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Protein

Cystathionine beta-synthase

Gene

Cbs

Organism
Mus musculus (Mouse)
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 (By similarity).By similarity

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

  • blood vessel remodeling Source: MGI
  • cartilage development involved in endochondral bone morphogenesis Source: MGI
  • cellular amino acid biosynthetic process Source: UniProtKB-KW
  • cellular response to hypoxia Source: Ensembl
  • cerebellum morphogenesis Source: MGI
  • cysteine biosynthetic process Source: MGI
  • cysteine biosynthetic process from serine Source: GO_Central
  • cysteine biosynthetic process via cystathionine Source: InterPro
  • endochondral ossification Source: MGI
  • homocysteine catabolic process Source: UniProtKB
  • homocysteine metabolic process Source: UniProtKB
  • hydrogen sulfide biosynthetic process Source: UniProtKB
  • L-serine metabolic process Source: UniProtKB
  • maternal process involved in female pregnancy Source: MGI
  • negative regulation of apoptotic process Source: Ensembl
  • regulation of blood vessel size Source: MGI
  • regulation of cGMP metabolic process Source: MGI
  • regulation of JUN kinase activity Source: MGI
  • response to folic acid Source: MGI
  • superoxide metabolic process Source: MGI
  • transsulfuration Source: Ensembl
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

BRENDAi4.2.1.22. 3474.
ReactomeiR-MMU-1614603. Cysteine formation from homocysteine.
UniPathwayiUPA00136; UER00201.

Names & Taxonomyi

Protein namesi
Recommended name:
Cystathionine beta-synthaseCurated (EC:4.2.1.22By similarity)
Alternative name(s):
Beta-thionase
Serine sulfhydrase
Gene namesi
Name:Cbs
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:88285. 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 methionineiRemovedBy similarity
ChainiPRO_00002625922 – 561Cystathionine beta-synthaseAdd BLAST560

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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

PaxDbiQ91WT9.
PeptideAtlasiQ91WT9.
PRIDEiQ91WT9.

PTM databases

iPTMnetiQ91WT9.
PhosphoSitePlusiQ91WT9.
SwissPalmiQ91WT9.

Expressioni

Gene expression databases

BgeeiENSMUSG00000024039.
CleanExiMM_CBS.
ExpressionAtlasiQ91WT9. baseline and differential.
GenevisibleiQ91WT9. MM.

Interactioni

Subunit structurei

Homotetramer.By similarity

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-60823N.
IntActiQ91WT9. 1 interactor.
MINTiMINT-4121506.
STRINGi10090.ENSMUSP00000066878.

Structurei

3D structure databases

ProteinModelPortaliQ91WT9.
SMRiQ91WT9.
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.
InParanoidiQ91WT9.
KOiK01697.
OMAiWMASYGF.
OrthoDBiEOG091G02TP.
PhylomeDBiQ91WT9.
TreeFamiTF300784.

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 (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q91WT9-1) [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 GSAGGFQHLD MHSEKRQLEK GPSGDKDRVW IRPDTPSRCT
60 70 80 90 100
WQLGRAMADS PHYHTVLTKS PKILPDILRK IGNTPMVRIN KISKNAGLKC
110 120 130 140 150
ELLAKCEFFN AGGSVKDRIS LRMIEDAERA GNLKPGDTII EPTSGNTGIG
160 170 180 190 200
LALAAAVKGY RCIIVMPEKM SMEKVDVLRA LGAEIVRTPT NARFDSPESH
210 220 230 240 250
VGVAWRLKNE IPNSHILDQY RNASNPLAHY DDTAEEILQQ CDGKLDMLVA
260 270 280 290 300
SAGTGGTITG IARKLKEKCP GCKIIGVDPE GSILAEPEEL NQTEQTAYEV
310 320 330 340 350
EGIGYDFIPT VLDRAVVDKW FKSNDEDSFA FARMLIAQEG LLCGGSSGSA
360 370 380 390 400
MAVAVKAARE LQEGQRCVVI LPDSVRNYMS KFLSDKWMLQ KGFMKEELSV
410 420 430 440 450
KRPWWWRLRV QELSLSAPLT VLPTVTCEDT IAILREKGFD QAPVVNESGA
460 470 480 490 500
ILGMVTLGNM LSSLLAGKVR PSDEVCKVLY KQFKPIHLTD TLGTLSHILE
510 520 530 540 550
MDHFALVVHE QIQSRDQAWS GVVGGPTDCS NGMSSKQQMV FGVVTAIDLL
560
NFVAAREQTQ T
Length:561
Mass (Da):61,544
Last modified:January 23, 2007 - v3
Checksum:i072CF81AFE10372E
GO
Isoform 2 (identifier: Q91WT9-2) [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):60,193
Checksum:i5DC0F6E3DAED8461
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_021790514 – 528SRDQA…GGPTD → Y in isoform 2. 2 PublicationsAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK077669 mRNA. Translation: BAC36943.1.
BC013472 mRNA. Translation: AAH13472.1.
BC013480 mRNA. Translation: AAH13480.1.
BC026595 mRNA. Translation: AAH26595.1.
CCDSiCCDS28609.1. [Q91WT9-1]
CCDS28610.1. [Q91WT9-2]
RefSeqiNP_001258282.1. NM_001271353.1. [Q91WT9-2]
NP_659104.1. NM_144855.3. [Q91WT9-1]
NP_835742.1. NM_178224.3. [Q91WT9-2]
XP_006523612.1. XM_006523549.3. [Q91WT9-1]
XP_006523613.1. XM_006523550.3. [Q91WT9-1]
XP_006523614.1. XM_006523551.3. [Q91WT9-1]
UniGeneiMm.206417.
Mm.486781.

