ID NGB_MOUSE Reviewed; 151 AA.
AC Q9ER97;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 27-MAR-2024, entry version 149.
DE RecName: Full=Neuroglobin {ECO:0000303|PubMed:11029004};
DE AltName: Full=Nitrite reductase {ECO:0000250|UniProtKB:Q9NPG2};
DE EC=1.7.-.- {ECO:0000250|UniProtKB:Q9NPG2};
GN Name=Ngb {ECO:0000312|MGI:MGI:2151886};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=11029004; DOI=10.1038/35035093;
RA Burmester T., Weich B., Reinhardt S., Hankeln T.;
RT "A vertebrate globin expressed in the brain.";
RL Nature 407:520-522(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 FUNCTION.
RX PubMed=11473111; DOI=10.1074/jbc.m103907200;
RA Couture M., Burmester T., Hankeln T., Rousseau D.L.;
RT "The heme environment of mouse neuroglobin. Evidence for the presence of
RT two conformations of the heme pocket.";
RL J. Biol. Chem. 276:36377-36382(2001).
RN [4]
RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF HIS-64.
RX PubMed=11473128; DOI=10.1074/jbc.m106438200;
RA Dewilde S., Kiger L., Burmester T., Hankeln T., Baudin-Creuza V., Aerts T.,
RA Marden M.C., Caubergs R., Moens L.;
RT "Biochemical characterization and ligand binding properties of neuroglobin,
RT a novel member of the globin family.";
RL J. Biol. Chem. 276:38949-38955(2001).
RN [5]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=22659017; DOI=10.1016/j.neuroscience.2012.05.054;
RA Yu Z., Xu J., Liu N., Wang Y., Li X., Pallast S., van Leyen K., Wang X.;
RT "Mitochondrial distribution of neuroglobin and its response to oxygen-
RT glucose deprivation in primary-cultured mouse cortical neurons.";
RL Neuroscience 218:235-242(2012).
RN [6] {ECO:0007744|PDB:1W92}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH CARBON MONOXIDE AND
RP HEME.
RX PubMed=15548613; DOI=10.1073/pnas.0407633101;
RA Vallone B., Nienhaus K., Matthes A., Brunori M., Nienhaus G.U.;
RT "The structure of carbonmonoxy neuroglobin reveals a heme-sliding mechanism
RT for control of ligand affinity.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:17351-17356(2004).
RN [7] {ECO:0007744|PDB:1Q1F}
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) IN A HEXACOORDINATED FE(3+)-BOUND
RP FORM.
RX PubMed=15162488; DOI=10.1002/prot.20113;
RA Vallone B., Nienhaus K., Brunori M., Nienhaus G.U.;
RT "The structure of murine neuroglobin: Novel pathways for ligand migration
RT and binding.";
RL Proteins 56:85-92(2004).
CC -!- FUNCTION: Monomeric globin with a bis-histidyl six-coordinate heme-iron
CC atom through which it can bind dioxygen, carbon monoxide and nitric
CC oxide (PubMed:11029004, PubMed:11473111, PubMed:11473128). Could help
CC transport oxygen and increase its availability to the metabolically
CC active neuronal tissues, though its low quantity in tissues as well as
CC its high affinity for dioxygen, which may limit its oxygen-releasing
CC ability, argue against it (PubMed:11029004, PubMed:11473128). The
CC ferrous/deoxygenated form exhibits a nitrite reductase activity and it
CC could produce nitric oxide which in turn inhibits cellular respiration
CC in response to hypoxia. In its ferrous/deoxygenated state, it may also
CC exhibit GDI (Guanine nucleotide Dissociation Inhibitor) activity toward
CC heterotrimeric G-alpha proteins, thereby regulating signal transduction
CC to facilitate neuroprotective responses in the wake of hypoxia and
CC associated oxidative stress (By similarity).
