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Protein

Natural resistance-associated macrophage protein 2

Gene

Slc11a2

Organism
Rattus norvegicus (Rat)
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. 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.By similarity1 Publication

GO - Molecular functioni

  • cadmium ion binding Source: RGD
  • cadmium ion transmembrane transporter activity Source: RGD
  • cobalt ion binding Source: RGD
  • cobalt ion transmembrane transporter activity Source: RGD
  • copper ion binding Source: RGD
  • copper ion transmembrane transporter activity Source: RGD
  • ferrous iron transmembrane transporter activity Source: RGD
  • ferrous iron uptake transmembrane transporter activity Source: UniProtKB
  • iron ion binding Source: RGD
  • iron ion transmembrane transporter activity Source: RGD
  • lead ion transmembrane transporter activity Source: RGD
  • manganese ion binding Source: RGD
  • manganese ion transmembrane transporter activity Source: RGD
  • nickel cation binding Source: RGD
  • nickel cation transmembrane transporter activity Source: RGD
  • zinc ion binding Source: RGD

GO - Biological processi

  • cellular copper ion homeostasis Source: RGD
  • cellular response to hypoxia Source: RGD
  • cellular response to iron ion Source: RGD
  • cellular response to tumor necrosis factor Source: RGD
  • copper ion import into cell Source: RGD
  • ferrous iron transport Source: UniProtKB
  • iron ion homeostasis Source: UniProtKB-KW
  • response to cadmium ion Source: RGD
  • response to hypoxia Source: RGD
  • response to iron ion Source: RGD
  • response to lead ion Source: RGD
  • response to manganese ion Source: RGD
  • transition metal ion transport Source: RGD
Complete GO annotation...

Keywords - Biological processi

Ion transport, Iron transport, Transport

Keywords - Ligandi

Iron

Protein family/group databases

TCDBi2.A.55.2.2. the metal ion (mn(2+)-iron) transporter (nramp) family.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3684. 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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 6969CytoplasmicSequence analysisAdd
BLAST
Transmembranei70 – 9021HelicalSequence analysisAdd
BLAST
Topological domaini91 – 955ExtracellularSequence analysis
Transmembranei96 – 11722HelicalSequence analysisAdd
BLAST
Topological domaini118 – 15437CytoplasmicSequence analysisAdd
BLAST
Transmembranei155 – 17521HelicalSequence analysisAdd
BLAST
Topological domaini176 – 1794ExtracellularSequence analysis
Transmembranei180 – 19415HelicalSequence analysisAdd
BLAST
Topological domaini195 – 20814CytoplasmicSequence analysisAdd
BLAST
Transmembranei209 – 22921HelicalSequence analysisAdd
BLAST
Topological domaini230 – 25526ExtracellularSequence analysisAdd
BLAST
Transmembranei256 – 27621HelicalSequence analysisAdd
BLAST
Topological domaini277 – 30125CytoplasmicSequence analysisAdd
BLAST
Transmembranei302 – 32221HelicalSequence analysisAdd
BLAST
Topological domaini323 – 36038ExtracellularSequence analysisAdd
BLAST
Transmembranei361 – 38121HelicalSequence analysisAdd
BLAST
Topological domaini382 – 40827CytoplasmicSequence analysisAdd
BLAST
Transmembranei409 – 42921HelicalSequence analysisAdd
BLAST
Topological domaini430 – 44011ExtracellularSequence analysisAdd
BLAST
Transmembranei441 – 46121HelicalSequence analysisAdd
BLAST
Topological domaini462 – 48221CytoplasmicSequence analysisAdd
BLAST
Transmembranei483 – 50321HelicalSequence analysisAdd
BLAST
Topological domaini504 – 5063ExtracellularSequence analysis
Transmembranei507 – 52721HelicalSequence analysisAdd
BLAST
Topological domaini528 – 56841CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • apical part of cell Source: RGD
  • cytoplasm Source: RGD
  • early endosome Source: UniProtKB
  • integral component of membrane Source: RGD
  • integral component of plasma membrane Source: UniProtKB
  • late endosome membrane Source: RGD
  • lysosomal membrane Source: RGD
  • mitochondrial outer membrane Source: UniProtKB-SubCell
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 (Belgrade or b). Homozygous b/b rats have hypochromic microcytic anemia due to severe defects in intestinal iron absorption and erythroid iron utilization.

