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P49279 (NRAM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Natural resistance-associated macrophage protein 1

Short name=NRAMP 1
Alternative name(s):
Solute carrier family 11 member 1
Gene names
Name:SLC11A1
Synonyms:LSH, NRAMP, NRAMP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length550 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Divalent transition metal (iron and manganese) transporter involved in iron metabolism and host resistance to certain pathogens. Macrophage-specific membrane transport function. Controls natural resistance to infection with intracellular parasites. Pathogen resistance involves sequestration of Fe2+ and Mn2+, cofactors of both prokaryotic and eukaryotic catalases and superoxide dismutases, not only to protect the macrophage against its own generation of reactive oxygen species, but to deny the cations to the pathogen for synthesis of its protective enzymes. HAMAP-Rule MF_00221

Subcellular location

Membrane; Multi-pass membrane protein Probable HAMAP-Rule MF_00221.

Tissue specificity

Macrophages; peripheral blood leukocytes, lung, spleen and liver.

Induction

In response to lymphokine or bacterial products. HAMAP-Rule MF_00221

Polymorphism

Genetic variation in SLC11A1 is associated with susceptibility to infection with Mycobacterium ulcerans [MIM:610446]. HAMAP-Rule MF_00221

Genetic variations in SLC11A1 determine Mycobacterium tuberculosis susceptibility [MIM:607948]. HAMAP-Rule MF_00221

Sequence similarities

Belongs to the NRAMP family.

Ontologies

Keywords
   Biological processIon transport
Iron transport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandIron
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processL-arginine import

Inferred from sequence or structural similarity. Source: BHF-UCL

MHC class II biosynthetic process

Inferred from sequence or structural similarity. Source: BHF-UCL

T cell cytokine production

Inferred from sequence or structural similarity. Source: BHF-UCL

T cell proliferation involved in immune response

Inferred from sequence or structural similarity. Source: BHF-UCL

activation of protein kinase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

antigen processing and presentation of peptide antigen

Inferred from sequence or structural similarity. Source: BHF-UCL

cadmium ion transmembrane transport

Inferred from genetic interaction PubMed 17932044. Source: BHF-UCL

cellular cadmium ion homeostasis

Inferred from genetic interaction PubMed 17932044. Source: BHF-UCL

cellular iron ion homeostasis

Inferred from mutant phenotype PubMed 16510578. Source: BHF-UCL

defense response to Gram-negative bacterium

Inferred from sequence or structural similarity. Source: BHF-UCL

defense response to bacterium

Inferred from sequence or structural similarity. Source: BHF-UCL

defense response to protozoan

Inferred from sequence or structural similarity. Source: BHF-UCL

divalent metal ion export

Inferred from sequence or structural similarity PubMed 17932044. Source: BHF-UCL

inflammatory response

Inferred from sequence or structural similarity. Source: BHF-UCL

interaction with host

Traceable author statement. Source: Reactome

interleukin-2 production

Inferred from sequence or structural similarity. Source: BHF-UCL

interleukin-3 production

Inferred from sequence or structural similarity. Source: BHF-UCL

iron ion homeostasis

Inferred from sequence or structural similarity. Source: BHF-UCL

iron ion transport

Inferred from mutant phenotype PubMed 16510578. Source: BHF-UCL

mRNA stabilization

Inferred from sequence or structural similarity. Source: BHF-UCL

macrophage activation

Inferred from sequence or structural similarity. Source: BHF-UCL

manganese ion transport

Inferred from sequence or structural similarity. Source: BHF-UCL

multicellular organismal iron ion homeostasis

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of cytokine production

Inferred from sequence or structural similarity. Source: BHF-UCL

nitrite transport

Inferred from sequence or structural similarity. Source: BHF-UCL

phagocytosis

Inferred from sequence or structural similarity. Source: BHF-UCL

phagosome maturation

Traceable author statement. Source: Reactome

positive regulation of T-helper 1 type immune response

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of cytokine production

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of dendritic cell antigen processing and presentation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of gene expression

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of interferon-gamma production

