NFKBID

NFKBID
Identifikatori
Aliasi	NFKBID, IkappaBNS, TA-NFKBH, IkBNS
Vanjski ID-jevi	MGI: 3041243 HomoloGene: 13101 GeneCards: NFKBID
Lokacija gena (čovjek)
Hrom.	Hromosom 19 (čovjek)
Kraj	35,902,303 bp
Lokacija gena (miš)
Hrom.	Hromosom 7 (miš)
Kraj	30,128,171 bp
Ontologija gena
Molekularna funkcija	• GO:0001948, GO:0016582 vezivanje za proteine; • GO:0001104 transcription coregulator activity; • NF-kappaB binding;
Ćelijska komponenta	• jedro;
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; • negative regulation of T cell differentiation in thymus; • positive regulation of thymocyte apoptotic process; • inflammatory response; • negative regulation of NF-kappaB transcription factor activity; • negative regulation of I-kappaB kinase/NF-kappaB signaling; • T cell receptor signaling pathway; • positive regulation of T-helper 17 cell differentiation;
	Izvori:Amigo / QuickGO
Ortolozi
	84807
	243910
	ENSG00000167604
	ENSMUSG00000036931
	Q8NI38
	Q2TB02
	NM_139239; NM_001321831; NM_001365705; NM_001365706; NM_032721
	NM_172142; NM_001360906; NM_001360907
	NP_001308760; NP_640332; NP_001352634; NP_001352635; NP_116110
	NP_742154; NP_001347835; NP_001347836
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Delta jedarni faktor pojačivača kapa lahkog polipeptidnog gena B-ćelija, znan i kao IκBNS, je protein koji je kod ljudi kodiran genom NFKBID.^[5]

IκBNS je član nepskih inhibitora NF-κB (koji se nazivaju i jedarni IκB). NF-κB je faktor transkripcije, koji regulira ekspresiju svojih ciljnih gena, ovisno o unutarćelijskim i vanćelijskim signalima. Kako NFKBID utiče na efekte NF-κB na nekoliko gena, uključen je u ćelijske odgovore na podražaje kao što su stres i bakterijski ili virusni antigeni.

Struktura

NFKBID je jedarni protein sa 327 aminokiselina. Sadrži šest ponavljanja ankirina (ANK), koji su okruženi sekvencom jedarnog lokalizacijskog signala (NLS) na N-kraju i kratkim C-krajem.^[6]^[7] ANK su karakteristični za sve IκB proteine. NLS je dodatni karakteristični strukturni element samo nepskih proteina IκB, koji je odgovoran za lokalizaciju proteina u jedru. Suprotno tome, klasični inhibitori, npr. IκBα i IκBβ, nalaze se u citoplazmi. Još nije dostupna struktura NFKBID visoke rezolucije.

Shma NFKBID. Sastoji se od šest ankirinskih domena (ANK - plava) i signalne sekvence jedarne lokalizacije (NLS - zelena).

Aminokiselinski sastav

Simboli

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
MEAGPWRVSA	PPSGPPQFPA	VVPGPSLEVA	RAHMLALGPQ	QLLAQDEEGD
TLLHLFAARG	LRWAAYAAAE	VLQVYRRLDI	REHKGKTPLL	VAAAANQPLI
VEDLLNLGAE	PNAADHQGRS	VLHVAATYGL	PGVLLAVLNS	GVQVDLEARD
FEGLTPLHTA	ILALNVAMRP	SDLCPRVLST	QARDRLDCVH	MLLQMGANHT
SQEIKSNKTV	LHLAVQAANP	TLVQLLLELP	RGDLRTFVNM	KAHGNTALHM
AAALPPGPAQ	EAIVRHLLAA	GADPTLRNLE	NEQPVHLLRP	GPGPEGLRQL
LKRSRVAPPG	LSS

