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Protein

Cystathionine beta-synthase

Gene

Cbs

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hydro-lyase catalyzing the first step of the transsulfuration pathway, where the hydroxyl group of L-serine is displaced by L-homocysteine in a beta-replacement reaction to form L-cystathionine, the precursor of L-cysteine. This catabolic route allows the elimination of L-methionine and the toxic metabolite L-homocysteine (By similarity). Also involved in the production of hydrogen sulfide, a gasotransmitter with signaling and cytoprotective effects on neurons (PubMed:20149843, PubMed:8558235).By similarity2 Publications

Catalytic activityi

L-serine + L-homocysteine = L-cystathionine + H2O.By similarity

Cofactori

pyridoxal 5'-phosphateBy similarity

Enzyme regulationi

Allosterically activated by S-adenosyl-methionine/AdoMet. Activated by S-adenosylhomocysteine/AdoHcy. Binds non-covalently to a heme group that may control the redox sensitivity of the enzyme.By similarity

Pathwayi: L-cysteine biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes L-cysteine from L-homocysteine and L-serine.By similarity
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Cystathionine beta-synthase (Cbs)
  2. Cystathionine gamma-lyase (Cth)
This subpathway is part of the pathway L-cysteine biosynthesis, which is itself part of Amino-acid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-cysteine from L-homocysteine and L-serine, the pathway L-cysteine biosynthesis and in Amino-acid biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi49Iron (heme axial ligand)By similarity1
Metal bindingi62Iron (heme axial ligand)By similarity1
Binding sitei146Pyridoxal phosphateBy similarity1
Binding sitei346Pyridoxal phosphateBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

Amino-acid biosynthesis, Cysteine biosynthesis

Keywords - Ligandi

Heme, Iron, Metal-binding, Pyridoxal phosphate

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-8583.
ReactomeiR-RNO-1614603. Cysteine formation from homocysteine.
R-RNO-2408508. Metabolism of ingested SeMet, Sec, MeSec into H2Se.
SABIO-RKP32232.
UniPathwayiUPA00136; UER00201.

Names & Taxonomyi

Protein namesi
Recommended name:
Cystathionine beta-synthaseCurated (EC:4.2.1.22By similarity)
Alternative name(s):
Beta-thionase
Hemoprotein H-450
Serine sulfhydrase
Gene namesi
Name:Cbs
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 20

Organism-specific databases

RGDi2287. Cbs.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001671342 – 561Cystathionine beta-synthaseAdd BLAST560

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei42PhosphoserineCombined sources1
Modified residuei116N6-(pyridoxal phosphate)lysineBy similarity1
Modified residuei196PhosphoserineBy similarity1
Cross-linki208Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP32232.
PRIDEiP32232.

PTM databases

iPTMnetiP32232.
PhosphoSitePlusiP32232.

Expressioni

Tissue specificityi

Expressed in liver, kidney and brain. Highly expressed in the hippocamus and cerebellum.2 Publications

Gene expression databases

BgeeiENSRNOG00000029528.
GenevisibleiP32232. RN.

Interactioni

Subunit structurei

Homotetramer.By similarity

GO - Molecular functioni

Protein-protein interaction databases

MINTiMINT-1531985.
STRINGi10116.ENSRNOP00000039968.

Structurei

3D structure databases

ProteinModelPortaliP32232.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini414 – 474CBSPROSITE-ProRule annotationAdd BLAST61

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni253 – 257Pyridoxal phosphate bindingBy similarity5

Sequence similaritiesi

Contains 1 CBS domain.PROSITE-ProRule annotation

Keywords - Domaini

CBS domain

Phylogenomic databases

eggNOGiKOG1252. Eukaryota.
COG0031. LUCA.
GeneTreeiENSGT00510000047027.
HOGENOMiHOG000217392.
HOVERGENiHBG000918.
InParanoidiP32232.
KOiK01697.
OMAiWMASYGF.
OrthoDBiEOG091G02TP.
PhylomeDBiP32232.

Family and domain databases

InterProiIPR000644. CBS_dom.
IPR005857. Cysta_beta_synth.
IPR001216. P-phosphate_BS.
IPR001926. TrpB-like_PLP-dep.
[Graphical view]
PfamiPF00571. CBS. 1 hit.
PF00291. PALP. 1 hit.
[Graphical view]
SMARTiSM00116. CBS. 1 hit.
[Graphical view]
SUPFAMiSSF53686. SSF53686. 1 hit.
TIGRFAMsiTIGR01137. cysta_beta. 1 hit.
PROSITEiPS51371. CBS. 1 hit.
PS00901. CYS_SYNTHASE. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform I (identifier: P32232-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPSGTSQCED GSAGCPQDLE VQPEKGQLEK GASGDKERVW ISPDTPSRCT
60 70 80 90 100
WQLGRPMADS PHYHTVPTKS PKILPDILRK IGNTPMVRIN RISKNAGLKC
110 120 130 140 150
ELLAKCEFFN AGGSVKDRIS LRMIEDAERA GTLKPGDTII EPTSGNTGIG
160 170 180 190 200
LALAAAVKGY RCIIVMPEKM SMEKVDVLRA LGAEIVRTPT NARFDSPESH
210 220 230 240 250
VGVAWRLKNE IPNSHILDQY RNASNPLAHY DDTAEEILQQ CDGKVDMLVA
260 270 280 290 300
SAGTGGTITG IARKLKEKCP GCKIIGVDPE GSILAEPEEL NQTEQTAYEV
310 320 330 340 350
EGIGYDFIPT VLDRAVVDRW FKSNDDDSFA FARMLISQEG LLCGGSSGSA
360 370 380 390 400
MAVAVKAAQE LKEGQRCVVI LPDSVRNYMS KFLSDKWMLQ KGFMKEELSV
410 420 430 440 450
KRPWWWHLRV QELSLSAPLT VLPTVTCEHT IAILREKGFD QAPVVNESGA
460 470 480 490 500
ILGMVTLGNM LSSLLAGKVR PSDEVCKVLY KQFKPIHLTD TLGMLSHILE
510 520 530 540 550
MDHFALVVHE QIQSRDQAWS GVVGGPTDRN NGVSSKQLMV FGVVTAIDLL
560
NFVAAREQTR K
Length:561
Mass (Da):61,455
Last modified:January 23, 2007 - v3
Checksum:i0199FCAF492AE3A2
GO
Isoform II (identifier: P32232-4)
Sequence is not available
Length:
Mass (Da):
Isoform III (identifier: P32232-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     514-528: SRDQAWSGVVGGPTD → Y

