AEDO_MOUSE
ID AEDO_MOUSE Reviewed; 256 AA.
AC Q6PDY2; Q3U2E1;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2006, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=2-aminoethanethiol dioxygenase;
DE EC=1.13.11.19 {ECO:0000269|PubMed:17581819, ECO:0000269|PubMed:32601061};
DE AltName: Full=Cysteamine dioxygenase;
GN Name=Ado; Synonyms=Gm237;
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 [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Dendritic cell;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; 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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, TISSUE SPECIFICITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF HIS-102, AND IRON-BINDING
RP SITE.
RX PubMed=17581819; DOI=10.1074/jbc.m703089200;
RA Dominy J.E. Jr., Simmons C.R., Hirschberger L.L., Hwang J., Coloso R.M.,
RA Stipanuk M.H.;
RT "Discovery and characterization of a second mammalian thiol dioxygenase,
RT cysteamine dioxygenase.";
RL J. Biol. Chem. 282:25189-25198(2007).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Lung, Pancreas, Spleen, and 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 [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=32601061; DOI=10.1074/jbc.ra120.013915;
RA Wang Y., Davis I., Chan Y., Naik S.G., Griffith W.P., Liu A.;
RT "Characterization of the nonheme iron center of cysteamine dioxygenase and
RT its interaction with substrates.";
RL J. Biol. Chem. 295:11789-11802(2020).
RN [6] {ECO:0007744|PDB:7LVZ}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS), SUBUNIT, COFACTOR, AND IRON-BINDING
RP SITES.
RX PubMed=34762398; DOI=10.1021/acs.biochem.1c00463;
RA Fernandez R.L., Elmendorf L.D., Smith R.W., Bingman C.A., Fox B.G.,
RA Brunold T.C.;
RT "The Crystal Structure of Cysteamine Dioxygenase Reveals the Origin of the
RT Large Substrate Scope of This Vital Mammalian Enzyme.";
RL Biochemistry 60:3728-3737(2021).
CC -!- FUNCTION: Plays a vital role in regulating thiol metabolism and
CC preserving oxygen homeostasis by oxidizing the sulfur of cysteamine and
CC N-terminal cysteine-containing proteins to their corresponding sulfinic
CC acids using O2 as a cosubstrate (PubMed:17581819, PubMed:32601061).
CC Catalyzes the oxidation of cysteamine (2-aminoethanethiol) to
CC hypotaurine (PubMed:17581819, PubMed:32601061). Catalyzes the oxidation
CC of the regulator of G-protein signaling 5 (RGS5) (PubMed:32601061).
CC Also oxidizes proteins RGS4 and interleukin-32 (IL32) (By similarity).
CC {ECO:0000250|UniProtKB:Q96SZ5, ECO:0000269|PubMed:17581819,
CC ECO:0000269|PubMed:32601061}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cysteamine + O2 = H(+) + hypotaurine; Xref=Rhea:RHEA:14409,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57853,
CC ChEBI:CHEBI:58029; EC=1.13.11.19;
CC Evidence={ECO:0000269|PubMed:17581819, ECO:0000269|PubMed:32601061};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14410;
CC Evidence={ECO:0000305|PubMed:17581819};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-terminal L-cysteinyl-[protein] + O2 = H(+) + N-terminal S-
CC hydroxy-S-oxy-L-cysteinyl-[protein]; Xref=Rhea:RHEA:70895, Rhea:RHEA-
CC COMP:12707, Rhea:RHEA-COMP:17973, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:65250, ChEBI:CHEBI:156254;
CC Evidence={ECO:0000269|PubMed:32601061};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70896;
CC Evidence={ECO:0000305|PubMed:32601061};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:17581819, ECO:0000269|PubMed:34762398};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.8 mM for cysteamine {ECO:0000269|PubMed:17581819};
CC Vmax=2300 nmol/min/mg enzyme for cysteamine
CC {ECO:0000269|PubMed:17581819};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:34762398}.
CC -!- TISSUE SPECIFICITY: Ubiquitous, with highest expression in brain, heart
CC and skeletal muscle (at protein level). {ECO:0000269|PubMed:17581819}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH57106.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH58407.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK155334; BAE33200.1; -; mRNA.
DR EMBL; BC057106; AAH57106.1; ALT_INIT; mRNA.
DR EMBL; BC058407; AAH58407.1; ALT_INIT; mRNA.
DR CCDS; CCDS48588.1; -.
DR RefSeq; NP_001005419.2; NM_001005419.2.
DR PDB; 7LVZ; X-ray; 1.89 A; A/B/C/D=1-256.
DR PDBsum; 7LVZ; -.
DR AlphaFoldDB; Q6PDY2; -.
DR SMR; Q6PDY2; -.
