TRPC6

TRPC6
Identifikatori
Aliasi	TRPC6
Vanjski ID-jevi	OMIM: 603652 MGI: 109523 HomoloGene: 37944 GeneCards: TRPC6
Lokacija gena (čovjek)
Hrom.	Hromosom 11 (čovjek)
Kraj	101,872,562 bp
Lokacija gena (miš)
Hrom.	Hromosom 9 (miš)
Kraj	8,680,742 bp
Ontologija gena
Molekularna funkcija	• actinin binding; • store-operated calcium channel activity; • clathrin binding; • inositol 1,4,5 trisphosphate binding; • ion channel activity; • GO:0001948, GO:0016582 vezivanje za proteine; • actin binding; • calcium channel activity; • cation channel activity; • protein homodimerization activity; • ATPase binding;
Ćelijska komponenta	• citoplazma; • integral component of membrane; • membrana; • ćelijska membrana; • integral component of plasma membrane; • slit diaphragm; • cation channel complex;
Biološki proces	• regulation of cytosolic calcium ion concentration; • positive regulation of cytosolic calcium ion concentration; • GO:0010260 starenje; • cation transport; • ion transport; • single fertilization; • platelet activation; • positive regulation of ion transmembrane transporter activity; • negative regulation of dendrite morphogenesis; • positive regulation of peptidyl-threonine phosphorylation; • calcium ion transmembrane transport; • positive regulation of neuron differentiation; • neuron differentiation; • manganese ion transport; • cellular response to hypoxia; • calcium ion transport; • cellular response to hydrogen peroxide; • positive regulation of calcium ion transport; • transmembrane transport;
	Izvori:Amigo / QuickGO
Ortolozi
	7225
	22068
	ENSG00000137672
	ENSMUSG00000031997
	Q9Y210
	Q61143
	NM_004621
	NM_001282086; NM_001282087; NM_013838
	NP_004612
	NP_001269015; NP_001269016; NP_038866
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Član 6 potporodice C potencijalni kationski kanal prolaznog receptora, također poznat kao TRPC6, je ljudski gen koji kodira istoimeni protein. TRPC6 je prolazni receptor potencijalnog kanala klasične potporodice TRPC, sa hromosoma 11.. Povezana je sa depresijom i ankilozom (vidi ispod), kao i sa fokusnom segmentnom glomerulosklerozom.^[5]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 931 aminokiselina, a molekulska težina 106.326 Da.

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MSQSPAFGPR	RGSSPRGAAG	AAARRNESQD	YLLMDSELGE	DGCPQAPLPC
YGYYPCFRGS	DNRLAHRRQT	VLREKGRRLA	NRGPAYMFSD	RSTSLSIEEE
RFLDAAEYGN	IPVVRKMLEE	CHSLNVNCVD	YMGQNALQLA	VANEHLEITE
LLLKKENLSR	VGDALLLAIS	KGYVRIVEAI	LSHPAFAEGK	RLATSPSQSE
LQQDDFYAYD	EDGTRFSHDV	TPIILAAHCQ	EYEIVHTLLR	KGARIERPHD
YFCKCNDCNQ	KQKHDSFSHS	RSRINAYKGL	ASPAYLSLSS	EDPVMTALEL
SNELAVLANI	EKEFKNDYKK	LSMQCKDFVV	GLLDLCRNTE	EVEAILNGDV
ETLQSGDHGR	PNLSRLKLAI	KYEVKKFVAH	PNCQQQLLSI	WYENLSGLRQ
QTMAVKFLVV	LAVAIGLPFL	ALIYWFAPCS	KMGKIMRGPF	MKFVAHAASF
TIFLGLLVMN	AADRFEGTKL	LPNETSTDNA	KQLFRMKTSC	FSWMEMLIIS
WVIGMIWAEC	KEIWTQGPKE	YLFELWNMLD	FGMLAIFAAS	FIARFMAFWH
ASKAQSIIDA	NDTLKDLTKV	TLGDNVKYYN	LARIKWDPSD	PQIISEGLYA
IAVVLSFSRI	AYILPANESF	GPLQISLGRT	VKDIFKFMVI	FIMVFVAFMI
GMFNLYSYYI	GAKQNEAFTT	VEESFKTLFW	AIFGLSEVKS	VVINYNHKFI
ENIGYVLYGV	YNVTMVIVLL	NMLIAMINSS	FQEIEDDADV	EWKFARAKLW
FSYFEEGRTL	PVPFNLVPSP	KSLFYLLLKL	KKWISELFQG	HKKGFQEDAE
MNKINEEKKL	GILGSHEDLS	KLSLDKKQVG	HNKQPSIRSS	EDFHLNSFNN
PPRQYQKIMK	RLIKRYVLQA	QIDKESDEVN	EGELKEIKQD	ISSLRYELLE
EKSQNTEDLA	ELIRELGEKL	SMEPNQEETN	R

