NGAL_RAT
ID NGAL_RAT Reviewed; 198 AA.
AC P30152; Q5HZF1;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Neutrophil gelatinase-associated lipocalin;
DE Short=NGAL;
DE AltName: Full=Alpha-2-microglobulin-related protein {ECO:0000303|PubMed:2462726};
DE AltName: Full=Alpha-2U globulin-related protein;
DE AltName: Full=Lipocalin 24p3 {ECO:0000303|PubMed:12453413};
DE AltName: Full=Lipocalin-2;
DE AltName: Full=Siderocalin LCN2;
DE AltName: Full=p25;
DE Flags: Precursor;
GN Name=Lcn2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2462726; DOI=10.1093/nar/16.23.11368;
RA Chan Y.-L., Paz V., Wool I.G.;
RT "The primary structure of rat alpha 2 mu globulin-related protein.";
RL Nucleic Acids Res. 16:11368-11368(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=12453413; DOI=10.1016/s1097-2765(02)00710-4;
RA Yang J., Goetz D., Li J.Y., Wang W., Mori K., Setlik D., Du T.,
RA Erdjument-Bromage H., Tempst P., Strong R., Barasch J.;
RT "An iron delivery pathway mediated by a lipocalin.";
RL Mol. Cell 10:1045-1056(2002).
RN [4]
RP STRUCTURE BY NMR OF 21-198, AND DISULFIDE BOND.
RX PubMed=21538546; DOI=10.1002/prot.23031;
RA Peng Y., Zhang X., Liu J., Liu Q., Guo C., Zhang Y., Lin D.;
RT "Solution structure of the protein lipocalin 12 from rat epididymis.";
RL Proteins 79:2316-2320(2011).
CC -!- FUNCTION: Iron-trafficking protein involved in multiple processes such
CC as apoptosis, innate immunity and renal development (By similarity).
CC Binds iron through association with 2,3-dihydroxybenzoic acid (2,3-
CC DHBA), a siderophore that shares structural similarities with bacterial
CC enterobactin, and delivers or removes iron from the cell, depending on
CC the context. Iron-bound form (holo-24p3) is internalized following
CC binding to the SLC22A17 (24p3R) receptor, leading to release of iron
CC and subsequent increase of intracellular iron concentration. In
CC contrast, association of the iron-free form (apo-24p3) with the
CC SLC22A17 (24p3R) receptor is followed by association with an
CC intracellular siderophore, iron chelation and iron transfer to the
CC extracellular medium, thereby reducing intracellular iron
CC concentration. Involved in apoptosis due to interleukin-3 (IL3)
CC deprivation: iron-loaded form increases intracellular iron
CC concentration without promoting apoptosis, while iron-free form
CC decreases intracellular iron levels, inducing expression of the
CC proapoptotic protein BCL2L11/BIM, resulting in apoptosis (By
CC similarity). Involved in innate immunity; limits bacterial
CC proliferation by sequestering iron bound to microbial siderophores,
CC such as enterobactin. Can also bind siderophores from M.tuberculosis
CC (By similarity). {ECO:0000250|UniProtKB:P11672,
CC ECO:0000250|UniProtKB:P80188}.
CC -!- SUBUNIT: Monomer. Homodimer; disulfide-linked. Heterodimer; disulfide-
CC linked with MMP9. {ECO:0000250|UniProtKB:P80188}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P80188}.
CC Cytoplasmic granule lumen {ECO:0000250|UniProtKB:P80188}. Cytoplasmic
CC vesicle lumen {ECO:0000250|UniProtKB:P80188}. Note=Upon binding to the
CC SLC22A17 (24p3R) receptor, it is internalized (By similarity). Releases
CC the bound iron in the acidic lumen of cytoplasmic vesicles (By
CC similarity). {ECO:0000250|UniProtKB:P11672,
CC ECO:0000250|UniProtKB:P80188}.
CC -!- TISSUE SPECIFICITY: Detected in the ureteric bud in embryonic kidney
CC (at protein level). {ECO:0000269|PubMed:12453413}.
