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   19-OCT-2011, entry version 60.
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.
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). Directly interacts with MEN1 (By
CC       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   -!- 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).
CC   -!- SIMILARITY: Contains 7 ANK repeats.
CC   -!- SIMILARITY: Contains 1 death domain.
CC   -!- SIMILARITY: Contains 1 RHD (Rel-like) domain.
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DR   EMBL; AB183419; BAD27479.1; -; mRNA.
DR   RefSeq; NP_001003344.1; NM_001003344.1.
DR   UniGene; Cfa.10766; -.
DR   ProteinModelPortal; Q6F3J0; -.
DR   SMR; Q6F3J0; 40-352, 801-886.
DR   STRING; Q6F3J0; -.
DR   GeneID; 442859; -.
DR   KEGG; cfa:442859; -.
DR   CTD; 4790; -.
DR   eggNOG; maNOG12635; -.
DR   GeneTree; ENSGT00500000044765; -.
DR   HOVERGEN; HBG052613; -.
DR   InParanoid; Q6F3J0; -.
DR   OrthoDB; EOG4SN1MX; -.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:InterPro.
DR   GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR   InterPro; IPR002110; Ankyrin_rpt.
DR   InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR   InterPro; IPR000488; Death.
DR   InterPro; IPR011029; DEATH-like.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR014756; Ig_E-set.
DR   InterPro; IPR002909; IPT_TIG_rcpt.
DR   InterPro; IPR000451; NF_Rel_dor.
DR   InterPro; IPR008967; p53-like_TF_DNA-bd.
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; 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; SSF48403; ANK; 1.
DR   SUPFAM; SSF47986; DEATH_like; 1.
DR   SUPFAM; SSF81296; Ig_E-set; 1.
DR   SUPFAM; SSF49417; P53_like_DNA_bnd; 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; Complete proteome; Cytoplasm;
KW   DNA-binding; Lipoprotein; Nucleus; Phosphoprotein; Reference proteome;
KW   Repeat; S-nitrosylation; Transcription; 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; alternate (By
FT                                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     898    898       Phosphoserine (By 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).
FT   MOD_RES     941    941       Phosphoserine (By similarity).
FT   LIPID        61     61       S-(15-deoxy-Delta12,14-prostaglandin J2-
FT                                9-yl)cysteine; alternate (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
//