APOA4

APOA4
Identifikatori
Aliasi	APOA4
Vanjski ID-jevi	OMIM: 107690 MGI: 88051 HomoloGene: 47927 GeneCards: APOA4
Lokacija gena (čovjek)
Hrom.	Hromosom 11 (čovjek)
Kraj	116,823,304 bp
Lokacija gena (miš)
Hrom.	Hromosom 9 (miš)
Kraj	46,154,757 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ortolozi
	337
	11808
	ENSG00000110244
	ENSMUSG00000032080
	n; a
	P06728
	NM_000482
	NM_007468
	n/a
	NP_031494
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Apolipoprotein A-IV (znan i kao apoA-IV, apoAIV ili apoA4) je plazmatski protein koji je kod ljudi kodiran genom APOA4.^[5]^[6]

Gen

APOA4 se nalazi na hromosomu 11 u bliskoj vezi sa APOA1 i APOC3. APOA4 sadrži tri egzona odvojena s dva introna i predstavlja polimorfni), iako se većina prijavljenih polimorfnih sekvenci javlja u egzonu 3. Najbolje potvrđeni i proučeni nesinonimni jednonuklrotidni polimorfizmi (SNP9) su supstitucija glutamin → histidin na kodonu 360 i treonin → serin zamjena na kodonu 347; polimorfizam sekvence je također identifikovan u 3' UTR trećeg egzona.^[7] Uporedna analiza sekvenci gena unutar vrste sugeriše da je gen APOA4 nastao iz APOA1, duplikacijom gena prije približno 270 miliona godina.^[8]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 396 aminokiselina, a molekulska težina 45 399 Da.^[9]

10	20	30	40	50
MFLKAVVLTL	ALVAVAGARA	EVSADQVATV	MWDYFSQLSN	NAKEAVEHLQ
KSELTQQLNA	LFQDKLGEVN	TYAGDLQKKL	VPFATELHER	LAKDSEKLKE
EIGKELEELR	ARLLPHANEV	SQKIGDNLRE	LQQRLEPYAD	QLRTQVNTQA
EQLRRQLTPY	AQRMERVLRE	NADSLQASLR	PHADELKAKI	DQNVEELKGR
LTPYADEFKV	KIDQTVEELR	RSLAPYAQDT	QEKLNHQLEG	LTFQMKKNAE
ELKARISASA	EELRQRLAPL	AEDVRGNLRG	NTEGLQKSLA	ELGGHLDQQV
EEFRRRVEPY	GENFNKALVQ	QMEQLRQKLG	PHAGDVEGHL	SFLEKDLRDK
VNSFFSTFKE	KESQDKTLSL	PELEQQQEQQ	QEQQQEQVQM	LAPLES

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

Funkcija

Primarni produkt translacije gena APOA4 je preprotein sa 396 ostataka, koji se podvrgava proteolitskoj obradi, kako bi se dobio apo A-IV, zreli O-vezani glikoprotein sa 376 ostataka. Kod većine sisavara, uključujući ljude, sinteza apo A-IV ograničena je na crijeva; međutim, kod miševa i pacova dolazi do sinteze u jetri. Apo A-IV se izlučuje u cirkulaciju na površini novosintetiziranih hilomikronskih čestica. Apsorpcija masti u crijevima dramatično povećava sintezu i lučenje apo A-IV. Iako njegova primarna funkcija u metabolizmu lipida u ljudi nije utvrđena, otkriveno je da apo A-IV:

in vitro aktivira lecitin-holesterol aciltransferazu i protein transpotra holesteril-holesterola;
imaju ulogu u regulaciji apetita i sitosti u modelima glodara;
pokazivanje antioksidativnih i antiaterogenih svojstava in vitro i kod modela glodara;
modulirati efikasnost enterocitnog i jetrenog transcelularnog lipidnog transporta in vitro.^[7]

Nedostatak judskog apo A-IV nije prijavljen.

