Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Cystathionine beta-synthase  

UniProtKB / Swiss-Prot ID :  CBS_HUMAN

Gene Name (Synonyms) : 
CBS  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Cytoplasm. Nucleus. 

Protein Function :  Only known pyridoxal phosphate-dependent enzyme that contains heme. Important regulator of hydrogen sulfide, especially in the brain, utilizing cysteine instead of serine to catalyze the formation of hydrogen sulfide. Hydrogen sulfide is a gastratransmitter with signaling and cytoprotective effects such as acting as a neuromodulator in the brain to protect neurons against hypoxic injury (By similarity). 

Protein Sequence MPSETPQAEVGPTGCPHRSGPHSAKGSLEKGSPEDKEAKEPLWIRPDAPSRCTWQLGRPASESPHHHTAP...
Predicted Secondary Structure CCCCCCCCCCCCCCCCCCCCCCCHHHHHHHCCCCCCCCCCEEEECCCCCCCCCCCCCCCCCCCCCCCHHH...
Protein Variant
LocationDescription
18R -> C (associated with 1/3 to 2/3 theenzyme activity of the wild-type).
49P -> L (in CBSD). VAR_008049
58R -> W (in CBSD; 18% of activity; linkedwith Val-113).
65H -> R (in CBSD). VAR_021790
69A -> P (in dbSNP:rs17849313). VAR_046922
78P -> R (in CBSD; 50% of activity; severeform).
85G -> R (in CBSD; loss of activity). VAR_008051
88P -> S (in CBSD). VAR_002172
101L -> P (in CBSD; common mutation in Irishpopulation; loss of activity).
102K -> N (in CBSD; 50% of activity). VAR_002173
102K -> Q (in CBSD; severe form; linked withArg-77; dbSNP:rs34040148).
109C -> R (in CBSD; loss of activity). VAR_021792
114A -> V (in CBSD; mild form; when linkedwith W-58 severe form; partial loss of
116G -> R (in CBSD). VAR_008053
121R -> C (in CBSD). VAR_008054
121R -> H (in CBSD). VAR_008055
121R -> L (in CBSD; mild form). VAR_008056
125R -> P (in CBSD). VAR_046923
125R -> Q (in CBSD; severe form; loss ofactivity; when linked with D-132 moderate
125R -> W (in CBSD; exhibits an activitylower than 4% of the wild-type enzyme;
126M -> V (in CBSD; loss of activity). VAR_008058
128E -> D (in CBSD). VAR_008059
131E -> D (in CBSD; loss of activity; linkedwith Q-125).
139G -> R (in CBSD; mild form). VAR_008060
143I -> M (in CBSD; 4% of activity; stable). VAR_021793
144E -> K (in CBSD; loss of activity). VAR_002177
145P -> L (in CBSD; linked with Q-438). VAR_002178
148G -> R (in CBSD; loss of activity; absentcapacity to form multimeric quaternary
151Missing (in CBSD). VAR_008063
151G -> R (in CBSD). VAR_008062
152I -> M (in CBSD; severe form). VAR_008064
154L -> Q (in CBSD; protein expression iscomparable to wild-type; significant
155A -> T (in CBSD; complete loss ofactivity; severely affects tetramer
155A -> V (in CBSD; protein expression iscomparable to wild-type; significant
165C -> Y (in CBSD; severe form; proteinexpression is comparable to wild-type;
168V -> A (in CBSD). VAR_046926
168V -> M (in CBSD). VAR_002180
173M -> V (in CBSD; presents 40% of thewild-type activity; dramatically reduced
173Missing (in CBSD; loss of activity). VAR_066098
176E -> K (in CBSD; severe form; loss ofactivity; severely affects tetramer
180V -> A (in CBSD). VAR_008067
191T -> M (in CBSD; moderate and severeforms; exhibits an activity lower than 4%
198D -> V (in CBSD). VAR_008069
200P -> L (in CBSD). VAR_066099
224R -> H (in CBSD). VAR_002181
226A -> T (in CBSD; presents 20% of thewild-type activity; dramatically reduced
228N -> K (in CBSD; loss of activity). VAR_021794
228N -> S (in CBSD; has significantlydecreased levels of enzyme activity).
231A -> P (in CBSD; has significantlydecreased levels of enzyme activity).
234D -> N (in CBSD). VAR_008071
234Missing (in CBSD; protein expression iscomparable to wild-type; significant
239E -> K (in CBSD). VAR_002182
247Missing (in CBSD). VAR_046931
257T -> M (in CBSD; moderate to severe form;protein expression is comparable to wild-
262T -> M (in CBSD; moderate form). VAR_008072
262T -> R (in CBSD; severe form). VAR_021795
266R -> G (in CBSD). VAR_008073
266R -> K (in CBSD; mild form;dbSNP:rs28934275).
270Missing (in CBSD). VAR_008075
275C -> Y (in CBSD; severe form; exhibits anactivity lower than 4% of the wild-type
278I -> S (in CBSD; loss of activity). VAR_066100
278I -> T (in CBSD; mild to severe form;common mutation; loss of activity;
281D -> N (in CBSD; loss of activity). VAR_066101
288A -> P (in CBSD). VAR_046932
288A -> T (in CBSD; protein expression iscomparable to wild-type; significant
290P -> L (in CBSD). VAR_002185
302E -> K (in CBSD; 5% of activity). VAR_008076
305G -> R (in CBSD). VAR_008077
307G -> S (in CBSD; moderate to severe form;linked with D-534; has significantly
320V -> A (in CBSD; has 36% of wild-typeenzyme activity).
321D -> V (in CBSD; loss of activity). VAR_066102
331A -> E (in CBSD). VAR_008079