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of phagocytosis

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

protein import into nucleus, translocation

Inferred from electronic annotation. Source: Ensembl

respiratory burst

Inferred from sequence or structural similarity. Source: BHF-UCL

response to bacterium

Inferred from direct assay Ref.9. Source: UniProtKB

response to interferon-gamma

Inferred from sequence or structural similarity. Source: BHF-UCL

response to lipopolysaccharide

Inferred from sequence or structural similarity. Source: BHF-UCL

transmembrane transport

Traceable author statement. Source: Reactome

vacuolar acidification

Inferred from sequence or structural similarity. Source: BHF-UCL

wound healing

Inferred from sequence or structural similarity. Source: BHF-UCL

   Cellular_componentcell outer membrane

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Non-traceable author statement Ref.2. Source: UniProtKB

late endosome

Inferred from sequence or structural similarity. Source: BHF-UCL

late endosome membrane

Traceable author statement. Source: Reactome

lysosome

Inferred from sequence or structural similarity. Source: BHF-UCL

phagocytic vesicle membrane

Inferred from direct assay PubMed 12070036. Source: BHF-UCL

plasma membrane

Inferred from mutant phenotype PubMed 17932044. Source: BHF-UCL

tertiary granule membrane

Inferred from direct assay PubMed 12070036. Source: BHF-UCL

   Molecular_functionmanganese ion transmembrane transporter activity

Inferred from sequence or structural similarity. Source: BHF-UCL

metal ion:proton antiporter activity

Inferred from genetic interaction PubMed 17932044. Source: BHF-UCL

protein homodimerization activity

Inferred from direct assay Ref.2. Source: UniProtKB

transition metal ion transmembrane transporter activity

Inferred from genetic interaction PubMed 17932044. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P49279-1)

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.
Isoform 2 (identifier: P49279-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-13: MTGDKGPQRLSGS → MVRCQLTATSTSQ
     14-131: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 550550Natural resistance-associated macrophage protein 1 HAMAP-Rule MF_00221
PRO_0000212588

Regions

Topological domain1 – 5858Cytoplasmic Potential
Transmembrane59 – 7618Helical; Potential
Topological domain77 – 859Extracellular Potential
Transmembrane86 – 10520Helical; Potential
Topological domain106 – 14237Cytoplasmic Potential
Transmembrane143 – 16321Helical; Potential
Topological domain164 – 1674Extracellular Potential
Transmembrane168 – 18720Helical; Potential
Topological domain188 – 1969Cytoplasmic Potential
Transmembrane197 – 21721Helical; Potential
Topological domain218 – 24023Extracellular Potential
Transmembrane241 – 25919Helical; Potential
Topological domain260 – 28728Cytoplasmic Potential
Transmembrane288 – 30720Helical; Potential
Topological domain308 – 34942Extracellular Potential
Transmembrane350 – 36920Helical; Potential
Topological domain370 – 40031Cytoplasmic Potential
Transmembrane401 – 41818Helical; Potential
Topological domain419 – 42911Extracellular Potential
Transmembrane430 – 45021Helical; Potential
Topological domain451 – 46616Cytoplasmic Potential
Transmembrane467 – 48822Helical; Potential
Topological domain489 – 4968Extracellular Potential
Transmembrane497 – 51620Helical; Potential
Topological domain517 – 55034Cytoplasmic Potential
Compositional bias3 – 8078Pro/Ser-rich HAMAP-Rule MF_00221

Amino acid modifications

Glycosylation3241N-linked (GlcNAc...) Potential
Glycosylation3381N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 1313MTGDK…RLSGS → MVRCQLTATSTSQ in isoform 2.
VSP_047875
Alternative sequence14 – 131118Missing in isoform 2.
VSP_047876
Natural variant301Q → R.
VAR_004629
Natural variant3181A → V. Ref.9
Corresponds to variant rs201565523 [ dbSNP | Ensembl ].
VAR_004630
Natural variant5431D → N Associated with susceptibility to infection with Mycobacterium ulcerans. Ref.9 Ref.11
Corresponds to variant rs17235409 [ dbSNP | Ensembl ].
VAR_004631

