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 T00239 Target Info
Target Name Interleukin-4 (IL4)
Synonyms Pitrakinra; Lymphocyte stimulatory factor 1; IL-4; Binetrakin; BSF-1; B-cell stimulatory factor 1
Target Type Clinical trial Target
Gene Name IL4
Biochemical Class Cytokine: interleukin
UniProt ID
IL4_HUMAN
The Transcription Factors (TFs) Regulating This Target  Top
TF Name Nuclear transcription factor Y A/B/C (NF-Y) heterotrimer
Classification Superclass beta-Scaffold Factors with Minor Groove Contacts
Class Heteromeric CCAAT factors
Family Heteromeric CCAAT factors
Evidence Score (E-score) 2 +
1 Electrophoretic Mobility Shift Assay [1]
2 Electrophoretic Mobility Shift Assay [3]
UniProt ID
NFYA_HUMAN/NFYB_HUMAN/NFYC_HUMAN
Sequence
MEQYTANSNSSTEQIVVQAGQIQQQQQGGVTAVQLQTEAQVASASGQQVQTLQVVQGQPL
MVQVSGGQLITSTGQPIMVQAVPGGQGQTIMQVPVSGTQGLQQIQLVPPGQIQIQGGQAV
QVQGQQGQTQQIIIQQPQTAVTAGQTQTQQQIAVQGQQVAQTAEGQTIVYQPVNADGTIL
QQVTVPVSGMITIPAASLAGAQIVQTGANTNTTSSGQGTVTVTLPVAGNVVNSGGMVMMV
PGAGSVPAIQRIPLPGAEMLEEEPLYVNAKQYHRILKRRQARAKLEAEGKIPKERRKYLH
ESRHRHAMARKRGEGGRFFSPKEKDSPHMQDPNQADEEAMTQIIRVS
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Apolipoproteins [+] 1 Apolipoproteins Co-regulated By This TF +
1 Apolipoprotein A-I (APOA1) Clinical trial Target Target Info [5]
Coagulation factors [+] 1 Coagulation factors Co-regulated By This TF +
1 Coagulation factor VIII (F8) Successful Target Target Info [6]
Cytokines / Cytokine receptors [+] 2 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Apoptosis mediating surface antigen FAS (FAS) Clinical trial Target Target Info [7]
2 Interleukin-4 (IL4) Clinical trial Target Target Info [1]
Ester hydrolases [+] 1 Ester hydrolases Co-regulated By This TF +
1 M-phase inducer phosphatase 3 (MPIP3) Literature-reported Target Target Info [8]
Oxidoreductases [+] 1 Oxidoreductases Co-regulated By This TF +
1 Catalase (CAT) Clinical trial Target Target Info [9]
TF Name Nuclear factor of activated T-cells 1 (NF-ATc1)
Classification Superclass Zinc-coordinating DNA-binding domains
Class diverse Cys4 zinc fingers
Regulation Type Increase
Regulation Mechanism The activation of human IL4 transcription through the Ca(2+)-dependent pathway is diminished by protein kinase C stimulation in Jurkat T cells. This phenomenon is due to mutually exclusive binding ofNF-ATp andNF-kappa B to the P sequence, an element located 69 bp upstream of theIL4 transcription initiation site. [2]
Evidence Score (E-score) 2 +
1 Electrophoretic Mobility Shift Assay [2]
2 Electrophoretic Mobility Shift Assay, Methylation Interference Assay [4]
UniProt ID
NFAC1_HUMAN
Sequence
MPSTSFPVPSKFPLGPAAAVFGRGETLGPAPRAGGTMKSAEEEHYGYASSNVSPALPLPT
AHSTLPAPCHNLQTSTPGIIPPADHPSGYGAALDGGPAGYFLSSGHTRPDGAPALESPRI
EITSCLGLYHNNNQFFHDVEVEDVLPSSKRSPSTATLSLPSLEAYRDPSCLSPASSLSSR
SCNSEASSYESNYSYPYASPQTSPWQSPCVSPKTTDPEEGFPRGLGACTLLGSPRHSPST
SPRASVTEESWLGARSSRPASPCNKRKYSLNGRQPPYSPHHSPTPSPHGSPRVSVTDDSW
LGNTTQYTSSAIVAAINALTTDSSLDLGDGVPVKSRKTTLEQPPSVALKVEPVGEDLGSP
PPPADFAPEDYSSFQHIRKGGFCDQYLAVPQHPYQWAKPKPLSPTSYMSPTLPALDWQLP
SHSGPYELRIEVQPKSHHRAHYETEGSRGAVKASAGGHPIVQLHGYLENEPLMLQLFIGT
ADDRLLRPHAFYQVHRITGKTVSTTSHEAILSNTKVLEIPLLPENSMRAVIDCAGILKLR
NSDIELRKGETDIGRKNTRVRLVFRVHVPQPSGRTLSLQVASNPIECSQRSAQELPLVEK