331A -> V (in CBSD). VAR_002187
336R -> C (in CBSD; protein expression iscomparable to wild-type; loss of
336R -> H (in CBSD; mild form; exhibits anactivity lower than 4% of the wild-type
338L -> P (in CBSD; severe form; exhibits anactivity lower than 4% of the wild-type
347G -> S (in CBSD; protein expression iscomparable to wild-type; loss of
349S -> N (in CBSD; severe form; exhibits anactivity lower than 4% of the wild-type
352S -> N (in CBSD). VAR_008081
353T -> M (in CBSD; protein expression iscomparable to wild-type; significant
354V -> M (in CBSD). VAR_008083
355A -> P (in CBSD). VAR_021800
361A -> T (in CBSD). VAR_046934
369R -> C (in CBSD; when linked with C-491severe form).
369R -> H (in CBSD; dbSNP:rs11700812). VAR_002189
370C -> Y (in CBSD). VAR_008085
371V -> M (in CBSD). VAR_002190
376D -> N (in CBSD; has significantlydecreased levels of enzyme activity).
379R -> Q (in CBSD; exhibits an activitylower than 4% of the wild-type enzyme;
379R -> W (in CBSD). VAR_046936
384K -> E (in CBSD; severe form). VAR_002191
384K -> N (in CBSD; moderate form). VAR_008086
391M -> I (in CBSD). VAR_008087
422P -> L (in CBSD; increased activity; doesnot affect tetramer formation; impaired
434T -> N (in CBSD). VAR_008088
435I -> T (in CBSD; does not affectactivity; does not affect tetramer
439R -> Q (in CBSD; linked with K-143). VAR_008090
444D -> N (in CBSD; impaired stimulation byS-adenosylmethionine; dbSNP:rs28934891).
446A -> S (in CBSD). VAR_066103
454V -> E (in CBSD). VAR_002193
456L -> P (in CBSD; severe; exhibits anactivity lower than 4% of the wild-type
466S -> L (in CBSD; increased activity; doesnot affect tetramer formation; impaired
491R -> C (in CBSD; linked with C-368). VAR_008092
526Q -> K (in CBSD; has significantlydecreased levels of enzyme activity).
534V -> D (in CBSD; linked with S-306). VAR_008093
539L -> S (in CBSD). VAR_002194
548R -> Q (presents 60% of the wild-typeactivity; dramatically reduced capacity
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
19PhosphoserineCPHRSGPHS
CCCCCCCCC
54.35HPRD
Link-
19Phosphoserine.CPHRSGPHS
CCCCCCCCC
54.35UniProtKB
Link-
27PhosphoserineSAKGSLEKG
CHHHHHHHC
32.42Phosphositeplus
Link-
32PhosphoserineLEKGSPEDK
HHHCCCCCC
35.86HPRD
Link-
32PhosphoserineLEKGSPEDK
HHHCCCCCC
35.86Phosphositeplus
Link-
119N6-(pyridoxal phosphate)lysine.GGSVKDRIS
CCHHHHHHH
42.88UniProtKB
Link
191PhosphothreonineEIVRTPTNA
EEEEECCCC
24.46Phosphositeplus
Link
193PhosphothreonineVRTPTNARF
EEECCCCCC
40.68Phosphositeplus
Link-
211Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)AWRLKNEIP
HHHHHHHCC
43.91Phosphositeplus
Link
211Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO).AWRLKNEIP
HHHHHHHCC
43.91UniProtKB
Link
394Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)WMLQKGFLK
HHHHCCCCC
47.90Phosphositeplus
Link
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
CBS_HUMANphysical interactionMINT-68447MINT16189514
HD_HUMANphysical interactionMINT-15856MINT10823891
CBS_HUMANphysical interactionEBI-760348
intact16189514
VTA1_HUMANphysical interactionEBI-752584
intact16189514
FXR2_HUMANphysical interactionEBI-754864
intact16189514
CQ028_HUMANphysical interactionEBI-756832
intact16189514
HD_HUMANin vivo
yeast 2-hybrid
HPRD:01994HPRD9466992
10434301
FXR2_HUMANyeast 2-hybridHPRD:01994HPRD16189514
CQ028_HUMANyeast 2-hybridHPRD:01994HPRD16189514
VTA1_HUMANyeast 2-hybridHPRD:01994HPRD16189514
CBS_HUMANin vitro
yeast 2-hybrid
HPRD:01994HPRD11173483
11483494
12173932
16189514
SAHH_HUMANENSP00000344460STRING
SYSM_HUMANENSP00000344460STRING
SYSC_HUMANENSP00000344460STRING
SYSC_HUMANENSP00000344460STRING
SDHL_HUMANENSP00000344460STRING
BHMT1_HUMANENSP00000344460STRING
SERB_HUMANENSP00000344460STRING
SPYA_HUMANENSP00000344460STRING
SAHH3_HUMANENSP00000344460STRING
GLYC_HUMANENSP00000344460STRING
SP1_HUMANENSP00000344460STRING
GLYM_HUMANENSP00000344460STRING
HD_HUMANENSP00000344460STRING
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Disease Reference
Kegg disease
OMIM disease
236200Cystathionine beta-synthase deficiency (CBSD)
Drug Reference
DrugBank
DB00151L-Cysteine
DB00133L-Serine
DB00118S-Adenosylmethionine
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Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach.";
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.;
Anal. Chem. 81:4493-4501(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, AND MASSSPECTROMETRY.
Sumoylation
ReferencePubMed
"Human cystathionine beta-synthase is a target for sumoylation.";
Kabil O., Zhou Y., Banerjee R.;
Biochemistry 45:13528-13536(2006).
Cited for: SUMOYLATION AT LYS-211, AND SUBCELLULAR LOCATION.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures