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Protein

Natural resistance-associated macrophage protein 1

Gene

SLC11A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

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.

GO - Molecular functioni

  • manganese ion transmembrane transporter activity Source: BHF-UCL
  • metal ion:proton antiporter activity Source: BHF-UCL
  • protein homodimerization activity Source: UniProtKB
  • transition metal ion transmembrane transporter activity Source: BHF-UCL

GO - Biological processi

Keywordsi

Biological processIon transport, Iron transport, Transport
LigandIron

Enzyme and pathway databases

ReactomeiR-HSA-1222556 ROS, RNS production in phagocytes
R-HSA-425410 Metal ion SLC transporters
R-HSA-6798695 Neutrophil degranulation
R-HSA-6803544 Ion influx/efflux at host-pathogen interface
SIGNORiP49279

Protein family/group databases

TCDBi2.A.55.2.3 the metal ion (mn(2+)-iron) transporter (nramp) family

Names & Taxonomyi

Protein namesi
Recommended name:
Natural resistance-associated macrophage protein 1
Short name:
NRAMP 1
Alternative name(s):
Solute carrier family 11 member 1
Gene namesi
Name:SLC11A1
Synonyms:LSH, NRAMP, NRAMP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000018280.16
HGNCiHGNC:10907 SLC11A1
MIMi600266 gene
neXtProtiNX_P49279

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 58CytoplasmicSequence analysisAdd BLAST58
Transmembranei59 – 76HelicalSequence analysisAdd BLAST18
Topological domaini77 – 85ExtracellularSequence analysis9
Transmembranei86 – 105HelicalSequence analysisAdd BLAST20
Topological domaini106 – 142CytoplasmicSequence analysisAdd BLAST37
Transmembranei143 – 163HelicalSequence analysisAdd BLAST21
Topological domaini164 – 167ExtracellularSequence analysis4
Transmembranei168 – 187HelicalSequence analysisAdd BLAST20
Topological domaini188 – 196CytoplasmicSequence analysis9
Transmembranei197 – 217HelicalSequence analysisAdd BLAST21
Topological domaini218 – 240ExtracellularSequence analysisAdd BLAST23
Transmembranei241 – 259HelicalSequence analysisAdd BLAST19
Topological domaini260 – 287CytoplasmicSequence analysisAdd BLAST28
Transmembranei288 – 307HelicalSequence analysisAdd BLAST20
Topological domaini308 – 349ExtracellularSequence analysisAdd BLAST42
Transmembranei350 – 369HelicalSequence analysisAdd BLAST20
Topological domaini370 – 400CytoplasmicSequence analysisAdd BLAST31
Transmembranei401 – 418HelicalSequence analysisAdd BLAST18
Topological domaini419 – 429ExtracellularSequence analysisAdd BLAST11
Transmembranei430 – 450HelicalSequence analysisAdd BLAST21
Topological domaini451 – 466CytoplasmicSequence analysisAdd BLAST16
Transmembranei467 – 488HelicalSequence analysisAdd BLAST22
Topological domaini489 – 496ExtracellularSequence analysis8
Transmembranei497 – 516HelicalSequence analysisAdd BLAST20
Topological domaini517 – 550CytoplasmicSequence analysisAdd BLAST34

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi6556
MalaCardsiSLC11A1
MIMi607948 phenotype
610446 phenotype
OpenTargetsiENSG00000018280
Orphaneti3389 Tuberculosis
PharmGKBiPA319

Chemistry databases

ChEMBLiCHEMBL2052040

Polymorphism and mutation databases

BioMutaiSLC11A1
DMDMi1352521

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002125881 – 550Natural resistance-associated macrophage protein 1Add BLAST550

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi324N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi338N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP49279
PeptideAtlasiP49279
PRIDEiP49279

PTM databases

iPTMnetiP49279
PhosphoSitePlusiP49279

Expressioni

Tissue specificityi

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

Inductioni

In response to lymphokine or bacterial products.

Gene expression databases

BgeeiENSG00000018280
CleanExiHS_SLC11A1
ExpressionAtlasiP49279 baseline and differential
GenevisibleiP49279 HS

Organism-specific databases

HPAiHPA029590

Interactioni

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

STRINGi9606.ENSP00000233202

Chemistry databases

BindingDBiP49279

Structurei

3D structure databases

ProteinModelPortaliP49279
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi3 – 80Pro/Ser-richAdd BLAST78

Sequence similaritiesi

Belongs to the NRAMP family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1291 Eukaryota
COG1914 LUCA
GeneTreeiENSGT00390000006526
HOGENOMiHOG000152203
HOVERGENiHBG052665
InParanoidiP49279
KOiK12347
OMAiGYNLFLH
OrthoDBiEOG091G05M9
PhylomeDBiP49279
TreeFamiTF315185

