Target Regulator(s) Information (Transcription Factor)
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T45758 | Target Info | |||
| Target Name | CD40L receptor (CD40) | ||||
| Synonyms | Tumor necrosis factor receptor superfamily member 5; TNFRSF5; CDw40; Bp50; B-cell surfaceantigen CD40; B-cell surface antigen CD40 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | CD40 | ||||
| Biochemical Class | Cytokine receptor | ||||
| UniProt ID | |||||
| The Transcription Factors (TFs) Regulating This Target | Top | ||||
|---|---|---|---|---|---|
| TF Name | Signal transducer and activator of transcription 1 (STAT1) homodimer | ||||
| Classification | Superclass | beta-Scaffold Factors with Minor Groove Contacts | |||
| Class | Signal transducer and activator of transcription | ||||
| Family | Signal transducer and activator of transcription | ||||
| Regulation Type | Increase | ||||
| Regulation Mechanism | IL-4 inhibition of IFN-gamma-inducedCD40gene expression is mediated by directSTAT binding to theCD40promoter. | [1] | |||
| Evidence Score (E-score) | 2 | + | |||
| 1 | Electrophoretic Mobility Shift Assay | [1] | |||
| 2 | Electrophoretic Mobility Shift Assay | [2] | |||
| UniProt ID | |||||
| Sequence |
MSQWYELQQLDSKFLEQVHQLYDDSFPMEIRQYLAQWLEKQDWEHAANDVSFATIRFHDL
LSQLDDQYSRFSLENNFLLQHNIRKSKRNLQDNFQEDPIQMSMIIYSCLKEERKILENAQ RFNQAQSGNIQSTVMLDKQKELDSKVRNVKDKVMCIEHEIKSLEDLQDEYDFKCKTLQNR EHETNGVAKSDQKQEQLLLKKMYLMLDNKRKEVVHKIIELLNVTELTQNALINDELVEWK RRQQSACIGGPPNACLDQLQNWFTIVAESLQQVRQQLKKLEELEQKYTYEHDPITKNKQV LWDRTFSLFQQLIQSSFVVERQPCMPTHPQRPLVLKTGVQFTVKLRLLVKLQELNYNLKV KVLFDKDVNERNTVKGFRKFNILGTHTKVMNMEESTNGSLAAEFRHLQLKEQKNAGTRTN EGPLIVTEELHSLSFETQLCQPGLVIDLETTSLPVVVISNVSQLPSGWASILWYNMLVAE PRNLSFFLTPPCARWAQLSEVLSWQFSSVTKRGLNVDQLNMLGEKLLGPNASPDGLIPWT RFCKENINDKNFPFWLWIESILELIKKHLLPLWNDGCIMGFISKERERALLKDQQPGTFL LRFSESSREGAITFTWVERSQNGGEPDFHAVEPYTKKELSAVTFPDIIRNYKVMAAENIP ENPLKYLYPNIDKDHAFGKYYSRPKEAPEPMELDGPKGTGYIKTELISVSEVHPSRLQTT DNLLPMSPEEFDEVSRIVGSVEFDSMMNTV |
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| 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 | CD40L receptor (CD40) | Clinical trial Target | Target Info | [1] | |
| 2 | Interleukin 2 receptor alpha (IL2RA) | Successful Target | Target Info | [3] | |
| Immunoglobulins | [+] 1 Immunoglobulins Co-regulated By This TF | + | |||
| 1 | Intercellular adhesion molecule ICAM-1 (ICAM1) | Successful Target | Target Info | [4] | |
| Oxidoreductases | [+] 1 Oxidoreductases Co-regulated By This TF | + | |||
| 1 | NADPH oxidase 2 (CYBB) | Literature-reported Target | Target Info | [5] | |
| Transcription factors | [+] 2 Transcription factors Co-regulated By This TF | + | |||
| 1 | Interferon regulatory factor 1 (IRF1) | Literature-reported Target | Target Info | [6] | |
| 2 | Signal transducer and activator of transcription 1 (STAT1) | Patented-recorded Target | Target Info | [6] | |
| TF Name | PU.1 proto-oncogene (SPI1) | ||||
| Classification | Superclass | Helix-turn-helix | |||
| Class | Tryptophan clusters | ||||
| Family | Ets-type | ||||
| Regulation Type | Increase | ||||
| Regulation Mechanism | The Ets proteins PU.1 and/or SPIB are required for IFN-gamma-induced CD40 promoter activity. | [1] | |||
| Evidence Score (E-score) | 1 | + | |||
| 1 | Electrophoretic Mobility Shift Assay | [1] | |||
| UniProt ID | |||||
| Sequence |
MLQACKMEGFPLVPPPSEDLVPYDTDLYQRQTHEYYPYLSSDGESHSDHYWDFHPHHVHS
EFESFAENNFTELQSVQPPQLQQLYRHMELEQMHVLDTPMVPPHPSLGHQVSYLPRMCLQ YPSLSPAQPSSDEEEGERQSPPLEVSDGEADGLEPGPGLLPGETGSKKKIRLYQFLLDLL RSGDMKDSIWWVDKDKGTFQFSSKHKEALAHRWGIQKGNRKKMTYQKMARALRNYGKTGE VKKVKKKLTYQFSGEVLGRGGLAERRHPPH |
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| 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 | [1] | |
| 2 | Granulocyte colony-stimulating factor receptor (G-CSF-R) | Successful Target | Target Info | [7] | |
| 3 | Interleukin-1 beta (IL1B) | Successful Target | Target Info | [8] | |
| 4 | Interleukin-12 beta (IL12B) | Successful Target | Target Info | [9] | |
| Integrins | [+] 1 Integrins Co-regulated By This TF | + | |||
