Target Regulator(s) Information (Transcription Factor)

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Target General Information
The Transcription Factors (TFs) Regulating This Target
References
Target General Information  Top
Target ID T95385 Target Info
Target Name Interleukin-12 beta (IL12B)
Synonyms NKSF2; NK cell stimulatory factor chain 2; Interleukin12 subunit beta; Interleukin-12 subunit beta; IL12 subunit p40; IL-12B; IL-12 subunit p40; Cytotoxic lymphocyte maturation factor 40 kDa subunit; CLMF p40
Target Type Successful Target
Gene Name IL12B
Biochemical Class Cytokine: interleukin
UniProt ID
IL12B_HUMAN
The Transcription Factors (TFs) Regulating This Target  Top
TF Name ETS proto-oncogene 2 (C-ets-2)
Classification Superclass Helix-turn-helix
Class Tryptophan clusters
Family Ets-type
Regulation Mechanism One of the DNA-protein interactions observed around anEts-2 element situated at 211/207 of the IL12B p40promoter, which is known to be a functionally critical site. [1]
Evidence Score (E-score) 2 +
1 Electrophoretic Mobility Shift Assay [1]
2 Electrophoretic Mobility Shift Assay [3]
UniProt ID
ETS2_HUMAN
Sequence
MNDFGIKNMDQVAPVANSYRGTLKRQPAFDTFDGSLFAVFPSLNEEQTLQEVPTGLDSIS
HDSANCELPLLTPCSKAVMSQALKATFSGFKKEQRRLGIPKNPWLWSEQQVCQWLLWATN
EFSLVNVNLQRFGMNGQMLCNLGKERFLELAPDFVGDILWEHLEQMIKENQEKTEDQYEE
NSHLTSVPHWINSNTLGFGTEQAPYGMQTQNYPKGGLLDSMCPASTPSVLSSEQEFQMFP
KSRLSSVSVTYCSVSQDFPGSNLNLLTNNSGTPKDHDSPENGADSFESSDSLLQSWNSQS
SLLDVQRVPSFESFEDDCSQSLCLNKPTMSFKDYIQERSDPVEQGKPVIPAAVLAGFTGS
GPIQLWQFLLELLSDKSCQSFISWTGDGWEFKLADPDEVARRWGKRKNKPKMNYEKLSRG
LRYYYDKNIIHKTSGKRYVYRFVCDLQNLLGFTPEELHAILGVQPDTED
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Apoptosis regulators [+] 1 Apoptosis regulators Co-regulated By This TF +
1 Apoptosis regulator Bcl-2 (BCL-2) Successful Target Target Info [4]
Cytokines / Cytokine receptors [+] 1 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interleukin-12 beta (IL12B) Successful Target Target Info [1]
Glycoproteins [+] 1 Glycoproteins Co-regulated By This TF +
1 von Willebrand factor (VWF) Successful Target Target Info [5]
Oxidoreductases [+] 1 Oxidoreductases Co-regulated By This TF +
1 Nitric-oxide synthase endothelial (NOS3) Clinical trial Target Target Info [6]
TF Name NF-kappa-B c-Rel-c-Rel (NFKB) homodimer
Classification Superclass beta-Scaffold Factors with Minor Groove Contacts
Class RHR (Rel homology region)
Family Rel/ankyrin
Regulation Mechanism Within the 400 proximal promoter region of the human IL12 p40 gene, several putative transcription factor binding sites are very well conserved: Ets-2,PU.1, and an NFKB-like element, which has been postulated to be a critical response element in the murine p40promoterfor LPS stimulation in macrophagic J774 cells. [1]
Evidence Score (E-score) 1 +
1 Electrophoretic Mobility Shift Assay [1]
UniProt ID
REL_HUMAN
Sequence
MASGAYNPYIEIIEQPRQRGMRFRYKCEGRSAGSIPGEHSTDNNRTYPSIQIMNYYGKGK
