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Protein

Neutrophil gelatinase-associated lipocalin

Gene

LCN2

Organism
Homo sapiens (Human)
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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei126Catecholate-type ferric siderophore1
Binding sitei145Catecholate-type ferric siderophore1
Binding sitei154Catecholate-type ferric siderophore1

GO - Molecular functioni

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

BioCyciZFISH:ENSG00000148346-MONOMER.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
R-HSA-6799990. Metal sequestration by antimicrobial proteins.
R-HSA-917937. Iron uptake and transport.

Names & Taxonomyi

Protein namesi
Recommended name:
Neutrophil gelatinase-associated lipocalin
Short name:
NGAL
Alternative name(s):
25 kDa alpha-2-microglobulin-related subunit of MMP-9
Lipocalin-2
Oncogene 24p3
Siderocalin LCN2
p25
Gene namesi
Name:LCN2
Synonyms:HNL, NGAL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:6526. LCN2.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi3934.
OpenTargetsiENSG00000148346.
PharmGKBiPA30309.

Polymorphism and mutation databases

BioMutaiLCN2.
DMDMi1171700.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 201 PublicationAdd BLAST20
ChainiPRO_000001793321 – 198Neutrophil gelatinase-associated lipocalinAdd BLAST178

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei21Pyrrolidone carboxylic acid1 Publication1
Glycosylationi85N-linked (GlcNAc...)5 Publications1
Disulfide bondi96 ↔ 195

Keywords - PTMi

Disulfide bond, Glycoprotein, Pyrrolidone carboxylic acid

Proteomic databases

MaxQBiP80188.
PaxDbiP80188.
PeptideAtlasiP80188.
PRIDEiP80188.

PTM databases

PhosphoSitePlusiP80188.

Expressioni

Tissue specificityi

Expressed in bone marrow and in tissues that are prone to exposure to microorganism. High expression is found in bone marrow as well as in uterus, prostate, salivary gland, stomach, appendix, colon, trachea and lung. Not found in the small intestine or peripheral blood leukocytes.1 Publication

Inductioni

Expression is activated by the oncoprotein BCR-ABL; BCR-ABL misregulates expression via the JAK/STAT pathway and binding of STAT5A to the promoter.1 Publication

Gene expression databases

BgeeiENSG00000148346.
CleanExiHS_LCN2.
ExpressionAtlasiP80188. baseline and differential.
GenevisibleiP80188. HS.

Organism-specific databases

HPAiCAB016549.
CAB016550.
HPA002695.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
TXNDC5Q86UY04EBI-11911016,EBI-2825190

Protein-protein interaction databases

BioGridi110126. 16 interactors.
DIPiDIP-29952N.
IntActiP80188. 7 interactors.
STRINGi9606.ENSP00000277480.

Chemistry databases

BindingDBiP80188.

Structurei

Secondary structure

1198
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi33 – 35Combined sources3
Helixi44 – 47Combined sources4
Beta strandi49 – 60Combined sources12
Beta strandi64 – 66Combined sources3
Beta strandi73 – 78Combined sources6
Turni80 – 82Combined sources3
Beta strandi84 – 91Combined sources8
Beta strandi93 – 105Combined sources13
Beta strandi111 – 114Combined sources4
Beta strandi116 – 118Combined sources3
Beta strandi119 – 121Combined sources3
Beta strandi124 – 133Combined sources10
Beta strandi135 – 147Combined sources13
Beta strandi150 – 162Combined sources13
Helixi166 – 178Combined sources13
Helixi183 – 185Combined sources3
Turni194 – 196Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DFVX-ray2.60A/B21-197[»]
1L6MX-ray2.40A/B/C21-198[»]
1NGLNMR-A21-198[»]
1QQSX-ray2.40A24-197[»]
1X71X-ray2.10A/B/C21-198[»]
1X89X-ray2.10A/B/C21-198[»]
1X8UX-ray2.20A/B/C21-198[»]
3BY0X-ray2.57A/B/C1-198[»]
3CBCX-ray2.17A/B/C1-198[»]
3CMPX-ray2.80A/B/C1-198[»]
3DSZX-ray2.00A/B21-198[»]
3DTQX-ray2.50A/B/C21-198[»]
3FW4X-ray2.30A/B/C21-198[»]
3FW5X-ray2.30A/B/C21-198[»]
3HWDX-ray2.95A/B/C1-198[»]
3HWEX-ray2.80A/B/C1-198[»]
3HWFX-ray3.20A/B/C1-198[»]
3HWGX-ray2.19A/B/C1-198[»]
3I0AX-ray2.60A/B/C1-198[»]
3K3LX-ray2.62A/B/C21-198[»]
3PECX-ray2.19A/B/C21-198[»]
3PEDX-ray2.30A/B/C21-198[»]
3T1DX-ray2.30A/B/C1-198[»]
3TF6X-ray2.35A/B/C21-198[»]
3TZSX-ray2.45A/B/C21-198[»]
3U03X-ray2.40A/C1-198[»]
3U0DX-ray2.51A/B/C/D1-198[»]
4GH7X-ray2.60A/C21-198[»]
4IAWX-ray2.40A/B/C21-198[»]
4IAXX-ray1.90A21-198[»]
4K19X-ray2.74A/B/C21-198[»]
4MVIX-ray1.70A21-198[»]
4MVKX-ray1.50A21-198[»]
4MVLX-ray2.30A/B/C/D21-198[»]
4QAEX-ray2.10A/B/C/D/E/F21-198[»]
4ZFXX-ray2.55A/B/C21-198[»]
4ZHCX-ray2.04A/B/C21-198[»]
4ZHDX-ray2.05A/B/C21-198[»]
4ZHFX-ray2.45A/B/C/D/E/F21-198[»]
4ZHGX-ray2.05A/B/C/D/E/F21-198[»]
4ZHHX-ray2.04A/B/C/D/E/F21-198[»]
5JR8X-ray2.65A/B21-198[»]
ProteinModelPortaliP80188.
SMRiP80188.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP80188.

