InterPro domain: IPR002550

Proteins containing the ancient conserved domain protein/cyclin M (CNNM) areintegral membrane proteins that are conserved from bacteria to humans. CNNMfamily members influence metal ion homeostasis through mechanisms that may notinvolve direct membrane transport of the ions. Structurally, CNNMs are complexproteins that contain an extracellular N-terminal domain preceding atransmembrane domain, a "Bateman module", which consists of two cystathionine-beta-synthase (CBS) domains, and a C-terminal cNMP (cyclicnucleotide monophosphate) binding domain [ 1 , 2 , 3 , 4 ].

The CNNM transmembrane domain contains four hydrophobic regions. The secondone is the shortest and the least hydrophobic, indicating that the secondhydrophobic region might not be completely membrane-spanning, but insteadforms a re-entrant loop. Hence, the CNNM integral membrane domain has beenproposed to contain three full membrane-spanning regions and an additionalre-entrant loop [ 5 ].

1. Manganese toxicity and Saccharomyces cerevisiae Mam3p, a member of the ACDP (ancient conserved domain protein) family. Biochem. J. 386, 479-87
2. Membrane topology and intracellular processing of cyclin M2 (CNNM2). J. Biol. Chem. 287, 13644-55
3. Phosphocysteine in the PRL-CNNM pathway mediates magnesium homeostasis. EMBO Rep. 17, 1890-1900
4. Structural Basis of the Oncogenic Interaction of Phosphatase PRL-1 with the Magnesium Transporter CNNM2. J. Biol. Chem. 292, 786-801