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NUAK family SNF1-like kinase 1; AMPK-related protein kinase 5; ARK5; omphalocele kinase 1 (NUAK1, ARK5, KIAA0537, OMPHK1)
Function:
- serine/threonine protein kinase
- role in various processes such as
a) cell adhesion
b) regulation of cell ploidy & cellular senescence
c) cell proliferation
d) tumor progression
- phosphorylates ATM, CASP6, LATS1, PPP1R12A & p53/TP53
- acts as a regulator of cellular senescence & cell ploidy by mediating phosphorylation of Ser-464 of LATS1, thus controlling its stability
- controls cell adhesion by regulating activity of the myosin protein phosphatase 1 (PP1) complex
- acts by mediating phosphorylation of PPP1R12A subunit of myosin PP1
- phosphorylated PPP1R12A then interacts with 14-3-3, leading to diminished dephosphorylation of myosin MLC2 by myosin PP1
- may be involved in DNA damage response
- phosphorylates p53/TP53 at Ser-15 & Ser-392 & is recruited to the CDKN1A/WAF1 promoter to participate in transcription activation by p53/TP53
- may also act as a tumor malignancy-associated factor by promoting tumor invasion & metastasis under regulation & phosphorylation by AKT1
- suppresses Fas-induced apoptosis by mediating phosphorylation of CASP6, thus suppressing activation of caspase & subsequent cleavage of CFLAR
- activated by phosphorylation on Thr-211
- activated by phosphorylation at Ser-600 AKT1 during glucose starvation (relevance in normal cells is unknown)
- ubiquitinated with Lys-29- & Lys-33-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation
- deubiquitinated by USP9X
- phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase & CAB39
- not dephosphorylated by the myosin PP1 complex when regulating its activity, due to the presence of PPP1R12A, which prevents myosin PP1 from dephosphorylating NUAK1
- phosphorylated by STK38L upon stimulation with IGF1
- interaction (via GILK motif) with PPP1CB bridges NUAK1 & PPP1R12A
Cofactor: Mg+2
Structure:
- the GILK motif mediates interaction with PPP1CB
- belongs to the protein kinase superfamily, CAMK Ser/Thr protein kinase family, SNF1 subfamily
- contains 1 protein kinase domain
Compartment: nucleus. cytoplasm
Alternative splicing: named isoforms=2
Expression:
- expressed at high levels in heart & brain
- expressed at lower levels in skeletal muscle, kidney, ovary, placenta, lung & liver
- up-regulated in colorectal cancer cell lines
- transcriptionally regulated by members of the MAF family
General
nuclear protein
serine/threonine kinase
Properties
SIZE: entity length = 661 aa
MW = 74 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: Ser phosphorylation site {S22}
kinase domain
SITE: 55-306
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 61-69
ATP-binding site
NAME: ATP-binding site
SITE: 84-84
aspartate residue {D178}
Thr phosphorylation site {T211}
Ser phosphorylation site {S215}
Ser phosphorylation site {S371}
Ser phosphorylation site {S380}
Ser phosphorylation site {S388}
GILK {399-402}
Ser phosphorylation site {S444}
Ser phosphorylation site {S445}
Ser phosphorylation site {S455}
Ser phosphorylation site {S600}
STATE: active state
Database Correlations
OMIM 608130
UniProt O60285
Pfam PF00069
Entrez Gene 9891
Kegg hsa:9891
ENZYME 2.7.11.1
References
UniProt :accession O60285