Experimental info

Sequence conflict541S → R in CAA57541. Ref.8
Sequence conflict841A → L Ref.8
Sequence conflict861A → P Ref.8
Sequence conflict2751A → V in CAA57541. Ref.8
Sequence conflict3051V → A in CAA57541. Ref.8
Sequence conflict3151N → K in CAA57541. Ref.8
Sequence conflict3971R → S in CAA57541. Ref.8
Sequence conflict4411F → V in CAA57541. Ref.8
Sequence conflict4781A → T in CAA57541. Ref.8
Sequence conflict5441Q → H in CAA57541. Ref.8

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1996. Version 1.
Checksum: AA670763D52EEECC

FASTA55059,872
        10         20         30         40         50         60 
MTGDKGPQRL SGSSYGSISS PTSPTSPGPQ QAPPRETYLS EKIPIPDTKP GTFSLRKLWA 

        70         80         90        100        110        120 
FTGPGFLMSI AFLDPGNIES DLQAGAVAGF KLLWVLLWAT VLGLLCQRLA ARLGVVTGKD 

       130        140        150        160        170        180 
LGEVCHLYYP KVPRTVLWLT IELAIVGSDM QEVIGTAIAF NLLSAGRIPL WGGVLITIVD 

       190        200        210        220        230        240 
TFFFLFLDNY GLRKLEAFFG LLITIMALTF GYEYVVARPE QGALLRGLFL PSCPGCGHPE 

       250        260        270        280        290        300 
LLQAVGIVGA IIMPHNIYLH SALVKSREID RARRADIREA NMYFLIEATI ALSVSFIINL 

       310        320        330        340        350        360 
FVMAVFGQAF YQKTNQAAFN ICANSSLHDY AKIFPMNNAT VAVDIYQGGV ILGCLFGPAA 

       370        380        390        400        410        420 
LYIWAIGLLA AGQSSTMTGT YAGQFVMEGF LRLRWSRFAR VLLTRSCAIL PTVLVAVFRD 

       430        440        450        460        470        480 
LRDLSGLNDL LNVLQSLLLP FAVLPILTFT SMPTLMQEFA NGLLNKVVTS SIMVLVCAIN 

       490        500        510        520        530        540 
LYFVVSYLPS LPHPAYFGLA ALLAAAYLGL STYLVWTCCL AHGATFLAHS SHHHFLYGLL 

       550 
EEDQKGETSG 

« Hide

Isoform 2 [UniParc].

Checksum: 1C005994A512B944
Show »

