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Protein

Cystathionine beta-synthase

Gene

CBS

Organism
Homo sapiens (Human)
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 (PubMed:23981774, PubMed:20506325, PubMed:23974653). Also involved in the production of hydrogen sulfide, a gasotransmitter with signaling and cytoprotective effects on neurons (By similarity).By similarity3 Publications

Catalytic activityi

L-serine + L-homocysteine = L-cystathionine + H2O.4 Publications

Cofactori

pyridoxal 5'-phosphate1 Publication

Enzyme regulationi

Allosterically activated by S-adenosyl-methionine/AdoMet. Activated by S-adenosylhomocysteine/AdoHcy (PubMed:20506325). Binds non-covalently to a heme group that may control the redox sensitivity of the enzyme (PubMed:11483494, PubMed:12173932, PubMed:22738154).5 Publications

Pathwayi: L-cysteine biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes L-cysteine from L-homocysteine and L-serine.3 Publications
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Cystathionine beta-synthase-like protein (CBSL), 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 bindingi52Iron (heme axial ligand)2 Publications1
Metal bindingi65Iron (heme axial ligand)2 Publications1
Binding sitei149Pyridoxal phosphate2 Publications1
Binding sitei349Pyridoxal phosphate2 Publications1

GO - Molecular functioni

  • carbon monoxide binding Source: BHF-UCL
  • cystathionine beta-synthase activity Source: UniProtKB
  • cysteine synthase activity Source: GO_Central
  • enzyme binding Source: UniProtKB
  • heme binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • modified amino acid binding Source: UniProtKB
  • nitric oxide binding Source: BHF-UCL
  • nitrite reductase (NO-forming) activity Source: BHF-UCL
  • oxygen binding Source: BHF-UCL
  • protein homodimerization activity Source: UniProtKB
  • pyridoxal phosphate binding Source: UniProtKB
  • S-adenosyl-L-methionine binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • cellular amino acid biosynthetic process Source: UniProtKB-KW
  • cysteine biosynthetic process Source: BHF-UCL
  • cysteine biosynthetic process from serine Source: GO_Central
  • cysteine biosynthetic process via cystathionine Source: InterPro
  • DNA protection Source: BHF-UCL
  • homocysteine catabolic process Source: UniProtKB
  • homocysteine metabolic process Source: UniProtKB
  • hydrogen sulfide biosynthetic process Source: UniProtKB
  • L-cysteine catabolic process Source: UniProtKB
  • L-serine catabolic process Source: UniProtKB
  • L-serine metabolic process Source: UniProtKB
  • transsulfuration Source: Reactome
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:HS08461-MONOMER.
ZFISH:HS08461-MONOMER.
BRENDAi4.2.1.22. 2681.
ReactomeiR-HSA-1614603. Cysteine formation from homocysteine.
R-HSA-2408508. Metabolism of ingested SeMet, Sec, MeSec into H2Se.
SABIO-RKP35520.
UniPathwayiUPA00136; UER00201.

Names & Taxonomyi

Protein namesi
Recommended name:
Cystathionine beta-synthaseCurated (EC:4.2.1.224 Publications)
Alternative name(s):
Beta-thionase
Serine sulfhydrase
Gene namesi
Name:CBS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:1550. CBS.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Cystathionine beta-synthase deficiency (CBSD)38 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn enzymatic deficiency resulting in altered sulfur metabolism and homocystinuria. The clinical features of untreated homocystinuria due to CBS deficiency include myopia, ectopia lentis, mental retardation, skeletal anomalies resembling Marfan syndrome, and thromboembolic events. Light skin and hair can also be present. Biochemical features include increased urinary homocystine and methionine.
See also OMIM:236200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00804949P → L in CBSD; decreased expression; no effect on cystathionine beta-synthase activity; increased homotetramer formation. 3 PublicationsCorresponds to variant rs148865119dbSNPEnsembl.1
Natural variantiVAR_00805058R → W in CBSD; linked with V-114; 18% of activity. 1 PublicationCorresponds to variant rs555959266dbSNPEnsembl.1
Natural variantiVAR_02179065H → R in CBSD; decreased cystathionine beta-synthase activity; inhibited by AdoMet and AdoHcy; decreased homotetramer formation. 2 Publications1
Natural variantiVAR_00217178P → R in CBSD; severe form; linked with Q-102; decreased cystathionine beta-synthase activity; decreased homotetramer formation. 2 PublicationsCorresponds to variant rs786204608dbSNPEnsembl.1
Natural variantiVAR_00805185G → R in CBSD; loss of cystathionine beta-synthase activity. 2 Publications1
Natural variantiVAR_07459087T → N in CBSD; decreased cystathionine beta-synthase activity; increased aggregation. 1 Publication1
Natural variantiVAR_00217288P → S in CBSD. 1 Publication1
Natural variantiVAR_021791101L → P in CBSD; common mutation in Irish population; loss of activity. 3 PublicationsCorresponds to variant rs786204757dbSNPEnsembl.1
Natural variantiVAR_002173102K → N in CBSD; decreased cystathionine beta-synthase activity; decreased homotetramer formation. 2 PublicationsCorresponds to variant rs786204609dbSNPEnsembl.1
Natural variantiVAR_008052102K → Q in CBSD; severe form; linked with R-78. 1 PublicationCorresponds to variant rs34040148dbSNPEnsembl.1
Natural variantiVAR_021792109C → R in CBSD; loss of activity. 1 PublicationCorresponds to variant rs778220779dbSNPEnsembl.1
Natural variantiVAR_002174114A → V in CBSD; mild form; when linked with W-58 severe form; decreased cystathionine beta-synthase activity; decreases homotetramer formation by promoting formation of larger aggregates. 3 PublicationsCorresponds to variant rs121964964dbSNPEnsembl.1
Natural variantiVAR_008053116G → R in CBSD. 1 PublicationCorresponds to variant rs760214620dbSNPEnsembl.1
Natural variantiVAR_008054121R → C in CBSD. Corresponds to variant rs775992753dbSNPEnsembl.1
Natural variantiVAR_008055121R → H in CBSD. Corresponds to variant rs770095972dbSNPEnsembl.1
Natural variantiVAR_008056121R → L in CBSD; mild form. Corresponds to variant rs770095972dbSNPEnsembl.1
Natural variantiVAR_046923125R → P in CBSD. 1 Publication1
Natural variantiVAR_002175125R → Q in CBSD; severe form; when linked with D-131 moderate form; loss of cystathionine beta-synthase activity; decreased homotetramer formation. 4 PublicationsCorresponds to variant rs781444670dbSNPEnsembl.1
Natural variantiVAR_008057125R → W in CBSD; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure. 2 Publications1
Natural variantiVAR_008058126M → V in CBSD; loss of activity. 1 Publication1
Natural variantiVAR_008059128E → D in CBSD. 1
Natural variantiVAR_002176131E → D in CBSD; linked with Q-125; loss of activity. 1 Publication1
Natural variantiVAR_008060139G → R in CBSD; mild form. 1 PublicationCorresponds to variant rs121964965dbSNPEnsembl.1
Natural variantiVAR_021793143I → M in CBSD; 4% of activity; stable. 1 Publication1