Interakcije

Pokazalo se da TRPC6 ima interakcije sa:

Ligandi

Dva od primarnih aktivnih sastojka odgovornih za antidepresive i anksiolitike koriste Hypericum perforatum, također poznat kao kantarion, su hiperforin i adhiperforin.^[9]^[10] Ovi spojevi su inhibitori ponovnog preuzimanja serotonina, noradrenalina, dopamina, γ-izobutene kiseline i glutamata, a prijavljeno je da ispoljavaju ove efekt vezivanje za i aktiviranje TRPC6.^[10]^[11] Nedavni rezultati sa hiperforinom doveli su u sumnju ove nalaze jer se slične struje vide nakon liječenja hiperforinom bez obzira na prisustvo TRPC6.^[12]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000137672 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000031997 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Winn MP, Conlon PJ, Lynn KL, Farrington MK, Creazzo T, Hawkins AF, Daskalakis N, Kwan SY, Ebersviller S, Burchette JL, Pericak-Vance MA, Howell DN, Vance JM, Rosenberg PB (juni 2005). "A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis". Science. 308 (5729): 1801–4. doi:10.1126/science.1106215. PMID 15879175. S2CID 23967918.
^ Hisatsune C, Kuroda Y, Nakamura K, Inoue T, Nakamura T, Michikawa T, Mizutani A, Mikoshiba K (april 2004). "Regulation of TRPC6 channel activity by tyrosine phosphorylation". The Journal of Biological Chemistry. 279 (18): 18887–94. doi:10.1074/jbc.M311274200. PMID 14761972.
^ Chu X, Tong Q, Cheung JY, Wozney J, Conrad K, Mazack V, Zhang W, Stahl R, Barber DL, Miller BA (mart 2004). "Interaction of TRPC2 and TRPC6 in erythropoietin modulation of calcium influx". The Journal of Biological Chemistry. 279 (11): 10514–22. doi:10.1074/jbc.M308478200. PMID 14699131.
^ Hofmann T, Schaefer M, Schultz G, Gudermann T (maj 2002). "Subunit composition of mammalian transient receptor potential channels in living cells". Proceedings of the National Academy of Sciences of the United States of America. 99 (11): 7461–6. doi:10.1073/pnas.102596199. PMC 124253. PMID 12032305.
^ Müller WE, Singer A, Wonnemann M (juli 2001). "Hyperforin--antidepressant activity by a novel mechanism of action". Pharmacopsychiatry. 34 Suppl 1: S98-102. doi:10.1055/s-2001-15512. PMID 11518085.
^ ^a ^b Chatterjee SS, Bhattacharya SK, Wonnemann M, Singer A, Müller WE (1998). "Hyperforin as a possible antidepressant component of hypericum extracts". Life Sciences. 63 (6): 499–510. doi:10.1016/S0024-3205(98)00299-9. PMID 9718074.
^ Leuner K, Kazanski V, Müller M, Essin K, Henke B, Gollasch M, Harteneck C, Müller WE (decembar 2007). "Hyperforin--a key constituent of St. John's wort specifically activates TRPC6 channels". FASEB Journal. 21 (14): 4101–11. doi:10.1096/fj.07-8110com. PMID 17666455. S2CID 14097884.
^ Sell TS, Belkacemi T, Flockerzi V, Beck A (decembar 2014). "Protonophore properties of hyperforin are essential for its pharmacological activity". Scientific Reports. 4: 7500. doi:10.1038/srep07500. PMC 4266863. PMID 25511254.

