CBS_RAT
ID CBS_RAT Reviewed; 561 AA.
AC P32232;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Cystathionine beta-synthase {ECO:0000305};
DE EC=4.2.1.22 {ECO:0000250|UniProtKB:P35520};
DE AltName: Full=Beta-thionase;
DE AltName: Full=Hemoprotein H-450;
DE AltName: Full=Serine sulfhydrase;
GN Name=Cbs;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND ALTERNATIVE
RP SPLICING (ISOFORMS I; II; III AND IV).
RC TISSUE=Liver;
RX PubMed=1597473; DOI=10.1016/s0021-9258(19)49931-6;
RA Swaroop M., Bradley K., Ohura T., Tahara T., Roper M.D., Rosenberg L.E.,
RA Kraus J.P.;
RT "Rat cystathionine beta-synthase. Gene organization and alternative
RT splicing.";
RL J. Biol. Chem. 267:11455-11461(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-23 AND 39-48, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=2089036; DOI=10.1093/oxfordjournals.jbchem.a123310;
RA Ishihara S., Morohashi K., Sadano H., Kawabata S., Gotoh O., Omura T.;
RT "Molecular cloning and sequence analysis of cDNA coding for rat liver
RT hemoprotein H-450.";
RL J. Biochem. 108:899-902(1990).
RN [3]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=8558235; DOI=10.1523/jneurosci.16-03-01066.1996;
RA Abe K., Kimura H.;
RT "The possible role of hydrogen sulfide as an endogenous neuromodulator.";
RL J. Neurosci. 16:1066-1071(1996).
RN [4]
RP FUNCTION.
RX PubMed=20149843; DOI=10.1016/j.neuroscience.2010.02.006;
RA Tay A.S., Hu L.F., Lu M., Wong P.T., Bian J.S.;
RT "Hydrogen sulfide protects neurons against hypoxic injury via stimulation
RT of ATP-sensitive potassium channel/protein kinase C/extracellular signal-
RT regulated kinase/heat shock protein 90 pathway.";
RL Neuroscience 167:277-286(2010).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Hydro-lyase catalyzing the first step of the transsulfuration
CC pathway, where the hydroxyl group of L-serine is displaced by L-
CC homocysteine in a beta-replacement reaction to form L-cystathionine,
CC the precursor of L-cysteine. This catabolic route allows the
CC elimination of L-methionine and the toxic metabolite L-homocysteine (By
CC similarity). Also involved in the production of hydrogen sulfide, a
CC gasotransmitter with signaling and cytoprotective effects on neurons
CC (PubMed:20149843, PubMed:8558235). {ECO:0000250|UniProtKB:P35520,
CC ECO:0000269|PubMed:20149843, ECO:0000269|PubMed:8558235}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-homocysteine + L-serine = H2O + L,L-cystathionine;
CC Xref=Rhea:RHEA:10112, ChEBI:CHEBI:15377, ChEBI:CHEBI:33384,
CC ChEBI:CHEBI:58161, ChEBI:CHEBI:58199; EC=4.2.1.22;
CC Evidence={ECO:0000250|UniProtKB:P35520};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P35520};
CC -!- ACTIVITY REGULATION: Allosterically activated by S-adenosyl-
CC methionine/AdoMet. Activated by S-adenosylhomocysteine/AdoHcy. Binds
CC non-covalently to a heme group that may control the redox sensitivity
CC of the enzyme. {ECO:0000250|UniProtKB:P35520}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-cysteine biosynthesis; L-cysteine
CC from L-homocysteine and L-serine: step 1/2.
CC {ECO:0000250|UniProtKB:P35520}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P35520}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P35520}. Nucleus
CC {ECO:0000250|UniProtKB:P35520}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=I;
CC IsoId=P32232-1; Sequence=Displayed;
CC Name=II;
CC IsoId=P32232-4; Sequence=Not described;
CC Name=III;
CC IsoId=P32232-2; Sequence=VSP_001218;
CC Name=IV;
CC IsoId=P32232-3; Sequence=VSP_001220, VSP_001221;
CC -!- TISSUE SPECIFICITY: Expressed in liver, kidney and brain. Highly
CC expressed in the hippocamus and cerebellum.
