPHA).
RC TISSUE=Kidney;
RX PubMed=11042129; DOI=10.1042/bj3510735;
RA McKay R.R., Szymeczek-Seay C.L., Lievremont J.-P., Bird G.S., Zitt C.,
RA Juengling E., Lueckhoff A., Putney J.W. Jr.;
RT "Cloning and expression of the human transient receptor potential 4 (TRP4)
RT gene: localization and functional expression of human TRP4 and TRP3.";
RL Biochem. J. 351:735-746(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA; BETA; DELTA AND GAMMA), AND
RP INTERACTION WITH ITPR1; ITPR2 AND ITPR3.
RC TISSUE=Embryonic kidney;
RX PubMed=11163362; DOI=10.1016/s0014-5793(00)02362-0;
RA Mery L., Magnino F., Schmidt K., Krause K.-H., Dufour J.-F.;
RT "Alternative splice variants of hTrp4 differentially interact with the C-
RT terminal portion of the inositol 1,4,5-trisphosphate receptors.";
RL FEBS Lett. 487:377-383(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA; BETA; EPSILON; ETA AND ZETA),
RP AND SUBCELLULAR LOCATION.
RX PubMed=11713258; DOI=10.1074/jbc.m109850200;
RA Schaefer M., Plant T.D., Stresow N., Albrecht N., Schultz G.;
RT "Functional differences between TRPC4 splice variants.";
RL J. Biol. Chem. 277:3752-3759(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 514-633.
RC TISSUE=Kidney;
RX PubMed=8646775; DOI=10.1016/s0092-8674(00)81233-7;
RA Zhu X., Jiang M., Peyton M., Boulay G., Hurst R., Stefani E.,
RA Birnbaumer L.;
RT "trp, a novel mammalian gene family essential for agonist-activated
RT capacitative Ca2+ entry.";
RL Cell 85:661-671(1996).
RN [8]
RP MUTAGENESIS OF 975-THR--LEU-977, INTERACTION WITH SLC9A3R1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12154080; DOI=10.1242/jcs.115.17.3497;
RA Mery L., Strauss B., Dufour J.F., Krause K.H., Hoth M.;
RT "The PDZ-interacting domain of TRPC4 controls its localization and surface
RT expression in HEK293 cells.";
RL J. Cell Sci. 115:3497-3508(2002).
RN [9]
RP SUBUNIT.
RX PubMed=12032305; DOI=10.1073/pnas.102596199;
RA Hofmann T., Schaefer M., Schultz G., Gudermann T.;
RT "Subunit composition of mammalian transient receptor potential channels in
RT living cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7461-7466(2002).
RN [10]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH EPB41L2.
RX PubMed=16254212; DOI=10.1161/01.res.0000193597.65217.00;
RA Cioffi D.L., Wu S., Alexeyev M., Goodman S.R., Zhu M.X., Stevens T.;
RT "Activation of the endothelial store-operated ISOC Ca2+ channel requires
RT interaction of protein 4.1 with TRPC4.";
RL Circ. Res. 97:1164-1172(2005).
RN [11]
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 [12]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-959 AND TYR-972, AND
RP MUTAGENESIS OF TYR-959 AND TYR-972.
RX PubMed=16144838; DOI=10.1074/jbc.m503646200;
RA Odell A.F., Scott J.L., Van Helden D.F.;
RT "Epidermal growth factor induces tyrosine phosphorylation, membrane
RT insertion, and activation of transient receptor potential channel 4.";
RL J. Biol. Chem. 280:37974-37987(2005).
RN [13]
RP INTERACTION WITH RNF24.
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 [14]
RP INTERACTION WITH SPTAN1 AND SPTBN5.
RX PubMed=18048348; DOI=10.1074/jbc.m709729200;
RA Odell A.F., Van Helden D.F., Scott J.L.;
RT "The spectrin cytoskeleton influences the surface expression and activation
RT of human transient receptor potential channel 4 channels.";
RL J. Biol. Chem. 283:4395-4407(2008).
RN [15]
RP INTERACTION WITH SESTD1.
