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Protein

Natural resistance-associated macrophage protein 2

Gene

Slc11a2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May serve to import iron into the mitochondria (By similarity). Important in metal transport, in particular iron. 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.By similarity2 Publications

GO - Molecular functioni

GO - Biological processi

  • cadmium ion transmembrane transport Source: UniProtKB
  • cobalt ion transport Source: MGI
  • copper ion transport Source: MGI
  • dendrite morphogenesis Source: MGI
  • erythrocyte development Source: MGI
  • ferrous iron import Source: MGI
  • ferrous iron transport Source: MGI
  • heme biosynthetic process Source: MGI
  • iron ion transport Source: MGI
  • lead ion transport Source: MGI
  • learning or memory Source: MGI
  • manganese ion transport Source: MGI
  • multicellular organismal iron ion homeostasis Source: MGI
  • porphyrin-containing compound biosynthetic process Source: MGI
  • porphyrin-containing compound metabolic process Source: MGI
  • proton transport Source: MGI
  • response to iron ion Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Ion transport, Iron transport, Transport

Keywords - Ligandi

Iron

Enzyme and pathway databases

ReactomeiR-MMU-425410. Metal ion SLC transporters.
R-MMU-917937. Iron uptake and transport.

Names & Taxonomyi

Protein namesi
Recommended 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
Solute carrier family 11 member 2
Gene namesi
Name:Slc11a2
Synonyms:Dct1, Dmt1, Nramp2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:1345279. Slc11a2.

Subcellular locationi

  • Endosome membrane By similarity; Multi-pass membrane protein By similarity
  • Mitochondrion outer membrane By similarity; Multi-pass membrane protein By similarity
  • Cell membrane By similarity; Multi-pass membrane protein By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 69CytoplasmicSequence analysisAdd BLAST69
Transmembranei70 – 90HelicalSequence analysisAdd BLAST21
Topological domaini91 – 95ExtracellularSequence analysis5
Transmembranei96 – 117HelicalSequence analysisAdd BLAST22
Topological domaini118 – 154CytoplasmicSequence analysisAdd BLAST37
Transmembranei155 – 175HelicalSequence analysisAdd BLAST21
Topological domaini176 – 179ExtracellularSequence analysis4
Transmembranei180 – 194HelicalSequence analysisAdd BLAST15
Topological domaini195 – 208CytoplasmicSequence analysisAdd BLAST14
Transmembranei209 – 229HelicalSequence analysisAdd BLAST21
Topological domaini230 – 255ExtracellularSequence analysisAdd BLAST26
Transmembranei256 – 276HelicalSequence analysisAdd BLAST21
Topological domaini277 – 301CytoplasmicSequence analysisAdd BLAST25
Transmembranei302 – 322HelicalSequence analysisAdd BLAST21
Topological domaini323 – 360ExtracellularSequence analysisAdd BLAST38
Transmembranei361 – 381HelicalSequence analysisAdd BLAST21
Topological domaini382 – 408CytoplasmicSequence analysisAdd BLAST27
Transmembranei409 – 429HelicalSequence analysisAdd BLAST21
Topological domaini430 – 440ExtracellularSequence analysisAdd BLAST11
Transmembranei441 – 461HelicalSequence analysisAdd BLAST21
Topological domaini462 – 482CytoplasmicSequence analysisAdd BLAST21
Transmembranei483 – 503HelicalSequence analysisAdd BLAST21
Topological domaini504 – 506ExtracellularSequence analysis3
Transmembranei507 – 527HelicalSequence analysisAdd BLAST21
Topological domaini528 – 568CytoplasmicSequence analysisAdd BLAST41

