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1.C.126 The HlyC  (HlyC) Family of Haemolysins

The hemolysin C of Brachyspira hyodysenteriae (268 aas; ter Huurne et al., 1994Hyatt and Joens 1997) and the Co2+-resistance protein, CorC of Salmonella typhimurium (273 aas; with one putative TMS (residues 163-181)) are homologous throughout most of their lengths to each other. They are also homologous to the C-terminal portions of 5 close paralogues in Bacillus subtilis, all of which are about 440 aas long and have an N-terminal 4 TMS domain. One representative B. subtilis paralogue is YrkA (434 aas; P54428). The CorC protein was believed to function as an auxiliary protein to the CorA Co2+/Mg2+ channel of S. typhimurium (Gibson et al., 1991). CorA is a member of the Metal Ion Transporter (MIT) family of α-type channels (TC #1.A.35). The HlyC family corresponds to SwissProt family UPF0053. MstE (1.A.26.1.2), CLC (2.A.49.6.1) and HlyC/CorC may all share a hydrophilic domain, and members of the HlyC family lack the 4 TMS transmembrane region and therefore are probably not transporters (see below).

The bacterial proteins, YrkA and YhdP have three recognized domains: the 4-TMS DUF21 domain (residues 1-170), a nucleotide binding CBS domain (residues 225-335) and a CorC/HlyC domain (residues 360-430).  The mammalian homologues have at least the first two of these domains which are preceded by an N-terminal TMS and an unidentified hydrophilic domain. The bacterial HlyC and CorC proteins (1.C.126.1.1 and 1.C.126.1.2) lack the 4 TMS DUF21 domain, but have the CBS and CorC/HlyC domains. Only the proteins with the DUF21 domain are likely to be transporters.  The evidence is consistent with the conclusion that these homologues form divalent-cation-specific porters, possibly exporters.



This family belongs to the: CNNM/HlyC Superfamily.

References associated with 1.C.126 family:

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Gómez-García, I., M. Stuiver, J. Ereño, I. Oyenarte, M.A. Corral-Rodríguez, D. Müller, and L.A. Martínez-Cruz. (2012). Purification, crystallization and preliminary crystallographic analysis of the CBS-domain pair of cyclin M2 (CNNM2). Acta Crystallogr Sect F Struct Biol Cryst Commun 68: 1198-1203. 23027747
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Gulerez, I., Y. Funato, H. Wu, M. Yang, G. Kozlov, H. Miki, and K. Gehring. (2016). Phosphocysteine in the PRL-CNNM pathway mediates magnesium homeostasis. EMBO Rep 17: 1890-1900. 27856537
Hirata, Y., Y. Funato, and H. Miki. (2014). Basolateral sorting of the Mg²⁺ transporter CNNM4 requires interaction with AP-1A and AP-1B. Biochem. Biophys. Res. Commun. 455: 184-189. 25449265
Hirata, Y., Y. Funato, Y. Takano, and H. Miki. (2014). Mg2+-dependent interactions of ATP with the cystathionine-β-synthase (CBS) domains of a magnesium transporter. J. Biol. Chem. 289: 14731-14739. 24706765
Hyatt, D.R. and L.A. Joens. (1997). Analysis of the lytic activity of the Serpulina hyodysenteriae hemolysin. Infect. Immun. 65: 4877-4879. 9353080
Ishii, T., Y. Funato, O. Hashizume, D. Yamazaki, Y. Hirata, K. Nishiwaki, N. Kono, H. Arai, and H. Miki. (2016). Mg2+ Extrusion from Intestinal Epithelia by CNNM Proteins Is Essential for Gonadogenesis via AMPK-TORC1 Signaling in Caenorhabditis elegans. PLoS Genet 12: e1006276. 27564576
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Simonin A. and Fuster D. (2010). Nedd4-1 and beta-arrestin-1 are key regulators of Na+/H+ exchanger 1 ubiquitylation, endocytosis, and function. J Biol Chem. 285(49):38293-303. 20855896
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ter Huurne, A.A., Muir, S., van Houten, M., van der Zeijst, B.A., Gaastra, W., and Kusters, J.G. (1994). Characterization of three putative Serpulina hyodysenteriae hemolysins. Microb Pathog. 16: 269-282. 7968456
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