PNPLA3

PNPLA3
Identifikatori
Aliasi	PNPLA3
Vanjski ID-jevi	OMIM: 609567 MGI: 2151796 HomoloGene: 11883 GeneCards: PNPLA3
Lokacija gena (čovjek)
Hrom.	Hromosom 22 (čovjek)
Kraj	43,964,488 bp
Lokacija gena (miš)
Hrom.	Hromosom 15 (miš)
Kraj	84,071,437 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• mono-olein transacylation activity; • aktivnost sa transferazom; • phospholipase A2 activity; • acyltransferase activity; • hydrolase activity; • diolein transacylation activity; • acylglycerol O-acyltransferase activity; • lipoprotein lipase activity; • triglyceride lipase activity; • lysophosphatidic acid binding; • long-chain fatty acyl-CoA binding; • lysophosphatidic acid acyltransferase activity; • 1-acylglycerol-3-phosphate O-acyltransferase activity;
Ćelijska komponenta	• integral component of membrane; • endoplasmic reticulum membrane; • citoplazma; • Lipidna kapljica; • membrana;
Biološki proces	• lipid catabolic process; • triglyceride biosynthetic process; • metabolizam; • acylglycerol acyl-chain remodeling; • lipid metabolism; • triglyceride catabolic process; • triglyceride acyl-chain remodeling; • lipid homeostasis; • long-chain fatty acid metabolic process; • glycerophospholipid metabolic process; • phosphatidic acid biosynthetic process; • lipid droplet organization; • phospholipid biosynthetic process;
	Izvori:Amigo / QuickGO
Ortolozi
	80339
	116939
	ENSG00000100344
	ENSMUSG00000041653
	Q9NST1
	Q91WW7
	NM_025225
	NM_054088
	NP_079501
	NP_473429; NP_001395268; NP_001395269; NP_001395270; NP_001395271
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Patatin-lika fosfolipaza proteina 3 sa domenom (PNPLA3), znana i kao adiponutrin (ADPN), acilglicerol O-aciltransferaza ili kalcij-neovisna fosfolipaza A2-epsilon (iPLA2-epsilon) jest enzim koji je kod ljudi kodiran genom PNPLA3 sa hromosoma 22.^[5]^[6]^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 481 aminokiselina, a molekulska težina 52.865 Da^[7]

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
MYDAERGWSL	SFAGCGFLGF	YHVGATRCLS	EHAPHLLRDA	RMLFGASAGA
LHCVGVLSGI	PLEQTLQVLS	DLVRKARSRN	IGIFHPSFNL	SKFLRQGLCK
CLPANVHQLI	SGKIGISLTR	VSDGENVLVS	DFRSKDEVVD	ALVCSCFIPF
YSGLIPPSFR	GVRYVDGGVS	DNVPFIDAKT	TITVSPFYGE	YDICPKVKST
NFLHVDITKL	SLRLCTGNLY	LLSRAFVPPD	LKVLGEICLR	GYLDAFRFLE
EKGICNRPQP	GLKSSSEGMD	PEVAMPSWAN	MSLDSSPESA	ALAVRLEGDE
LLDHLRLSIL	PWDESILDTL	SPRLATALSE	EMKDKGGYMS	KICNLLPIRI
MSYVMLPCTL	PVESAIAIVQ	RLVTWLPDMP	DDVLWLQWVT	SQVFTRVLMC
LLPASRSQMP	VSSQQASPCT	PEQDWPCWTP	CSPKGCPAET	KAEATPRSIL
RSSLNFFLGN	KVPAGAEGLS	TFPSFSLEKS	L

Funkcija

Adiponutrin je triacilglicerolska lipaza koji posreduje u hidrolizi triacilglicerola u adipocitima. Kodirani protein, za koji se čini da je vezan za membranu, može biti uključen u ravnotežu korištenja/skladišta energije u adipocitima.^[7]

Genomika

Gen se nalazi na dugom (q) kraku hromosoma 22 u regiji 13.31 (22q13.31), na Watsonovom (plus) lancu i dug je 40.750 nukleobaza.

Identifikovana su pretpostavljena mesta za vezivanje gena uzvodno za nekoliko transkripcijskih faktora. To uključuje PPAR-gama, POU2F1 i POU2F2. Još nije poznato da li je bilo koji od ovih faktora transkripcije uključen u regulaciju ovog gena.

Biohemija

Preporučeni naziv za genski proizvod je protein 3 koji sadrži domen fosfolipaze nalik patatinu. To je jednoprolazni membranski protein tipa II i multifunkcionalni je enzim sa aktivnostima triacilglicerol lipaze i acilglicerol O-aciltransferaze. Uključen je u hidrolizu triacilglicerola u adipocitima i može imati ulogu u energetskom metabolizmu.

Zreli protein ima dužinu od 481 aminokiseline, a predviđena molekulska težina je 52.865 kDa. Opisane su dvije izoforme, tj. varijante transkripta, ali funkcionalni značaj – ako ga ima – ovih oblika nije poznat.

Klinički značaj

Potvrđena je povezanost između alkoholne bolesti jetre kod kavkazoide i varijacija ovog gena.^[8] Potvrđeno je da mutacija izoleucina u metionin (I[ATC]>M[ATG]) jednonukleotidnog polimorfizma rs738409 povećava osjetljivost na nealkoholnu bolest jetre, kao i da ima efekte na dijabetes.^[9]

Tokom izolacije zbog COVID-19 u Italiji, genotip PNPLA3 GG bio je najvažnija determinanta povećanja tjelesne težine u skupini pacijenata sa steatozom jetre. Zanimljivo je da je kod pacijenata koji nose alel PNPLA3 GG, uticaj životnog stila bio gotovo poništen, pri čemu je genetički polimorfizam bio najjači prediktor.^[10]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000100344 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000041653 - 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.
^ Wilson PA, Gardner SD, Lambie NM, Commans SA, Crowther DJ (September 2006). "Characterization of the human patatin-like phospholipase family". Journal of Lipid Research. 47 (9): 1940–9. doi:10.1194/jlr.M600185-JLR200. PMID 16799181.
^ Kienesberger PC, Oberer M, Lass A, Zechner R (April 2009). "Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions". Journal of Lipid Research. 50 Suppl: S63-8. doi:10.1194/jlr.R800082-JLR200. PMC 2674697. PMID 19029121.
^ ^a ^b ^c "Entrez Gene: PNPLA3 patatin-like phospholipase domain containing 3".
^ Stickel F, Hampe J (January 2012). "Genetic determinants of alcoholic liver disease". Gut. 61 (1): 150–9. doi:10.1136/gutjnl-2011-301239. PMID 22110053.
^ Pingitore P, Romeo S (June 2019). "The role of PNPLA3 in health and disease". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1864 (6): 900–906. doi:10.1016/j.bbalip.2018.06.018. PMID 29935383.
^ Cinque F, Cespiati A, Lombardi R, Costantino A, Maffi G, Alletto F, Colavolpe L, Francione P, Oberti G, Fatta E (2022). "Interaction between Lifestyle Changes and PNPLA3 Genotype in NAFLD Patients during the COVID-19 Lockdown". Nutrients. 14: 556. doi:10.3390/nu14030556.

Dopunska literatura

Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (December 1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. Bibcode:1999Natur.402..489D. doi:10.1038/990031. PMID 10591208.
Collins JE, Goward ME, Cole CG, Smink LJ, Huckle EJ, Knowles S, Bye JM, Beare DM, Dunham I (January 2003). "Reevaluating human gene annotation: a second-generation analysis of chromosome 22". Genome Research. 13 (1): 27–36. doi:10.1101/gr.695703. PMC 430954. PMID 12529303.
Liu YM, Moldes M, Bastard JP, Bruckert E, Viguerie N, Hainque B, Basdevant A, Langin D, Pairault J, Clément K (June 2004). "Adiponutrin: A new gene regulated by energy balance in human adipose tissue". The Journal of Clinical Endocrinology and Metabolism. 89 (6): 2684–9. doi:10.1210/jc.2003-031978. PMID 15181042.
Jenkins CM, Mancuso DJ, Yan W, Sims HF, Gibson B, Gross RW (November 2004). "Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities". The Journal of Biological Chemistry. 279 (47): 48968–75. doi:10.1074/jbc.M407841200. PMID 15364929.
Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I (2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biology. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC 545604. PMID 15461802.
Lake AC, Sun Y, Li JL, Kim JE, Johnson JW, Li D, Revett T, Shih HH, Liu W, Paulsen JE, Gimeno RE (November 2005). "Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members". Journal of Lipid Research. 46 (11): 2477–87. doi:10.1194/jlr.M500290-JLR200. PMID 16150821.

Vanjski linkovi

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000100344 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000041653 - 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.

[pmid16799181-5] Wilson PA, Gardner SD, Lambie NM, Commans SA, Crowther DJ (September 2006). "Characterization of the human patatin-like phospholipase family". Journal of Lipid Research. 47 (9): 1940–9. doi:10.1194/jlr.M600185-JLR200. PMID 16799181.

[pmid19029121-6] Kienesberger PC, Oberer M, Lass A, Zechner R (April 2009). "Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions". Journal of Lipid Research. 50 Suppl: S63-8. doi:10.1194/jlr.R800082-JLR200. PMC 2674697. PMID 19029121.

[entrez-7] "Entrez Gene: PNPLA3 patatin-like phospholipase domain containing 3".

[pmid22110053-8] Stickel F, Hampe J (January 2012). "Genetic determinants of alcoholic liver disease". Gut. 61 (1): 150–9. doi:10.1136/gutjnl-2011-301239. PMID 22110053.

[pmid29935383-9] Pingitore P, Romeo S (June 2019). "The role of PNPLA3 in health and disease". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1864 (6): 900–906. doi:10.1016/j.bbalip.2018.06.018. PMID 29935383.

[10] Cinque F, Cespiati A, Lombardi R, Costantino A, Maffi G, Alletto F, Colavolpe L, Francione P, Oberti G, Fatta E (2022). "Interaction between Lifestyle Changes and PNPLA3 Genotype in NAFLD Patients during the COVID-19 Lockdown". Nutrients. 14: 556. doi:10.3390/nu14030556.

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