CBS

Protein identityUniProt · HPA

UniProt accession

P35520

Gene

CBS

Ensembl

ENSG00000160200

Chromosome

21

Canonical length

551 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoli,Vesicles

Quaternary structure

Homotetramer

OverviewNCBI Gene

The protein encoded by this gene acts as a homotetramer to catalyze the conversion of homocysteine to cystathionine, the first step in the transsulfuration pathway. The encoded protein is allosterically activated by adenosyl-methionine and uses pyridoxal phosphate as a cofactor. Defects in this gene can cause cystathionine beta-synthase deficiency (CBSD), which can lead to homocystinuria. This gene is a major contributor to cellular hydrogen sulfide production. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2016]

Canonical amino-acid sequenceUniProt

551 residues, UniProt reviewed canonical sequence.

>P35520|CBS
     1  MPSETPQAEV GPTGCPHRSG PHSAKGSLEK GSPEDKEAKE PLWIRPDAPS RCTWQLGRPA
    61  SESPHHHTAP AKSPKILPDI LKKIGDTPMV RINKIGKKFG LKCELLAKCE FFNAGGSVKD
   121  RISLRMIEDA ERDGTLKPGD TIIEPTSGNT GIGLALAAAV RGYRCIIVMP EKMSSEKVDV
   181  LRALGAEIVR TPTNARFDSP ESHVGVAWRL KNEIPNSHIL DQYRNASNPL AHYDTTADEI
   241  LQQCDGKLDM LVASVGTGGT ITGIARKLKE KCPGCRIIGV DPEGSILAEP EELNQTEQTT
   301  YEVEGIGYDF IPTVLDRTVV DKWFKSNDEE AFTFARMLIA QEGLLCGGSA GSTVAVAVKA
   361  AQELQEGQRC VVILPDSVRN YMTKFLSDRW MLQKGFLKEE DLTEKKPWWW HLRVQELGLS
   421  APLTVLPTIT CGHTIEILRE KGFDQAPVVD EAGVILGMVT LGNMLSSLLA GKVQPSDQVG
   481  KVIYKQFKQI RLTDTLGRLS HILEMDHFAL VVHEQIQYHS TGKSSQRQMV FGVVTAIDLL
   541  NFVAAQERDQ K

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CBS can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

177 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CBS.

Disease | AllUniProt

Conditions CBS is implicated in, by any mechanism.

• Cystathionine beta-synthase deficiency (CBSD) MIM:236200

Disease | GeneticClinVar

280 pathogenic / likely-pathogenic of 1,429 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Classic homocystinuria
• HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
• Homocystinuria
• Familial thoracic aortic aneurysm and aortic dissection
• CBS-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.73

gnomAD pLI

0

gnomAD missense Z

0.83

DepMap mean gene effect

0.07

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood vessel diameter maintenance
• blood vessel remodeling
• cartilage development involved in endochondral bone morphogenesis
• cellular response to hypoxia
• cerebellum morphogenesis
• cysteine biosynthetic process
• cysteine biosynthetic process via cystathionine
• DNA protection
• endochondral ossification
• homocysteine catabolic process
• homocysteine metabolic process
• hydrogen sulfide biosynthetic process
• L-cysteine catabolic process
• L-serine catabolic process
• L-serine metabolic process
• maternal process involved in female pregnancy
• negative regulation of apoptotic process
• regulation of JNK cascade
• regulation of nitric oxide mediated signal transduction
• response to folic acid
• superoxide metabolic process
• transsulfuration
• cysteine biosynthetic process from serine

Molecular functions

• carbon monoxide binding
• enzyme binding
• heme binding
• identical protein binding
• metal ion binding
• modified amino acid binding
• nitric oxide binding
• oxygen binding
• protein homodimerization activity
• pyridoxal phosphate binding
• S-adenosyl-L-methionine binding
• ubiquitin protein ligase binding
• cystathionine beta-synthase activity
• nitrite reductase (NO-forming) activity

Cellular components

• cytoplasm
• cytosol
• nucleus

Protein domainsUniProt · Pfam · InterPro

• CBS domain
• Tryptophan synthase beta chain-like, PALP domain
• Tryptophan synthase beta chain-like, PALP domain superfamily
• CBS domain superfamily
• Pyridoxal-phosphate dependent enzyme
• CBS domain
• Cysteine synthase/cystathionine beta-synthase, pyridoxal-phosphate attachment site
• Cystathionine beta-synthase
• Cystathionine beta-synthase, C-terminal domain
• Cysteine synthase/Cystathionine beta-synthase

KeywordsUniProt

• Allosteric enzyme
• Amino-acid biosynthesis
• CBS domain
• Cysteine biosynthesis
• Cytoplasm
• Heme
• Iron
• Isopeptide bond
• Lyase
• Metal-binding
• Nucleus
• Phosphoprotein
• Pyridoxal phosphate
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of CBS in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FXR2