RX PubMed=20164195; DOI=10.1074/jbc.m109.068304;
RA Miehe S., Bieberstein A., Arnould I., Ihdene O., Rutten H., Strubing C.;
RT "The phospholipid-binding protein SESTD1 is a novel regulator of the
RT transient receptor potential channels TRPC4 and TRPC5.";
RL J. Biol. Chem. 285:12426-12434(2010).
RN [16]
RP FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH CDH5 AND CTNNB1.
RX PubMed=19996314; DOI=10.1074/jbc.m109.060301;
RA Graziani A., Poteser M., Heupel W.M., Schleifer H., Krenn M.,
RA Drenckhahn D., Romanin C., Baumgartner W., Groschner K.;
RT "Cell-cell contact formation governs Ca2+ signaling by TRPC4 in the
RT vascular endothelium: evidence for a regulatory TRPC4-beta-catenin
RT interaction.";
RL J. Biol. Chem. 285:4213-4223(2010).
RN [17]
RP VARIANT [LARGE SCALE ANALYSIS] LYS-138.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Forms a receptor-activated non-selective calcium permeant
CC cation channel. Acts as a cell-cell contact-dependent endothelial
CC calcium entry channel. Probably operated by a phosphatidylinositol
CC second messenger system activated by receptor tyrosine kinases or G-
CC protein coupled receptors. Mediates cation entry, with an enhanced
CC permeability to barium over calcium. May also be activated by
CC intracellular calcium store depletion. {ECO:0000269|PubMed:16144838,
CC ECO:0000269|PubMed:19996314}.
CC -!- SUBUNIT: Interacts with TRPC4AP (By similarity). Homotetramer and
CC heterotetramer with TRPC1 and/or TRPC5 (PubMed:12032305). Isoform alpha
CC but not isoform beta interacts with ITPR1, ITPR2 and ITPR3
CC (PubMed:11163362). Interacts with (via PDZ-binding domain) with
CC SLC9A3R1/NHERF (PubMed:12154080). Interacts with MX1 and RNF24
CC (PubMed:15757897, PubMed:17850865). Interacts (via CIRB domain) with
CC SESTD1 (via spectrin 1 repeat) (PubMed:20164195). Interacts with CDH5
CC and CTNNB1 (PubMed:19996314). Interacts with SPTAN1 (via C-terminal
CC spectrin repeats) and SPTBN5 (via C-terminus) (PubMed:18048348).
CC Interacts (via protein 4.1-binding domain) with EPB41L2
CC (PubMed:16254212). Interacts with PLSCR1 (By similarity).
CC {ECO:0000250|UniProtKB:Q9QUQ5, ECO:0000269|PubMed:11163362,
CC ECO:0000269|PubMed:12032305, ECO:0000269|PubMed:12154080,
CC ECO:0000269|PubMed:15757897, ECO:0000269|PubMed:16254212,
CC ECO:0000269|PubMed:17850865, ECO:0000269|PubMed:18048348,
CC ECO:0000269|PubMed:19996314, ECO:0000269|PubMed:20164195}.
CC -!- INTERACTION:
CC Q9UBN4; P20591: MX1; NbExp=2; IntAct=EBI-929504, EBI-929476;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Cell
CC membrane; Multi-pass membrane protein. Note=Enhanced insertion into the
CC cell membrane after activation of the EGF receptor.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=Alpha;
CC IsoId=Q9UBN4-1; Sequence=Displayed;
CC Name=Beta;
CC IsoId=Q9UBN4-2; Sequence=VSP_006569;
CC Name=Delta;
CC IsoId=Q9UBN4-3; Sequence=VSP_006568;
CC Name=Gamma;
CC IsoId=Q9UBN4-4; Sequence=VSP_006567, VSP_006569;
CC Name=Epsilon;
CC IsoId=Q9UBN4-5; Sequence=VSP_041262;
CC Name=Zeta;
CC IsoId=Q9UBN4-6; Sequence=VSP_041439;
CC Name=Eta;
CC IsoId=Q9UBN4-7; Sequence=VSP_047747, VSP_047748;
CC -!- TISSUE SPECIFICITY: Strongly expressed in placenta. Expressed at lower
CC levels in heart, pancreas, kidney and brain. Expressed in endothelial
CC cells. Isoform alpha was found to be the predominant isoform. Isoform
CC beta was not found in pancreas and brain.
