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Protein

Metal transporter CNNM2

Gene

CNNM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Divalent metal cation transporter. Mediates transport of divalent metal cations in an order of Mg2+ > Co2+ > Mn2+ > Sr2+ > Ba2+ > Cu2+ > Fe2+ (By similarity).By similarity

Miscellaneous

Shares weak sequence similarity with the cyclin family, hence its name. However, it has no cyclin-like function in vivo.

GO - Molecular functioni

GO - Biological processi

  • magnesium ion homeostasis Source: MGI

Keywordsi

Biological processIon transport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Metal transporter CNNM2
Alternative name(s):
Ancient conserved domain-containing protein 2
Cyclin-M2
Gene namesi
Name:CNNM2
Synonyms:ACDP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000148842.17
HGNCiHGNC:103 CNNM2
MIMi607803 gene
neXtProtiNX_Q9H8M5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 250ExtracellularSequence analysisAdd BLAST250
Transmembranei251 – 271HelicalSequence analysisAdd BLAST21
Topological domaini272 – 313CytoplasmicSequence analysisAdd BLAST42
Intramembranei314 – 334HelicalSequence analysisAdd BLAST21
Topological domaini335 – 338CytoplasmicSequence analysis4
Transmembranei339 – 359HelicalSequence analysisAdd BLAST21
Topological domaini360 – 368ExtracellularSequence analysis9
Transmembranei369 – 389HelicalSequence analysisAdd BLAST21
Topological domaini390 – 875CytoplasmicSequence analysisAdd BLAST486

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Hypomagnesemia 6 (HOMG6)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA renal disease characterized by severely lowered serum magnesium levels in the absence of other electrolyte disturbances. Affected individuals show an inappropriately normal urinary magnesium excretion, demonstrating a defect in tubular reabsorption. Age of clinical onset is highly variable and some affected individuals are asymptomatic.
See also OMIM:613882
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065260568T → I in HOMG6; reduced activity; electrophysiological analysis shows that magnesium-sensitive sodium currents are significantly diminished and are blocked by increased extracellular magnesium concentrations. 1 PublicationCorresponds to variant dbSNP:rs387906975EnsemblClinVar.1
Hypomagnesemia, seizures, and mental retardation (HOMGSMR)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by renal wasting of magnesium, low serum magnesium, seizures, and variable degrees of delayed psychomotor development.
See also OMIM:616418
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073848122E → K in HOMGSMR; results in reduced protein membrane expression. 1 PublicationCorresponds to variant dbSNP:rs786205909EnsemblClinVar.1
Natural variantiVAR_073849269S → W in HOMGSMR; results in reduced protein membrane expression; decreases cellular uptake of magnesium. 1 PublicationCorresponds to variant dbSNP:rs794726858EnsemblClinVar.1
Natural variantiVAR_073850330L → F in HOMGSMR. 1 Publication1
Natural variantiVAR_073851357E → K in HOMGSMR; results in decreased cellular uptake of magnesium. 1 PublicationCorresponds to variant dbSNP:rs786205910EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Epilepsy, Mental retardation, Primary hypomagnesemia

Organism-specific databases

DisGeNETi54805
MalaCardsiCNNM2
MIMi613882 phenotype
616418 phenotype
OpenTargetsiENSG00000148842
Orphaneti34527 Familial primary hypomagnesemia with normocalciuria and normocalcemia
PharmGKBiPA26669

Polymorphism and mutation databases

BioMutaiCNNM2
DMDMi156631023

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002957601 – 875Metal transporter CNNM2Add BLAST875

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi112N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei761PhosphoserineCombined sources1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9H8M5
MaxQBiQ9H8M5
PaxDbiQ9H8M5
PeptideAtlasiQ9H8M5
PRIDEiQ9H8M5

PTM databases

iPTMnetiQ9H8M5
PhosphoSitePlusiQ9H8M5

Expressioni

Tissue specificityi

Widely expressed. Expressed at higher level in brain, kidney and placenta, while it is weakly expressed in skeletal muscle. In the kidney, it is expressed in the distal convoluted tubule and the thick ascending limb of Henle loop.1 Publication

Gene expression databases

BgeeiENSG00000148842
CleanExiHS_CNNM2
GenevisibleiQ9H8M5 HS

Organism-specific databases

HPAiHPA059954
HPA071631

Interactioni

Protein-protein interaction databases

BioGridi120162, 7 interactors
IntActiQ9H8M5, 3 interactors
STRINGi9606.ENSP00000358894

