The reference OMIM entry for this protein is 600526

Map/microtubule affinity-regulating kinase 2; mark2
Elkl motif kinase; emk1
Par1, c. elegans, homolog of, b; par1b

CLONING

Inglis et al. (1993) cloned mouse Emk1 from embryos and found that it encoded a serine/threonine protein kinase with an ELKL-box region. By subtractive hybridization, Espinosa and Navarro (1998) cloned a partial human EMK1 cDNA. They cloned the remaining coding region and 5-prime UTR by plaque hybridization. Two isoforms were isolated that differed by the presence or absence of a 162-bp alternative exon. The largest cDNA encodes a 745-amino acid protein with conserved kinase and ELKL-box domains. RT-PCR demonstrated that both isoforms were coexpressed in a number of epithelial cell lines and tissues. Northern blot analysis detected expression of a major EMK1 band of approximately 4.4 kb at high levels in heart, brain, placenta, skeletal muscle, and pancreas, and at lower levels in lung, liver, and kidney. Using Western blot analysis, Lennerz et al. (2010) found that Par1b was expressed in all mouse tissues examined.

GENE FUNCTION

Saadat et al. (2007) showed that H. pylori CagA specifically interacts with PAR1/MARK kinase, which has an essential role in epithelial cell polarity. Association of CagA inhibited PAR1b (MARK2) kinase activity and prevented atypical protein kinase C-mediated PAR1 phosphorylation, which dissociates PAR1 from the membrane, collectively causing junctional and polarity defects. Because of the multimeric nature of PAR1, PAR1 also promoted CagA multimerization, which stabilized the CagA-SHP2 (PTPN11; 176876) interaction. Furthermore, induction of the hummingbird phenotype by CagA-activated SHP2 required simultaneous inhibition of PAR1 kinase activity by CagA. Thus, Saadat et al. (2007) concluded that the CagA-PAR1 interaction not only elicits the junctional and polarity defects but also promotes the morphogenetic activity of CagA. Their findings revealed that PAR1 is a key target of H. pylori CagA in the disorganization of gastric epithelial architecture underlying mucosal damage, inflammation, and carcinogenesis.

MAPPING

Inglis et al. (1993) mapped the Emk gene to the pericentromeric region of mouse chromosome 19. Courseaux et al. (1995) showed by fluorescence in situ hybridization that the human homolog is located on 11q12-q13. The localization was confirmed by Southern blot analysis of somatic cell hybrids and by long-range restriction mapping, which linked the gene to both FTH1 (134770) and COX8 (123870), probably within 110-150 kb of these 2 genes. EMK1 is a candidate gene for carcinogenic events originating from 11q13. Courseaux et al. (1996) used a combination of methods to refine maps of the approximately 5-Mb region of 11q13 that includes MEN1 (131100). They proposed the following gene order: cen--PGA--FTH1--UGB--AHNAK--ROM1--MDU1--CHRM1--COX8--EMK1--FKBP2--PLCB3--[PYGM, ZFM1]--FAU--CAPN1--[MLK3, RELA]--FOSL1--SEA--CFL1--tel.

ANIMAL MODEL

Lennerz et al. (2010) found that Par1b -/- mice showed reduced body weight and decreased adiposity compared with wildtype littermates, although they were hyperphagic. Par1b -/- mice had reduced serum insulin levels under both fed and fasting conditions, with increased insulin sensitivity on standard chow diet and enhanced glucose uptake in brown adipose tissue. When fed a high-fat diet, Par1b -/- mice showed enhanced glucose uptake in liver, but resistance to weight gain and development of hepatic steatosis. This phenotype partly overlapped that displayed by Par1a -/- mice. Double knockout of Par1a and Par1b was embryonic ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 600526 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).