ID   SIHH_METMA              Reviewed;         411 AA.
AC   Q8PUQ4;
DT   25-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   03-AUG-2022, entry version 131.
DE   RecName: Full=S-inosyl-L-homocysteine hydrolase {ECO:0000255|HAMAP-Rule:MF_00563};
DE            Short=SIHH {ECO:0000255|HAMAP-Rule:MF_00563};
DE            EC=3.13.1.9 {ECO:0000255|HAMAP-Rule:MF_00563};
GN   OrderedLocusNames=MM_2278;
OS   Methanosarcina mazei (strain ATCC BAA-159 / DSM 3647 / Goe1 / Go1 / JCM
OS   11833 / OCM 88) (Methanosarcina frisia).
OC   Archaea; Euryarchaeota; Stenosarchaea group; Methanomicrobia;
OC   Methanosarcinales; Methanosarcinaceae; Methanosarcina.
OX   NCBI_TaxID=192952;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC BAA-159 / DSM 3647 / Goe1 / Go1 / JCM 11833 / OCM 88;
RX   PubMed=12125824;
RA   Deppenmeier U., Johann A., Hartsch T., Merkl R., Schmitz R.A.,
RA   Martinez-Arias R., Henne A., Wiezer A., Baeumer S., Jacobi C.,
RA   Brueggemann H., Lienard T., Christmann A., Boemecke M., Steckel S.,
RA   Bhattacharyya A., Lykidis A., Overbeek R., Klenk H.-P., Gunsalus R.P.,
RA   Fritz H.-J., Gottschalk G.;
RT   "The genome of Methanosarcina mazei: evidence for lateral gene transfer
RT   between Bacteria and Archaea.";
RL   J. Mol. Microbiol. Biotechnol. 4:453-461(2002).
CC   -!- FUNCTION: Catalyzes the hydrolysis of S-inosyl-L-homocysteine (SIH) to
CC       L-homocysteine (Hcy) and inosine. Likely functions in a S-adenosyl-L-
CC       methionine (SAM) recycling pathway from S-adenosyl-L-homocysteine (SAH)
CC       produced from SAM-dependent methylation reactions. Can also catalyze
CC       the reverse reaction in vitro, i.e. the synthesis of SIH from Hcy and
CC       inosine. {ECO:0000255|HAMAP-Rule:MF_00563}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + S-inosyl-L-homocysteine = inosine + L-homocysteine;
CC         Xref=Rhea:RHEA:59828, ChEBI:CHEBI:15377, ChEBI:CHEBI:17596,
CC         ChEBI:CHEBI:57985, ChEBI:CHEBI:58199; EC=3.13.1.9;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_00563};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59829;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_00563};
CC   -!- COFACTOR:
CC       Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_00563};
CC       Note=Binds 1 NAD(+) per subunit. {ECO:0000255|HAMAP-Rule:MF_00563};
CC   -!- PATHWAY: Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis.
CC       {ECO:0000255|HAMAP-Rule:MF_00563}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00563}.
CC   -!- MISCELLANEOUS: SAH is a product of SAM methyltransferases and is known
CC       to be a feedback inhibitor of these enzymes. As a result of this
CC       inhibition, organisms have evolved efficient enzymes to metabolize SAH
CC       via different pathways. The pathway found in methanogens differs from
CC       the canonical pathway, it uses the deamination of S-adenosyl-L-
CC       homocysteine to form S-inosyl-L-homocysteine for the regeneration of
CC       SAM from S-adenosyl-L-homocysteine. {ECO:0000255|HAMAP-Rule:MF_00563}.
CC   -!- SIMILARITY: Belongs to the adenosylhomocysteinase family.
CC       {ECO:0000255|HAMAP-Rule:MF_00563}.
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DR   EMBL; AE008384; AAM31974.1; -; Genomic_DNA.
DR   RefSeq; WP_011034205.1; NC_003901.1.
DR   AlphaFoldDB; Q8PUQ4; -.
DR   SMR; Q8PUQ4; -.
DR   STRING; 192952.MM_2278; -.
DR   EnsemblBacteria; AAM31974; AAM31974; MM_2278.
DR   GeneID; 1480620; -.
DR   KEGG; mma:MM_2278; -.
DR   PATRIC; fig|192952.21.peg.2611; -.
DR   eggNOG; arCOG04137; Archaea.
DR   HOGENOM; CLU_025194_0_2_2; -.
DR   OMA; NKYGCRE; -.
DR   UniPathway; UPA00315; -.
DR   Proteomes; UP000000595; Chromosome.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0004013; F:adenosylhomocysteinase activity; IEA:InterPro.
DR   GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-UniRule.
DR   GO; GO:0006556; P:S-adenosylmethionine biosynthetic process; IEA:UniProtKB-UniPathway.
DR   CDD; cd00401; SAHH; 1.
DR   Gene3D; 3.40.50.1480; -; 1.
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; 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   3: Inferred from homology;
KW   Cytoplasm; Hydrolase; NAD; One-carbon metabolism; Reference proteome.
FT   CHAIN           1..411
FT                   /note="S-inosyl-L-homocysteine hydrolase"
FT                   /id="PRO_0000117006"
FT   BINDING         121
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT   BINDING         146
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT   BINDING         147..149
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT   BINDING         176
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT   BINDING         180
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT   BINDING         181
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT   BINDING         210..215
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT   BINDING         233
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT   BINDING         268
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT   BINDING         289..291
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
FT   BINDING         335
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_00563"
SQ   SEQUENCE   411 AA;  44835 MW;  84C06648A679A840 CRC64;
     MTEKELIESG NMKMEWARNH MPVLAIIREK FEKEKPLKGL KVGMALHVEA KTAVLVETLA
     AGGAQVAISG CNPLSTQDDV AAALDTRENI NCFAKYGCCT GEYYEAIDRV LDIEPDITID
     DGADLIFKLH KERQEMLAKI LGGCEETTTG VHRLHAMEKD GALKMPVIAV NDAMTKYLFD
     NRYGTGQSAW DGINRTTNLL VAGKNVVVAG YGWCGRGVAM RATGLGASVI VTEIDPIRAL
     EARMDGHRVM KMSEAAKIGD LFVTATGNRD ILTADNFKVM KDGAILANSG HFNVEIDMEA
     LDSLAKSTRT VRHNIKEYDI GNRRINVIAE GRLVNLAAGD GHPAEVMDMS FANQALCVRY
     IAENKLSSGV HGVPRELDTY VAKLKLESMG IATDELTSKQ ECYMSGWECG T