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Sep. 10, 2014:
A total of 174 experimentally verified S-nitrosylation sites on 94 S-nitrosylated proteins from individualized human colorectal cancer tissues using a label-free quantitation strategy.

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Protein Name: Mitogen-activated protein kinase kinase kinase 5

UniprotKB/SwissProt ID: M3K5_HUMAN (Q99683)

Gene Name: MAP3K5

Synonyms: ASK1, MAPKKK5, MEKK5

Organism: Homo sapiens (Human).

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).

Other Modifications: View all modification sites in dbPTM

Protein Subcellular Localization: Cytoplasm. Endoplasmic reticulum. Note=Interaction with 14-3-3 proteins alters the distribution of MAP3K5/ASK1 and restricts it to the perinuclear endoplasmic reticulum region.

PDB :
( If your security settings prevent Jmol from running, please register http://140.138.144.145/ as a safe location in your Java settings. )

Network with metabolic pathway:
Kegg map ID Pathway Link
map05014Amyotrophic lateral sclerosis (ALS)
map04722Neurotrophin signaling pathway
map04010MAPK signaling pathway
map04141Protein processing in endoplasmic reticulum
Graphical Visualization of S-nitrosylation Sites:
Overview of Protein S-nitrosylation Sites with Functional and Structural Information
InterPro ID Domain
IPR000719
IPR002290
IPR008271
IPR010993
IPR011009

3D Structure Databases:
3D structure databases
EntryMethodResolution (A)ChainPositionsView
2CLQ X-ray 2.30 A A/B659-951Link
3VW6 X-ray 2.40 A A/B671-939Link
4BF2 X-ray 2.11 A A/B660-977Link
4BHN X-ray 2.30 A A/B660-977Link
4BIB X-ray 2.43 A A/B660-977Link
4BIC X-ray 2.62 A A/B660-977Link
4BID X-ray 2.80 A A/B660-977Link
4BIE X-ray 2.36 A A/B660-977Link

The S-nitrosylation sites of M3K5_HUMAN

No. Position S-nitrosylated Peptide Secondary Structure of S-nitrosylated Peptide Solvent Accessibility of nitrosylated Site Substrate Motifs PubMed ID Experiment
1869GKAADIWSLG C TIIEMATGKP CCCHHHHHHH H HHHHHHCCCC 2.75%HC0822178444-
2869GKAADIWSLG C TIIEMATGKP CCCHHHHHHH H HHHHHHCCCC 2.75%HC0814668338-
3869GKAADIWSLG C TIIEMATGKP CCCHHHHHHH H HHHHHHCCCC 2.75%HC0815688001-