CC {ECO:0000269|PubMed:19996314}.
CC -!- DOMAIN: The protein 4.1-binding domain (654-685) is required for
CC binding to EPB41L2 and channel activation.
CC -!- DOMAIN: The calmodulin- and inositol 1,4,5-trisphosphate receptor-
CC binding (CIRB) domain (695-724) is sufficient for the interaction with
CC SESTD1.
CC -!- DOMAIN: The spectrin-binding domain (730-758) is required for binding
CC to SPTAN1 and SPTBN5.
CC -!- PTM: Phosphorylation modulates TRPC channel function by regulating the
CC level of TRPC4 at the cell surface and by increasing the association
CC with SLC9A3R1/NHERF. {ECO:0000269|PubMed:16144838}.
CC -!- MISCELLANEOUS: The interaction with spectrin is important in
CC controlling the translocation of TRPC4 channels to the plasma membrane
CC following EGF stimulation.
CC -!- MISCELLANEOUS: The cell membrane presentation, the calcium entry
CC function and the interaction with junctional proteins (CTNNB1 and CDH5)
CC are controlled by endothelial cell-cell contacts.
CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. STrpC
CC subfamily. TRPC4 sub-subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF063822; AAF22927.1; -; mRNA.
DR EMBL; AF063823; AAF22928.1; -; mRNA.
DR EMBL; AF063824; AAF22929.1; -; mRNA.
DR EMBL; AF063825; AAF22930.1; -; mRNA.
DR EMBL; AF175406; AAD51736.1; -; mRNA.
DR EMBL; AF421358; AAL24549.1; -; mRNA.
DR EMBL; AF421359; AAL24550.1; -; mRNA.
DR EMBL; AF421360; AAL24551.1; -; mRNA.
DR EMBL; AF421361; AAL24552.1; -; mRNA.
DR EMBL; AF421362; AAL24553.1; -; mRNA.
DR EMBL; AL138679; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL354802; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471075; EAX08595.1; -; Genomic_DNA.
DR EMBL; CH471075; EAX08596.1; -; Genomic_DNA.
DR EMBL; CH471075; EAX08597.1; -; Genomic_DNA.
DR EMBL; CH471075; EAX08598.1; -; Genomic_DNA.
DR EMBL; CH471075; EAX08600.1; -; Genomic_DNA.
DR EMBL; CH471075; EAX08601.1; -; Genomic_DNA.
DR EMBL; BC104725; AAI04726.1; -; mRNA.
DR EMBL; U40983; AAC50630.1; -; mRNA.
DR CCDS; CCDS45035.1; -. [Q9UBN4-6]
DR CCDS; CCDS45036.1; -. [Q9UBN4-4]
DR CCDS; CCDS45037.1; -. [Q9UBN4-5]
DR CCDS; CCDS45038.1; -. [Q9UBN4-2]
DR CCDS; CCDS45039.1; -. [Q9UBN4-3]
DR CCDS; CCDS9365.1; -. [Q9UBN4-1]
DR RefSeq; NP_001129427.1; NM_001135955.1. [Q9UBN4-2]
DR RefSeq; NP_001129428.1; NM_001135956.1. [Q9UBN4-4]
DR RefSeq; NP_001129429.1; NM_001135957.1. [Q9UBN4-3]
DR RefSeq; NP_001129430.1; NM_001135958.1. [Q9UBN4-6]
DR RefSeq; NP_003297.1; NM_003306.1. [Q9UBN4-5]
DR RefSeq; NP_057263.1; NM_016179.2. [Q9UBN4-1]
DR AlphaFoldDB; Q9UBN4; -.
DR SMR; Q9UBN4; -.
DR BioGRID; 113074; 19.
DR CORUM; Q9UBN4; -.
DR IntAct; Q9UBN4; 3.
DR MINT; Q9UBN4; -.
DR STRING; 9606.ENSP00000369027; -.