FASTA43247,292

References

« Hide 'large scale' references
[1]"Human natural resistance-associated macrophage protein: cDNA cloning, chromosomal mapping, genomic organization, and tissue-specific expression."
Cellier M., Govoni G., Vidal S., Kwan T., Groulx N., Liu J., Sanchez F., Skamene E., Schurr E., Gros P.
J. Exp. Med. 180:1741-1752(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
Tissue: Spleen.
[2]"Identification of natural resistance-associated macrophage protein in peripheral blood lymphocytes."
Kishi F., Nobumoto M.
Immunol. Lett. 47:93-96(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Spleen.
[3]"Complete nucleotide sequence and genomic structure of the human NRAMP1 gene region on chromosome region 2q35."
Marquet S., Lepage P., Hudson T.J., Musser J.M., Schurr E.
Mamm. Genome 11:755-762(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Blood.
[7]"Isolation and characterization of human Nramp cDNA."
Kishi F.
Biochem. Biophys. Res. Commun. 204:1074-1080(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 68-550 (ISOFORM 1).
[8]"Genomic organization and sequence of the human NRAMP gene: identification and mapping of a promoter region polymorphism."
Blackwell J.M., Barton C.H., White J.K., Searle S., Baker A.-M., Williams H., Shaw M.-A.
Mol. Med. 1:194-205(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[9]"Identification of polymorphisms and sequence variants in the human homologue of the mouse natural resistance-associated macrophage protein gene."
Liu J., Fujiwara T.M., Buu N.T., Sanchez F.O., Cellier M., Paradis A.J., Frappier D., Skamene E., Gros P., Morgan K., Schurr E.
Am. J. Hum. Genet. 56:845-853(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VAL-318 AND ASN-543.
[10]"Alleles of the NRAMP1 gene are risk factors for pediatric tuberculosis disease."
Malik S., Abel L., Tooker H., Poon A., Simkin L., Girard M., Adams G.J., Starke J.R., Smith K.C., Graviss E.A., Musser J.M., Schurr E.
Proc. Natl. Acad. Sci. U.S.A. 102:12183-12188(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MYCOBACTERIUM TUBERCULOSIS SUSCEPTIBILITY.
[11]"Susceptibility to Buruli ulcer is associated with the SLC11A1 (NRAMP1) D543N polymorphism."
Stienstra Y., van der Werf T.S., Oosterom E., Nolte I.M., van der Graaf W.T.A., Etuaful S., Raghunathan P.L., Whitney E.A.S., Ampadu E.O., Asamoa K., Klutse E.Y., te Meerman G.J., Tappero J.W., Ashford D.A., van der Steege G.
Genes Immun. 7:185-189(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION OF VARIANT ASN-543 WITH SUSCEPTIBILITY TO INFECTION WITH MYCOBACTERIUM ULCERANS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L32185 mRNA. Translation: AAA57521.1.
L38593, L38592 Genomic DNA. Translation: AAA57557.1.
AF229163 Genomic DNA. Translation: AAG15405.1.
AC021016 Genomic DNA. No translation available.
CH471063 Genomic DNA. Translation: EAW70611.1.
BC071165 mRNA. Translation: AAH71165.1.
D50402 mRNA. Translation: BAA08907.1.
D50403 mRNA. Translation: BAA08908.1.
D38171 mRNA. Translation: BAA07370.1.
X82015 Genomic DNA. Translation: CAA57541.1.
CCDSCCDS2415.1. [P49279-1]
PIRI55679.
JC4095.
RefSeqNP_000569.3. NM_000578.3. [P49279-1]
XP_005246850.1. XM_005246793.1.
XP_005246851.1. XM_005246794.1.
XP_006712772.1. XM_006712709.1. [P49279-2]
XP_006712773.1. XM_006712710.1. [P49279-2]
UniGeneHs.591607.

3D structure databases

ProteinModelPortalP49279.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000233202.

Chemistry

ChEMBLCHEMBL2052040.

Protein family/group databases

TCDB2.A.55.2.3. the metal ion (mn(2+)-iron) transporter (nramp) family.

PTM databases

PhosphoSiteP49279.

Polymorphism databases

DMDM1352521.

Proteomic databases

PaxDbP49279.
PRIDEP49279.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000233202; ENSP00000233202; ENSG00000018280. [P49279-1]
ENST00000539932; ENSP00000443435; ENSG00000018280. [P49279-2]
GeneID6556.
KEGGhsa:6556.
UCSCuc002vhu.1. human. [P49279-1]
uc002vhw.3. human.

Organism-specific databases

CTD6556.
GeneCardsGC02P219246.
HGNCHGNC:10907. SLC11A1.
HPAHPA029590.
MIM600266. gene.
607948. phenotype.
610446. phenotype.
neXtProtNX_P49279.
Orphanet3389. Tuberculosis.
PharmGKBPA319.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1914.
HOGENOMHOG000152203.
HOVERGENHBG052665.
InParanoidP49279.
KOK12347.
OMATSMPTLM.
OrthoDBEOG77127K.
PhylomeDBP49279.
TreeFamTF315185.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.
REACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressP49279.
BgeeP49279.
CleanExHS_SLC11A1.
GenevestigatorP49279.

Family and domain databases

HAMAPMF_00221. NRAMP.
InterProIPR001046. NRAMP-like.
[Graphical view]
PANTHERPTHR11706. PTHR11706. 1 hit.
PfamPF01566. Nramp. 1 hit.
[Graphical view]
PRINTSPR00447. NATRESASSCMP.
TIGRFAMsTIGR01197. nramp. 1 hit.
ProtoNetSearch...

Other

GeneWikiSLC11A1.
GenomeRNAi6556.
NextBio25511.
PROP49279.
SOURCESearch...

Entry information

Entry nameNRAM1_HUMAN
AccessionPrimary (citable) accession number: P49279
Secondary accession number(s): C0H5Y3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: July 9, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM