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NFKBIZ
Identifikatori
Aliasi	NFKBIZ
Vanjski ID-jevi	OMIM: 608004 MGI: 1931595 HomoloGene: 12734 GeneCards: NFKBIZ
Lokacija gena (čovjek)
Hrom.	Hromosom 3 (čovjek)
Kraj	101,861,022 bp
Lokacija gena (miš)
Hrom.	Hromosom 16 (miš)
Kraj	55,659,262 bp
Ontologija gena
Molekularna funkcija	• GO:0001948, GO:0016582 vezivanje za proteine; • GO:0001104 transcription coregulator activity;
Ćelijska komponenta	• jedro; • nuclear speck; • cytoplasmic ribonucleoprotein granule;
Biološki proces	• GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1900094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II; • inflammatory response; • GO:0009373 regulation of transcription, DNA-templated; • transcription, DNA-templated; • T cell receptor signaling pathway; • positive regulation of T-helper 17 cell differentiation; • positive regulation of inflammatory response;
	Izvori:Amigo / QuickGO
Ortolozi
	64332
	80859
	ENSG00000144802
	ENSMUSG00000035356
	Q9BYH8
	Q9EST8
	NM_031419; NM_001005474
	NM_001159394; NM_001159395; NM_030612
	NP_001005474; NP_113607
	NP_001152866; NP_001152867; NP_085115
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

NF-kapa-B inhibitor zeta (IκBζ) jest protein koji je kod ljudi kodiran genom NFKBIZ sa hromosoma 3.^[5]^[6]^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 718 aminokiselina, а molekulska težina 78.061 Da.^[8]

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
MIVDKLLDDS	RGGEGLRDAA	GGCGLMTSPL	NLSYFYGASP	PAAAPGACDA
SCSVLGPSAP	GSPGSDSSDF	SSASSVSSCG	AVESRSRGGA	RAERQPVEPH
MGVGRQQRGP	FQGVRVKNSV	KELLLHIRSH	KQKASGQAVD	DFKTQGVNIE
QFRELKNTVS	YSGKRKGPDS	LSDGPACKRP	ALLHSQFLTP	PQTPTPGESM
EDVHLNEPKQ	ESSADLLQNI	INIKNECSPV	SLNTVQVSWL	NPVVVPQSSP
AEQCQDFHGG	QVFSPPQKCQ	PFQVRGSQQM	IDQASLYQYS	PQNQHVEQQP
HYTHKPTLEY	SPFPIPPQSP	AYEPNLFDGP	ESQFCPNQSL	VSLLGDQRES
ENIANPMQTS	SSVQQQNDAH	LHSFSMMPSS	ACEAMVGHEM	ASDSSNTSLP
FSNMGNPMNT	TQLGKSLFQW	QVEQEESKLA	NISQDQFLSK	DADGDTFLHI
AVAQGRRALS	YVLARKMNAL	HMLDIKEHNG	QSAFQVAVAA	NQHLIVQDLV
NIGAQVNTTD	CWGRTPLHVC	AEKGHSQVLQ	AIQKGAVGSN	QFVDLEATNY
DGLTPLHCAV	IAHNAVVHEL	QRNQQPHSPE	VQELLLKNKS	LVDTIKCLIQ
MGAAVEAKDR	KSGRTALHLA	AEEANLELIR	LFLELPSCLS	FVNAKAYNGN
TALHVAASLQ	YRLTQLDAVR	LLMRKGADPS	TRNLENEQPV	HLVPDGPVGE
QIRRILKGKS	IQQRAPPY

Funkcija

Ovaj gen je član porodice ankirinskihponavcljanja i induciran je lipopolisaharidom (LPS). C-terminalni dio kodiranog proizvoda koji sadrži ankirinska ponavljanja, dijeli veliku sličnost sa porodicom proteina sa slučnošću sekvence I kapa B. Poznato je da potonji imaju ulogu u upalnim odgovorima na LPS njihovom interakcijom sa NF-B proteinima preko domena za ponavljanje ankirina. Studije na miševima pokazuju da je ovaj genski proizvod jedan od jedarnih I kapa B proteina i aktivator proizvodnje IL-6. Za ovaj gen su pronađene dvije varijante transkripta koje kodiraju različite izoforme.^[9]

Klinički značaj

NFKBIZ je impliciran kao onkogen u difuznom velikom B-ćelijskom limfomu (DLBCL). Konkretno, genomski lokus koji sadrži ovaj gen se rekurentno umnožava u broju kopija u aktiviranoj B-ćelijskoj (ABC) podgrupi DLBCL.^[10] Nedavno je otkriveno da ponavljanje somatskih mutacija koje utjiču na 3-prim neprevedenu regiju NFKBIZ promovira ekspresiju NFKBIZ u ABC DLBCL.^[11]

IκBζ potreban je za ekspresiju sekretornog fenotipa povezanog sa starenjem (SASP) CCL2 (MCP1) citokina, koji regrutuje makrofage za uklanjanje ćelija raka.^[7]