Show »
Length:547
Mass (Da):60,104
Checksum:iA71FF5D43137A5E1
GO
Isoform IV (identifier: P32232-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     450-478: AILGMVTLGNMLSSLLAGKVRPSDEVCKV → LRQSKDICHPTKRHIIQAHGLRKVPDTEA
     479-561: Missing.

Show »
Length:478
Mass (Da):52,513
Checksum:i1E582906BBA255C5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti415L → P in BAA00883 (PubMed:2089036).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001220450 – 478AILGM…EVCKV → LRQSKDICHPTKRHIIQAHG LRKVPDTEA in isoform IV. CuratedAdd BLAST29
Alternative sequenceiVSP_001221479 – 561Missing in isoform IV. CuratedAdd BLAST83
Alternative sequenceiVSP_001218514 – 528SRDQA…GGPTD → Y in isoform III. CuratedAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M88344 mRNA. Translation: AAB02042.1.
M88346 mRNA. Translation: AAA42024.1.
D01098 mRNA. Translation: BAA00883.1.
PIRiA42790.
C42790.
RefSeqiNP_036654.2. NM_012522.2. [P32232-2]
UniGeneiRn.87853.

Genome annotation databases

EnsembliENSRNOT00000042432; ENSRNOP00000039968; ENSRNOG00000029528. [P32232-1]
ENSRNOT00000045275; ENSRNOP00000042958; ENSRNOG00000029528. [P32232-2]
GeneIDi24250.
KEGGirno:24250.
UCSCiRGD:2287. rat. [P32232-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M88344 mRNA. Translation: AAB02042.1.
M88346 mRNA. Translation: AAA42024.1.
D01098 mRNA. Translation: BAA00883.1.
PIRiA42790.
C42790.
RefSeqiNP_036654.2. NM_012522.2. [P32232-2]
UniGeneiRn.87853.

3D structure databases

ProteinModelPortaliP32232.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-1531985.
STRINGi10116.ENSRNOP00000039968.

PTM databases

iPTMnetiP32232.
PhosphoSitePlusiP32232.

Proteomic databases

PaxDbiP32232.
PRIDEiP32232.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000042432; ENSRNOP00000039968; ENSRNOG00000029528. [P32232-1]
ENSRNOT00000045275; ENSRNOP00000042958; ENSRNOG00000029528. [P32232-2]
GeneIDi24250.
KEGGirno:24250.
UCSCiRGD:2287. rat. [P32232-1]

Organism-specific databases

CTDi875.
RGDi2287. Cbs.

Phylogenomic databases

eggNOGiKOG1252. Eukaryota.
COG0031. LUCA.
GeneTreeiENSGT00510000047027.
HOGENOMiHOG000217392.
HOVERGENiHBG000918.
InParanoidiP32232.
KOiK01697.
OMAiWMASYGF.
OrthoDBiEOG091G02TP.
PhylomeDBiP32232.

Enzyme and pathway databases

UniPathwayiUPA00136; UER00201.
BioCyciMetaCyc:MONOMER-8583.
ReactomeiR-RNO-1614603. Cysteine formation from homocysteine.
R-RNO-2408508. Metabolism of ingested SeMet, Sec, MeSec into H2Se.
SABIO-RKP32232.

Miscellaneous databases

PROiP32232.

Gene expression databases

BgeeiENSRNOG00000029528.
GenevisibleiP32232. RN.

Family and domain databases

InterProiIPR000644. CBS_dom.
IPR005857. Cysta_beta_synth.
IPR001216. P-phosphate_BS.
IPR001926. TrpB-like_PLP-dep.
[Graphical view]
PfamiPF00571. CBS. 1 hit.
PF00291. PALP. 1 hit.
[Graphical view]
SMARTiSM00116. CBS. 1 hit.
[Graphical view]
SUPFAMiSSF53686. SSF53686. 1 hit.
TIGRFAMsiTIGR01137. cysta_beta. 1 hit.
PROSITEiPS51371. CBS. 1 hit.
PS00901. CYS_SYNTHASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCBS_RAT
AccessioniPrimary (citable) accession number: P32232
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 154 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.