Dopunska literatura

Heiner I, Eisfeld J, Lückhoff A (2004). "Role and regulation of TRP channels in neutrophil granulocytes". Cell Calcium. 33 (5–6): 533–40. doi:10.1016/S0143-4160(03)00058-7. PMID 12765698.
Walz G (septembar 2005). "Slit or pore? A mutation of the ion channel TRPC6 causes FSGS". Nephrology, Dialysis, Transplantation. 20 (9): 1777–9. doi:10.1093/ndt/gfh961. PMID 15998650.
Clapham DE, Julius D, Montell C, Schultz G (decembar 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacological Reviews. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100. S2CID 17936350.
Schlöndorff JS, Pollak MR (decembar 2006). "TRPC6 in glomerular health and disease: what we know and what we believe". Seminars in Cell & Developmental Biology. 17 (6): 667–74. doi:10.1016/j.semcdb.2006.11.003. PMC 2705932. PMID 17116414.
Dietrich A, Gudermann T (2007). "TRPC6". Transient Receptor Potential (TRP) Channels. Handbook of Experimental Pharmacology. 179. str. 125–41. doi:10.1007/978-3-540-34891-7_7. ISBN 978-3-540-34889-4. PMID 17217054.

Vanjski linkovi

TRPC6 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)

Šablon:Modulatori potencijalnog prolaznog kanalskog receptora

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000137672 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000031997 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Winn MP, Conlon PJ, Lynn KL, Farrington MK, Creazzo T, Hawkins AF, Daskalakis N, Kwan SY, Ebersviller S, Burchette JL, Pericak-Vance MA, Howell DN, Vance JM, Rosenberg PB (juni 2005). "A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis". Science. 308 (5729): 1801–4. doi:10.1126/science.1106215. PMID 15879175. S2CID 23967918.

[pmid14761972-6] Hisatsune C, Kuroda Y, Nakamura K, Inoue T, Nakamura T, Michikawa T, Mizutani A, Mikoshiba K (april 2004). "Regulation of TRPC6 channel activity by tyrosine phosphorylation". The Journal of Biological Chemistry. 279 (18): 18887–94. doi:10.1074/jbc.M311274200. PMID 14761972.

[pmid14699131-7] Chu X, Tong Q, Cheung JY, Wozney J, Conrad K, Mazack V, Zhang W, Stahl R, Barber DL, Miller BA (mart 2004). "Interaction of TRPC2 and TRPC6 in erythropoietin modulation of calcium influx". The Journal of Biological Chemistry. 279 (11): 10514–22. doi:10.1074/jbc.M308478200. PMID 14699131.

[pmid12032305-8] Hofmann T, Schaefer M, Schultz G, Gudermann T (maj 2002). "Subunit composition of mammalian transient receptor potential channels in living cells". Proceedings of the National Academy of Sciences of the United States of America. 99 (11): 7461–6. doi:10.1073/pnas.102596199. PMC 124253. PMID 12032305.

[pmid11518085-9] Müller WE, Singer A, Wonnemann M (juli 2001). "Hyperforin--antidepressant activity by a novel mechanism of action". Pharmacopsychiatry. 34 Suppl 1: S98-102. doi:10.1055/s-2001-15512. PMID 11518085.

[pmid9718074-10] Chatterjee SS, Bhattacharya SK, Wonnemann M, Singer A, Müller WE (1998). "Hyperforin as a possible antidepressant component of hypericum extracts". Life Sciences. 63 (6): 499–510. doi:10.1016/S0024-3205(98)00299-9. PMID 9718074.

[pmid17666455-11] Leuner K, Kazanski V, Müller M, Essin K, Henke B, Gollasch M, Harteneck C, Müller WE (decembar 2007). "Hyperforin--a key constituent of St. John's wort specifically activates TRPC6 channels". FASEB Journal. 21 (14): 4101–11. doi:10.1096/fj.07-8110com. PMID 17666455. S2CID 14097884.

[12] Sell TS, Belkacemi T, Flockerzi V, Beck A (decembar 2014). "Protonophore properties of hyperforin are essential for its pharmacological activity". Scientific Reports. 4: 7500. doi:10.1038/srep07500. PMC 4266863. PMID 25511254.

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