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 568568Natural resistance-associated macrophage protein 2PRO_0000212596Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi336 – 3361N-linked (GlcNAc...)Sequence analysis
Glycosylationi349 – 3491N-linked (GlcNAc...)Sequence analysis
Modified residuei564 – 5641PhosphoserineBy similarity
Modified residuei567 – 5671PhosphoserineBy similarity
Isoform 1 (identifier: O54902-2)
Modified residuei556 – 5561PhosphoserineCombined sources

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO54902.

PTM databases

PhosphoSiteiO54902.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSRNOG00000019550.
GenevisibleiO54902. RN.

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

BioGridi247744. 1 interaction.
STRINGi10116.ENSRNOP00000026531.

Structurei

3D structure databases

ProteinModelPortaliO54902.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the NRAMP family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1291. Eukaryota.
COG1914. LUCA.
HOGENOMiHOG000152203.
HOVERGENiHBG052665.
InParanoidiO54902.
KOiK12347.
OrthoDBiEOG091G05M9.
PhylomeDBiO54902.

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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: O54902-1) [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
MVLDPEEKIP 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 PLYGGVLITI ADTFVFLFLD
210 220 230 240 250
KYGLRKLEAF FGFLITIMAL TFGYEYVTVK PSQSQVLRGM FVPSCSGCHT
260 270 280 290 300
PQVEQAVGIV GAVIMPHNMY LHSALVKSRQ VNRANKQEVR EANKYFFIES
310 320 330 340 350
CIALFVSFII NVFVVSVFAE AFFEKTNEQV VEVCRNSSSP HADLFPNDNS
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 GILVLLVCSI NMYFVVVYVQ
510 520 530 540 550
ELGHVALYVV AAVVSVAYLG FVFYLGWQCL IALGLSFLDC GRSYHLGLTA
560
RPEIYLLNTV DAVSLVSR
Length:568
Mass (Da):62,277
Last modified:June 1, 1998 - v1
Checksum:iC7B77E964E741F4D
GO
Isoform 1 (identifier: O54902-2) [UniParc]FASTAAdd to basket
Also known as: IRE

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

Show »
Length:561
Mass (Da):61,310
Checksum:i2AEFE5E5EFFA48D4
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti185 – 1851G → R in microcytic anemia. 1 Publication

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei544 – 56825YHLGL…SLVSR → VSISKVLLSEDTSGGNTK in isoform 1. 1 PublicationVSP_003597Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF008439 mRNA. Translation: AAC53319.1.
AF029757 mRNA. Translation: AAC24495.1.
RefSeqiNP_037305.2. NM_013173.2.
UniGeneiRn.11418.

Genome annotation databases

GeneIDi25715.
KEGGirno:25715.
UCSCiRGD:3684. rat. [O54902-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF008439 mRNA. Translation: AAC53319.1.
AF029757 mRNA. Translation: AAC24495.1.
RefSeqiNP_037305.2. NM_013173.2.
UniGeneiRn.11418.

3D structure databases

ProteinModelPortaliO54902.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247744. 1 interaction.
STRINGi10116.ENSRNOP00000026531.

Protein family/group databases

TCDBi2.A.55.2.2. the metal ion (mn(2+)-iron) transporter (nramp) family.

PTM databases

PhosphoSiteiO54902.

Proteomic databases

PaxDbiO54902.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25715.
KEGGirno:25715.
UCSCiRGD:3684. rat. [O54902-1]

Organism-specific databases

CTDi4891.
RGDi3684. Slc11a2.

Phylogenomic databases

eggNOGiKOG1291. Eukaryota.
COG1914. LUCA.
HOGENOMiHOG000152203.
HOVERGENiHBG052665.
InParanoidiO54902.
KOiK12347.
OrthoDBiEOG091G05M9.
PhylomeDBiO54902.

Miscellaneous databases

PROiO54902.

Gene expression databases

BgeeiENSRNOG00000019550.
GenevisibleiO54902. RN.

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_RAT
AccessioniPrimary (citable) accession number: O54902
Secondary accession number(s): O35172
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 1, 1998
Last modified: September 7, 2016
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.