Natural variantiVAR_002177144E → K in CBSD; loss of cystathionine beta-synthase activity; impaired stimulation by AdoMet and AdoHcy; decreased homotetramer formation. 6 PublicationsCorresponds to variant rs121964966dbSNPEnsembl.1
Natural variantiVAR_002178145P → L in CBSD. 1 PublicationCorresponds to variant rs121964963dbSNPEnsembl.1
Natural variantiVAR_008061148G → R in CBSD; loss of cystathionine beta-synthase activity; impaired stimulation by AdoMet and AdoHcy; loss of homotetramer formation. 3 PublicationsCorresponds to variant rs755952006dbSNPEnsembl.1
Natural variantiVAR_008063151 – 159Missing in CBSD. 9
Natural variantiVAR_008062151G → R in CBSD. Corresponds to variant rs373782713dbSNPEnsembl.1
Natural variantiVAR_008064152I → M in CBSD; severe form. 1
Natural variantiVAR_046924154L → Q in CBSD; protein expression is comparable to wild-type; significant decrease of enzyme activity. 1 Publication1
Natural variantiVAR_008065155A → T in CBSD; complete loss of activity; severely affects homotetramer formation by promoting formation of larger aggregates. 1 Publication1
Natural variantiVAR_046925155A → V in CBSD; protein expression is comparable to wild-type; significant decrease of enzyme activity. 1 Publication1
Natural variantiVAR_002179165C → Y in CBSD; severe form; protein expression is comparable to wild-type; loss of cystathionine beta-synthase activity; no effect on homotetramer formation. 5 Publications1
Natural variantiVAR_046926168V → A in CBSD. 1 Publication1
Natural variantiVAR_002180168V → M in CBSD. 1 PublicationCorresponds to variant rs121964970dbSNPEnsembl.1
Natural variantiVAR_046927173M → V in CBSD; presents 40% of the wild-type activity; highly reduced capacity to form multimeric quaternary structure. 1 Publication1
Natural variantiVAR_066098173Missing in CBSD; loss of activity. 1 Publication1
Natural variantiVAR_008066176E → K in CBSD; severe form; loss of cystathionine beta-synthase activity; inhibited by AdoMet; severely decreases homotetramer formation by promoting formation of larger aggregates. 3 Publications1
Natural variantiVAR_008067180V → A in CBSD; decreased cystathionine beta-synthase activity; decreases homotetramer formation. 1 Publication1
Natural variantiVAR_008068191T → M in CBSD; moderate and severe forms; loss of cystathionine beta-synthase activity; absent capacity to form multimeric quaternary structure. 4 PublicationsCorresponds to variant rs121964973dbSNPEnsembl.1
Natural variantiVAR_008069198D → V in CBSD. 1
Natural variantiVAR_066099200P → L in CBSD. 1 PublicationCorresponds to variant rs758712880dbSNPEnsembl.1
Natural variantiVAR_002181224R → H in CBSD. 1 PublicationCorresponds to variant rs761647392dbSNPEnsembl.1
Natural variantiVAR_008070226A → T in CBSD; presents 20% of the wild-type activity; dramatically reduced capacity to form multimeric quaternary structure. 2 Publications1
Natural variantiVAR_021794228N → K in CBSD; loss of cystathionine beta-synthase activity; decreased homotetramer formation. 4 Publications1
Natural variantiVAR_046928228N → S in CBSD; has significantly decreased levels of enzyme activity. 1 Publication1
Natural variantiVAR_046929231A → P in CBSD; has significantly decreased levels of enzyme activity. 1 Publication1
Natural variantiVAR_008071234D → N in CBSD; decreased cystathionine beta-synthase activity; changed localization; decreased interaction with pyridoxal 5'-phosphate; no effect on homotetramer formation. 1 PublicationCorresponds to variant rs773734233dbSNPEnsembl.1
Natural variantiVAR_046930234Missing in CBSD; protein expression is comparable to wild-type; significant decrease of enzyme activity. 1 Publication1
Natural variantiVAR_002182239E → K in CBSD. 1
Natural variantiVAR_046931247 – 256Missing in CBSD. 1 Publication10
Natural variantiVAR_002183257T → M in CBSD; moderate to severe form; protein expression is comparable to wild-type; significant decrease of enzyme activity. 2 PublicationsCorresponds to variant rs758236584dbSNPEnsembl.1
Natural variantiVAR_008072262T → M in CBSD; moderate form. 2 PublicationsCorresponds to variant rs149119723dbSNPEnsembl.1
