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Q13507 (TRPC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Short transient receptor potential channel 3

Short name=TrpC3
Alternative name(s):
Transient receptor protein 3
Short name=TRP-3
Short name=hTrp-3
Short name=hTrp3
Gene names
Name:TRPC3
Synonyms:TRP3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length836 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, and by inositol 1,4,5-triphosphate receptors (ITPR) with bound IP3. May also be activated by internal calcium store depletion. Ref.1 Ref.9 Ref.11 Ref.15

Subunit structure

Interacts with TRPC1, ITPR1, ITPR3, MX1 and RNF24. Interacts with JPH2; the interaction is involved in maintaining Ca2+ homeostasis in skeletal muscle and is mediated by JPH2 'Ser-165' phosphorylation. Ref.10 Ref.12 Ref.13 Ref.14 Ref.15

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Expressed predominantly in brain and at much lower levels in ovary, colon, small intestine, lung, prostate, placenta and testis.

Sequence similarities

Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC3 sub-subfamily. [View classification]

Contains 4 ANK repeats.

Ontologies

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

Traceable author statement. Source: Reactome

blood coagulation

Traceable author statement. Source: Reactome

calcium ion transmembrane transport

Inferred from direct assay PubMed 21062895. Source: UniProtKB

calcium ion transport

Traceable author statement Ref.2. Source: ProtInc

ion transmembrane transport

Traceable author statement. Source: Reactome

phototransduction

Traceable author statement Ref.2. Source: ProtInc

platelet activation

Traceable author statement. Source: Reactome

positive regulation of calcium ion transport into cytosol

Inferred from direct assay PubMed 21062895. Source: UniProtKB

response to ATP

Inferred from direct assay PubMed 21062895. Source: UniProtKB

response to calcium ion

Inferred from direct assay PubMed 21062895. Source: UniProtKB

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentintegral component of plasma membrane

Inferred from direct assay PubMed 9368034. Source: MGI

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functioncalcium channel activity

Traceable author statement Ref.11. Source: ProtInc

inositol 1,4,5 trisphosphate binding

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

protein binding

Inferred from physical interaction Ref.15. Source: UniProtKB

store-operated calcium channel activity

Traceable author statement Ref.2. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ITPR3Q145735EBI-520807,EBI-351055
MX1P205912EBI-520807,EBI-929476
Plcg1P106862EBI-520807,EBI-520788From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13507-1)

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: Q13507-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MSTKVRKCKE...SPSLRRMTVM
Isoform 3 (identifier: Q13507-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MEGSPSLRRMTVM

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 836836Short transient receptor potential channel 3
PRO_0000215310

Regions

Topological domain1 – 369369Cytoplasmic Potential
Transmembrane370 – 39021Helical; Potential
Topological domain391 – 41828Extracellular Potential
Transmembrane419 – 43921Helical; Potential
Topological domain440 – 45112Cytoplasmic Potential
Transmembrane452 – 47221Helical; Potential
Topological domain473 – 52351Extracellular Potential
Transmembrane524 – 54421Helical; Potential
Topological domain545 – 56723Cytoplasmic Potential
Transmembrane568 – 58821Helical; Potential
Topological domain589 – 63749Extracellular Potential
Transmembrane638 – 65821Helical; Potential
Topological domain659 – 836178Cytoplasmic Potential
Repeat26 – 5530ANK 1
Repeat61 – 9030ANK 2
Repeat92 – 11827ANK 3
Repeat147 – 17630ANK 4
Region765 – 78521Binds to IP3R3

Amino acid modifications

Glycosylation4041N-linked (GlcNAc...) Ref.8

Natural variations

Alternative sequence11M → MSTKVRKCKEQARVTFPAPE EEEDEGEDEGAEPQRRRRGW RGVNGGLEPRSAPSQREPHG YCPPPFSHGPDLSMEGSPSL RRMTVM in isoform 2.
VSP_042446
Alternative sequence11M → MEGSPSLRRMTVM in isoform 3.
VSP_042445

Experimental info

Sequence conflict5251I → L in BAF76424. Ref.4
Sequence conflict6621Y → C in BAF76424. Ref.4

Sequences

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

Last modified May 3, 2011. Version 3.
Checksum: 4179CB3DA8B3F508

FASTA83696,009
        10         20         30         40         50         60 
MREKGRRQAV RGPAFMFNDR GTSLTAEEER FLDAAEYGNI PVVRKMLEES KTLNVNCVDY 

        70         80         90        100        110        120 
MGQNALQLAV GNEHLEVTEL LLKKENLARI GDALLLAISK GYVRIVEAIL NHPGFAASKR 