Funkcija

NFKBID djeluje kao inhibitor kaskade NF-κB. Svojim funkcijama, uključujući promociju reakcija zametnih centara i potrebe za imunosupresivnim regulatornim T-ćelijama, NFKBID regulira homeostazu imunskog sistema i ima različite daljnje posljedice na njega.^[6] Furthermore, NFKBID influences B cells and plasma cells substantially, concerning their functions and development.^[8]

Ekspresija NFKBID je precizno regulirana. Nakon aktivacije NF-κB, netipski IkB inducira transkripcijski faktor. Atipski IkB, zauzvrat, mogu regulirati transkripciju NF-κB, kao induktori ili inhibitori. Suprotno tome, klasični proteini mogu potisnuti samo transkripciju NF-κB. U zrelim T-ćelijama (CD4 +) stimulacija receptora T-ćelija (TCR) može inducirati ekspresiju NFKBID, dok u makrofagu u ovoj aktivnosti djeluju TLR ligandi.^[9]^[10]

Da bi uticao na transkripciju gena, NFKBID ima neke interakcijske proteinske partnere. Izvješteno je da NFKBID komunicira s p50, koji je podjedinica NF-κB, p52, p65, RelB i c-Rel. NFKBID veže ove proteine samo u jedru, osim za p50, koji se može vezati i u citoplazmi i u jedru.^[11]^[12]

Istraživanja sugeriraju da osim ovoga, NFKBID može komunicirati i sa homo- i heterodimerima, koji se sastoje od nekih od ovih podjedinica, npr. p50/p50 i p65/p50.^[13] Ovisno o ciljnom genu i o tome na koji je protein vezan NFKBID, on može funkcionirati i kao represor i kao aktivator.

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000167604 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000036931 - 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.
^ "Entrez Gene: Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, delta".
^ ^a ^b Schuster M, Annemann M, Plaza-Sirvent C, Schmitz I (2013). "Atypical IκB proteins - nuclear modulators of NF-κB signaling". Cell Commun Signal. 11 (1): 23. doi:10.1186/1478-811X-11-23. PMC 3639191. PMID 23578005.
^ Chiba T, Inoko H, Kimura M, Sato T (2013). "Role of nuclear IκBs in inflammation regulation". Biomol Concepts. 4 (2): 187–96. doi:10.1515/bmc-2012-0039. PMID 25436575. S2CID 4544736.
^ Touma M, Keskin DB, Shiroki F, Saito I, Koyasu S, Reinherz EL, Clayton LK (2011). "Impaired B cell development and function in the absence of IkappaBNS". J. Immunol. 187 (8): 3942–52. doi:10.4049/jimmunol.1002109. PMC 3348541. PMID 21900180.
^ Schuster M, Glauben R, Plaza-Sirvent C, Schreiber L, Annemann M, Floess S, Kühl AA, Clayton LK, Sparwasser T, Schulze-Osthoff K, Pfeffer K, Huehn J, Siegmund B, Schmitz I (2012). "IκB(NS) protein mediates regulatory T cell development via induction of the Foxp3 transcription factor". Immunity. 37 (6): 998–1008. doi:10.1016/j.immuni.2012.08.023. PMID 23200824.
^ Kuwata H, Matsumoto M, Atarashi K, Morishita H, Hirotani T, Koga R, Takeda K (2006). "IkappaBNS inhibits induction of a subset of Toll-like receptor-dependent genes and limits inflammation". Immunity. 24 (1): 41–51. doi:10.1016/j.immuni.2005.11.004. PMID 16413922.
^ Hirotani T, Lee PY, Kuwata H, Yamamoto M, Matsumoto M, Kawase I, Akira S, Takeda K (2005). "The nuclear IkappaB protein IkappaBNS selectively inhibits lipopolysaccharide-induced IL-6 production in macrophages of the colonic lamina propria". J. Immunol. 174 (6): 3650–7. doi:10.4049/jimmunol.174.6.3650. PMID 15749903.
^ Fiorini E, Schmitz I, Marissen WE, Osborn SL, Touma M, Sasada T, Reche PA, Tibaldi EV, Hussey RE, Kruisbeek AM, Reinherz EL, Clayton LK (2002). "Peptide-induced negative selection of thymocytes activates transcription of an NF-kappa B inhibitor". Mol. Cell. 9 (3): 637–48. doi:10.1016/s1097-2765(02)00469-0. PMID 11931770.
^ ^a ^b Manavalan B, Basith S, Choi YM, Lee G, Choi S (2010). "Structure-function relationship of cytoplasmic and nuclear IκB proteins: an in silico analysis". PLOS ONE. 5 (12): e15782. doi:10.1371/journal.pone.0015782. PMC 3009747. PMID 21203422.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000167604 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000036931 - 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.