CC -!- SIMILARITY: Belongs to the calycin superfamily. Lipocalin family.
CC {ECO:0000305}.
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DR EMBL; X13295; CAA31657.1; -; mRNA.
DR EMBL; BC089053; AAH89053.1; -; mRNA.
DR PIR; S01989; S01989.
DR RefSeq; NP_570097.1; NM_130741.1.
DR PDB; 2K23; NMR; -; A=21-198.
DR PDBsum; 2K23; -.
DR AlphaFoldDB; P30152; -.
DR BMRB; P30152; -.
DR SMR; P30152; -.
DR STRING; 10116.ENSRNOP00000018776; -.
DR GlyGen; P30152; 1 site.
DR iPTMnet; P30152; -.
DR PhosphoSitePlus; P30152; -.
DR PaxDb; P30152; -.
DR PRIDE; P30152; -.
DR Ensembl; ENSRNOT00000018776; ENSRNOP00000018776; ENSRNOG00000013973.
DR GeneID; 170496; -.
DR KEGG; rno:170496; -.
DR UCSC; RGD:69408; rat.
DR CTD; 3934; -.
DR RGD; 69408; Lcn2.
DR eggNOG; ENOG502T7VZ; Eukaryota.
DR GeneTree; ENSGT01050000244868; -.
DR HOGENOM; CLU_094061_2_0_1; -.
DR InParanoid; P30152; -.
DR OMA; IDKCIDD; -.
DR OrthoDB; 1341030at2759; -.
DR PhylomeDB; P30152; -.
DR TreeFam; TF336103; -.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-6799990; Metal sequestration by antimicrobial proteins.
DR Reactome; R-RNO-917937; Iron uptake and transport.
DR EvolutionaryTrace; P30152; -.
DR PRO; PR:P30152; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000013973; Expressed in ovary and 19 other tissues.
DR Genevisible; P30152; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0060205; C:cytoplasmic vesicle lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:1903981; F:enterobactin binding; IPI:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
DR GO; GO:0002020; F:protease binding; IPI:RGD.
DR GO; GO:0036094; F:small molecule binding; IEA:InterPro.
DR GO; GO:0006953; P:acute-phase response; IEP:RGD.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IEP:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:RGD.
DR GO; GO:0036295; P:cellular response to increased oxygen levels; IEP:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
DR GO; GO:0071354; P:cellular response to interleukin-6; IEP:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEP:RGD.
DR GO; GO:0031669; P:cellular response to nutrient levels; IEP:RGD.
DR GO; GO:0090650; P:cellular response to oxygen-glucose deprivation; IEP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0071481; P:cellular response to X-ray; IEP:RGD.
DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0007616; P:long-term memory; IMP:RGD.
DR GO; GO:0110091; P:negative regulation of hippocampal neuron apoptotic process; IMP:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IGI:RGD.
DR GO; GO:0031346; P:positive regulation of cell projection organization; IDA:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:RGD.
DR GO; GO:1905956; P:positive regulation of endothelial tube morphogenesis; IDA:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:RGD.
DR GO; GO:1904440; P:positive regulation of iron ion import across plasma membrane; IDA:RGD.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:1901216; P:positive regulation of neuron death; IDA:RGD.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; IDA:RGD.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IMP:RGD.
DR GO; GO:0009617; P:response to bacterium; IEP:RGD.
DR GO; GO:0009637; P:response to blue light; IEP:RGD.
DR GO; GO:0009750; P:response to fructose; IEP:RGD.
DR GO; GO:0009635; P:response to herbicide; IDA:RGD.
DR GO; GO:0010040; P:response to iron(II) ion; IEP:RGD.
DR GO; GO:0010046; P:response to mycotoxin; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0006979; P:response to oxidative stress; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR GO; GO:0009615; P:response to virus; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:RGD.
DR GO; GO:0097577; P:sequestering of iron ion; ISS:UniProtKB.
DR GO; GO:0007614; P:short-term memory; IMP:RGD.
DR GO; GO:0015891; P:siderophore transport; ISS:UniProtKB.
DR Gene3D; 2.40.128.20; -; 1.
DR InterPro; IPR012674; Calycin.
DR InterPro; IPR003087; LCN2/LCN12.
DR InterPro; IPR002345; Lipocalin.
DR InterPro; IPR000566; Lipocln_cytosolic_FA-bd_dom.
DR PANTHER; PTHR11430; PTHR11430; 1.
DR Pfam; PF00061; Lipocalin; 1.
DR PRINTS; PR01275; NGELATINASE.
DR SUPFAM; SSF50814; SSF50814; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Cytoplasmic vesicle; Disulfide bond; Glycoprotein;
KW Immunity; Innate immunity; Ion transport; Iron; Iron transport;
KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal;
KW Transport.
FT SIGNAL 1..20
FT /evidence="ECO:0000250"
FT CHAIN 21..198
FT /note="Neutrophil gelatinase-associated lipocalin"
FT /id="PRO_0000017935"
FT BINDING 72..74
FT /ligand="a carboxymycobactin"
FT /ligand_id="ChEBI:CHEBI:178051"
FT /evidence="ECO:0000250|UniProtKB:P80188"
FT BINDING 126
FT /ligand="enterobactin"
FT /ligand_id="ChEBI:CHEBI:77805"
FT /evidence="ECO:0000250|UniProtKB:P80188"
FT BINDING 145
FT /ligand="a carboxymycobactin"
FT /ligand_id="ChEBI:CHEBI:178051"
FT /evidence="ECO:0000250|UniProtKB:P80188"
FT BINDING 154
FT /ligand="a carboxymycobactin"
FT /ligand_id="ChEBI:CHEBI:178051"
FT /evidence="ECO:0000250|UniProtKB:P80188"
FT BINDING 154
FT /ligand="enterobactin"
FT /ligand_id="ChEBI:CHEBI:77805"
FT /evidence="ECO:0000250|UniProtKB:P80188"
FT BINDING 158
FT /ligand="a carboxymycobactin"
FT /ligand_id="ChEBI:CHEBI:178051"
FT /evidence="ECO:0000250|UniProtKB:P80188"
FT MOD_RES 21
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250|UniProtKB:P80188"
FT CARBOHYD 85
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 96..195
FT /evidence="ECO:0000269|PubMed:21538546"
FT CONFLICT 18
FT /note="S -> R (in Ref. 1; CAA31657)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="G -> A (in Ref. 1; CAA31657)"
FT /evidence="ECO:0000305"
FT HELIX 33..35
FT /evidence="ECO:0007829|PDB:2K23"
FT HELIX 44..47
FT /evidence="ECO:0007829|PDB:2K23"
FT STRAND 49..58
FT /evidence="ECO:0007829|PDB:2K23"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:2K23"
FT STRAND 73..78
FT /evidence="ECO:0007829|PDB:2K23"
FT STRAND 84..90
FT /evidence="ECO:0007829|PDB:2K23"
FT STRAND 97..105
FT /evidence="ECO:0007829|PDB:2K23"
FT STRAND 111..114
FT /evidence="ECO:0007829|PDB:2K23"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:2K23"
FT STRAND 121..132
FT /evidence="ECO:0007829|PDB:2K23"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:2K23"
FT STRAND 139..147
FT /evidence="ECO:0007829|PDB:2K23"
FT STRAND 150..162
FT /evidence="ECO:0007829|PDB:2K23"
FT HELIX 166..178
FT /evidence="ECO:0007829|PDB:2K23"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:2K23"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:2K23"
SQ SEQUENCE 198 AA; 22476 MW; 7673F036DCA5654E CRC64;
MGLGVLCLAL VLLGVLQSQA QDSTQNLIPA PPLISVPLQP GFWTERFQGR WFVVGLAGNA
VQKERQSRFT MYSTIYELQE DNSYNVTSIL VRGQGCRYWI RTFVPSSRPG QFTLGNIHSY
PQIQSYDVQV ADTDYDQFAM VFFQKTSENK QYFKVTLYGR TKGLSDELKE RFVSFAKSLG
LKDNNIVFSV PTDQCIDN