Interakcije

Dokazano je da APOA4 stupa u interakciju sa ^[10]

Interaktivna mapa puta

Šablon:StatinPathway WP430

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000110244 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000032080 - 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.
^ Karathanasis SK, Oettgen P, Haddad IA, Antonarakis SE (novembar 1986). "Structure, evolution, and polymorphisms of the human apolipoprotein A4 gene (APOA4)". Proceedings of the National Academy of Sciences of the United States of America. 83 (22): 8457–61. Bibcode:1986PNAS...83.8457K. doi:10.1073/pnas.83.22.8457. PMC 386949. PMID 3095836.
^ Elshourbagy NA, Walker DW, Paik YK, Boguski MS, Freeman M, Gordon JI, Taylor JM (juni 1987). "Structure and expression of the human apolipoprotein A-IV gene". J. Biol. Chem. 262 (17): 7973–81. PMID 3036793.
^ ^a ^b "Entrez Gene: APOA4 apolipoprotein A-IV".
^ Luo CC, Li WH, Moore MN, Chan L (februar 1986). "Structure and evolution of the apolipoprotein multigene family". J. Mol. Biol. 187 (3): 325–340. doi:10.1016/0022-2836(86)90436-5. PMID 3084795.
^ "UniProt, P06727". Pristupljeno 16. 8. 2021.
^ Deeg, M A; Bierman E L; Cheung M C (mart 2001). "GPI-specific phospholipase D associates with an apoA-I- and apoA-IV-containing complex". J. Lipid Res. United States. 42 (3): 442–51. ISSN 0022-2275. PMID 11254757.

Dopunska literatura

von Eckardstein A, Funke H, Schulte M, et al. (1992). "Nonsynonymous polymorphic sites in the apolipoprotein (apo) A-IV gene are associated with changes in the concentration of apo B- and apo A-I-containing lipoproteins in a normal population". American Journal of Human Genetics. 50 (5): 1115–28. PMC 1682587. PMID 1349197.
Kamboh MI, Williams ER, Law JC, et al. (1993). "Molecular basis of a unique African variant (A-IV 5) of human apolipoprotein A-IV and its significance in lipid metabolism". Genet. Epidemiol. 9 (6): 379–88. doi:10.1002/gepi.1370090602. PMID 1487136. S2CID 40107026.
Lohse P, Kindt MR, Rader DJ, Brewer HB (1991). "Three genetic variants of human plasma apolipoprotein A-IV. apoA-IV-1(Thr347----Ser), apoA-IV-0(Lys167----Glu,Gln360----His), and apoA-IV-3(Glu165----Lys)". J. Biol. Chem. 266 (21): 13513–8. PMID 1677358.
Tenkanen H, Koskinen P, Metso J, et al. (1992). "A novel polymorphism of apolipoprotein A-IV is the result of an asparagine to serine substitution at residue 127". Biochim. Biophys. Acta. 1138 (1): 27–33. doi:10.1016/0925-4439(92)90147-f. PMID 1737067.
Lohse P, Kindt MR, Rader DJ, Brewer HB (1990). "Human plasma apolipoproteins A-IV-0 and A-IV-3. Molecular basis for two rare variants of apolipoprotein A-IV-1". J. Biol. Chem. 265 (21): 12734–9. PMID 1973689.
Tenkanen H, Lukka M, Jauhiainen M, et al. (1991). "The mutation causing the common apolipoprotein A-IV polymorphism is a glutamine to histidine substitution of amino acid 360". Arterioscler. Thromb. 11 (4): 851–6. doi:10.1161/01.atv.11.4.851. PMID 2065039.
de Temmerman P, Visvikis S, Boerwinkle E, Siest G (1990). "Study of the sequence tagged site (STS) in the beginning of human apo A4 gene region". Nucleic Acids Res. 18 (18): 5576. doi:10.1093/nar/18.18.5576. PMC 332267. PMID 2216752.
Wei S, Rocchi M, Archidiacono N, et al. (1990). "Physical mapping of the human chromosome 11q23 region containing the ataxia-telangiectasia locus". Cancer Genet. Cytogenet. 46 (1): 1–8. doi:10.1016/0165-4608(90)90002-R. PMID 2331673.
Lohse P, Kindt MR, Rader DJ, Brewer HB (1990). "Genetic polymorphism of human plasma apolipoprotein A-IV is due to nucleotide substitutions in the apolipoprotein A-IV gene". J. Biol. Chem. 265 (17): 10061–4. PMID 2351649.
Yang CY, Gu ZW, Chong IS, et al. (1989). "The primary structure of human apolipoprotein A-IV". Biochim. Biophys. Acta. 1002 (2): 231–7. doi:10.1016/0005-2760(89)90292-0. PMID 2930771.
Elshourbagy NA, Walker DW, Boguski MS, et al. (1986). "The nucleotide and derived amino acid sequence of human apolipoprotein A-IV mRNA and the close linkage of its gene to the genes of apolipoproteins A-I and C-III". J. Biol. Chem. 261 (5): 1998–2002. PMID 3080432.
Bisgaier CL, Sachdev OP, Lee ES, et al. (1987). "Effect of lecithin:cholesterol acyltransferase on distribution of apolipoprotein A-IV among lipoproteins of human plasma". J. Lipid Res. 28 (6): 693–703. PMID 3611972.
Karathanasis SK, Yunis I, Zannis VI (1986). "Structure, evolution, and tissue-specific synthesis of human apolipoprotein AIV". Biochemistry. 25 (13): 3962–70. doi:10.1021/bi00361a034. PMID 3755616.
Karathanasis SK (1985). "Apolipoprotein multigene family: tandem organization of human apolipoprotein AI, CIII, and AIV genes". Proceedings of the National Academy of Sciences of the United States of America. 82 (19): 6374–8. Bibcode:1985PNAS...82.6374K. doi:10.1073/pnas.82.19.6374. PMC 390718. PMID 3931073.
Gordon JI, Bisgaier CL, Sims HF, et al. (1984). "Biosynthesis of human preapolipoprotein A-IV". J. Biol. Chem. 259 (1): 468–74. PMID 6706947.
Menzel HJ, Dieplinger H, Sandholzer C, et al. (1995). "Apolipoprotein A-IV polymorphism in the Hungarian population: gene frequencies, effect on lipid levels, and sequence of two new variants". Hum. Mutat. 5 (1): 58–65. doi:10.1002/humu.1380050108. PMID 7728150. S2CID 3063305.
Duverger N, Tremp G, Caillaud JM, et al. (1996). "Protection against atherogenesis in mice mediated by human apolipoprotein A-IV". Science. 273 (5277): 966–8. Bibcode:1996Sci...273..966D. doi:10.1126/science.273.5277.966. PMID 8688083. S2CID 30484255.
Deeb SS, Nevin DN, Iwasaki L, Brunzell JD (1997). "Two novel apolipoprotein A-IV variants in individuals with familial combined hyperlipidemia and diminished levels of lipoprotein lipase activity". Hum. Mutat. 8 (4): 319–25. doi:10.1002/(SICI)1098-1004(1996)8:4<319::AID-HUMU4>3.0.CO;2-2. PMID 8956036.

