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1.A.4.2.11
TRPV6 epithelial Ca2+ channel (ECaC2) (forms homo- and heterotetrameric channels with TRPV5; requires the S100A10-annexin 2 complex for routing to the plasma membrane) (Hoenderop et al., 2003; van de Graaf et al., 2003). Epithelial TrpV6, but not TrpV5, is inhibited by the regulator of G-protein signaling 2 (RGS2; Q9JHX0; 211 aas) by direct binding (Schoeber et al., 2006). Cyclophilin B is an accessory activating protein (Stumpf et al., 2008).  The crystal structure of rat TRPV6 at 3.25 A resolution revealed shared and unique features compared with other TRP channels (Saotome et al. 2016). Intracellular domains engage in extensive interactions to form an intracellular 'skirt' involved in allosteric modulation. In the K+ channel-like transmembrane domain, Ca2+ selectivity is determined by direct coordination of Ca2+ by a ring of aspartate side chains in the selectivity filter (Saotome et al. 2016).  Replacing Gly-516 within the cytosolic S4-S5 linker (conserved in all TRP channel proteins) by ser forces the channels into an open conformation, thereby enhancing constitutive Ca2+ entry and preventing inactivation (Hofmann et al. 2016). Tetrameric ion channels have either swapped or non-swapped arrangements of the S1-S4 and pore domains. Singh et al. 2017 showed that mutations in the transmembrane domain can result in conversion from a domain-swapped to the non-swapped fold. These results raise the possibility that a single ion channel subtype can fold into either arrangement in vivo, affecting its function in normal or disease states.

Accession Number:Q9H1D0
Protein Name:TRPV6
Length:725
Molecular Weight:83210.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:7
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate Ca2+

Cross database links:

Genevestigator: Q9H1D0
HEGENOM: HBG444402
RefSeq: NP_061116.2   
Entrez Gene ID: 55503   
Pfam: PF00023    PF00520   
OMIM: 606680  gene
KEGG: hsa:55503   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005262 F:calcium channel activity
GO:0005516 F:calmodulin binding
GO:0006816 P:calcium ion transport
GO:0017158 P:regulation of calcium ion-dependent exocytosis
GO:0055085 P:transmembrane transport

References (8)

[1] “Human calcium transport protein CaT1.”  Peng J.-B.et.al.   11097838
[2] “1,25-dihydroxyvitamin D3 increases the expression of the CaT1 epithelial calcium channel in the Caco-2 human intestinal cell line.”  Wood R.J.et.al.   11545681
[3] “Structural conservation of the genes encoding CaT1, CaT2, and related cation channels.”  Peng J.-B.et.al.   11549322
[4] “Expression of CaT-like, a novel calcium selective channel, correlates with the malignancy of prostate cancer.”  Wissenbach U.et.al.   11278579
[5] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[6] “Human chromosome 7: DNA sequence and biology.”  Scherer S.W.et.al.   12690205
[7] “Competitive regulation of CaT-like-mediated Ca2+ entry by protein kinase C and calmodulin.”  Niemeyer B.A.et.al.   11248124
[8] “Ca2+ dependence of the Ca2+-selective TRPV6 channel.”  Bodding M.et.al.   15184369

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MGLSLPKEKG LILCLWSKFC RWFQRRESWA QSRDEQNLLQ QKRIWESPLL LAAKDNDVQA 
61:	LNKLLKYEDC KVHQRGAMGE TALHIAALYD NLEAAMVLME AAPELVFEPM TSELYEGQTA 
121:	LHIAVVNQNM NLVRALLARR ASVSARATGT AFRRSPCNLI YFGEHPLSFA ACVNSEEIVR 
181:	LLIEHGADIR AQDSLGNTVL HILILQPNKT FACQMYNLLL SYDRHGDHLQ PLDLVPNHQG 
241:	LTPFKLAGVE GNTVMFQHLM QKRKHTQWTY GPLTSTLYDL TEIDSSGDEQ SLLELIITTK 
301:	KREARQILDQ TPVKELVSLK WKRYGRPYFC MLGAIYLLYI ICFTMCCIYR PLKPRTNNRT 
361:	SPRDNTLLQQ KLLQEAYMTP KDDIRLVGEL VTVIGAIIIL LVEVPDIFRM GVTRFFGQTI 
421:	LGGPFHVLII TYAFMVLVTM VMRLISASGE VVPMSFALVL GWCNVMYFAR GFQMLGPFTI 
481:	MIQKMIFGDL MRFCWLMAVV ILGFASAFYI IFQTEDPEEL GHFYDYPMAL FSTFELFLTI 
541:	IDGPANYNVD LPFMYSITYA AFAIIATLLM LNLLIAMMGD THWRVAHERD ELWRAQIVAT 
601:	TVMLERKLPR CLWPRSGICG REYGLGDRWF LRVEDRQDLN RQRIQRYAQA FHTRGSEDLD 
661:	KDSVEKLELG CPFSPHLSLP MPSVSRSTSR SSANWERLRQ GTLRRDLRGI INRGLEDGES 
721:	WEYQI