TRPV5_RABIT
ID TRPV5_RABIT Reviewed; 730 AA.
AC Q9XSM3;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Transient receptor potential cation channel subfamily V member 5;
DE Short=TrpV5;
DE AltName: Full=Epithelial calcium channel 1 {ECO:0000303|PubMed:10085067, ECO:0000303|PubMed:12634930};
DE Short=ECaC1 {ECO:0000303|PubMed:10085067, ECO:0000303|PubMed:12634930};
DE AltName: Full=Osm-9-like TRP channel 3;
DE Short=OTRPC3;
GN Name=Trpv5; Synonyms=Ecac1 {ECO:0000303|PubMed:12634930};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=New Zealand white; TISSUE=Kidney;
RX PubMed=10085067; DOI=10.1074/jbc.274.13.8375;
RA Hoenderop J.G.J., van der Kemp A.W.C.M., Hartog A., van de Graaf S.F.J.,
RA van Os C.H., Willems P.H.G.M., Bindels R.J.M.;
RT "Molecular identification of the apical Ca2+ channel in 1, 25-
RT dihydroxyvitamin D3-responsive epithelia.";
RL J. Biol. Chem. 274:8375-8378(1999).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF CHANNEL PORE, AND
RP MUTAGENESIS OF GLU-535; ASP-542 AND ASP-550.
RX PubMed=11035011; DOI=10.1074/jbc.m006184200;
RA Nilius B., Vennekens R., Prenen J., Hoenderop J.G., Droogmans G.,
RA Bindels R.J.M.;
RT "The single pore residue Asp542 determines Ca2+ permeation and Mg2+ block
RT of the epithelial Ca2+ channel.";
RL J. Biol. Chem. 276:1020-1025(2001).
RN [3]
RP FUNCTION, SUBUNIT, INTERACTION WITH TRPV6, SUBCELLULAR LOCATION, AND
RP GLYCOSYLATION.
RX PubMed=12574114; DOI=10.1093/emboj/cdg080;
RA Hoenderop J.G., Voets T., Hoefs S., Weidema F., Prenen J., Nilius B.,
RA Bindels R.J.M.;
RT "Homo- and heterotetrameric architecture of the epithelial Ca2+ channels
RT TRPV5 and TRPV6.";
RL EMBO J. 22:776-785(2003).
RN [4]
RP DOMAIN.
RX PubMed=12634930; DOI=10.1007/s00424-002-0923-9;
RA Nilius B., Weidema F., Prenen J., Hoenderop J.G., Vennekens R., Hoefs S.,
RA Droogmans G., Bindels R.J.M.;
RT "The carboxyl terminus of the epithelial Ca(2+) channel ECaC1 is involved
RT in Ca(2+)-dependent inactivation.";
RL Pflugers Arch. 445:584-588(2003).
RN [5] {ECO:0007744|PDB:6B5V}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.80 ANGSTROMS) IN COMPLEX WITH THE
RP INHIBITOR ECONAZOLE AND CALCIUM IONS, FUNCTION, SUBCELLULAR LOCATION,
RP TOPOLOGY, SUBUNIT, AND MUTAGENESIS OF PHE-425.
RX PubMed=29323279; DOI=10.1038/s41594-017-0009-1;
RA Hughes T.E.T., Lodowski D.T., Huynh K.W., Yazici A., Del Rosario J.,
RA Kapoor A., Basak S., Samanta A., Han X., Chakrapani S., Zhou Z.H.,
RA Filizola M., Rohacs T., Han S., Moiseenkova-Bell V.Y.;
RT "Structural basis of TRPV5 channel inhibition by econazole revealed by
RT cryo-EM.";
RL Nat. Struct. Mol. Biol. 25:53-60(2018).
CC -!- FUNCTION: Constitutively active calcium selective cation channel
CC thought to be involved in Ca(2+) reabsorption in kidney and intestine
CC (PubMed:10085067, PubMed:11035011, PubMed:12574114, PubMed:29323279).
CC Required for normal Ca(2+) reabsorption in the kidney distal convoluted
CC tubules (By similarity). The channel is activated by low internal
CC calcium level and the current exhibits an inward rectification
CC (PubMed:29323279). A Ca(2+)-dependent feedback regulation includes fast
CC channel inactivation and slow current decay (PubMed:11035011).
CC Heteromeric assembly with TRPV6 seems to modify channel properties.
CC TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent
CC gating (PubMed:12574114). {ECO:0000250|UniProtKB:P69744,
CC ECO:0000250|UniProtKB:Q9NQA5, ECO:0000269|PubMed:10085067,
CC ECO:0000269|PubMed:11035011, ECO:0000269|PubMed:12574114,
CC ECO:0000269|PubMed:29323279}.