[entrez-5] "Entrez Gene: Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, delta".

[Atypical_IkB_proteins-6] Schuster M, Annemann M, Plaza-Sirvent C, Schmitz I (2013). "Atypical IκB proteins - nuclear modulators of NF-κB signaling". Cell Commun Signal. 11 (1): 23. doi:10.1186/1478-811X-11-23. PMC 3639191. PMID 23578005.

[Role_of_nuclear_IkBs-7] Chiba T, Inoko H, Kimura M, Sato T (2013). "Role of nuclear IκBs in inflammation regulation". Biomol Concepts. 4 (2): 187–96. doi:10.1515/bmc-2012-0039. PMID 25436575. S2CID 4544736.

[Impaired_B_cell_development-8] Touma M, Keskin DB, Shiroki F, Saito I, Koyasu S, Reinherz EL, Clayton LK (2011). "Impaired B cell development and function in the absence of IkappaBNS". J. Immunol. 187 (8): 3942–52. doi:10.4049/jimmunol.1002109. PMC 3348541. PMID 21900180.

[IκB(NS)_protein_mediates-9] Schuster M, Glauben R, Plaza-Sirvent C, Schreiber L, Annemann M, Floess S, Kühl AA, Clayton LK, Sparwasser T, Schulze-Osthoff K, Pfeffer K, Huehn J, Siegmund B, Schmitz I (2012). "IκB(NS) protein mediates regulatory T cell development via induction of the Foxp3 transcription factor". Immunity. 37 (6): 998–1008. doi:10.1016/j.immuni.2012.08.023. PMID 23200824.

[IkappaBNS_inhibits-10] Kuwata H, Matsumoto M, Atarashi K, Morishita H, Hirotani T, Koga R, Takeda K (2006). "IkappaBNS inhibits induction of a subset of Toll-like receptor-dependent genes and limits inflammation". Immunity. 24 (1): 41–51. doi:10.1016/j.immuni.2005.11.004. PMID 16413922.

[The_nuclear_IkappaB_protein-11] Hirotani T, Lee PY, Kuwata H, Yamamoto M, Matsumoto M, Kawase I, Akira S, Takeda K (2005). "The nuclear IkappaB protein IkappaBNS selectively inhibits lipopolysaccharide-induced IL-6 production in macrophages of the colonic lamina propria". J. Immunol. 174 (6): 3650–7. doi:10.4049/jimmunol.174.6.3650. PMID 15749903.

[Peptide-induced_negative_selection-12] Fiorini E, Schmitz I, Marissen WE, Osborn SL, Touma M, Sasada T, Reche PA, Tibaldi EV, Hussey RE, Kruisbeek AM, Reinherz EL, Clayton LK (2002). "Peptide-induced negative selection of thymocytes activates transcription of an NF-kappa B inhibitor". Mol. Cell. 9 (3): 637–48. doi:10.1016/s1097-2765(02)00469-0. PMID 11931770.

[Structure-function_relationship-13] Manavalan B, Basith S, Choi YM, Lee G, Choi S (2010). "Structure-function relationship of cytoplasmic and nuclear IκB proteins: an in silico analysis". PLOS ONE. 5 (12): e15782. doi:10.1371/journal.pone.0015782. PMC 3009747. PMID 21203422.

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