SAHH2_DROME
ID SAHH2_DROME Reviewed; 521 AA.
AC Q9VZX9; Q6NR07;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Adenosylhomocysteinase-like 1 {ECO:0000312|FlyBase:FBgn0035371};
DE Short=dAhcyL1 {ECO:0000303|PubMed:27313316};
DE AltName: Full=Inactive S-adenosyl-L-homocysteine hydrolase {ECO:0000305};
DE AltName: Full=S-adenosylhomocysteine hydrolase-like protein 1 {ECO:0000305};
GN Name=AhcyL1 {ECO:0000303|PubMed:27313316, ECO:0000312|FlyBase:FBgn0035371};
GN ORFNames=CG9977 {ECO:0000312|FlyBase:FBgn0035371};
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 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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 [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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 [3] {ECO:0000312|EMBL:ACM16691.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:ACM16691.1};
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000312|EMBL:AAQ23595.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAQ23595.1};
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., Celniker S.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP FUNCTION, INTERACTION WITH AHCY, 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: Might play a role in the regulation of methionine metabolism
CC possibly by binding and inactivating Ahcy.
CC {ECO:0000269|PubMed:27313316}.
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000255|RuleBase:RU000548};
CC Note=Binds 1 NAD(+) per subunit. {ECO:0000255|RuleBase:RU000548};
CC -!- SUBUNIT: Interacts with Ahcy; the interaction may negatively regulate
CC Ahcy catalytic activity. {ECO:0000269|PubMed:27313316}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in extended
CC lifespan with increased fecundity and suppression of age-related
CC decreased climbing activity and intestinal integrity (PubMed:27313316).
CC Does not affect oxidative stress resistance (PubMed:27313316).
CC Decreases levels of S-adenosyl-homocysteine and homocysteine
CC (PubMed:27313316). Suppresses histone H3K4 trimethylation
CC (PubMed:27313316). RNAi-mediated knockdown in neurons results in
CC extended life span (PubMed:27313316). RNAi-mediated knockdown in the
CC fat body does not show any phenotype (PubMed:27313316). Simultaneous
CC knockdown of AhcyL2 in intestine results in extended life span
CC (PubMed:27313316). {ECO:0000269|PubMed:27313316}.
CC -!- SIMILARITY: Belongs to the adenosylhomocysteinase family.
CC {ECO:0000255|RuleBase:RU004166}.
CC -!- CAUTION: Although it belongs to the adenosylhomocysteinase family,
CC recombinant mouse homolog AHCYL1 expressed in bacteria shows no
CC hydrolase activity, suggesting that Drosophila AhcyL1 may also lack
CC this activity. {ECO:0000305}.
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DR EMBL; AE014296; AAF47685.1; -; Genomic_DNA.
DR EMBL; BT057981; ACM16691.1; -; mRNA.
DR EMBL; BT010277; AAQ23595.1; -; mRNA.
DR RefSeq; NP_647746.1; NM_139489.2.
DR AlphaFoldDB; Q9VZX9; -.
DR SMR; Q9VZX9; -.
DR IntAct; Q9VZX9; 5.
DR STRING; 7227.FBpp0072886; -.
DR PaxDb; Q9VZX9; -.
DR PRIDE; Q9VZX9; -.
DR DNASU; 38342; -.
DR EnsemblMetazoa; FBtr0073016; FBpp0072886; FBgn0035371.
DR GeneID; 38342; -.
DR KEGG; dme:Dmel_CG9977; -.
DR UCSC; CG9977-RA; d. melanogaster.
DR CTD; 10768; -.
DR FlyBase; FBgn0035371; AhcyL1.
DR VEuPathDB; VectorBase:FBgn0035371; -.
DR eggNOG; KOG1370; Eukaryota.
DR GeneTree; ENSGT00950000182981; -.
DR HOGENOM; CLU_025194_2_1_1; -.
DR InParanoid; Q9VZX9; -.
DR OMA; QPTHLCE; -.
DR OrthoDB; 371693at2759; -.
DR PhylomeDB; Q9VZX9; -.
DR Reactome; R-DME-5578775; Ion homeostasis.
DR SignaLink; Q9VZX9; -.
DR BioGRID-ORCS; 38342; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 38342; -.
DR PRO; PR:Q9VZX9; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0035371; Expressed in seminal fluid secreting gland and 39 other tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
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; -; 2.
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; 1.
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 NAD; One-carbon metabolism; Reference proteome.
FT CHAIN 1..521
FT /note="Adenosylhomocysteinase-like 1"
FT /id="PRO_0000446367"
FT REGION 1..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 35..73
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 220
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 245
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 246..248
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 275
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 279
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 311..316
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 332
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 388..390
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 435
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 515..519
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 515
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 519
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT CONFLICT 502
FT /note="Q -> K (in Ref. 4; AAQ23595)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 521 AA; 56978 MW; F63E2627E1DA3092 CRC64;
MNNLADTVVV DPGFGGGDKQ QQAGPAPQDA SVVVPPPATK QSSALKKTSR YRSRSLSASS
TDSFSSASYT GSSEDGDDVP PREKVQKNSK GSSDFCVRNI GAQHAFGRRE IEIAEQEMPG
IIALKKRAAE DKPLKDAKIV GCTHINAQTA VLIETLVELG ASVRWAACNI YSTQNEVAAA
LAESGIPIFA WRGETEEDFW WCIDRCVNAE NWQPNMILDD GGDATHLMLK KYPTMFKLVK
GIVEESVTGV HRLYQLSKAG KLTVPAMNVN DSVTKTKFDN LYSCKESILD SLKRSTDVMF
GGKQVVVCGY GDVGKGCAQA LKGQGCIVYI TEIDPICALQ ASMDGFRVVK LNEVIRNVDI
VVTATGNKNV VVREHMDKMK SGCIVCNMGH SNTEIDVNGL RTPDLTWEKV RSQVDHIIWP
EGKYIILLAE GRLVNLSCSS IPSFAVSITS ATQALALIEL FNAPPGRYKS DVYLLPKKMD
EYVASLHLPT FDAHLTELSD EQAKYMGLNK AGPFKPNYYR Y