| 1 | Integrin beta-2 (ITGB2) | Clinical trial Target | Target Info | [10] | |
| TF Name | Signal transducer and activator of transcription 6 (STAT6) homodimer | ||||
| Classification | Superclass | beta-Scaffold Factors with Minor Groove Contacts | |||
| Class | Signal transducer and activator of transcription | ||||
| Family | Signal transducer and activator of transcription | ||||
| Regulation Type | Decrease | ||||
| Regulation Mechanism | IL-4 inhibition of IFN-gamma-inducedCD40gene expression is mediated by directSTAT binding to theCD40promoter. | [1] | |||
| Evidence Score (E-score) | 1 | + | |||
| 1 | Electrophoretic Mobility Shift Assay | [1] | |||
| UniProt ID | |||||
| Sequence |
MSLWGLVSKMPPEKVQRLYVDFPQHLRHLLGDWLESQPWEFLVGSDAFCCNLASALLSDT
VQHLQASVGEQGEGSTILQHISTLESIYQRDPLKLVATFRQILQGEKKAVMEQFRHLPMP FHWKQEELKFKTGLRRLQHRVGEIHLLREALQKGAEAGQVSLHSLIETPANGTGPSEALA MLLQETTGELEAAKALVLKRIQIWKRQQQLAGNGAPFEESLAPLQERCESLVDIYSQLQQ EVGAAGGELEPKTRASLTGRLDEVLRTLVTSCFLVEKQPPQVLKTQTKFQAGVRFLLGLR FLGAPAKPPLVRADMVTEKQARELSVPQGPGAGAESTGEIINNTVPLENSIPGNCCSALF KNLLLKKIKRCERKGTESVTEEKCAVLFSASFTLGPGKLPIQLQALSLPLVVIVHGNQDN NAKATILWDNAFSEMDRVPFVVAERVPWEKMCETLNLKFMAEVGTNRGLLPEHFLFLAQK IFNDNSLSMEAFQHRSVSWSQFNKEILLGRGFTFWQWFDGVLDLTKRCLRSYWSDRLIIG FISKQYVTSLLLNEPDGTFLLRFSDSEIGGITIAHVIRGQDGSPQIENIQPFSAKDLSIR SLGDRIRDLAQLKNLYPKKPKDEAFRSHYKPEQMGKDGRGYVPATIKMTVERDQPLPTPE LQMPTMVPSYDLGMAPDSSMSMQLGPDMVPQVYPPHSHSIPPYQGLSPEESVNVLSAFQE PHLQMPPSLGQMSLPFDQPHPQGLLPCQPQEHAVSSPDPLLCSDVTMVEDSCLSQPVTAF PQGTWIGEDIFPPLLPPTEQDLTKLLLEGQGESGGGSLGAQPLLQPSHYGQSGISMSHMD LRANPSW |
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| 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 | CD40L receptor (CD40) | Clinical trial Target | Target Info | [1] | |
| 2 | Interleukin 4 receptor alpha (IL4R) | Successful Target | Target Info | [11] | |
| TF Name | Spi-B transcription factor (SPIB) | ||||
| Classification | Superclass | Helix-turn-helix | |||
| Class | Tryptophan clusters | ||||
| Family | Ets-type | ||||
| Regulation Type | Increase | ||||
| Regulation Mechanism | The Ets proteins PU.1 and/or SPIB are required for IFN-gamma-induced CD40 promoter activity. | [1] | |||
| Evidence Score (E-score) | 1 | + | |||
| 1 | Electrophoretic Mobility Shift Assay | [1] | |||
| UniProt ID | |||||
| Sequence |
MLALEAAQLDGPHFSCLYPDGVFYDLDSCKHSSYPDSEGAPDSLWDWTVAPPVPATPYEA
FDPAAAAFSHPQAAQLCYEPPTYSPAGNLELAPSLEAPGPGLPAYPTENFASQTLVPPAY APYPSPVLSEEEDLPLDSPALEVSDSESDEALVAGPEGKGSEAGTRKKLRLYQFLLGLLT RGDMRECVWWVEPGAGVFQFSSKHKELLARRWGQQKGNRKRMTYQKLARALRNYAKTGEI RKVKRKLTYQFDSALLPAVRRA |
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| 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 | CD40L receptor (CD40) | Clinical trial Target | Target Info | [1] | |
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | 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 2 | Involvement of STAT-1 and ets family members in interferon-gamma induction of CD40 transcription in microglia/macrophages. J Biol Chem. 2000 Aug 4;275(31):23674-84. | ||||
| REF 3 | Interferon-alpha activates multiple STAT proteins and upregulates proliferation-associated IL-2Ralpha, c-myc, and pim-1 genes in human T cells. Blood. 1999 Mar 15;93(6):1980-91. | ||||
| REF 4 | Stat1 depends on transcriptional synergy with Sp1. J Biol Chem. 1995 Dec 22;270(51):30264-7. | ||||
| REF 5 | Cooperation of STAT-1 and IRF-1 in interferon-gamma-induced transcription of the gp91(phox) gene. J Biol Chem. 2002 Mar 15;277(11):9103-11. | ||||
| REF 6 | 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. | ||||
| REF 7 | 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 8 | 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 9 | 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 10 | 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 11 | DNA binding specificity of different STAT proteins. Comparison of in vitro specificity with natural target sites. J Biol Chem. 2001 Mar 2;276(9):6675-88. | ||||
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