ID ZEP3_MOUSE Reviewed; 2348 AA. AC A2A884; A2MZW0; Q69ZG6; Q6SNP9; DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot. DT 20-FEB-2007, sequence version 1. DT 19-OCT-2011, entry version 48. DE RecName: Full=Transcription factor HIVEP3; DE AltName: Full=Human immunodeficiency virus type I enhancer-binding protein 3 homolog; DE AltName: Full=KB-binding and regognition component; DE AltName: Full=Kappa-B and V(D)J recombination signal sequences-binding protein; DE AltName: Full=Kappa-binding protein 1; DE Short=KBP-1; DE AltName: Full=Recombinant component; DE AltName: Full=Schnurri-3; DE AltName: Full=Zinc finger protein ZAS3; GN Name=Hivep3; Synonyms=KBP1, Kiaa1555, Krc, Rc, shn3, Zas3; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., RA She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., RA Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., RA Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J., RA Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., RA Lindblad-Toh K., Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of RT the mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-2341, DOMAIN, FUNCTION, AND TISSUE RP SPECIFICITY. RC STRAIN=BALB/c; TISSUE=Brain; RX MEDLINE=97001141; PubMed=8812474; DOI=10.1006/geno.1996.0380; RA Wu L.-C., Liu Y., Strandtmann J., Mak C.-H., Lee B., Li Z., Yu C.Y.; RT "The mouse DNA binding protein Rc for the kappa B motif of RT transcription and for the V(D)J recombination signal sequences RT contains composite DNA-protein interaction domains and belongs to a RT new family of large transcriptional proteins."; RL Genomics 35:415-424(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1281-2348. RC TISSUE=Thymus; RX PubMed=15368895; DOI=10.1093/dnares/11.3.205; RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H., RA Nagase T., Ohara O., Koga H.; RT "Prediction of the coding sequences of mouse homologues of KIAA gene: RT IV. The complete nucleotide sequences of 500 mouse KIAA-homologous RT cDNAs identified by screening of terminal sequences of cDNA clones RT randomly sampled from size-fractionated libraries."; RL DNA Res. 11:205-218(2004). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1497-2295, FUNCTION, TISSUE SPECIFICITY, RP DEVELOPMENTAL STAGE, DOMAIN, AND REPEAT. RX PubMed=8255760; DOI=10.1093/nar/21.22.5067; RA Wu L.-C., Mak C.-H., Dear N., Boehm T., Foroni L., Rabbitts T.H.; RT "Molecular cloning of a zinc finger protein which binds to the RT heptamer of the signal sequence for V(D)J recombination."; RL Nucleic Acids Res. 21:5067-5073(1993). RN [5] RP PHOSPHORYLATION. RX PubMed=9862992; DOI=10.1093/nar/27.2.643; RA Bachmeyer C., Mak C.H., Yu C.Y., Wu L.-C.; RT "Regulation by phosphorylation of the zinc finger protein KRC that RT binds the kappaB motif and V(D)J recombination signal sequences."; RL Nucleic Acids Res. 27:643-648(1999). RN [6] RP FUNCTION. RX PubMed=11035930; DOI=10.1006/excr.2000.5029; RA Allen C.E., Wu L.