MCOLN1

MCOLN1
Identifikatori
Aliasi	MCOLN1
Vanjski ID-jevi	OMIM: 605248 MGI: 1890498 HomoloGene: 10744 GeneCards: MCOLN1
Lokacija gena (čovjek)
Hrom.	Hromosom 19 (čovjek)
Kraj	7,534,009 bp
Lokacija gena (miš)
Hrom.	Hromosom 8 (miš)
Kraj	3,565,232 bp
Ontologija gena
Molekularna funkcija	• cation channel activity; • NAADP-sensitive calcium-release channel activity; • GO:0097689 iron ion transmembrane transporter activity; • calcium channel activity; • GO:0001948, GO:0016582 vezivanje za proteine; • lipid binding; • intracellular phosphatidylinositol-3,5-bisphosphate-sensitive cation channel activity; • ligand-gated calcium channel activity;
Ćelijska komponenta	• lysosomal membrane; • endosome membrane; • integral component of membrane; • integral component of plasma membrane; • membrana; • receptor complex; • endozom; • late endosome membrane; • ćelijska membrana; • citosol; • phagocytic cup; • Lizozom; • late endosome; • phagocytic vesicle membrane; • GO:0016023 citoplazmatska vezikula; • projekcija ćelije; • cytoplasmic vesicle membrane;
Biološki proces	• calcium ion transport; • transferrin transport; • release of sequestered calcium ion into cytosol; • ion transport; • cation transport; • iron ion transmembrane transport; • GO:0000046 autophagosome maturation; • calcium ion transmembrane transport; • GO:0015915 transport; • adaptive immune response; • immune system process; • calcium-mediated signaling; • protein homotetramerization; • cellular response to calcium ion; • cellular response to pH; • cation transmembrane transport;
	Izvori:Amigo / QuickGO
Ortolozi
	57192
	94178
	ENSG00000090674
	ENSMUSG00000004567
	Q9GZU1
	Q99J21
	NM_020533
	NM_053177
	NP_065394
	NP_444407
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Mukolipin-1 znan i kao TRPML1 (član 1 pčotporodice mukolipina, tranzijentnog potencijalnog receptorskog kationskog kanala) jest protein koji je kod ljudi kodiran genom MCOLN1 sa hromosoma 19.^[5] Član je male porodice TRPML kanala, podgrupe velike porodice proteina TRP ionskih kanala.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 580 aminokiselina, a molekulska težina 65.022 Da.^[5]

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
MTAPAGPRGS	ETERLLTPNP	GYGTQAGPSP	APPTPPEEED	LRRRLKYFFM
SPCDKFRAKG	RKPCKLMLQV	VKILVVTVQL	ILFGLSNQLA	VTFREENTIA
FRHLFLLGYS	DGADDTFAAY	TREQLYQAIF	HAVDQYLALP	DVSLGRYAYV
RGGGDPWTNG	SGLALCQRYY	HRGHVDPAND	TFDIDPMVVT	DCIQVDPPER
PPPPPSDDLT	LLESSSSYKN	LTLKFHKLVN	VTIHFRLKTI	NLQSLINNEI
PDCYTFSVLI	TFDNKAHSGR	IPISLETQAH	IQECKHPSVF	QHGDNSFRLL
FDVVVILTCS	LSFLLCARSL	LRGFLLQNEF	VGFMWRQRGR	VISLWERLEF
VNGWYILLVT	SDVLTISGTI	MKIGIEAKNL	ASYDVCSILL	GTSTLLVWVG
VIRYLTFFHN	YNILIATLRV	ALPSVMRFCC	CVAVIYLGYC	FCGWIVLGPY
HVKFRSLSMV	SECLFSLING	DDMFVTFAAM	QAQQGRSSLV	WLFSQLYLYS
FISLFIYMVL	SLFIALITGA	YDTIKHPGGA	GAEESELQAY	IAQCQDSPTS
GKFRRGSGSA	CSLLCCCGRD	PSEEHSLLVN

Funkcija

TRPML1 je protein od 65 kDa povezan sa mukolipidozom tipa IV. Njegova predviđena struktura uključuje šest transmembranskih domena, tranzijentni receptorski potencijal (TRP) domena kationskog kanala i pore unutrašnjeg kanala.^[6] Vjeruje se da TRPML1 kanališe ione željeza preko endosomne/lizozomne membrane u ćeliju i tako njegov kvar uzrokuje ćelijski nedostatak željeza.^[7] Važan je u funkciji lizosoma i igra ulogu u procesima kao što su promet vezikula, egzocitoza i autofagija.^[8]^[9]

