SAHH3_MOUSE
ID SAHH3_MOUSE Reviewed; 613 AA.
AC Q68FL4; Q8BIH1;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Putative adenosylhomocysteinase 3;
DE Short=AdoHcyase 3;
DE EC=3.3.1.1;
DE AltName: Full=Long-IRBIT {ECO:0000303|PubMed:19220705};
DE AltName: Full=S-adenosyl-L-homocysteine hydrolase 3;
DE AltName: Full=S-adenosylhomocysteine hydrolase-like protein 2;
GN Name=Ahcyl2;
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] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Eye;
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] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [4]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=19220705; DOI=10.1111/j.1471-4159.2009.05979.x;
RA Ando H., Mizutani A., Mikoshiba K.;
RT "An IRBIT homologue lacks binding activity to inositol 1,4,5-trisphosphate
RT receptor due to the unique N-terminal appendage.";
RL J. Neurochem. 109:539-550(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-109, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Lung, Pancreas, Spleen, and
RC 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).
CC -!- FUNCTION: May regulate the electrogenic sodium/bicarbonate
CC cotransporter SLC4A4 activity and Mg(2+)-sensitivity. On the contrary
CC of its homolog AHCYL1, does not regulate ITPR1 sensitivity to inositol
CC 1,4,5-trisphosphate. {ECO:0000250|UniProtKB:A6QLP2,
CC ECO:0000250|UniProtKB:Q96HN2}.
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 -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540; Evidence={ECO:0000250};
CC Note=Binds 1 NAD(+) per subunit. {ECO:0000250};
CC -!- PATHWAY: Amino-acid biosynthesis; L-homocysteine biosynthesis; L-
CC homocysteine from S-adenosyl-L-homocysteine: step 1/1.
CC -!- SUBUNIT: Homotetramer. Forms heteromultimers with AHCYL1 (via the C-
CC terminal region). Interacts with ITPR1; with lower affinity than AHCYL1
CC and maybe via ITPR1. Interacts with SLC4A4. Interacts with ZCCHC4 (By
CC similarity). {ECO:0000250|UniProtKB:A6QLP2,
CC ECO:0000250|UniProtKB:Q96HN2}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:A6QLP2,
CC ECO:0000269|PubMed:19220705}. Microsome {ECO:0000269|PubMed:19220705}.
CC Note=Associates with membranes when phosphorylated, probably through
CC interaction with ITPR1. {ECO:0000269|PubMed:19220705}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q68FL4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q68FL4-2; Sequence=VSP_017821;
CC -!- TISSUE SPECIFICITY: Highly expressed in cerebrum, cerebellum and
CC kidney. Also expressed in thymus, spleen, testis, ovary and, at lower,
CC levels in lung and liver (at protein level). In cerebellum, expressed
CC in interneurons. {ECO:0000269|PubMed:19220705}.
CC -!- PTM: Phosphorylated during neuronal differentiation at the LISN domain.
CC {ECO:0000269|PubMed:19220705}.
CC -!- SIMILARITY: Belongs to the adenosylhomocysteinase family.
CC {ECO:0000305}.
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DR EMBL; AK053527; BAC35415.1; -; mRNA.
DR EMBL; BC079660; AAH79660.1; -; mRNA.
DR CCDS; CCDS19966.3; -. [Q68FL4-1]
DR CCDS; CCDS51738.1; -. [Q68FL4-2]
DR RefSeq; NP_001164471.2; NM_001171000.2.
DR RefSeq; NP_001164472.1; NM_001171001.1. [Q68FL4-2]
DR RefSeq; NP_067389.5; NM_021414.6. [Q68FL4-1]
DR AlphaFoldDB; Q68FL4; -.
DR SMR; Q68FL4; -.
DR BioGRID; 216676; 5.
DR STRING; 10090.ENSMUSP00000110897; -.
DR iPTMnet; Q68FL4; -.
DR PhosphoSitePlus; Q68FL4; -.
DR SwissPalm; Q68FL4; -.
DR EPD; Q68FL4; -.
DR jPOST; Q68FL4; -.
DR MaxQB; Q68FL4; -.
DR PaxDb; Q68FL4; -.
DR PRIDE; Q68FL4; -.
DR ProteomicsDB; 253393; -. [Q68FL4-1]
DR ProteomicsDB; 253394; -. [Q68FL4-2]
DR Antibodypedia; 17876; 70 antibodies from 18 providers.
DR DNASU; 74340; -.