GO - Cellular componenti

  • apical part of cell Source: MGI
  • apical plasma membrane Source: MGI
  • basal part of cell Source: MGI
  • brush border Source: MGI
  • brush border membrane Source: BHF-UCL
  • cell surface Source: MGI
  • cytoplasm Source: MGI
  • cytoplasmic vesicle Source: MGI
  • early endosome Source: MGI
  • endomembrane system Source: MGI
  • endosome Source: MGI
  • integral component of plasma membrane Source: MGI
  • late endosome membrane Source: MGI
  • lysosomal membrane Source: MGI
  • membrane Source: MGI
  • mitochondrial outer membrane Source: UniProtKB-SubCell
  • nucleus Source: MGI
  • paraferritin complex Source: MGI
  • perinuclear region of cytoplasm Source: MGI
  • plasma membrane Source: MGI
  • recycling endosome Source: MGI
  • vacuole Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Involvement in diseasei

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

Disruption phenotypei

Mice display no apparent anatomical abnormalities. They are however anemic, show progressive postnatal growth retardation, and at birth have elevated liver iron stores compared with wild-type littermates. None survive for more than 7 days. Heterozygotes appear normal, showing no significant hematological abnormalities. However, by 8 weeks, their liver iron content is lower than in wild-type littermates.1 Publication

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002125951 – 568Natural resistance-associated macrophage protein 2Add BLAST568

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi336N-linked (GlcNAc...)Sequence analysis1
Glycosylationi349N-linked (GlcNAc...)Sequence analysis1
Modified residuei564PhosphoserineCombined sources1
Modified residuei567PhosphoserineCombined sources1
Isoform 1 (identifier: P49282-2)
Modified residuei556PhosphoserineCombined sources1
Isoform 3 (identifier: P49282-3)
Modified residuei586PhosphoserineCombined sources1

Post-translational modificationi

N-glycosylated.By similarity
Ubiquitinated by WWP2.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP49282.
MaxQBiP49282.
PaxDbiP49282.
PeptideAtlasiP49282.
PRIDEiP49282.

PTM databases

iPTMnetiP49282.
PhosphoSitePlusiP49282.

Expressioni

Tissue specificityi

Isoform 2 is abundantly expressed in erythroid precursor cells (at protein level). Expressed at low levels in most tissues analyzed. Expressed at low levels in small intestine and at higher levels in kidney.2 Publications

Inductioni

Isoform 1 is up-regulated under iron-depletion conditions in the proximal portion of the duodenum where it is abundantly expressed in the brush border of absorptive epithelial cells (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000023030.
ExpressionAtlasiP49282. baseline and differential.
GenevisibleiP49282. MM.

Interactioni

Subunit structurei

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. Interacts with COX2 and TOM6 at the outer mitochondrion membrane (By similarity).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000023774.

Structurei

3D structure databases

ProteinModelPortaliP49282.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the NRAMP family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1291. Eukaryota.
COG1914. LUCA.
GeneTreeiENSGT00390000006526.
HOVERGENiHBG052665.
InParanoidiP49282.
KOiK12347.
OMAiWVLLMAT.
OrthoDBiEOG091G05M9.
PhylomeDBiP49282.
TreeFamiTF315185.