QSTDSYPVVGGKKMVLSGHNFLQDSKVIFVEKAPDGHHVWEMEAKTDRDLCKPNSLVVEI
PPFRNQRITSPVHVSFYVCNGKRKRSQYQRFTYLPANVPIIKTEPTDDYEPAPTCGPVSQ
GLSPLPRPYYSQQLAMPPDPSSCLVAGFPPCPQRSTLMPAAPGVSPKLHDLSPAAYTKGV
ASPGHCHLGLPQPAGEAPAVQDVPRPVATHPGSPGQPPPALLPQQVSAPPSSSCPPGLEH
SLCPSSPSPPLPPATQEPTCLQPCSPACPPATGRPQHLPSTVRRDESPTAGPRLLPEVHE
DGSPNLAPIPVTVKREPEELDQLYLDDVNEIIRNDLSSTSTHS
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Cytokines / Cytokine receptors [+] 2 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interleukin-4 (IL4) Clinical trial Target Target Info [2]
2 Interleukin-5 (IL5) Successful Target Target Info [10]
TF Name Nuclear factor of activated T-cells 2 (NF-ATc2)
Classification Superclass Zinc-coordinating DNA-binding domains
Class diverse Cys4 zinc fingers
Regulation Type Increase
Regulation Mechanism The activation of human IL4 transcription through the Ca(2+)-dependent pathway is diminished by protein kinase C stimulation in Jurkat T cells. This phenomenon is due to mutually exclusive binding ofNF-ATp andNF-kappa B to the P sequence, an element located 69 bp upstream of theIL4 transcription initiation site. [2]
Evidence Score (E-score) 2 +
1 Electrophoretic Mobility Shift Assay [2]
2 Electrophoretic Mobility Shift Assay, Methylation Interference Assay [4]
UniProt ID
NFAC2_HUMAN
Sequence
MNAPERQPQPDGGDAPGHEPGGSPQDELDFSILFDYEYLNPNEEEPNAHKVASPPSGPAY
PDDVLDYGLKPYSPLASLSGEPPGRFGEPDRVGPQKFLSAAKPAGASGLSPRIEITPSHE
LIQAVGPLRMRDAGLLVEQPPLAGVAASPRFTLPVPGFEGYREPLCLSPASSGSSASFIS
DTFSPYTSPCVSPNNGGPDDLCPQFQNIPAHYSPRTSPIMSPRTSLAEDSCLGRHSPVPR
PASRSSSPGAKRRHSCAEALVALPPGASPQRSRSPSPQPSSHVAPQDHGSPAGYPPVAGS
AVIMDALNSLATDSPCGIPPKMWKTSPDPSPVSAAPSKAGLPRHIYPAVEFLGPCEQGER
RNSAPESILLVPPTWPKPLVPAIPICSIPVTASLPPLEWPLSSQSGSYELRIEVQPKPHH
RAHYETEGSRGAVKAPTGGHPVVQLHGYMENKPLGLQIFIGTADERILKPHAFYQVHRIT
GKTVTTTSYEKIVGNTKVLEIPLEPKNNMRATIDCAGILKLRNADIELRKGETDIGRKNT
RVRLVFRVHIPESSGRIVSLQTASNPIECSQRSAHELPMVERQDTDSCLVYGGQQMILTG
QNFTSESKVVFTEKTTDGQQIWEMEATVDKDKSQPNMLFVEIPEYRNKHIRTPVKVNFYV
INGKRKRSQPQHFTYHPVPAIKTEPTDEYDPTLICSPTHGGLGSQPYYPQHPMVAESPSC
LVATMAPCQQFRTGLSSPDARYQQQNPAAVLYQRSKSLSPSLLGYQQPALMAAPLSLADA
HRSVLVHAGSQGQSSALLHPSPTNQQASPVIHYSPTNQQLRCGSHQEFQHIMYCENFAPG
TTRPGPPPVSQGQRLSPGSYPTVIQQQNATSQRAAKNGPPVSDQKEVLPAGVTIKQEQNL
DQTYLDDVNEIIRKEFSGPPARNQT
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Cytokines / Cytokine receptors [+] 2 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interleukin-4 (IL4) Clinical trial Target Target Info [2]
2 Interleukin-5 (IL5) Successful Target Target Info [10]
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 Type Decrease
Regulation Mechanism HumanIL4 promoter-mediated transcription is downregulated in Jurkat cells stimulated with theNFKB-activating cytokine tumor necrosis factor alpha and suppressed in RelA-overexpressing cells. [2]
Evidence Score (E-score) 1 +
1 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 [12]
2 Interleukin-12 beta (IL12B) Successful Target Target Info [13]
3 Interleukin-4 (IL4) Clinical trial Target Target Info [2]
Immunoglobulins [+] 1 Immunoglobulins Co-regulated By This TF +
1 Intercellular adhesion molecule ICAM-1 (ICAM1) Successful Target Target Info [14]
Oxidoreductases [+] 1 Oxidoreductases Co-regulated By This TF +
