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 T54156 Target Info
Target Name Matrix metalloproteinase-9 (MMP-9)
Synonyms Matrix metalloproteinase 9; GELB; CLG4B; 92 kDa type IV collagenase; 92 kDa gelatinase
Target Type Clinical trial Target
Gene Name MMP9
Biochemical Class Peptidase
UniProt ID
MMP9_HUMAN
The Transcription Factors (TFs) Regulating This Target  Top
TF Name NF-kappa-B p65-p50 (NFKB) heterodimer
Classification Superclass beta-Scaffold Factors with Minor Groove Contacts
Class RHR (Rel homology region)
Family Rel/ankyrin
Regulation Type Increase
Regulation Mechanism Down-regulateing NFKB binding to the promoter leads to MMP-9 expression inhibition. It is a consequence of NFKB-induced block of p65/p50 nuclear translocation. [1]
Evidence Score (E-score) 2 +
1 DNA Binding Assay [3]
2 Electrophoretic Mobility Shift Assay, Chromatin Immunoprecipitation Assay [1]
UniProt ID
TF65_HUMAN/NFKB1_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
CD antigens [+] 1 CD antigens Co-regulated By This TF +
1 Vascular cell adhesion protein 1 (VCAM1) Literature-reported Target Target Info [4]
Cytokines / Cytokine receptors [+] 1 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interleukin-1 beta (IL1B) Successful Target Target Info [5]
Immunoglobulins [+] 1 Immunoglobulins Co-regulated By This TF +
1 Intercellular adhesion molecule ICAM-1 (ICAM1) Successful Target Target Info [6]
Kinases [+] 1 Kinases Co-regulated By This TF +
1 Casein kinase II alpha (CSNK2A1) Clinical trial Target Target Info [7]
Peptidases [+] 1 Peptidases Co-regulated By This TF +
1 Matrix metalloproteinase-9 (MMP-9) Clinical trial Target Target Info [1]
Transcription factors [+] 1 Transcription factors Co-regulated By This TF +
1 Interferon regulatory factor 1 (IRF1) Literature-reported Target Target Info [8]
TF Name c-Jun/c-Jun (AP-1) homodimer
Classification Superclass Basic Domains
Class Leucine zipper factors (bZIP)
Family AP-1(-like) components
Subfamily Jun
Regulation Type Increase
Regulation Mechanism Stimulation of MMP-9 promoter activity by ras is mitogen-activated protein kinase kinase 1-independent and requires multiple transcription factor binding sites including closely spaced PEA3/ETS and AP-1 sequences. [2]
Evidence Score (E-score) 1 +
1 Chloramphenicol Acetyltransferase Assay [2]
UniProt ID
JUN_HUMAN
Sequence
MTAKMETTFYDDALNASFLPSESGPYGYSNPKILKQSMTLNLADPVGSLKPHLRAKNSDL
LTSPDVGLLKLASPELERLIIQSSNGHITTTPTPTQFLCPKNVTDEQEGFAEGFVRALAE
LHSQNTLPSVTSAAQPVNGAGMVAPAVASVAGGSGSGGFSASLHSEPPVYANLSNFNPGA
LSSGGGAPSYGAAGLAFPAQPQQQQQPPHHLPQQMPVQHPRLQALKEEPQTVPEMPGETP
PLSPIDMESQERIKAERKRMRNRIAASKCRKRKLERIARLEEKVKTLKAQNSELASTANM
LREQVAQLKQKVMNHVNSGCQLMLTQQLQTF
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 5 receptor alpha (IL5RA) Successful Target Target Info [9]
2 Interleukin-5 (IL5) Successful Target Target Info [10]
Fibronectin proteins [+] 1 Fibronectin proteins Co-regulated By This TF +
1 Fibronectin (FN1) Clinical trial Target Target Info [11]
Lipoprotein receptors [+] 1 Lipoprotein receptors Co-regulated By This TF +
1 Low-density lipoprotein receptor (LDL-R) Successful Target Target Info [12]
Peptidases [+] 2 Peptidases Co-regulated By This TF +
1 Matrix metalloproteinase-1 (MMP-1) Successful Target Target Info [13]
2 Matrix metalloproteinase-9 (MMP-9) Clinical trial Target Target Info [2]
TF Name ETS translocation variant 4 (ETV4)
Classification Superclass Helix-turn-helix
Class Tryptophan clusters
Family Ets-type
Regulation Type Increase
