ID CYGB_MOUSE Reviewed; 190 AA. AC Q9CX80; DT 27-MAY-2002, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 27-MAR-2024, entry version 152. DE RecName: Full=Cytoglobin {ECO:0000303|PubMed:11919282}; DE AltName: Full=Nitric oxygen dioxygenase {ECO:0000305|PubMed:33334890}; DE EC=1.14.12.- {ECO:0000269|PubMed:33334890}; DE AltName: Full=Nitrite reductase CYGB {ECO:0000250|UniProtKB:Q8WWM9}; DE EC=1.7.-.- {ECO:0000250|UniProtKB:Q8WWM9}; DE AltName: Full=Pseudoperoxidase CYGB {ECO:0000250|UniProtKB:Q8WWM9}; DE EC=1.11.1.- {ECO:0000250|UniProtKB:Q8WWM9}; DE AltName: Full=Superoxide dismutase CYGB {ECO:0000305|PubMed:34930834}; DE EC=1.15.1.1 {ECO:0000269|PubMed:34930834}; GN Name=Cygb {ECO:0000312|MGI:MGI:2149481}; 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]. RC TISSUE=Brain; RX PubMed=11919282; DOI=10.1093/oxfordjournals.molbev.a004096; RA Burmester T., Ebner B., Weich B., Hankeln T.; RT "Cytoglobin: a novel globin type ubiquitously expressed in vertebrate RT tissues."; RL Mol. Biol. Evol. 19:416-421(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Embryonic head; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Eye; 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 [4] RP SUBCELLULAR LOCATION. RX PubMed=14660570; DOI=10.1074/jbc.m310540200; RA Schmidt M., Gerlach F., Avivi A., Laufs T., Wystub S., Simpson J.C., RA Nevo E., Saaler-Reinhardt S., Reuss S., Hankeln T., Burmester T.; RT "Cytoglobin is a respiratory protein in connective tissue and neurons, RT which is up-regulated by hypoxia."; RL J. Biol. Chem. 279:8063-8069(2004). RN [5] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=15663964; DOI=10.1016/j.neulet.2004.10.071; RA Schmidt M., Laufs T., Reuss S., Hankeln T., Burmester T.; RT "Divergent distribution of cytoglobin and neuroglobin in the murine eye."; RL Neurosci. Lett. 374:207-211(2005). RN [6] RP FUNCTION. RX PubMed=19147491; DOI=10.1074/jbc.m808231200; RA Halligan K.E., Jourd'heuil F.L., Jourd'heuil D.; RT "Cytoglobin is expressed in the vasculature and regulates cell respiration RT and proliferation via nitric oxide dioxygenation."; RL J. Biol. Chem. 284:8539-8547(2009). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Liver, Lung, Spleen, and RC Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [8] RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=28393874; DOI=10.1038/ncomms14807; RA Liu X., El-Mahdy M.A., Boslett J., Varadharaj S., Hemann C., RA Abdelghany T.M., Ismail R.S., Little S.C., Zhou D., Thuy L.T., Kawada N., RA Zweier J.L.; RT "Cytoglobin regulates blood pressure and vascular tone through nitric oxide RT metabolism in the vascular wall."; RL Nat. Commun. 8:14807-14807(2017). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=33334890; DOI=10.1074/jbc.ra120.016394; RA Ilangovan G., Khaleel S.A., Kundu T., Hemann C., El-Mahdy M.A., RA Zweier J.L.; RT "Defining the reducing system of the NO dioxygenase cytoglobin in vascular RT smooth muscle cells and its critical role in regulating cellular NO RT decay."; RL J. Biol. Chem. 296:100196-100196(2021). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=34930834; DOI=10.1073/pnas.2105053118; RA Zweier J.L., Hemann C., Kundu T., Ewees M.G., Khaleel S.A., Samouilov A., RA Ilangovan G., El-Mahdy M.A.; RT "Cytoglobin has potent superoxide dismutase function."; RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021). CC -!