NGB_HUMAN
ID NGB_HUMAN Reviewed; 151 AA.
AC Q9NPG2;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Neuroglobin;
GN Name=NGB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, 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 [MRNA].
RX PubMed=11820779; DOI=10.1006/bbrc.2002.6360;
RA Zhang C.G., Wang C.L., Deng M.Y., Li L., Wang H.Y., Fan M., Xu W.L.,
RA Meng F.W., Qian L., He F.C.;
RT "Full-length cDNA cloning of human neuroglobin and tissue expression of rat
RT neuroglobin.";
RL Biochem. Biophys. Res. Commun. 290:1411-1419(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [5]
RP FUNCTION.
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 [6]
RP DISULFIDE BOND.
RX PubMed=15036292; DOI=10.1016/j.micron.2003.10.019;
RA Hamdane D., Kiger L., Dewilde S., Green B.N., Pesce A., Uzan J.,
RA Burmester T., Hankeln T., Bolognesi M., Moens L., Marden M.C.;
RT "Coupling of the heme and an internal disulfide bond in human
RT neuroglobin.";
RL Micron 35:59-62(2004).
RN [7]
RP FUNCTION.
RX PubMed=18416560; DOI=10.1021/bi800286m;
RA Watanabe S., Wakasugi K.;
RT "Zebrafish neuroglobin is a cell-membrane-penetrating globin.";
RL Biochemistry 47:5266-5270(2008).
RN [8]
RP FUNCTION IN APOPTOSIS.
RX PubMed=21190290; DOI=10.1002/iub.405;
RA Brittain T., Skommer J., Henty K., Birch N., Raychaudhuri S.;
RT "A role for human neuroglobin in apoptosis.";
RL IUBMB Life 62:878-885(2010).
RN [9]
RP FUNCTION, AND DISULFIDE BOND.
RX PubMed=21296891; DOI=10.1074/jbc.m110.159541;
RA Tiso M., Tejero J., Basu S., Azarov I., Wang X., Simplaceanu V.,
RA Frizzell S., Jayaraman T., Geary L., Shapiro C., Ho C., Shiva S.,
RA Kim-Shapiro D.B., Gladwin M.T.;
RT "Human neuroglobin functions as a redox-regulated nitrite reductase.";
RL J. Biol. Chem. 286:18277-18289(2011).
RN [10]
RP PHOSPHORYLATION DURING HYPOXIA, AND INTERACTION WITH 14-3-3.
RX PubMed=21965683; DOI=10.1074/jbc.m111.271973;
RA Jayaraman T., Tejero J., Chen B.B., Blood A.B., Frizzell S., Shapiro C.,
RA Tiso M., Hood B.L., Wang X., Zhao X., Conrads T.P., Mallampalli R.K.,
RA Gladwin M.T.;
RT "14-3-3 binding and phosphorylation of neuroglobin during hypoxia modulate
RT six-to-five heme pocket coordination and rate of nitrite reduction to
RT nitric oxide.";
RL J. Biol. Chem. 286:42679-42689(2011).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN A HEXACOORDINATED FE(3+)-BOUND
RP FORM.
RX PubMed=12962627; DOI=10.1016/s0969-2126(03)00166-7;
RA Pesce A., Dewilde S., Nardini M., Moens L., Ascenzi P., Hankeln T.,
RA Burmester T., Bolognesi M.;
RT "Human brain neuroglobin structure reveals a distinct mode of controlling
RT oxygen affinity.";
RL Structure 11:1087-1095(2003).
CC -!- FUNCTION: Involved in oxygen transport in the brain. Hexacoordinate
CC globin, displaying competitive binding of oxygen or the distal His
CC residue to the iron atom. Not capable of penetrating cell membranes.
CC The deoxygenated form exhibits nitrite reductase activity inhibiting
CC cellular respiration via NO-binding to cytochrome c oxidase. Involved
CC in neuroprotection during oxidative stress. May exert its anti-
CC apoptotic activity by acting to reset the trigger level of
CC mitochondrial cytochrome c release necessary to commit the cells to
CC apoptosis. {ECO:0000269|PubMed:11029004, ECO:0000269|PubMed:11473128,
CC ECO:0000269|PubMed:18416560, ECO:0000269|PubMed:21190290,
CC ECO:0000269|PubMed:21296891}.
CC -!- SUBUNIT: Monomer. Homodimer and homotetramer; disulfide-linked (By
CC similarity). Interacts with 14-3-3. {ECO:0000250,
CC ECO:0000269|PubMed:15036292, ECO:0000269|PubMed:21296891,
CC ECO:0000269|PubMed:21965683}.
