SAHH_DROME
ID SAHH_DROME Reviewed; 432 AA.
AC Q27580; Q8MZI1; Q9VXV5;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2005, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Adenosylhomocysteinase {ECO:0000303|PubMed:9037110, ECO:0000312|FlyBase:FBgn0014455};
DE Short=AdoHcyase {ECO:0000303|PubMed:9037110};
DE EC=3.3.1.1 {ECO:0000305|PubMed:27313316};
DE AltName: Full=S-adenosyl-L-homocysteine hydrolase {ECO:0000303|PubMed:9037110};
GN Name=Ahcy {ECO:0000303|PubMed:9037110, ECO:0000312|FlyBase:FBgn0014455};
GN Synonyms=Ahcy13 {ECO:0000303|PubMed:27313316,
GN ECO:0000312|FlyBase:FBgn0014455};
GN ORFNames=CG11654 {ECO:0000312|FlyBase:FBgn0014455};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9037110; DOI=10.1007/s004380050348;
RA Caggese C., Ragone G., Barsanti P., Moschetti R., Messina A., Massari S.,
RA Caizzi R.;
RT "The S-adenosyl-L-homocysteine hydrolase of Drosophila melanogaster:
RT identification, deduced amino acid sequence and cytological localization of
RT the structural gene.";
RL Mol. Gen. Genet. 253:492-498(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Ovary;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP INTERACTION WITH AHCYL1, AND DISRUPTION PHENOTYPE.
RX PubMed=27313316; DOI=10.1101/gad.282277.116;
RA Parkhitko A.A., Binari R., Zhang N., Asara J.M., Demontis F., Perrimon N.;
RT "Tissue-specific down-regulation of S-adenosyl-homocysteine via suppression
RT of dAhcyL1/dAhcyL2 extends health span and life span in Drosophila.";
RL Genes Dev. 30:1409-1422(2016).
CC -!- FUNCTION: Adenosylhomocysteine is a competitive inhibitor of S-
CC adenosyl-L-methionine-dependent methyl transferase reactions; therefore
CC adenosylhomocysteinase may play a key role in the control of
CC methylations via regulation of the intracellular concentration of
CC adenosylhomocysteine. {ECO:0000305|PubMed:27313316}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + S-adenosyl-L-homocysteine = adenosine + L-homocysteine;
CC Xref=Rhea:RHEA:21708, ChEBI:CHEBI:15377, ChEBI:CHEBI:16335,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:58199; EC=3.3.1.1;
CC Evidence={ECO:0000305|PubMed:27313316};
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000250|UniProtKB:P10760};
CC Note=Binds 1 NAD(+) per subunit. {ECO:0000250|UniProtKB:P10760};
CC -!- PATHWAY: Amino-acid biosynthesis; L-homocysteine biosynthesis; L-
CC homocysteine from S-adenosyl-L-homocysteine: step 1/1.
CC {ECO:0000305|PubMed:27313316}.
CC -!- SUBUNIT: Interacts with AhcyL1; the interaction may negatively regulate
CC Ahcy catalytic activity. {ECO:0000269|PubMed:27313316}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in increased S-
CC adenosyl-homocysteine levels and reduced lifespan.
CC {ECO:0000269|PubMed:27313316}.
CC -!- SIMILARITY: Belongs to the adenosylhomocysteinase family.
CC {ECO:0000305}.
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DR EMBL; X95636; CAA64892.1; -; mRNA.
DR EMBL; AE014298; AAF48453.1; -; Genomic_DNA.
DR EMBL; AY102668; AAM27497.1; -; mRNA.
DR RefSeq; NP_001285268.1; NM_001298339.1.
DR RefSeq; NP_511164.2; NM_078609.4.
DR AlphaFoldDB; Q27580; -.
DR SMR; Q27580; -.
DR BioGRID; 58824; 9.
DR IntAct; Q27580; 5.
DR STRING; 7227.FBpp0073847; -.
DR PaxDb; Q27580; -.
DR PRIDE; Q27580; -.
DR DNASU; 32471; -.
DR EnsemblMetazoa; FBtr0074030; FBpp0073847; FBgn0014455.
DR EnsemblMetazoa; FBtr0346181; FBpp0312000; FBgn0014455.
DR GeneID; 32471; -.
DR KEGG; dme:Dmel_CG11654; -.
DR CTD; 191; -.
DR FlyBase; FBgn0014455; Ahcy.
DR VEuPathDB; VectorBase:FBgn0014455; -.
DR eggNOG; KOG1370; Eukaryota.