VRITLVTKNDPYKPHPHDLVGKDCRDGYYEAEFGQERRPLFFQNLGIRCVKKKEVKEAII
TRIKAGINPFNVPEKQLNDIEDCDLNVVRLCFQVFLPDEHGNLTTALPPVVSNPIYDNRA
PNTAELRICRVNKNCGSVRGGDEIFLLCDKVQKDDIEVRFVLNDWEAKGIFSQADVHRQV
AIVFKTPPYCKAITEPVTVKMQLRRPSDQEVSESMDFRYLPDEKDTYGNKAKKQKTTLLF
QKLCQDHVETGFRHVDQDGLELLTSGDPPTLASQSAGITVNFPERPRPGLLGSIGEGRYF
KKEPNLFSHDAVVREMPTGVSSQAESYYPSPGPISSGLSHHASMAPLPSSSWSSVAHPTP
RSGNTNPLSSFSTRTLPSNSQGIPPFLRIPVGNDLNASNACIYNNADDIVGMEASSMPSA
DLYGISDPNMLSNCSVNMMTTSSDSMGETDNPRLLSMNLENPSCNSVLDPRDLRQLHQMS
SSSMSAGANSNTTVFVSQSDAFEGSDFSCADNSMINESGPSNSTNPNSHGFVQDSQYSGI
GSMQNEQLSDSFPYEFFQV
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Cytokines / Cytokine receptors [+] 4 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interferon-gamma (IFNG) Successful Target Target Info [7]
2 Interleukin 2 receptor alpha (IL2RA) Successful Target Target Info [8]
3 Interleukin-1 beta (IL1B) Successful Target Target Info [9]
4 Interleukin-12 beta (IL12B) Successful Target Target Info [1]
Oxidoreductases [+] 1 Oxidoreductases Co-regulated By This TF +
1 Arachidonate 12-lipoxygenase (12-LOX) Literature-reported Target Target Info [10]
TF Name NF-kappa-B p50-p50 (NFKB) homodimer
Classification Superclass beta-Scaffold Factors with Minor Groove Contacts
Class RHR (Rel homology region)
Family Rel/ankyrin
Regulation Mechanism The repressive effect maps to a region in the IL-12 p40 promoter containing a binding site for NFKB. [2]
Evidence Score (E-score) 1 +
1 Luciferase Reporter Assay, Electrophoretic Mobility Shift Assay [2]
UniProt ID
NFKB1_HUMAN
Sequence
MAEDDPYLGRPEQMFHLDPSLTHTIFNPEVFQPQMALPTDGPYLQILEQPKQRGFRFRYV
CEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCED
GICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGLLVHPDLAYLQA
EGGGDRQLGDREKELIRQAALQQTKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAIY
DSKAPNASNLKIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIRFYEEEENGGVWEGFGDF
SPTDVHRQFAIVFKTPKYKDINITKPASVFVQLRRKSDLETSEPKPFLYYPEIKDKEEVQ
RKRQKLMPNFSDSFGGGSGAGAGGGGMFGSGGGGGGTGSTGPGYSFPHYGFPTYGGITFH
PGTTKSNAGMKHGTMDTESKKDPEGCDKSDDKNTVNLFGKVIETTEQDQEPSEATVGNGE
VTLTYATGTKEESAGVQDNLFLEKAMQLAKRHANALFDYAVTGDVKMLLAVQRHLTAVQD
ENGDSVLHLAIIHLHSQLVRDLLEVTSGLISDDIINMRNDLYQTPLHLAVITKQEDVVED
LLRAGADLSLLDRLGNSVLHLAAKEGHDKVLSILLKHKKAALLLDHPNGDGLNAIHLAMM
SNSLPCLLLLVAAGADVNAQEQKSGRTALHLAVEHDNISLAGCLLLEGDAHVDSTTYDGT
TPLHIAAGRGSTRLAALLKAAGADPLVENFEPLYDLDDSWENAGEDEGVVPGTTPLDMAT
SWQVFDILNGKPYEPEFTSDDLLAQGDMKQLAEDVKLQLYKLLEIPDPDKNWATLAQKLG
LGILNNAFRLSPAPSKTLMDNYEVSGGTVRELVEALRQMGYTEAIEVIQAASSPVKTTSQ
AHSLPLSPASTRQQIDELRDSDSVCDSGVETSFRKLSFTESLTSGASLLTLNKMPHDYGQ
EGPLEGKI
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Apolipoproteins [+] 1 Apolipoproteins Co-regulated By This TF +
1 Apolipoprotein C-III (ApoCIII) Clinical trial Target Target Info [11]
Apoptosis regulators [+] 1 Apoptosis regulators Co-regulated By This TF +
1 Apoptosis regulator Bcl-2 (BCL-2) Successful Target Target Info [12]