- FUNCTION: Probable multifunctional globin with a hexacoordinated heme CC iron required for the catalysis of various reactions depending on redox CC condition of the cell as well as oxygen availability (PubMed:19147491, CC PubMed:28393874, PubMed:33334890, PubMed:34930834). Has a nitric oxide CC dioxygenase (NOD) activity and is most probably involved in cell- CC mediated and oxygen-dependent nitric oxide consumption CC (PubMed:19147491, PubMed:28393874, PubMed:33334890). By scavenging this CC second messenger may regulate several biological processes including CC endothelium-mediated vasodilation and vascular tone (PubMed:19147491, CC PubMed:28393874). Under normoxic conditions functions as a nitric oxide CC dioxygenase (NOD) but under hypoxic conditions the globin may switch CC its function to that of a nitrite (NO2) reductase (NiR), generating CC nitric oxide (By similarity). Could also have peroxidase and superoxide CC dismutase activities, detoxifying reactive oxygen species and CC protecting cells against oxidative stress (PubMed:34930834). Also binds CC dioxygen with low affinity and could function as an oxygen sensor but CC has probably no function as a respiratory oxygen carrier (By CC similarity). {ECO:0000250|UniProtKB:Q8WWM9, CC ECO:0000269|PubMed:19147491, ECO:0000269|PubMed:28393874, CC ECO:0000269|PubMed:33334890, ECO:0000269|PubMed:34930834}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Fe(II)-heme b-[protein] + nitric oxide + O2 = Fe(III)-heme b- CC [protein] + nitrate; Xref=Rhea:RHEA:78091, Rhea:RHEA-COMP:18975, CC Rhea:RHEA-COMP:18976, ChEBI:CHEBI:15379, ChEBI:CHEBI:16480, CC ChEBI:CHEBI:17632, ChEBI:CHEBI:55376, ChEBI:CHEBI:60344; CC Evidence={ECO:0000269|PubMed:33334890}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78092; CC Evidence={ECO:0000269|PubMed:33334890}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 H(+) + 2 superoxide = H2O2 + O2; Xref=Rhea:RHEA:20696, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, CC ChEBI:CHEBI:18421; EC=1.15.1.1; CC Evidence={ECO:0000269|PubMed:34930834}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20697; CC Evidence={ECO:0000269|PubMed:34930834}; 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:Q8WWM9}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:77713; CC Evidence={ECO:0000250|UniProtKB:Q8WWM9}; CC -!- CATALYTIC ACTIVITY: CC Reaction=AH2 + H2O2 = A + 2 H2O; Xref=Rhea:RHEA:30275, CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240, CC ChEBI:CHEBI:17499; Evidence={ECO:0000250|UniProtKB:Q8WWM9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30276; CC Evidence={ECO:0000250|UniProtKB:Q8WWM9}; CC -!- ACTIVITY REGULATION: The nitric oxide dioxygenase activity is activated CC by a reducing system composed of cytochrome b5, its upstream reductase CC CYB5R3 and NADH. {ECO:0000269|PubMed:33334890}. CC -!- SUBUNIT: Monomeric. Homodimer; disulfide-linked in vitro. Also CC homooligomeric in vitro. {ECO:0000250|UniProtKB:Q8WWM9}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14660570, CC ECO:0000269|PubMed:15663964, ECO:0000269|PubMed:34930834}. Nucleus CC {ECO:0000269|PubMed:14660570, ECO:0000269|PubMed:15663964}. CC Note=Nuclear localization is observed in neurons. CC {ECO:0000269|PubMed:14660570}. CC -!- TISSUE SPECIFICITY: Expressed in brain and retina by non-neuronal cells CC (at protein level) (PubMed:15663964). This is the major globin CC expressed in vascular smooth muscle and is not present in the CC endothelium (at protein level) (PubMed:28393874). CC {ECO:0000269|PubMed:15663964, ECO:0000269|PubMed:28393874}. CC -!- PTM: The formation of an intramolecular disulfide bond between CC cysteines Cys-38 and Cys-83 specifically enhances the nitrite reductase CC activity. {ECO:0000250|UniProtKB:Q8WWM9}. CC -!- DISRUPTION PHENOTYPE: Homozygous knockout mice display marked CC vasodilation with lower blood pressure and systemic vascular resistance CC associated with increased levels of nitric oxide. CC {ECO:0000269|PubMed:28393874}. CC -!- SIMILARITY: Belongs to the globin family. {ECO:0000255|PROSITE- CC ProRule:PRU00238}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ315163; CAC86187.1; -; mRNA. DR EMBL; AK019410; BAB31709.1; -; mRNA. DR EMBL; BC055040; AAH55040.1; -; mRNA. DR CCDS; CCDS25673.1; -. DR RefSeq; NP_084482.1; NM_030206.4. DR AlphaFoldDB; Q9CX80; -. DR SMR; Q9CX80; -. DR BioGRID; 227897; 4. DR STRING; 10090.ENSMUSP00000021166; -. DR GlyGen; Q9CX80; 5 sites, 1 O-linked glycan (5 sites). DR iPTMnet; Q9CX80; -. DR PhosphoSitePlus; Q9CX80; -. DR MaxQB; Q9CX80; -. DR PaxDb; 10090-ENSMUSP00000021166; -. DR ProteomicsDB; 277936; -. DR Antibodypedia; 2901; 366 antibodies from 32 providers. DR DNASU; 114886; -. DR Ensembl; ENSMUST00000021166.6; ENSMUSP00000021166.6; ENSMUSG00000020810.6. DR GeneID; 114886; -. DR KEGG; mmu:114886; -. DR UCSC; uc007mlv.1; mouse. DR AGR; MGI:2149481; -. DR CTD; 114757; -. DR MGI; MGI:2149481; Cygb. DR VEuPathDB; HostDB:ENSMUSG00000020810; -. DR eggNOG; KOG3378; Eukaryota. DR GeneTree; ENSGT00940000155004; -. DR HOGENOM; CLU_003827_10_1_1; -. DR InParanoid; Q9CX80; -. DR OMA; ETQRAWT; -. DR OrthoDB; 5347904at2759; -. DR PhylomeDB; Q9CX80; -. DR TreeFam; TF332967; -. DR Reactome; R-MMU-203615; eNOS activation. DR Reactome; R-MMU-8981607; Intracellular oxygen transport. DR BioGRID-ORCS; 114886; 3 hits in 77 CRISPR screens. DR ChiTaRS; Cygb; mouse. DR PRO; PR:Q9CX80; -. DR Proteomes; UP000000589; Chromosome 11. DR RNAct; Q9CX80; Protein. DR Bgee; ENSMUSG00000020810; Expressed in interventricular septum and 239 other cell types or tissues. DR ExpressionAtlas; Q9CX80; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0043005; C:neuron projection; IDA:MGI. DR GO; GO:0043025; C:neuronal cell body; IDA:MGI. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0070025; F:carbon monoxide binding; IEA:Ensembl. DR GO; GO:0004096; F:catalase activity; ISO:MGI. DR GO; GO:0047888; F:fatty acid peroxidase activity; ISO:MGI. DR GO; GO:0020037; F:heme binding; ISO:MGI. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0098809; F:nitrite reductase activity; ISS:UniProtKB. DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central. DR GO; GO:0016675; F:oxidoreductase activity, acting on a heme group of donors; IDA:UniProtKB. DR GO; GO:0019825; F:oxygen binding; IEA:Ensembl. DR GO; GO:0005344; F:oxygen carrier activity; IEA:UniProtKB-KW. DR GO; GO:0004601; F:peroxidase activity; ISS:UniProtKB. DR GO; GO:0004784; F:superoxide dismutase activity; IMP:UniProtKB. DR GO; GO:0019395; P:fatty acid oxidation; ISO:MGI. DR GO; GO:0032966; P:negative regulation of collagen biosynthetic process; ISO:MGI. DR GO; GO:0010764; P:negative regulation of fibroblast migration; ISO:MGI. DR GO; GO:2000490; P:negative regulation of hepatic stellate cell activation; ISO:MGI. DR GO; GO:0046210; P:nitric oxide catabolic process; IDA:UniProtKB. DR GO; GO:0019430; P:removal of superoxide radicals; IMP:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0006979; P:response to oxidative stress; ISS:UniProtKB. DR CDD; cd08924; Cygb; 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 InterPro; IPR013314; Globin_lamprey/hagfish. DR PANTHER; PTHR46783; CYTOGLOBIN; 1. DR PANTHER; PTHR46783:SF1; CYTOGLOBIN; 1. DR Pfam; PF00042; Globin; 1. DR PRINTS; PR01906; FISHGLOBIN. DR SUPFAM; SSF46458; Globin-like; 1. DR PROSITE; PS01033; GLOBIN; 1. DR Genevisible; Q9CX80; MM. PE 1: Evidence at protein level; KW Cytoplasm; Disulfide bond; Heme; Iron; Metal-binding; Nucleus; KW Oxidoreductase; Reference proteome. FT CHAIN 1..190 FT /note="Cytoglobin" FT /id="PRO_0000053385" FT REGION 1..21 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 81 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:0000250|UniProtKB:Q8WWM9, FT ECO:0000255|PROSITE-ProRule:PRU00238" FT BINDING 113 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:0000250|UniProtKB:Q8WWM9, FT ECO:0000255|PROSITE-ProRule:PRU00238" FT DISULFID 38..83 FT /note="Redox-active; in monomeric form" FT /evidence="ECO:0000250|UniProtKB:Q8WWM9" FT DISULFID 38 FT /note="Interchain (with C-83); in dimeric form" FT /evidence="ECO:0000250|UniProtKB:Q8WWM9" FT DISULFID 83 FT /note="Interchain (with C-38); in dimeric form" FT /evidence="ECO:0000250|UniProtKB:Q8WWM9" SQ SEQUENCE 190 AA; 21466 MW; 6B1A50403F790FF7 CRC64; MEKVPGDMEI ERRERSEELS EAERKAVQAT WARLYANCED VGVAILVRFF VNFPSAKQYF SQFRHMEDPL EMERSPQLRK HACRVMGALN TVVENLHDPD KVSSVLALVG KAHALKHKVE PMYFKILSGV ILEVIAEEFA NDFPVETQKA WAKLRGLIYS HVTAAYKEVG WVQQVPNTTT PPATLPSSGP //