ID NFKB1_CANFA Reviewed; 972 AA. AC Q6F3J0; F1PM82; DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot. DT 18-APR-2012, sequence version 2. DT 29-OCT-2014, entry version 81. DE RecName: Full=Nuclear factor NF-kappa-B p105 subunit; DE AltName: Full=Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1; DE Contains: DE RecName: Full=Nuclear factor NF-kappa-B p50 subunit; GN Name=NFKB1; OS Canis familiaris (Dog) (Canis lupus familiaris). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; OC Canis. OX NCBI_TaxID=9615; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Oguma K., Kano R., Hasegawa A.; RT "Canis familiaris nuclear factor of kappa light polypeptide gene RT enhancer in B-cells 1 (p105) (NFKB1), mRNA."; RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Boxer; RX PubMed=16341006; DOI=10.1038/nature04338; RA Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B., RA Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., RA Mauceli E., Xie X., Breen M., Wayne R.K., Ostrander E.A., RA Ponting C.P., Galibert F., Smith D.R., deJong P.J., Kirkness E.F., RA Alvarez P., Biagi T., Brockman W., Butler J., Chin C.-W., Cook A., RA Cuff J., Daly M.J., DeCaprio D., Gnerre S., Grabherr M., Kellis M., RA Kleber M., Bardeleben C., Goodstadt L., Heger A., Hitte C., Kim L., RA Koepfli K.-P., Parker H.G., Pollinger J.P., Searle S.M.J., RA Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A., RA Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P., RA Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., RA Bachantsang P., Barry A., Bayul T., Benamara M., Berlin A., RA Bessette D., Blitshteyn B., Bloom T., Blye J., Boguslavskiy L., RA Bonnet C., Boukhgalter B., Brown A., Cahill P., Calixte N., RA Camarata J., Cheshatsang Y., Chu J., Citroen M., Collymore A., RA Cooke P., Dawoe T., Daza R., Decktor K., DeGray S., Dhargay N., RA Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L., Duffey N., RA Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S., RA Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., RA Foley C., Franke A., Friedrich D., Gage D., Garber M., Gearin G., RA Giannoukos G., Goode T., Goyette A., Graham J., Grandbois E., RA Gyaltsen K., Hafez N., Hagopian D., Hagos B., Hall J., Healy C., RA Hegarty R., Honan T., Horn A., Houde N., Hughes L., Hunnicutt L., RA Husby M., Jester B., Jones C., Kamat A., Kanga B., Kells C., RA Khazanovich D., Kieu A.C., Kisner P., Kumar M., Lance K., Landers T., RA Lara M., Lee W., Leger J.-P., Lennon N., Leuper L., LeVine S., Liu J., RA Liu X., Lokyitsang Y., Lokyitsang T., Lui A., Macdonald J., Major J., RA Marabella R., Maru K., Matthews C., McDonough S., Mehta T., RA Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T., Miller K., RA Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A., Naylor J., RA Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N., RA Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., RA Osman S., Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., RA Priest M., Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., RA Rege F., Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., RA Sharpe T., Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., RA Smith C., Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., RA Stone C., Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., RA Thoulutsang D., Thoulutsang Y., Topham K., Topping I., Tsamla T., RA Vassiliev H., Venkataraman V., Vo A., Wangchuk T., Wangdi T., RA Weiand M., Wilkinson J., Wilson A., Yadav S., Yang S., Yang X., RA Young G., Yu Q., Zainoun J., Zembek L., Zimmer A., Lander E.S.; RT "Genome sequence, comparative analysis and haplotype structure of the RT domestic dog."; RL Nature 438:803-819(2005). CC -!