CC -!- ACTIVITY REGULATION: Activated by WNK3. {ECO:0000250|UniProtKB:Q9NQA5}.
CC -!- SUBUNIT: Homotetramer (PubMed:29323279). Probably forms heterotetramers
CC with TRPV6 (PubMed:12574114). Interacts with TRPV6 (PubMed:12574114).
CC Interacts with S100A10 and probably with the ANAX2-S100A10
CC heterotetramer. The interaction with S100A10 is required for the
CC trafficking to the plasma membrane. Interacts with calmodulin.
CC Interacts with BSPRY, which results in its inactivation.
CC {ECO:0000250|UniProtKB:P69744, ECO:0000269|PubMed:12574114,
CC ECO:0000269|PubMed:29323279}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10085067,
CC ECO:0000269|PubMed:11035011, ECO:0000269|PubMed:12574114,
CC ECO:0000269|PubMed:29323279}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:29323279}. Apical cell membrane
CC {ECO:0000269|PubMed:10085067}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:29323279}. Note=Colocalized with S100A10 and ANAX2
CC along the apical domain of kidney distal tubular cells (By similarity).
CC The expression of the glycosylated form in the cell membrane is
CC increased in the presence of WNK3 (By similarity).
CC {ECO:0000250|UniProtKB:P69744, ECO:0000250|UniProtKB:Q9NQA5}.
CC -!- TISSUE SPECIFICITY: Detected in kidney cortex, in distal convoluted
CC tubules and cortical collecting ducts (at protein level)
CC (PubMed:10085067). Detected in duodenum, jejunum, ileum, kidney and
CC placenta (PubMed:10085067). {ECO:0000269|PubMed:10085067}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:12574114}.
CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. TrpV
CC subfamily. TRPV5 sub-subfamily. {ECO:0000305}.
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DR EMBL; AJ133128; CAB40138.1; -; mRNA.
DR RefSeq; NP_001076126.1; NM_001082657.1.
DR PDB; 6B5V; EM; 4.80 A; A/B/C/D=1-730.
DR PDB; 6DMR; EM; 3.90 A; A/B/C/D=1-730.
DR PDB; 6DMU; EM; 4.00 A; A/B/C/D=1-730.
DR PDB; 6DMW; EM; 4.40 A; A/B/C/D=1-730.
DR PDB; 6O1N; EM; 2.90 A; A/B/C/D=1-730.
DR PDB; 6O1P; EM; 3.00 A; A/B/C/D=1-730.
DR PDB; 6O1U; EM; 2.80 A; A/B/C/D=1-730.
DR PDB; 6O20; EM; 3.30 A; A/B/C/D/E=1-730.
DR PDB; 6PBE; EM; 3.78 A; A/B/C/D=1-730.
DR PDB; 6PBF; EM; 4.20 A; A/B/C/D=1-730.
DR PDBsum; 6B5V; -.
DR PDBsum; 6DMR; -.
DR PDBsum; 6DMU; -.
DR PDBsum; 6DMW; -.
DR PDBsum; 6O1N; -.
DR PDBsum; 6O1P; -.
DR PDBsum; 6O1U; -.
DR PDBsum; 6O20; -.
DR PDBsum; 6PBE; -.
DR PDBsum; 6PBF; -.
DR AlphaFoldDB; Q9XSM3; -.
DR SMR; Q9XSM3; -.
DR DIP; DIP-46154N; -.
DR IntAct; Q9XSM3; 1.
DR STRING; 9986.ENSOCUP00000006536; -.
DR TCDB; 1.A.4.2.3; the transient receptor potential ca(2+) channel (trp-cc) family.
DR iPTMnet; Q9XSM3; -.
DR Ensembl; ENSOCUT00000007559; ENSOCUP00000006536; ENSOCUG00000007559.
DR GeneID; 100009364; -.
DR KEGG; ocu:100009364; -.
DR CTD; 56302; -.
DR eggNOG; KOG3676; Eukaryota.
DR GeneTree; ENSGT00940000161809; -.
DR HOGENOM; CLU_012795_2_0_1; -.
DR InParanoid; Q9XSM3; -.
DR OMA; SFKWRKY; -.
DR OrthoDB; 693004at2759; -.
DR TreeFam; TF314711; -.
DR Proteomes; UP000001811; Chromosome 7.