Natural variantiVAR_021795262T → R in CBSD; severe form; loss of cystathionine beta-synthase activity; loss of homotetramer formation. 2 Publications1
Natural variantiVAR_008073266R → G in CBSD. 1
Natural variantiVAR_008074266R → K in CBSD; mild form; decreased cystathionine beta-synthase activity; decreased homotetramer formation; no effect on heme-binding; decreased stability. 3 PublicationsCorresponds to variant rs28934275dbSNPEnsembl.1
Natural variantiVAR_074591269Missing in CBSD; loss of expression. 1 Publication1
Natural variantiVAR_008075270Missing in CBSD. 1
Natural variantiVAR_021796275C → Y in CBSD; severe form; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure. 2 Publications1
Natural variantiVAR_066100278I → S in CBSD; loss of activity. 1 Publication1
Natural variantiVAR_002184278I → T in CBSD; mild to severe form; common mutation; decreased expression; loss of cystathionine beta-synthase activity; impaired stimulation by AdoMet and AdoHcy; severely affects homotetramer formation by promoting formation of larger aggregates. 19 PublicationsCorresponds to variant rs5742905dbSNPEnsembl.1
Natural variantiVAR_066101281D → N in CBSD; loss of activity. 1 Publication1
Natural variantiVAR_046932288A → P in CBSD. 1 Publication1
Natural variantiVAR_046933288A → T in CBSD; protein expression is comparable to wild-type; significant decrease of enzyme activity. 1 PublicationCorresponds to variant rs141502207dbSNPEnsembl.1
Natural variantiVAR_002185290P → L in CBSD. 2 PublicationsCorresponds to variant rs760912339dbSNPEnsembl.1
Natural variantiVAR_008076302E → K in CBSD; no effect on cystathionine beta-synthase activity; inhibited by AdoHcy and impaired activation by AdoMet; no effect on homotetramer formation. 3 PublicationsCorresponds to variant rs779270933dbSNPEnsembl.1
Natural variantiVAR_008077305G → R in CBSD; loss of cystathionine beta-synthase activity; no effect on homotetramer formation. 1 Publication1
Natural variantiVAR_002186307G → S in CBSD; moderate to severe form; linked with D-534; common mutation; loss of cystathionine beta-synthase activity; impaired stimulation by AdoMet and AdoHcy; no effect on homotetramer formation. 8 PublicationsCorresponds to variant rs121964962dbSNPEnsembl.1
Natural variantiVAR_008078320V → A in CBSD; has 36% of wild-type enzyme activity. 2 PublicationsCorresponds to variant rs781567152dbSNPEnsembl.1
Natural variantiVAR_066102321D → V in CBSD; loss of activity. 1 Publication1
Natural variantiVAR_008079331A → E in CBSD. 2 PublicationsCorresponds to variant rs777919630dbSNPEnsembl.1
Natural variantiVAR_002187331A → V in CBSD. 1 Publication1
Natural variantiVAR_002188336R → C in CBSD; protein expression is comparable to wild-type; loss of activity; absent capacity to form multimeric quaternary structure. 6 PublicationsCorresponds to variant rs398123151dbSNPEnsembl.1
Natural variantiVAR_008080336R → H in CBSD; mild form; no effect on expression; exhibits an activity lower than 4% of the wild-type enzyme; altered stimulation by AdoMet; absent capacity to form multimeric quaternary structure. 2 PublicationsCorresponds to variant rs760417941dbSNPEnsembl.1
Natural variantiVAR_021797338L → P in CBSD; severe form; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure. 2 Publications1
Natural variantiVAR_021798347G → S in CBSD; protein expression is comparable to wild-type; loss of activity. 2 PublicationsCorresponds to variant rs771298943dbSNPEnsembl.1
Natural variantiVAR_021799349S → N in CBSD; severe form; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure. 2 Publications1
Natural variantiVAR_008081352S → N in CBSD. 1
Natural variantiVAR_008082353T → M in CBSD; protein expression is comparable to wild-type; significant decrease of enzyme activity. 4 PublicationsCorresponds to variant rs121964972dbSNPEnsembl.1
Natural variantiVAR_008083354V → M in CBSD. Corresponds to variant rs267606146dbSNPEnsembl.1
Natural variantiVAR_021800355A → P in CBSD. 1 Publication1
Natural variantiVAR_046934361A → T in CBSD. 1 PublicationCorresponds to variant rs745764562dbSNPEnsembl.1