Genome annotation databases

EnsembliENSMUST00000067801; ENSMUSP00000066878; ENSMUSG00000024039. [Q91WT9-1]
ENSMUST00000078509; ENSMUSP00000077597; ENSMUSG00000024039. [Q91WT9-2]
ENSMUST00000118504; ENSMUSP00000113209; ENSMUSG00000024039. [Q91WT9-2]
GeneIDi12411.
KEGGimmu:12411.
UCSCiuc008bvl.2. mouse. [Q91WT9-1]
uc008bvm.2. mouse. [Q91WT9-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK077669 mRNA. Translation: BAC36943.1.
BC013472 mRNA. Translation: AAH13472.1.
BC013480 mRNA. Translation: AAH13480.1.
BC026595 mRNA. Translation: AAH26595.1.
CCDSiCCDS28609.1. [Q91WT9-1]
CCDS28610.1. [Q91WT9-2]
RefSeqiNP_001258282.1. NM_001271353.1. [Q91WT9-2]
NP_659104.1. NM_144855.3. [Q91WT9-1]
NP_835742.1. NM_178224.3. [Q91WT9-2]
XP_006523612.1. XM_006523549.3. [Q91WT9-1]
XP_006523613.1. XM_006523550.3. [Q91WT9-1]
XP_006523614.1. XM_006523551.3. [Q91WT9-1]
UniGeneiMm.206417.
Mm.486781.

3D structure databases

ProteinModelPortaliQ91WT9.
SMRiQ91WT9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60823N.
IntActiQ91WT9. 1 interactor.
MINTiMINT-4121506.
STRINGi10090.ENSMUSP00000066878.

PTM databases

iPTMnetiQ91WT9.
PhosphoSitePlusiQ91WT9.
SwissPalmiQ91WT9.

Proteomic databases

PaxDbiQ91WT9.
PeptideAtlasiQ91WT9.
PRIDEiQ91WT9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000067801; ENSMUSP00000066878; ENSMUSG00000024039. [Q91WT9-1]
ENSMUST00000078509; ENSMUSP00000077597; ENSMUSG00000024039. [Q91WT9-2]
ENSMUST00000118504; ENSMUSP00000113209; ENSMUSG00000024039. [Q91WT9-2]
GeneIDi12411.
KEGGimmu:12411.
UCSCiuc008bvl.2. mouse. [Q91WT9-1]
uc008bvm.2. mouse. [Q91WT9-2]

Organism-specific databases

CTDi875.
MGIiMGI:88285. Cbs.

Phylogenomic databases

eggNOGiKOG1252. Eukaryota.
COG0031. LUCA.
GeneTreeiENSGT00510000047027.
HOGENOMiHOG000217392.
HOVERGENiHBG000918.
InParanoidiQ91WT9.
KOiK01697.
OMAiWMASYGF.
OrthoDBiEOG091G02TP.
PhylomeDBiQ91WT9.
TreeFamiTF300784.

Enzyme and pathway databases

UniPathwayiUPA00136; UER00201.
BRENDAi4.2.1.22. 3474.
ReactomeiR-MMU-1614603. Cysteine formation from homocysteine.

Miscellaneous databases

ChiTaRSiCbs. mouse.
PROiQ91WT9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024039.
CleanExiMM_CBS.
ExpressionAtlasiQ91WT9. baseline and differential.
GenevisibleiQ91WT9. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: Q91WT9
Secondary accession number(s): Q91WU3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 127 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, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. 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.