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O54902 (NRAM2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Natural resistance-associated macrophage protein 2
Short name=NRAMP 2
Alternative name(s):
Divalent cation transporter 1
Divalent metal transporter 1
Short name=DMT-1
Gene names
Name:Slc11a2
Synonyms:Dct1, Dmt1, Nramp2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length568 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Important in metal transport, in particular iron. Can also transport zinc, manganese, cobalt, cadmium, copper, nickel and lead. Involved in apical iron uptake into duodenal enterocytes. Involved in iron transport from acidified endosomes into the cytoplasm of erythroid precursor cells. May play an important role in hepatic iron accumulation and tissue iron distribution. Ref.1

Subunit structure

Forms a complex with NDFIP1 and NEDD4L, in cortical neurons, in response to iron and colbalt exposure; this interaction leads to ubiquitination by NEDD4L and proteasome-dependent degradation. Interacts with NDFIP2 By similarity.

Subcellular location

Endosome membrane; Multi-pass membrane protein By similarity.

Tissue specificity

Ubiquitous.

Post-translational modification

Ubiquitinated by WWP2 By similarity.

Involvement in disease

Defects in Slc11a2 are the cause of microcytic anemia (Belgrade or b). Homozygous b/b rats have hypochromic microcytic anemia due to severe defects in intestinal iron absorption and erythroid iron utilization.

Sequence similarities

Belongs to the NRAMP family.

Ontologies

Keywords
   Biological processIon transport
Iron transport
Transport
   Cellular componentEndosome
Membrane
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainTransmembrane
Transmembrane helix
   LigandIron
   PTMGlycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to hypoxia

Inferred from expression pattern PubMed 21325818. Source: RGD

cellular response to iron ion

Inferred from expression pattern PubMed 17663481. Source: RGD

cellular response to tumor necrosis factor

Inferred from expression pattern PubMed 16221503. Source: RGD

iron ion homeostasis

Inferred from electronic annotation. Source: UniProtKB-KW

response to cadmium ion

Inferred from expression pattern PubMed 19083094. Source: RGD

response to lead ion

Inferred from expression pattern PubMed 19083094. Source: RGD

response to manganese ion

Inferred from mutant phenotype PubMed 18849539. Source: RGD

   Cellular_componentapical part of cell

Inferred from direct assay PubMed 18420243. Source: RGD

integral to membrane

Inferred from direct assay Ref.1. Source: RGD

late endosome membrane

Inferred from direct assay PubMed 16449358. Source: RGD

lysosomal membrane

Inferred from direct assay PubMed 16449358. Source: RGD

   Molecular_functioncadmium ion binding

Inferred from direct assay Ref.1. Source: RGD

cadmium ion transmembrane transporter activity

Inferred from direct assay Ref.1. Source: RGD

cobalt ion binding

Inferred from direct assay Ref.1. Source: RGD

cobalt ion transmembrane transporter activity

Inferred from direct assay Ref.1. Source: RGD

copper ion binding

Inferred from direct assay Ref.1. Source: RGD

copper ion transmembrane transporter activity

Inferred from direct assay Ref.1. Source: RGD

ferrous iron transmembrane transporter activity

Inferred from mutant phenotype PubMed 16091957. Source: RGD

iron ion binding

Inferred from direct assay Ref.1. Source: RGD

lead ion transmembrane transporter activity

Inferred from direct assay Ref.1. Source: RGD

manganese ion binding

Inferred from direct assay Ref.1. Source: RGD

manganese ion transmembrane transporter activity

Inferred from direct assay Ref.1. Source: RGD

nickel cation binding

Inferred from direct assay Ref.1. Source: RGD

nickel cation transmembrane transporter activity

Inferred from direct assay Ref.1. Source: RGD

zinc ion binding

Inferred from direct assay Ref.1. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 (identifier: O54902-1)

Also known as: Non-IRE;

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.
Isoform 1 (identifier: O54902-2)

Also known as: IRE;

The sequence of this isoform differs from the canonical sequence as follows:
     544-568: YHLGLTARPEIYLLNTVDAVSLVSR → VSISKVLLSEDTSGGNTK

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 568568Natural resistance-associated macrophage protein 2
PRO_0000212596

Regions

Topological domain1 – 6969Cytoplasmic Potential
Transmembrane70 – 9021Helical; Potential
Topological domain91 – 955Extracellular Potential
Transmembrane96 – 11722Helical; Potential
Topological domain118 – 15437Cytoplasmic Potential
Transmembrane155 – 17521Helical; Potential
Topological domain176 – 1794Extracellular Potential
Transmembrane180 – 19415Helical; Potential
Topological domain195 – 20814Cytoplasmic Potential
Transmembrane209 – 22921Helical; Potential
Topological domain230 – 25526Extracellular Potential
Transmembrane256 – 27621Helical; Potential
Topological domain277 – 30125Cytoplasmic Potential
Transmembrane302 – 32221Helical; Potential
Topological domain323 – 36038Extracellular Potential
Transmembrane361 – 38121Helical; Potential
Topological domain382 – 40827Cytoplasmic Potential
Transmembrane409 – 42921Helical; Potential
Topological domain430 – 44011Extracellular Potential
Transmembrane441 – 46121Helical; Potential
Topological domain462 – 48221Cytoplasmic Potential
Transmembrane483 – 50321Helical; Potential
Topological domain504 – 5063Extracellular Potential
Transmembrane507 – 52721Helical; Potential
Topological domain528 – 56841Cytoplasmic Potential