Natural variantiVAR_008084369R → C in CBSD; when linked with C-491 severe form; decreased cystathionine beta-synthase activity; decreased homotetramer formation. 3 PublicationsCorresponds to variant rs117687681dbSNPEnsembl.1
Natural variantiVAR_002189369R → H in CBSD. Corresponds to variant rs11700812dbSNPEnsembl.1
Natural variantiVAR_008085370C → Y in CBSD. 1 PublicationCorresponds to variant rs757920190dbSNPEnsembl.1
Natural variantiVAR_002190371V → M in CBSD. 2 PublicationsCorresponds to variant rs372010465dbSNPEnsembl.1
Natural variantiVAR_046935376D → N in CBSD; has significantly decreased levels of enzyme activity. 1 Publication1
Natural variantiVAR_021801379R → Q in CBSD; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure. 2 PublicationsCorresponds to variant rs763036586dbSNPEnsembl.1
Natural variantiVAR_046936379R → W in CBSD. 1 PublicationCorresponds to variant rs769080151dbSNPEnsembl.1
Natural variantiVAR_002191384K → E in CBSD; severe form. 1 PublicationCorresponds to variant rs121964967dbSNPEnsembl.1
Natural variantiVAR_008086384K → N in CBSD; moderate form. 1
Natural variantiVAR_008087391M → I in CBSD. 1
Natural variantiVAR_021802422P → L in CBSD; changed cystathionine beta-synthase activity; impaired stimulation by AdoMet; does not affect homotetramer formation. 2 PublicationsCorresponds to variant rs28934892dbSNPEnsembl.1
Natural variantiVAR_074592427P → L in CBSD; no effect on cystathionine beta-synthase activity; altered stimulation by AdoMet. 2 Publications1
Natural variantiVAR_008088434T → N in CBSD. 1
Natural variantiVAR_008089435I → T in CBSD; no effect on cystathionine beta-synthase activity; impaired stimulation by AdoMet and AdoHcy; does not affect homotetramer formation. 2 Publications1
Natural variantiVAR_008090439R → Q in CBSD; no effect on cystathionine beta-synthase activity; increased homotetramer formation. 4 PublicationsCorresponds to variant rs756467921dbSNPEnsembl.1
Natural variantiVAR_002192444D → N in CBSD; decreased expression; no effect on cystathionine beta-synthase activity; altered stimulation by AdoMet; increased homotetramer formation. 5 PublicationsCorresponds to variant rs28934891dbSNPEnsembl.1
Natural variantiVAR_066103446A → S in CBSD. 1 Publication1
Natural variantiVAR_074593449V → G in CBSD; no effect on cystathionine beta-synthase activity; altered stimulation by AdoMet. 1 Publication1
Natural variantiVAR_002193454V → E in CBSD. 1 Publication1
Natural variantiVAR_021803456L → P in CBSD; severe; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure. 2 Publications1
Natural variantiVAR_008091466S → L in CBSD; increased cystathionine beta-synthase activity; impaired stimulation by AdoMet and AdoHcy; decreased homotetramer formation. 2 PublicationsCorresponds to variant rs121964971dbSNPEnsembl.1
Natural variantiVAR_008092491R → C in CBSD; linked with C-369. 1
Natural variantiVAR_074594500S → L in CBSD; no effect on cystathionine beta-synthase activity; altered stimulation by AdoMet. 2 PublicationsCorresponds to variant rs755106884dbSNPEnsembl.1
Natural variantiVAR_046937526Q → K in CBSD; has significantly decreased levels of enzyme activity. 1 Publication1
Natural variantiVAR_008093534V → D in CBSD; linked with S-307. 1
Natural variantiVAR_002194539L → S in CBSD; loss of cystathionine beta-synthase activity; impaired stimulation by AdoMet and AdoHcy; loss of homotetramer formation. 2 PublicationsCorresponds to variant rs121964968dbSNPEnsembl.1
Natural variantiVAR_074595540L → Q in CBSD; no effect on cystathionine beta-synthase activity; altered stimulation by AdoMet. 2 Publications1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi272C → A: Reduced heme content and cystathionine beta-synthase activity. 1 Publication1
Mutagenesisi275C → S: Reduced heme content and cystathionine beta-synthase activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi102724560.
875.
MalaCardsiCBS.
MIMi236200. phenotype.
OpenTargetsiENSG00000160200.
ENSG00000274276.
Orphaneti394. Classical homocystinuria.
PharmGKBiPA26123.

