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Protein

Metal transporter CNNM2

Gene

CNNM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Biological processi

  • magnesium ion homeostasis Source: MGI
  • magnesium ion transport Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Ion 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

HGNCiHGNC:103. CNNM2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 250250ExtracellularSequence analysisAdd
BLAST
Transmembranei251 – 27121HelicalSequence analysisAdd
BLAST
Topological domaini272 – 31342CytoplasmicSequence analysisAdd
BLAST
Intramembranei314 – 33421HelicalSequence analysisAdd
BLAST
Topological domaini335 – 3384CytoplasmicSequence analysis
Transmembranei339 – 35921HelicalSequence analysisAdd
BLAST
Topological domaini360 – 3689ExtracellularSequence analysis
Transmembranei369 – 38921HelicalSequence analysisAdd
BLAST
Topological domaini390 – 875486CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • basolateral plasma membrane Source: MGI
  • integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti568 – 5681T → 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 Publication
Corresponds to variant rs387906975 [ dbSNP | Ensembl ].
VAR_065260
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti122 – 1221E → K in HOMGSMR; results in reduced protein membrane expression. 1 Publication
Corresponds to variant rs786205909 [ dbSNP | Ensembl ].
VAR_073848
Natural varianti269 – 2691S → W in HOMGSMR; results in reduced protein membrane expression; decreases cellular uptake of magnesium. 1 Publication
Corresponds to variant rs794726858 [ dbSNP | Ensembl ].
VAR_073849
Natural varianti330 – 3301L → F in HOMGSMR. 1 Publication
VAR_073850
Natural varianti357 – 3571E → K in HOMGSMR; results in decreased cellular uptake of magnesium. 1 Publication
Corresponds to variant rs786205910 [ dbSNP | Ensembl ].
VAR_073851

Keywords - Diseasei

Disease mutation, Epilepsy, Mental retardation, Primary hypomagnesemia

Organism-specific databases

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

Polymorphism and mutation databases

BioMutaiCNNM2.
DMDMi156631023.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 875875Metal transporter CNNM2PRO_0000295760Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi112 – 1121N-linked (GlcNAc...)Sequence analysis
Modified residuei761 – 7611PhosphoserineCombined sources

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ9H8M5.
PaxDbiQ9H8M5.
PeptideAtlasiQ9H8M5.
PRIDEiQ9H8M5.

PTM databases

iPTMnetiQ9H8M5.
PhosphoSiteiQ9H8M5.

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.

Interactioni

Protein-protein interaction databases

BioGridi120162. 5 interactions.
IntActiQ9H8M5. 1 interaction.
STRINGi9606.ENSP00000358894.

Structurei

Secondary structure

1
875
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi430 – 44314Combined sources
Helixi446 – 4494Combined sources
Beta strandi450 – 4523Combined sources
Helixi453 – 4553Combined sources
Helixi467 – 47610Combined sources
Beta strandi479 – 4879Combined sources
Beta strandi491 – 4966Combined sources
Helixi497 – 5004Combined sources
Helixi505 – 5073Combined sources
Helixi511 – 5188Combined sources
Beta strandi524 – 5263Combined sources
Helixi531 – 5399Combined sources
Beta strandi540 – 5423Combined sources
Beta strandi544 – 5529Combined sources
Beta strandi554 – 5585Combined sources
Beta strandi560 – 5689Combined sources
Helixi569 – 57911Combined sources
Turni580 – 5823Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4IY0X-ray1.90A429-584[»]
4IY2X-ray3.60A/C430-584[»]
4IY4X-ray2.90A/C429-584[»]
4IYSX-ray1.80A430-584[»]
ProteinModelPortaliQ9H8M5.
SMRiQ9H8M5. Positions 429-580.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini258 – 430173DUF21Add
BLAST
Domaini450 – 51162CBS 1PROSITE-ProRule annotationAdd
BLAST
Domaini518 – 58467CBS 2PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the ACDP family.Curated
Contains 2 CBS domains.PROSITE-ProRule annotation
Contains 1 DUF21 domain.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

Gene3Di2.60.120.10. 2 hits.
InterProiIPR000644. CBS_dom.
IPR002550. DUF21.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PfamiPF00571. CBS. 1 hit.
PF01595. DUF21. 1 hit.
[Graphical view]
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti299 – 2991K → N in BAB14585 (PubMed:14702039).Curated
Sequence conflicti354 – 3541I → V in BAB14386 (PubMed:14702039).Curated
Sequence conflicti475 – 4751E → V in BAB14386 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti38 – 381R → Q.1 Publication
Corresponds to variant rs76057237 [ dbSNP | Ensembl ].
VAR_065259
Natural varianti122 – 1221E → K in HOMGSMR; results in reduced protein membrane expression. 1 Publication
Corresponds to variant rs786205909 [ dbSNP | Ensembl ].
VAR_073848
Natural varianti269 – 2691S → W in HOMGSMR; results in reduced protein membrane expression; decreases cellular uptake of magnesium. 1 Publication
Corresponds to variant rs794726858 [ dbSNP | Ensembl ].
VAR_073849
Natural varianti330 – 3301L → F in HOMGSMR. 1 Publication
VAR_073850
Natural varianti357 – 3571E → K in HOMGSMR; results in decreased cellular uptake of magnesium. 1 Publication
Corresponds to variant rs786205910 [ dbSNP | Ensembl ].
VAR_073851
Natural varianti568 – 5681T → 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 Publication
Corresponds to variant rs387906975 [ dbSNP | Ensembl ].
VAR_065260

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei541 – 55212GKSHL…VQRVN → EHTNKKPKSYQH in isoform 3. 1 PublicationVSP_027077Add
BLAST
Alternative sequencei553 – 875323Missing in isoform 3. 1 PublicationVSP_027078Add
BLAST
Alternative sequencei721 – 74222Missing in isoform 2. 1 PublicationVSP_027080Add
BLAST

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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4IY0X-ray1.90A429-584[»]
4IY2X-ray3.60A/C430-584[»]
4IY4X-ray2.90A/C429-584[»]
4IYSX-ray1.80A430-584[»]
ProteinModelPortaliQ9H8M5.
SMRiQ9H8M5. Positions 429-580.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120162. 5 interactions.
IntActiQ9H8M5. 1 interaction.
STRINGi9606.ENSP00000358894.

PTM databases

iPTMnetiQ9H8M5.
PhosphoSiteiQ9H8M5.

Polymorphism and mutation databases

BioMutaiCNNM2.
DMDMi156631023.

Proteomic databases

MaxQBiQ9H8M5.
PaxDbiQ9H8M5.
PeptideAtlasiQ9H8M5.
PRIDEiQ9H8M5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi54805.
GeneCardsiCNNM2.
H-InvDBHIX0009171.
HGNCiHGNC:103. CNNM2.
HPAiHPA059954.
MalaCardsiCNNM2.
MIMi607803. gene.
613882. phenotype.
616418. phenotype.
neXtProtiNX_Q9H8M5.
Orphaneti34527. Familial primary hypomagnesemia with normocalciuria and normocalcemia.
PharmGKBiPA26669.
GenAtlasiSearch...

Phylogenomic databases

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

Miscellaneous databases

ChiTaRSiCNNM2. human.
GenomeRNAii54805.
PROiQ9H8M5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000148842.
CleanExiHS_CNNM2.
GenevisibleiQ9H8M5. HS.

Family and domain databases

Gene3Di2.60.120.10. 2 hits.
InterProiIPR000644. CBS_dom.
IPR002550. DUF21.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PfamiPF00571. CBS. 1 hit.
PF01595. DUF21. 1 hit.
[Graphical view]
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCNNM2_HUMAN
AccessioniPrimary (citable) accession number: Q9H8M5
Secondary accession number(s): Q5T569
, Q5T570, Q8WU59, Q9H952, Q9NRK5, Q9NXT4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 24, 2007
Last sequence update: July 24, 2007
Last modified: September 7, 2016
This is version 112 of the entry and version 2 of the sequence. [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

Miscellaneous

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

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.