1 Arachidonate 12-lipoxygenase (12-LOX) Literature-reported Target Target Info [15]
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 [17]
TF Name NF-kappa-B (NFKB) homo/heterodimer
Classification Superclass beta-Scaffold Factors with Minor Groove Contacts
Class RHR (Rel homology region)
Regulation Type Decrease
Regulation Mechanism HumanIL4 promoter-mediated transcription is downregulated in Jurkat cells stimulated with theNFKB-activating cytokine tumor necrosis factor alpha and suppressed in RelA-overexpressing cells. [2]
Evidence Score (E-score) 1 +
1 Electrophoretic Mobility Shift Assay [2]
UniProt ID
NFKB1_HUMAN; NFKB2_HUMAN; RELB_HUMAN; REL_HUMAN; TF65_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
Cytokines / Cytokine receptors [+] 5 Cytokines / Cytokine receptors Co-regulated By This TF +
1 C-X-C motif chemokine 1 (CXCL1) Literature-reported Target Target Info [18]
2 C-X-C motif chemokine 2 (CXCL2) Clinical trial Target Target Info [19]
3 Interleukin 2 receptor alpha (IL2RA) Successful Target Target Info [20]
4 Interleukin-4 (IL4) Clinical trial Target Target Info [2]
5 Interleukin-8 (IL8) Successful Target Target Info [21]
Glycoproteins [+] 1 Glycoproteins Co-regulated By This TF +
1 E-selectin (SELE) Clinical trial Target Target Info [22]
Immunoglobulins [+] 1 Immunoglobulins Co-regulated By This TF +
1 Intercellular adhesion molecule ICAM-1 (ICAM1) Successful Target Target Info [14]
Transcription factors [+] 1 Transcription factors Co-regulated By This TF +
1 Cellular tumor antigen p53 (TP53) Clinical trial Target Target Info [23]
TF Name Interferon regulatory factor 2 (IRF2)
Classification Superclass Helix-turn-helix
Class Tryptophan clusters
Family Interferon-regulating factors
Evidence Score (E-score) 1 +
1 Electrophoretic Mobility Shift Assay [1]
UniProt ID
IRF2_HUMAN
Sequence
MPVERMRMRPWLEEQINSNTIPGLKWLNKEKKIFQIPWMHAARHGWDVEKDAPLFRNWAI
HTGKHQPGVDKPDPKTWKANFRCAMNSLPDIEEVKDKSIKKGNNAFRVYRMLPLSERPSK
KGKKPKTEKEDKVKHIKQEPVESSLGLSNGVSDLSPEYAVLTSTIKNEVDSTVNIIVVGQ
SHLDSNIENQEIVTNPPDICQVVEVTTESDEQPVSMSELYPLQISPVSSYAESETTDSVP
SDEESAEGRPHWRKRNIEGKQYLSNMGTRGSYLLPGMASFVTSNKPDLQVTIKEESNPVP
YNSSWPPFQDLPLSSSMTPASSSSRPDRETRASVIKKTSDITQARVKSC
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 [24]
Cytokines / Cytokine receptors [+] 1 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interleukin-4 (IL4) Clinical trial Target Target Info [1]
TF Name C/EBP gamma (CEBPG) homodimer
Classification Superclass Basic Domains
Class Leucine zipper factors (bZIP)
Family C/EBP-like factors
Regulation Type Increase
Regulation Mechanism CEBPG binds to the PRE-I (positive regulatory element-I), whichis a strong enhancer element essential for expression of the human IL4-encoding gene. [1]
Evidence Score (E-score) 1 +
1 Electrophoretic Mobility Shift Assay [1]
UniProt ID
CEBPG_HUMAN
Sequence
MSKISQQNSTPGVNGISVIHTQAHASGLQQVPQLVPAGPGGGGKAVAPSKQSKKSSPMDR
NSDEYRQRRERNNMAVKKSRLKSKQKAQDTLQRVNQLKEENERLEAKIKLLTKELSVLKD
LFLEHAHNLADNVQSISTENTTADGDNAGQ
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Cytokines / Cytokine receptors [+] 1 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interleukin-4 (IL4) Clinical trial Target Target Info [1]
