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Protein

Neutrophil gelatinase-associated lipocalin

Gene

Lcn2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development. Binds iron through association with 2,5-dihydroxybenzoic acid (2,5-DHBA), a siderophore that shares structural similarities with bacterial enterobactin, and delivers or removes iron from the cell, depending on the context. Iron-bound form (holo-24p3) is internalized following binding to the SLC22A17 (24p3R) receptor, leading to release of iron and subsequent increase of intracellular iron concentration. In contrast, association of the iron-free form (apo-24p3) with the SLC22A17 (24p3R) receptor is followed by association with an intracellular siderophore, iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration. Involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis, while iron-free form decreases intracellular iron levels, inducing expression of the proapoptotic protein BCL2L11/BIM, resulting in apoptosis. Involved in innate immunity, possibly by sequestrating iron, leading to limit bacterial growth.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei128Catecholate-type ferric siderophoreBy similarity1
Binding sitei147Catecholate-type ferric siderophoreBy similarity1
Binding sitei156Catecholate-type ferric siderophoreBy similarity1

GO - Molecular functioni

  • iron ion binding Source: UniProtKB
  • small molecule binding Source: InterPro
  • transporter activity Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis, Immunity, Innate immunity, Ion transport, Iron transport, Transport

Keywords - Ligandi

Iron

Enzyme and pathway databases

ReactomeiR-MMU-917937. Iron uptake and transport.

Names & Taxonomyi

Protein namesi
Recommended name:
Neutrophil gelatinase-associated lipocalin
Short name:
NGAL
Alternative name(s):
Lipocalin-2
SV-40-induced 24P3 protein
Siderocalin LCN2
p25
Gene namesi
Name:Lcn2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:96757. Lcn2.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: MGI
  • extracellular region Source: UniProtKB
  • extracellular space Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

Mice are normal with no visible phenotype. They however show an increased susceptibility to bacterial infections. Neutrophils show significantly less bacteriostatic activity.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20By similarityAdd BLAST20
ChainiPRO_000001793421 – 200Neutrophil gelatinase-associated lipocalinAdd BLAST180

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei21Pyrrolidone carboxylic acidBy similarity1
Glycosylationi81N-linked (GlcNAc...)Sequence analysis1
Glycosylationi85N-linked (GlcNAc...)1 Publication1
Disulfide bondi98 ↔ 1971 Publication

Post-translational modificationi

N-glycosylated.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Pyrrolidone carboxylic acid

Proteomic databases

MaxQBiP11672.
PaxDbiP11672.
PeptideAtlasiP11672.
PRIDEiP11672.

PTM databases

PhosphoSitePlusiP11672.

Expressioni

Tissue specificityi

Detected in lung, spleen, uterus, vagina and epididymis.1 Publication

Inductioni

Upon Toll-like receptor (TLRs) stimuli. By SV-40.1 Publication

Gene expression databases

BgeeiENSMUSG00000026822.
CleanExiMM_LCN2.
ExpressionAtlasiP11672. baseline and differential.
GenevisibleiP11672. MM.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Heterodimer; disulfide-linked with MMP9.1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000053962.

Structurei

Secondary structure

1200
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni33 – 35Combined sources3
Turni44 – 47Combined sources4
Beta strandi49 – 58Combined sources10
Turni63 – 65Combined sources3
Beta strandi73 – 78Combined sources6
Beta strandi84 – 91Combined sources8
Beta strandi98 – 107Combined sources10
Beta strandi113 – 117Combined sources5
Helixi119 – 121Combined sources3
Beta strandi125 – 135Combined sources11
Beta strandi137 – 149Combined sources13
Beta strandi152 – 164Combined sources13
Helixi168 – 180Combined sources13
Helixi185 – 187Combined sources3
Beta strandi188 – 192Combined sources5
Beta strandi195 – 197Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3S26X-ray1.80A21-200[»]
3U9PX-ray2.80C/D21-200[»]
ProteinModelPortaliP11672.
SMRiP11672.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the calycin superfamily. Lipocalin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410JAXJ. Eukaryota.
ENOG4111A75. LUCA.
GeneTreeiENSGT00530000063610.
HOGENOMiHOG000231660.
HOVERGENiHBG106490.
InParanoidiP11672.
PhylomeDBiP11672.
TreeFamiTF336103.