-C.; RT "Downregulation of KRC induces proliferation, anchorage independence, RT and mitotic cell death in HeLa cells."; RL Exp. Cell Res. 260:346-356(2000). RN [7] RP FUNCTION. RX PubMed=10625627; DOI=10.1074/jbc.275.2.913; RA Hjelmsoe I., Allen C.E., Cohn M.A., Tulchinsky E.M., Wu L.-C.; RT "The kappaB and V(D)J recombination signal sequence binding protein RT KRC regulates transcription of the mouse metastasis-associated gene RT S100A4/mts1."; RL J. Biol. Chem. 275:913-920(2000). RN [8] RP FUNCTION, AND DOMAIN ZAS. RX PubMed=12193271; DOI=10.1186/1471-2172-3-10; RA Allen C.E., Mak C.-H., Wu L.-C.; RT "The kappa B transcriptional enhancer motif and signal sequences of RT V(D)J recombination are targets for the zinc finger protein RT HIVEP3/KRC: a site selection amplification binding study."; RL BMC Immunol. 3:10-10(2002). RN [9] RP SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH TRAF1 AND TRAF2, AND RP REGION. RX PubMed=11804591; DOI=10.1016/S1097-2765(01)00434-8; RA Oukka M., Kim S.T., Lugo G., Sun J., Wu L.-C., Glimcher L.H.; RT "A mammalian homolog of Drosophila schnurri, KRC, regulates TNF RT receptor-driven responses and interacts with TRAF2."; RL Mol. Cell 9:121-131(2002). RN [10] RP FUNCTION, INDUCTION, AND DEVELOPMENTAL STAGE. RX PubMed=12001065; DOI=10.1002/gene.10084; RA Hicar M.D., Robinson M.L., Wu L.-C.; RT "Embryonic expression and regulation of the large zinc finger protein RT KRC."; RL Genesis 33:8-20(2002). RN [11] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=14530385; DOI=10.1073/pnas.2133048100; RA Hong J.W., Allen C.E., Wu L.-C.; RT "Inhibition of NF-kappaB by ZAS3, a zinc-finger protein that also RT binds to the kappaB motif."; RL Proc. Natl. Acad. Sci. U.S.A. 100:12301-12306(2003). RN [12] RP FUNCTION, INTERACTION WITH JUN, AND INDUCTION. RX PubMed=14707112; DOI=10.1084/jem.20030421; RA Oukka M., Wein M.N., Glimcher L.H.; RT "Schnurri-3 (KRC) interacts with c-Jun to regulate the IL-2 gene in T RT cells."; RL J. Exp. Med. 199:15-24(2004). RN [13] RP ALTERNATIVE PROMOTERS. RX PubMed=15627499; DOI=10.1016/j.bbaexp.2004.10.004; RA Hong J.-W., Wu L.-C.; RT "Structural characterization of the gene encoding the large zinc RT finger protein ZAS3: implication to the origin of multiple promoters RT in eukaryotic genes."; RL Biochim. Biophys. Acta 1681:74-87(2005). RN [14] RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND INTERACTION WITH RUNX2 RP AND WWP1. RX PubMed=16728642; DOI=10.1126/science.1126313; RA Jones D.C., Wein M.N., Oukka M., Hofstaetter J.G., Glimcher M.J., RA Glimcher L.H.; RT "Regulation of adult bone mass by the zinc finger adapter protein RT Schnurri-3."; RL Science 312:1223-1227(2006). CC -!