Regulation Mechanism Stimulation of MMP-9 promoter activity by ras is mitogen-activated protein kinase kinase 1-independent and requires multiple transcription factor binding sites including closely spaced PEA3/ETS and AP-1 sequences. [2]
Evidence Score (E-score) 1 +
1 Chloramphenicol Acetyltransferase Assay [2]
UniProt ID
ETV4_HUMAN
Sequence
MERRMKAGYLDQQVPYTFSSKSPGNGSLREALIGPLGKLMDPGSLPPLDSEDLFQDLSHF
QETWLAEAQVPDSDEQFVPDFHSENLAFHSPTTRIKKEPQSPRTDPALSCSRKPPLPYHH
GEQCLYSSAYDPPRQIAIKSPAPGALGQSPLQPFPRAEQRNFLRSSGTSQPHPGHGYLGE
HSSVFQQPLDICHSFTSQGGGREPLPAPYQHQLSEPCPPYPQQSFKQEYHDPLYEQAGQP
AVDQGGVNGHRYPGAGVVIKQEQTDFAYDSDVTGCASMYLHTEGFSGPSPGDGAMGYGYE
KPLRPFPDDVCVVPEKFEGDIKQEGVGAFREGPPYQRRGALQLWQFLVALLDDPTNAHFI
AWTGRGMEFKLIEPEEVARLWGIQKNRPAMNYDKLSRSLRYYYEKGIMQKVAGERYVYKF
VCEPEALFSLAFPDNQRPALKAEFDRPVSEEDTVPLSHLDESPAYLPELAGPAQPFGPKG
GYSY
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Oxidoreductases [+] 1 Oxidoreductases Co-regulated By This TF +
1 Nitric-oxide synthase endothelial (NOS3) Clinical trial Target Target Info [14]
Peptidases [+] 1 Peptidases Co-regulated By This TF +
1 Matrix metalloproteinase-9 (MMP-9) Clinical trial Target Target Info [2]
References  Top
REF 1 KiSS-1 represses 92-kDa type IV collagenase expression by down-regulating NF-kappa B binding to the promoter as a consequence of Ikappa Balpha -ind... J Biol Chem. 2001 Jan 12;276(2):1164-72.
REF 2 Stimulation of 92-kDa gelatinase B promoter activity by ras is mitogen-activated protein kinase kinase 1-independent and requires multiple transcription factor binding sites including closely spaced PEA3/ets and AP-1 sequences. J Biol Chem. 1996 May 3;271(18):10672-80.
REF 3 Expression of angiogenic factors vascular endothelial growth factor and interleukin-8/CXCL8 is highly responsive to ambient glutamine availability:... Cancer Res. 2004 Jul 15;64(14):4858-69.
REF 4 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 5 NF-kappa B regulates IL-1 beta transcription through a consensus NF-kappa B binding site and a nonconsensus CRE-like site. J Immunol. 1994 Jul 15;153(2):712-23.
REF 6 Transcriptional regulation of the intercellular adhesion molecule-1 gene by inflammatory cytokines in human endothelial cells. Essential roles of a variant NF-kappa B site and p65 homodimers. J Biol Chem. 1995 Jan 13;270(2):933-43.
REF 7 Transcription factors ets1, NF-kappa B, and Sp1 are major determinants of the promoter activity of the human protein kinase CK2alpha gene. J Biol Chem. 2000 Jun 16;275(24):18327-36.
REF 8 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 9 An AP-1 site in the promoter of the human IL-5R alpha gene is necessary for promoter activity in eosinophilic HL60 cells. FEBS Lett. 1998 Sep 4;434(3):251-4.
REF 10 Identification of transcription factor binding sites important in the regulation of the human interleukin-5 gene. J Biol Chem. 1997 Jun 27;272(26):16453-65.
REF 11 Cyclic AMP inhibits fibronectin gene expression in a newly developed granulosa cell line by a mechanism that suppresses cAMP-responsive element-dependent transcriptional activation. J Biol Chem. 1990 Oct 25;265(30):18219-26.
REF 12 Identification of a novel sterol-independent regulatory element in the human low density lipoprotein receptor promoter. J Biol Chem. 2000 Feb 18;275(7):5214-21.
REF 13 Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729-39.
REF 14 Transcriptional regulation of endothelial nitric-oxide synthase by lysophosphatidylcholine. J Biol Chem. 1998 Jun 12;273(24):14885-90.

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