ID   TRPC5_HUMAN             Reviewed;         973 AA.
AC   Q9UL62; B2RP53; O75233; Q5JXY8; Q9Y514;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   11-MAY-2016, entry version 143.
DE   RecName: Full=Short transient receptor potential channel 5;
DE            Short=TrpC5;
DE   AltName: Full=Transient receptor protein 5;
DE            Short=TRP-5;
DE            Short=hTRP-5;
DE            Short=hTRP5;
GN   Name=TRPC5; Synonyms=TRP5;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Fetal brain;
RX   PubMed=10493832; DOI=10.1006/geno.1999.5924;
RA   Sossey-Alaoui K., Lyon J.A., Jones L., Abidi F.E., Hartung A.J.,
RA   Hane B., Schwartz C.E., Stevenson R.E., Srivastava A.K.;
RT   "Molecular cloning and characterization of TRPC5 (HTRP5), the human
RT   homologue of a mouse brain receptor-activated capacitative Ca(2+)
RT   entry channel.";
RL   Genomics 60:330-340(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15772651; DOI=10.1038/nature03440;
RA   Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA   Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA   Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA   Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA   Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA   Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA   Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA   Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA   Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA   Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA   Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA   Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA   Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA   Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA   Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA   Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA   Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA   Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA   Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA   Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA   Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA   Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA   Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA   Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA   Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA   Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA   de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA   Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA   Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA   Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA   Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA   McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA   Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA   Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA   Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA   Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA   Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA   Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA   Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA   Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA   Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA   Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA   Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA   Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA   Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA   Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA   Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA   Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA   Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA   Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA   Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA   Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence of the human X chromosome.";
RL   Nature 434:325-337(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   TISSUE SPECIFICITY.
RX   PubMed=9687496; DOI=10.1093/emboj/17.15.4274;
RA   Philipp S., Hambrecht J., Braslavski L., Schroth G., Freichel M.,
RA   Murakami M., Cavalie A., Flockerzi V.;
RT   "A novel capacitative calcium entry channel expressed in excitable
RT   cells.";
RL   EMBO J. 17:4274-4282(1998).
RN   [6]
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
RT   channels in living cells.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:7461-7466(2002).
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-
RT   like repeat domain of TRPC.";
RL   J. Biol. Chem. 280:19393-19400(2005).
RN   [8]
RP   INTERACTION WITH CABP1.
RX   PubMed=15895247; DOI=10.1007/s00424-005-1419-1;
RA   Kinoshita-Kawada M., Tang J., Xiao R., Kaneko S., Foskett J.K.,
RA   Zhu M.X.;
RT   "Inhibition of TRPC5 channels by Ca2+-binding protein 1 in Xenopus
RT   oocytes.";
RL   Pflugers Arch. 450:345-354(2005).
RN   [9]
RP   FUNCTION AS CALCIUM CHANNEL, ENZYME REGULATION, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=16284075; DOI=10.1113/jphysiol.2005.097998;
RA   Shimizu S., Yoshida T., Wakamori M., Ishii M., Okada T., Takahashi M.,
RA   Seto M., Sakurada K., Kiuchi Y., Mori Y.;
RT   "Ca2+-calmodulin-dependent myosin light chain kinase is essential for
RT   activation of TRPC5 channels expressed in HEK293 cells.";
RL   J. Physiol. (Lond.) 570:219-235(2006).
RN   [10]
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
RT   retention of TRPC.";
RL   Cell Calcium 43:432-443(2008).
RN   [11]
RP   INTERACTION WITH SESTD1.
RX   PubMed=20164195; DOI=10.1074/jbc.M109.068304;
RA   Miehe S., Bieberstein A., Arnould I., Ihdene O., Rutten H.,
RA   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   [12]
RP   VARIANT THR-667.
RX   PubMed=23033978; DOI=10.1056/NEJMoa1206524;
RA   de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA   Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P.,
RA   Gilissen C., del Rosario M., Hoischen A., Scheffer H., de Vries B.B.,
RA   Brunner H.G., Veltman J.A., Vissers L.E.;
RT   "Diagnostic exome sequencing in persons with severe intellectual
RT   disability.";
RL   N. Engl. J. Med. 367:1921-1929(2012).
CC   -!- FUNCTION: Thought to form a receptor-activated non-selective
CC       calcium permeant cation channel. Probably is operated by a
CC       phosphatidylinositol second messenger system activated by receptor
CC       tyrosine kinases or G-protein coupled receptors. Has also been
CC       shown to be calcium-selective (By similarity). May also be
CC       activated by intracellular calcium store depletion. {ECO:0000250,
CC       ECO:0000269|PubMed:16284075}.
CC   -!- ENZYME REGULATION: Calcium channel activity is enhanced by MYLK,
CC       that promotes its subcellular localization at the plasma membrane.
CC       {ECO:0000269|PubMed:16284075}.
