MTND_MOUSE
ID MTND_MOUSE Reviewed; 179 AA.
AC Q99JT9;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Acireductone dioxygenase {ECO:0000255|HAMAP-Rule:MF_03154};
DE AltName: Full=Acireductone dioxygenase (Fe(2+)-requiring) {ECO:0000255|HAMAP-Rule:MF_03154};
DE Short=ARD' {ECO:0000255|HAMAP-Rule:MF_03154};
DE Short=Fe-ARD {ECO:0000255|HAMAP-Rule:MF_03154};
DE EC=1.13.11.54 {ECO:0000269|PubMed:26858196};
DE AltName: Full=Acireductone dioxygenase (Ni(2+)-requiring) {ECO:0000255|HAMAP-Rule:MF_03154};
DE Short=ARD {ECO:0000255|HAMAP-Rule:MF_03154};
DE Short=Ni-ARD {ECO:0000255|HAMAP-Rule:MF_03154};
DE EC=1.13.11.53 {ECO:0000269|PubMed:26858196};
DE AltName: Full=Membrane-type 1 matrix metalloproteinase cytoplasmic tail-binding protein 1 {ECO:0000255|HAMAP-Rule:MF_03154};
DE Short=MTCBP-1 {ECO:0000255|HAMAP-Rule:MF_03154};
GN Name=Adi1; Synonyms=Mtcbp1;
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].
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=FVB/N; TISSUE=Mammary tumor;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC 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 [4]
RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) IN COMPLEX WITH NICKEL, COFACTOR,
RP AND SUBUNIT.
RX PubMed=16783794; DOI=10.1002/prot.20947;
RA Xu Q., Schwarzenbacher R., Krishna S.S., McMullan D., Agarwalla S.,
RA Quijano K., Abdubek P., Ambing E., Axelrod H., Biorac T., Canaves J.M.,
RA Chiu H.J., Elsliger M.A., Grittini C., Grzechnik S.K., DiDonato M.,
RA Hale J., Hampton E., Han G.W., Haugen J., Hornsby M., Jaroszewski L.,
RA Klock H.E., Knuth M.W., Koesema E., Kreusch A., Kuhn P., Miller M.D.,
RA Moy K., Nigoghossian E., Paulsen J., Reyes R., Rife C., Spraggon G.,
RA Stevens R.C., van den Bedem H., Velasquez J., White A., Wolf G.,
RA Hodgson K.O., Wooley J., Deacon A.M., Godzik A., Lesley S.A., Wilson I.A.;
RT "Crystal structure of acireductone dioxygenase (ARD) from Mus musculus at
RT 2.06 angstrom resolution.";
RL Proteins 64:808-813(2006).
RN [5] {ECO:0007744|PDB:5I8S, ECO:0007744|PDB:5I8T, ECO:0007744|PDB:5I8Y, ECO:0007744|PDB:5I91, ECO:0007744|PDB:5I93}
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEXES WITH NICKEL AND
RP SUBSTRATE ANALOGS, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP FUNCTION, AND COFACTOR.
RX PubMed=26858196; DOI=10.1021/acs.biochem.5b01319;
RA Deshpande A.R., Wagenpfeil K., Pochapsky T.C., Petsko G.A., Ringe D.;
RT "Metal-dependent function of a mammalian acireductone dioxygenase.";
RL Biochemistry 55:1398-1407(2016).
CC -!- FUNCTION: Catalyzes 2 different reactions between oxygen and the
CC acireductone 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene)
CC depending upon the metal bound in the active site (PubMed:26858196).