DR HOGENOM; CLU_025194_2_1_1; -.
DR InParanoid; Q27580; -.
DR OMA; NKYGCRE; -.
DR OrthoDB; 371693at2759; -.
DR PhylomeDB; Q27580; -.
DR Reactome; R-DME-156581; Methylation.
DR Reactome; R-DME-1614635; Sulfur amino acid metabolism.
DR UniPathway; UPA00314; UER00076.
DR BioGRID-ORCS; 32471; 1 hit in 1 CRISPR screen.
DR ChiTaRS; Ahcy13; fly.
DR GenomeRNAi; 32471; -.
DR PRO; PR:Q27580; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0014455; Expressed in secondary oocyte and 48 other tissues.
DR ExpressionAtlas; Q27580; baseline and differential.
DR Genevisible; Q27580; DM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0004013; F:adenosylhomocysteinase activity; ISS:FlyBase.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0019510; P:S-adenosylhomocysteine catabolic process; IMP:UniProtKB.
DR GO; GO:0033353; P:S-adenosylmethionine cycle; IBA:GO_Central.
DR CDD; cd00401; SAHH; 1.
DR Gene3D; 3.40.50.1480; -; 3.
DR HAMAP; MF_00563; AdoHcyase; 1.
DR InterPro; IPR042172; Adenosylhomocyst_ase-like_sf.
DR InterPro; IPR000043; Adenosylhomocysteinase-like.
DR InterPro; IPR015878; Ado_hCys_hydrolase_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020082; S-Ado-L-homoCys_hydrolase_CS.
DR PANTHER; PTHR23420; PTHR23420; 1.
DR Pfam; PF05221; AdoHcyase; 2.
DR Pfam; PF00670; AdoHcyase_NAD; 1.
DR PIRSF; PIRSF001109; Ad_hcy_hydrolase; 1.
DR SMART; SM00996; AdoHcyase; 1.
DR SMART; SM00997; AdoHcyase_NAD; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR00936; ahcY; 1.
DR PROSITE; PS00738; ADOHCYASE_1; 1.
DR PROSITE; PS00739; ADOHCYASE_2; 1.
PE 1: Evidence at protein level;
KW Hydrolase; NAD; One-carbon metabolism; Reference proteome.
FT CHAIN 1..432
FT /note="Adenosylhomocysteinase"
FT /id="PRO_0000116913"
FT BINDING 56
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 131
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 156
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 157..159
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 186
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 190
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 222..227
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 243
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 248
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 299..301
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 346
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 353
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 426..430
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 426
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 430
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT CONFLICT 146
FT /note="Y -> F (in Ref. 1; CAA64892)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="A -> G (in Ref. 1; CAA64892)"
FT /evidence="ECO:0000305"
FT CONFLICT 294
FT /note="A -> R (in Ref. 1; CAA64892)"
FT /evidence="ECO:0000305"
FT CONFLICT 326..328
FT /note="DRY -> IRH (in Ref. 4; AAM27497)"
FT /evidence="ECO:0000305"
FT CONFLICT 331
FT /note="Q -> K (in Ref. 1; CAA64892)"
FT /evidence="ECO:0000305"
FT CONFLICT 351
FT /note="H -> D (in Ref. 1; CAA64892)"
FT /evidence="ECO:0000305"
FT CONFLICT 379..380
FT /note="YA -> S (in Ref. 1; CAA64892)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 432 AA; 47366 MW; 2977DAF12B40C324 CRC64;
MSKPSYKVAD ISLAEWGRKA IIIAENEMPG LMACRKKYGP SKPLKGARIT GCLHMTVQTA
VLIETLVELG AQVQWSSCNI FSTQDNAAAA IAATGVPVYA WKGETDEEYM WCIEQTLVFP
DGQPLNMILD DGGDLTNLVH EKFPQYLKNI KGLSEETTTG VHNLYKMFKE GRLGVPAINV
NDSVTKSKFD NLYGCRESLI DGIKRATDVM IAGKVCCVAG YGDVGKGCAQ ALKGFGGRVI
VTEVDPINAL QAAMEGYEVT TMEEASKEAS IFVTTTGCRD IITSVHLQQM PDDAIVCNIG
HFDIEIDVDW LNANAKEKVN VKPQVDRYTM QSGKHIILLA EGRLVNLGCA HGHPSFVMSN
SFTNQVLAQI ELWTKSDKYA VGVHVLPKIL DEEVASLHLE KLGVKLTKLT EKQATYLGVS
QTGPFKPDHY RY