Family and domain databases

HAMAPiMF_00221. NRAMP. 1 hit.
InterProiIPR001046. NRAMP_fam.
[Graphical view]
PANTHERiPTHR11706. PTHR11706. 1 hit.
PfamiPF01566. Nramp. 1 hit.
[Graphical view]
PRINTSiPR00447. NATRESASSCMP.
TIGRFAMsiTIGR01197. nramp. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: P49282-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MVLDPKEKMP DDGASGDHGD SASLGAINPA YSNSSLPHST GDSEEPFTTY
60 70 80 90 100
FDEKIPIPEE EYSCFSFRKL WAFTGPGFLM SIAYLDPGNI ESDLQSGAVA
110 120 130 140 150
GFKLLWVLLL ATIVGLLLQR LAARLGVVTG LHLAEVCHRQ YPKVPRIILW
160 170 180 190 200
LMVELAIIGS DMQEVIGSAI AINLLSAGRV PLWGGVLITI ADTFVFLFLD
210 220 230 240 250
KYGLRKLEAF FGFLITIMAL TFGYEYITVK PSQSQVLRGM FVPSCPGCRT
260 270 280 290 300
PQVEQAVGIV GAVIMPHNMY LHSALVKSRQ VNRANKQEVR EANKYFFIES
310 320 330 340 350
CIALFVSFII NVFVVSVFAE AFFEKTNKQV VEVCKNNSSP HADLFPSDNS
360 370 380 390 400
TLAVDIYKGG VVLGCYFGPA ALYIWAVGIL AAGQSSTMTG TYSGQFVMEG
410 420 430 440 450
FLNLKWSRFA RVILTRSIAI IPTLLVAVFQ DVEHLTGMND FLNVLQSLQL
460 470 480 490 500
PFALIPILTF TSLRPVMSEF SNGIGWRIAG GILVLIVCSI NMYFVVVYVQ
510 520 530 540 550
ELGHVALYVV AAVVSVAYLT FVFYLGWQCL IALGLSFLDC GRSYRLGLTA
560
QPELYLLNTV DADSVVSR
Length:568
Mass (Da):62,368
Last modified:September 22, 2009 - v2
Checksum:i603AAF697AAD3C74
GO
Isoform 1 (identifier: P49282-2) [UniParc]FASTAAdd to basket
Also known as: IRE

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

Show »
Length:561
Mass (Da):61,421
Checksum:iD2FAA52B8F73FFBC
GO
Isoform 3 (identifier: P49282-3) [UniParc]FASTAAdd to basket
Also known as: 1A-IRE

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGKKQPRAAAAAPNCELKSYSKSTDPQVSTM
     544-568: YRLGLTAQPELYLLNTVDADSVVSR → VSISKVLLSEDTSGGNIK

Note: No experimental confirmation available.Combined sources
Show »
Length:591
Mass (Da):64,568
Checksum:iF8119C955315B2F6
GO
Isoform 4 (identifier: P49282-4) [UniParc]FASTAAdd to basket
Also known as: 1A-Non-IRE

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGKKQPRAAAAAPNCELKSYSKSTDPQVSTM

Note: No experimental confirmation available.
Show »
Length:598
Mass (Da):65,515
Checksum:iED4B62ED656BAEBE
GO

Sequence cautioni

The sequence CAD38518 differs from that shown. Reason: Frameshift at position 69.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6K → E in BAE28454 (PubMed:16141072).Curated1
Sequence conflicti6K → E in CAD38518 (PubMed:12209011).Curated1
Sequence conflicti68R → S in AAC24496 (Ref. 2) Curated1
Sequence conflicti69 – 70Missing in CAD38518 (PubMed:12209011).Curated2
Sequence conflicti142P → R in BAC38930 (PubMed:16141072).Curated1
Sequence conflicti182L → V in AAC42051 (PubMed:7789986).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti185G → R in microcytic anemia. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0381451M → MGKKQPRAAAAAPNCELKSY SKSTDPQVSTM in isoform 3 and isoform 4. Curated1
Alternative sequenceiVSP_003596544 – 568YRLGL…SVVSR → VSISKVLLSEDTSGGNIK in isoform 1 and isoform 3. 2 PublicationsAdd BLAST25

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L33415 mRNA. Translation: AAC42051.1.
AF029758 mRNA. Translation: AAC24496.1.
AK049856 mRNA. Translation: BAC33960.1.
AK083478 mRNA. Translation: BAC38930.1.
AK148276 mRNA. Translation: BAE28454.1.
CH466550 Genomic DNA. Translation: EDL04090.1.
BC019137 mRNA. Translation: AAH19137.1.
AJ493663 mRNA. Translation: CAD38518.1. Frameshift.
CCDSiCCDS37211.1. [P49282-1]
CCDS49733.1. [P49282-2]
PIRiA56852.
RefSeqiNP_001139633.1. NM_001146161.1. [P49282-2]
NP_032758.2. NM_008732.2. [P49282-1]
XP_006520640.1. XM_006520577.3. [P49282-1]
XP_006520641.1. XM_006520578.3. [P49282-1]
XP_011243789.1. XM_011245487.2. [P49282-4]
UniGeneiMm.234608.

