P49279 (NRAM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Natural resistance-associated macrophage protein 1
Short name=NRAMP 1

Gene names

Name:	SLC11A1
Synonyms:	LSH, NRAMP, NRAMP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	550 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
Subcellular location	Membrane; Multi-pass membrane protein Probable.
Tissue specificity	Macrophages; peripheral blood leukocytes, lung, spleen and liver.
Induction	In response to lymphokine or bacterial products.
Polymorphism	Genetic variation in SLC11A1 is associated with susceptibility to infection with Mycobacterium ulcerans [MIM:610446]. Genetic variations in SLC11A1 determine Mycobacterium tuberculosis susceptibility [MIM:607948].
Sequence similarities	Belongs to the NRAMP family.

Ontologies

Keywords
Biological process	Ion transport Iron transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Iron
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	L-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 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 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 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 dendritic cell antigen processing and presentation 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: Compara respiratory burst Inferred from sequence or structural similarity. Source: BHF-UCL 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 vacuolar acidification Inferred from sequence or structural similarity. Source: BHF-UCL wound healing Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	cell outer membrane Inferred from electronic annotation. Source: Compara integral to plasma membrane Non-traceable author statement Ref.2. Source: UniProtKB 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 tertiary granule membrane Inferred from direct assay PubMed 12070036. Source: BHF-UCL
Molecular_function	manganese ion transmembrane transporter activity Inferred from sequence or structural similarity. Source: BHF-UCL metal ion:hydrogen antiporter activity Inferred from genetic interaction PubMed 17932044. Source: BHF-UCL protein homodimerization activity Inferred from direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 550	550	Natural resistance-associated macrophage protein 1		PRO_0000212588
Regions
	Topological domain	1 – 58	58	Cytoplasmic Potential
	Transmembrane	59 – 76	18	Helical; Potential
	Topological domain	77 – 85	9	Extracellular Potential
	Transmembrane	86 – 105	20	Helical; Potential
	Topological domain	106 – 142	37	Cytoplasmic Potential
	Transmembrane	143 – 163	21	Helical; Potential
	Topological domain	164 – 167	4	Extracellular Potential
	Transmembrane	168 – 187	20	Helical; Potential
	Topological domain	188 – 196	9	Cytoplasmic Potential
	Transmembrane	197 – 217	21	Helical; Potential
	Topological domain	218 – 240	23	Extracellular Potential
	Transmembrane	241 – 259	19	Helical; Potential
	Topological domain	260 – 287	28	Cytoplasmic Potential
	Transmembrane	288 – 307	20	Helical; Potential
	Topological domain	308 – 349	42	Extracellular Potential
	Transmembrane	350 – 369	20	Helical; Potential
	Topological domain	370 – 400	31	Cytoplasmic Potential
	Transmembrane	401 – 418	18	Helical; Potential
	Topological domain	419 – 429	11	Extracellular Potential
	Transmembrane	430 – 450	21	Helical; Potential
	Topological domain	451 – 466	16	Cytoplasmic Potential
	Transmembrane	467 – 488	22	Helical; Potential
	Topological domain	489 – 496	8	Extracellular Potential
	Transmembrane	497 – 516	20	Helical; Potential
	Topological domain	517 – 550	34	Cytoplasmic Potential
	Compositional bias	3 – 80	78	Pro/Ser-rich
Amino acid modifications
	Glycosylation	324	1	N-linked (GlcNAc...) Potential
	Glycosylation	338	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	30	1	Q → R.		VAR_004629
	Natural variant	318	1	A → V. Ref.6		VAR_004630
	Natural variant	543	1	D → N Associated with susceptibility to infection with Mycobacterium ulcerans. Ref.6 Ref.8 Corresponds to variant rs17235409 [ dbSNP | Ensembl ].		VAR_004631
Experimental info
	Sequence conflict	54	1	S → R in CAA57541. Ref.5
	Sequence conflict	84	1	A → L Ref.5
	Sequence conflict	86	1	A → P Ref.5
	Sequence conflict	275	1	A → V in CAA57541. Ref.5
	Sequence conflict	305	1	V → A in CAA57541. Ref.5
	Sequence conflict	315	1	N → K in CAA57541. Ref.5
	Sequence conflict	397	1	R → S in CAA57541. Ref.5
	Sequence conflict	441	1	F → V in CAA57541. Ref.5
	Sequence conflict	478	1	A → T in CAA57541. Ref.5
	Sequence conflict	544	1	Q → H in CAA57541. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P49279 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: AA670763D52EEECC	FASTA	550	59,872
	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

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]. 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]. 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]	"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.
[5]	"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].
[6]	"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.
[7]	"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.
[8]	"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. D50402 mRNA. Translation: BAA08907.1. D50403 mRNA. Translation: BAA08908.1. D38171 mRNA. Translation: BAA07370.1. X82015 Genomic DNA. Translation: CAA57541.1.
IPI	IPI00290432.
PIR	I55679. JC4095.
RefSeq	NP_000569.3. NM_000578.3.
UniGene	Hs.591607.
3D structure databases
ProteinModelPortal	P49279.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000233202.
Protein family/group databases
TCDB	2.A.55.2.3. metal ion (Mn2+-iron) transporter (Nramp) family.
PTM databases
PhosphoSite	P49279.
Polymorphism databases
DMDM	1352521.
Proteomic databases
PaxDb	P49279.
PRIDE	P49279.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000233202; ENSP00000233202; ENSG00000018280.
GeneID	6556.
KEGG	hsa:6556.
UCSC	uc002vhu.1. human.
Organism-specific databases
CTD	6556.
GeneCards	GC02P219246.
HGNC	HGNC:10907. SLC11A1.
HPA	HPA029590.
MIM	600266. gene. 607948. phenotype. 610446. phenotype.
neXtProt	NX_P49279.
Orphanet	3389. Tuberculosis.
PharmGKB	PA319.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1914.
HOGENOM	HOG000152203.
HOVERGEN	HBG052665.
InParanoid	P49279.
KO	K12347.
OMA	AGPGYMV.
OrthoDB	EOG4RFKSH.
PhylomeDB	P49279.
Enzyme and pathway databases
Reactome	REACT_116125. Disease. REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	P49279.
Bgee	P49279.
CleanEx	HS_SLC11A1.
Genevestigator	P49279.
GermOnline	ENSG00000018280. Homo sapiens.
Family and domain databases
InterPro	IPR001046. Nat-R-assoc-macro_Nramp. [Graphical view]
PANTHER	PTHR11706. PTHR11706. 1 hit.
Pfam	PF01566. Nramp. 1 hit. [Graphical view]
PRINTS	PR00447. NATRESASSCMP.
TIGRFAMs	TIGR01197. nramp. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	6556.
NextBio	25511.
SOURCE	Search...

Entry information

Entry name

NRAM1_HUMAN

Accession

Primary (citable) accession number: P49279

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	May 1, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.