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   22-NOV-2017, entry version 103.
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;
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   ---------------------------------------------------------------------------
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   SMR; Q6F3J0; -.
DR   STRING; 9615.ENSCAFP00000015815; -.
DR   PaxDb; Q6F3J0; -.
DR   GeneID; 442859; -.
DR   KEGG; cfa:442859; -.
DR   CTD; 4790; -.
DR   eggNOG; KOG0504; Eukaryota.
DR   eggNOG; COG0666; LUCA.
DR   HOGENOM; HOG000004822; -.
DR   HOVERGEN; HBG052613; -.
DR   InParanoid; Q6F3J0; -.
DR   KO; K02580; -.
DR   Proteomes; UP000002254; Unplaced.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0033256; C:I-kappaB/NF-kappaB complex; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
DR   GO; GO:0000975; F:regulatory region DNA binding; ISS:UniProtKB.
DR   GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0000981; F:RNA polymerase II transcription factor activity, sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; ISS:UniProtKB.
DR   GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR   GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR   GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR   GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
DR   GO; GO:0038061; P:NIK/NF-kappaB signaling; IBA:GO_Central.
DR   GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IBA:GO_Central.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR   GO; GO:0034097; P:response to cytokine; IBA:GO_Central.
DR   GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR   CDD; cd00204; ANK; 1.
DR   CDD; cd01177; IPT_NFkappaB; 1.
DR   Gene3D; 1.25.40.20; -; 3.
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; 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.
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; Complete proteome; Cytoplasm;
KW   DNA-binding; Hydroxylation; Isopeptide bond; Lipoprotein; Nucleus;
KW   Phosphoprotein; Reference proteome; Repeat; S-nitrosylation;
KW   Transcription; Transcription regulation; Ubl conjugation.
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.
FT                                {ECO:0000250|UniProtKB:P19838}.
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     756    756       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q63369}.
FT   MOD_RES     908    908       Phosphoserine; by GSK3-beta; in vitro.
FT                                {ECO:0000250|UniProtKB:P19838}.
FT   MOD_RES     912    912       Phosphoserine; by GSK3-beta; in vitro.
FT                                {ECO:0000250|UniProtKB:P19838}.
FT   MOD_RES     931    931       Phosphoserine; by IKKB.
FT                                {ECO:0000250|UniProtKB:P19838}.
FT   MOD_RES     936    936       Phosphoserine; by IKKB.
FT                                {ECO:0000250|UniProtKB:P19838}.
FT   MOD_RES     941    941       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P19838}.
FT   MOD_RES     947    947       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:P25799}.
FT   LIPID        61     61       S-(15-deoxy-Delta12,14-prostaglandin J2-
FT                                9-yl)cysteine; alternate. {ECO:0000250}.
FT   CROSSLNK    325    325       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO2).
FT                                {ECO:0000250|UniProtKB:P19838}.
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
//