Pokazalo se da flavonoid apigenin smanjuje ekspresiju gena IκBζ.^[12]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000144802 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000035356 - 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.
^ Eto A, Muta T, Yamazaki S, Takeshige K (februar 2003). "Essential roles for NF-kappa B and a Toll/IL-1 receptor domain-specific signal(s) in the induction of I kappa B-zeta". Biochemical and Biophysical Research Communications. 301 (2): 495–501. doi:10.1016/S0006-291X(02)03082-6. PMID 12565889.
^ Totzke G, Essmann F, Pohlmann S, Lindenblatt C, Jänicke RU, Schulze-Osthoff K (maj 2006). "A novel member of the IkappaB family, human IkappaB-zeta, inhibits transactivation of p65 and its DNA binding". The Journal of Biological Chemistry. 281 (18): 12645–54. doi:10.1074/jbc.M511956200. PMID 16513645.
^ ^a ^b Alexander E, Hildebrand DG, Schulze-Osthoff K, Essmann F (2013). "IκBζ is a regulator of the senescence-associated secretory phenotype in DNA damage- and oncogene-induced senescence". Journal of Cell Science. 126 (Pt 16): 3738–3745. doi:10.1242/jcs.128835. PMID 23781024.
^ "UniProt, Q9BYH8" (jezik: engleski). Pristupljeno 8. 11. 2021.
^ "Entrez Gene: NFKBIZ nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta".
^ Nogai H, Wenzel SS, Hailfinger S, Grau M, Kaergel E, Seitz V, et al. (septembar 2013). "IκB-ζ controls the constitutive NF-κB target gene network and survival of ABC DLBCL". Blood. 122 (13): 2242–50. doi:10.1182/blood-2013-06-508028. PMID 23869088.
^ Arthur SE, Jiang A, Grande BM, Alcaide M, Cojocaru R, Rushton CK, et al. (oktobar 2018). "Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma". Nature Communications. 9 (1): 4001. Bibcode:2018NatCo...9.4001A. doi:10.1038/s41467-018-06354-3. PMC 6167379. PMID 30275490.
^ Lim H, Heo MY, Kim HP (2019). "Flavonoids: Broad Spectrum Agents on Chronic Inflammation". Biomolecules & Therapeutics. 27 (3): 241–253. doi:10.4062/biomolther.2019.034. PMC 6513185. PMID 31006180.

Dopunska literatura

Kitamura H, Kanehira K, Okita K, Morimatsu M, Saito M (novembar 2000). "MAIL, a novel nuclear I kappa B protein that potentiates LPS-induced IL-6 production". FEBS Letters. 485 (1): 53–6. doi:10.1016/S0014-5793(00)02185-2. PMID 11086164. S2CID 85416608.
Shiina T, Morimatsu M, Kitamura H, Ito T, Kidou S, Matsubara K, Matsuda Y, Saito M, Syuto B (oktobar 2001). "Genomic organization, chromosomal localization, and promoter analysis of the mouse Mail gene". Immunogenetics. 53 (8): 649–55. doi:10.1007/s00251-001-0376-x. PMID 11797098. S2CID 12387932.
Haruta H, Kato A, Todokoro K (april 2001). "Isolation of a novel interleukin-1-inducible nuclear protein bearing ankyrin-repeat motifs". The Journal of Biological Chemistry. 276 (16): 12485–8. doi:10.1074/jbc.C100075200. PMID 11278262.
Yamazaki S, Muta T, Takeshige K (juli 2001). "A novel IkappaB protein, IkappaB-zeta, induced by proinflammatory stimuli, negatively regulates nuclear factor-kappaB in the nuclei". The Journal of Biological Chemistry. 276 (29): 27657–62. doi:10.1074/jbc.M103426200. PMID 11356851.
Kitamura H, Kanehira K, Shiina T, Morimatsu M, Jung BD, Akashi S, Saito M (maj 2002). "Bacterial lipopolysaccharide induces mRNA expression of an IkappaB MAIL through toll-like receptor 4". The Journal of Veterinary Medical Science. 64 (5): 419–22. doi:10.1292/jvms.64.419. PMID 12069074.
Kitamura H, Matsushita Y, Iwanaga T, Mori K, Kanehira K, Fujikura D, Morimatsu M, Saito M (mart 2003). "Bacterial lipopolysaccharide-induced expression of the IkappaB protein MAIL in B-lymphocytes and macrophages". Archives of Histology and Cytology. 66 (1): 53–62. doi:10.1679/aohc.66.53. PMID 12703554.
Shiina T, Konno A, Oonuma T, Kitamura H, Imaoka K, Takeda N, Todokoro K, Morimatsu M (decembar 2004). "Targeted disruption of MAIL, a nuclear IkappaB protein, leads to severe atopic dermatitis-like disease". The Journal of Biological Chemistry. 279 (53): 55493–8. doi:10.1074/jbc.M409770200. PMID 15491998.
Ito T, Morimatsu M, Oonuma T, Shiina T, Kitamura H, Syuto B (novembar 2004). "Transcriptional regulation of the MAIL gene in LPS-stimulated RAW264 mouse macrophages". Gene. 342 (1): 137–43. doi:10.1016/j.gene.2004.07.032. PMID 15527973.
Yamamoto M, Yamazaki S, Uematsu S, Sato S, Hemmi H, Hoshino K, Kaisho T, Kuwata H, Takeuchi O, Takeshige K, Saitoh T, Yamaoka S, Yamamoto N, Yamamoto S, Muta T, Takeda K, Akira S (juli 2004). "Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IkappaBzeta". Nature. 430 (6996): 218–22. doi:10.1038/nature02738. PMID 15241416. S2CID 4384768.
Yamaji D, Kitamura H, Kimura K, Matsushita Y, Okada H, Shiina T, Morimatsu M, Saito M (april 2004). "Cloning of bovine MAIL and its mRNA expression in white blood cells of Holstein cows". Veterinary Immunology and Immunopathology. 98 (3–4): 175–84. doi:10.1016/j.vetimm.2003.12.004. PMID 15010226.
Yamazaki S, Muta T, Matsuo S, Takeshige K (januar 2005). "Stimulus-specific induction of a novel nuclear factor-kappaB regulator, IkappaB-zeta, via Toll/Interleukin-1 receptor is mediated by mRNA stabilization". The Journal of Biological Chemistry. 280 (2): 1678–87. doi:10.1074/jbc.M409983200. PMID 15522867.
Motoyama M, Yamazaki S, Eto-Kimura A, Takeshige K, Muta T (mart 2005). "Positive and negative regulation of nuclear factor-kappaB-mediated transcription by IkappaB-zeta, an inducible nuclear protein". The Journal of Biological Chemistry. 280 (9): 7444–51. doi:10.1074/jbc.M412738200. PMID 15618216.
Cowland JB, Muta T, Borregaard N (maj 2006). "IL-1beta-specific up-regulation of neutrophil gelatinase-associated lipocalin is controlled by IkappaB-zeta". Journal of Immunology. 176 (9): 5559–66. doi:10.4049/jimmunol.176.9.5559. PMID 16622025.
Oonuma T, Morimatsu M, Ochiai K, Iwanaga T, Hashizume K (mart 2007). "Role of NF-kappaB in constitutive expression of MAIL in epidermal keratinocytes". The Journal of Veterinary Medical Science. 69 (3): 279–84. doi:10.1292/jvms.69.279. PMID 17409644.
Matsuo S, Yamazaki S, Takeshige K, Muta T (august 2007). "Crucial roles of binding sites for NF-kappaB and C/EBPs in IkappaB-zeta-mediated transcriptional activation". The Biochemical Journal. 405 (3): 605–15. doi:10.1042/BJ20061797. PMC 2267307. PMID 17447895.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000144802 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000035356 - 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.