- FUNCTION: NF-kappa-B is a pleiotropic transcription factor present CC in almost all cell types and is the endpoint of a series of signal CC transduction events that are initiated by a vast array of stimuli CC related to many biological processes such as inflammation, CC immunity, differentiation, cell growth, tumorigenesis and CC apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed CC by the Rel-like domain-containing proteins RELA/p65, RELB, CC NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric CC p65-p50 complex appears to be most abundant one. The dimers bind CC at kappa-B sites in the DNA of their target genes and the CC individual dimers have distinct preferences for different kappa-B CC sites that they can bind with distinguishable affinity and CC specificity. Different dimer combinations act as transcriptional CC activators or repressors, respectively. NF-kappa-B is controlled CC by various mechanisms of post-translational modification and CC subcellular compartmentalization as well as by interactions with CC other cofactors or corepressors. NF-kappa-B complexes are held in CC the cytoplasm in an inactive state complexed with members of the CC NF-kappa-B inhibitor (I-kappa-B) family. In a conventional CC activation pathway, I-kappa-B is phosphorylated by I-kappa-B CC kinases (IKKs) in response to different activators, subsequently CC degraded thus liberating the active NF-kappa-B complex which CC translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and CC RelB-p50 complexes are transcriptional activators. The NF-kappa-B CC p50-p50 homodimer is a transcriptional repressor, but can act as a CC transcriptional activator when associated with BCL3. NFKB1 appears CC to have dual functions such as cytoplasmic retention of attached CC NF-kappa-B proteins by p105 and generation of p50 by a CC cotranslational processing. The proteasome-mediated process CC ensures the production of both p50 and p105 and preserves their CC independent function, although processing of NFKB1/p105 also CC appears to occur post-translationally. p50 binds to the kappa-B CC consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region CC of genes involved in immune response and acute phase reactions. In CC a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK CC signaling; active MAP3K8 is released by proteasome-dependent CC degradation of NFKB1/p105 (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Component of the NF-kappa-B p65-p50 complex. Component of CC the NF-kappa-B p65-p50 complex. Homodimer; component of the NF- CC kappa-B p50-p50 complex. Component of the NF-kappa-B p105-p50 CC complex. Component of the NF-kappa-B p50-c-Rel complex. Component CC of a complex consisting of the NF-kappa-B p50-p50 homodimer and CC BCL3. Also interacts with MAP3K8. NF-kappa-B p50 subunit interacts CC with NCOA3 coactivator, which may coactivate NF-kappa-B dependent CC expression via its histone acetyltransferase activity. Interacts CC with DSIPI; this interaction prevents nuclear translocation and CC DNA-binding. Interacts with SPAG9 and UNC5CL. NFKB1/p105 interacts CC with CFLAR; the interaction inhibits p105 processing into p50. CC NFKB1/p105 forms a ternary complex with MAP3K8 and TNIP2. CC Interacts with GSK3B; the interaction prevents processing of p105 CC to p50. NFKB1/p50 interacts with NFKBIE. NFKB1/p50 interacts with CC NFKBIZ. Nuclear factor NF-kappa-B p50 subunit interacts with CC NFKBID (By similarity). Directly interacts with MEN1 (By CC similarity). Interacts with HIF1AN (By similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm CC {ECO:0000250}. Note=Nuclear, but also found in the cytoplasm in an CC inactive form complexed to an inhibitor (I-kappa-B). CC {ECO:0000250}. CC -!- DOMAIN: The C-terminus of p105 might be involved in cytoplasmic CC retention, inhibition of DNA-binding by p50 homodimers, and/or CC transcription activation. CC -!- PTM: While translation occurs, the particular unfolded structure CC after the GRR repeat promotes the generation of p50 making it an CC acceptable substrate for the proteasome. This process is known as CC cotranslational processing. The processed form is active and the CC unprocessed form acts as an inhibitor (I kappa B-like), being able CC to form cytosolic complexes with NF-kappa B, trapping it in the CC cytoplasm. Complete folding of the region downstream of the GRR CC repeat precludes processing (By similarity). {ECO:0000250}. CC -!- PTM: Phosphorylation at 'Ser-931' and 'Ser-936' are required for CC BTRC/BTRCP-mediated proteolysis. {ECO:0000250}. CC -!- PTM: S-nitrosylation of Cys-61 affects DNA binding. {ECO:0000250}. CC -!- PTM: The covalent modification of cysteine by 15-deoxy-Delta12,14- CC prostaglandin-J2 is autocatalytic and reversible. It may occur as CC an alternative to other cysteine modifications, such as S- CC nitrosylation and S-palmitoylation (By similarity). {ECO:0000250}. CC -!- SIMILARITY: Contains 7 ANK repeats. {ECO:0000255|PROSITE- CC ProRule:PRU00023}. CC -!- SIMILARITY: Contains 1 death domain. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 RHD (Rel-like) domain. CC {ECO:0000255|PROSITE-ProRule:PRU00265}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB183419; BAD27479.1; -; mRNA. DR RefSeq; NP_001003344.1; NM_001003344.1. DR UniGene; Cfa.10766; -. DR ProteinModelPortal; Q6F3J0; -. DR PaxDb; Q6F3J0; -. DR GeneID; 442859; -. DR KEGG; cfa:442859; -. DR CTD; 4790; -. DR eggNOG; NOG119056; -. DR HOGENOM; HOG000004822; -. DR HOVERGEN; HBG052613; -. DR InParanoid; Q6F3J0; -. DR KO; K02580; -. DR Reactome; REACT_174810; RIP-mediated NFkB activation via ZBP1. DR Reactome; REACT_175220; Senescence-Associated Secretory Phenotype (SASP). DR Reactome; REACT_175518; FCERI mediated NF-kB activation. DR Reactome; REACT_182274; Activation of NF-kappaB in B cells. DR NextBio; 20831583; -. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-KW. DR GO; GO:0001071; F:nucleic acid binding transcription factor activity; ISS:UniProtKB. DR GO; GO:0000975; F:regulatory region DNA binding; ISS:UniProtKB. DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:InterPro. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IEA:Ensembl. DR GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl. DR GO; GO:0071354; P:cellular response to interleukin-6; IEA:Ensembl. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0071316; P:cellular response to nicotine; IEA:Ensembl. DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IEA:Ensembl. DR GO; GO:0010956; P:negative regulation of calcidiol 1-monooxygenase activity; IEA:Ensembl. DR GO; GO:0001818; P:negative regulation of cytokine production; IEA:Ensembl. DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl. DR GO; GO:0045083; P:negative regulation of interleukin-12 biosynthetic process; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:1900127; P:positive regulation of hyaluronan biosynthetic process; IEA:Ensembl. DR GO; GO:2000630; P:positive regulation of miRNA metabolic process; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB. DR GO; GO:0007165; P:signal transduction; IEA:InterPro. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 1.10.533.10; -; 1. DR Gene3D; 1.25.40.20; -; 1. DR Gene3D; 2.60.40.10; -; 1. DR Gene3D; 2.60.40.340; -; 1. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR020683; Ankyrin_rpt-contain_dom. DR InterPro; IPR011029; DEATH-like_dom. DR InterPro; IPR000488; Death_domain. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR002909; IPT. DR InterPro; IPR000451; NF_Rel_Dor. DR InterPro; IPR008967; p53-like_TF_DNA-bd. DR InterPro; IPR011539; RHD. DR Pfam; PF00023; Ank; 2. DR Pfam; PF12796; Ank_2; 1. DR Pfam; PF00531; Death; 1. DR Pfam; PF00554; RHD; 1. DR PRINTS; PR00057; NFKBTNSCPFCT. DR SMART; SM00248; ANK; 6. DR SMART; SM00005; DEATH; 1. DR SMART; SM00429; IPT; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR SUPFAM; SSF48403; SSF48403; 1. DR SUPFAM; SSF49417; SSF49417; 1. DR SUPFAM; SSF81296; SSF81296; 1. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 5. DR PROSITE; PS01204; REL_1; 1. DR PROSITE; PS50254; REL_2; 1. PE 2: Evidence at transcript level; KW Acetylation; Activator; ANK repeat; Complete proteome; Cytoplasm; KW DNA-binding; Hydroxylation; Lipoprotein; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; S-nitrosylation; Transcription; KW Transcription regulation. FT CHAIN 1 972 Nuclear factor NF-kappa-B p105 subunit. FT /FTId=PRO_0000223240. FT CHAIN 1 433 Nuclear factor NF-kappa-B p50 subunit. FT {ECO:0000250}. FT /FTId=PRO_0000223241. FT DOMAIN 39 246 RHD. {ECO:0000255|PROSITE- FT ProRule:PRU00265}. FT REPEAT 539 568 ANK 1. FT REPEAT 578 607 ANK 2. FT REPEAT 611 640 ANK 3. FT REPEAT 647 676 ANK 4. FT REPEAT 681 711 ANK 5. FT REPEAT 715 744 ANK 6. FT REPEAT 768 798 ANK 7. FT DOMAIN 814 889 Death. FT REGION 372 394 GRR. {ECO:0000250}. FT REGION 435 972 Interaction with CFLAR. {ECO:0000250}. FT REGION 647 681 Essential for interaction with HIF1AN. FT {ECO:0000250}. FT MOTIF 360 365 Nuclear localization signal. FT {ECO:0000255}. FT COMPBIAS 375 433 Gly-rich. FT SITE 433 434 Cleavage (when cotranslationally FT processed). {ECO:0000250}. FT MOD_RES 61 61 S-nitrosocysteine; alternate. FT {ECO:0000250}. FT MOD_RES 337 337 Phosphoserine; by PKA. {ECO:0000255}. FT MOD_RES 431 431 N6-acetyllysine; by EP300. {ECO:0000250}. FT MOD_RES 440 440 N6-acetyllysine; by EP300. {ECO:0000250}. FT MOD_RES 675 675 (3S)-3-hydroxyasparagine; by HIF1AN. FT {ECO:0000250}. FT MOD_RES 908 908 Phosphoserine; by GSK3-beta; in vitro. FT {ECO:0000250}. FT MOD_RES 912 912 Phosphoserine; by GSK3-beta; in vitro. FT {ECO:0000250}. FT MOD_RES 931 931 Phosphoserine; by IKKB. {ECO:0000250}. FT MOD_RES 936 936 Phosphoserine; by IKKB. {ECO:0000250}. FT MOD_RES 941 941 Phosphoserine. {ECO:0000250}. FT LIPID 61 61 S-(15-deoxy-Delta12,14-prostaglandin J2- FT 9-yl)cysteine; alternate. {ECO:0000250}. FT CONFLICT 289 289 E -> G (in Ref. 1; BAD27479). FT {ECO:0000305}. FT CONFLICT 295 295 E -> G (in Ref. 1; BAD27479). FT {ECO:0000305}. FT CONFLICT 327 327 A -> T (in Ref. 1; BAD27479). FT {ECO:0000305}. FT CONFLICT 432 432 H -> N (in Ref. 1; BAD27479). FT {ECO:0000305}. FT CONFLICT 538 538 E -> G (in Ref. 1; BAD27479). FT {ECO:0000305}. FT CONFLICT 822 822 I -> T (in Ref. 1; BAD27479). FT {ECO:0000305}. FT CONFLICT 838 838 L -> Q (in Ref. 1; BAD27479). FT {ECO:0000305}. FT CONFLICT 939 939 K -> R (in Ref. 1; BAD27479). FT {ECO:0000305}. SQ SEQUENCE 972 AA; 105631 MW; 189557C55699014F CRC64; MAEDDTYLGA HEQMFHLDPL THTIFNPELF QPEMPLPTAD GPYLQILEQP KQRGFRFRYV CEGPSHGGLP GASSEKNKKS YPQVKICNYV GPAKVIVQLV TNGKNIHLHA HSLVGKHCED GICTVTAGPK DMVVGFANLG ILHVTKKKVF ETLEARMTEA CTKGYNPGLL VHPDLAYLQA EGGGDRQLTD REKEIIRQAA LQQTKEMDLS VVRLMFTAFL PDSTGSFTRR LEPVVSDAIY DSKAPNASNL KIVRMDRTAG CVTGGEEIYL LCDKVQKDDI QIRFYEEEEN GGIWEGFGDF SPTDVHRQFA IVFKTPKYKD VNITKPASVF VQLRRKSDLE TSEPKPFLYY PEIKDKEEVQ RKRQKLMPNF SDSFGGGSGA GAGGGGMFGS GGGGGGAGST GPGYGFPHYG FPTYGGITFH PGTTKSNAGM KHGTIDTPSK NDSEGCGKNV DREAVNLSGK VTEPTEQDKE SSMGVDEVTL TYTVGIKEEN SRFQDNLFLE KAMQLAKRHA NALFDYAVTG DVKMLLAVQR HLTAVQDENG DSVLHLAIIH LHAQLVRDLL EVTSGLISDD IINMRNDLYQ TPLHLAVITK QEAVVDDLLR AGADLSLLDR LGNSVLHLAA KEGQDKILSI LLKHKKAALL MDHPNGEGLN AIHIAVMSNS MPCLLLLVAA GADVNAQERK SGRTALHLAV EHDNISLAGC LLLEGDAHVD STTYDGTTPL HIAAGRGSTR LAALLKAAGA DPLVENFEPL YDLDDSWEKD GEDEGVVPGT TPLDMATNWQ VFDILNGKPY EPEFTSDDLL AQGDMKQLTE DAKLQLYKLL EIPDPDKNWA TLAQKLGLGI LNNAFRLSPA PSKTLMDNYE VSGGTIKELV EALRQMGYTE AIEVIQAAFC APETAAPSPG KGAPQTLSLP LSSASTRSPV DEVRDDSICD SGVETSFRKL SFTESLTSGS SLLTLNKAPH EYGQEGPIEG KI //