Mitogen-activated protein kinase kinase kinase 5 (Q99683)

Uniprot ID Q99683
Protein Name Mitogen-activated protein kinase kinase kinase 5
Gene Name MAP3K5
Species Homo sapiens (Human)
Signal peptide(a) N Secretome P(b)
Function Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1). .
GO - Molecular function
  • ATP binding : IDA:UniProtKB
  • identical protein binding : IPI:IntAct
  • magnesium ion binding : IDA:UniProtKB
  • MAP kinase kinase kinase activity : IDA:UniProtKB
  • protein domain specific binding : IPI:CAFA
  • protein homodimerization activity : IDA:UniProtKB
  • protein kinase activity : IDA:UniProtKB
  • protein kinase binding : IEA:Ensembl
  • protein phosphatase binding : IPI:BHF-UCL
  • protein serine/threonine kinase activity : TAS:Reactome
GO - Biological process
  • activation of JUN kinase activity : TAS:ProtInc
  • activation of MAPKK activity : IDA:BHF-UCL
  • apoptotic signaling pathway : TAS:ProtInc
  • cellular response to amino acid starvation : IDA:CAFA
  • cellular response to hydrogen peroxide : IDA:BHF-UCL
  • cellular response to reactive nitrogen species : IEA:Ensembl
  • cellular response to tumor necrosis factor : IEA:Ensembl
  • endothelial cell apoptotic process : IEA:Ensembl
  • innate immune response : IEA:UniProtKB-KW
  • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress : ISS:ParkinsonsUK-UCL
  • intrinsic apoptotic signaling pathway in response to oxidative stress : IDA:UniProtKB
  • JNK cascade : IDA:UniProtKB
  • MAPK cascade : IDA:UniProtKB
  • p38MAPK cascade : IEA:Ensembl
  • positive regulation of apoptotic process : IDA:UniProtKB
  • positive regulation of cardiac muscle cell apoptotic process : IEA:Ensembl
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process : IDA:BHF-UCL
  • positive regulation of JNK cascade : ISS:ParkinsonsUK-UCL
  • positive regulation of JUN kinase activity : IMP:ParkinsonsUK-UCL
  • positive regulation of myoblast differentiation : IEA:Ensembl
  • positive regulation of neuron death : IGI:ParkinsonsUK-UCL
  • positive regulation of p38MAPK cascade : IEA:Ensembl
  • positive regulation of transcription, DNA-templated : IDA:CAFA
  • positive regulation of vascular smooth muscle cell proliferation : IEA:Ensembl
  • programmed necrotic cell death : IEA:Ensembl
  • protein phosphorylation : IDA:CAFA
  • response to endoplasmic reticulum stress : IMP:ParkinsonsUK-UCL
  • response to ischemia : IEA:Ensembl
  • stress-activated MAPK cascade : IDA:CAFA
  • viral process : IEA:UniProtKB-KW
  • wound healing : IEA:Ensembl
Back
(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.
(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.