DR BindingDB; Q9UBN4; -.
DR ChEMBL; CHEMBL4295971; -.
DR GuidetoPHARMACOLOGY; 489; -.
DR TCDB; 1.A.4.1.12; the transient receptor potential ca(2+) channel (trp-cc) family.
DR GlyGen; Q9UBN4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UBN4; -.
DR PhosphoSitePlus; Q9UBN4; -.
DR BioMuta; TRPC4; -.
DR DMDM; 13633994; -.
DR EPD; Q9UBN4; -.
DR jPOST; Q9UBN4; -.
DR MassIVE; Q9UBN4; -.
DR MaxQB; Q9UBN4; -.
DR PaxDb; Q9UBN4; -.
DR PeptideAtlas; Q9UBN4; -.
DR PRIDE; Q9UBN4; -.
DR ProteomicsDB; 77587; -.
DR ProteomicsDB; 84012; -. [Q9UBN4-1]
DR ProteomicsDB; 84013; -. [Q9UBN4-2]
DR ProteomicsDB; 84014; -. [Q9UBN4-3]
DR ProteomicsDB; 84015; -. [Q9UBN4-4]
DR ProteomicsDB; 84016; -. [Q9UBN4-5]
DR ProteomicsDB; 84017; -. [Q9UBN4-6]
DR Antibodypedia; 8254; 306 antibodies from 34 providers.
DR DNASU; 7223; -.
DR Ensembl; ENST00000338947.9; ENSP00000342580.5; ENSG00000133107.15. [Q9UBN4-6]
DR Ensembl; ENST00000355779.6; ENSP00000348025.2; ENSG00000133107.15. [Q9UBN4-3]
DR Ensembl; ENST00000358477.6; ENSP00000351264.2; ENSG00000133107.15. [Q9UBN4-2]
DR Ensembl; ENST00000379673.2; ENSP00000368995.2; ENSG00000133107.15. [Q9UBN4-4]
DR Ensembl; ENST00000379679.5; ENSP00000369001.1; ENSG00000133107.15. [Q9UBN4-6]
DR Ensembl; ENST00000379705.8; ENSP00000369027.4; ENSG00000133107.15. [Q9UBN4-1]
DR Ensembl; ENST00000488717.5; ENSP00000435969.1; ENSG00000133107.15. [Q9UBN4-7]
DR Ensembl; ENST00000625583.2; ENSP00000486109.1; ENSG00000133107.15. [Q9UBN4-5]
DR GeneID; 7223; -.
DR KEGG; hsa:7223; -.
DR MANE-Select; ENST00000379705.8; ENSP00000369027.4; NM_016179.4; NP_057263.1.
DR UCSC; uc001uws.4; human. [Q9UBN4-1]
DR CTD; 7223; -.
DR DisGeNET; 7223; -.
DR GeneCards; TRPC4; -.
DR HGNC; HGNC:12336; TRPC4.
DR HPA; ENSG00000133107; Tissue enhanced (endometrium, seminal vesicle, smooth muscle).
DR MIM; 603651; gene.
DR neXtProt; NX_Q9UBN4; -.
DR OpenTargets; ENSG00000133107; -.
DR PharmGKB; PA37009; -.
DR VEuPathDB; HostDB:ENSG00000133107; -.
DR eggNOG; KOG3609; Eukaryota.
DR GeneTree; ENSGT01050000244831; -.
DR HOGENOM; CLU_005716_1_1_1; -.
DR InParanoid; Q9UBN4; -.
DR OMA; QSPDEKC; -.
DR OrthoDB; 824310at2759; -.
DR PhylomeDB; Q9UBN4; -.
DR TreeFam; TF313147; -.
DR PathwayCommons; Q9UBN4; -.
DR Reactome; R-HSA-3295583; TRP channels.
DR Reactome; R-HSA-418890; Role of second messengers in netrin-1 signaling.
DR SignaLink; Q9UBN4; -.
DR BioGRID-ORCS; 7223; 14 hits in 1066 CRISPR screens.
DR ChiTaRS; TRPC4; human.
DR GeneWiki; TRPC4; -.
