O54902 · NRAM2_RAT
- ProteinNatural resistance-associated macrophage protein 2
- GeneSlc11a2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids568 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Proton-coupled metal ion symporter operating with a proton to metal ion stoichiometry of 1:1 (PubMed:16091957, PubMed:9242408).
Selectively transports various divalent metal cations, in decreasing affinity: Cd2+ > Fe2+ > Co2+, Mn2+ >> Zn2+, Ni2+, VO2+ (By similarity) (PubMed:16091957, PubMed:29317744, PubMed:9242408).
Essential for maintenance of iron homeostasis by modulating intestinal absorption of dietary Fe2+ and TF-associated endosomal Fe2+ transport in erythroid precursors and other cells (By similarity) (PubMed:9242408).
Enables Fe2+ and Mn2+ ion entry into mitochondria, and is thus expected to promote mitochondrial heme synthesis, iron-sulfur cluster biogenesis and antioxidant defense (PubMed:29317744).
Can mediate uncoupled fluxes of either protons or metal ions
Selectively transports various divalent metal cations, in decreasing affinity: Cd2+ > Fe2+ > Co2+, Mn2+ >> Zn2+, Ni2+, VO2+ (By similarity) (PubMed:16091957, PubMed:29317744, PubMed:9242408).
Essential for maintenance of iron homeostasis by modulating intestinal absorption of dietary Fe2+ and TF-associated endosomal Fe2+ transport in erythroid precursors and other cells (By similarity) (PubMed:9242408).
Enables Fe2+ and Mn2+ ion entry into mitochondria, and is thus expected to promote mitochondrial heme synthesis, iron-sulfur cluster biogenesis and antioxidant defense (PubMed:29317744).
Can mediate uncoupled fluxes of either protons or metal ions
Catalytic activity
Isoform 2
Fe2+(in) + H+(in) = Fe2+(out) + H+(out)This reaction proceeds in the forward and the backward directions.Isoform 2
Cd2+(out) + H+(out) = Cd2+(in) + H+(in)This reaction proceeds in the forward direction.Isoform 2
Co2+(out) + H+(out) = Co2+(in) + H+(in)This reaction proceeds in the forward direction.Isoform 2
H+(in) + Mn2+(in) = H+(out) + Mn2+(out)This reaction proceeds in the forward and the backward directions.Isoform 2
H+(out) + Zn2+(out) = H+(in) + Zn2+(in)This reaction proceeds in the forward direction.Isoform 2
H+(out) + Ni2+(out) = H+(in) + Ni2+(in)This reaction proceeds in the forward direction.Isoform 2
H+(in) = H+(out)Isoform 2
Fe2+(in) = Fe2+(out)
Activity regulation
Inhibited by 2-(3-carbamimidoylsulfanylmethyl-benzyl)-isothiourea.
Kinetics
Isoform 2
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.9 μM | Fe2+ | |||||
1.4 μM | H+ | |||||
1.3 μM | Fe2+ |
GO annotations
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameNatural resistance-associated macrophage protein 2
- Short namesNRAMP 2
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionO54902
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Golgi apparatus, trans-Golgi network membrane ; Multi-pass membrane protein
Early endosome membrane ; Multi-pass membrane protein
Recycling endosome membrane ; Multi-pass membrane protein
Late endosome membrane ; Multi-pass membrane protein
Lysosome membrane ; Multi-pass membrane protein
Apical cell membrane ; Multi-pass membrane protein
Mitochondrion outer membrane ; Multi-pass membrane protein
Extracellular vesicle membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-69 | Cytoplasmic | ||||
Sequence: MVLDPEEKIPDDGASGDHGDSASLGAINPAYSNSSLPHSTGDSEEPFTTYFDEKIPIPEEEYSCFSFRK | ||||||
Transmembrane | 70-90 | Helical | ||||
Sequence: LWAFTGPGFLMSIAYLDPGNI | ||||||
Topological domain | 91-95 | Extracellular | ||||
Sequence: ESDLQ | ||||||
Transmembrane | 96-117 | Helical | ||||
Sequence: SGAVAGFKLLWVLLLATIVGLL | ||||||
Topological domain | 118-154 | Cytoplasmic | ||||