Amino acid modifications

Modified residue211Phosphoserine By similarity
Modified residue5641Phosphoserine By similarity
Modified residue5671Phosphoserine By similarity
Glycosylation3361N-linked (GlcNAc...) Potential
Glycosylation3491N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence544 – 56825YHLGL…SLVSR → VSISKVLLSEDTSGGNTK in isoform 1.
VSP_003597
Natural variant1851G → R in microcytic anemia. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 (Non-IRE) [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: C7B77E964E741F4D

FASTA56862,277
        10         20         30         40         50         60 
MVLDPEEKIP DDGASGDHGD SASLGAINPA YSNSSLPHST GDSEEPFTTY FDEKIPIPEE 

        70         80         90        100        110        120 
EYSCFSFRKL WAFTGPGFLM SIAYLDPGNI ESDLQSGAVA GFKLLWVLLL ATIVGLLLQR 

       130        140        150        160        170        180 
LAARLGVVTG LHLAEVCHRQ YPKVPRIILW LMVELAIIGS DMQEVIGSAI AINLLSAGRV 

       190        200        210        220        230        240 
PLYGGVLITI ADTFVFLFLD KYGLRKLEAF FGFLITIMAL TFGYEYVTVK PSQSQVLRGM 

       250        260        270        280        290        300 
FVPSCSGCHT PQVEQAVGIV GAVIMPHNMY LHSALVKSRQ VNRANKQEVR EANKYFFIES 

       310        320        330        340        350        360 
CIALFVSFII NVFVVSVFAE AFFEKTNEQV VEVCRNSSSP HADLFPNDNS TLAVDIYKGG 

       370        380        390        400        410        420 
VVLGCYFGPA ALYIWAVGIL AAGQSSTMTG TYSGQFVMEG FLNLKWSRFA RVILTRSIAI 

       430        440        450        460        470        480 
IPTLLVAVFQ DVEHLTGMND FLNVLQSLQL PFALIPILTF TSLRPVMSEF SNGIGWRIAG 

       490        500        510        520        530        540 
GILVLLVCSI NMYFVVVYVQ ELGHVALYVV AAVVSVAYLG FVFYLGWQCL IALGLSFLDC 

       550        560 
GRSYHLGLTA RPEIYLLNTV DAVSLVSR

« Hide

Isoform 1 (IRE) [UniParc].

Checksum: 2AEFE5E5EFFA48D4
Show »

FASTA56161,310

References

[1]"Cloning and characterization of a mammalian proton-coupled metal-ion transporter."
Gunshin H., Mackenzie B., Berger U.V., Gunshin Y., Romero M.F., Boron W.F., Nussberger S., Gollan J.L., Hediger M.A.
Nature 388:482-488(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
Strain: Sprague-Dawley.
[2]"Rat natural resistance associated macrophage protein-2 (Nramp2), C-terminal exon alternative splice variant."
Fleming M.D., Romano M.A., Su M.A., Garrick L.M., Garrick M.D., Andrews N.C.
Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Cerebellum.
[3]"Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport."
Fleming M.D., Romano M.A., Su M.A., Garrick L.M., Garrick M.D., Andrews N.C.
Proc. Natl. Acad. Sci. U.S.A. 95:1148-1153(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT B ARG-185.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF008439 mRNA. Translation: AAC53319.1.
AF029757 mRNA. Translation: AAC24495.1.
IPIIPI00392541.
IPI00952249.
RefSeqNP_037305.2. NM_013173.2.
UniGeneRn.11418.

3D structure databases

ModBaseSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000026494.

Protein family/group databases

TCDB2.A.55.2.2. metal ion (Mn2+-iron) transporter (Nramp) family.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000026531; ENSRNOP00000026531; ENSRNOG00000019550.
GeneID25715.
KEGGrno:25715.
UCSCRGD:3684. rat.

Organism-specific databases

CTD4891.
RGD3684. Slc11a2.

Phylogenomic databases

eggNOGCOG1914.
GeneTreeENSGT00390000006526.
HOGENOMHOG000152203.
HOVERGENHBG052665.
InParanoidO54902.
KOK12347.
OrthoDBEOG4RFKSH.

Gene expression databases

ArrayExpressO54902.
GenevestigatorO54902.
GermOnlineENSRNOG00000019550. Rattus norvegicus.

Family and domain databases

InterProIPR001046. NRAMP-like.
[Graphical view]
PANTHERPTHR11706. PTHR11706. 1 hit.
PfamPF01566. Nramp. 1 hit.
[Graphical view]
PRINTSPR00447. NATRESASSCMP.
TIGRFAMsTIGR01197. nramp. 1 hit.
ProtoNetSearch...

Other

NextBio607793.

Entry information

Entry nameNRAM2_RAT
AccessionPrimary (citable) accession number: O54902
Secondary accession number(s): O35172
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 1, 1998
Last modified: May 29, 2013
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents