Human Gene SLC11A2 (ENST00000262052.9_9) from GENCODE V47lift37
  Description: Proton-coupled metal ion symporter operating with a proton to metal ion stoichiometry of 1:1 (PubMed:17109629, PubMed:22736759, PubMed:25491917, PubMed:17293870, PubMed:25326704). 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:22736759, PubMed:25491917, PubMed:17293870, PubMed:25326704). 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 (PubMed:24448823) (By similarity). Can mediate uncoupled fluxes of either protons or metal ions. (from UniProt P49281)
Gencode Transcript: ENST00000262052.9_9
Gencode Gene: ENSG00000110911.17_16
Transcript (Including UTRs)
   Position: hg19 chr12:51,379,775-51,420,167 Size: 40,393 Total Exon Count: 16 Strand: -
Coding Region
   Position: hg19 chr12:51,382,108-51,404,511 Size: 22,404 Coding Exon Count: 15 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:51,379,775-51,420,167)mRNA (may differ from genome)Protein (561 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblExonPrimerGeneCardsHGNC
MalacardsMGIPubMedReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: NRAM2_HUMAN
DESCRIPTION: RecName: Full=Natural resistance-associated macrophage protein 2; Short=NRAMP 2; AltName: Full=Divalent cation transporter 1; AltName: Full=Divalent metal transporter 1; Short=DMT-1;
FUNCTION: Important in metal transport, in particular iron. Can also transport manganese, cobalt, cadmium, nickel, vanadium 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.
BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 5.5-6.5 for Fe(2+) uptake;
SUBUNIT: 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.
SUBCELLULAR LOCATION: Endosome membrane; Multi-pass membrane protein.
TISSUE SPECIFICITY: Ubiquitously expressed. Isoform 1 is highly expressed in brain. Isoform 2 is highly expressed in spleen, thymus and pancreas. Isoform 3 and isoform 4 are abundantly expressed in duodenum and kidney.
PTM: Ubiquitinated by WWP2 (By similarity).
DISEASE: Defects in SLC11A2 are a cause of hypochromic microcytic anemia (HCMA) [MIM:206100]. The disease is characterized by an abnormal hemoglobin content in the erythrocytes which are reduced in size. It may be hereditary or acquired. Mutations in SLC11A2 are associated with progressive liver iron overload and normal to moderately elevated serum ferritin levels.
MISCELLANEOUS: NRAMP2-mediated iron uptake is markedly stimulated by nifedipine in a concentration-dependent manner.
SIMILARITY: Belongs to the NRAMP family.
SEQUENCE CAUTION: Sequence=AAH02592.1; Type=Erroneous initiation; Sequence=BAA34374.1; Type=Erroneous gene model prediction;

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: SLC11A2
Diseases sorted by gene-association score: anemia, hypochromic microcytic, with iron overload 1* (1581), hypochromic microcytic anemia with iron overload* (520), hypochromic microcytic anemia (35), microcytic anemia (33), hemosiderosis (16), deficiency anemia (15), hemochromatosis (15), iron deficiency anemia (14), hfe-associated hereditary hemochromatosis (13), iron metabolism disease (11), restless legs syndrome (6), atransferrinemia (5), metal metabolism disorder (4), parkinson disease, late-onset (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 14.10 RPKM in Thyroid
Total median expression: 373.65 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -43.50113-0.385 Picture PostScript Text
3' UTR -616.202333-0.264 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001046 - Nat-R-assoc-macro_Nramp

Pfam Domains:
PF01566 - Natural resistance-associated macrophage protein

ModBase Predicted Comparative 3D Structure on P49281
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005375 copper ion transmembrane transporter activity
GO:0005381 iron ion transmembrane transporter activity
GO:0005384 manganese ion transmembrane transporter activity
GO:0005385 zinc ion transmembrane transporter activity
GO:0005515 protein binding
GO:0015078 hydrogen ion transmembrane transporter activity
GO:0015086 cadmium ion transmembrane transporter activity
GO:0015087 cobalt ion transmembrane transporter activity
GO:0015093 ferrous iron transmembrane transporter activity
GO:0015094 lead ion transmembrane transporter activity
GO:0015099 nickel cation transmembrane transporter activity
GO:0015100 vanadium ion transmembrane transporter activity
GO:0015295 solute:proton symporter activity
GO:0022890 inorganic cation transmembrane transporter activity
GO:0046870 cadmium ion binding
GO:0046873 metal ion transmembrane transporter activity
GO:0046915 transition metal ion transmembrane transporter activity
GO:0015085 calcium ion transmembrane transporter activity
GO:0070835 chromium ion transmembrane transporter activity