CC {ECO:0000250|UniProtKB:Q9NPG2, ECO:0000269|PubMed:11029004,
CC ECO:0000269|PubMed:11473111, ECO:0000269|PubMed:11473128}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Fe(III)-heme b-[protein] + H2O + nitric oxide = Fe(II)-heme b-
CC [protein] + 2 H(+) + nitrite; Xref=Rhea:RHEA:77711, Rhea:RHEA-
CC COMP:18975, Rhea:RHEA-COMP:18976, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16301, ChEBI:CHEBI:16480,
CC ChEBI:CHEBI:55376, ChEBI:CHEBI:60344;
CC Evidence={ECO:0000250|UniProtKB:Q9NPG2};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:77713;
CC Evidence={ECO:0000250|UniProtKB:Q9NPG2};
CC -!- SUBUNIT: Monomer (PubMed:11029004). Homodimer and homotetramer;
CC disulfide-linked. Mainly monomeric but also detected as part of
CC homodimers and homotetramers (PubMed:11473128). Interacts with 14-3-3
CC proteins; regulates the phosphorylation of NGB. Could interact (ferrous
CC form) with G-alpha(i) proteins (GTP-bound form) (By similarity).
CC {ECO:0000250|UniProtKB:Q9NPG2, ECO:0000269|PubMed:11029004,
CC ECO:0000269|PubMed:11473128}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:22659017}.
CC Mitochondrion matrix {ECO:0000269|PubMed:22659017}. Note=Enriched in
CC mitochondrial matrix upon oxygen-glucose deprivation.
CC {ECO:0000269|PubMed:22659017}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain.
CC {ECO:0000269|PubMed:11029004}.
CC -!- INDUCTION: Up-regulated upon oxygen-glucose deprivation.
CC {ECO:0000269|PubMed:22659017}.
CC -!- PTM: Phosphorylated during hypoxia by ERK1/ERK2. Phosphorylation
CC regulates the heme pocket hexacoordination preventing the association
CC of His-64 with the heme metal center. Thereby, promotes the access of
CC dioxygen and nitrite to the heme and stimulates the nitrite reductase
CC activity. Phosphorylation during hypoxia is stabilized by 14-3-3
CC proteins. {ECO:0000250|UniProtKB:Q9NPG2}.
CC -!- SIMILARITY: Belongs to the globin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00238}.
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DR EMBL; AJ245945; CAC11135.1; -; mRNA.
DR EMBL; BC024263; AAH24263.1; -; mRNA.
DR CCDS; CCDS36501.1; -.
DR RefSeq; NP_071859.1; NM_022414.2.
DR PDB; 1Q1F; X-ray; 1.50 A; A=1-151.
DR PDB; 1W92; X-ray; 1.70 A; A=1-151.
DR PDB; 2VRY; X-ray; 1.87 A; A=1-151.
DR PDB; 3GK9; X-ray; 1.80 A; A=1-151.
DR PDB; 3GKT; X-ray; 1.86 A; A=1-151.
DR PDB; 3GLN; X-ray; 2.26 A; A=1-151.
DR PDB; 4MU5; X-ray; 1.80 A; A=1-151.
DR PDB; 4NZI; X-ray; 2.10 A; A=1-151.
DR PDB; 4O1T; X-ray; 1.60 A; A=1-151.
DR PDB; 4O2G; X-ray; 2.70 A; A=1-151.
DR PDB; 4O35; X-ray; 1.80 A; A=1-151.
DR PDB; 4O4T; X-ray; 1.90 A; A=1-151.
DR PDB; 4O4Z; X-ray; 1.70 A; A=1-151.
DR PDB; 5EET; X-ray; 2.00 A; A=3-150.
DR PDB; 5EOH; X-ray; 1.90 A; A=3-150.
DR PDB; 5EQM; X-ray; 2.05 A; A=3-150.
DR PDB; 5EU2; X-ray; 2.00 A; A=3-150.
DR PDB; 5EV5; X-ray; 2.00 A; A=3-150.
DR PDB; 5EYJ; X-ray; 2.40 A; A=3-150.
DR PDB; 5EYS; X-ray; 1.75 A; A=3-150.
DR PDB; 5F0B; X-ray; 2.15 A; A=3-151.
DR PDB; 5F2A; X-ray; 2.10 A; A=1-151.
DR PDB; 5MJC; X-ray; 1.62 A; A=3-150.
DR PDB; 5MJD; X-ray; 1.70 A; A=3-150.