CC -!- INTERACTION:
CC Q9NPG2; Q9BX70: BTBD2; NbExp=3; IntAct=EBI-10311409, EBI-710091;
CC Q9NPG2; Q6P1W5: C1orf94; NbExp=3; IntAct=EBI-10311409, EBI-946029;
CC Q9NPG2; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-10311409, EBI-742054;
CC Q9NPG2; Q8WXI9: GATAD2B; NbExp=3; IntAct=EBI-10311409, EBI-923440;
CC Q9NPG2; Q8IYA8: IHO1; NbExp=6; IntAct=EBI-10311409, EBI-8638439;
CC Q9NPG2; Q96JM7: L3MBTL3; NbExp=3; IntAct=EBI-10311409, EBI-2686809;
CC Q9NPG2; Q96JM7-2: L3MBTL3; NbExp=3; IntAct=EBI-10311409, EBI-11985629;
CC Q9NPG2; A8MW99: MEI4; NbExp=3; IntAct=EBI-10311409, EBI-19944212;
CC Q9NPG2; Q9GZT8: NIF3L1; NbExp=5; IntAct=EBI-10311409, EBI-740897;
CC Q9NPG2; Q04864: REL; NbExp=3; IntAct=EBI-10311409, EBI-307352;
CC Q9NPG2; Q04864-2: REL; NbExp=3; IntAct=EBI-10311409, EBI-10829018;
CC Q9NPG2; P48775: TDO2; NbExp=6; IntAct=EBI-10311409, EBI-743494;
CC Q9NPG2; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-10311409, EBI-11139477;
CC Q9NPG2; Q08AM6: VAC14; NbExp=6; IntAct=EBI-10311409, EBI-2107455;
CC Q9NPG2; Q8N720: ZNF655; NbExp=3; IntAct=EBI-10311409, EBI-625509;
CC -!- SUBCELLULAR LOCATION: Perikaryon {ECO:0000250}. Cytoplasm.
CC Mitochondrion.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain, the strongest
CC expression is seen in the frontal lobe, the subthalamic nucleus and the
CC thalamus. {ECO:0000269|PubMed:11029004}.
CC -!- PTM: A redox disulfide bond regulates the heme pocket coordination and
CC the rate of nitrite reduction to NO.
CC -!- PTM: Phosphorylated in vitro by ERK1, ERK2 and PKA, and in vivo during
CC hypoxia. Phosphorylation increases nitrite reductase activity.
CC {ECO:0000269|PubMed:21965683}.
CC -!- SIMILARITY: Belongs to the globin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00238}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Neuroglobin entry;
CC URL="https://en.wikipedia.org/wiki/Neuroglobin";
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DR EMBL; AJ245944; CAC12994.1; -; Genomic_DNA.
DR EMBL; AJ245946; CAC11133.1; -; mRNA.
DR EMBL; AF422796; AAL98923.1; -; Genomic_DNA.
DR EMBL; AF422797; AAL98924.1; -; mRNA.
DR EMBL; AC007375; AAF63183.1; -; Genomic_DNA.
DR EMBL; AC007954; AAF62557.1; -; Genomic_DNA.
DR EMBL; BC032509; AAH32509.1; -; mRNA.
DR CCDS; CCDS9856.1; -.
DR RefSeq; NP_067080.1; NM_021257.3.
DR PDB; 1OJ6; X-ray; 1.95 A; A/B/C/D=1-151.
DR PDB; 4MPM; X-ray; 1.74 A; A/B=1-151.
DR PDBsum; 1OJ6; -.
DR PDBsum; 4MPM; -.
DR AlphaFoldDB; Q9NPG2; -.
DR BMRB; Q9NPG2; -.
DR SMR; Q9NPG2; -.
DR BioGRID; 121798; 185.
DR IntAct; Q9NPG2; 16.
DR STRING; 9606.ENSP00000298352; -.
DR TCDB; 1.A.107.1.4; the pore-forming globin (globin) family.
DR BioMuta; NGB; -.
DR DMDM; 32171399; -.
DR MassIVE; Q9NPG2; -.
DR PaxDb; Q9NPG2; -.
DR PeptideAtlas; Q9NPG2; -.
DR PRIDE; Q9NPG2; -.
DR ProteomicsDB; 81990; -.
DR Antibodypedia; 25998; 301 antibodies from 30 providers.
DR DNASU; 58157; -.
DR Ensembl; ENST00000298352.5; ENSP00000298352.4; ENSG00000165553.5.
DR GeneID; 58157; -.
DR KEGG; hsa:58157; -.
DR MANE-Select; ENST00000298352.5; ENSP00000298352.4; NM_021257.4; NP_067080.1.
