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kinase suppressor of ras-1 (KSR, KSR1)
Function:
- location-regulated scaffold connecting MEK to RAF
- promotes MEK & RAF phosphorylation & activity via assembly of activated signaling complex
- by itself, it has no kinase activity
- interacts with HSP90, 14-3-3, CDC37, MEK, MARK3, PPP2R1A & PPP2CA.
- interacts with RAF & ERK Ras-dependent)
- phosphorylated KSR1 binds 14-3-3 & sequesters in cytoplasm
- phosphorylated on Ser-309 & Ser-404 by MARK3
- dephosphorylated on Ser-404 by PPP2CA
- binding of 14-3-3 proteins to phosphorylated KSR1 prevents the membrane localization
- interacts with isoform 1 of VRK2
Structure:
- belongs to the protein kinase superfamily, TKL Ser/Thr protein kinase family
- contains 1 phorbol-ester/DAG-type Zn+2 finger
- contains 1 protein kinase domain
Compartment:
- cytoplasmic
- membrane-associated, endoplasmic reticulum membrane
- in resting cells, phosphorylated KSR1 is cytoplasmic
- in stimulated cells, dephosphorylated KSR1 is membrane-associated
Alternative splicing: named isoforms=3
General
phosphoprotein
zinc finger protein
Properties
SIZE: MW = 102 kD
entity length = 921 aa
COMPARTMENT: cytoplasm
MOTIF: glycine-rich region {17-21}
Thr phosphorylation site {T268}
Thr phosphorylation site {T272}
proline-rich region
SITE: 287-290
MOTIF: proline residue (SEVERAL)
Ser phosphorylation site {S309}
Ser phosphorylation site {S332}
Zinc finger
NAME: Zinc finger
SITE: 345-389
EFFECTOR-BOUND: Zn+2
MOTIF: Zn+2-binding site
SITE: 346-346
Zn+2-binding site
SITE: 358-358
Zn+2-binding site
SITE: 361-361
Zn+2-binding site
SITE: 371-371
Zn+2-binding site
SITE: 374-374
Zn+2-binding site
SITE: 379-379
Zn+2-binding site
SITE: 382-382
Zn+2-binding site
SITE: 389-389
Ser phosphorylation site {S404}
Ser phosphorylation site {S567}
kinase domain
SITE: 611-881
MOTIF: ATP-binding site
NAME: ATP-binding site
Database Correlations
OMIM 601132
UniProt Q8IVT5
PFAM correlations
Entrez Gene 8844
Kegg hsa:8844
References
UniProt :accession Q8IVT5