Chemistry databases

ChEMBLiCHEMBL3399911.
DrugBankiDB00151. L-Cysteine.
DB00133. L-Serine.
DB00118. S-Adenosylmethionine.
GuidetoPHARMACOLOGYi1443.

Polymorphism and mutation databases

BioMutaiCBS.
DMDMi543959.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001671332 – 551Cystathionine beta-synthaseAdd BLAST550

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei27PhosphoserineCombined sources1
Modified residuei119N6-(pyridoxal phosphate)lysine2 Publications1
Modified residuei199PhosphoserineCombined sources1
Cross-linki211Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP35520.
MaxQBiP35520.
PaxDbiP35520.
PeptideAtlasiP35520.
PRIDEiP35520.

PTM databases

iPTMnetiP35520.
PhosphoSitePlusiP35520.

Expressioni

Tissue specificityi

In the adult strongly expressed in liver and pancreas, some expression in heart and brain, weak expression in lung and kidney. In the fetus, expressed in brain, liver and kidney.

Gene expression databases

BgeeiENSG00000160200.
CleanExiHS_CBS.
ExpressionAtlasiP35520. baseline and differential.
GenevisibleiP35520. HS.

Organism-specific databases

HPAiHPA001223.

Interactioni

Subunit structurei

Homotetramer.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-740135,EBI-740135
EHHADHQ084263EBI-740135,EBI-2339219
PIN1Q135263EBI-740135,EBI-714158
PRKAG1P546193EBI-740135,EBI-1181439
PSMA1P257863EBI-740135,EBI-359352
UBASH3AP570753EBI-740135,EBI-2105393
UBE2IQ7KZS03EBI-740135,EBI-10180829

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107321. 66 interactors.
IntActiP35520. 20 interactors.
MINTiMINT-133409.
STRINGi9606.ENSP00000344460.

Chemistry databases

BindingDBiP35520.

Structurei

Secondary structure

1551
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi60 – 62Combined sources3
Beta strandi75 – 79Combined sources5
Helixi80 – 82Combined sources3
Beta strandi83 – 85Combined sources3
Beta strandi89 – 91Combined sources3
Helixi95 – 98Combined sources4
Beta strandi103 – 109Combined sources7
Helixi110 – 112Combined sources3
Beta strandi113 – 117Combined sources5
Helixi119 – 132Combined sources14
Beta strandi141 – 145Combined sources5
Helixi149 – 161Combined sources13
Beta strandi164 – 170Combined sources7
Helixi175 – 183Combined sources9
Beta strandi187 – 191Combined sources5
Beta strandi197 – 199Combined sources3
Helixi203 – 213Combined sources11
Beta strandi217 – 219Combined sources3
Turni222 – 224Combined sources3
Helixi227 – 234Combined sources8
Helixi236 – 243Combined sources8
Turni244 – 246Combined sources3
Beta strandi249 – 254Combined sources6
Beta strandi256 – 258Combined sources3
Helixi259 – 271Combined sources13
Beta strandi272 – 274Combined sources3
Beta strandi276 – 282Combined sources7
Beta strandi288 – 290Combined sources3
Helixi291 – 294Combined sources4
Helixi317 – 319Combined sources3
Beta strandi322 – 326Combined sources5
Helixi328 – 342Combined sources15
Helixi348 – 360Combined sources13
Helixi361 – 363Combined sources3
Beta strandi369 – 374Combined sources6
Helixi378 – 381Combined sources4
Turni382 – 386Combined sources5
Helixi388 – 393Combined sources6
Helixi399 – 404Combined sources6
Turni408 – 411Combined sources4
Helixi414 – 417Combined sources4
Helixi431 – 441Combined sources11
Beta strandi444 – 449Combined sources6
Beta strandi455 – 460Combined sources6
Helixi461 – 469Combined sources9
Helixi479 – 482Combined sources4
Beta strandi489 – 491Combined sources3
Helixi496 – 505Combined sources10
Beta strandi509 – 515Combined sources7
Beta strandi526 – 534Combined sources9
Helixi536 – 544Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JBQX-ray2.60A/B/C/D/E/F2-413[»]
1M54X-ray2.90A/B/C/D/E/F44-406[»]
4COOX-ray2.00A/B1-551[»]
4L0DX-ray2.97A/B1-551[»]
4L27X-ray3.39A/B/C/D2-551[»]
4L28X-ray2.63A/B/C/D2-551[»]
4L3VX-ray3.63A/B/C2-551[»]
4PCUX-ray3.58A/B1-551[»]
4UUUX-ray1.71A/B406-547[»]
ProteinModelPortaliP35520.
SMRiP35520.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35520.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini418 – 476CBSPROSITE-ProRule annotationAdd BLAST59

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni256 – 260Pyridoxal phosphate binding2 Publications5

Sequence similaritiesi

Contains 1 CBS domain.PROSITE-ProRule annotation

Keywords - Domaini

CBS domain

Phylogenomic databases

eggNOGiKOG1252. Eukaryota.
COG0031. LUCA.
GeneTreeiENSGT00510000047027.
HOGENOMiHOG000217392.
HOVERGENiHBG000918.
InParanoidiP35520.
KOiK01697.
OMAiWMASYGF.
OrthoDBiEOG091G02TP.
PhylomeDBiP35520.
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: P35520-1) [UniParc]FASTAAdd to basket
Also known as: Major

