NFKBID

NFKBID
Identifikatori
AliasiNFKBID, IkappaBNS, TA-NFKBH, IkBNS
Vanjski ID-jeviMGI: 3041243 HomoloGene: 13101 GeneCards: NFKBID
Lokacija gena (čovjek)
Hromosom 19 (čovjek)
Hrom.Hromosom 19 (čovjek)[1]
Hromosom 19 (čovjek)
Genomska lokacija za NFKBID
Genomska lokacija za NFKBID
Bend19q13.12Početak35,887,653 bp[1]
Kraj35,902,303 bp[1]
Lokacija gena (miš)
Hromosom 7 (miš)
Hrom.Hromosom 7 (miš)[2]
Hromosom 7 (miš)
Genomska lokacija za NFKBID
Genomska lokacija za NFKBID
Bend7|7 B1Početak30,121,157 bp[2]
Kraj30,128,171 bp[2]
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
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_139239
NM_001321831
NM_001365705
NM_001365706
NM_032721

NM_172142
NM_001360906
NM_001360907

RefSeq (bjelančevina)

NP_001308760
NP_640332
NP_001352634
NP_001352635
NP_116110

NP_742154
NP_001347835
NP_001347836

Lokacija (UCSC)Chr 19: 35.89 – 35.9 MbChr 7: 30.12 – 30.13 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/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
1020304050
MEAGPWRVSAPPSGPPQFPAVVPGPSLEVARAHMLALGPQQLLAQDEEGD
TLLHLFAARGLRWAAYAAAEVLQVYRRLDIREHKGKTPLLVAAAANQPLI
VEDLLNLGAEPNAADHQGRSVLHVAATYGLPGVLLAVLNSGVQVDLEARD
FEGLTPLHTAILALNVAMRPSDLCPRVLSTQARDRLDCVHMLLQMGANHT
SQEIKSNKTVLHLAVQAANPTLVQLLLELPRGDLRTFVNMKAHGNTALHM
AAALPPGPAQEAIVRHLLAAGADPTLRNLENEQPVHLLRPGPGPEGLRQL
LKRSRVAPPGLSS

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.

Model interakcije NFKBID-a (ljubičasta) sa p50 homodimerom (zelena i plava) vezanim za DNK (crvena).
Kompleks je proučavan eksperimentima molekulskog vezanja. Kompleks NFKBID-p50/p50 elektrostatički djeluje s fosfatima DNK okosnice.
Zato proteinski kompleks ne može izaći iz jedra. Uglavnom pozitivno nabijena površina NFKBID blizu DNK, blokira razmjenu dimera p50 p50 s drugim dimerama, koji aktiviraju transkripcijske faktore.[13]

Reference

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000167604 - Ensembl, maj 2017
  2. ^ a b c 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.
  5. ^ "Entrez Gene: Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, delta".
  6. ^ 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.
  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.
  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.
  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.
  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.
  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.
  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.
  13. ^ 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.

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