DR GenomeRNAi; 7223; -.
DR Pharos; Q9UBN4; Tchem.
DR PRO; PR:Q9UBN4; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q9UBN4; protein.
DR Bgee; ENSG00000133107; Expressed in stromal cell of endometrium and 119 other tissues.
DR ExpressionAtlas; Q9UBN4; baseline and differential.
DR Genevisible; Q9UBN4; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:BHF-UCL.
DR GO; GO:0034704; C:calcium channel complex; IDA:UniProtKB.
DR GO; GO:0034703; C:cation channel complex; IBA:GO_Central.
DR GO; GO:0005901; C:caveola; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0030863; C:cortical cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; IPI:BHF-UCL.
DR GO; GO:0045296; F:cadherin binding; IPI:BHF-UCL.
DR GO; GO:0005262; F:calcium channel activity; TAS:Reactome.
DR GO; GO:0070679; F:inositol 1,4,5 trisphosphate binding; IBA:GO_Central.
DR GO; GO:0015279; F:store-operated calcium channel activity; IMP:UniProtKB.
DR GO; GO:0070509; P:calcium ion import; IDA:BHF-UCL.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006816; P:calcium ion transport; TAS:ProtInc.
DR GO; GO:0014051; P:gamma-aminobutyric acid secretion; IEA:Ensembl.
DR GO; GO:0006828; P:manganese ion transport; IBA:GO_Central.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; 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; IPR005460; TRPC4_channel.
DR InterPro; IPR002153; TRPC_channel.
DR PANTHER; PTHR10117; PTHR10117; 1.
DR PANTHER; PTHR10117:SF25; PTHR10117:SF25; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF08344; TRP_2; 1.
DR PRINTS; PR01097; TRNSRECEPTRP.
DR PRINTS; PR01645; TRPCHANNEL4.
DR SMART; SM00248; ANK; 2.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Calcium; Calcium channel;
KW Calcium transport; Cell membrane; Coiled coil; Ion channel; Ion transport;
KW Membrane; Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..977
FT /note="Short transient receptor potential channel 4"
FT /id="PRO_0000215314"
FT TOPO_DOM 1..329
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 330..350
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 351..362
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 363..383
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 384..436
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 437..457
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 458..469
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 470..490
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 491..511
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 512..532
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 533..599
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 600..620
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 621..977
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 31..60
FT /note="ANK 1"
FT REPEAT 69..97
FT /note="ANK 2"
FT REPEAT 98..124
FT /note="ANK 3"
FT REPEAT 141..170
FT /note="ANK 4"
FT REGION 87..172
FT /note="Multimerization domain"
FT /evidence="ECO:0000250"
FT REGION 254..304
FT /note="Multimerization domain"
FT /evidence="ECO:0000250"
FT REGION 615..977
FT /note="Binds to ITPR1, ITPR2 and ITPR3"
FT REGION 762..790
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 975..977
FT /note="PDZ-binding domain"
FT COILED 223..260
FT /evidence="ECO:0000255"
FT COMPBIAS 773..790
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 959
FT /note="Phosphotyrosine; by FYN"
FT /evidence="ECO:0000269|PubMed:16144838"
FT MOD_RES 972
FT /note="Phosphotyrosine; by FYN"
FT /evidence="ECO:0000269|PubMed:16144838"
FT VAR_SEQ 127..299
FT /note="Missing (in isoform Zeta)"
FT /evidence="ECO:0000303|PubMed:11713258"
FT /id="VSP_041439"
FT VAR_SEQ 300..323
FT /note="FVAQPNCQQLLASRWYDEFPGWRR -> ASYGEKLNRCGMADFRTTSMIGGI
FT (in isoform Eta)"
FT /evidence="ECO:0000303|PubMed:11713258"
FT /id="VSP_047747"
FT VAR_SEQ 324..977
FT /note="Missing (in isoform Eta)"
FT /evidence="ECO:0000303|PubMed:11713258"
FT /id="VSP_047748"
FT VAR_SEQ 629..693
FT /note="Missing (in isoform Gamma)"
FT /evidence="ECO:0000303|PubMed:11163362"
FT /id="VSP_006567"
FT VAR_SEQ 693
FT /note="G -> GVRTQH (in isoform Epsilon)"
FT /evidence="ECO:0000303|PubMed:11713258"
FT /id="VSP_041262"
FT VAR_SEQ 730..870
FT /note="Missing (in isoform Delta)"
FT /evidence="ECO:0000303|PubMed:11163362"
FT /id="VSP_006568"
FT VAR_SEQ 785..868
FT /note="Missing (in isoform Beta and isoform Gamma)"
FT /evidence="ECO:0000303|PubMed:11163362,
FT ECO:0000303|PubMed:11713258"
FT /id="VSP_006569"
FT VARIANT 138
FT /note="E -> K (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036452"
FT MUTAGEN 959
FT /note="Y->F: Reduced EGF-induced phosphorylation and
FT decreased association with SLC9A3R1/NHERF. Loss of EGF-
FT induced phosphorylation and decreased association with
FT SLC9A3R1/NHERF; when associated with F-972."