Structurei

Secondary structure

1875
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi430 – 443Combined sources14
Helixi446 – 449Combined sources4
Beta strandi450 – 452Combined sources3
Helixi453 – 455Combined sources3
Helixi467 – 476Combined sources10
Beta strandi479 – 487Combined sources9
Beta strandi491 – 496Combined sources6
Helixi497 – 500Combined sources4
Helixi505 – 507Combined sources3
Helixi511 – 518Combined sources8
Beta strandi524 – 526Combined sources3
Helixi531 – 539Combined sources9
Beta strandi540 – 542Combined sources3
Beta strandi544 – 552Combined sources9
Beta strandi554 – 558Combined sources5
Beta strandi560 – 568Combined sources9
Helixi569 – 579Combined sources11
Turni580 – 582Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4IY0X-ray1.90A429-584[»]
4IY2X-ray3.60A/C430-584[»]
4IY4X-ray2.90A/C429-584[»]
4IYSX-ray1.80A430-584[»]
ProteinModelPortaliQ9H8M5
SMRiQ9H8M5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini251 – 431CNNM transmembranePROSITE-ProRule annotationAdd BLAST181
Domaini450 – 511CBS 1PROSITE-ProRule annotationAdd BLAST62
Domaini518 – 584CBS 2PROSITE-ProRule annotationAdd BLAST67

Sequence similaritiesi

Belongs to the ACDP family.Curated

Keywords - Domaini

CBS domain, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2118 Eukaryota
COG1253 LUCA
GeneTreeiENSGT00390000002383
HOVERGENiHBG074775
InParanoidiQ9H8M5
KOiK16302
OMAiVMASRMD
OrthoDBiEOG091G02YS
PhylomeDBiQ9H8M5
TreeFamiTF101012

Family and domain databases

InterProiView protein in InterPro
IPR000644 CBS_dom
IPR002550 CNNM
PfamiView protein in Pfam
PF00571 CBS, 1 hit
PF01595 DUF21, 1 hit
PROSITEiView protein in PROSITE
PS51371 CBS, 2 hits
PS51846 CNNM, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H8M5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MIGCGACEPK VKMAGGQAAA ALPTWKMAAR RSLSARGRGI LQAAAGRLLP
60 70 80 90 100
LLLLSCCCGA GGCAAVGENE ETVIIGLRLE DTNDVSFMEG GALRVSERTR
110 120 130 140 150
VKLRVYGQNI NNETWSRIAF TEHERRRHSP GERGLGGPAP PEPDSGPQRC
160 170 180 190 200
GIRTSDIIIL PHIILNRRTS GIIEIEIKPL RKMEKSKSYY LCTSLSTPAL
210 220 230 240 250
GAGGSGSTGG AVGGKGGSGV AGLPPPPWAE TTWIYHDGED TKMIVGEEKK
260 270 280 290 300
FLLPFWLQVI FISLLLCLSG MFSGLNLGLM ALDPMELRIV QNCGTEKEKN
310 320 330 340 350
YAKRIEPVRR QGNYLLCSLL LGNVLVNTTL TILLDDIAGS GLVAVVVSTI
360 370 380 390 400
GIVIFGEIVP QAICSRHGLA VGANTIFLTK FFMMMTFPAS YPVSKLLDCV
410 420 430 440 450
LGQEIGTVYN REKLLEMLRV TDPYNDLVKE ELNIIQGALE LRTKTVEDVM
460 470 480 490 500
TPLRDCFMIT GEAILDFNTM SEIMESGYTR IPVFEGERSN IVDLLFVKDL
510 520 530 540 550
AFVDPDDCTP LKTITKFYNH PLHFVFNDTK LDAMLEEFKK GKSHLAIVQR
560 570 580 590 600
VNNEGEGDPF YEVLGIVTLE DVIEEIIKSE ILDETDLYTD NRTKKKVAHR
610 620 630 640 650
ERKQDFSAFK QTDSEMKVKI SPQLLLAMHR FLATEVEAFS PSQMSEKILL
660 670 680 690 700
RLLKHPNVIQ ELKYDEKNKK APEYYLYQRN KPVDYFVLIL QGKVEVEAGK
710 720 730 740 750
EGMKFEASAF SYYGVMALTA SPVPLSLSRT FVVSRTELLA AGSPGENKSP
760 770 780 790 800
PRPCGLNHSD SLSRSDRIDA VTPTLGSSNN QLNSSLLQVY IPDYSVRALS
810 820 830 840 850
DLQFVKISRQ QYQNALMASR MDKTPQSSDS ENTKIELTLT ELHDGLPDET
860 870
ANLLNEQNCV THSKANHSLH NEGAI
Length:875
Mass (Da):96,623
Last modified:July 24, 2007 - v2
Checksum:i6D19F35D1B7D9A30
GO
Isoform 2 (identifier: Q9H8M5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     721-742: Missing.

Show »
Length:853
Mass (Da):94,341
Checksum:i65841388C6BF3D36
GO
Isoform 3 (identifier: Q9H8M5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     541-552: GKSHLAIVQRVN → EHTNKKPKSYQH
     553-875: Missing.

Note: No experimental confirmation available.
Show »
Length:552
Mass (Da):60,487
Checksum:iF17231FE929027E2
GO

Sequence cautioni

The sequence AAF86374 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA90926 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB14386 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAI16511 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAI16512 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAI40076 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAI40077 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti299K → N in BAB14585 (PubMed:14702039).Curated1
Sequence conflicti354I → V in BAB14386 (PubMed:14702039).Curated1
Sequence conflicti475E → V in BAB14386 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06525938R → Q1 PublicationCorresponds to variant dbSNP:rs76057237EnsemblClinVar.1
Natural variantiVAR_073848122E → K in HOMGSMR; results in reduced protein membrane expression. 1 PublicationCorresponds to variant dbSNP:rs786205909EnsemblClinVar.1
Natural variantiVAR_073849269S → W in HOMGSMR; results in reduced protein membrane expression; decreases cellular uptake of magnesium. 1 PublicationCorresponds to variant dbSNP:rs794726858EnsemblClinVar.1
Natural variantiVAR_073850330L → F in HOMGSMR. 1 Publication1
Natural variantiVAR_073851357E → K in HOMGSMR; results in decreased cellular uptake of magnesium. 1 PublicationCorresponds to variant dbSNP:rs786205910EnsemblClinVar.1
Natural variantiVAR_065260568T → I in HOMG6; reduced activity; electrophysiological analysis shows that magnesium-sensitive sodium currents are significantly diminished and are blocked by increased extracellular magnesium concentrations. 1 PublicationCorresponds to variant dbSNP:rs387906975EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_027077541 – 552GKSHL…VQRVN → EHTNKKPKSYQH in isoform 3. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_027078553 – 875Missing in isoform 3. 1 PublicationAdd BLAST323
Alternative sequenceiVSP_027080721 – 742Missing in isoform 2. 1 PublicationAdd BLAST22

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK000071 mRNA Translation: BAA90926.1 Different initiation.
AK023066 mRNA Translation: BAB14386.1 Different initiation.
AK023479 mRNA Translation: BAB14585.1
AL356608, AL139817 Genomic DNA Translation: CAI16511.1 Sequence problems.
AL356608, AL139817 Genomic DNA Translation: CAI16512.1 Sequence problems.
AL356608 Genomic DNA Translation: CAI16513.1
AL139817, AL356608 Genomic DNA Translation: CAI40076.1 Sequence problems.
AL139817, AL356608 Genomic DNA Translation: CAI40077.1 Sequence problems.
BC021222 mRNA Translation: AAH21222.3
AF216962 mRNA Translation: AAF86374.1 Different initiation.
CCDSiCCDS44474.1 [Q9H8M5-1]
CCDS44475.1 [Q9H8M5-2]
CCDS7543.1 [Q9H8M5-3]
RefSeqiNP_060119.3, NM_017649.4 [Q9H8M5-1]
NP_951058.1, NM_199076.2 [Q9H8M5-2]
NP_951059.1, NM_199077.2 [Q9H8M5-3]
UniGeneiHs.643509

Genome annotation databases

EnsembliENST00000369875; ENSP00000358891; ENSG00000148842 [Q9H8M5-3]
ENST00000369878; ENSP00000358894; ENSG00000148842 [Q9H8M5-1]
ENST00000433628; ENSP00000392875; ENSG00000148842 [Q9H8M5-2]
GeneIDi54805
KEGGihsa:54805
UCSCiuc001kwl.4 human [Q9H8M5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCNNM2_HUMAN
AccessioniPrimary (citable) accession number: Q9H8M5
Secondary accession number(s): Q5T569
, Q5T570, Q8WU59, Q9H952, Q9NRK5, Q9NXT4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 24, 2007
Last sequence update: July 24, 2007
Last modified: May 23, 2018
This is version 126 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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