References  Top
REF 1 Cloning of the cDNA encoding human C/EBP gamma, a protein binding to the PRE-I enhancer element of the human interleukin-4 promoter. Gene. 1995 Aug 19;161(2):271-5.
REF 2 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 3 The role of NF-Y and IRF-2 in the regulation of human IL-4 gene expression. J Immunol. 1994 Nov 1;153(9):4122-33.
REF 4 Characterization of constitutive and inducible transcription factors binding to the P2 NF-AT site in the human interleukin-4 promoter. Gene. 1997 Apr 1;188(2):253-60.
REF 5 NFY transcription factor binds to regulatory element AIC and transactivates the human apolipoprotein A-I promoter in HEPG2 cells. Biochem Biophys Res Commun. 1997 Feb 3;231(1):140-3.
REF 6 Role of the liver-enriched transcription factor hepatocyte nuclear factor 1 in transcriptional regulation of the factor V111 gene. Mol Cell Biol. 1996 May;16(5):1936-45.
REF 7 Identification of thyroid hormone response elements in the human fatty acid synthase promoter. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12260-5.
REF 8 Cell cycle regulation of cdc25C transcription is mediated by the periodic repression of the glutamine-rich activators NF-Y and Sp1. Nucleic Acids Res. 1995 Oct 11;23(19):3822-30.
REF 9 Regulation of the catalase gene promoter by Sp1, CCAAT-recognizing factors, and a WT1/Egr-related factor in hydrogen peroxide-resistant HP100 cells. Cancer Res. 2001 Aug 1;61(15):5885-94.
REF 10 A nuclear factor of activated T cell-like transcription factor in mast cells is involved in IL-5 gene regulation after IgE plus antigen stimulation. J Immunol. 1995 Jun 1;154(11):6112-9.
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 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 13 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 14 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 15 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 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 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 18 HMGI(Y) and Sp1 in addition to NF-kappa B regulate transcription of the MGSA/GRO alpha gene. Nucleic Acids Res. 1995 Oct 25;23(20):4210-9.
REF 19 An NF-kappa B-like transcription factor mediates IL-1/TNF-alpha induction of gro in human fibroblasts. J Immunol. 1991 Jul 15;147(2):520-7.
REF 20 Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y... Mol Cell Biol. 1995 Mar;15(3):1786-96.
REF 21 Cooperation between transcription factor AP-1 and NF-kappaB in the induction of interleukin-8 in human pancreatic adenocarcinoma cells by hypoxia. J Interferon Cytokine Res. 1999 Dec;19(12):1363-71.
REF 22 Interleukin-4 suppression of tumor necrosis factor alpha-stimulated E-selectin gene transcription is mediated by STAT6 antagonism of NF-kappaB. J Biol Chem. 1997 Apr 11;272(15):10212-9.
REF 23 Additive effect between NF-kappaB subunits and p53 protein for transcriptional activation of human p53 promoter. Oncogene. 2000 Sep 28;19(41):4787-94.
REF 24 Interferon regulatory factor-2 is a transcriptional activator in muscle where It regulates expression of vascular cell adhesion molecule-1. J Cell Biol. 1998 Mar 9;140(5):1265-76.

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