FT /evidence="ECO:0000269|PubMed:16144838"
FT MUTAGEN 972
FT /note="Y->F: Reduced EGF-induced phosphorylation and
FT decreased association with SLC9A3R1/NHERF. Loss of EGF-
FT induced phosphorylation and decreased association with
FT SLC9A3R1/NHERF; when associated with F-959."
FT /evidence="ECO:0000269|PubMed:16144838"
FT MUTAGEN 975..977
FT /note="Missing: Loss of interaction with SLC9A3R1/NHERF."
FT /evidence="ECO:0000269|PubMed:12154080"
SQ SEQUENCE 977 AA; 112101 MW; 77E4D27C374D660E CRC64;
MAQFYYKRNV NAPYRDRIPL RIVRAESELS PSEKAYLNAV EKGDYASVKK SLEEAEIYFK
ININCIDPLG RTALLIAIEN ENLELIELLL SFNVYVGDAL LHAIRKEVVG AVELLLNHKK
PSGEKQVPPI LLDKQFSEFT PDITPIILAA HTNNYEIIKL LVQKGVSVPR PHEVRCNCVE
CVSSSDVDSL RHSRSRLNIY KALASPSLIA LSSEDPFLTA FQLSWELQEL SKVENEFKSE
YEELSRQCKQ FAKDLLDQTR SSRELEIILN YRDDNSLIEE QSGNDLARLK LAIKYRQKEF
VAQPNCQQLL ASRWYDEFPG WRRRHWAVKM VTCFIIGLLF PVFSVCYLIA PKSPLGLFIR
KPFIKFICHT ASYLTFLFLL LLASQHIDRS DLNRQGPPPT IVEWMILPWV LGFIWGEIKQ
MWDGGLQDYI HDWWNLMDFV MNSLYLATIS LKIVAFVKYS ALNPRESWDM WHPTLVAEAL
FAIANIFSSL RLISLFTANS HLGPLQISLG RMLLDILKFL FIYCLVLLAF ANGLNQLYFY
YEETKGLTCK GIRCEKQNNA FSTLFETLQS LFWSIFGLIN LYVTNVKAQH EFTEFVGATM
FGTYNVISLV VLLNMLIAMM NNSYQLIADH ADIEWKFART KLWMSYFEEG GTLPTPFNVI
PSPKSLWYLI KWIWTHLCKK KMRRKPESFG TIGRRAADNL RRHHQYQEVM RNLVKRYVAA
MIRDAKTEEG LTEENFKELK QDISSFRFEV LGLLRGSKLS TIQSANASKE SSNSADSDEK
SDSEGNSKDK KKNFSLFDLT TLIHPRSAAI ASERHNISNG SALVVQEPPR EKQRKVNFVT
DIKNFGLFHR RSKQNAAEQN ANQIFSVSEE VARQQAAGPL ERNIQLESRG LASRGDLSIP
GLSEQCVLVD HRERNTDTLG LQVGKRVCPF KSEKVVVEDT VPIIPKEKHA KEEDSSIDYD
LNLPDTVTHE DYVTTRL