DR PDB; 5NVI; X-ray; 1.60 A; A=3-150.
DR PDB; 5NW6; X-ray; 1.70 A; A=3-150.
DR PDB; 5O17; X-ray; 1.80 A; A=3-150.
DR PDB; 5O18; X-ray; 1.86 A; A=3-150.
DR PDB; 5O1K; X-ray; 2.05 A; A=3-150.
DR PDB; 5O27; X-ray; 2.31 A; A=3-150.
DR PDB; 6EYE; X-ray; 1.70 A; A=1-151.
DR PDB; 6H5Z; X-ray; 1.80 A; A=4-149.
DR PDB; 6H6C; X-ray; 1.75 A; A=1-151.
DR PDB; 6H6I; X-ray; 1.60 A; A=1-151.
DR PDB; 6H6J; X-ray; 2.60 A; A=1-150.
DR PDB; 6I3T; X-ray; 2.00 A; A=1-150.
DR PDB; 6I40; X-ray; 1.90 A; A=1-150.
DR PDB; 6R1Q; X-ray; 1.95 A; A=3-150.
DR PDB; 6RA6; X-ray; 2.30 A; A=1-148.
DR PDB; 7OHD; X-ray; 1.80 A; A/B=1-42, A/B=57-151.
DR PDBsum; 1Q1F; -.
DR PDBsum; 1W92; -.
DR PDBsum; 2VRY; -.
DR PDBsum; 3GK9; -.
DR PDBsum; 3GKT; -.
DR PDBsum; 3GLN; -.
DR PDBsum; 4MU5; -.
DR PDBsum; 4NZI; -.
DR PDBsum; 4O1T; -.
DR PDBsum; 4O2G; -.
DR PDBsum; 4O35; -.
DR PDBsum; 4O4T; -.
DR PDBsum; 4O4Z; -.
DR PDBsum; 5EET; -.
DR PDBsum; 5EOH; -.
DR PDBsum; 5EQM; -.
DR PDBsum; 5EU2; -.
DR PDBsum; 5EV5; -.
DR PDBsum; 5EYJ; -.
DR PDBsum; 5EYS; -.
DR PDBsum; 5F0B; -.
DR PDBsum; 5F2A; -.
DR PDBsum; 5MJC; -.
DR PDBsum; 5MJD; -.
DR PDBsum; 5NVI; -.
DR PDBsum; 5NW6; -.
DR PDBsum; 5O17; -.
DR PDBsum; 5O18; -.
DR PDBsum; 5O1K; -.
DR PDBsum; 5O27; -.
DR PDBsum; 6EYE; -.
DR PDBsum; 6H5Z; -.
DR PDBsum; 6H6C; -.
DR PDBsum; 6H6I; -.
DR PDBsum; 6H6J; -.
DR PDBsum; 6I3T; -.
DR PDBsum; 6I40; -.
DR PDBsum; 6R1Q; -.
DR PDBsum; 6RA6; -.
DR PDBsum; 7OHD; -.
DR AlphaFoldDB; Q9ER97; -.
DR BMRB; Q9ER97; -.
DR SMR; Q9ER97; -.
DR BioGRID; 211041; 4.
DR STRING; 10090.ENSMUSP00000105806; -.
DR PaxDb; 10090-ENSMUSP00000021420; -.
DR ProteomicsDB; 287505; -.
DR Antibodypedia; 25998; 317 antibodies from 30 providers.
DR DNASU; 64242; -.
DR Ensembl; ENSMUST00000021420.14; ENSMUSP00000021420.8; ENSMUSG00000021032.14.
DR GeneID; 64242; -.
DR KEGG; mmu:64242; -.
DR UCSC; uc007oii.1; mouse.
DR AGR; MGI:2151886; -.
DR CTD; 58157; -.
DR MGI; MGI:2151886; Ngb.
DR VEuPathDB; HostDB:ENSMUSG00000021032; -.
DR eggNOG; KOG3378; Eukaryota.
DR GeneTree; ENSGT00510000048375; -.
DR HOGENOM; CLU_003827_13_5_1; -.
DR InParanoid; Q9ER97; -.
DR OMA; KAMRRGW; -.
