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FLASH GENE

Symbol

CBS

contributors: mct - updated : 05-06-2016

HGNC name	cystathionine-beta-synthase
HGNC id	1550

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CBSD homocystinuria, cystathionine beta-synthase deficiency
Location	21q22.3      Physical location : 44.473.300 - 44.496.472
Synonym name	beta-thionase
	serine sulfhydrase
	methylcysteine synthase
Synonym symbol(s)	HIP4
EC.number	4.2.1.22

DNA

TYPE	functioning gene
STRUCTURE	22.74 kb     17 Exon(s)

10 Kb 5' upstream gene genomic sequence study

text structure

five alternative exons

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	see COL6A2 , TFF1 , PFKL PFKL

RNA

TRANSCRIPTS	type	messenger

text	other alternative transcripts differing at their 5' ends and/or presence/absence of exon 15

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000071 17 initiation site 2609 NP_000062 60.5 551 - 1998 9790750 NM_001178008 - initiation site 2586 NP_001171479 - 551 - 1998 9790750 NM_001178009 - - 2372 NP_001171480 - 551 - 1998 9790750

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive liver       highly Endocrine adrenal gland         Mus musculus   pancreas       highly Nervous brain         Visual eye lens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	brain, liver, kidney

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	catalytic domain of 409 AA in the N terminal
	a regulatory domain of 142 AA at the C terminus

mono polymer

homomer , tetramer

HOMOLOGY

interspecies

ortholog to murine Cbs

Homologene

FAMILY

cysteine synthase/cystathionine beta-synthase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleolus

basic FUNCTION	converting homocysteine to cystathionine, first step of the transsulfuration pathway
	playing an essential role for female reproductive function
	participates in the process of oocyte maturation
	critical role in antioxidant and methylation metabolism
	catalyzes the rate-limiting step in the transsulfuration pathway for the metabolism of homocysteine (Hcy) in the kidney
	rate-limiting enzyme responsible for the de novo synthesis of cysteine
	CBS and CTH are critical for maintenance of mitochondrial function and glucocorticoid production in adrenal cortex
	key role for the H2S-generating enzymes CBS and CTH in pulmonary vascular development and homeostasis and in lung alveolarization
	BHMT and CBS are major enzymes in the metabolism of plasma homocysteine (Hcy)

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

aminoacid

signaling

sulfur aminoacid

a component

INTERACTION

DNA

RNA

small molecule	metal binding, cofactor,
	pyridoxal-phosphate

protein

huntingtin

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

CBSD

related resource

Cystathionebeta-synthetase

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   is a cause of maternal obstetric complications such as preeclampsia, pregnancy loss constitutional       loss of function ischemia-reperfusion reduces the activity of CBS leading to Hcy accumulation in the kidney, which in turn contributes to renal injury tumoral     --low   in hepatocellular carcinoma and associated with poor prognosis

Susceptibility

to neural tube defect (NTD) in association with MTHFR, but no evidence of association with NTD in Netherlands and U.K to the development of premature occlusive arterial disease to cleft lip and palate to intracranial aneurysms

Variant & Polymorphism SNP	699 C>T,1080C>T, maybe involved in plasma homocysteine levels
	insertion c844ins68 associated with cleft lip and palate
	olymorphisms of homocysteine metabolism are possible risk factors for the formation of intracranial aneurysms (

Candidate gene
Marker	lower levels of BHMT and CBS methylation are all predictors of failure in folic acid therapy for HHCY (hyperhomocysteinemia)
Therapy target
	System Type Disorder Pubmed metabolism amino acids   chemical chaperones present during the initial folding process can facilitate proper folding of several mutant CBS proteins and suggest it may be possible to treat some inborn errors of metabolism with agents that enhance proper protein folding

ANIMAL & CELL MODELS

	CBS deficient TgI278T Cbs(-/-) mice have significantly decreased fat mass and tCys compared to heterozygous sibling mice
	mice with methionine-deficient diet, had a 50p100 reduction in the levels of liver CBS protein and enzyme activity, because diet induces post-transcriptional downregulation of Cbs