CC   -!- SUBUNIT: Interacts with TRPC4AP (By similarity). Homotetramer and
CC       heterotetramer with TRPC1 and/or TRPC4. Interacts with NHERF (By
CC       similarity). Interacts with MX1 and RNF24. Interacts (via C-
CC       terminus) with CABP1. Interacts with SESTD1 (via the spectrin 1
CC       repeat). {ECO:0000250, ECO:0000269|PubMed:12032305,
CC       ECO:0000269|PubMed:15757897, ECO:0000269|PubMed:15895247,
CC       ECO:0000269|PubMed:17850865, ECO:0000269|PubMed:20164195}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16284075};
CC       Multi-pass membrane protein {ECO:0000269|PubMed:16284075}.
CC   -!- TISSUE SPECIFICITY: Expressed in brain with higher levels in fetal
CC       brain. Found in cerebellum and occipital pole.
CC       {ECO:0000269|PubMed:9687496}.
CC   -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family.
CC       STrpC subfamily. TRPC5 sub-subfamily. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 4 ANK repeats. {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; AF054568; AAF00002.1; -; mRNA.
DR   EMBL; AC005191; AAC24563.1; -; Genomic_DNA.
DR   EMBL; AL049563; CAI43017.1; -; Genomic_DNA.
DR   EMBL; AC005191; CAI43017.1; JOINED; Genomic_DNA.
DR   EMBL; CH471120; EAX02630.1; -; Genomic_DNA.
DR   EMBL; BC137271; AAI37272.1; -; mRNA.
DR   EMBL; BC137274; AAI37275.1; -; mRNA.
DR   CCDS; CCDS14561.1; -.
DR   RefSeq; NP_036603.1; NM_012471.2.
DR   UniGene; Hs.657709; -.
DR   ProteinModelPortal; Q9UL62; -.
DR   SMR; Q9UL62; 45-180.
DR   BioGrid; 113075; 18.
DR   IntAct; Q9UL62; 1.
DR   STRING; 9606.ENSP00000262839; -.
DR   ChEMBL; CHEMBL1250411; -.
DR   GuidetoPHARMACOLOGY; 490; -.
DR   TCDB; 1.A.4.1.7; the transient receptor potential ca(2+) channel (trp-cc) family.
DR   iPTMnet; Q9UL62; -.
DR   PhosphoSite; Q9UL62; -.
DR   BioMuta; TRPC5; -.
DR   DMDM; 10720321; -.
DR   EPD; Q9UL62; -.
DR   MaxQB; Q9UL62; -.
DR   PaxDb; Q9UL62; -.
DR   PRIDE; Q9UL62; -.
DR   Ensembl; ENST00000262839; ENSP00000262839; ENSG00000072315.
DR   GeneID; 7224; -.
DR   KEGG; hsa:7224; -.
DR   UCSC; uc004epl.2; human.
DR   CTD; 7224; -.
DR   GeneCards; TRPC5; -.
DR   HGNC; HGNC:12337; TRPC5.
DR   HPA; HPA000510; -.
DR   MIM; 300334; gene.
DR   neXtProt; NX_Q9UL62; -.
DR   PharmGKB; PA37010; -.
DR   eggNOG; KOG3609; Eukaryota.
DR   eggNOG; ENOG410XQ0Y; LUCA.
DR   GeneTree; ENSGT00760000119180; -.
DR   HOGENOM; HOG000020589; -.
DR   HOVERGEN; HBG068337; -.
DR   InParanoid; Q9UL62; -.
DR   KO; K04968; -.
DR   OMA; NCSKSEI; -.
DR   OrthoDB; EOG72G17P; -.
DR   PhylomeDB; Q9UL62; -.
DR   TreeFam; TF313147; -.
DR   Reactome; R-HSA-3295583; TRP channels.
DR   Reactome; R-HSA-418890; Role of second messengers in netrin-1 signaling.
DR   ChiTaRS; TRPC5; human.
DR   GeneWiki; TRPC5; -.
DR   GenomeRNAi; 7224; -.
DR   NextBio; 28291; -.
DR   PRO; PR:Q9UL62; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   Bgee; Q9UL62; -.
DR   CleanEx; HS_TRPC5; -.
DR   Genevisible; Q9UL62; HS.
DR   GO; GO:0034704; C:calcium channel complex; IDA:UniProtKB.
DR   GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0005262; F:calcium channel activity; IDA:UniProtKB.
DR   GO; GO:0070679; F:inositol 1,4,5 trisphosphate binding; IEA:Ensembl.
DR   GO; GO:0015279; F:store-operated calcium channel activity; TAS:ProtInc.
DR   GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR   GO; GO:0070588; P:calcium ion transmembrane transport; TAS:Reactome.
DR   GO; GO:0006816; P:calcium ion transport; TAS:ProtInc.
DR   GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR   GO; GO:0006828; P:manganese ion transport; IBA:GO_Central.
DR   GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR   GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR   GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
DR   Gene3D; 1.25.40.20; -; 1.
DR   InterPro; IPR002110; Ankyrin_rpt.
DR   InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR   InterPro; IPR005821; Ion_trans_dom.
DR   InterPro; IPR004729; TRP_channel.
DR   InterPro; IPR013555; TRP_dom.
DR   InterPro; IPR005461; TRPC5_channel.
DR   InterPro; IPR002153; TRPC_channel.