CC {ECO:0000269|PubMed:2089036, ECO:0000269|PubMed:8558235}.
CC -!- SIMILARITY: Belongs to the cysteine synthase/cystathionine beta-
CC synthase family. {ECO:0000305}.
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DR EMBL; M88344; AAB02042.1; -; mRNA.
DR EMBL; M88346; AAA42024.1; -; mRNA.
DR EMBL; D01098; BAA00883.1; -; mRNA.
DR PIR; A42790; A42790.
DR PIR; C42790; C42790.
DR RefSeq; NP_036654.2; NM_012522.2. [P32232-2]
DR AlphaFoldDB; P32232; -.
DR SMR; P32232; -.
DR STRING; 10116.ENSRNOP00000039968; -.
DR iPTMnet; P32232; -.
DR PhosphoSitePlus; P32232; -.
DR PaxDb; P32232; -.
DR PRIDE; P32232; -.
DR Ensembl; ENSRNOT00000042432; ENSRNOP00000039968; ENSRNOG00000029528. [P32232-1]
DR Ensembl; ENSRNOT00000045275; ENSRNOP00000042958; ENSRNOG00000029528. [P32232-2]
DR Ensembl; ENSRNOT00000116783; ENSRNOP00000082078; ENSRNOG00000029528. [P32232-3]
DR GeneID; 24250; -.
DR KEGG; rno:24250; -.
DR UCSC; RGD:2287; rat. [P32232-1]
DR CTD; 875; -.
DR RGD; 2287; Cbs.
DR eggNOG; KOG1252; Eukaryota.
DR GeneTree; ENSGT00510000047027; -.
DR HOGENOM; CLU_021018_0_0_1; -.
DR InParanoid; P32232; -.
DR OMA; KFADDEW; -.
DR OrthoDB; 1016546at2759; -.
DR PhylomeDB; P32232; -.
DR BioCyc; MetaCyc:MON-8583; -.
DR Reactome; R-RNO-1614603; Cysteine formation from homocysteine.
DR SABIO-RK; P32232; -.
DR UniPathway; UPA00136; UER00201.
DR PRO; PR:P32232; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Bgee; ENSRNOG00000029528; Expressed in pancreas and 18 other tissues.
DR Genevisible; P32232; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0070025; F:carbon monoxide binding; ISO:RGD.
DR GO; GO:0004122; F:cystathionine beta-synthase activity; IDA:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0020037; F:heme binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0072341; F:modified amino acid binding; ISO:RGD.
DR GO; GO:0070026; F:nitric oxide binding; ISO:RGD.
DR GO; GO:0050421; F:nitrite reductase (NO-forming) activity; ISO:RGD.
DR GO; GO:0019825; F:oxygen binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; ISS:UniProtKB.
DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0097746; P:blood vessel diameter maintenance; ISO:RGD.
DR GO; GO:0001974; P:blood vessel remodeling; ISO:RGD.
DR GO; GO:0060351; P:cartilage development involved in endochondral bone morphogenesis; ISO:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
DR GO; GO:0021587; P:cerebellum morphogenesis; ISO:RGD.
DR GO; GO:0019344; P:cysteine biosynthetic process; ISO:RGD.
DR GO; GO:0006535; P:cysteine biosynthetic process from serine; TAS:RGD.
DR GO; GO:0019343; P:cysteine biosynthetic process via cystathionine; IEA:InterPro.
DR GO; GO:0042262; P:DNA protection; ISO:RGD.
DR GO; GO:0001958; P:endochondral ossification; ISO:RGD.
DR GO; GO:0043418; P:homocysteine catabolic process; ISS:UniProtKB.
DR GO; GO:0050667; P:homocysteine metabolic process; IDA:RGD.
DR GO; GO:0070814; P:hydrogen sulfide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0019448; P:L-cysteine catabolic process; ISO:RGD.
DR GO; GO:0006565; P:L-serine catabolic process; ISO:RGD.
DR GO; GO:0006563; P:L-serine metabolic process; ISS:UniProtKB.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0043506; P:regulation of JUN kinase activity; ISO:RGD.
DR GO; GO:0010749; P:regulation of nitric oxide mediated signal transduction; ISO:RGD.
DR GO; GO:0051593; P:response to folic acid; ISO:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0006801; P:superoxide metabolic process; ISO:RGD.
DR GO; GO:0019346; P:transsulfuration; IDA:RGD.
DR CDD; cd04608; CBS_pair_CBS; 1.
DR Gene3D; 3.10.580.10; -; 1.
DR Gene3D; 3.40.50.1100; -; 2.
DR InterPro; IPR046353; CBS_C.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR InterPro; IPR005857; Cysta_beta_synth.
DR InterPro; IPR001216; P-phosphate_BS.
DR InterPro; IPR001926; PLP-dep.
DR InterPro; IPR036052; Trypto_synt_PLP_dependent.
DR Pfam; PF00571; CBS; 1.
DR Pfam; PF00291; PALP; 1.
DR SMART; SM00116; CBS; 1.
DR SUPFAM; SSF53686; SSF53686; 1.
DR SUPFAM; SSF54631; SSF54631; 1.
DR TIGRFAMs; TIGR01137; cysta_beta; 1.
DR PROSITE; PS51371; CBS; 1.
DR PROSITE; PS00901; CYS_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Amino-acid biosynthesis; CBS domain;
KW Cysteine biosynthesis; Cytoplasm; Direct protein sequencing; Heme; Iron;
KW Isopeptide bond; Lyase; Metal-binding; Nucleus; Phosphoprotein;
KW Pyridoxal phosphate; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2089036"
FT CHAIN 2..561
FT /note="Cystathionine beta-synthase"
FT /id="PRO_0000167134"
FT DOMAIN 414..474
FT /note="CBS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 23..37
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 49
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P35520"
FT BINDING 62
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P35520"
FT BINDING 146
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P35520"
FT BINDING 253..257
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P35520"
FT BINDING 346
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P35520"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 116
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P35520"
FT MOD_RES 196
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35520"
FT CROSSLNK 208
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:P35520"
FT VAR_SEQ 450..478
FT /note="AILGMVTLGNMLSSLLAGKVRPSDEVCKV -> LRQSKDICHPTKRHIIQAH
FT GLRKVPDTEA (in isoform IV)"
FT /evidence="ECO:0000305"
FT /id="VSP_001220"
FT VAR_SEQ 479..561
FT /note="Missing (in isoform IV)"
FT /evidence="ECO:0000305"
FT /id="VSP_001221"
FT VAR_SEQ 514..528
FT /note="SRDQAWSGVVGGPTD -> Y (in isoform III)"
FT /evidence="ECO:0000305"
FT /id="VSP_001218"
FT CONFLICT 415
FT /note="L -> P (in Ref. 2; BAA00883)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 561 AA; 61455 MW; 0199FCAF492AE3A2 CRC64;
MPSGTSQCED GSAGCPQDLE VQPEKGQLEK GASGDKERVW ISPDTPSRCT WQLGRPMADS
PHYHTVPTKS PKILPDILRK IGNTPMVRIN RISKNAGLKC ELLAKCEFFN AGGSVKDRIS
LRMIEDAERA GTLKPGDTII EPTSGNTGIG LALAAAVKGY RCIIVMPEKM SMEKVDVLRA
LGAEIVRTPT NARFDSPESH VGVAWRLKNE IPNSHILDQY RNASNPLAHY DDTAEEILQQ
CDGKVDMLVA SAGTGGTITG IARKLKEKCP GCKIIGVDPE GSILAEPEEL NQTEQTAYEV
EGIGYDFIPT VLDRAVVDRW FKSNDDDSFA FARMLISQEG LLCGGSSGSA MAVAVKAAQE
LKEGQRCVVI LPDSVRNYMS KFLSDKWMLQ KGFMKEELSV KRPWWWHLRV QELSLSAPLT
VLPTVTCEHT IAILREKGFD QAPVVNESGA ILGMVTLGNM LSSLLAGKVR PSDEVCKVLY
KQFKPIHLTD TLGMLSHILE MDHFALVVHE QIQSRDQAWS GVVGGPTDRN NGVSSKQLMV
FGVVTAIDLL NFVAAREQTR K