CC Fe-containing acireductone dioxygenase (Fe-ARD) produces formate and 2-
CC keto-4-methylthiobutyrate (KMTB), the alpha-ketoacid precursor of
CC methionine in the methionine recycle pathway (PubMed:26858196). Ni-
CC containing acireductone dioxygenase (Ni-ARD) produces
CC methylthiopropionate, carbon monoxide and formate, and does not lie on
CC the methionine recycle pathway (PubMed:26858196). Also down-regulates
CC cell migration mediated by MMP14 (By similarity). {ECO:0000255|HAMAP-
CC Rule:MF_03154, ECO:0000269|PubMed:26858196}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihydroxy-5-(methylsulfanyl)pent-1-en-3-one + O2 = 4-
CC methylsulfanyl-2-oxobutanoate + formate + 2 H(+);
CC Xref=Rhea:RHEA:24504, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:16723, ChEBI:CHEBI:49252;
CC EC=1.13.11.54; Evidence={ECO:0000269|PubMed:26858196};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihydroxy-5-(methylsulfanyl)pent-1-en-3-one + O2 = 3-
CC (methylsulfanyl)propanoate + CO + formate + 2 H(+);
CC Xref=Rhea:RHEA:14161, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:17245, ChEBI:CHEBI:49016,
CC ChEBI:CHEBI:49252; EC=1.13.11.53;
CC Evidence={ECO:0000269|PubMed:26858196};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:26858196};
CC Name=Ni(2+); Xref=ChEBI:CHEBI:49786;
CC Evidence={ECO:0000269|PubMed:16783794, ECO:0000269|PubMed:26858196};
CC Note=Binds either 1 Fe or Ni cation per monomer (PubMed:26858196).
CC Iron-binding promotes an acireductone dioxygenase reaction producing 2-
CC keto-4-methylthiobutyrate, while nickel-binding promotes an
CC acireductone dioxygenase reaction producing 3-
CC (methylsulfanyl)propanoate (PubMed:26858196).
CC {ECO:0000269|PubMed:26858196};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.123 mM for 1,2-dihydroxy-5-(methylsulfanyl)pent-1-en-3-one
CC (using iron as cofactor) {ECO:0000269|PubMed:26858196};
CC KM=0.44 mM for 1,2-dihydroxy-5-(methylsulfanyl)pent-1-en-3-one (using
CC cobalt as cofactor) {ECO:0000269|PubMed:26858196};
CC KM=0.302 mM for 1,2-dihydroxy-5-(methylsulfanyl)pent-1-en-3-one
CC (using nickel as cofactor) {ECO:0000269|PubMed:26858196};
CC Note=kcat is 114.3 sec(-1) with 1,2-dihydroxy-5-(methylsulfanyl)pent-
CC 1-en-3-one as substrate (using iron as cofactor) (PubMed:26858196).
CC kcat is 7.55 sec(-1) with 1,2-dihydroxy-5-(methylsulfanyl)pent-1-en-
CC 3-one as substrate (using cobalt as cofactor) (PubMed:26858196). kcat
CC is 17.7 sec(-1) with 1,2-dihydroxy-5-(methylsulfanyl)pent-1-en-3-one
CC as substrate (using nickel as cofactor) (PubMed:26858196).
CC {ECO:0000269|PubMed:26858196};
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via salvage
CC pathway; L-methionine from S-methyl-5-thio-alpha-D-ribose 1-phosphate:
CC step 5/6. {ECO:0000255|HAMAP-Rule:MF_03154}.
CC -!- SUBUNIT: Monomer. Interacts with MMP14. {ECO:0000255|HAMAP-
CC Rule:MF_03154}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03154}.
CC Nucleus {ECO:0000255|HAMAP-Rule:MF_03154}. Cell membrane
CC {ECO:0000255|HAMAP-Rule:MF_03154}; Peripheral membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_03154}; Cytoplasmic side {ECO:0000255|HAMAP-
CC Rule:MF_03154}. Note=Localizes to the plasma membrane when complexed to
CC MMP14. {ECO:0000255|HAMAP-Rule:MF_03154}.
CC -!- SIMILARITY: Belongs to the acireductone dioxygenase (ARD) family.
CC {ECO:0000255|HAMAP-Rule:MF_03154}.
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DR EMBL; AK145831; BAE26682.1; -; mRNA.
DR EMBL; BC005695; AAH05695.1; -; mRNA.
DR CCDS; CCDS25853.1; -.
DR RefSeq; NP_598813.1; NM_134052.2.
DR PDB; 1VR3; X-ray; 2.06 A; A=1-179.
DR PDB; 5I8S; X-ray; 1.89 A; A=1-179.
DR PDB; 5I8T; X-ray; 1.75 A; A=1-179.
DR PDB; 5I8Y; X-ray; 1.94 A; A=1-179.
DR PDB; 5I91; X-ray; 1.76 A; A=1-179.
DR PDB; 5I93; X-ray; 2.24 A; A=1-179.
DR PDBsum; 1VR3; -.
DR PDBsum; 5I8S; -.
DR PDBsum; 5I8T; -.
DR PDBsum; 5I8Y; -.
DR PDBsum; 5I91; -.
DR PDBsum; 5I93; -.
DR AlphaFoldDB; Q99JT9; -.
DR SMR; Q99JT9; -.
DR BioGRID; 222731; 1.
DR STRING; 10090.ENSMUSP00000020957; -.
DR iPTMnet; Q99JT9; -.
DR PhosphoSitePlus; Q99JT9; -.
DR EPD; Q99JT9; -.
DR jPOST; Q99JT9; -.
DR MaxQB; Q99JT9; -.
DR PaxDb; Q99JT9; -.
DR PeptideAtlas; Q99JT9; -.
DR PRIDE; Q99JT9; -.
DR ProteomicsDB; 287514; -.
DR Antibodypedia; 26318; 314 antibodies from 29 providers.
DR DNASU; 104923; -.
DR Ensembl; ENSMUST00000020957; ENSMUSP00000020957; ENSMUSG00000020629.
DR GeneID; 104923; -.
DR KEGG; mmu:104923; -.
DR UCSC; uc007nfv.1; mouse.
DR CTD; 55256; -.
DR MGI; MGI:2144929; Adi1.
DR VEuPathDB; HostDB:ENSMUSG00000020629; -.
DR eggNOG; KOG2107; Eukaryota.
DR GeneTree; ENSGT00390000008195; -.
DR HOGENOM; CLU_090154_0_1_1; -.
DR InParanoid; Q99JT9; -.
DR OMA; RGQEDEW; -.
DR OrthoDB; 1166094at2759; -.
DR PhylomeDB; Q99JT9; -.
DR TreeFam; TF300231; -.
DR BRENDA; 1.13.11.53; 3474.
DR BRENDA; 1.13.11.54; 3474.
DR Reactome; R-MMU-1237112; Methionine salvage pathway.
DR UniPathway; UPA00904; UER00878.
DR BioGRID-ORCS; 104923; 0 hits in 72 CRISPR screens.
DR EvolutionaryTrace; Q99JT9; -.
DR PRO; PR:Q99JT9; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q99JT9; protein.
DR Bgee; ENSMUSG00000020629; Expressed in left lobe of liver and 268 other tissues.
DR Genevisible; Q99JT9; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0010308; F:acireductone dioxygenase (Ni2+-requiring) activity; IEA:RHEA.
DR GO; GO:0010309; F:acireductone dioxygenase [iron(II)-requiring] activity; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0016491; F:oxidoreductase activity; ISS:UniProtKB.
DR GO; GO:0019509; P:L-methionine salvage from methylthioadenosine; ISS:UniProtKB.
DR GO; GO:0006555; P:methionine metabolic process; IBA:GO_Central.
DR CDD; cd02232; cupin_ARD; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR HAMAP; MF_03154; Salvage_MtnD_euk; 1.
DR InterPro; IPR004313; ARD.
DR InterPro; IPR027496; ARD_euk.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR011051; RmlC_Cupin_sf.
DR PANTHER; PTHR23418; PTHR23418; 1.
DR Pfam; PF03079; ARD; 1.
DR SUPFAM; SSF51182; SSF51182; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Cell membrane; Cytoplasm;
KW Dioxygenase; Iron; Membrane; Metal-binding; Methionine biosynthesis;
KW Nickel; Nucleus; Oxidoreductase; Reference proteome.