CD antigens [+] 1 CD antigens Co-regulated By This TF +
1 Vascular cell adhesion protein 1 (VCAM1) Literature-reported Target Target Info [13]
Coagulation factors [+] 1 Coagulation factors Co-regulated By This TF +
1 Coagulation factor VIII (F8) Successful Target Target Info [14]
Cytokines / Cytokine receptors [+] 2 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interleukin-1 beta (IL1B) Successful Target Target Info [9]
2 Interleukin-12 beta (IL12B) Successful Target Target Info [2]
Immunoglobulins [+] 1 Immunoglobulins Co-regulated By This TF +
1 Intercellular adhesion molecule ICAM-1 (ICAM1) Successful Target Target Info [15]
Oxidoreductases [+] 1 Oxidoreductases Co-regulated By This TF +
1 Arachidonate 12-lipoxygenase (12-LOX) Literature-reported Target Target Info [10]
Transcription factors [+] 1 Transcription factors Co-regulated By This TF +
1 Cellular tumor antigen p53 (TP53) Clinical trial Target Target Info [16]
TF Name NF-kappa-B p65-p65 (NFKB) homodimer
Classification Superclass beta-Scaffold Factors with Minor Groove Contacts
Class RHR (Rel homology region)
Family Rel/ankyrin
Regulation Mechanism The repressive effect maps to a region in the IL-12 p40 promoter containing a binding site for NFKB. [2]
Evidence Score (E-score) 1 +
1 Luciferase Reporter Assay, Electrophoretic Mobility Shift Assay [2]
UniProt ID
TF65_HUMAN
Sequence
MDELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPT
IKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRCIHSFQNLGIQC
VKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLS
HPIFDNRAPNTAELKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYFTGPGWEARGSFS
QADVHRQVAIVFRTPPYADPSLQAPVRVSMQLRRPSDRELSEPMEFQYLPDTDDRHRIEE
KRKRTYETFKSIMKKSPFSGPTDPRPPPRRIAVPSRSSASVPKPAPQPYPFTSSLSTINY
DEFPTMVFPSGQISQASALAPAPPQVLPQAPAPAPAPAMVSALAQAPAPVPVLAPGPPQA
VAPPAPKPTQAGEGTLSEALLQLQFDDEDLGALLGNSTDPAVFTDLASVDNSEFQQLLNQ
GIPVAPHTTEPMLMEYPEAITRLVTGAQRPPDPAPAPLGAPGLPNGLLSGDEDFSSIADM
DFSALLSQISS
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Apolipoproteins [+] 1 Apolipoproteins Co-regulated By This TF +
1 Apolipoprotein C-III (ApoCIII) Clinical trial Target Target Info [11]
Cytokines / Cytokine receptors [+] 3 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interleukin-1 beta (IL1B) Successful Target Target Info [9]
2 Interleukin-12 beta (IL12B) Successful Target Target Info [2]
3 Interleukin-4 (IL4) Clinical trial Target Target Info [17]
Immunoglobulins [+] 1 Immunoglobulins Co-regulated By This TF +
1 Intercellular adhesion molecule ICAM-1 (ICAM1) Successful Target Target Info [15]
Oxidoreductases [+] 1 Oxidoreductases Co-regulated By This TF +
1 Arachidonate 12-lipoxygenase (12-LOX) Literature-reported Target Target Info [10]
Transcription factors [+] 2 Transcription factors Co-regulated By This TF +
1 Cellular tumor antigen p53 (TP53) Clinical trial Target Target Info [16]
2 Interferon regulatory factor 1 (IRF1) Literature-reported Target Target Info [18]