Genome annotation databases

EnsembliENSMUST00000023774; ENSMUSP00000023774; ENSMUSG00000023030. [P49282-1]
ENSMUST00000138843; ENSMUSP00000116463; ENSMUSG00000023030. [P49282-2]
GeneIDi18174.
KEGGimmu:18174.
UCSCiuc007xrc.2. mouse. [P49282-1]
uc007xrd.2. mouse. [P49282-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L33415 mRNA. Translation: AAC42051.1.
AF029758 mRNA. Translation: AAC24496.1.
AK049856 mRNA. Translation: BAC33960.1.
AK083478 mRNA. Translation: BAC38930.1.
AK148276 mRNA. Translation: BAE28454.1.
CH466550 Genomic DNA. Translation: EDL04090.1.
BC019137 mRNA. Translation: AAH19137.1.
AJ493663 mRNA. Translation: CAD38518.1. Frameshift.
CCDSiCCDS37211.1. [P49282-1]
CCDS49733.1. [P49282-2]
PIRiA56852.
RefSeqiNP_001139633.1. NM_001146161.1. [P49282-2]
NP_032758.2. NM_008732.2. [P49282-1]
XP_006520640.1. XM_006520577.3. [P49282-1]
XP_006520641.1. XM_006520578.3. [P49282-1]
XP_011243789.1. XM_011245487.2. [P49282-4]
UniGeneiMm.234608.

3D structure databases

ProteinModelPortaliP49282.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000023774.

PTM databases

iPTMnetiP49282.
PhosphoSitePlusiP49282.

Proteomic databases

EPDiP49282.
MaxQBiP49282.
PaxDbiP49282.
PeptideAtlasiP49282.
PRIDEiP49282.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000023774; ENSMUSP00000023774; ENSMUSG00000023030. [P49282-1]
ENSMUST00000138843; ENSMUSP00000116463; ENSMUSG00000023030. [P49282-2]
GeneIDi18174.
KEGGimmu:18174.
UCSCiuc007xrc.2. mouse. [P49282-1]
uc007xrd.2. mouse. [P49282-2]

Organism-specific databases

CTDi4891.
MGIiMGI:1345279. Slc11a2.

Phylogenomic databases

eggNOGiKOG1291. Eukaryota.
COG1914. LUCA.
GeneTreeiENSGT00390000006526.
HOVERGENiHBG052665.
InParanoidiP49282.
KOiK12347.
OMAiWVLLMAT.
OrthoDBiEOG091G05M9.
PhylomeDBiP49282.
TreeFamiTF315185.

Enzyme and pathway databases

ReactomeiR-MMU-425410. Metal ion SLC transporters.
R-MMU-917937. Iron uptake and transport.

Miscellaneous databases

ChiTaRSiSlc11a2. mouse.
PROiP49282.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000023030.
ExpressionAtlasiP49282. baseline and differential.
GenevisibleiP49282. MM.

Family and domain databases

HAMAPiMF_00221. NRAMP. 1 hit.
InterProiIPR001046. NRAMP_fam.
[Graphical view]
PANTHERiPTHR11706. PTHR11706. 1 hit.
PfamiPF01566. Nramp. 1 hit.
[Graphical view]
PRINTSiPR00447. NATRESASSCMP.
TIGRFAMsiTIGR01197. nramp. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiNRAM2_MOUSE
AccessioniPrimary (citable) accession number: P49282
Secondary accession number(s): O54903
, Q3UFV5, Q8BJL2, Q8BWV3, Q8CFA0, Q8VCU6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: September 22, 2009
Last modified: November 2, 2016
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Nifedipine induces duodenal iron accumulation and mobilizes iron from the liver of iron-overloaded mice.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.