ID NFKB1_CANFA Reviewed; 972 AA. AC Q6F3J0; DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot. DT 16-AUG-2004, sequence version 1. DT 24-MAR-2009, entry version 38. DE RecName: Full=Nuclear factor NF-kappa-B p105 subunit; DE Contains: DE RecName: Full=Nuclear factor NF-kappa-B p50 subunit; GN Name=NFKB1; OS Canis familiaris (Dog). 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. CC -!- FUNCTION: NF-kappa-B is a pleiotropic transcription factor which CC is present in almost all cell types and is involved in many CC biological processed such as inflammation, immunity, CC differentiation, cell growth, tumorigenesis and apoptosis. NF- CC kappa-B is a homo- or heterodimeric complex formed by the Rel-like CC domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, CC REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to CC be most abundant one. The dimers bind at kappa-B sites in the DNA CC of their target genes and the individual dimers have distinct CC preferences for different kappa-B sites that they can bind with CC distinguishable affinity and specificity. Different dimer CC combinations act as transcriptional activators or repressors, CC respectively. NF-kappa-B is controlled by various mechanisms of CC post-translational modification and subcellular CC 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- CC kappa-B inhibitor (I-kappa-B) family. In a conventional activation CC pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) CC in response to different activators, subsequently degraded thus CC liberating the active NF-kappa-B complex which translocates to the CC nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes CC are transcriptional activators. The NF-kappa-B p50-p50 homodimer CC is a transcriptional repressor, but can act as a transcriptional CC activator when associated with BCL3. NFKB1 appears to have dual CC functions such as cytoplasmic retention of attached NF-kappa-B CC proteins by p105 and generation of p50 by a cotranslational CC processing. The proteasome-mediated process ensures the production CC of both p50 and p105 and preserves their independent function, CC although processing of NFKB1/p105 also appears to occur post- CC translationally. p50 binds to the kappa-B consensus sequence 5'- CC GGRNNYYCC-3', located in the enhancer region of genes involved in CC immune response and acute phase reactions. In a complex with CC MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active CC MAP3K8 is released by proteasome-dependent degradation of CC NFKB1/p105 (By similarity). 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). CC -!- SUBCELLULAR LOCATION: Nucleus (By similarity). Cytoplasm (By CC similarity). Note=Nuclear, but also found in the cytoplasm in an CC inactive form complexed to an inhibitor (I-kappa-B) (By CC similarity). 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). CC -!- PTM: Phosphorylation at 'Ser-931' and 'Ser-936' are required for CC BTRC/BTRCP-mediated proteolysis (By similarity). CC -!- PTM: S-nitrosylation of Cys-61 affects DNA binding (By CC similarity). CC -!- SIMILARITY: Contains 7 ANK repeats. CC -!- SIMILARITY: Contains 1 death domain. CC -!- SIMILARITY: Contains 1 RHD (Rel-like) domain. 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; -. DR UniGene; Cfa.10766; -. DR SMR; Q6F3J0; 1-82, 41-352, 801-886. DR Ensembl; ENSCAFG00000010730; Canis familiaris. DR GeneID; 442859; -. DR KEGG; cfa:442859; -. DR HOVERGEN; Q6F3J0; -. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW. DR GO; GO:0005634; C:nucleus; IEA:InterPro. DR GO; GO:0003700; F:transcription factor activity; IEA:InterPro. DR GO; GO:0007165; P:signal transduction; IEA:InterPro. DR InterPro; IPR002110; ANK. DR InterPro; IPR000488; Death. DR InterPro; IPR011029; DEATH_like. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR002909; IPT_TIG_rcpt. DR InterPro; IPR000451; NF_Rel_dor. DR InterPro; IPR011539; RHD. DR Gene3D; G3DSA:1.25.40.20; ANK; 1. DR Gene3D; G3DSA:1.10.533.10; DEATH_like; 1. DR Gene3D; G3DSA:2.60.40.10; Ig-like_fold; 1. DR Gene3D; G3DSA:2.60.40.340; RHD; 1. DR Pfam; PF00023; Ank; 6. DR Pfam; PF00531; Death; 1. DR Pfam; PF00554; RHD; 1. DR Pfam; PF01833; TIG; 1. DR PRINTS; PR00057; NFKBTNSCPFCT. DR SMART; SM00248; ANK; 6. DR SMART; SM00005; DEATH; 1. DR SMART; SM00429; IPT; 1. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 5. DR PROSITE; PS50017; DEATH_DOMAIN; FALSE_NEG. 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; Nucleus; KW Phosphoprotein; 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 (By FT similarity). FT /FTId=PRO_0000223241. FT DOMAIN 39 246 RHD. 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 (By similarity). FT REGION 435 972 Interaction with CFLAR (By similarity). FT MOTIF 360 365 Nuclear localization signal (Potential). FT COMPBIAS 375 433 Gly-rich. FT SITE 433 434 Cleavage (when cotranslationally FT processed) (By similarity). FT MOD_RES 61 61 S-nitrosocysteine (By similarity). FT MOD_RES 337 337 Phosphoserine; by PKA (Potential). FT MOD_RES 431 431 N6-acetyllysine; by EP300 (By FT similarity). FT MOD_RES 440 440 N6-acetyllysine; by EP300 (By FT similarity). FT MOD_RES 908 908 Phosphoserine; by GSK3-beta; in vitro (By FT similarity). FT MOD_RES 912 912 Phosphoserine; by GSK3-beta; in vitro (By FT similarity). FT MOD_RES 931 931 Phosphoserine; by IKKB (By similarity). FT MOD_RES 936 936 Phosphoserine; by IKKB (By similarity). SQ SEQUENCE 972 AA; 105453 MW; 4B6472280209A09C 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 QIRFYEEEGN GGIWGGFGDF SPTDVHRQFA IVFKTPKYKD VNITKPTSVF VQLRRKSDLE TSEPKPFLYY PEIKDKEEVQ RKRQKLMPNF SDSFGGGSGA GAGGGGMFGS GGGGGGAGST GPGYGFPHYG FPTYGGITFH PGTTKSNAGM KNGTIDTPSK NDSEGCGKNV DREAVNLSGK VTEPTEQDKE SSMGVDEVTL TYTVGIKEEN SRFQDNLFLE KAMQLAKRHA NALFDYAVTG DVKMLLAVQR HLTAVQDGNG 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 ETPDPDKNWA TLAQKLGQGI LNNAFRLSPA PSKTLMDNYE VSGGTIKELV EALRQMGYTE AIEVIQAAFC APETAAPSPG KGAPQTLSLP LSSASTRSPV DEVRDDSICD SGVETSFRRL SFTESLTSGS SLLTLNKAPH EYGQEGPIEG KI //