AEDO_HUMAN
ID AEDO_HUMAN Reviewed; 270 AA.
AC Q96SZ5; B1AL29;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2006, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=2-aminoethanethiol dioxygenase;
DE EC=1.13.11.19 {ECO:0000269|PubMed:17581819, ECO:0000269|PubMed:29752763, ECO:0000269|PubMed:32601061};
DE AltName: Full=Cysteamine dioxygenase;
GN Name=ADO; Synonyms=C10orf22;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS TRP-25 AND ALA-39.
RC TISSUE=Brain, and Testis;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 35-270, AND VARIANT ALA-39.
RC TISSUE=Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, CROSS-LINK,
RP AND MUTAGENESIS OF TYR-87; TYR-222 AND TYR-223.
RX PubMed=29752763; DOI=10.1002/anie.201803907;
RA Wang Y., Griffith W.P., Li J., Koto T., Wherritt D.J., Fritz E., Liu A.;
RT "Cofactor Biogenesis in Cysteamine Dioxygenase: C-F Bond Cleavage with
RT Genetically Incorporated Unnatural Tyrosine.";
RL Angew. Chem. Int. Ed. 57:8149-8153(2018).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=31273118; DOI=10.1126/science.aaw0112;
RA Masson N., Keeley T.P., Giuntoli B., White M.D., Puerta M.L., Perata P.,
RA Hopkinson R.J., Flashman E., Licausi F., Ratcliffe P.J.;
RT "Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia
RT in animals and plants.";
RL Science 365:65-69(2019).
RN [9]
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 [10] {ECO:0007744|PDB:7REI}
RP X-RAY CRYSTALLOGRAPHY (1.78 ANGSTROMS) OF MUTANTS SER-18/SER-239 IN COMPLEX
RP WITH NICKEL, SUBUNIT, COFACTOR, AND IRON-BINDING SITES.
RX PubMed=34508780; DOI=10.1016/j.jbc.2021.101176;
RA Wang Y., Shin I., Li J., Liu A.;
RT "Crystal structure of human cysteamine dioxygenase provides a structural
RT rationale for its function as an oxygen sensor.";
RL J. Biol. Chem. 297:101176-101176(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:29752763,
CC PubMed:31273118, PubMed:32601061). Catalyzes the oxidation of
CC cysteamine (2-aminoethanethiol) to hypotaurine (PubMed:17581819,
CC PubMed:29752763, PubMed:32601061). Catalyzes the oxidation of
CC regulators of G-protein signaling 4 (RGS4) and 5 (RGS5) and
CC interleukin-32 (IL32) (PubMed:31273118, PubMed:32601061).
CC {ECO:0000269|PubMed:17581819, ECO:0000269|PubMed:29752763,
CC ECO:0000269|PubMed:31273118, 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:29752763,
CC 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:31273118, ECO:0000269|PubMed:32601061};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70896;
CC Evidence={ECO:0000305|PubMed:31273118};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:34508780};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.4 mM for cysteamine {ECO:0000269|PubMed:29752763};
CC KM=123 uM for RGS4 {ECO:0000269|PubMed:31273118};
CC KM=71.51 uM for RGS5 {ECO:0000269|PubMed:31273118};
CC KM=33.6 uM for IL32 {ECO:0000269|PubMed:31273118};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:34508780}.
CC -!- INTERACTION:
CC Q96SZ5; P40123: CAP2; NbExp=3; IntAct=EBI-11102284, EBI-1051165;
CC Q96SZ5; Q9NRI5-2: DISC1; NbExp=3; IntAct=EBI-11102284, EBI-11988027;
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB55123.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL133417; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471083; EAW54235.1; -; Genomic_DNA.
DR EMBL; BC018660; AAH18660.3; -; mRNA.
DR EMBL; BC028589; AAH28589.2; -; mRNA.
DR EMBL; BC067740; AAH67740.2; -; mRNA.
DR EMBL; AK027453; BAB55123.1; ALT_INIT; mRNA.
DR CCDS; CCDS7266.2; -.
DR RefSeq; NP_116193.2; NM_032804.5.
DR PDB; 7REI; X-ray; 1.78 A; A=1-270.
DR PDBsum; 7REI; -.
DR AlphaFoldDB; Q96SZ5; -.
DR SMR; Q96SZ5; -.
DR BioGRID; 124330; 18.
DR IntAct; Q96SZ5; 10.
DR STRING; 9606.ENSP00000362888; -.
DR GlyGen; Q96SZ5; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96SZ5; -.
DR MetOSite; Q96SZ5; -.
DR PhosphoSitePlus; Q96SZ5; -.
DR BioMuta; ADO; -.
DR DMDM; 88984104; -.
DR EPD; Q96SZ5; -.
DR jPOST; Q96SZ5; -.
DR MassIVE; Q96SZ5; -.
DR MaxQB; Q96SZ5; -.
DR PaxDb; Q96SZ5; -.
DR PeptideAtlas; Q96SZ5; -.
DR PRIDE; Q96SZ5; -.
DR ProteomicsDB; 78164; -.
DR Antibodypedia; 45164; 201 antibodies from 26 providers.
DR DNASU; 84890; -.
DR Ensembl; ENST00000373783.3; ENSP00000362888.1; ENSG00000181915.5.
