Kinase Family POMK

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Kinase Classification: Group Other: Kinase Family POMK

POMK (Protein O-Mannose Kinase) is a poorly studied kinase family, reported to phosphorylate O-mannose as part of protein glycosylation. It was originally published as SgK196 (Sugen Kinase 196).


POMK is found in holozoans but it lost from several lineages, including insects and nematodes. It is a single copy gene in all vertebrates.

Domain Structure

The protein is composed mostly of an ePK kinase domain with a moderate N-term extension. No clear signal peptide is seen but most homologs have a predicted transmembrane region (TM-HMM) just upstream of the kinase domain. The kinase domain contains four highly conserved cysteine residues within the kinase domain, another two close to its N-terminal border and a further conserved Cys just upstream. Similar to the RESK kinases, these conserved cysteines are unusual in kinases and may indicate presence in the Golgi or ER. Several of the canonical kinase motifs are divergent or unclear, and the gene was originally reported as a pseudokinase. The HRD motif lacks the Mg-coordinating N171 and the HRD is changed to MCD in most homologs.


POMK was found in a haploid genetic screen for defects in glycosylation of the ECM receptor α-dystroglycan [1]. Biochemical analysis showed that POMK could phosphorylate protein-linked mannose (α-dystroglycan-O-Mannose), presumably in the Golgi apparatus [2]. POMK may also be involved in post-translational modification of other O-mannose linked proteins including cadherins [3]. Knockdown of the zebrafish homolog shows that it is required for muscle development [4], while mouse knockout [5] showed a hydrocephalus phenotype, both correlating with observed expression in muscle and brain.

Disease Association

Mutation of a conserved Q (Q258R) just after the APE motif and a conserved L (L137R) [1] were found in one patient with Walker-Warburg syndrome (WWS), a disease caused by failure to glycosylate α-dystroglycan. A stop mutation (Q109*) was found in a case of congenital muscular dystrophy (CMD), correlating with a lack of expression of α-dystroglycan protein [6].


  1. Jae LT, Raaben M, Riemersma M, van Beusekom E, Blomen VA, Velds A, Kerkhoven RM, Carette JE, Topaloglu H, Meinecke P, Wessels MW, Lefeber DJ, Whelan SP, van Bokhoven H, and Brummelkamp TR. Deciphering the glycosylome of dystroglycanopathies using haploid screens for lassa virus entry. Science. 2013 Apr 26;340(6131):479-83. DOI:10.1126/science.1233675 | PubMed ID:23519211 | HubMed [Jae]
  2. Yoshida-Moriguchi T, Willer T, Anderson ME, Venzke D, Whyte T, Muntoni F, Lee H, Nelson SF, Yu L, and Campbell KP. SGK196 is a glycosylation-specific O-mannose kinase required for dystroglycan function. Science. 2013 Aug 23;341(6148):896-9. DOI:10.1126/science.1239951 | PubMed ID:23929950 | HubMed [Yoshida-Moriguchi]
  3. Vester-Christensen MB, Halim A, Joshi HJ, Steentoft C, Bennett EP, Levery SB, Vakhrushev SY, and Clausen H. Mining the O-mannose glycoproteome reveals cadherins as major O-mannosylated glycoproteins. Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):21018-23. DOI:10.1073/pnas.1313446110 | PubMed ID:24101494 | HubMed [Vester]
  4. Di Costanzo S, Balasubramanian A, Pond HL, Rozkalne A, Pantaleoni C, Saredi S, Gupta VA, Sunu CM, Yu TW, Kang PB, Salih MA, Mora M, Gussoni E, Walsh CA, and Manzini MC. POMK mutations disrupt muscle development leading to a spectrum of neuromuscular presentations. Hum Mol Genet. 2014 Nov 1;23(21):5781-92. DOI:10.1093/hmg/ddu296 | PubMed ID:24925318 | HubMed [DiCostanzo]
  5. Vogel P, Read RW, Hansen GM, Payne BJ, Small D, Sands AT, and Zambrowicz BP. Congenital hydrocephalus in genetically engineered mice. Vet Pathol. 2012 Jan;49(1):166-81. DOI:10.1177/0300985811415708 | PubMed ID:21746835 | HubMed [Vogel]
  6. von Renesse A, Petkova MV, Lützkendorf S, Heinemeyer J, Gill E, Hübner C, von Moers A, Stenzel W, and Schuelke M. POMK mutation in a family with congenital muscular dystrophy with merosin deficiency, hypomyelination, mild hearing deficit and intellectual disability. J Med Genet. 2014 Apr;51(4):275-82. DOI:10.1136/jmedgenet-2013-102236 | PubMed ID:24556084 | HubMed [vonRenesse]
All Medline abstracts: PubMed | HubMed