- FUNCTION: Plays a role of transcription factor; binds to CC recognition signal sequences (Rss heptamer) for somatic CC recombination of immunoglobulin and T-cell receptor gene segments; CC Binds also to the kappa-B motif of gene such as S100A4, involved CC in cell progression and differentiation. Kappa-B motif is a gene CC regulatory element found in promoters and enhancers of genes CC involved in immunity, inflammation, and growth and that responds CC to viral antigens, mitogens, and cytokines. Involvement of HIVEP3 CC in cell growth is strengthened by the fact that its down- CC regulation promotes cell cycle progression with ultimate formation CC of multinucleated giant cells. Strongly inhibits TNF-alpha-induced CC NF-kappa-B activation; Interferes with nuclear factor NF-kappa-B CC by several mechanisms: as transcription factor, by competing for CC Kappa-B motif and by repressing transcription in the nucleus; CC Trough non transcriptional process, by inhibiting nuclear CC translocation of RELA by association with TRAF2, an adapter CC molecule in the tumor necrosis factor signaling, which blocks the CC formation of IKK complex. Interaction with TRAF proteins inhibits CC both NF-Kappa-B-mediated and c-Jun N-terminal kinase/JNK-mediated CC responses that include apoptosis and proinflammatory cytokine gene CC expression. Positively regulates the expression of IL2 in T-cell. CC Essential regulator of adult bone formation. CC -!- SUBUNIT: Interacts with TRAF1 AND TRAF2 as well as with JUN. Forms CC a multimeric complex with RUNX2 and E3 ubiquitin ligase WWP1. CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. CC -!- TISSUE SPECIFICITY: Expressed in macrophages, lymphocytes, brain, CC thymus, spleen and bone marrow. Expressed in osteoblasts, whole CC bone and, to a lesser extend, in osteoclasts. CC -!- DEVELOPMENTAL STAGE: Expressed in the thymus with increasing CC level, approximately 4-fold, from E15.5 to E16.5, constant level CC from E16.5 to birth, then decrease to a low level by P30. CC Expressed at E13.5 in the dorsal root ganglia of the peripheral CC nervous system and the trigeminal ganglion of the metencephalon CC and at relatively low levels in the cerebral cortex; no CC significant expression was observed prior to E13.5. Expressed in CC the spinal cord at E19, but weakly detected in the lung and the CC liver. CC -!- INDUCTION: Upon CD3/CD28 stimulation in CD4 T-cells. Induced by CC LPS in pre-B-cells. CC -!- DOMAIN: ZAS2 domain binds DNA as dimers, tetramers, and multiple CC of tetramers and readily forms highly ordred DNA-protein CC structures. CC -!- PTM: Phosphorylated on threonine and serine residues. CC Phosphorylation by cyclin-dependent kinase CDK1 decreases HIVEP3 CC DNA binding affinity, and by epidermal growth factor receptor CC kinase increases its DNA binding affinity. CC -!- DISRUPTION PHENOTYPE: Mice display adult-onset osteosclerosis with CC increased bone mass due to increased osteoblast activity; the CC osteoblasts contain elevated levels of Runx2. CC -!- MISCELLANEOUS: Hivep3 gene expression is probably controlled by a CC combination of differential promoter usage, alternative splicing, CC and possible intergenic splicing. CC -!- SIMILARITY: Contains 5 C2H2-type zinc fingers. CC -!