TF Name PU.1 proto-oncogene (SPI1)
Classification Superclass Helix-turn-helix
Class Tryptophan clusters
Family Ets-type
Regulation Mechanism Within the 400 proximal promoter region of the human IL12 p40 gene, several putative transcription factor binding sites are very well conserved: Ets-2,PU.1, and an NFKB-like element, which has been postulated to be a critical response element in the murine p40promoterfor LPS stimulation in macrophagic J774 cells. [1]
Evidence Score (E-score) 1 +
1 Electrophoretic Mobility Shift Assay [1]
UniProt ID
SPI1_HUMAN
Sequence
MLQACKMEGFPLVPPPSEDLVPYDTDLYQRQTHEYYPYLSSDGESHSDHYWDFHPHHVHS
EFESFAENNFTELQSVQPPQLQQLYRHMELEQMHVLDTPMVPPHPSLGHQVSYLPRMCLQ
YPSLSPAQPSSDEEEGERQSPPLEVSDGEADGLEPGPGLLPGETGSKKKIRLYQFLLDLL
RSGDMKDSIWWVDKDKGTFQFSSKHKEALAHRWGIQKGNRKKMTYQKMARALRNYGKTGE
VKKVKKKLTYQFSGEVLGRGGLAERRHPPH
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Cytokines / Cytokine receptors [+] 4 Cytokines / Cytokine receptors Co-regulated By This TF +
1 CD40L receptor (CD40) Clinical trial Target Target Info [19]
2 Granulocyte colony-stimulating factor receptor (G-CSF-R) Successful Target Target Info [20]
3 Interleukin-1 beta (IL1B) Successful Target Target Info [21]
4 Interleukin-12 beta (IL12B) Successful Target Target Info [1]
Integrins [+] 1 Integrins Co-regulated By This TF +
1 Integrin beta-2 (ITGB2) Clinical trial Target Target Info [22]
TF Name Interferon regulatory factor 1 (IRF1)
Classification Superclass Helix-turn-helix
Class Tryptophan clusters
Family Interferon-regulating factors
Regulation Mechanism A nuclear factor, termed GLp109, is inducible by either IFN-gamma or LPS and is part of a complex including IRF1 and possibly NFKB c-Rel that interacts with the Ets-2 element in the IL12B p40 promoter. [1]
Evidence Score (E-score) 1 +
1 Electrophoretic Mobility Shift Assay [1]
UniProt ID
IRF1_HUMAN
Sequence
MPITRMRMRPWLEMQINSNQIPGLIWINKEEMIFQIPWKHAAKHGWDINKDACLFRSWAI
HTGRYKAGEKEPDPKTWKANFRCAMNSLPDIEEVKDQSRNKGSSAVRVYRMLPPLTKNQR
KERKSKSSRDAKSKAKRKSCGDSSPDTFSDGLSSSTLPDDHSSYTVPGYMQDLEVEQALT
PALSPCAVSSTLPDWHIPVEVVPDSTSDLYNFQVSPMPSTSEATTDEDEEGKLPEDIMKL
LEQSEWQPTNVDGKGYLLNEPGVQPTSVYGDFSCKEEPEIDSPGGDIGLSLQRVFTDLKN
MDATWLDSLLTPVRLPSIQAIPCAP
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
CD antigens [+] 1 CD antigens Co-regulated By This TF +
1 Vascular cell adhesion protein 1 (VCAM1) Literature-reported Target Target Info [13]
Cytokines / Cytokine receptors [+] 1 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interleukin-12 beta (IL12B) Successful Target Target Info [1]
Transcription factors [+] 1 Transcription factors Co-regulated By This TF +
1 Signal transducer and activator of transcription 1 (STAT1) Patented-recorded Target Target Info [23]
References  Top
REF 1 Identification and characterization of a novel Ets-2-related nuclear complex implicated in the activation of the human interleukin-12 p40 gene prom... J Biol Chem. 1997 Apr 18;272(16):10389-95.