DR GeneID; 84890; -.
DR KEGG; hsa:84890; -.
DR MANE-Select; ENST00000373783.3; ENSP00000362888.1; NM_032804.6; NP_116193.2.
DR UCSC; uc001jmg.4; human.
DR CTD; 84890; -.
DR DisGeNET; 84890; -.
DR GeneCards; ADO; -.
DR HGNC; HGNC:23506; ADO.
DR HPA; ENSG00000181915; Low tissue specificity.
DR MIM; 611392; gene.
DR neXtProt; NX_Q96SZ5; -.
DR OpenTargets; ENSG00000181915; -.
DR PharmGKB; PA162375713; -.
DR VEuPathDB; HostDB:ENSG00000181915; -.
DR eggNOG; KOG4281; Eukaryota.
DR GeneTree; ENSGT00390000014082; -.
DR HOGENOM; CLU_061320_2_1_1; -.
DR InParanoid; Q96SZ5; -.
DR OMA; CVLTPHR; -.
DR OrthoDB; 929927at2759; -.
DR PhylomeDB; Q96SZ5; -.
DR TreeFam; TF314673; -.
DR BioCyc; MetaCyc:HS17749-MON; -.
DR BRENDA; 1.13.11.19; 2681.
DR PathwayCommons; Q96SZ5; -.
DR Reactome; R-HSA-1614558; Degradation of cysteine and homocysteine.
DR SignaLink; Q96SZ5; -.
DR BioGRID-ORCS; 84890; 46 hits in 1078 CRISPR screens.
DR ChiTaRS; ADO; human.
DR GenomeRNAi; 84890; -.
DR Pharos; Q96SZ5; Tbio.
DR PRO; PR:Q96SZ5; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q96SZ5; protein.
DR Bgee; ENSG00000181915; Expressed in sperm and 208 other tissues.
DR Genevisible; Q96SZ5; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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; IDA: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; Thioether bond.
FT CHAIN 1..270
FT /note="2-aminoethanethiol dioxygenase"
FT /id="PRO_0000089784"
FT REGION 21..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 140..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 112
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:34508780,
FT ECO:0007744|PDB:7REI"
FT BINDING 114
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:34508780,
FT ECO:0007744|PDB:7REI"
FT BINDING 193
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:34508780,
FT ECO:0007744|PDB:7REI"
FT CROSSLNK 220..223
FT /note="3'-(S-cysteinyl)-tyrosine (Cys-Tyr)"
FT /evidence="ECO:0000269|PubMed:29752763"
FT VARIANT 25
FT /note="G -> W (in dbSNP:rs2236295)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_025333"
FT VARIANT 39
FT /note="P -> A (in dbSNP:rs10995311)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_025334"
FT VARIANT 266
FT /note="P -> S (in dbSNP:rs569705)"
FT /id="VAR_033691"
FT MUTAGEN 87
FT /note="Y->A: Moderate reduction in enzyme activity."
FT /evidence="ECO:0000269|PubMed:29752763"
FT MUTAGEN 222
FT /note="Y->A,F: Significant reduction in enzyme activity."
FT /evidence="ECO:0000269|PubMed:29752763"
FT MUTAGEN 223
FT /note="Y->A: No significant reduction in enzyme activity."
FT /evidence="ECO:0000269|PubMed:29752763"
FT HELIX 9..21
FT /evidence="ECO:0007829|PDB:7REI"
FT HELIX 47..60
FT /evidence="ECO:0007829|PDB:7REI"
FT HELIX 63..66
FT /evidence="ECO:0007829|PDB:7REI"
FT STRAND 84..92
FT /evidence="ECO:0007829|PDB:7REI"
FT STRAND 97..103
FT /evidence="ECO:0007829|PDB:7REI"
FT STRAND 108..112
FT /evidence="ECO:0007829|PDB:7REI"
FT STRAND 118..135
FT /evidence="ECO:0007829|PDB:7REI"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:7REI"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:7REI"
FT HELIX 159..164
FT /evidence="ECO:0007829|PDB:7REI"
FT STRAND 166..176
FT /evidence="ECO:0007829|PDB:7REI"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:7REI"
FT STRAND 192..210
FT /evidence="ECO:0007829|PDB:7REI"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:7REI"
FT STRAND 222..225
FT /evidence="ECO:0007829|PDB:7REI"
FT STRAND 241..250
FT /evidence="ECO:0007829|PDB:7REI"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:7REI"
SQ SEQUENCE 270 AA; 29751 MW; 6B496CCF16E92C9D CRC64;
MPRDNMASLI QRIARQACLT FRGSGGGRGA SDRDAASGPE APMQPGFPEN LSKLKSLLTQ
LRAEDLNIAP RKATLQPLPP NLPPVTYMHI YETDGFSLGV FLLKSGTSIP LHDHPGMHGM
LKVLYGTVRI SCMDKLDAGG GQRPRALPPE QQFEPPLQPR EREAVRPGVL RSRAEYTEAS
GPCILTPHRD NLHQIDAVEG PAAFLDILAP PYDPDDGRDC HYYRVLEPVR PKEASSSACD
LPREVWLLET PQADDFWCEG EPYPGPKVFP