Family & Domainsi

Sequence similaritiesi

Belongs to the calycin superfamily. Lipocalin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410JAXJ. Eukaryota.
ENOG4111A75. LUCA.
GeneTreeiENSGT00530000063610.
HOVERGENiHBG106490.
InParanoidiP80188.
PhylomeDBiP80188.
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]

Sequences (2)i

Sequence statusi: Complete.

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

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

Isoform 1 (identifier: P80188-1) [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
MPLGLLWLGL ALLGALHAQA QDSTSDLIPA PPLSKVPLQQ NFQDNQFQGK
60 70 80 90 100
WYVVGLAGNA ILREDKDPQK MYATIYELKE DKSYNVTSVL FRKKKCDYWI
110 120 130 140 150
RTFVPGCQPG EFTLGNIKSY PGLTSYLVRV VSTNYNQHAM VFFKKVSQNR
160 170 180 190
EYFKITLYGR TKELTSELKE NFIRFSKSLG LPENHIVFPV PIDQCIDG
Length:198
Mass (Da):22,588
Last modified:November 1, 1995 - v2
Checksum:iCD761805723FEF1E
GO
Isoform 2 (identifier: P80188-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     193-198: DQCIDG → GNGQSG

Show »
Length:198
Mass (Da):22,457
Checksum:iCD691E83A0AD3F1E
GO

Sequence cautioni

The sequence CAI13824 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti9G → R in BAG63166 (PubMed:14702039).Curated1
Sequence conflicti13L → S in CAG46889 (Ref. 4) Curated1
Sequence conflicti82K → N AA sequence (PubMed:1281792).Curated1
Sequence conflicti155I → V AA sequence (PubMed:1281792).Curated1
Sequence conflicti178S → Y in CAA67574 (PubMed:9339356).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_039780193 – 198DQCIDG → GNGQSG in isoform 2. 1 Publication6

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X83006 mRNA. Translation: CAA58127.1.
X99133 Genomic DNA. Translation: CAA67574.1.
AK301694 mRNA. Translation: BAG63166.1.
AK316217 mRNA. Translation: BAH14588.1.
CR542092 mRNA. Translation: CAG46889.1.
AL590708 Genomic DNA. Translation: CAI13823.1.
AL590708 Genomic DNA. Translation: CAI13824.1. Sequence problems.
CH471090 Genomic DNA. Translation: EAW87750.1.
BC033089 mRNA. Translation: AAH33089.1.
S75256 mRNA. Translation: AAD14168.1.
CCDSiCCDS6892.1. [P80188-1]
PIRiJC2339.
RefSeqiNP_005555.2. NM_005564.4. [P80188-1]
UniGeneiHs.204238.