Vanjski linkovi

Apolipoprotein A-IV na US National Library of Medicine Medical Subject Headings (MeSH)
Lokacija ljudskog genoma APOA4 i stranica sa detaljima o genu APOA4 u UCSC Genome Browseru.

Šablon:Lipoproteini

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000110244 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000032080 - 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.

[pmid3095836-5] Karathanasis SK, Oettgen P, Haddad IA, Antonarakis SE (novembar 1986). "Structure, evolution, and polymorphisms of the human apolipoprotein A4 gene (APOA4)". Proceedings of the National Academy of Sciences of the United States of America. 83 (22): 8457–61. Bibcode:1986PNAS...83.8457K. doi:10.1073/pnas.83.22.8457. PMC 386949. PMID 3095836.

[pmid3036793-6] Elshourbagy NA, Walker DW, Paik YK, Boguski MS, Freeman M, Gordon JI, Taylor JM (juni 1987). "Structure and expression of the human apolipoprotein A-IV gene". J. Biol. Chem. 262 (17): 7973–81. PMID 3036793.

[entrez-7] "Entrez Gene: APOA4 apolipoprotein A-IV".

[pmid3084795-8] Luo CC, Li WH, Moore MN, Chan L (februar 1986). "Structure and evolution of the apolipoprotein multigene family". J. Mol. Biol. 187 (3): 325–340. doi:10.1016/0022-2836(86)90436-5. PMID 3084795.

[UniProt-9] "UniProt, P06727". Pristupljeno 16. 8. 2021.

[pmid11254757-10] Deeg, M A; Bierman E L; Cheung M C (mart 2001). "GPI-specific phospholipase D associates with an apoA-I- and apoA-IV-containing complex". J. Lipid Res. United States. 42 (3): 442–51. ISSN 0022-2275. PMID 11254757.

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