DR Bgee; ENSOCUG00000007559; Expressed in kidney and 4 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005262; F:calcium channel activity; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0055074; P:calcium ion homeostasis; ISS:UniProtKB.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; IDA:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0035809; P:regulation of urine volume; ISS:UniProtKB.
DR Gene3D; 1.25.40.20; -; 2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR024862; TRPV.
DR InterPro; IPR008346; TRPV5.
DR InterPro; IPR008344; TRPV5/TRPV6.
DR PANTHER; PTHR10582; PTHR10582; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF13637; Ank_4; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR PRINTS; PR01415; ANKYRIN.
DR PRINTS; PR01765; ECACCHANNEL.
DR PRINTS; PR01767; ECACCHANNEL2.
DR SMART; SM00248; ANK; 5.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 2.
PE 1: Evidence at protein level;
KW 3D-structure; ANK repeat; Calcium; Calcium channel; Calcium transport;
KW Calmodulin-binding; Cell membrane; Glycoprotein; Ion channel;
KW Ion transport; Membrane; Metal-binding; Phosphoprotein; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..730
FT /note="Transient receptor potential cation channel
FT subfamily V member 5"
FT /id="PRO_0000215352"
FT TOPO_DOM 1..327
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29323279"
FT TRANSMEM 328..348
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29323279"
FT TOPO_DOM 349..385
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29323279"
FT TRANSMEM 386..408
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29323279"
FT TOPO_DOM 409..419
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29323279"
FT TRANSMEM 420..442
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29323279"
FT TOPO_DOM 443..448
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29323279"
FT TRANSMEM 449..469
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29323279"
FT TOPO_DOM 470..492
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29323279"
FT TRANSMEM 493..513
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29323279"
FT INTRAMEM 524..544
FT /note="Pore-forming"
FT /evidence="ECO:0000269|PubMed:29323279"
FT TRANSMEM 557..577
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29323279"
FT TOPO_DOM 578..730
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29323279"
FT REPEAT 44..74
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 78..107
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 116..145
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 162..191
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 195..228
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REPEAT 239..268
FT /note="ANK 6"
FT /evidence="ECO:0000255"
FT REGION 598..602
FT /note="Interaction with S100A10"
FT /evidence="ECO:0000250|UniProtKB:P69744"
FT REGION 650..653
FT /note="Involved in Ca(2+)-dependent inactivation"
FT REGION 701..730
FT /note="Involved in Ca(2+)-dependent inactivation"
FT BINDING 542
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000269|PubMed:29323279"
FT MOD_RES 685
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P69744"
FT MOD_RES 689
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P69744"
FT CARBOHYD 358
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 425
FT /note="F->A: Decreased inhibition by the synthetic drug
FT econazole."
FT /evidence="ECO:0000269|PubMed:29323279"
FT MUTAGEN 535
FT /note="E->A: Minor effects on Ca(2+) permeation."
FT /evidence="ECO:0000269|PubMed:11035011"
FT MUTAGEN 542
FT /note="D->A: Abolishes Ca(2+) permeation and Ca(2+)-
FT dependent current decay; no effect on monovalent cations
FT permeation."
FT /evidence="ECO:0000269|PubMed:11035011"
FT MUTAGEN 542
FT /note="D->E,N,M: Attenuates Ca(2+) permeation and Ca(2+)-
FT dependent current decay."
FT /evidence="ECO:0000269|PubMed:11035011"
FT MUTAGEN 542
FT /note="D->K: Abolishes channel activity."
FT /evidence="ECO:0000269|PubMed:11035011"
FT MUTAGEN 550
FT /note="D->A: Minor effects on Ca(2+) permeation."