Sequence: LQRLAARLGVVTGLHLAEVCHRQYPKVPRIILWLMVE | ||||||
Transmembrane | 155-175 | Helical | ||||
Sequence: LAIIGSDMQEVIGSAIAINLL | ||||||
Topological domain | 176-179 | Extracellular | ||||
Sequence: SAGR | ||||||
Transmembrane | 180-194 | Helical | ||||
Sequence: VPLYGGVLITIADTF | ||||||
Topological domain | 195-208 | Cytoplasmic | ||||
Sequence: VFLFLDKYGLRKLE | ||||||
Transmembrane | 209-229 | Helical | ||||
Sequence: AFFGFLITIMALTFGYEYVTV | ||||||
Topological domain | 230-255 | Extracellular | ||||
Sequence: KPSQSQVLRGMFVPSCSGCHTPQVEQ | ||||||
Transmembrane | 256-276 | Helical | ||||
Sequence: AVGIVGAVIMPHNMYLHSALV | ||||||
Topological domain | 277-301 | Cytoplasmic | ||||
Sequence: KSRQVNRANKQEVREANKYFFIESC | ||||||
Transmembrane | 302-322 | Helical | ||||
Sequence: IALFVSFIINVFVVSVFAEAF | ||||||
Topological domain | 323-360 | Extracellular | ||||
Sequence: FEKTNEQVVEVCRNSSSPHADLFPNDNSTLAVDIYKGG | ||||||
Transmembrane | 361-381 | Helical | ||||
Sequence: VVLGCYFGPAALYIWAVGILA | ||||||
Topological domain | 382-408 | Cytoplasmic | ||||
Sequence: AGQSSTMTGTYSGQFVMEGFLNLKWSR | ||||||
Transmembrane | 409-429 | Helical | ||||
Sequence: FARVILTRSIAIIPTLLVAVF | ||||||
Topological domain | 430-440 | Extracellular | ||||
Sequence: QDVEHLTGMND | ||||||
Transmembrane | 441-461 | Helical | ||||
Sequence: FLNVLQSLQLPFALIPILTFT | ||||||
Topological domain | 462-482 | Cytoplasmic | ||||
Sequence: SLRPVMSEFSNGIGWRIAGGI | ||||||
Transmembrane | 483-503 | Helical | ||||
Sequence: LVLLVCSINMYFVVVYVQELG | ||||||
Topological domain | 504-506 | Extracellular | ||||
Sequence: HVA | ||||||
Transmembrane | 507-527 | Helical | ||||
Sequence: LYVVAAVVSVAYLGFVFYLGW | ||||||
Topological domain | 528-568 | Cytoplasmic | ||||
Sequence: QCLIALGLSFLDCGRSYHLGLTARPEIYLLNTVDAVSLVSR |
Keywords
- Cellular component
Phenotypes & Variants
Involvement in disease
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | 185 | in microcytic anemia; impairs metal ion transport | ||||
Sequence: G → R | ||||||
Mutagenesis | 267 | Reduces expression at the plasma membrane. Does not affect H+-coupled Fe2+ transport. | ||||
Sequence: H → A | ||||||
Mutagenesis | 267 | Impairs expression at the plasma membrane. | ||||
Sequence: H → D or N | ||||||
Mutagenesis | 272 | Uncouples Fe2+ and H+ fluxes. Mediates facilitative Fe2+ transport independently of pH gradient. | ||||
Sequence: H → A | ||||||
Mutagenesis | 272 | Loss of proton-coupled Fe2+ transporter activity. | ||||
Sequence: H → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1 variant from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
PTM/Processing
Features
Showing features for chain, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000212596 | 1-568 | Natural resistance-associated macrophage protein 2 | |||
Sequence: MVLDPEEKIPDDGASGDHGDSASLGAINPAYSNSSLPHSTGDSEEPFTTYFDEKIPIPEEEYSCFSFRKLWAFTGPGFLMSIAYLDPGNIESDLQSGAVAGFKLLWVLLLATIVGLLLQRLAARLGVVTGLHLAEVCHRQYPKVPRIILWLMVELAIIGSDMQEVIGSAIAINLLSAGRVPLYGGVLITIADTFVFLFLDKYGLRKLEAFFGFLITIMALTFGYEYVTVKPSQSQVLRGMFVPSCSGCHTPQVEQAVGIVGAVIMPHNMYLHSALVKSRQVNRANKQEVREANKYFFIESCIALFVSFIINVFVVSVFAEAFFEKTNEQVVEVCRNSSSPHADLFPNDNSTLAVDIYKGGVVLGCYFGPAALYIWAVGILAAGQSSTMTGTYSGQFVMEGFLNLKWSRFARVILTRSIAIIPTLLVAVFQDVEHLTGMNDFLNVLQSLQLPFALIPILTFTSLRPVMSEFSNGIGWRIAGGILVLLVCSINMYFVVVYVQELGHVALYVVAAVVSVAYLGFVFYLGWQCLIALGLSFLDCGRSYHLGLTARPEIYLLNTVDAVSLVSR | ||||||
Glycosylation | 336 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 349 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 556 | In isoform O54902-2; Phosphoserine | ||||
Sequence: L | ||||||
Modified residue | 564 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 567 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Ubiquitinated by WWP2.
N-glycosylated.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Forms a complex with NDFIP1 and NEDD4L, in cortical neurons, in response to iron and cobalt exposure; this interaction leads to SLC11A2 ubiquitination by NEDD4L and proteasome-dependent degradation (By similarity).
Interacts with NDFIP1, NDFIP2 and WWP2; this interaction leads to SLC11A2 ubiquitination by WWP2 and subsequent proteasome-dependent degradation (By similarity).
Interacts with COX2 and TOM6 at the outer mitochondrion membrane. Interacts with ARRDC1; this interaction regulates the incorporation of SLC11A2 into extracellular vesicles through an ubiquitination-dependent mechanism (By similarity).
Interacts with ARRDC4; controls the incorporation of SLC11A2 into extracellular vesicles through an ubiquitination-dependent mechanism (By similarity).
Interacts with NDFIP1, NDFIP2 and WWP2; this interaction leads to SLC11A2 ubiquitination by WWP2 and subsequent proteasome-dependent degradation (By similarity).
Interacts with COX2 and TOM6 at the outer mitochondrion membrane. Interacts with ARRDC1; this interaction regulates the incorporation of SLC11A2 into extracellular vesicles through an ubiquitination-dependent mechanism (By similarity).
Interacts with ARRDC4; controls the incorporation of SLC11A2 into extracellular vesicles through an ubiquitination-dependent mechanism (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-15 | Basic and acidic residues | ||||
Sequence: MVLDPEEKIPDDGAS | ||||||
Region | 1-45 | Disordered | ||||
Sequence: MVLDPEEKIPDDGASGDHGDSASLGAINPAYSNSSLPHSTGDSEE | ||||||
Compositional bias | 26-45 | Polar residues | ||||
Sequence: AINPAYSNSSLPHSTGDSEE | ||||||
Region | 555-559 | Required for early endosome targeting | ||||
Sequence: YLLNT |
Sequence similarities
Belongs to the NRAMP family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
O54902-1
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.
- Name2
- SynonymsNon-IRE
- Length568
- Mass (Da)62,277
- Last updated1998-06-01 v1
- ChecksumC7B77E964E741F4D
O54902-2
- Name1
- SynonymsIRE
- Differences from canonical
- 544-568: YHLGLTARPEIYLLNTVDAVSLVSR → VSISKVLLSEDTSGGNTK
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0G2JT15 | A0A0G2JT15_RAT | Slc11a2 | 520 | ||
A0A0G2JTX4 | A0A0G2JTX4_RAT | Slc11a2 | 572 | ||
A0A8I6ABD7 | A0A8I6ABD7_RAT | Slc11a2 | 568 | ||
A0A140TAD8 | A0A140TAD8_RAT | Slc11a2 | 592 | ||
Q4QR92 | Q4QR92_RAT | Slc11a2 | 492 |
Features
Showing features for compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-15 | Basic and acidic residues | ||||
Sequence: MVLDPEEKIPDDGAS | ||||||
Compositional bias | 26-45 | Polar residues | ||||
Sequence: AINPAYSNSSLPHSTGDSEE | ||||||
Alternative sequence | VSP_003597 | 544-568 | in isoform 1 | |||
Sequence: YHLGLTARPEIYLLNTVDAVSLVSR → VSISKVLLSEDTSGGNTK |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF008439 EMBL· GenBank· DDBJ | AAC53319.1 EMBL· GenBank· DDBJ | mRNA | ||
AF029757 EMBL· GenBank· DDBJ | AAC24495.1 EMBL· GenBank· DDBJ | mRNA |