Kinase Subfamily SgK493
Kinase Classification: Group Other: Family RESK: Subfamily SgK493
SgK493 is a little-studied subfamily family of divergent kinases, with a single copy in human, SgK493 (PKDCC, Vlk, Adtk1). It appears to be localized to the secretory system and is involved in bone and lung development in mammals, possibly as part of the Hedgehog pathway.
Evolution
SgK493 is found in most eumetazoans, though lost in arthropods and most nematodes. It is single-copy in mammals, but has two copies in other vertebrates, and multiple copies in some invertebrates
Domain Structure
SgK493 usually consists of a divergent kinase domain preceeded by a N-terminal signal peptide. The kinase domain has an atypical HRD motif (LLDFRPR), lacking the N171 residue. The kinase domain also has eight highly conserved cysteine residues, similar to other RESK family kinases
Functions
Two GWAS studies have implicated SgK493 in both atopic and nonatopic asthma [1, 2], and with bone mineral density [3].
A mouse knockout of SgK493 [4] shows several defects at birth, including short limbs, likely due to involvement of SgK493 in the hedgehog pathway, where IHH and Gli3 synergize with SgK493 in development of chondrocytes [5].
SgK493 was required for Golgi to Plasma Membrane transport and required for lung develoment [6].
References
- Perin P and Potočnik U. Polymorphisms in recent GWA identified asthma genes CA10, SGK493, and CTNNA3 are associated with disease severity and treatment response in childhood asthma. Immunogenetics. 2014 Mar;66(3):143-51. DOI:10.1007/s00251-013-0755-0 |
- Castro-Giner F, Bustamante M, Ramon González J, Kogevinas M, Jarvis D, Heinrich J, Antó JM, Wjst M, Estivill X, and de Cid R. A pooling-based genome-wide analysis identifies new potential candidate genes for atopy in the European Community Respiratory Health Survey (ECRHS). BMC Med Genet. 2009 Dec 6;10:128. DOI:10.1186/1471-2350-10-128 |
- Estrada K, Styrkarsdottir U, Evangelou E, Hsu YH, Duncan EL, Ntzani EE, Oei L, Albagha OM, Amin N, Kemp JP, Koller DL, Li G, Liu CT, Minster RL, Moayyeri A, Vandenput L, Willner D, Xiao SM, Yerges-Armstrong LM, Zheng HF, Alonso N, Eriksson J, Kammerer CM, Kaptoge SK, Leo PJ, Thorleifsson G, Wilson SG, Wilson JF, Aalto V, Alen M, Aragaki AK, Aspelund T, Center JR, Dailiana Z, Duggan DJ, Garcia M, Garcia-Giralt N, Giroux S, Hallmans G, Hocking LJ, Husted LB, Jameson KA, Khusainova R, Kim GS, Kooperberg C, Koromila T, Kruk M, Laaksonen M, Lacroix AZ, Lee SH, Leung PC, Lewis JR, Masi L, Mencej-Bedrac S, Nguyen TV, Nogues X, Patel MS, Prezelj J, Rose LM, Scollen S, Siggeirsdottir K, Smith AV, Svensson O, Trompet S, Trummer O, van Schoor NM, Woo J, Zhu K, Balcells S, Brandi ML, Buckley BM, Cheng S, Christiansen C, Cooper C, Dedoussis G, Ford I, Frost M, Goltzman D, González-Macías J, Kähönen M, Karlsson M, Khusnutdinova E, Koh JM, Kollia P, Langdahl BL, Leslie WD, Lips P, Ljunggren Ö, Lorenc RS, Marc J, Mellström D, Obermayer-Pietsch B, Olmos JM, Pettersson-Kymmer U, Reid DM, Riancho JA, Ridker PM, Rousseau F, Slagboom PE, Tang NL, Urreizti R, Van Hul W, Viikari J, Zarrabeitia MT, Aulchenko YS, Castano-Betancourt M, Grundberg E, Herrera L, Ingvarsson T, Johannsdottir H, Kwan T, Li R, Luben R, Medina-Gómez C, Palsson ST, Reppe S, Rotter JI, Sigurdsson G, van Meurs JB, Verlaan D, Williams FM, Wood AR, Zhou Y, Gautvik KM, Pastinen T, Raychaudhuri S, Cauley JA, Chasman DI, Clark GR, Cummings SR, Danoy P, Dennison EM, Eastell R, Eisman JA, Gudnason V, Hofman A, Jackson RD, Jones G, Jukema JW, Khaw KT, Lehtimäki T, Liu Y, Lorentzon M, McCloskey E, Mitchell BD, Nandakumar K, Nicholson GC, Oostra BA, Peacock M, Pols HA, Prince RL, Raitakari O, Reid IR, Robbins J, Sambrook PN, Sham PC, Shuldiner AR, Tylavsky FA, van Duijn CM, Wareham NJ, Cupples LA, Econs MJ, Evans DM, Harris TB, Kung AW, Psaty BM, Reeve J, Spector TD, Streeten EA, Zillikens MC, Thorsteinsdottir U, Ohlsson C, Karasik D, Richards JB, Brown MA, Stefansson K, Uitterlinden AG, Ralston SH, Ioannidis JP, Kiel DP, and Rivadeneira F. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet. 2012 Apr 15;44(5):491-501. DOI:10.1038/ng.2249 |
- Imuta Y, Nishioka N, Kiyonari H, and Sasaki H. Short limbs, cleft palate, and delayed formation of flat proliferative chondrocytes in mice with targeted disruption of a putative protein kinase gene, Pkdcc (AW548124). Dev Dyn. 2009 Jan;238(1):210-22. DOI:10.1002/dvdy.21822 |
- Probst S, Zeller R, and Zuniga A. The hedgehog target Vlk genetically interacts with Gli3 to regulate chondrocyte differentiation during mouse long bone development. Differentiation. 2013 Apr-Jun;85(4-5):121-30. DOI:10.1016/j.diff.2013.03.002 |
- Kinoshita M, Era T, Jakt LM, and Nishikawa S. The novel protein kinase Vlk is essential for stromal function of mesenchymal cells. Development. 2009 Jun;136(12):2069-79. DOI:10.1242/dev.026435 |