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
MPSETPQAEV GPTGCPHRSG PHSAKGSLEK GSPEDKEAKE PLWIRPDAPS
60 70 80 90 100
RCTWQLGRPA SESPHHHTAP AKSPKILPDI LKKIGDTPMV RINKIGKKFG
110 120 130 140 150
LKCELLAKCE FFNAGGSVKD RISLRMIEDA ERDGTLKPGD TIIEPTSGNT
160 170 180 190 200
GIGLALAAAV RGYRCIIVMP EKMSSEKVDV LRALGAEIVR TPTNARFDSP
210 220 230 240 250
ESHVGVAWRL KNEIPNSHIL DQYRNASNPL AHYDTTADEI LQQCDGKLDM
260 270 280 290 300
LVASVGTGGT ITGIARKLKE KCPGCRIIGV DPEGSILAEP EELNQTEQTT
310 320 330 340 350
YEVEGIGYDF IPTVLDRTVV DKWFKSNDEE AFTFARMLIA QEGLLCGGSA
360 370 380 390 400
GSTVAVAVKA AQELQEGQRC VVILPDSVRN YMTKFLSDRW MLQKGFLKEE
410 420 430 440 450
DLTEKKPWWW HLRVQELGLS APLTVLPTIT CGHTIEILRE KGFDQAPVVD
460 470 480 490 500
EAGVILGMVT LGNMLSSLLA GKVQPSDQVG KVIYKQFKQI RLTDTLGRLS
510 520 530 540 550
HILEMDHFAL VVHEQIQYHS TGKSSQRQMV FGVVTAIDLL NFVAAQERDQ

K
Length:551
Mass (Da):60,587
Last modified:January 23, 2007 - v2
Checksum:iF89E69C67BDE6701
GO
Isoform 2 (identifier: P35520-2) [UniParc]FASTAAdd to basket
Also known as: Minor

The sequence of this isoform differs from the canonical sequence as follows:
     518-518: Y → SQDQAWAGVVGGPAD

Show »
Length:565
Mass (Da):61,863
Checksum:i8BD062B080067092
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti58R → P in CAA61252 (PubMed:9383285).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04692118R → C Functional polymorphism; associated with 1/3 to 2/3 the enzyme activity of the wild-type. 1 PublicationCorresponds to variant rs201827340dbSNPEnsembl.1
Natural variantiVAR_00804949P → L in CBSD; decreased expression; no effect on cystathionine beta-synthase activity; increased homotetramer formation. 3 PublicationsCorresponds to variant rs148865119dbSNPEnsembl.1
Natural variantiVAR_00805058R → W in CBSD; linked with V-114; 18% of activity. 1 PublicationCorresponds to variant rs555959266dbSNPEnsembl.1
Natural variantiVAR_02179065H → R in CBSD; decreased cystathionine beta-synthase activity; inhibited by AdoMet and AdoHcy; decreased homotetramer formation. 2 Publications1
Natural variantiVAR_04692269A → P.1 PublicationCorresponds to variant rs17849313dbSNPEnsembl.1
Natural variantiVAR_00217178P → R in CBSD; severe form; linked with Q-102; decreased cystathionine beta-synthase activity; decreased homotetramer formation. 2 PublicationsCorresponds to variant rs786204608dbSNPEnsembl.1
Natural variantiVAR_00805185G → R in CBSD; loss of cystathionine beta-synthase activity. 2 Publications1
Natural variantiVAR_07459087T → N in CBSD; decreased cystathionine beta-synthase activity; increased aggregation. 1 Publication1
Natural variantiVAR_00217288P → S in CBSD. 1 Publication1
Natural variantiVAR_021791101L → P in CBSD; common mutation in Irish population; loss of activity. 3 PublicationsCorresponds to variant rs786204757dbSNPEnsembl.1
Natural variantiVAR_002173102K → N in CBSD; decreased cystathionine beta-synthase activity; decreased homotetramer formation. 2 PublicationsCorresponds to variant rs786204609dbSNPEnsembl.1
Natural variantiVAR_008052102K → Q in CBSD; severe form; linked with R-78. 1 PublicationCorresponds to variant rs34040148dbSNPEnsembl.1
Natural variantiVAR_021792109C → R in CBSD; loss of activity. 1 PublicationCorresponds to variant rs778220779dbSNPEnsembl.1
Natural variantiVAR_002174114A → V in CBSD; mild form; when linked with W-58 severe form; decreased cystathionine beta-synthase activity; decreases homotetramer formation by promoting formation of larger aggregates. 3 PublicationsCorresponds to variant rs121964964dbSNPEnsembl.1
Natural variantiVAR_008053116G → R in CBSD. 1 PublicationCorresponds to variant rs760214620dbSNPEnsembl.1
Natural variantiVAR_008054121R → C in CBSD. Corresponds to variant rs775992753dbSNPEnsembl.1
Natural variantiVAR_008055121R → H in CBSD. Corresponds to variant rs770095972dbSNPEnsembl.1
Natural variantiVAR_008056121R → L in CBSD; mild form. Corresponds to variant rs770095972dbSNPEnsembl.1
Natural variantiVAR_046923125R → P in CBSD. 1 Publication1
Natural variantiVAR_002175125R → Q in CBSD; severe form; when linked with D-131 moderate form; loss of cystathionine beta-synthase activity; decreased homotetramer formation. 4 PublicationsCorresponds to variant rs781444670dbSNPEnsembl.1
Natural variantiVAR_008057125R → W in CBSD; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure. 2 Publications1
Natural variantiVAR_008058126M → V in CBSD; loss of activity. 1 Publication1
Natural variantiVAR_008059128E → D in CBSD. 1
Natural variantiVAR_002176131E → D in CBSD; linked with Q-125; loss of activity. 1 Publication1
Natural variantiVAR_008060139G → R in CBSD; mild form. 1 PublicationCorresponds to variant rs121964965dbSNPEnsembl.1
Natural variantiVAR_021793143I → M in CBSD; 4% of activity; stable. 1 Publication1
Natural variantiVAR_002177144E → K in CBSD; loss of cystathionine beta-synthase activity; impaired stimulation by AdoMet and AdoHcy; decreased homotetramer formation. 6 PublicationsCorresponds to variant rs121964966dbSNPEnsembl.1
Natural variantiVAR_002178145P → L in CBSD. 1 PublicationCorresponds to variant rs121964963dbSNPEnsembl.1
Natural variantiVAR_008061148G → R in CBSD; loss of cystathionine beta-synthase activity; impaired stimulation by AdoMet and AdoHcy; loss of homotetramer formation. 3 PublicationsCorresponds to variant rs755952006dbSNPEnsembl.1
Natural variantiVAR_008063151 – 159Missing in CBSD. 9
Natural variantiVAR_008062151G → R in CBSD. Corresponds to variant rs373782713dbSNPEnsembl.1
Natural variantiVAR_008064152I → M in CBSD; severe form. 1
Natural variantiVAR_046924154L → Q in CBSD; protein expression is comparable to wild-type; significant decrease of enzyme activity. 1 Publication1
Natural variantiVAR_008065155A → T in CBSD; complete loss of activity; severely affects homotetramer formation by promoting formation of larger aggregates. 1 Publication1
Natural variantiVAR_046925155A → V in CBSD; protein expression is comparable to wild-type; significant decrease of enzyme activity. 1 Publication1
Natural variantiVAR_002179165C → Y in CBSD; severe form; protein expression is comparable to wild-type; loss of cystathionine beta-synthase activity; no effect on homotetramer formation. 5 Publications1
Natural variantiVAR_046926168V → A in CBSD. 1 Publication1
Natural variantiVAR_002180168V → M in CBSD. 1 PublicationCorresponds to variant rs121964970dbSNPEnsembl.1
Natural variantiVAR_046927173M → V in CBSD; presents 40% of the wild-type activity; highly reduced capacity to form multimeric quaternary structure. 1 Publication1
Natural variantiVAR_066098173Missing in CBSD; loss of activity. 1 Publication1
Natural variantiVAR_008066176E → K in CBSD; severe form; loss of cystathionine beta-synthase activity; inhibited by AdoMet; severely decreases homotetramer formation by promoting formation of larger aggregates. 3 Publications