FT CHAIN 1..179
FT /note="Acireductone dioxygenase"
FT /id="PRO_0000162943"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 88
FT /ligand="Fe(2+)"
FT /ligand_id="ChEBI:CHEBI:29033"
FT /ligand_note="for iron-dependent acireductone dioxygenase
FT activity"
FT /evidence="ECO:0000305|PubMed:26858196"
FT BINDING 88
FT /ligand="Ni(2+)"
FT /ligand_id="ChEBI:CHEBI:49786"
FT /ligand_note="for nickel-dependent acireductone dioxygenase
FT activity"
FT /evidence="ECO:0000269|PubMed:16783794,
FT ECO:0000269|PubMed:26858196, ECO:0007744|PDB:1VR3,
FT ECO:0007744|PDB:5I8S, ECO:0007744|PDB:5I8T,
FT ECO:0007744|PDB:5I91, ECO:0007744|PDB:5I93"
FT BINDING 90
FT /ligand="Fe(2+)"
FT /ligand_id="ChEBI:CHEBI:29033"
FT /ligand_note="for iron-dependent acireductone dioxygenase
FT activity"
FT /evidence="ECO:0000305|PubMed:26858196"
FT BINDING 90
FT /ligand="Ni(2+)"
FT /ligand_id="ChEBI:CHEBI:49786"
FT /ligand_note="for nickel-dependent acireductone dioxygenase
FT activity"
FT /evidence="ECO:0000269|PubMed:16783794,
FT ECO:0000269|PubMed:26858196, ECO:0007744|PDB:1VR3,
FT ECO:0007744|PDB:5I8S, ECO:0007744|PDB:5I8T,
FT ECO:0007744|PDB:5I91, ECO:0007744|PDB:5I93"
FT BINDING 94
FT /ligand="Fe(2+)"
FT /ligand_id="ChEBI:CHEBI:29033"
FT /ligand_note="for iron-dependent acireductone dioxygenase
FT activity"
FT /evidence="ECO:0000305|PubMed:26858196"
FT BINDING 94
FT /ligand="Ni(2+)"
FT /ligand_id="ChEBI:CHEBI:49786"
FT /ligand_note="for nickel-dependent acireductone dioxygenase
FT activity"
FT /evidence="ECO:0000269|PubMed:16783794,
FT ECO:0000269|PubMed:26858196, ECO:0007744|PDB:1VR3,
FT ECO:0007744|PDB:5I8S, ECO:0007744|PDB:5I8T,
FT ECO:0007744|PDB:5I91, ECO:0007744|PDB:5I93"
FT BINDING 133
FT /ligand="Fe(2+)"
FT /ligand_id="ChEBI:CHEBI:29033"
FT /ligand_note="for iron-dependent acireductone dioxygenase
FT activity"
FT /evidence="ECO:0000305|PubMed:26858196"
FT BINDING 133
FT /ligand="Ni(2+)"
FT /ligand_id="ChEBI:CHEBI:49786"
FT /ligand_note="for nickel-dependent acireductone dioxygenase
FT activity"
FT /evidence="ECO:0000269|PubMed:16783794,
FT ECO:0000269|PubMed:26858196, ECO:0007744|PDB:1VR3,
FT ECO:0007744|PDB:5I8S, ECO:0007744|PDB:5I8T,
FT ECO:0007744|PDB:5I91, ECO:0007744|PDB:5I93"
FT STRAND 3..7
FT /evidence="ECO:0007829|PDB:5I8T"
FT HELIX 28..33
FT /evidence="ECO:0007829|PDB:5I8T"
FT STRAND 37..40
FT /evidence="ECO:0007829|PDB:5I8T"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:5I8T"
FT HELIX 50..59
FT /evidence="ECO:0007829|PDB:5I8T"
FT STRAND 63..69
FT /evidence="ECO:0007829|PDB:5I8T"
FT TURN 71..73
FT /evidence="ECO:0007829|PDB:5I8T"
FT HELIX 77..85
FT /evidence="ECO:0007829|PDB:5I8T"
FT STRAND 94..108
FT /evidence="ECO:0007829|PDB:5I8T"
FT STRAND 114..120
FT /evidence="ECO:0007829|PDB:5I8T"
FT STRAND 123..127
FT /evidence="ECO:0007829|PDB:5I8T"
FT STRAND 133..137
FT /evidence="ECO:0007829|PDB:5I8T"
FT STRAND 143..152
FT /evidence="ECO:0007829|PDB:5I8T"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:5I8T"
FT HELIX 166..176
FT /evidence="ECO:0007829|PDB:5I8T"
SQ SEQUENCE 179 AA; 21524 MW; 02CE7B89181EBEFE CRC64;
MVQAWYMDES TADPRKPHRA QPDRPVSLEQ LRTLGVLYWK LDADKYENDP ELEKIRKMRN
YSWMDIITIC KDTLPNYEEK IKMFFEEHLH LDEEIRYILE GSGYFDVRDK EDKWIRISME
KGDMITLPAG IYHRFTLDEK NYVKAMRLFV GEPVWTPYNR PADHFDARVQ YMSFLEGTA
