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 14-DEC-2011, entry version 84. DE RecName: Full=Neutrophil gelatinase-associated lipocalin; DE Short=NGAL; DE AltName: Full=Alpha-2-microglobulin-related protein; DE AltName: Full=Alpha-2U globulin-related protein; DE AltName: Full=Lipocalin-2; DE AltName: Full=p25; DE Flags: Precursor; GN Name=Lcn2; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=89083570; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). CC -!- FUNCTION: Iron-trafficking protein involved in multiple processes CC such as apoptosis, innate immunity and renal development. Binds CC iron through association with 2,5-dihydroxybenzoic acid (2,5- CC DHBA), a siderophore that shares structural similarities with CC bacterial enterobactin, and delivers or removes iron from the CC cell, depending on the context. Iron-bound form (holo-24p3) is CC internalized following binding to the SLC22A17 (24p3R) receptor, CC leading to release of iron and subsequent increase of CC intracellular iron concentration. In contrast, association of the CC iron-free form (apo-24p3) with the SLC22A17 (24p3R) receptor is CC followed by association with an intracellular siderophore, iron CC chelation and iron transfer to the extracellular medium, thereby CC reducing intracellular iron concentration. Involved in apoptosis CC due to interleukin-3 (IL3) deprivation: iron-loaded form increases CC intracellular iron concentration without promoting apoptosis, CC while iron-free form decreases intracellular iron levels, inducing CC expression of the proapoptotic protein BCL2L11/BIM, resulting in CC apoptosis. Involved in innate immunity, possibly by sequestrating CC iron, leading to limit bacterial growth (By similarity). CC -!- SUBUNIT: Homodimer; disulfide-linked. Heterodimer; disulfide- CC linked with MMP9 (By similarity). CC -!- SUBCELLULAR LOCATION: Secreted (By similarity). Note=Upon binding CC to the SLC22A17 (24p3R) receptor, it is internalized (By CC similarity). CC -!- SIMILARITY: Belongs to the calycin superfamily. Lipocalin family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X13295; CAA31657.1; -; mRNA. DR EMBL; BC089053; AAH89053.1; -; mRNA. DR IPI; IPI00205907; -. DR PIR; S01989; S01989. DR RefSeq; NP_570097.1; NM_130741.1. DR UniGene; Rn.11303; -. DR PDB; 2K23; NMR; -; A=21-198. DR PDBsum; 2K23; -. DR ProteinModelPortal; P30152; -. DR SMR; P30152; 21-197. DR STRING; P30152; -. DR Ensembl; ENSRNOT00000018776; ENSRNOP00000018776; ENSRNOG00000013973. DR GeneID; 170496; -. DR KEGG; rno:170496; -. DR UCSC; NM_130741; rat. DR CTD; 3934; -. DR RGD; 69408; Lcn2. DR eggNOG; roNOG16531; -. DR GeneTree; ENSGT00530000063610; -. DR HOVERGEN; HBG106490; -. DR InParanoid; P30152; -. DR OMA; PIDQCID; -. DR OrthoDB; EOG447FVG; -. DR PhylomeDB; P30152; -. DR NextBio; 620993; -. DR ArrayExpress; P30152; -. DR Genevestigator; P30152; -. DR GermOnline; ENSRNOG00000013973; Rattus norvegicus. DR GO; GO:0005829; C:cytosol; IDA:RGD. DR GO; GO:0005615; C:extracellular space; IDA:RGD. DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB. DR GO; GO:0002020; F:protease binding; IPI:RGD. DR GO; GO:0042803; F:protein homodimerization activity; IDA:RGD. DR GO; GO:0005215; F:transporter activity; IEA:InterPro. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:RGD. DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD. DR GO; GO:0031669; P:cellular response to nutrient levels; IEP:RGD. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD. DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB. DR GO; GO:0031346; P:positive regulation of cell projection organization; IDA:RGD. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:RGD. DR GO; GO:0070207; P:protein homotrimerization; IDA:RGD. DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0042493; P:response to drug; IMP:RGD. DR GO; GO:0009635; P:response to herbicide; IDA:RGD. DR GO; GO:0015891; P:siderophore transport; ISS:UniProtKB. DR InterPro; IPR012674; Calycin. DR InterPro; IPR011038; Calycin-like. DR InterPro; IPR002345; Lipocalin. DR InterPro; IPR000566; Lipocln_cytosolic_FA-bd_dom. DR InterPro; IPR003087; N_gelatinase. DR Gene3D; G3DSA:2.40.128.20; Calycin; 1. DR Pfam; PF00061; Lipocalin; 1. DR PRINTS; PR00179; LIPOCALIN. DR PRINTS; PR01275; NGELATINASE. DR SUPFAM; SSF50814; Calycin; 1. DR PROSITE; PS00213; LIPOCALIN; FALSE_NEG. PE 1: Evidence at protein level; KW 3D-structure; Apoptosis; Complete proteome; Disulfide bond; KW Glycoprotein; Immunity; Innate immunity; Ion transport; Iron; KW Iron transport; Pyrrolidone carboxylic acid; Reference proteome; KW Secreted; Signal; Transport. FT SIGNAL 1 20 By similarity. FT CHAIN 21 198 Neutrophil gelatinase-associated FT lipocalin. FT /FTId=PRO_0000017935. FT BINDING 126 126 Catecholate-type ferric siderophore (By FT similarity). FT BINDING 145 145 Catecholate-type ferric siderophore (By FT similarity). FT BINDING 154 154 Catecholate-type ferric siderophore (By FT similarity). FT MOD_RES 21 21 Pyrrolidone carboxylic acid (By FT similarity). FT CARBOHYD 85 85 N-linked (GlcNAc...) (Potential). FT DISULFID 96 195 By similarity. FT CONFLICT 18 18 S -> R (in Ref. 1; CAA31657). FT CONFLICT 58 58 G -> A (in Ref. 1; CAA31657). FT HELIX 33 35 FT HELIX 44 47 FT STRAND 64 66 FT STRAND 73 78 FT STRAND 84 90 FT STRAND 97 105 FT HELIX 117 119 FT STRAND 121 132 FT STRAND 135 137 FT STRAND 139 147 FT STRAND 150 158 FT HELIX 166 178 FT HELIX 183 185 FT STRAND 193 195 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 //