Family and domain databases

HAMAPiMF_00221 NRAMP, 1 hit
InterProiView protein in InterPro
IPR001046 NRAMP_fam
PANTHERiPTHR11706 PTHR11706, 1 hit
PfamiView protein in Pfam
PF01566 Nramp, 1 hit
PRINTSiPR00447 NATRESASSCMP
TIGRFAMsiTIGR01197 nramp, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P49279-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MTGDKGPQRL SGSSYGSISS PTSPTSPGPQ QAPPRETYLS EKIPIPDTKP
60 70 80 90 100
GTFSLRKLWA FTGPGFLMSI AFLDPGNIES DLQAGAVAGF KLLWVLLWAT
110 120 130 140 150
VLGLLCQRLA ARLGVVTGKD LGEVCHLYYP KVPRTVLWLT IELAIVGSDM
160 170 180 190 200
QEVIGTAIAF NLLSAGRIPL WGGVLITIVD TFFFLFLDNY GLRKLEAFFG
210 220 230 240 250
LLITIMALTF GYEYVVARPE QGALLRGLFL PSCPGCGHPE LLQAVGIVGA
260 270 280 290 300
IIMPHNIYLH SALVKSREID RARRADIREA NMYFLIEATI ALSVSFIINL
310 320 330 340 350
FVMAVFGQAF YQKTNQAAFN ICANSSLHDY AKIFPMNNAT VAVDIYQGGV
360 370 380 390 400
ILGCLFGPAA LYIWAIGLLA AGQSSTMTGT YAGQFVMEGF LRLRWSRFAR
410 420 430 440 450
VLLTRSCAIL PTVLVAVFRD LRDLSGLNDL LNVLQSLLLP FAVLPILTFT
460 470 480 490 500
SMPTLMQEFA NGLLNKVVTS SIMVLVCAIN LYFVVSYLPS LPHPAYFGLA
510 520 530 540 550
ALLAAAYLGL STYLVWTCCL AHGATFLAHS SHHHFLYGLL EEDQKGETSG
Length:550
Mass (Da):59,872
Last modified:February 1, 1996 - v1
Checksum:iAA670763D52EEECC
GO
Isoform 2 (identifier: P49279-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-13: MTGDKGPQRLSGS → MVRCQLTATSTSQ
     14-131: Missing.

Note: No experimental confirmation available.
Show »
Length:432
Mass (Da):47,292
Checksum:i1C005994A512B944
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti54S → R in CAA57541 (PubMed:8529098).Curated1
Sequence conflicti84A → L (PubMed:8529098).Curated1
Sequence conflicti86A → P (PubMed:8529098).Curated1
Sequence conflicti275A → V in CAA57541 (PubMed:8529098).Curated1
Sequence conflicti305V → A in CAA57541 (PubMed:8529098).Curated1
Sequence conflicti315N → K in CAA57541 (PubMed:8529098).Curated1
Sequence conflicti397R → S in CAA57541 (PubMed:8529098).Curated1
Sequence conflicti441F → V in CAA57541 (PubMed:8529098).Curated1
Sequence conflicti478A → T in CAA57541 (PubMed:8529098).Curated1
Sequence conflicti544Q → H in CAA57541 (PubMed:8529098).Curated1

Polymorphismi

Genetic variation in SLC11A1 is associated with susceptibility to infection with Mycobacterium ulcerans [MIMi:610446].
Genetic variations in SLC11A1 determine Mycobacterium tuberculosis susceptibility [MIMi:607948].

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00462930Q → R. Corresponds to variant dbSNP:rs751872662Ensembl.1
Natural variantiVAR_004630318A → V1 PublicationCorresponds to variant dbSNP:rs201565523Ensembl.1
Natural variantiVAR_004631543D → N Associated with susceptibility to infection with Mycobacterium ulcerans. 1 PublicationCorresponds to variant dbSNP:rs17235409EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0478751 – 13MTGDK…RLSGS → MVRCQLTATSTSQ in isoform 2. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_04787614 – 131Missing in isoform 2. 1 PublicationAdd BLAST118

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS2415.1 [P49279-1]
PIRiI55679
JC4095
RefSeqiNP_000569.3, NM_000578.3 [P49279-1]
XP_005246850.1, XM_005246793.3
XP_005246851.1, XM_005246794.3 [P49279-2]
XP_006712772.1, XM_006712709.3 [P49279-2]
XP_006712773.1, XM_006712710.3 [P49279-2]
XP_016860255.1, XM_017004766.1
UniGeneiHs.591607

Genome annotation databases

EnsembliENST00000233202; ENSP00000233202; ENSG00000018280 [P49279-1]
GeneIDi6556
KEGGihsa:6556
UCSCiuc002vhv.3 human [P49279-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNRAM1_HUMAN
AccessioniPrimary (citable) accession number: P49279
Secondary accession number(s): C0H5Y3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: May 23, 2018
This is version 158 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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