DR STRING; 10090.ENSMUSP00000075107; -.
DR iPTMnet; Q6PDY2; -.
DR PhosphoSitePlus; Q6PDY2; -.
DR EPD; Q6PDY2; -.
DR MaxQB; Q6PDY2; -.
DR PaxDb; Q6PDY2; -.
DR PeptideAtlas; Q6PDY2; -.
DR PRIDE; Q6PDY2; -.
DR ProteomicsDB; 296192; -.
DR Antibodypedia; 45164; 201 antibodies from 26 providers.
DR DNASU; 211488; -.
DR Ensembl; ENSMUST00000075686; ENSMUSP00000075107; ENSMUSG00000057134.
DR GeneID; 211488; -.
DR KEGG; mmu:211488; -.
DR UCSC; uc007flz.2; mouse.
DR CTD; 84890; -.
DR MGI; MGI:2685083; Ado.
DR VEuPathDB; HostDB:ENSMUSG00000057134; -.
DR eggNOG; KOG4281; Eukaryota.
DR GeneTree; ENSGT00390000014082; -.
DR HOGENOM; CLU_061320_2_1_1; -.
DR InParanoid; Q6PDY2; -.
DR OMA; CVLTPHR; -.
DR OrthoDB; 929927at2759; -.
DR PhylomeDB; Q6PDY2; -.
DR TreeFam; TF314673; -.
DR BRENDA; 1.13.11.19; 3474.
DR Reactome; R-MMU-1614558; Degradation of cysteine and homocysteine.
DR BioGRID-ORCS; 211488; 7 hits in 73 CRISPR screens.
DR PRO; PR:Q6PDY2; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q6PDY2; protein.
DR Bgee; ENSMUSG00000057134; Expressed in neural tube and 65 other tissues.
DR Genevisible; Q6PDY2; MM.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0047800; F:cysteamine dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR012864; PCO/ADO.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR011051; RmlC_Cupin_sf.
DR PANTHER; PTHR22966; PTHR22966; 1.
DR Pfam; PF07847; PCO_ADO; 1.
DR SUPFAM; SSF51182; SSF51182; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Dioxygenase; Iron; Metal-binding; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..256
FT /note="2-aminoethanethiol dioxygenase"
FT /id="PRO_0000089785"
FT BINDING 100
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:34762398,
FT ECO:0007744|PDB:7LVZ"
FT BINDING 102
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:17581819,
FT ECO:0000269|PubMed:34762398, ECO:0007744|PDB:7LVZ"
FT BINDING 179
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:34762398,
FT ECO:0007744|PDB:7LVZ"
FT MUTAGEN 102
FT /note="H->A: Loss of enzyme activity and iron
FT incorporation."
FT /evidence="ECO:0000269|PubMed:17581819"
FT HELIX 9..20
FT /evidence="ECO:0007829|PDB:7LVZ"
FT HELIX 35..47
FT /evidence="ECO:0007829|PDB:7LVZ"
FT HELIX 51..54
FT /evidence="ECO:0007829|PDB:7LVZ"
FT STRAND 72..80
FT /evidence="ECO:0007829|PDB:7LVZ"
FT STRAND 85..91
FT /evidence="ECO:0007829|PDB:7LVZ"
FT STRAND 96..100
FT /evidence="ECO:0007829|PDB:7LVZ"
FT STRAND 106..123
FT /evidence="ECO:0007829|PDB:7LVZ"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:7LVZ"
FT HELIX 145..150
FT /evidence="ECO:0007829|PDB:7LVZ"
FT STRAND 152..163
FT /evidence="ECO:0007829|PDB:7LVZ"
FT STRAND 169..172
FT /evidence="ECO:0007829|PDB:7LVZ"
FT STRAND 178..196
FT /evidence="ECO:0007829|PDB:7LVZ"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:7LVZ"
FT STRAND 208..212
FT /evidence="ECO:0007829|PDB:7LVZ"
FT STRAND 227..236
FT /evidence="ECO:0007829|PDB:7LVZ"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:7LVZ"
SQ SEQUENCE 256 AA; 28372 MW; C5E23C4A72A79678 CRC64;
MPRDNMASLI QRIARQACLT FRGSSTGSEG PAPGFPENLS LLKSLLTQVR AEDLNIAPRK
ALPQPLPRNL PPVTYMHIYE TEGFSLGVFL LKSGTCIPLH DHPGMHGMLK VLYGTVRISC
MDKLDTGAGH RRPPPEQQFE PPLQPLEREA VRPGVLRSRA EYTEASGPCV LTPHRDNLHQ
IDAVDGPAAF LDILAPPYDP EDGRDCHYYR VVEPIRPKEA SGSACDLPRE VWLLETPQAD
DFWCEGEPYP GPKVLP