DR OrthoDB; 2015093at2759; -.
DR PhylomeDB; Q9ER97; -.
DR TreeFam; TF333247; -.
DR Reactome; R-MMU-8981607; Intracellular oxygen transport.
DR BioGRID-ORCS; 64242; 2 hits in 84 CRISPR screens.
DR ChiTaRS; Gtpbp4; mouse.
DR EvolutionaryTrace; Q9ER97; -.
DR PRO; PR:Q9ER97; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q9ER97; Protein.
DR Bgee; ENSMUSG00000021032; Expressed in interventricular septum and 62 other cell types or tissues.
DR ExpressionAtlas; Q9ER97; baseline and differential.
DR Genevisible; Q9ER97; MM.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0005092; F:GDP-dissociation inhibitor activity; ISS:UniProtKB.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0098809; F:nitrite reductase activity; ISS:UniProtKB.
DR GO; GO:0019825; F:oxygen binding; IDA:UniProtKB.
DR GO; GO:0005344; F:oxygen carrier activity; IDA:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0031175; P:neuron projection development; ISO:MGI.
DR GO; GO:0015671; P:oxygen transport; IDA:MGI.
DR GO; GO:0001666; P:response to hypoxia; IBA:GO_Central.
DR CDD; cd08920; Ngb; 1.
DR Gene3D; 1.10.490.10; Globins; 1.
DR InterPro; IPR000971; Globin.
DR InterPro; IPR009050; Globin-like_sf.
DR InterPro; IPR012292; Globin/Proto.
DR PANTHER; PTHR46458; BLR2807 PROTEIN; 1.
DR PANTHER; PTHR46458:SF19; NEUROGLOBIN; 1.
DR Pfam; PF00042; Globin; 1.
DR SUPFAM; SSF46458; Globin-like; 1.
DR PROSITE; PS01033; GLOBIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Disulfide bond; Heme; Iron; Metal-binding;
KW Mitochondrion; Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..151
FT /note="Neuroglobin"
FT /id="PRO_0000053392"
FT BINDING 64
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="distal binding residue; reversible"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00238,
FT ECO:0000269|PubMed:15162488, ECO:0007744|PDB:1Q1F"
FT BINDING 96
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="proximal binding residue"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00238,
FT ECO:0000269|PubMed:15162488, ECO:0000269|PubMed:15548613,
FT ECO:0007744|PDB:1Q1F, ECO:0007744|PDB:1W92"
FT MUTAGEN 64
FT /note="H->L: Improved binding of dioxygen and carbon
FT monoxide to the iron atom."
FT /evidence="ECO:0000269|PubMed:11473128"
FT HELIX 6..17
FT /evidence="ECO:0007829|PDB:1Q1F"
FT HELIX 20..34
FT /evidence="ECO:0007829|PDB:1Q1F"
FT HELIX 36..41
FT /evidence="ECO:0007829|PDB:1Q1F"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:4O1T"
FT HELIX 52..55
FT /evidence="ECO:0007829|PDB:1Q1F"
FT HELIX 59..77
FT /evidence="ECO:0007829|PDB:1Q1F"
FT TURN 78..80
FT /evidence="ECO:0007829|PDB:4O1T"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:1Q1F"
FT HELIX 86..99
FT /evidence="ECO:0007829|PDB:1Q1F"
FT HELIX 105..121
FT /evidence="ECO:0007829|PDB:1Q1F"
FT HELIX 122..124
FT /evidence="ECO:0007829|PDB:1Q1F"
FT HELIX 127..145
FT /evidence="ECO:0007829|PDB:1Q1F"
FT HELIX 146..148
FT /evidence="ECO:0007829|PDB:1Q1F"
SQ SEQUENCE 151 AA; 17037 MW; 377BBE4BF723CCF1 CRC64;
MERPESELIR QSWRVVSRSP LEHGTVLFAR LFALEPSLLP LFQYNGRQFS SPEDCLSSPE
FLDHIRKVML VIDAAVTNVE DLSSLEEYLT SLGRKHRAVG VRLSSFSTVG ESLLYMLEKC
LGPDFTPATR TAWSRLYGAV VQAMSRGWDG E
//
