ID NFKB1_CANLF Reviewed; 972 AA. AC Q6F3J0; F1PM82; DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot. DT 18-APR-2012, sequence version 2. DT 12-OCT-2022, entry version 128. 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 lupus familiaris (Dog) (Canis familiaris). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; 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 enhancer RT 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., Mauceli E., RA Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F., RA Smith D.R., deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W., RA Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S., RA Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A., RA Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P., RA Searle S.M.J., 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., Bachantsang P., RA Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B., RA Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A., RA Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M., RA Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S., RA Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L., RA Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S., RA Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C., RA Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G., RA Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N., RA Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A., RA Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A., RA Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M., RA Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L., RA LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A., RA Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S., RA Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T., RA Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A., RA Naylor J., 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., Osman S., RA Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M., RA Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F., RA Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T., RA Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C., RA Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C., RA Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D., RA Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H., RA Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J., RA Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J., RA 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 in CC 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, immunity, CC differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B CC is a homo- or heterodimeric complex formed by the Rel-like domain- CC containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and CC NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most CC abundant one. The dimers bind at kappa-B sites in the DNA of their CC target genes and the individual dimers have distinct preferences for CC different kappa-B sites that they can bind with distinguishable CC affinity and specificity. Different dimer combinations act as CC transcriptional activators or repressors, respectively. NF-kappa-B is CC controlled by various mechanisms of post-translational modification and CC subcellular compartmentalization as well as by interactions with other CC cofactors or corepressors. NF-kappa-B complexes are held in the CC cytoplasm in an inactive state complexed with members of the NF-kappa-B CC inhibitor (I-kappa-B) family. In a conventional activation pathway, I- CC kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to CC different activators, subsequently degraded thus liberating the active CC NF-kappa-B complex which translocates to the nucleus. NF-kappa-B CC heterodimeric p65-p50 and RelB-p50 complexes are transcriptional CC activators. The NF-kappa-B p50-p50 homodimer is a transcriptional CC repressor, but can act as a transcriptional activator when associated CC with BCL3. NFKB1 appears to have dual functions such as cytoplasmic CC retention of attached NF-kappa-B proteins by p105 and generation of p50 CC by a 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 appears to CC occur post-translationally. p50 binds to the kappa-B consensus sequence CC 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in CC immune response and acute phase reactions. In a complex with MAP3K8, CC NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is CC released by proteasome-dependent degradation of NFKB1/p105 (By CC similarity). {ECO:0000250}. CC -!- SUBUNIT: Component of the NF-kappa-B p65-p50 complex (By similarity). CC Homodimer; component of the NF-kappa-B p50-p50 complex (By similarity). CC Component of the NF-kappa-B p105-p50 complex (By similarity). Component CC of the NF-kappa-B p50-c-Rel complex (By similarity). Component of a CC complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3 (By CC similarity). Also interacts with MAP3K8 (By similarity). NF-kappa-B p50 CC subunit interacts with NCOA3 coactivator, which may coactivate NF- CC kappa-B dependent expression via its histone acetyltransferase activity CC (By similarity). Interacts with DSIPI; this interaction prevents CC nuclear translocation and DNA-binding (By similarity). Interacts with CC SPAG9 and UNC5CL (By similarity). NFKB1/p105 interacts with CFLAR; the CC interaction inhibits p105 processing into p50 (By similarity). CC NFKB1/p105 forms a ternary complex with MAP3K8 and TNIP2 (By CC similarity). Interacts with GSK3B; the interaction prevents processing CC of p105 to p50 (By similarity). NFKB1/p50 interacts with NFKBIE (By CC similarity). NFKB1/p50 interacts with NFKBIZ. Nuclear factor NF-kappa-B CC p50 subunit interacts with NFKBID (By similarity). Directly interacts CC with MEN1 (By similarity). Interacts with HIF1AN (By similarity). CC Interacts with FEM1A; interaction is direct (By similarity). CC {ECO:0000250|UniProtKB:P19838, ECO:0000250|UniProtKB:P25799}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. CC Note=Nuclear, but also found in the cytoplasm in an inactive form CC complexed to an inhibitor (I-kappa-B). {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 after CC the GRR repeat promotes the generation of p50 making it an acceptable CC substrate for the proteasome. This process is known as cotranslational CC processing. The processed form is active and the unprocessed form acts CC as an inhibitor (I kappa B-like), being able to form cytosolic CC complexes with NF-kappa B, trapping it in the cytoplasm. Complete CC folding of the region downstream of the GRR repeat precludes processing CC (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 an CC alternative to other cysteine modifications, such as S-nitrosylation CC and S-palmitoylation (By similarity). {ECO:0000250}. 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 AlphaFoldDB; Q6F3J0; -. DR SMR; Q6F3J0; -. DR STRING; 9615.ENSCAFP00000056706; -. DR PaxDb; Q6F3J0; -. DR Ensembl; ENSCAFT00000017092; ENSCAFP00000015815; ENSCAFG00000010730. DR Ensembl; ENSCAFT00030037443; ENSCAFP00030032664; ENSCAFG00030020386. DR Ensembl; ENSCAFT00040043145; ENSCAFP00040037640; ENSCAFG00040022966. DR Ensembl; ENSCAFT00845045189; ENSCAFP00845035432; ENSCAFG00845025570. DR GeneID; 442859; -. DR KEGG; cfa:442859; -. DR CTD; 4790; -. DR VEuPathDB; HostDB:ENSCAFG00845025570; -. DR VGNC; VGNC:43780; NFKB1. DR eggNOG; KOG0504; Eukaryota. DR GeneTree; ENSGT00940000158625; -. DR InParanoid; Q6F3J0; -. DR OrthoDB; 916931at2759; -. DR Reactome; R-CFA-1169091; Activation of NF-kappaB in B cells. DR Reactome; R-CFA-1810476; RIP-mediated NFkB activation via ZBP1. DR Reactome; R-CFA-193692; Regulated proteolysis of p75NTR. DR Reactome; R-CFA-202424; Downstream TCR signaling. DR Reactome; R-CFA-209560; NF-kB is activated and signals survival. DR Reactome; R-CFA-2871837; FCERI mediated NF-kB activation. DR Reactome; R-CFA-3134963; DEx/H-box helicases activate type I IFN and inflammatory cytokines production. DR Reactome; R-CFA-3214841; PKMTs methylate histone lysines. DR Reactome; R-CFA-445989; TAK1-dependent IKK and NF-kappa-B activation. DR Reactome; R-CFA-448706; Interleukin-1 processing. DR Reactome; R-CFA-5607764; CLEC7A (Dectin-1) signaling. DR Reactome; R-CFA-5621575; CD209 (DC-SIGN) signaling. DR Reactome; R-CFA-6798695; Neutrophil degranulation. DR Reactome; R-CFA-9020702; Interleukin-1 signaling. DR Reactome; R-CFA-933542; TRAF6 mediated NF-kB activation. DR Proteomes; UP000002254; Chromosome 32. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0007165; P:signal transduction; IEA:InterPro. DR CDD; cd01177; IPT_NFkappaB; 1. 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; IPR036770; Ankyrin_rpt-contain_sf. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR000488; Death_domain. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR002909; IPT_dom. DR InterPro; IPR033926; IPT_NFkappaB. DR InterPro; IPR030503; NF-kB_p105. DR InterPro; IPR000451; NFkB/Dor. DR InterPro; IPR008967; p53-like_TF_DNA-bd. DR InterPro; IPR030492; RHD_CS. DR InterPro; IPR032397; RHD_dimer. DR InterPro; IPR011539; RHD_DNA_bind_dom. DR InterPro; IPR037059; RHD_DNA_bind_dom_sf. DR PANTHER; PTHR24169; PTHR24169; 1. DR PANTHER; PTHR24169:SF9; PTHR24169:SF9; 1. DR Pfam; PF00023; Ank; 1. DR Pfam; PF12796; Ank_2; 1. DR Pfam; PF00531; Death; 1. DR Pfam; PF16179; RHD_dimer; 1. DR Pfam; PF00554; RHD_DNA_bind; 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; Cytoplasm; DNA-binding; Hydroxylation; KW Isopeptide bond; Lipoprotein; Nucleus; Phosphoprotein; Reference proteome; KW Repeat; S-nitrosylation; Transcription; Transcription regulation; KW Ubl conjugation. FT CHAIN 1..972 FT /note="Nuclear factor NF-kappa-B p105 subunit" FT /id="PRO_0000223240" FT CHAIN 1..433 FT /note="Nuclear factor NF-kappa-B p50 subunit" FT /evidence="ECO:0000250" FT /id="PRO_0000223241" FT DOMAIN 39..246 FT /note="RHD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00265" FT REPEAT 539..568 FT /note="ANK 1" FT REPEAT 578..607 FT /note="ANK 2" FT REPEAT 611..640 FT /note="ANK 3" FT REPEAT 647..676 FT /note="ANK 4" FT REPEAT 681..711 FT /note="ANK 5" FT REPEAT 715..744 FT /note="ANK 6" FT REPEAT 768..798 FT /note="ANK 7" FT DOMAIN 814..889 FT /note="Death" FT REGION 372..394 FT /note="GRR" FT /evidence="ECO:0000250" FT REGION 425..473 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 435..972 FT /note="Interaction with CFLAR" FT /evidence="ECO:0000250" FT REGION 647..681 FT /note="Essential for interaction with HIF1AN" FT /evidence="ECO:0000250" FT REGION 894..926 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 360..365 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 425..444 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 433..434 FT /note="Cleavage (when cotranslationally processed)" FT /evidence="ECO:0000250" FT MOD_RES 61 FT /note="S-nitrosocysteine; alternate" FT /evidence="ECO:0000250|UniProtKB:P19838" FT MOD_RES 337 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000255" FT MOD_RES 431 FT /note="N6-acetyllysine; by EP300" FT /evidence="ECO:0000250|UniProtKB:P19838" FT MOD_RES 440 FT /note="N6-acetyllysine; by EP300" FT /evidence="ECO:0000250|UniProtKB:P19838" FT MOD_RES 675 FT /note="(3S)-3-hydroxyasparagine; by HIF1AN" FT /evidence="ECO:0000250" FT MOD_RES 756 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q63369" FT MOD_RES 908 FT /note="Phosphoserine; by GSK3-beta; in vitro" FT /evidence="ECO:0000250|UniProtKB:P19838" FT MOD_RES 912 FT /note="Phosphoserine; by GSK3-beta; in vitro" FT /evidence="ECO:0000250|UniProtKB:P19838" FT MOD_RES 931 FT /note="Phosphoserine; by IKKB" FT /evidence="ECO:0000250|UniProtKB:P19838" FT MOD_RES 936 FT /note="Phosphoserine; by IKKB" FT /evidence="ECO:0000250|UniProtKB:P19838" FT MOD_RES 941 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19838" FT MOD_RES 947 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P25799" FT LIPID 61 FT /note="S-(15-deoxy-Delta12,14-prostaglandin J2-9- FT yl)cysteine; alternate" FT /evidence="ECO:0000250" FT CROSSLNK 325 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P19838" FT CONFLICT 289 FT /note="E -> G (in Ref. 1; BAD27479)" FT /evidence="ECO:0000305" FT CONFLICT 295 FT /note="E -> G (in Ref. 1; BAD27479)" FT /evidence="ECO:0000305" FT CONFLICT 327 FT /note="A -> T (in Ref. 1; BAD27479)" FT /evidence="ECO:0000305" FT CONFLICT 432 FT /note="H -> N (in Ref. 1; BAD27479)" FT /evidence="ECO:0000305" FT CONFLICT 538 FT /note="E -> G (in Ref. 1; BAD27479)" FT /evidence="ECO:0000305" FT CONFLICT 822 FT /note="I -> T (in Ref. 1; BAD27479)" FT /evidence="ECO:0000305" FT CONFLICT 838 FT /note="L -> Q (in Ref. 1; BAD27479)" FT /evidence="ECO:0000305" FT CONFLICT 939 FT /note="K -> R (in Ref. 1; BAD27479)" FT /evidence="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 //