Family and domain databases

Gene3Di2.40.128.20. 1 hit.
InterProiIPR012674. Calycin.
IPR011038. Calycin-like.
IPR003087. LCN2/LCN12.
IPR002345. Lipocalin.
IPR022272. Lipocalin_CS.
IPR000566. Lipocln_cytosolic_FA-bd_dom.
[Graphical view]
PfamiPF00061. Lipocalin. 1 hit.
[Graphical view]
PRINTSiPR00179. LIPOCALIN.
PR01275. NGELATINASE.
SUPFAMiSSF50814. SSF50814. 1 hit.
PROSITEiPS00213. LIPOCALIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P11672-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALSVMCLGL ALLGVLQSQA QDSTQNLIPA PSLLTVPLQP DFRSDQFRGR
60 70 80 90 100
WYVVGLAGNA VQKKTEGSFT MYSTIYELQE NNSYNVTSIL VRDQDQGCRY
110 120 130 140 150
WIRTFVPSSR AGQFTLGNMH RYPQVQSYNV QVATTDYNQF AMVFFRKTSE
160 170 180 190 200
NKQYFKITLY GRTKELSPEL KERFTRFAKS LGLKDDNIIF SVPTDQCIDN
Length:200
Mass (Da):22,875
Last modified:October 1, 1989 - v1
Checksum:iDD9A8D08750E6863
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14607 mRNA. Translation: CAA32762.1.
X81627 Genomic DNA. Translation: CAA57283.1.
AK149774 mRNA. Translation: BAE29077.1.
AL808027 Genomic DNA. Translation: CAM15869.1.
CH466542 Genomic DNA. Translation: EDL08545.1.
BC132069 mRNA. Translation: AAI32070.1.
BC132071 mRNA. Translation: AAI32072.1.
S82469 mRNA. No translation available.
CCDSiCCDS15913.1.
PIRiS07397.
RefSeqiNP_032517.1. NM_008491.1.
UniGeneiMm.9537.

Genome annotation databases

EnsembliENSMUST00000050785; ENSMUSP00000053962; ENSMUSG00000026822.
GeneIDi16819.
KEGGimmu:16819.
UCSCiuc008jfl.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14607 mRNA. Translation: CAA32762.1.
X81627 Genomic DNA. Translation: CAA57283.1.
AK149774 mRNA. Translation: BAE29077.1.
AL808027 Genomic DNA. Translation: CAM15869.1.
CH466542 Genomic DNA. Translation: EDL08545.1.
BC132069 mRNA. Translation: AAI32070.1.
BC132071 mRNA. Translation: AAI32072.1.
S82469 mRNA. No translation available.
CCDSiCCDS15913.1.
PIRiS07397.
RefSeqiNP_032517.1. NM_008491.1.
UniGeneiMm.9537.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3S26X-ray1.80A21-200[»]
3U9PX-ray2.80C/D21-200[»]
ProteinModelPortaliP11672.
SMRiP11672.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000053962.

PTM databases

PhosphoSitePlusiP11672.

Proteomic databases

MaxQBiP11672.
PaxDbiP11672.
PeptideAtlasiP11672.
PRIDEiP11672.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000050785; ENSMUSP00000053962; ENSMUSG00000026822.
GeneIDi16819.
KEGGimmu:16819.
UCSCiuc008jfl.1. mouse.

Organism-specific databases

CTDi3934.
MGIiMGI:96757. Lcn2.

Phylogenomic databases

eggNOGiENOG410JAXJ. Eukaryota.
ENOG4111A75. LUCA.
GeneTreeiENSGT00530000063610.
HOGENOMiHOG000231660.
HOVERGENiHBG106490.
InParanoidiP11672.
PhylomeDBiP11672.
TreeFamiTF336103.

Enzyme and pathway databases

ReactomeiR-MMU-917937. Iron uptake and transport.

Miscellaneous databases

ChiTaRSiLcn2. mouse.
PROiP11672.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000026822.
CleanExiMM_LCN2.
ExpressionAtlasiP11672. baseline and differential.
GenevisibleiP11672. MM.

Family and domain databases

Gene3Di2.40.128.20. 1 hit.
InterProiIPR012674. Calycin.
IPR011038. Calycin-like.
IPR003087. LCN2/LCN12.
IPR002345. Lipocalin.
IPR022272. Lipocalin_CS.
IPR000566. Lipocln_cytosolic_FA-bd_dom.
[Graphical view]
PfamiPF00061. Lipocalin. 1 hit.
[Graphical view]
PRINTSiPR00179. LIPOCALIN.
PR01275. NGELATINASE.
SUPFAMiSSF50814. SSF50814. 1 hit.
PROSITEiPS00213. LIPOCALIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNGAL_MOUSE
AccessioniPrimary (citable) accession number: P11672
Secondary accession number(s): Q3UE34
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: November 2, 2016
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.