Q9NQA5 (TRPV5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transient receptor potential cation channel subfamily V member 5
Short name=TrpV5

Alternative name(s):
Calcium transport protein 2
Short name=CaT2
Epithelial calcium channel 1
Short name=ECaC
Short name=ECaC1
Osm-9-like TRP channel 3
Short name=OTRPC3

Gene names

Name:	TRPV5
Synonyms:	ECAC1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	729 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Constitutively active calcium selective cation channel thought to be involved in Ca2+ reabsorption in kidney and intestine. The channel is activated by low internal calcium level and the current exhibits an inward rectification. A Ca2+-dependent feedback regulation includes fast channel inactivation and slow current decay. Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating By similarity. Ref.2
Enzyme regulation	Activated by WNK3. Ref.7
Subunit structure	Homotetramer and probably heterotetramer with TRPV6. Interacts with TRPV6. Interacts with S100A10 and probably with the ANAX2-S100A10 heterotetramer. The interaction with S100A10 is required for the trafficking to the plasma membrane. Interacts with calmodulin. Interacts with BSPRY, which results in its inactivation By similarity.
Subcellular location	Apical cell membrane; Multi-pass membrane protein. Note: Colocalized with S100A10 and ANAX2 along the apical domain of kidney distal tubular cells By similarity. The expression of the glycosylated form in the cell membrane is increased in the presence of WNK3. Ref.7
Tissue specificity	Expressed at high levels in kidney, small intestine and pancreas, and at lower levels in testis, prostate, placenta, brain, colon and rectum. Ref.1 Ref.2
Post-translational modification	Glycosylated. Ref.7
Sequence similarities	Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV5 sub-subfamily. [View classification] Contains 5 ANK repeats.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	ANK repeat Repeat Transmembrane Transmembrane helix
Ligand	Calcium Calmodulin-binding
Molecular function	Calcium channel Ion channel
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein tetramerization Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Inferred from direct assay PubMed 15489237. Source: UniProtKB
Molecular_function	calcium channel activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 729	729	Transient receptor potential cation channel subfamily V member 5		PRO_0000215350
Regions
	Topological domain	1 – 328	328	Cytoplasmic Potential
	Transmembrane	329 – 349	21	Helical; Potential
	Topological domain	350 – 387	38	Extracellular Potential
	Transmembrane	388 – 408	21	Helical; Potential
	Topological domain	409 – 419	11	Cytoplasmic Potential
	Transmembrane	420 – 440	21	Helical; Potential
	Topological domain	441 – 448	8	Extracellular Potential
	Transmembrane	449 – 469	21	Helical; Potential
	Topological domain	470 – 492	23	Cytoplasmic Potential
	Transmembrane	493 – 513	21	Helical; Potential
	Intramembrane	524 – 544	21	Pore-forming; Probable
	Transmembrane	557 – 577	21	Helical; Potential
	Topological domain	578 – 729	152	Cytoplasmic Potential
	Repeat	44 – 74	31	ANK 1
	Repeat	78 – 107	30	ANK 2
	Repeat	116 – 145	30	ANK 3
	Repeat	162 – 191	30	ANK 4
	Repeat	239 – 268	30	ANK 5
	Region	598 – 602	5	Interaction with S100A10 By similarity
	Region	650 – 653	4	Involved in Ca(2+)-dependent inactivation By similarity
	Region	700 – 729	30	Involved in Ca(2+)-dependent inactivation By similarity
Amino acid modifications
	Glycosylation	358	1	N-linked (GlcNAc...) Ref.7
Natural variations
	Natural variant	8	1	A → V. Ref.4 Corresponds to variant rs4252372 [ dbSNP | Ensembl ].		VAR_022247
	Natural variant	154	1	R → H. Ref.3 Ref.4 Corresponds to variant rs4236480 [ dbSNP | Ensembl ].		VAR_022248
	Natural variant	563	1	A → T. Ref.4 Corresponds to variant rs4252499 [ dbSNP | Ensembl ].		VAR_022249
	Natural variant	712	1	L → F. Ref.4 Corresponds to variant rs4252509 [ dbSNP | Ensembl ].		VAR_022250
Experimental info
	Mutagenesis	358	1	N → Q: Loss of glycosylation. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Q9NQA5 [UniParc]. Last modified March 1, 2002. Version 2. Checksum: A10FB80205FD0DBB	FASTA	729	82,551