DR   PANTHER; PTHR10117; PTHR10117; 1.
DR   PANTHER; PTHR10117:SF24; PTHR10117:SF24; 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; PR01646; TRPCHANNEL5.
DR   SMART; SM00248; ANK; 2.
DR   SUPFAM; SSF48403; SSF48403; 1.
DR   TIGRFAMs; TIGR00870; trp; 1.
PE   1: Evidence at protein level;
KW   ANK repeat; Calcium; Calcium channel; Calcium transport;
KW   Cell membrane; Complete proteome; Glycoprotein; Ion channel;
KW   Ion transport; Membrane; Polymorphism; Reference proteome; Repeat;
KW   Transmembrane; Transmembrane helix; Transport.
FT   CHAIN         1    973       Short transient receptor potential
FT                                channel 5.
FT                                /FTId=PRO_0000215318.
FT   TOPO_DOM      1    330       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    331    351       Helical. {ECO:0000255}.
FT   TOPO_DOM    352    398       Extracellular. {ECO:0000255}.
FT   TRANSMEM    399    419       Helical. {ECO:0000255}.
FT   TOPO_DOM    420    437       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    438    458       Helical. {ECO:0000255}.
FT   TOPO_DOM    459    470       Extracellular. {ECO:0000255}.
FT   TRANSMEM    471    491       Helical. {ECO:0000255}.
FT   TOPO_DOM    492    512       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    513    533       Helical. {ECO:0000255}.
FT   TOPO_DOM    534    603       Extracellular. {ECO:0000255}.
FT   TRANSMEM    604    624       Helical. {ECO:0000255}.
FT   TOPO_DOM    625    973       Cytoplasmic. {ECO:0000255}.
FT   REPEAT       31     60       ANK 1.
FT   REPEAT       69     97       ANK 2.
FT   REPEAT       98    124       ANK 3.
FT   REPEAT      141    170       ANK 4.
FT   REGION      971    973       Essential for binding to NHERF PDZ
FT                                domain. {ECO:0000250}.
FT   CARBOHYD    461    461       N-linked (GlcNAc...). {ECO:0000255}.
FT   VARIANT     667    667       P -> T (found in a patient with severe
FT                                delayed speech, autism spectrum and
FT                                Gilles de la Tourette disorders).
FT                                {ECO:0000269|PubMed:23033978}.
FT                                /FTId=VAR_069415.
FT   VARIANT     702    702       R -> H (in dbSNP:rs36047478).
FT                                /FTId=VAR_052369.
SQ   SEQUENCE   973 AA;  111412 MW;  FBC8CBF17BE42166 CRC64;
     MAQLYYKKVN YSPYRDRIPL QIVRAETELS AEEKAFLNAV EKGDYATVKQ ALQEAEIYYN
     VNINCMDPLG RSALLIAIEN ENLEIMELLL NHSVYVGDAL LYAIRKEVVG AVELLLSYRR
     PSGEKQVPTL MMDTQFSEFT PDITPIMLAA HTNNYEIIKL LVQKRVTIPR PHQIRCNCVE
     CVSSSEVDSL RHSRSRLNIY KALASPSLIA LSSEDPILTA FRLGWELKEL SKVENEFKAE
     YEELSQQCKL FAKDLLDQAR SSRELEIILN HRDDHSEELD PQKYHDLAKL KVAIKYHQKE
     FVAQPNCQQL LATLWYDGFP GWRRKHWVVK LLTCMTIGFL FPMLSIAYLI SPRSNLGLFI
     KKPFIKFICH TASYLTFLFM LLLASQHIVR TDLHVQGPPP TVVEWMILPW VLGFIWGEIK
     EMWDGGFTEY IHDWWNLMDF AMNSLYLATI SLKIVAYVKY NGSRPREEWE MWHPTLIAEA
     LFAISNILSS LRLISLFTAN SHLGPLQISL GRMLLDILKF LFIYCLVLLA FANGLNQLYF
     YYETRAIDEP NNCKGIRCEK QNNAFSTLFE TLQSLFWSVF GLLNLYVTNV KARHEFTEFV
     GATMFGTYNV ISLVVLLNML IAMMNNSYQL IADHADIEWK FARTKLWMSY FDEGGTLPPP
     FNIIPSPKSF LYLGNWFNNT FCPKRDPDGR RRRRNLRSFT ERNADSLIQN QHYQEVIRNL
     VKRYVAAMIR NSKTHEGLTE ENFKELKQDI SSFRYEVLDL LGNRKHPRSF STSSTELSQR
     DDNNDGSGGA RAKSKSVSFN LGCKKKTCHG PPLIRTMPRS SGAQGKSKAE SSSKRSFMGP
     SLKKLGLLFS KFNGHMSEPS SEPMYTISDG IVQQHCMWQD IRYSQMEKGK AEACSQSEIN
     LSEVELGEVQ GAAQSSECPL ACSSSLHCAS SICSSNSKLL DSSEDVFETW GEACDLLMHK
     WGDGQEEQVT TRL
//