SAHH3_DROME
ID SAHH3_DROME Reviewed; 492 AA.
AC P50245; Q27587; Q8MYX7; Q9VEQ4;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2003, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Adenosylhomocysteinase-like 2 {ECO:0000312|FlyBase:FBgn0015011};
DE Short=dAhcyL2 {ECO:0000303|PubMed:27313316};
DE AltName: Full=Inactive S-adenosyl-L-homocysteine hydrolase 2 {ECO:0000305};
DE AltName: Full=S-adenosylhomocysteine hydrolase-like protein 2 {ECO:0000305};
GN Name=AhcyL2 {ECO:0000312|FlyBase:FBgn0015011};
GN Synonyms=AHCY {ECO:0000312|FlyBase:FBgn0015011},
GN Ahcy89E {ECO:0000312|FlyBase:FBgn0015011},
GN pH200 {ECO:0000312|FlyBase:FBgn0015011};
GN ORFNames=CG8956 {ECO:0000312|FlyBase:FBgn0015011};
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 [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC TISSUE=Embryo;
RX PubMed=2903049; DOI=10.1002/j.1460-2075.1988.tb03189.x;
RA Delorenzi M., Ali N., Saari G., Henry C., Wilcox M., Bienz M.;
RT "Evidence that the Abdominal-B r element function is conferred by a trans-
RT regulatory homeoprotein.";
RL EMBO J. 7:3223-3231(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Canton-S;
RX PubMed=7667301; DOI=10.1073/pnas.92.18.8398;
RA Martin C.H., Mayeda C.A., Davis C.A., Ericsson C.L., Knafels J.D.,
RA Mathog D.R., Celniker S.E., Lewis E.B., Palazzolo M.J.;
RT "Complete sequence of the bithorax complex of Drosophila.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:8398-8402(1995).
RN [3]
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
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 [6]
RP DEVELOPMENTAL STAGE.
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 [7]
RP 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 {ECO:0000305|PubMed:27313316}.
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000250|UniProtKB:O43865};
CC Note=Binds 1 NAD(+) per subunit. {ECO:0000250|UniProtKB:O43865};
CC -!- DEVELOPMENTAL STAGE: Expressed in all developmental stages from early
CC embryo to adult (PubMed:9037110). Expressed in extended germ band
CC embryos and in somatic mesoderm, yolk cells and midgut during late
CC embryonic stages (PubMed:2903049). {ECO:0000269|PubMed:2903049,
CC ECO:0000269|PubMed:9037110}.
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). RNAi-
CC mediated knockdown in fat body or neurons does not show any phenotype
CC (PubMed:27313316). Simultaneous knockdown of AhcyL1 in intestine
CC results in extended life span (PubMed:27313316).
CC {ECO:0000269|PubMed:27313316}.
CC -!- SIMILARITY: Belongs to the adenosylhomocysteinase family.
CC {ECO:0000305}.
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 AhcyL2 may also lack
CC this activity. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA84400.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; X13168; CAA31566.1; -; Genomic_DNA.
DR EMBL; U31961; AAA84400.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AE014297; AAF55367.2; -; Genomic_DNA.
DR EMBL; AY113501; AAM29506.1; -; mRNA.
DR PIR; S01302; S01302.
DR RefSeq; NP_996221.1; NM_206499.2.
DR RefSeq; NP_996222.1; NM_206500.2.
DR AlphaFoldDB; P50245; -.
DR SMR; P50245; -.
DR BioGRID; 67084; 6.
DR DIP; DIP-24031N; -.
DR IntAct; P50245; 3.
DR STRING; 7227.FBpp0089085; -.
DR PaxDb; P50245; -.
DR PRIDE; P50245; -.
DR DNASU; 42043; -.
DR EnsemblMetazoa; FBtr0083378; FBpp0082821; FBgn0015011.
DR GeneID; 42043; -.
DR KEGG; dme:Dmel_CG8956; -.
DR CTD; 23382; -.
DR FlyBase; FBgn0015011; AhcyL2.
DR VEuPathDB; VectorBase:FBgn0015011; -.
DR eggNOG; KOG1370; Eukaryota.
DR GeneTree; ENSGT00950000182981; -.
DR HOGENOM; CLU_025194_2_1_1; -.
DR InParanoid; P50245; -.
DR OMA; CVKNIGK; -.
DR PhylomeDB; P50245; -.
DR Reactome; R-DME-5578775; Ion homeostasis.
DR BioGRID-ORCS; 42043; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 42043; -.
DR PRO; PR:P50245; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0015011; Expressed in adult hindgut (Drosophila) and 28 other tissues.
DR ExpressionAtlas; P50245; baseline and differential.
DR Genevisible; P50245; DM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0033353; P:S-adenosylmethionine cycle; IBA:GO_Central.
DR CDD; cd00401; SAHH; 1.
DR Gene3D; 3.40.50.1480; -; 3.
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 2: Evidence at transcript level;
KW NAD; One-carbon metabolism; Reference proteome.
FT CHAIN 1..492
FT /note="Adenosylhomocysteinase-like 2"
FT /id="PRO_0000116914"
FT REGION 43..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 192
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 217
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 218..220
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 247
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 251
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 283..288
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 304
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 360..362
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 407
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 486..490
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 486
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT BINDING 490
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P10760"
FT CONFLICT 127
FT /note="T -> A (in Ref. 1; CAA31566)"
FT /evidence="ECO:0000305"
FT CONFLICT 484..492
FT /note="PFKANYYRY -> LLKPITTGWLPFFPFQFCTLVNNILISFADINQYLMLYP
FT VILVL (in Ref. 1; CAA31566)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 492 AA; 54241 MW; F4916A43A2A3B288 CRC64;
MAKMPETTFA DLSLADKTAV KKSSIEARRF SDVSTCSFSS TCFTGSSDEE DVSPKDNHQR
NSAGGTDFCV KSISKSAFGR REIEIAESEM PGIMTLRKRA KDEKPLKGAN IVGCTHVNAQ
SAVLIETLVQ LGATVRWAAC NIYSTQNAVA AALAEAGIPI FAWRGETEEE FWWCLDRAIY
SDGWQPNLIL DDGGDATHLM LKKYPDYFKA IRGIVEESVT GVHRLYMLSK GGKLTVPAIN
VNDSVTKNKF DTFYTCRDSI LDSLKRTTDI MFGGKQVVIC GYGDVGKGCA QSLKGQGCIV
YVTEVDPICA LQAAMDGFRV VRLNEVIRTV DVVVTATGNK NVITRDHMNR MKNGCILCNM
GHSCSEIDVN GLHTPELTWE RVRSQVDHIR WPDGRMIILL AEGRLVNLSC STISSFVVSV
ASSTQALALI ELFSAPGRYK SDVYLLPKKM DEYVASLHLA TFDAHLTELT DEQSKFMGLN
KAGPFKANYY RY