Biological Process:
GO:0001666 response to hypoxia
GO:0003032 detection of oxygen
GO:0006778 porphyrin-containing compound metabolic process
GO:0006779 porphyrin-containing compound biosynthetic process
GO:0006783 heme biosynthetic process
GO:0006811 ion transport
GO:0006824 cobalt ion transport
GO:0006825 copper ion transport
GO:0006826 iron ion transport
GO:0006828 manganese ion transport
GO:0006879 cellular iron ion homeostasis
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0007611 learning or memory
GO:0010039 response to iron ion
GO:0015675 nickel cation transport
GO:0015676 vanadium ion transport
GO:0015684 ferrous iron transport
GO:0015692 lead ion transport
GO:0030001 metal ion transport
GO:0034599 cellular response to oxidative stress
GO:0035434 copper ion transmembrane transport
GO:0035444 nickel cation transmembrane transport
GO:0048813 dendrite morphogenesis
GO:0048821 erythrocyte development
GO:0055072 iron ion homeostasis
GO:0060586 multicellular organismal iron ion homeostasis
GO:0070574 cadmium ion transmembrane transport
GO:0070627 ferrous iron import
GO:0071421 manganese ion transmembrane transport
GO:0071577 zinc II ion transmembrane transport
GO:0098655 cation transmembrane transport
GO:1902600 hydrogen ion transmembrane transport
GO:1903874 ferrous iron transmembrane transport

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005741 mitochondrial outer membrane
GO:0005764 lysosome
GO:0005765 lysosomal membrane
GO:0005768 endosome
GO:0005769 early endosome
GO:0005770 late endosome
GO:0005773 vacuole
GO:0005802 trans-Golgi network
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0005903 brush border
GO:0009986 cell surface
GO:0010008 endosome membrane
GO:0012505 endomembrane system
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016324 apical plasma membrane
GO:0031410 cytoplasmic vesicle
GO:0031526 brush border membrane
GO:0031902 late endosome membrane
GO:0045177 apical part of cell
GO:0045178 basal part of cell
GO:0048471 perinuclear region of cytoplasm
GO:0055037 recycling endosome
GO:0070826 paraferritin complex
GO:1903561 extracellular vesicle
GO:0030904 retromer complex


-  Descriptions from all associated GenBank mRNAs
  AF064484 - Homo sapiens natural resistance-associated macrophage protein 2 non-IRE form (NRAMP2) mRNA, complete cds.
AK128640 - Homo sapiens cDNA FLJ46799 fis, clone TRACH3031678, highly similar to Natural resistance-associated macrophage protein 2.
JA482258 - Sequence 241 from Patent WO2011072091.
JA482259 - Sequence 242 from Patent WO2011072091.
JA482264 - Sequence 247 from Patent WO2011072091.
JE980550 - Sequence 241 from Patent EP2862929.
JE980551 - Sequence 242 from Patent EP2862929.
JE980556 - Sequence 247 from Patent EP2862929.
AB062284 - Homo sapiens OK/SW-cl.20 mRNA for natural resistance-associated macrophage protein 2 non-IRE form, complete cds.
KT455015 - Homo sapiens isolate LP-DMT1-TV3 natural resistance-associated macrophage protein 2 isoform 2 (SLC11A2) mRNA, complete cds.
JA482262 - Sequence 245 from Patent WO2011072091.
JE980554 - Sequence 245 from Patent EP2862929.
JA482261 - Sequence 244 from Patent WO2011072091.
JE980553 - Sequence 244 from Patent EP2862929.
BC100014 - Homo sapiens solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2, mRNA (cDNA clone MGC:110880 IMAGE:5300266), complete cds.
JA482260 - Sequence 243 from Patent WO2011072091.
JA482263 - Sequence 246 from Patent WO2011072091.
JE980552 - Sequence 243 from Patent EP2862929.
JE980555 - Sequence 246 from Patent EP2862929.
LF385081 - JP 2014500723-A/192584: Polycomb-Associated Non-Coding RNAs.
JA482257 - Sequence 240 from Patent WO2011072091.
JE980549 - Sequence 240 from Patent EP2862929.
AB004857 - Homo sapiens mRNA for NRAMP2, complete cds.
AL832886 - Homo sapiens mRNA; cDNA DKFZp667N193 (from clone DKFZp667N193).
MA620658 - JP 2018138019-A/192584: Polycomb-Associated Non-Coding RNAs.
JD045294 - Sequence 26318 from Patent EP1572962.
JD314330 - Sequence 295354 from Patent EP1572962.
JD363574 - Sequence 344598 from Patent EP1572962.
JD311252 - Sequence 292276 from Patent EP1572962.
JD081217 - Sequence 62241 from Patent EP1572962.
JD248888 - Sequence 229912 from Patent EP1572962.
JD087794 - Sequence 68818 from Patent EP1572962.
JD359790 - Sequence 340814 from Patent EP1572962.
JD265696 - Sequence 246720 from Patent EP1572962.
JD360066 - Sequence 341090 from Patent EP1572962.
JD268255 - Sequence 249279 from Patent EP1572962.
JD470916 - Sequence 451940 from Patent EP1572962.
JD505036 - Sequence 486060 from Patent EP1572962.
JD292251 - Sequence 273275 from Patent EP1572962.
JD026810 - Sequence 7834 from Patent EP1572962.
JD534043 - Sequence 515067 from Patent EP1572962.
JD029552 - Sequence 10576 from Patent EP1572962.
JD284427 - Sequence 265451 from Patent EP1572962.
JD354176 - Sequence 335200 from Patent EP1572962.
JD500368 - Sequence 481392 from Patent EP1572962.
JD220594 - Sequence 201618 from Patent EP1572962.
JD417308 - Sequence 398332 from Patent EP1572962.
JD563938 - Sequence 544962 from Patent EP1572962.
JD399831 - Sequence 380855 from Patent EP1572962.
JD553117 - Sequence 534141 from Patent EP1572962.
JD297817 - Sequence 278841 from Patent EP1572962.
JD410410 - Sequence 391434 from Patent EP1572962.
JD042764 - Sequence 23788 from Patent EP1572962.
JD539434 - Sequence 520458 from Patent EP1572962.
JD515898 - Sequence 496922 from Patent EP1572962.
JD091636 - Sequence 72660 from Patent EP1572962.
KP411015 - Homo sapiens clone IRE SLC11A2 mRNA, 3' UTR.
JD245115 - Sequence 226139 from Patent EP1572962.
BC002592 - Homo sapiens solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2, mRNA (cDNA clone MGC:1990 IMAGE:3160522), complete cds.
AK094735 - Homo sapiens cDNA FLJ37416 fis, clone BRAWH2000353, highly similar to Natural resistance-associated macrophage protein 2.
L37347 - Human integral membrane protein (Nramp2) mRNA, partial.
JD046434 - Sequence 27458 from Patent EP1572962.
JD310800 - Sequence 291824 from Patent EP1572962.
JD242270 - Sequence 223294 from Patent EP1572962.
JD254591 - Sequence 235615 from Patent EP1572962.
AK316507 - Homo sapiens cDNA, FLJ79406 complete cds, highly similar to Natural resistance-associated macrophage protein 2.
JD459362 - Sequence 440386 from Patent EP1572962.
AF046997 - Homo sapiens NRAMP2 iron transporter mRNA, complete cds.
AK296445 - Homo sapiens cDNA FLJ54692 complete cds, highly similar to Natural resistance-associated macrophage protein 2.
JD411780 - Sequence 392804 from Patent EP1572962.
AK315987 - Homo sapiens cDNA, FLJ78886 complete cds, highly similar to Natural resistance-associated macrophage protein 2.
GQ129269 - Synthetic construct Homo sapiens clone HAIB:100068666; DKFZo004C0436 solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2 protein (SLC11A2) gene, partial cds.
GQ129270 - Synthetic construct Homo sapiens clone HAIB:100068569; DKFZo008C0435 solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2 protein (SLC11A2) gene, complete cds.
AB529051 - Synthetic construct DNA, clone: pF1KB3655, Homo sapiens SLC11A2 gene for solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2, without stop codon, in Flexi system.
AJ493662 - Homo sapiens partial mRNA for divalent metal transporter (SLC11A2 gene), 5' splice variant 1A.
LF337986 - JP 2014500723-A/145489: Polycomb-Associated Non-Coding RNAs.
LF337988 - JP 2014500723-A/145491: Polycomb-Associated Non-Coding RNAs.
LF337989 - JP 2014500723-A/145492: Polycomb-Associated Non-Coding RNAs.
MA573563 - JP 2018138019-A/145489: Polycomb-Associated Non-Coding RNAs.
MA573565 - JP 2018138019-A/145491: Polycomb-Associated Non-Coding RNAs.
MA573566 - JP 2018138019-A/145492: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P49281 (Reactome details) participates in the following event(s):

R-HSA-435349 SLC11A2 cotransports Fe2+, H+ from extracellular region to cytosol
R-HSA-425410 Metal ion SLC transporters
R-HSA-917937 Iron uptake and transport
R-HSA-425366 Transport of bile salts and organic acids, metal ions and amine compounds
R-HSA-382551 Transport of small molecules
R-HSA-425407 SLC-mediated transmembrane transport

-  Other Names for This Gene
  Alternate Gene Symbols: B3KT08, B4DK84, DCT1, DMT1, ENST00000262052.1, ENST00000262052.2, ENST00000262052.3, ENST00000262052.4, ENST00000262052.5, ENST00000262052.6, ENST00000262052.7, ENST00000262052.8, F5H741, NRAM2_HUMAN, NRAMP2, NR_183179, O43288, O60932, O94801, OK/SW-cl.20, P49281, Q498Z5, Q8IUD7, Q96J35, uc317gwf.1, uc317gwf.2
UCSC ID: ENST00000262052.9_9
RefSeq Accession: NM_000617.3
Protein: P49281 (aka NRAM2_HUMAN or NRM2_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.