Genome annotation databases

EnsembliENST00000277480; ENSP00000277480; ENSG00000148346. [P80188-1]
ENST00000373017; ENSP00000362108; ENSG00000148346. [P80188-1]
GeneIDi3934.
KEGGihsa:3934.
UCSCiuc004bto.1. human. [P80188-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X83006 mRNA. Translation: CAA58127.1.
X99133 Genomic DNA. Translation: CAA67574.1.
AK301694 mRNA. Translation: BAG63166.1.
AK316217 mRNA. Translation: BAH14588.1.
CR542092 mRNA. Translation: CAG46889.1.
AL590708 Genomic DNA. Translation: CAI13823.1.
AL590708 Genomic DNA. Translation: CAI13824.1. Sequence problems.
CH471090 Genomic DNA. Translation: EAW87750.1.
BC033089 mRNA. Translation: AAH33089.1.
S75256 mRNA. Translation: AAD14168.1.
CCDSiCCDS6892.1. [P80188-1]
PIRiJC2339.
RefSeqiNP_005555.2. NM_005564.4. [P80188-1]
UniGeneiHs.204238.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DFVX-ray2.60A/B21-197[»]
1L6MX-ray2.40A/B/C21-198[»]
1NGLNMR-A21-198[»]
1QQSX-ray2.40A24-197[»]
1X71X-ray2.10A/B/C21-198[»]
1X89X-ray2.10A/B/C21-198[»]
1X8UX-ray2.20A/B/C21-198[»]
3BY0X-ray2.57A/B/C1-198[»]
3CBCX-ray2.17A/B/C1-198[»]
3CMPX-ray2.80A/B/C1-198[»]
3DSZX-ray2.00A/B21-198[»]
3DTQX-ray2.50A/B/C21-198[»]
3FW4X-ray2.30A/B/C21-198[»]
3FW5X-ray2.30A/B/C21-198[»]
3HWDX-ray2.95A/B/C1-198[»]
3HWEX-ray2.80A/B/C1-198[»]
3HWFX-ray3.20A/B/C1-198[»]
3HWGX-ray2.19A/B/C1-198[»]
3I0AX-ray2.60A/B/C1-198[»]
3K3LX-ray2.62A/B/C21-198[»]
3PECX-ray2.19A/B/C21-198[»]
3PEDX-ray2.30A/B/C21-198[»]
3T1DX-ray2.30A/B/C1-198[»]
3TF6X-ray2.35A/B/C21-198[»]
3TZSX-ray2.45A/B/C21-198[»]
3U03X-ray2.40A/C1-198[»]
3U0DX-ray2.51A/B/C/D1-198[»]
4GH7X-ray2.60A/C21-198[»]
4IAWX-ray2.40A/B/C21-198[»]
4IAXX-ray1.90A21-198[»]
4K19X-ray2.74A/B/C21-198[»]
4MVIX-ray1.70A21-198[»]
4MVKX-ray1.50A21-198[»]
4MVLX-ray2.30A/B/C/D21-198[»]
4QAEX-ray2.10A/B/C/D/E/F21-198[»]
4ZFXX-ray2.55A/B/C21-198[»]
4ZHCX-ray2.04A/B/C21-198[»]
4ZHDX-ray2.05A/B/C21-198[»]
4ZHFX-ray2.45A/B/C/D/E/F21-198[»]
4ZHGX-ray2.05A/B/C/D/E/F21-198[»]
4ZHHX-ray2.04A/B/C/D/E/F21-198[»]
5JR8X-ray2.65A/B21-198[»]
ProteinModelPortaliP80188.
SMRiP80188.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110126. 16 interactors.
DIPiDIP-29952N.
IntActiP80188. 7 interactors.
STRINGi9606.ENSP00000277480.

Chemistry databases

BindingDBiP80188.

PTM databases

PhosphoSitePlusiP80188.

Polymorphism and mutation databases

BioMutaiLCN2.
DMDMi1171700.

Proteomic databases

MaxQBiP80188.
PaxDbiP80188.
PeptideAtlasiP80188.
PRIDEiP80188.

Protocols and materials databases

DNASUi3934.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000277480; ENSP00000277480; ENSG00000148346. [P80188-1]
ENST00000373017; ENSP00000362108; ENSG00000148346. [P80188-1]
GeneIDi3934.
KEGGihsa:3934.
UCSCiuc004bto.1. human. [P80188-1]

Organism-specific databases

CTDi3934.
DisGeNETi3934.
GeneCardsiLCN2.
HGNCiHGNC:6526. LCN2.
HPAiCAB016549.
CAB016550.
HPA002695.
MIMi600181. gene.
neXtProtiNX_P80188.
OpenTargetsiENSG00000148346.
PharmGKBiPA30309.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JAXJ. Eukaryota.
ENOG4111A75. LUCA.
GeneTreeiENSGT00530000063610.
HOVERGENiHBG106490.
InParanoidiP80188.
PhylomeDBiP80188.
TreeFamiTF336103.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000148346-MONOMER.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
R-HSA-6799990. Metal sequestration by antimicrobial proteins.
R-HSA-917937. Iron uptake and transport.

Miscellaneous databases

ChiTaRSiLCN2. human.
EvolutionaryTraceiP80188.
GeneWikiiLCN2.
GenomeRNAii3934.
PROiP80188.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000148346.
CleanExiHS_LCN2.
ExpressionAtlasiP80188. baseline and differential.
GenevisibleiP80188. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P80188
Secondary accession number(s): A6NII8
, B4DWV4, B7ZAA2, P30150, Q5SYV9, Q5SYW0, Q6FGL5, Q92683
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: November 1, 1995
Last modified: November 30, 2016
This is version 173 of the entry and version 2 of the sequence. [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

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

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.