Ligandi

Agonisti

ML-SA1
MK6-83^[10]

Također pogledajte

Kationski kanal prolaznog receptorskog potencijala, potporodica mukolipina, član 2 (MCOLN2)
Kationski kanal prolaznog receptorskog potencijala, potporodica mukolipina, član 3 (MCOLN3)
Mukolipidoza tip IV
TRPML

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000090674 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000004567 - 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.
^ ^a ^b 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". Pharmacol. Rev. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100. S2CID 17936350.
^ Venugopal B, Browning MF, Curcio-Morelli C, Varro A, Michaud N, Nanthakumar N, Walkley SU, Pickel J, Slaugenhaupt SA (novembar 2007). "Neurologic, gastric, and opthalmologic [sic] pathologies in a murine model of mucolipidosis type IV". Am. J. Hum. Genet. 81 (5): 1070–83. doi:10.1086/521954. PMC 2265643. PMID 17924347.
^ Dong X, Cheng X, Mills E, Delling M, Wang F, Kurz T, Xu H (2008). "The Type IV Mucolipidosis-Associated Protein TRPML1 is an Endo-lysosomal Iron Release Channel". Nature. 455 (7215): 992–6. Bibcode:2008Natur.455..992D. doi:10.1038/nature07311. PMC 4301259. PMID 18794901.
^ Wang W, Zhang X, Gao Q, Xu H (2014). "TRPML1: an ion channel in the lysosome". Handbook of Experimental Pharmacology. 222: 631–45. doi:10.1007/978-3-642-54215-2_24. ISBN 978-3-642-54214-5. PMID 24756723.
^ Di Paola S, Scotto-Rosato A, Medina DL (januar 2018). "TRPML1: The Ca(2+)retaker of the lysosome". Cell Calcium. 69: 112–121. doi:10.1016/j.ceca.2017.06.006. PMID 28689729.
^ Schmiege P, Fine M, Blobel G, Li X (oktobar 2017). "Human TRPML1 channel structures in open and closed conformations". Nature. 550 (7676): 366–370. Bibcode:2017Natur.550..366S. doi:10.1038/nature24036. PMC 5920536. PMID 29019983.

Vanjski linkovi

GeneReviews/NIH/NCBI/UW entry on Mucolipidosis IV
mucolipin-1 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)

Šablon:Modulatori potencijalnog prolaznog receptorskog kanala

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000090674 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000004567 - 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.

[pmid16382100-5] 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". Pharmacol. Rev. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100. S2CID 17936350.

[pmid17924347-6] Venugopal B, Browning MF, Curcio-Morelli C, Varro A, Michaud N, Nanthakumar N, Walkley SU, Pickel J, Slaugenhaupt SA (novembar 2007). "Neurologic, gastric, and opthalmologic [sic] pathologies in a murine model of mucolipidosis type IV". Am. J. Hum. Genet. 81 (5): 1070–83. doi:10.1086/521954. PMC 2265643. PMID 17924347.

[7] Dong X, Cheng X, Mills E, Delling M, Wang F, Kurz T, Xu H (2008). "The Type IV Mucolipidosis-Associated Protein TRPML1 is an Endo-lysosomal Iron Release Channel". Nature. 455 (7215): 992–6. Bibcode:2008Natur.455..992D. doi:10.1038/nature07311. PMC 4301259. PMID 18794901.

[pmid24756723-8] Wang W, Zhang X, Gao Q, Xu H (2014). "TRPML1: an ion channel in the lysosome". Handbook of Experimental Pharmacology. 222: 631–45. doi:10.1007/978-3-642-54215-2_24. ISBN 978-3-642-54214-5. PMID 24756723.

[pmid28689729-9] Di Paola S, Scotto-Rosato A, Medina DL (januar 2018). "TRPML1: The Ca(2+)retaker of the lysosome". Cell Calcium. 69: 112–121. doi:10.1016/j.ceca.2017.06.006. PMID 28689729.

[pmid29019983-10] Schmiege P, Fine M, Blobel G, Li X (oktobar 2017). "Human TRPML1 channel structures in open and closed conformations". Nature. 550 (7676): 366–370. Bibcode:2017Natur.550..366S. doi:10.1038/nature24036. PMC 5920536. PMID 29019983.

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