- SEQUENCE CAUTION: CC Sequence=AAA40039.1; Type=Erroneous initiation; Note=Translation N-terminally extended; CC Sequence=AAA40039.1; Type=Frameshift; Positions=1502, 2242; CC Sequence=AAR88090.1; Type=Frameshift; Positions=752, 781, 1045, 1054, 2242; 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; AL607142; CAM27499.1; -; Genomic_DNA. DR EMBL; AY454345; AAR88090.1; ALT_FRAME; mRNA. DR EMBL; AK173200; BAD32478.1; -; mRNA. DR EMBL; L07911; AAA40039.1; ALT_SEQ; mRNA. DR IPI; IPI00121314; -. DR PIR; S41479; S41479. DR PIR; T42717; T42717. DR RefSeq; NP_034787.2; NM_010657.3. DR UniGene; Mm.302758; -. DR UniGene; Mm.394479; -. DR UniGene; Mm.422538; -. DR ProteinModelPortal; A2A884; -. DR SMR; A2A884; 184-240, 1719-1775. DR STRING; A2A884; -. DR PRIDE; A2A884; -. DR Ensembl; ENSMUST00000106307; ENSMUSP00000101914; ENSMUSG00000028634. DR GeneID; 16656; -. DR KEGG; mmu:16656; -. DR UCSC; uc008una.1; mouse. DR CTD; 59269; -. DR MGI; MGI:106589; Hivep3. DR HOGENOM; HBG283020; -. DR HOVERGEN; HBG095595; -. DR InParanoid; A2A884; -. DR OMA; MERIPGE; -. DR OrthoDB; EOG4F7NJ3; -. DR NextBio; 290349; -. DR Bgee; A2A884; -. DR Genevestigator; A2A884; -. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR Gene3D; G3DSA:3.30.160.60; Znf_C2H2/integrase_DNA-bd; 4. DR Pfam; PF00096; zf-C2H2; 4. DR SMART; SM00355; ZnF_C2H2; 5. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 4. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 5. PE 1: Evidence at protein level; KW Coiled coil; Complete proteome; Cytoplasm; Metal-binding; Nucleus; KW Phosphoprotein; Reference proteome; Repeat; Transcription; KW Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 2348 Transcription factor HIVEP3. FT /FTId=PRO_0000331628. FT REPEAT 1897 1900 1. FT REPEAT 1927 1930 2. FT REPEAT 1933 1936 3. FT REPEAT 1961 1964 4. FT REPEAT 2024 2027 5. FT ZN_FING 185 207 C2H2-type 1. FT ZN_FING 213 235 C2H2-type 2. FT ZN_FING 636 658 C2H2-type 3; degenerate. FT ZN_FING 1720 1742 C2H2-type 4. FT ZN_FING 1748 1772 C2H2-type 5. FT REGION 185 235 ZAS1. FT REGION 204 1055 No DNA binding activity or FT transactivation activity, but complete FT prevention of TRAF-dependent NF-Kappa-B FT activation; associates with TRAF2 and FT JUN. FT REGION 257 280 Acidic 1. FT REGION 844 865 Acidic 2. FT REGION 1720 1772 ZAS2. FT REGION 1783 1841 Acidic 3. FT REGION 2053 2148 5 X 4 AA tandem repeats of [ST]-P-X-[RK]. FT COILED 1409 1433 Potential. FT MOTIF 885 891 Nuclear localization signal (Potential). FT COMPBIAS 301 327 Ser-rich. FT COMPBIAS 371 407 Ser-rich. FT COMPBIAS 780 802 Ser-rich. FT COMPBIAS 826 862 Glu/Pro-rich. FT COMPBIAS 898 930 Ser-rich. FT COMPBIAS 1873 1902 Ser-rich. FT MOD_RES 2000 2000 Phosphothreonine (By similarity). FT CONFLICT 131 131 L -> S (in Ref. 2; AAR88090). FT CONFLICT 583 584 QP -> HA (in Ref. 2; AAR88090). FT CONFLICT 721 722 GS -> AC (in Ref. 2; AAR88090). FT CONFLICT 872 872 S -> T (in Ref. 2; AAR88090). FT CONFLICT 1129 1129 E -> Q (in Ref. 2; AAR88090). FT CONFLICT 1507 1507 K -> F (in Ref. 4; AAA40039). FT CONFLICT 1660 1660 L -> V (in Ref. 2; AAR88090 and 4; FT AAA40039). FT CONFLICT 1880 1880 Q -> E (in