[pmid12565889-5] Eto A, Muta T, Yamazaki S, Takeshige K (februar 2003). "Essential roles for NF-kappa B and a Toll/IL-1 receptor domain-specific signal(s) in the induction of I kappa B-zeta". Biochemical and Biophysical Research Communications. 301 (2): 495–501. doi:10.1016/S0006-291X(02)03082-6. PMID 12565889.

[pmid16513645-6] Totzke G, Essmann F, Pohlmann S, Lindenblatt C, Jänicke RU, Schulze-Osthoff K (maj 2006). "A novel member of the IkappaB family, human IkappaB-zeta, inhibits transactivation of p65 and its DNA binding". The Journal of Biological Chemistry. 281 (18): 12645–54. doi:10.1074/jbc.M511956200. PMID 16513645.

[pmid23781024-7] Alexander E, Hildebrand DG, Schulze-Osthoff K, Essmann F (2013). "IκBζ is a regulator of the senescence-associated secretory phenotype in DNA damage- and oncogene-induced senescence". Journal of Cell Science. 126 (Pt 16): 3738–3745. doi:10.1242/jcs.128835. PMID 23781024.

[UniProt-8] "UniProt, Q9BYH8" (jezik: engleski). Pristupljeno 8. 11. 2021.

[entrez-9] "Entrez Gene: NFKBIZ nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta".

[nogai-10] Nogai H, Wenzel SS, Hailfinger S, Grau M, Kaergel E, Seitz V, et al. (septembar 2013). "IκB-ζ controls the constitutive NF-κB target gene network and survival of ABC DLBCL". Blood. 122 (13): 2242–50. doi:10.1182/blood-2013-06-508028. PMID 23869088.

[arthur-11] Arthur SE, Jiang A, Grande BM, Alcaide M, Cojocaru R, Rushton CK, et al. (oktobar 2018). "Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma". Nature Communications. 9 (1): 4001. Bibcode:2018NatCo...9.4001A. doi:10.1038/s41467-018-06354-3. PMC 6167379. PMID 30275490.

[pmid31006180-12] Lim H, Heo MY, Kim HP (2019). "Flavonoids: Broad Spectrum Agents on Chronic Inflammation". Biomolecules & Therapeutics. 27 (3): 241–253. doi:10.4062/biomolther.2019.034. PMC 6513185. PMID 31006180.

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