RIPK1 - Receptor-interacting serine/threonine-protein kinase 1 - human protein (Function)
 
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RIPK1 »  Receptor-interacting serine/threonine-protein kinase 1   [ EC 2.7.11.1 ]
 
Protein also known as:  Serine/threonine-protein kinase RIP.
Gene name:  RIPK1
Entry whose protein(s) existence is based on evidence at protein level
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1 125 2
GENE REF ISO

Function

 show evidences
Overview 
Serine-threonine kinase which transduces inflammatory and cell-death signals (programmed necrosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. Ubiquitination by TRAF2 via 'Lys-63'-link chains acts as a critical enhancer of communication with downstream signal transducers in the mitogen-activated protein kinase pathway and the NF-kappa-B pathway, which in turn mediate downstream events including the activation of genes encoding inflammatory molecules. Polyubiquitinated protein binds to IKBKG/NEMO, the regulatory subunit of the IKK complex, a critical event for NF-kappa-B activation. Interaction with other cellular RHIM-containing adapters initiates gene activation and cell death. RIPK1 and RIPK3 association, in particular, forms a necrosis-inducing complex.  
4
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Death domain bindingdefinition[GO:0070513]  
2
  • IPIBHF-UCL
Death receptor bindingdefinition[GO:0005123]  
1
  • IPIBHF-UCL
Identical protein bindingdefinition[GO:0042802]  
1
  • IPIIntAct
Protein bindingdefinition[GO:0005515]  
28
  • IPIIntAct
  • IPIUniProtKB
  • IPIBHF-UCL
Protein complex bindingdefinition[GO:0032403]  
1
  • IDAUniProtKB
Protein kinase activitydefinition[GO:0004672]  
3
  • IMPUniProtKB
  • IDAMGI
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • IDAUniProtKB
  • IDABHF-UCL
Ubiquitin protein ligase bindingdefinition[GO:0031625]  
1
  • IPIUniProtKB
GO biological process 
Activation of JUN kinase activitydefinition[GO:0007257]  
1
  • TASBHF-UCL
Amyloid fibril formationdefinition[GO:1990000]  
1
  • IMPUniProtKB
Apoptotic processdefinition[GO:0006915]  
2
  • IMPUniProtKB
Cellular protein catabolic processdefinition[GO:0044257]  
1
  • IDAUniProtKB
Cellular response to tumor necrosis factordefinition[GO:0071356]  
1
  • IDAUniProtKB
Extrinsic apoptotic signaling pathwaydefinition[GO:0097191]  
3
  • IMPBHF-UCL
Necroptotic processdefinition[GO:0070266]  
3
  • IMPUniProtKB
Necroptotic signaling pathwaydefinition[GO:0097527]  
1
  • IMPBHF-UCL
Negative regulation of extrinsic apoptotic signaling pathwaydefinition[GO:2001237]  
1
  • IMPUniProtKB
Negative regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043124]  
1
  • IMPUniProtKB
Negative regulation of intrinsic apoptotic signaling pathwaydefinition[GO:2001243] silver  
  • IEAOrtholog Compara
Peptidyl-serine autophosphorylationdefinition[GO:0036289]  
1
  • IDAUniProtKB
Positive regulation of apoptotic processdefinition[GO:0043065]  
3
  • IMPUniProtKB
  • IDABHF-UCL
Positive regulation of extrinsic apoptotic signaling pathwaydefinition[GO:2001238]  
2
  • IMPUniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043123]  
2
  • IDAUniProtKB
Positive regulation of interleukin-8 productiondefinition[GO:0032757]  
1
  • IDABHF-UCL
Positive regulation of JNK cascadedefinition[GO:0046330]  
1
  • IDAUniProtKB
Positive regulation of macrophage differentiationdefinition[GO:0045651]  
1
  • IMPUniProtKB
Positive regulation of necroptotic processdefinition[GO:0060545]  
3
  • IMPUniProtKB
Positive regulation of necrotic cell deathdefinition[GO:0010940]  
1
  • IMPBHF-UCL
Positive regulation of NF-kappaB transcription factor activitydefinition[GO:0051092]  
3
  • IMPUniProtKB
  • IMPBHF-UCL
Positive regulation of programmed cell deathdefinition[GO:0043068]  
1
  • IMPUniProtKB
Positive regulation of protein phosphorylationdefinition[GO:0001934]  
1
  • IMPUniProtKB
Positive regulation of reactive oxygen species metabolic processdefinition[GO:2000379]  
1
  • TASBHF-UCL
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
2
  • IDAUniProtKB
  • IDABHF-UCL
Positive regulation of tumor necrosis factor productiondefinition[GO:0032760]  
1
  • IDABHF-UCL
Protein autophosphorylationdefinition[GO:0046777]  
1
  • IDABHF-UCL
Protein heterooligomerizationdefinition[GO:0051291]  
1
  • IMPUniProtKB
Protein homooligomerizationdefinition[GO:0051260]  
1
  • IDAUniProtKB
Regulation of ATP:ADP antiporter activitydefinition[GO:0070926]  
1
  • IMPBHF-UCL
Response to tumor necrosis factordefinition[GO:0034612]  
1
  • IMPBHF-UCL
Ripoptosome assemblydefinition[GO:0097343]  
1
  • IMPUniProtKB
T cell apoptotic processdefinition[GO:0070231]  
  • ISSOrtholog Curator
Tumor necrosis factor-mediated signaling pathwaydefinition[GO:0033209]  
1
  • ICBHF-UCL
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
1
  • CuratedUniProtKB
It is regulated in the following manner
Inhibited by necrostatins, including necrostatin-1, necrostatin-3 and necrostatin-4.  
1
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Apoptosis  hsa04210+8737  
Cytosolic DNA-sensing pathway  hsa04623+8737  
Hepatitis C  hsa05160+8737  
RIG-I-like receptor signaling pathway  hsa04622+8737  
Toll-like receptor signaling pathway  hsa04620+8737  
According to Reactome, this protein belongs to the following pathways:
Apoptosis  REACT_578  
Immune System  REACT_6900  
 

Keywords

Biological process 
Necrosis  definition   [KW-1210]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: RIPK1
GenomeRNAi: 8737
PRO: PR:Q13546
Chemistry
GuidetoPHARMACOLOGY: 2189