FT /evidence="ECO:0000269|PubMed:11035011"
FT HELIX 29..46
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 48..55
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 58..66
FT /evidence="ECO:0007829|PDB:6O1U"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 82..88
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 92..101
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 120..126
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 130..138
FT /evidence="ECO:0007829|PDB:6O1U"
FT TURN 150..152
FT /evidence="ECO:0007829|PDB:6O1U"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:6O20"
FT HELIX 166..172
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 176..182
FT /evidence="ECO:0007829|PDB:6O1U"
FT TURN 183..186
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 199..204
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 209..221
FT /evidence="ECO:0007829|PDB:6O1U"
FT TURN 222..225
FT /evidence="ECO:0007829|PDB:6O1U"
FT STRAND 228..230
FT /evidence="ECO:0007829|PDB:6O1P"
FT TURN 231..233
FT /evidence="ECO:0007829|PDB:6O1U"
FT STRAND 238..240
FT /evidence="ECO:0007829|PDB:6O1N"
FT HELIX 243..249
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 253..259
FT /evidence="ECO:0007829|PDB:6O1U"
FT STRAND 261..270
FT /evidence="ECO:0007829|PDB:6O1U"
FT STRAND 273..278
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 281..284
FT /evidence="ECO:0007829|PDB:6O1U"
FT STRAND 287..289
FT /evidence="ECO:0007829|PDB:6O1P"
FT HELIX 292..297
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 303..309
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 313..323
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 325..348
FT /evidence="ECO:0007829|PDB:6O1U"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:6O1U"
FT TURN 362..365
FT /evidence="ECO:0007829|PDB:6O1U"
FT STRAND 370..372
FT /evidence="ECO:0007829|PDB:6O1U"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:6O1N"
FT HELIX 380..410
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 414..417
FT /evidence="ECO:0007829|PDB:6O1U"
FT STRAND 419..422
FT /evidence="ECO:0007829|PDB:6O1N"
FT HELIX 426..445
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 451..463
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 464..471
FT /evidence="ECO:0007829|PDB:6O1U"
FT TURN 473..475
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 476..486
FT /evidence="ECO:0007829|PDB:6O1U"
FT TURN 487..489
FT /evidence="ECO:0007829|PDB:6O1U"
FT TURN 491..493
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 494..498
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 500..511
FT /evidence="ECO:0007829|PDB:6O1U"
FT TURN 512..514
FT /evidence="ECO:0007829|PDB:6O1U"
FT TURN 517..519
FT /evidence="ECO:0007829|PDB:6O20"
FT HELIX 521..523
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 526..538
FT /evidence="ECO:0007829|PDB:6O1U"
FT STRAND 547..550
FT /evidence="ECO:0007829|PDB:6O1P"
FT HELIX 553..565
FT /evidence="ECO:0007829|PDB:6O1U"
FT TURN 566..568
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 569..583
FT /evidence="ECO:0007829|PDB:6O1U"
FT TURN 584..588
FT /evidence="ECO:0007829|PDB:6O1U"
FT TURN 590..592
FT /evidence="ECO:0007829|PDB:6O1U"
FT TURN 594..597
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 598..607
FT /evidence="ECO:0007829|PDB:6O1U"
FT TURN 610..612
FT /evidence="ECO:0007829|PDB:6O1P"
FT STRAND 617..619
FT /evidence="ECO:0007829|PDB:6O1U"
FT TURN 620..625
FT /evidence="ECO:0007829|PDB:6O1U"
FT STRAND 629..636
FT /evidence="ECO:0007829|PDB:6O1U"
FT HELIX 642..652
FT /evidence="ECO:0007829|PDB:6O20"
FT HELIX 699..709
FT /evidence="ECO:0007829|PDB:6O20"
SQ SEQUENCE 730 AA; 82814 MW; 0CB9FBAD916B1400 CRC64;
MGACPPKAKG PWAQLQKLLI SWPVGEQDWE QYRDRVNMLQ QERIRDSPLL QAAKENDLRL
LKILLLNQSC DFQQRGAVGE TALHVAALYD NLEAATLLME AAPELAKEPA LCEPFVGQTA
LHIAVMNQNL NLVRALLARG ASVSARATGA AFRRSPHNLI YYGEHPLSFA ACVGSEEIVR
LLIEHGADIR AQDSLGNTVL HILILQPNKT FACQMYNLLL SYDEHSDHLQ SLELVPNHQG
LTPFKLAGVE GNTVMFQHLM QKRKHVQWTC GPLTSTLYDL TEIDSWGEEL SFLELVVSSK
KREARQILEQ TPVKELVSFK WKKYGRPYFC VLASLYILYM ICFTTCCIYR PLKLRDDNRT
DPRDITILQQ KLLQEAYVTH QDNIRLVGEL VTVTGAVIIL LLEIPDIFRV GASRYFGQTI
LGGPFHVIII TYASLVLLTM VMRLTNMNGE VVPLSFALVL GWCSVMYFAR GFQMLGPFTI
MIQKMIFGDL MRFCWLMAVV ILGFASAFHI TFQTEDPNNL GEFSDYPTAL FSTFELFLTI
IDGPANYSVD LPFMYCITYA AFAIIATLLM LNLFIAMMGD THWRVAQERD ELWRAQVVAT
TVMLERKMPR FLWPRSGICG YEYGLGDRWF LRVENHHDQN PLRVLRYVEA FKCSDKEDGQ
EQLSEKRPST VESGMLSRAS VAFQTPSLSR TTSQSSNSHR GWEILRRNTL GHLNLGLDLG
EGDGEEVYHF