DR Ensembl; ENSMUST00000115238; ENSMUSP00000110893; ENSMUSG00000029772. [Q68FL4-2]
DR Ensembl; ENSMUST00000115242; ENSMUSP00000110897; ENSMUSG00000029772. [Q68FL4-1]
DR GeneID; 74340; -.
DR KEGG; mmu:74340; -.
DR UCSC; uc009bei.2; mouse. [Q68FL4-1]
DR UCSC; uc009bek.2; mouse. [Q68FL4-2]
DR CTD; 23382; -.
DR MGI; MGI:1921590; Ahcyl2.
DR VEuPathDB; HostDB:ENSMUSG00000029772; -.
DR eggNOG; KOG1370; Eukaryota.
DR GeneTree; ENSGT00950000182981; -.
DR InParanoid; Q68FL4; -.
DR OMA; QPTHLCE; -.
DR OrthoDB; 371693at2759; -.
DR PhylomeDB; Q68FL4; -.
DR TreeFam; TF300415; -.
DR Reactome; R-MMU-425381; Bicarbonate transporters.
DR UniPathway; UPA00314; UER00076.
DR BioGRID-ORCS; 74340; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Ahcyl2; mouse.
DR PRO; PR:Q68FL4; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q68FL4; protein.
DR Bgee; ENSMUSG00000029772; Expressed in choroid plexus epithelium and 259 other tissues.
DR ExpressionAtlas; Q68FL4; baseline and differential.
DR Genevisible; Q68FL4; MM.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
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 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 Acetylation; Alternative splicing; Cytoplasm; Endoplasmic reticulum;
KW Hydrolase; Microsome; NAD; One-carbon metabolism; Phosphoprotein;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q96HN2"
FT CHAIN 2..613
FT /note="Putative adenosylhomocysteinase 3"
FT /id="PRO_0000230301"
FT REGION 1..186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..111
FT /note="LISN domain, inhibits interaction with ITPR1"
FT /evidence="ECO:0000250|UniProtKB:Q96HN2"
FT COMPBIAS 48..70
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 88..106
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 144..168
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 238
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 312
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 337
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 338..340
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 367
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 371
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 372
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 403..408
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 424
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q96HN2"
FT BINDING 459
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q96HN2"
FT BINDING 480..482
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 527
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q96HN2"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q96HN2"
FT MOD_RES 109
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 151
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96HN2"
FT MOD_RES 154
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96HN2"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96HN2"
FT MOD_RES 160
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96HN2"
FT VAR_SEQ 1..123
FT /note="MSVQVVSAAAAAKVPEVELKDLSPSEAEPQLGLSAAAVGAMVPPAGGGDPEA
FT PAPAPAAERPPAPGPGSGPTAALSPAAGKVPQASAMKRSDPHHQHQRHRDGGEALVSPD
FT GTVTEAPRTVKK -> MLSSKKKYIVNSNSGIKA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_017821"
FT CONFLICT 440
FT /note="L -> V (in Ref. 1; BAC35415)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 613 AA; 66899 MW; 4413DBF1F4825860 CRC64;
MSVQVVSAAA AAKVPEVELK DLSPSEAEPQ LGLSAAAVGA MVPPAGGGDP EAPAPAPAAE
RPPAPGPGSG PTAALSPAAG KVPQASAMKR SDPHHQHQRH RDGGEALVSP DGTVTEAPRT
VKKQIQFADQ KQEFNKRPTK IGRRSLSRSI SQSSTDSYSS AASYTDSSDD ETSPRDKQQK
NSKGSSDFCV KNIKQAEFGR REIEIAEQEM PALMALRKRA QGEKPLAGAK IVGCTHITAQ
TAVLMETLGA LGAQCRWAAC NIYSTLNEVA AALAESGFPV FAWKGESEDD FWWCIDRCVN
VEGWQPNMIL DDGGDLTHWI YKKYPNMFKK IKGIVEESVT GVHRLYQLSK AGKLCVPAMN
VNDSVTKQKF DNLYCCRESI LDGLKRTTDM MFGGKQVVVC GYGEVGKGCC AALKAMGSIV
YVTEIDPICA LQACMDGFRL VKLNEVIRQV DIVITCTGNK NVVTREHLDR MKNSCIVCNM
GHSNTEIDVA SLRTPELTWE RVRSQVDHVI WPDGKRIVLL AEGRLLNLSC STVPTFVLSI
TATTQALALI ELYNAPEGRY KQDVYLLPKK MDEYVASLHL PTFDAHLTEL TDEQAKYLGL
NKNGPFKPNY YRY