Ref. 2; AAR88090 and 4; FT AAA40039). FT CONFLICT 1944 1944 L -> V (in Ref. 2; AAR88090 and 4; FT AAA40039). FT CONFLICT 1994 1994 L -> P (in Ref. 2; AAR88090 and 4; FT AAA40039). FT CONFLICT 1998 1998 C -> R (in Ref. 2; AAR88090 and 4; FT AAA40039). FT CONFLICT 2014 2014 R -> P (in Ref. 4; AAA40039). FT CONFLICT 2105 2105 A -> G (in Ref. 2; AAR88090 and 4; FT AAA40039). SQ SEQUENCE 2348 AA; 253413 MW; E226133774AD50C8 CRC64; MDPDQSIKGT KKADGSPRKR LTKGEAIQTS VSSSAPYPGS GTTAPSESAT QELLATQPFS GPSQEKTGQQ QKPARRPSIE ASVHISQLPQ HPLTPAFMSP GKPEHLLEGS TWQLVDPMRP GPSGSFVAPG LHPQSQLLPS HASILPPEEL PGIPKVFVPR PSQVSLKPAE EAHKKERKPQ KPGKYICQYC SRPCAKPSVL QKHIRSHTGE RPYPCGPCGF SFKTKSNLYK HRKSHAHRIK AGLASGSSSE MYPPGLEMER IPGEEFEEPT EGESTDSEEE TGAASGPSTD VLPKPKHPLL SSSLYSSGSH GSSQERCSLS QSSTGPSLED PAPFAEASSE HPLSHKPEDT HTIKQKLALR LSERKKLIEE QTFLSPGSKG STESGYFSRS ESAEQQVSPP NTNAKSYAEI IFGKCGRIGQ RTSMLASTST QPLLPLSSED KPSLVPLSVP RTQVIEHITK LITINEAVVD TSEIDSVKPR RSSLTRRSSV ESPKSSLYRD SLSSHGEKTK QEQSLLSLQH PPSSTHPVPL LRSHSMPSAA CTISTHHHTF RGSYSFDDHV ADPEVPSRNT PVFTSHPRML KRQPAIELPL GGEYSSEEPG PSSKDPTSKP SDEPEPKESD LTKKTKKGFK TKGANYECTI CGARYKKRDN YEAHKKYYCS ELQITKAHSV GAHEVEKTQA EPEPWSQMMH YKLGATLELT PLRKRRKEKS LGDEEEPPAF GSPGPSETAH NRPLGSTKSP AEASKSAPSL EGPTSFQPRT PKPGAGSEPG KERRTMSKEI SVIQHTSSFE KSDPPEQPSG LEEDKPPAQF SSPPPAPHGR SAHSLQPRLV RQPNIQVPEI LVTEEPDRPD TEPEPPPKEP EKTEEFQWPQ RSQTLAQLPA EKLPPKKKRL RLAEMAQSSG ESSFESSVPL SRSPSQESSI SLSGSSRSAS FDREDHGKAE APGPFSDTRS KTLGSHMLTV PSHHPHAREM RRSASEQSPN VPHSSHMTET RSKSFDYGSL SPTGPSLAVP AAPPPPAAPP ERRKCFLVRQ ASLNRPPEAE LEAVPKGKQE SSEEPAASKP STKSSVPQIS VGTTQGGPSG GKSQMQDRPP LGSSPPYTEA LQVFQPLGTQ LPPPASLFSL QQLLPQEQEQ SSEFFPTQAM AGLLSSPYSM PPLPPSLFQA PPLPLQPTVL HPSQLHLPQL LPHAADIPFQ QPPSFLPMPC PAPSTLSGYF LPLQSQFALQ LPGEIESHLP PVKTSLPPLA TGPPGPSSST EYSSDIQLPP VTPQATSPAP TSAPPLALPA CPDAMVSLVV PVRIQTHMPS YGSAMYTTLS QILVTQSPGS PASTALTKYE EPSSKSMTVC EADVYEAEPG PSSISKEQNR GYQTPYLRVP ERKGTSLSSE GILSLEGCSS TASGSKRVLS PAGSLELTME TQQQKRVKEE EASKADEKLE LVSTCSVVLT STEDRKKTEK PHVGGQGRSR REAETLSSLS SDVSDPKELS PLSHSTLSHG TAPGSEALKE YAQPSSKAHR RGLPPMSVKK EDPKEQTDLP PLAPPSSLPL SDTSPKPAKL QEGTDSKKVL QFPSLHTTTN VSWCYLNYIK PNHIQHADRR SSVYAGWCIS LYNPNLPGVS TKAALSLLRS KQKVSKETYT MATAPHPEAG RLVPSNSRKP RMTEVHLPSL VSPESQKDPA RVEKEEKQGK AEEGTPTSKR GEPARVKIFE GGYKSNEEYI YVRGRGRGRY VCEECGIRCK KPSMLKKHIR THTDVRPYVC KHCHFAFKTK GNLTKHMKSK AHSKKCQETG VLEELEAEEG TSDDLHQDSE GQEGAEAVEE HQFSDLEDSD SDSDLDEDEE EEEEEEESQD ELSGPCSEAA PPCLPPTLQE NSSPVEGPQA PDSTSDEVPQ GSSISEATHL TASSCSTPSR GTQGLPRLGL APLEKDMSSA PSPKATSPRR PWSPSKEAGS RPSLTRKHSL TKNDSSPQQC SPAREAQASV TSTPGPQMGP GRDLGPHLCG SPRLELSCLT PYPIGREAPA GLERATDTGT PRYSPTRRWS LGQAESPPQT VLPGKWALAG PCSPSADKSG LGLGPVPRAL LQPVPLPHTL LSRSPETCTS AWRKTESRSP SAGPAPLFPR PFSAPHDFHG HLPSRSEENL FSHLPLHSQL LSRAPCPLIP IGGIQMVQAR PGAQPTVLPG PCAAWVSGFS GGGSDLTGAR EAQERSRWSP TESPSASVSP VAKVSKFTLS SELEEERTGR GPGRPPDWEP HRAEAPPGPM GTHSPCSPQL PQGHQVAPSW RGLLGSPHTL ANLKASSFPP LDRSSSMDCL AETSTYSPPR SRNLSGEPRT RQGSPELLGR GELRTPLFLP KGSGPPSI //