DR UCSC; uc001xtg.2; human.
DR CTD; 58157; -.
DR DisGeNET; 58157; -.
DR GeneCards; NGB; -.
DR HGNC; HGNC:14077; NGB.
DR HPA; ENSG00000165553; Tissue enhanced (brain, choroid plexus, pituitary gland).
DR MIM; 605304; gene.
DR neXtProt; NX_Q9NPG2; -.
DR OpenTargets; ENSG00000165553; -.
DR PharmGKB; PA31612; -.
DR VEuPathDB; HostDB:ENSG00000165553; -.
DR eggNOG; KOG3378; Eukaryota.
DR GeneTree; ENSGT00510000048375; -.
DR HOGENOM; CLU_003827_13_5_1; -.
DR InParanoid; Q9NPG2; -.
DR OMA; MQRGWET; -.
DR OrthoDB; 1529889at2759; -.
DR PhylomeDB; Q9NPG2; -.
DR TreeFam; TF333247; -.
DR PathwayCommons; Q9NPG2; -.
DR Reactome; R-HSA-8981607; Intracellular oxygen transport.
DR SignaLink; Q9NPG2; -.
DR BioGRID-ORCS; 58157; 14 hits in 1069 CRISPR screens.
DR ChiTaRS; NGB; human.
DR EvolutionaryTrace; Q9NPG2; -.
DR GenomeRNAi; 58157; -.
DR Pharos; Q9NPG2; Tbio.
DR PRO; PR:Q9NPG2; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9NPG2; protein.
DR Bgee; ENSG00000165553; Expressed in right frontal lobe and 91 other tissues.
DR ExpressionAtlas; Q9NPG2; baseline and differential.
DR Genevisible; Q9NPG2; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019825; F:oxygen binding; IBA:GO_Central.
DR GO; GO:0005344; F:oxygen carrier activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0015671; P:oxygen transport; IBA:GO_Central.
DR GO; GO:0001666; P:response to hypoxia; IBA:GO_Central.
DR Gene3D; 1.10.490.10; -; 1.
DR InterPro; IPR000971; Globin.
DR InterPro; IPR009050; Globin-like_sf.
DR InterPro; IPR012292; Globin/Proto.
DR Pfam; PF00042; Globin; 1.
DR SUPFAM; SSF46458; SSF46458; 1.
DR PROSITE; PS01033; GLOBIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Cytoplasm; Disulfide bond; Heme; Iron;
KW Metal-binding; Mitochondrion; Oxygen transport; Phosphoprotein;
KW Reference proteome; Transport.
FT CHAIN 1..151
FT /note="Neuroglobin"
FT /id="PRO_0000053390"
FT REGION 1..149
FT /note="Globin"
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"
FT /evidence="ECO:0000269|PubMed:12962627,
FT ECO:0007744|PDB:1OJ6, ECO:0007744|PDB:4MPM"
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:0000269|PubMed:12962627,
FT ECO:0007744|PDB:1OJ6, ECO:0007744|PDB:4MPM"
FT DISULFID 46..55
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:15036292,
FT ECO:0000269|PubMed:21296891"
FT HELIX 6..13
FT /evidence="ECO:0007829|PDB:4MPM"
FT TURN 14..18
FT /evidence="ECO:0007829|PDB:4MPM"
FT HELIX 20..34
FT /evidence="ECO:0007829|PDB:4MPM"
FT HELIX 38..49
FT /evidence="ECO:0007829|PDB:4MPM"
FT HELIX 55..57
FT /evidence="ECO:0007829|PDB:4MPM"
FT HELIX 59..77
FT /evidence="ECO:0007829|PDB:4MPM"
FT HELIX 79..85
FT /evidence="ECO:0007829|PDB:4MPM"
FT HELIX 86..98
FT /evidence="ECO:0007829|PDB:4MPM"
FT HELIX 105..121
FT /evidence="ECO:0007829|PDB:4MPM"
FT HELIX 122..124
FT /evidence="ECO:0007829|PDB:4MPM"
FT HELIX 127..144
FT /evidence="ECO:0007829|PDB:4MPM"
FT HELIX 145..148
FT /evidence="ECO:0007829|PDB:4MPM"
SQ SEQUENCE 151 AA; 16933 MW; 45A292A7D77B9CE3 CRC64;
MERPEPELIR QSWRAVSRSP LEHGTVLFAR LFALEPDLLP LFQYNCRQFS SPEDCLSSPE
FLDHIRKVML VIDAAVTNVE DLSSLEEYLA SLGRKHRAVG VKLSSFSTVG ESLLYMLEKC
LGPAFTPATR AAWSQLYGAV VQAMSRGWDG E