REF 2 Inhibition of IL-12 production by 1,25-dihydroxyvitamin D3. Involvement of NF-kappaB downregulation in transcriptional repression of the p40 gene. J Clin Invest. 1998 Jan 1;101(1):252-62.
REF 3 Inhibition of IL-12 production in human monocyte-derived macrophages by TNF. J Immunol. 2000 Feb 15;164(4):1722-9.
REF 4 Pi 1 binding sites are negative regulators of bcl-2 expression in pre-B cells. Mol Cell Biol. 1995 Jul;15(7):3840-7.
REF 5 Ets transcription factors bind and transactivate the core promoter of the von Willebrand factor gene. Oncogene. 1997 Dec 18;15(25):3091-102.
REF 6 Transcriptional regulation of endothelial nitric-oxide synthase by lysophosphatidylcholine. J Biol Chem. 1998 Jun 12;273(24):14885-90.
REF 7 The c-rel protooncogene product c-Rel but not NF-kappa B binds to the intronic region of the human interferon-gamma gene at a site related to an in... Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1740-4.
REF 8 Kappa B site-dependent activation of the interleukin-2 receptor alpha-chain gene promoter by human c-Rel. Mol Cell Biol. 1992 Sep;12(9):4067-75.
REF 9 Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop. Mol Cell Biol. 1993 Oct;13(10):6231-40.
REF 10 The transcriptional regulation of human arachidonate 12-lipoxygenase gene by NF kappa B/Rel. FEBS Lett. 1995 Apr 17;363(1-2):105-10.
REF 11 Apo CIII gene transcription is regulated by a cytokine inducible NF-kappa B element. Nucleic Acids Res. 1994 Jun 25;22(12):2417-22.
REF 12 NF-kappaB1 (p50) homodimers contribute to transcription of the bcl-2 oncogene. J Biol Chem. 2001 Nov 30;276(48):45380-6.
REF 13 Endothelial interferon regulatory factor 1 cooperates with NF-kappa B as a transcriptional activator of vascular cell adhesion molecule 1. Mol Cell Biol. 1995 May;15(5):2558-69.
REF 14 cis-acting elements and transcription factors involved in the promoter activity of the human factor VIII gene. J Biol Chem. 1995 May 19;270(20):11828-38.
REF 15 Flanking sequences for the human intercellular adhesion molecule-1 NF-kappaB response element are necessary for tumor necrosis factor alpha-induced gene expression. J Biol Chem. 1997 Jun 20;272(25):15928-35.
REF 16 Expression of human p53 requires synergistic activation of transcription from the p53 promoter by AP-1, NF-kappaB and Myc/Max. Oncogene. 1999 Apr 29;18(17):2728-38.
REF 17 Inhibition of NF-AT-dependent transcription by NF-kappa B: implications for differential gene expression in T helper cell subsets. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11623-7.
REF 18 Synergy between interferon-gamma and tumor necrosis factor-alpha in transcriptional activation is mediated by cooperation between signal transducer and activator of transcription 1 and nuclear factor kappaB. J Biol Chem. 1997 Jun 6;272(23):14899-907.
REF 19 IL-4-activated STAT-6 inhibits IFN-gamma-induced CD40 gene expression in macrophages/microglia. J Immunol. 2000 Dec 1;165(11):6235-43.
REF 20 PU.1 (Spi-1) and C/EBP alpha regulate the granulocyte colony-stimulating factor receptor promoter in myeloid cells. Blood. 1996 Aug 15;88(4):1234-47.
REF 21 Monocyte expression of the human prointerleukin 1 beta gene (IL1B) is dependent on promoter sequences which bind the hematopoietic transcription fa... Mol Cell Biol. 1995 Jan;15(1):58-68.
REF 22 CD18 (beta 2 leukocyte integrin) promoter requires PU.1 transcription factor for myeloid activity. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):801-5.
REF 23 Isolation and characterization of a human STAT1 gene regulatory element. Inducibility by interferon (IFN) types I and II and role of IFN regulatory... J Biol Chem. 2002 May 31;277(22):19408-17.

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