       130        140        150        160        170        180 
LTLSPCEQEL QDDDFYAYDE DGTRFSPDIT PIILAAHCQK YEVVHMLLMK GARIERPHDY 

       190        200        210        220        230        240 
FCKCGDCMEK QRHDSFSHSR SRINAYKGLA SPAYLSLSSE DPVLTALELS NELAKLANIE 

       250        260        270        280        290        300 
KEFKNDYRKL SMQCKDFVVG VLDLCRDSEE VEAILNGDLE SAEPLEVHRH KASLSRVKLA 

       310        320        330        340        350        360 
IKYEVKKFVA HPNCQQQLLT IWYENLSGLR EQTIAIKCLV VLVVALGLPF LAIGYWIAPC 

       370        380        390        400        410        420 
SRLGKILRSP FMKFVAHAAS FIIFLGLLVF NASDRFEGIT TLPNITVTDY PKQIFRVKTT 

       430        440        450        460        470        480 
QFTWTEMLIM VWVLGMMWSE CKELWLEGPR EYILQLWNVL DFGMLSIFIA AFTARFLAFL 

       490        500        510        520        530        540 
QATKAQQYVD SYVQESDLSE VTLPPEIQYF TYARDKWLPS DPQIISEGLY AIAVVLSFSR 

       550        560        570        580        590        600 
IAYILPANES FGPLQISLGR TVKDIFKFMV LFIMVFFAFM IGMFILYSYY LGAKVNAAFT 

       610        620        630        640        650        660 
TVEESFKTLF WSIFGLSEVT SVVLKYDHKF IENIGYVLYG IYNVTMVVVL LNMLIAMINS 

       670        680        690        700        710        720 
SYQEIEDDSD VEWKFARSKL WLSYFDDGKT LPPPFSLVPS PKSFVYFIMR IVNFPKCRRR 

       730        740        750        760        770        780 
RLQKDIEMGM GNSKSRLNLF TQSNSRVFES HSFNSILNQP TRYQQIMKRL IKRYVLKAQV 

       790        800        810        820        830 
DKENDEVNEG ELKEIKQDIS SLRYELLEDK SQATEELAIL IHKLSEKLNP SMLRCE 

« Hide

Isoform 2 [UniParc].

Checksum: 8D7E0D144EF4BE51
Show »

FASTA921105,538
Isoform 3 [UniParc].

Checksum: 1DBC92BC941DF416
Show »

FASTA84897,355

References

« Hide 'large scale' references
[1]"trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry."
Zhu X., Jiang M., Peyton M., Boulay G., Hurst R., Stefani E., Birnbaumer L.
Cell 85:661-671(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION.
Tissue: Embryonic kidney.
[2]"Coassembly of TRP and TRPL produces a distinct store-operated conductance."
Xu X.-Z.S., Li H.-S., Guggino W.B., Montell C.
Cell 89:1155-1164(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[3]"Molecular cloning of TRPC3a, an N-terminally extended, store-operated variant of the human C3 transient receptor potential channel."
Yildirim E., Kawasaki B.T., Birnbaumer L.
Proc. Natl. Acad. Sci. U.S.A. 102:3307-3311(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]"Molecular cloning of novel TRPC3 isoform."
Yamazaki D., Yamamura H., Ohya S., Asai K., Imaizumi Y.
Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
Tissue: Brain.
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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 3).
Tissue: Brain.
[7]"TRPC1, a human homolog of a Drosophila store-operated channel."
Wes P.D., Chevesich J., Jeromin A., Rosenberg C., Stetten G., Montell C.
Proc. Natl. Acad. Sci. U.S.A. 92:9652-9656(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 620-735 (ISOFORMS 1/2/3).
Tissue: Fetal brain.
[8]"The membrane topology of human transient receptor potential 3 as inferred from glycosylation-scanning mutagenesis and epitope immunocytochemistry."
Vannier B., Zhu X., Brown D., Birnbaumer L.
J. Biol. Chem. 273:8675-8679(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-404, MEMBRANE TOPOLOGY.
[9]"Receptor-activated Ca2+ influx via human Trp3 stably expressed in human embryonic kidney (HEK)293 cells. Evidence for a non-capacitative Ca2+ entry."
Zhu X., Jiang M., Birnbaumer L.
J. Biol. Chem. 273:133-142(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Functional interaction between InsP3 receptors and store-operated Htrp3 channels."
Kiselyov K., Xu X., Mozhayeva G., Kuo T., Pessah I., Mignery G., Zhu X., Birnbaumer L., Muallem S.
Nature 396:478-482(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ITPR1.
[11]"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: FUNCTION.
[12]"Modulation of Ca(2+) entry by polypeptides of the inositol 1,4, 5-trisphosphate receptor (IP3R) that bind transient receptor potential (TRP): evidence for roles of TRP and IP3R in store depletion-activated Ca(2+) entry."
Boulay G., Brown D.M., Qin N., Jiang M., Dietrich A., Zhu M.X., Chen Z., Birnbaumer M., Mikoshiba K., Birnbaumer L.
Proc. Natl. Acad. Sci. U.S.A. 96:14955-14960(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ITPR3.
[13]"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.
[14]"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.
[15]"S165F mutation of junctophilin 2 affects Ca2+ signalling in skeletal muscle."
Woo J.S., Hwang J.H., Ko J.K., Weisleder N., Kim do H., Ma J., Lee E.H.
Biochem. J. 427:125-134(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH JPH2, FUNCTION.
[16]"The TRPC3 channel has a large internal chamber surrounded by signal sensing antennas."
Mio K., Ogura T., Kiyonaka S., Hiroaki Y., Tanimura Y., Fujiyoshi Y., Mori Y., Sato C.
J. Mol. Biol. 367:373-383(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ELECTRON MICROSCOPY (15 ANGSTROM), MEMBRANE TOPOLOGY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U47050 mRNA. Translation: AAC51653.1.
Y13758 mRNA. Translation: CAA74083.1.
AY865574 mRNA. Translation: AAW62292.1.
AB255424 mRNA. Translation: BAF76424.1.
AC079341 Genomic DNA. No translation available.
AC108930 Genomic DNA. No translation available.
BC093682 mRNA. Translation: AAH93682.1.
BC093684 mRNA. Translation: AAH93684.1.
X89068 mRNA. Translation: CAA61448.1.
CCDSCCDS3725.1. [Q13507-3]
CCDS47130.1. [Q13507-2]
RefSeqNP_001124170.1. NM_001130698.1. [Q13507-2]
NP_003296.1. NM_003305.2. [Q13507-3]
UniGeneHs.150981.

