UNIPROT #

Q99683

PROTEIN NAME

ASK1

SYNONYMS

Apoptosis signal regulating kinase 1 antibody; Apoptosis signal-regulating kinase 1 antibody; ASK 1 antibody; ASK-1 antibody; ASK1 antibody; M3K5 antibody; M3K5_HUMAN antibody; MAP/ERK kinase kinase 5 antibody; MAP3K5 antibody; MAPK/ERK kinase kinase 5 antibody; MAPKKK5 antibody; MEK kinase 5 antibody; MEKK 5 antibody; MEKK5 antibody; Mitogen activated protein kinase kinase kinase 5 antibody; Mitogen-activated protein kinase kinase kinase 5 antibody

SEQUENCE SIMILARITIES

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.

TISSUE SPECIFICITY

Abundantly expressed in heart and pancreas.

POST-TRANSLATIONAL MODIFICATION

Phosphorylated at Thr-838 through autophosphorylation and by MAP3K6/ASK2 which leads to activation. Thr-838 is dephosphorylated by PPP5C. Ser-83 and Ser-1033 are inactivating phosphorylation sites, the former of which is phosphorylated by AKT1 and AKT2. Phosphorylated at Ser-966 which induces association of MAP3K5/ASK1 with the 14-3-3 family proteins and suppresses MAP3K5/ASK1 activity. Calcineurin (CN) dephosphorylates this site. Also dephosphorylated and activated by PGAM5.; Ubiquitinated. Tumor necrosis factor (TNF) induces TNFR2-dependent ubiquitination leading to proteasomal degradation.

SUBCELLULAR LOCATION

Cytoplasm. Endoplasmic reticulum.

FUNCTION

Mitogen-activated protein (MAP) kinase cascades are activated by various extracellular stimuli including growth factors. The MEK kinases (also designated MAP kinase kinase kinases, MKKKs, MAP3Ks or MEKKs) phosphorylate and thereby activate the MEKs (also called MAP kinase kinases or MKKs), including ERK, JNK and p38. These activated MEKs in turn phosphorylate and activate the MAP kinases. The MEK kinases include Raf-1, Raf-B, Mos, MEK kinase-1, MEK kinase-2, MEK kinase-3, MEK kinase-4, ASK 1 (MEK kinase-5) and MAP3K6 (MEK kinase-6). MEK kinase-1 has been shown to phosphorylate MEK-1 via a Raf-independent pathway. Evidence suggests that MEK-3 is preferentially activated by MEK kinase-3 and that MEK-4 is activated by both MEK kinase-2 and MEK kinase-3. MEK kinase-4 has been shown to specifically activate the JNK pathway. ASK1 activates both MEK-4 and MEK-3/MEK-6 pathways.