	10 20 30 40 50 60 MGGFLPKAEG PGSQLQKLLP SFLVREQDWD QHLDKLHMLQ QKRILESPLL RASKENDLSV 70 80 90 100 110 120 LRQLLLDCTC DVRQRGALGE TALHIAALYD NLEAALVLME AAPELVFEPT TCEAFAGQTA 130 140 150 160 170 180 LHIAVVNQNV NLVRALLTRR ASVSARATGT AFRRSPRNLI YFGEHPLSFA ACVNSEEIVR 190 200 210 220 230 240 LLIEHGADIR AQDSLGNTVL HILILQPNKT FACQMYNLLL SYDGHGDHLQ PLDLVPNHQG 250 260 270 280 290 300 LTPFKLAGVE GNTVMFQHLM QKRRHIQWTY GPLTSILYDL TEIDSWGEEL SFLELVVSSD 310 320 330 340 350 360 KREARQILEQ TPVKELVSFK WNKYGRPYFC ILAALYLLYM ICFTTCCVYR PLKFRGGNRT 370 380 390 400 410 420 HSRDITILQQ KLLQEAYETR EDIIRLVGEL VSIVGAVIIL LLEIPDIFRV GASRYFGKTI 430 440 450 460 470 480 LGGPFHVIII TYASLVLVTM VMRLTNTNGE VVPMSFALVL GWCSVMYFTR GFQMLGPFTI 490 500 510 520 530 540 MIQKMIFGDL MRFCWLMAVV ILGFASAFYI IFQTEDPTSL GQFYDYPMAL FTTFELFLTV 550 560 570 580 590 600 IDAPANYDVD LPFMFSIVNF AFAIIATLLM LNLFIAMMGD THWRVAQERD ELWRAQVVAT 610 620 630 640 650 660 TVMLERKLPR CLWPRSGICG CEFGLGDRWF LRVENHNDQN PLRVLRYVEV FKNSDKEDDQ 670 680 690 700 710 720 EHPSEKQPSG AESGTLARAS LALPTSSLSR TASQSSSHRG WEILRQNTLG HLNLGLNLSE GDGEEVYHF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, tissue distribution, and chromosomal mapping of the human epithelial calcium channel (ECAC1)." Mueller D., Hoenderop J.G., Meij I.C., van den Heuvel L.P.J., Knoers N.V., den Hollander A.I., Eggert P., Garcia-Nieto V., Claverie-Martin F., Bindels R.J.M. Genomics 67:48-53(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]	"Structural conservation of the genes encoding CaT1, CaT2, and related cation channels." Peng J.-B., Brown E.M., Hediger M.A. Genomics 76:99-109(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
[3]	Kelsell R.E. Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT HIS-154.
[4]	SeattleSNPs variation discovery resource Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-8; HIS-154; THR-563 AND PHE-712.
[5]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"WNK3 positively regulates epithelial calcium channels TRPV5 and TRPV6 via a kinase-dependent pathway." Zhang W., Na T., Peng J.B. Am. J. Physiol. 295:F1472-F1484(2008) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-358, SUBCELLULAR LOCATION, ENZYME REGULATION, MUTAGENESIS OF ASN-358.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ271207 mRNA. Translation: CAB96365.2. AF304464 mRNA. Translation: AAL04015.1. AJ487965 mRNA. Translation: CAD32312.2. AY206695 Genomic DNA. Translation: AAO13488.1. CH236959 Genomic DNA. Translation: EAL23777.1. CH471198 Genomic DNA. Translation: EAW51896.1.
IPI	IPI00302133.
RefSeq	NP_062815.2. NM_019841.4.
UniGene	Hs.283369.
3D structure databases
ProteinModelPortal	Q9NQA5.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1470011.
STRING	9606.ENSP00000265310.
Protein family/group databases
TCDB	1.A.4.2.10. transient receptor potential Ca2+ channel (TRP-CC) family.
PTM databases
PhosphoSite	Q9NQA5.
Polymorphism databases
DMDM	62901471.
Proteomic databases
PaxDb	Q9NQA5.
PRIDE	Q9NQA5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265310; ENSP00000265310; ENSG00000127412. ENST00000566839; ENSP00000457041; ENSG00000261264.
GeneID	56302.
KEGG	hsa:56302.
UCSC	uc003wby.1. human.
Organism-specific databases
CTD	56302.
GeneCards	GC07M142606.
HGNC	HGNC:3145. TRPV5.
MIM	606679. gene.
neXtProt	NX_Q9NQA5.
PharmGKB	PA35045.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG278734.
HOGENOM	HOG000234397.
HOVERGEN	HBG061442.
InParanoid	Q9NQA5.
KO	K04974.
OMA	ENHHDQN.
OrthoDB	EOG4SBDXG.
PhylomeDB	Q9NQA5.
Gene expression databases
ArrayExpress	Q9NQA5.
Bgee	Q9NQA5.
CleanEx	HS_TRPV5.
Genevestigator	Q9NQA5.
GermOnline	ENSG00000127412. Homo sapiens.
Family and domain databases
Gene3D	1.25.40.20. 2 hits.
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR005821. Ion_trans_dom. IPR004729. TRP_channel. IPR008344. TRPV5/TRPV6_channel. IPR008346. TRPV5_channel. IPR024862. TRPV_channel. [Graphical view]
PANTHER	PTHR10582. PTHR10582. 1 hit. PTHR10582:SF11. PTHR10582:SF11. 1 hit.
Pfam	PF12796. Ank_2. 2 hits. PF00520. Ion_trans. 1 hit. [Graphical view]
PRINTS	PR01415. ANKYRIN. PR01765. ECACCHANNEL. PR01767. ECACCHANNEL2.
SMART	SM00248. ANK. 5 hits. [Graphical view]
SUPFAM	SSF48403. ANK. 1 hit.
TIGRFAMs	TIGR00870. trp. 1 hit.
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1628474.
GenomeRNAi	56302.
NextBio	61971.
SOURCE	Search...

Entry information

Entry name

TRPV5_HUMAN

Accession

Primary (citable) accession number: Q9NQA5
Secondary accession number(s): A4D2H7 , Q8NDW5, Q8NDX7, Q8NDX8, Q96PM6

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2005
Last sequence update:	March 1, 2002
Last modified:	May 1, 2013
This is version 104 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.