GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on on inter-ontology links

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:21397062

CNNM2, encoding a basolateral protein required for renal Mg2+ handling, is mutated in dominant hypomagnesemia.

Human kidney staining places CNNM2 basolaterally, and segregating variants associate with renal magnesium wasting. Mouse construct recordings detect magnesium-sensitive sodium currents rather than magnesium current.

PMID:24706765

Mg2+-dependent interactions of ATP with the cystathionine-β-synthase (CBS) domains of a magnesium transporter.

Mouse CNNM2 supports cellular magnesium efflux; its purified CBS domain binds ATP in a magnesium-dependent assay, and T568I disrupts both measured responses.

PMID:25184538

Nucleotide binding triggers a conformational change of the CBS module of the magnesium transporter CNNM2 from a twisted towards a flat structure.

Purified human CNNM2 CBS domains bind adenine nucleotides and undergo conformational changes; magnesium facilitates ATP recognition.

PMID:24699222

CNNM2 mutations cause impaired brain development and seizures in patients with hypomagnesemia.

CNNM2 variants reduce cellular magnesium uptake, while zebrafish loss and rescue experiments connect cnnm2 function to magnesium balance and brain phenotypes.

PMID:38519529

Hypomagnesaemia with varying degrees of extrarenal symptoms as a consequence of heterozygous CNNM2 variants.

Human CNNM2 variants alter cellular 25Mg uptake, expression or surface delivery in a controlled expression assay.

PMID:34928937

CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells.

Mouse CNNM2 interacts with TRPM7 and stimulates pore-dependent ion entry, while its magnesium-lowering activity persists in TRPM7-knockout cells.

PMID:37449820

Structural insights into regulation of CNNM-TRPM7 divalent cation uptake by the small GTPase ARL15.

Human CNNM2 fragments bind ARL15 directly, with competition by PRLs; mouse CNNM2 cellular efflux is inhibited by ARL15 in a binding-dependent manner.

PMID:40962059

The cytoplasmic domains of the CNNM family of transmembrane proteins modulate the ion channel-kinase TRPM7.

Mouse CNNM2 regions physically associate with TRPM7 and regulate channel current, including ARL15-dependent inhibition; the isolated CNBH domain modestly enhances kinase activity in vitro.

PMID:15899945

Functional characterization of ACDP2 (ancient conserved domain protein), a divalent metal transporter.

A mouse MDCT-derived 693-residue ACDP2 construct elicits magnesium-dependent currents and reversal shifts in Xenopus oocytes relative to water and poly(A) controls.

PMID:20519162

Splice-variant 1 of the ancient domain protein 2 (ACDP2) complements the magnesium-deficient growth phenotype of Salmonella enterica sv. typhimurium strain MM281.

The complete abstract reports human splice-variant 1 complementation and magnesium uptake in deficient Salmonella, with splice-variant 2 and empty-vector controls negative.

PMID:27068403

Human CNNM2 is not a Mg(2+) transporter per se.

Controlled human CNNM2 isoform expression in HEK293 cells produces no increased magnesium currents, influx or efflux under the tested conditions, despite positive TRPM7 and SLC41A1 controls.

PMID:31171447

SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse.

SynGO provides expert-curated synaptic evidence with model-system and assay tracking and ortholog mapping.

file:human/CNNM2/CNNM2-source-evidence.json

CNNM2 source provenance and assay-scope index