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Protein

Neutrophil gelatinase-associated lipocalin

Gene

LCN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Biological processApoptosis, Immunity, Innate immunity, Ion transport, Iron transport, Transport
LigandIron

Enzyme and pathway databases

ReactomeiR-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-6798695 Neutrophil degranulation
R-HSA-6799990 Metal sequestration by antimicrobial proteins
R-HSA-917937 Iron uptake and transport
SIGNORiP80188

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

EuPathDBiHostDB:ENSG00000148346.11
HGNCiHGNC:6526 LCN2
MIMi600181 gene
neXtProtiNX_P80188

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

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi3934
OpenTargetsiENSG00000148346
PharmGKBiPA30309

Chemistry databases

DrugBankiDB01926 Carboxymycobactin S
DB04043 Carboxymycobactin T
DB01631 Methyl Nonanoate (Ester)

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...) asparagine5 Publications1
Disulfide bondi96 ↔ 195

Keywords - PTMi

Disulfide bond, Glycoprotein, Pyrrolidone carboxylic acid

Proteomic databases

MaxQBiP80188
PaxDbiP80188
PeptideAtlasiP80188
PRIDEiP80188

PTM databases

iPTMnetiP80188
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

Show more details

Protein-protein interaction databases

BioGridi110126, 25 interactors
DIPiDIP-29952N
IntActiP80188, 67 interactors
MINTiP80188
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
Turni119 – 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[»]
5KHPX-ray2.65A/B/C21-198[»]
5KICX-ray2.70A/B/C21-198[»]
5KIDX-ray2.15A/B/C21-198[»]
5MHHX-ray2.00A21-198[»]
5N47X-ray3.00A/C/E21-198[»]
5N48X-ray1.60A/C21-198[»]
5NKNX-ray2.20A25-198[»]
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
KOiK21129
PhylomeDBiP80188
TreeFamiTF336103

Family and domain databases

Gene3Di2.40.128.20, 1 hit
InterProiView protein in InterPro
IPR012674 Calycin
IPR003087 LCN2/LCN12
IPR002345 Lipocalin
IPR022272 Lipocalin_CS
IPR000566 Lipocln_cytosolic_FA-bd_dom
PANTHERiPTHR11430 PTHR11430, 1 hit
PfamiView protein in Pfam
PF00061 Lipocalin, 1 hit
PRINTSiPR01275 NGELATINASE
SUPFAMiSSF50814 SSF50814, 1 hit
PROSITEiView protein in PROSITE
PS00213 LIPOCALIN, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiNGAL_HUMAN
AccessioniPrimary (citable) accession number: P80188
Secondary accession number(s): A6NII8
, B4DWV4, B7ZAA2, P30150, Q5SYV9, Q5SYW0, Q6FGL5, Q92683
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: November 1, 1995
Last modified: May 23, 2018
This is version 188 of the entry and version 2 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

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

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