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Details on Person UniProt:P49281 SLC11A2
| Class:Id | ReferenceGeneProduct:60476 |
|---|---|
| _chainChangeLog | chain:1-568 added on Sat February 7 2015 |
| _displayName | UniProt:P49281 SLC11A2 |
| _timestamp | 2025-02-21 20:12:09 |
| chain | chain:1-568 |
| checksum | 4E45D6A448A23263 |
| comment | FUNCTION Proton-coupled metal ion symporter operating with a proton to metal ion stoichiometry of 1:1 (PubMed:17109629, PubMed:17293870, PubMed:22736759, PubMed:25326704, PubMed:25491917). Selectively transports various divalent metal cations, in decreasing affinity: Cd(2+) > Fe(2+) > Co(2+), Mn(2+) >> Zn(2+), Ni(2+), VO(2+) (PubMed:17109629, PubMed:17293870, PubMed:22736759, PubMed:25326704, PubMed:25491917). Essential for maintenance of iron homeostasis by modulating intestinal absorption of dietary Fe(2+) and TF-associated endosomal Fe(2+) transport in erythroid precursors and other cells (By similarity). Enables Fe(2+) and Mn(2+) ion entry into mitochondria, and is thus expected to promote mitochondrial heme synthesis, iron-sulfur cluster biogenesis and antioxidant defense (By similarity) (PubMed:24448823). Can mediate uncoupled fluxes of either protons or metal ions.CATALYTIC ACTIVITY Fe(2+)(in) + H(+)(in) = Fe(2+)(out) + H(+)(out)CATALYTIC ACTIVITY Fe(2+)(in) + H(+)(in) = Fe(2+)(out) + H(+)(out)CATALYTIC ACTIVITY Co(2+)(out) + H(+)(out) = Co(2+)(in) + H(+)(in)CATALYTIC ACTIVITY Cd(2+)(out) + H(+)(out) = Cd(2+)(in) + H(+)(in)CATALYTIC ACTIVITY Mn(2+)(in) + H(+)(in) = Mn(2+)(out) + H(+)(out)CATALYTIC ACTIVITY Zn(2+)(out) + H(+)(out) = Zn(2+)(in) + H(+)(in)CATALYTIC ACTIVITY Ni(2+)(out) + H(+)(out) = Ni(2+)(in) + H(+)(in)CATALYTIC ACTIVITY Fe(2+)(in) + H(+)(in) = Fe(2+)(out) + H(+)(out)CATALYTIC ACTIVITY Co(2+)(out) + H(+)(out) = Co(2+)(in) + H(+)(in)CATALYTIC ACTIVITY Cd(2+)(out) + H(+)(out) = Cd(2+)(in) + H(+)(in)CATALYTIC ACTIVITY Mn(2+)(in) + H(+)(in) = Mn(2+)(out) + H(+)(out)CATALYTIC ACTIVITY Zn(2+)(out) + H(+)(out) = Zn(2+)(in) + H(+)(in)CATALYTIC ACTIVITY Ni(2+)(out) + H(+)(out) = Ni(2+)(in) + H(+)(in)CATALYTIC ACTIVITY H(+)(in) = H(+)(out)CATALYTIC ACTIVITY Fe(2+)(in) = Fe(2+)(out)CATALYTIC ACTIVITY Fe(2+)(in) + H(+)(in) = Fe(2+)(out) + H(+)(out)BIOPHYSICOCHEMICAL PROPERTIES Optimum pH is 5.5-6.5 for Fe(2+) uptake.BIOPHYSICOCHEMICAL PROPERTIES 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 (PubMed:19706893). 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 (PubMed:24448823). Interacts with ARRDC1; this interaction regulates the incorporation of SLC11A2 into extracellular vesicles through an ubiquitination-dependent mechanism (PubMed:27462458). Interacts with ARRDC4; controls the incorporation of SLC11A2 into extracellular vesicles through an ubiquitination-dependent mechanism (PubMed:27462458).INTERACTION Predominantly localizes in early endosomes that underlie the apical membrane of polarized epithelia.SUBCELLULAR LOCATION Ubiquitously expressed. Expressed in erythroid progenitors.INDUCTION Up-regulated under iron-depletion conditions. Down-regulated in response to high extracellular iron levels.INDUCTION Up-regulated under iron-depletion conditions. Down-regulated in response to high extracellular iron levels.INDUCTION Up-regulated under iron-depletion conditions. Down-regulated in response to high extracellular iron levels.PTM Ubiquitinated by WWP2.PTM N-glycosylated.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS NRAMP2-mediated iron uptake is markedly stimulated by nifedipine in a concentration-dependent manner.SIMILARITY Belongs to the NRAMP family.CAUTION The capacity to transport copper ions remains controversial. |
| description | recommendedName: Natural resistance-associated macrophage protein 2 shortName: NRAMP 2 alternativeName: Divalent cation transporter 1 alternativeName: Divalent metal transporter 1 shortName: DMT-1 alternativeName: Solute carrier family 11 member 2 |
| geneName | SLC11A2 DCT1 DMT1 NRAMP2 OK/SW-cl.20 |
| identifier | P49281 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Cell membrane Disease variant Endosome Glycoprotein Golgi apparatus Ion transport Iron Iron transport Lysosome Membrane Mitochondrion Mitochondrion outer membrane Phosphoprotein Proteomics identification Reference proteome Symport Transmembrane Transmembrane helix Transport Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | SLC11A2 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8996139] ENSEMBL:ENSG00000110911 SLC11A2 [Homo sapiens] |
| secondaryIdentifier | NRAM2_HUMAN B3KT08 B4DK84 F5H741 O43288 O60932 O94801 Q498Z5 Q8IUD7 Q96J35 |
| sequenceLength | 568 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:151342] UniProt:P49281-2 SLC11A2 [Homo sapiens] [ReferenceIsoform:404173] UniProt:P49281-1 SLC11A2 [Homo sapiens] [ReferenceIsoform:8965718] UniProt:P49281-3 SLC11A2 [Homo sapiens] [ReferenceIsoform:8965719] UniProt:P49281-4 SLC11A2 [Homo sapiens] [ReferenceIsoform:8965720] UniProt:P49281-5 SLC11A2 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:435359] SLC11A2 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:5623707] SLC11A2 L104_P142del [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:5623732] SLC11A2 E399D [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:5623747] SLC11A2 V114del [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:5623758] SLC11A2 R416C [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:5623771] SLC11A2 G212V [plasma membrane] [Homo sapiens] |
| (referenceSequence) | [FragmentDeletionModification:5623679] Deletion of residues 104 to 142 [ReplacedResidue:5623684] L-arginine 416 replaced with L-cysteine [FragmentDeletionModification:5623688] Deletion of residues 114 to 114 [ReplacedResidue:5623693] L-glutamic acid 399 replaced with L-aspartic acid [ReplacedResidue:5623722] glycine 212 replaced with L-valine |
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No pathways have been reviewed or authored by UniProt:P49281 SLC11A2 (60476)