3D structure databases

ProteinModelPortalQ13507.
SMRQ13507. Positions 29-172.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113073. 8 interactions.
DIPDIP-34311N.
IntActQ13507. 3 interactions.
STRING9606.ENSP00000368966.

Chemistry

ChEMBLCHEMBL2417348.
GuidetoPHARMACOLOGY488.

Protein family/group databases

TCDB1.A.4.1.4. the transient receptor potential ca(2+) channel (trp-cc) family.

Polymorphism databases

DMDM332278239.

Proteomic databases

PaxDbQ13507.
PRIDEQ13507.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264811; ENSP00000264811; ENSG00000138741. [Q13507-3]
ENST00000379645; ENSP00000368966; ENSG00000138741. [Q13507-2]
GeneID7222.
KEGGhsa:7222.
UCSCuc003ief.2. human. [Q13507-3]
uc003ieg.2. human. [Q13507-2]
uc011cgl.1. human. [Q13507-1]

Organism-specific databases

CTD7222.
GeneCardsGC04M122800.
HGNCHGNC:12335. TRPC3.
HPAHPA037969.
MIM602345. gene.
neXtProtNX_Q13507.
PharmGKBPA37008.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG254238.
HOGENOMHOG000020590.
HOVERGENHBG068337.
InParanoidQ13507.
KOK04966.
OMALRRKTVM.
OrthoDBEOG77HDD1.
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

ArrayExpressQ13507.
BgeeQ13507.
CleanExHS_TRPC3.
GenevestigatorQ13507.

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.
IPR005459. TRPC3_channel.
IPR002153. TRPC_channel.
[Graphical view]
PANTHERPTHR10117. PTHR10117. 1 hit.
PTHR10117:SF8. PTHR10117:SF8. 1 hit.
PfamPF12796. Ank_2. 1 hit.
PF00520. Ion_trans. 1 hit.
PF08344. TRP_2. 1 hit.
[Graphical view]
PRINTSPR01097. TRNSRECEPTRP.
PR01644. TRPCHANNEL3.
SMARTSM00248. ANK. 3 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
TIGRFAMsTIGR00870. trp. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTRPC3. human.
GeneWikiTRPC3.
GenomeRNAi7222.
NextBio28283.
PROQ13507.
SOURCESearch...

Entry information

Entry nameTRPC3_HUMAN
AccessionPrimary (citable) accession number: Q13507
Secondary accession number(s): A7VJS1 expand/collapse secondary AC list , E9PCJ9, O00593, Q15660, Q52M35, Q5G1L5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 3, 2011
Last modified: July 9, 2014
This is version 141 of the entry and version 3 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 chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM