Reviewed, UniProtKB/Swiss-Prot P35520 (CBS_HUMAN)

Names and origin

Protein names

Recommended name:
    Cystathionine beta-synthase
    EC=4.2.1.22
Alternative name(s):
    Serine sulfhydrase
    Beta-thionase

Gene names

Name:

CBS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	551 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	L-serine + L-homocysteine = L-cystathionine + H2O.
Cofactor	Pyridoxal phosphate.
Enzyme regulation	Allosterically activated by adenosyl-methionine (AdoMet).
Pathway	Amino-acid biosynthesis; L-cysteine biosynthesis; L-cysteine from L-homocysteine and L-serine: step 1/2.
Subunit structure	Homotetramer. Ref.11
Subcellular location	Cytoplasm. Nucleus. Ref.9
Tissue specificity	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.
Involvement in disease	Defects in CBS are the cause of cystathionine beta-synthase deficiency (CBSD) [MIM:236200]. It is a recessively inherited error of sulfur amino acid metabolism leading to homocystinuria. Homocystinuria is associated with elevated levels of homocysteine in the blood (homocysteinemia) [MIM:603174]. Patients with homocystinuria have also methionine in their body fluid and usually benefit from dietary and pharmacological treatment (high doses of pyridoxine and vitamin B6). Other characteristics are dislocated optic lenses, vascular disorders (arteriosclerosis and thrombosis), skeletal abnormalities, and mental retardation. Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45 Ref.46
Sequence similarities	Belongs to the cysteine synthase/cystathionine beta-synthase family. Contains 1 CBS domain.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Cysteine biosynthesis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	CBS domain
Ligand	Heme Iron Metal-binding Pyridoxal phosphate
Molecular function	Lyase
PTM	Isopeptide bond Ubl conjugation
Technical term	3D-structure Allosteric enzyme
Gene Ontology (GO)
Biological process	cysteine biosynthetic process from serine Inferred from electronic annotation. Source: InterPro cysteine biosynthetic process via cystathionine Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Inferred from direct assay. Source: UniProtKB nucleolus Inferred from direct assay. Source: HPA
Molecular function	cystathionine beta-synthase activity Traceable author statement. Source: ProtInc iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P35520-1)

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.

Isoform 2 (identifier: P35520-2)

Also known as: Minor;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 551

550

Cystathionine beta-synthase

PRO_0000167133

Regions

Domain

418 – 476

59

CBS

Region

256 – 260

5

Pyridoxal phosphate binding

Sites

Metal binding

52

1

Iron (heme axial ligand)

Metal binding

65

1

Iron (heme axial ligand)

Binding site

149

1

Pyridoxal phosphate

Binding site

349

1

Pyridoxal phosphate

Amino acid modifications

Modified residue

119

1

N6-(pyridoxal phosphate)lysine

Cross-link

211

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.9

Natural variations

Alternative sequence

518

1

Y → SQDQAWAGVVGGPAD in isoform 2.

VSP_001217

Natural variant

18

1

R → C Associated with 1/3 to 2/3 the enzyme activity of the wild-type. Ref.45

VAR_046921

Natural variant

49

1

P → L in CBSD. Ref.39

VAR_008049

Natural variant

58

1

R → W in CBSD; 18% of activity; linked with Val-113. Ref.34

VAR_008050

Natural variant

65

1

H → R in CBSD. Ref.36

VAR_021790

Natural variant

69

1

A → P: dbSNP rs17849313. Ref.7

VAR_046922

Natural variant

78

1

P → R in CBSD; 50% of activity; severe form. Ref.17

VAR_002171

Natural variant

85

1

G → R in CBSD; loss of activity. Ref.38

VAR_008051

Natural variant

88

1

P → S in CBSD. Ref.21

VAR_002172

Natural variant

101

1

L → P in CBSD; common mutation in Irish population; loss of activity. Ref.33 Ref.39 Ref.41

VAR_021791

Natural variant

102

1

K → N in CBSD; 50% of activity. Ref.17 Ref.35

VAR_002173

Natural variant

102

1

K → Q in CBSD; severe form; linked with Arg-77. dbSNP rs34040148. Ref.17 Ref.35

VAR_008052

Natural variant

109

1

C → R in CBSD; loss of activity. Ref.39

VAR_021792

Natural variant

114

1

A → V in CBSD; mild form; when linked with W-58 severe form; partial loss of activity; affects tetramer formation by promoting formation of larger aggregates. Ref.15 Ref.36

VAR_002174

Natural variant

116

1

G → R in CBSD. Ref.26

VAR_008053

Natural variant

121

1

R → C in CBSD.

VAR_008054

Natural variant

121

1

R → H in CBSD.

VAR_008055

Natural variant

121

1

R → L in CBSD; mild form.

VAR_008056

Natural variant

125

1

R → P in CBSD. Ref.18 Ref.21 Ref.37 Ref.39 Ref.40 Ref.46

VAR_046923

Natural variant

125

1

R → Q in CBSD; severe form; loss of activity; when linked with D-132 moderate form. Ref.18 Ref.21 Ref.37 Ref.39 Ref.40 Ref.46

VAR_002175

Natural variant

125

1

R → W in CBSD; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure. Ref.18 Ref.21 Ref.37 Ref.39 Ref.40 Ref.46

VAR_008057

Natural variant

126

1

M → V in CBSD; loss of activity. Ref.34

VAR_008058

Natural variant

128

1

E → D in CBSD.

VAR_008059

Natural variant

131

1

E → D in CBSD; loss of activity; linked with Q-125. Ref.18

VAR_002176

Natural variant

139

1

G → R in CBSD; mild form. Ref.20

VAR_008060

Natural variant

143

1

I → M in CBSD; 4% of activity; stable. Ref.42

VAR_021793

Natural variant

144

1

E → K in CBSD; loss of activity. Ref.20 Ref.27 Ref.32 Ref.36 Ref.39

VAR_002177

Natural variant

145

1

P → L in CBSD; linked with Q-438. Ref.15

VAR_002178

Natural variant

148

1

G → R in CBSD; loss of activity; absent capacity to form multimeric quaternary structure. Ref.42 Ref.46

VAR_008061

Natural variant

151 – 159

9

Missing in CBSD.

VAR_008063

Natural variant

151

1

G → R in CBSD.

VAR_008062

Natural variant

152

1

I → M in CBSD; severe form.

VAR_008064

Natural variant

154

1

L → Q in CBSD; protein expression is comparable to wild-type; significant decrease of enzyme activity. Ref.45

VAR_046924

Natural variant

155

1

A → T in CBSD; complete loss of activity; severely affects tetramer formation by promoting formation of larger aggregates. Ref.36 Ref.45

VAR_008065

Natural variant

155

1

A → V in CBSD; protein expression is comparable to wild-type; significant decrease of enzyme activity. Ref.36 Ref.45

VAR_046925

Natural variant

165

1

C → Y in CBSD; severe form; protein expression is comparable to wild-type; significant decrease of enzyme activity. Ref.22 Ref.32 Ref.36 Ref.39

VAR_002179

Natural variant

168

1

V → A in CBSD. Ref.23 Ref.44

VAR_046926

Natural variant

168

1

V → M in CBSD. Ref.23 Ref.44

VAR_002180

Natural variant

173

1

M → V in CBSD; presents 40% of the wild-type activity; dramatically reduced capacity to form multimeric quaternary structure. Ref.46

VAR_046927

Natural variant

176

1

E → K in CBSD; severe form; loss of activity; severely affects tetramer formation by promoting formation of larger aggregates. Ref.30 Ref.36

VAR_008066

Natural variant

180

1

V → A in CBSD.

VAR_008067

Natural variant

191

1

T → M in CBSD; moderate and severe forms; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure. Ref.40 Ref.44 Ref.46

VAR_008068

Natural variant

198

1

D → V in CBSD.

VAR_008069

Natural variant

224

1

R → H in CBSD. Ref.23

VAR_002181

Natural variant

226

1

A → T in CBSD; presents 20% of the wild-type activity; dramatically reduced capacity to form multimeric quaternary structure. Ref.41 Ref.46

VAR_008070

Natural variant

228

1

N → K in CBSD; loss of activity. Ref.33 Ref.39 Ref.41 Ref.42

VAR_021794

Natural variant

228

1

N → S in CBSD; has significantly decreased levels of enzyme activity. Ref.33 Ref.39 Ref.41 Ref.42

VAR_046928

Natural variant

231

1

A → P in CBSD; has significantly decreased levels of enzyme activity. Ref.41

VAR_046929

Natural variant

234

1

D → N in CBSD. Ref.45

VAR_008071

Natural variant

234

1

Missing in CBSD; protein expression is comparable to wild-type; significant decrease of enzyme activity. Ref.45

VAR_046930

Natural variant

239

1

E → K in CBSD.

VAR_002182

Natural variant

247 – 256

10

Missing in CBSD.

VAR_046931

Natural variant

257

1

T → M in CBSD; moderate to severe form; protein expression is comparable to wild-type; significant decrease of enzyme activity. Ref.21 Ref.45

VAR_002183

Natural variant

262

1

T → M in CBSD; moderate form. Ref.28 Ref.33 Ref.35

VAR_008072

Natural variant

262

1

T → R in CBSD; severe form. Ref.28 Ref.33 Ref.35

VAR_021795

Natural variant

266

1

R → G in CBSD. Ref.28

VAR_008073

Natural variant

266

1

R → K in CBSD; mild form. Ref.28

VAR_008074

Natural variant

270

1

Missing in CBSD.

VAR_008075

Natural variant

275

1

C → Y in CBSD; severe form; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure. Ref.40 Ref.46

VAR_021796

Natural variant

278

1

I → T in CBSD; mild to severe form; common mutation; loss of activity; severely affects tetramer formation by promoting formation of larger aggregates. dbSNP rs5742905. Ref.14 Ref.16 Ref.20 Ref.23 Ref.26 Ref.27 Ref.28 Ref.30 Ref.33 Ref.35 Ref.36 Ref.38 Ref.39 Ref.41 Ref.42 Ref.44

VAR_002184

Natural variant

288

1

A → P in CBSD. Ref.43 Ref.45

VAR_046932

Natural variant

288

1

A → T in CBSD; protein expression is comparable to wild-type; significant decrease of enzyme activity. Ref.43 Ref.45

VAR_046933

Natural variant

290

1

P → L in CBSD. Ref.24 Ref.26

VAR_002185

Natural variant

302

1

E → K in CBSD; 5% of activity. Ref.34 Ref.39

VAR_008076

Natural variant

305

1

G → R in CBSD.

VAR_008077

Natural variant

307

1

G → S in CBSD; moderate to severe form; linked with D-534; has significantly decreased levels of enzyme activity; common mutation. Ref.16 Ref.23 Ref.28 Ref.30 Ref.33 Ref.39 Ref.41

VAR_002186

Natural variant

320

1

V → A in CBSD; has 36% of wild-type enzyme activity. Ref.28 Ref.41

VAR_008078

Natural variant

331

1

A → E in CBSD. Ref.23 Ref.27 Ref.39

VAR_008079

Natural variant

331

1

A → V in CBSD. Ref.23 Ref.27 Ref.39

VAR_002187

Natural variant

336

1

R → C in CBSD; protein expression is comparable to wild-type; loss of activity; absent capacity to form multimeric quaternary structure. Ref.34 Ref.39 Ref.40 Ref.45 Ref.46

VAR_002188

Natural variant

336

1

R → H in CBSD; mild form; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure. Ref.34 Ref.39 Ref.40 Ref.45 Ref.46

VAR_008080

Natural variant

338

1

L → P in CBSD; severe form; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure. Ref.40 Ref.46

VAR_021797

Natural variant

347

1

G → S in CBSD; protein expression is comparable to wild-type; loss of activity. Ref.39 Ref.45

VAR_021798

Natural variant

349

1

S → N in CBSD; severe form; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure. Ref.40 Ref.46

VAR_021799

Natural variant

352

1

S → N in CBSD.

VAR_008081

Natural variant

353

1

T → M in CBSD; protein expression is comparable to wild-type; significant decrease of enzyme activity. Ref.27 Ref.39 Ref.41 Ref.45

VAR_008082

Natural variant

354

1

V → M in CBSD.

VAR_008083

Natural variant

355

1

A → P in CBSD. Ref.33

VAR_021800

Natural variant

361

1

A → T in CBSD. Ref.37

VAR_046934

Natural variant

369

1

R → C in CBSD; when linked with C-491 severe form. Ref.28 Ref.39

VAR_008084

Natural variant

369

1

R → H in CBSD. dbSNP rs11700812. Ref.28 Ref.39

VAR_002189

Natural variant

370

1

C → Y in CBSD. Ref.31

VAR_008085

Natural variant

371

1

V → M in CBSD. Ref.22 Ref.39

VAR_002190

Natural variant

376

1

D → N in CBSD; has significantly decreased levels of enzyme activity. Ref.41

VAR_046935

Natural variant

379

1

R → Q in CBSD; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure. Ref.40 Ref.43 Ref.46

VAR_021801

Natural variant

379

1

R → W in CBSD. Ref.40 Ref.43 Ref.46

VAR_046936

Natural variant

384

1

K → E in CBSD; severe form. Ref.29

VAR_002191

Natural variant

384

1

K → N in CBSD; moderate form. Ref.29

VAR_008086

Natural variant

391

1

M → I in CBSD.

VAR_008087

Natural variant

422

1

P → L in CBSD; increased activity; does not affect tetramer formation; impaired stimulation by S-adenosylmethionine. Ref.38

VAR_021802

Natural variant

434

1

T → N in CBSD.

VAR_008088

Natural variant

435

1

I → T in CBSD; does not affect activity; does not affect tetramer formation; impaired stimulation by S-adenosylmethionine. Ref.38

VAR_008089

Natural variant

439

1

R → Q in CBSD; linked with K-143. Ref.27 Ref.31 Ref.39

VAR_008090

Natural variant

444

1

D → N in CBSD; impaired stimulation by S-adenosylmethionine. Ref.25 Ref.38

VAR_002192

Natural variant

454

1

V → E in CBSD. Ref.23

VAR_002193

Natural variant

456

1

L → P in CBSD; severe; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure. Ref.40 Ref.46

VAR_021803

Natural variant

466

1

S → L in CBSD; increased activity; does not affect tetramer formation; impaired stimulation by S-adenosylmethionine. Ref.38

VAR_008091

Natural variant

491

1

R → C in CBSD; linked with C-368.

VAR_008092

Natural variant

526

1

Q → K in CBSD; has significantly decreased levels of enzyme activity. Ref.41

VAR_046937

Natural variant

534

1

V → D in CBSD; linked with S-306.

VAR_008093

Natural variant

539

1

L → S in CBSD. Ref.29

VAR_002194

Natural variant

548

1

R → Q Presents 60% of the wild-type activity; dramatically reduced capacity to form multimeric quaternary structure. Ref.46

VAR_046938

Experimental info

Mutagenesis

272

1

C → A: Reduced heme content and cystathionine beta-synthase activity. Ref.12

Mutagenesis

275

1

C → S: Reduced heme content and cystathionine beta-synthase activity. Ref.12

Sequence conflict

58

1

R → P in CAA61252. Ref.4

Secondary structure

1

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551

Helix Strand Turn

Details...

Helix

60 – 62

3

Beta strand

75 – 79

5

Helix

80 – 83

4

Beta strand

89 – 91

3

Helix

95 – 98

4

Beta strand

103 – 109

7

Helix

110 – 112

3

Helix

119 – 132

14

Beta strand

141 – 145

5

Helix

149 – 161

13

Beta strand

164 – 169

6

Helix

175 – 183

9

Beta strand

187 – 190

4

Helix

203 – 213

11

Turn

222 – 224

3

Helix

227 – 234

8

Helix

236 – 243

8

Turn

244 – 246

3

Beta strand

250 – 254

5

Beta strand

256 – 258

3

Helix

259 – 271

13

Beta strand

276 – 282

7

Beta strand

288 – 290

3

Helix

291 – 294

4

Helix

317 – 319

3

Beta strand

322 – 326

5

Helix

328 – 341

14

Helix

348 – 360

13

Helix

361 – 363

3

Beta strand

369 – 374

6

Helix

378 – 381

4

Turn

382 – 386

5

Helix

388 – 393

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Major) [UniParc]. Last modified January 23, 2007. Version 2. Checksum: F89E69C67BDE6701	FASTA	551	60,587
	10 20 30 40 50 60 MPSETPQAEV GPTGCPHRSG PHSAKGSLEK GSPEDKEAKE PLWIRPDAPS RCTWQLGRPA 70 80 90 100 110 120 SESPHHHTAP AKSPKILPDI LKKIGDTPMV RINKIGKKFG LKCELLAKCE FFNAGGSVKD 130 140 150 160 170 180 RISLRMIEDA ERDGTLKPGD TIIEPTSGNT GIGLALAAAV RGYRCIIVMP EKMSSEKVDV 190 200 210 220 230 240 LRALGAEIVR TPTNARFDSP ESHVGVAWRL KNEIPNSHIL DQYRNASNPL AHYDTTADEI 250 260 270 280 290 300 LQQCDGKLDM LVASVGTGGT ITGIARKLKE KCPGCRIIGV DPEGSILAEP EELNQTEQTT 310 320 330 340 350 360 YEVEGIGYDF IPTVLDRTVV DKWFKSNDEE AFTFARMLIA QEGLLCGGSA GSTVAVAVKA 370 380 390 400 410 420 AQELQEGQRC VVILPDSVRN YMTKFLSDRW MLQKGFLKEE DLTEKKPWWW HLRVQELGLS 430 440 450 460 470 480 APLTVLPTIT CGHTIEILRE KGFDQAPVVD EAGVILGMVT LGNMLSSLLA GKVQPSDQVG 490 500 510 520 530 540 KVIYKQFKQI RLTDTLGRLS HILEMDHFAL VVHEQIQYHS TGKSSQRQMV FGVVTAIDLL 550 NFVAAQERDQ K
	Isoform 2 (Minor). Checksum: 8BD062B080067092	FASTA	565	61,863
	10 20 30 40 50 60 MPSETPQAEV GPTGCPHRSG PHSAKGSLEK GSPEDKEAKE PLWIRPDAPS RCTWQLGRPA 70 80 90 100 110 120 SESPHHHTAP AKSPKILPDI LKKIGDTPMV RINKIGKKFG LKCELLAKCE FFNAGGSVKD 130 140 150 160 170 180 RISLRMIEDA ERDGTLKPGD TIIEPTSGNT GIGLALAAAV RGYRCIIVMP EKMSSEKVDV 190 200 210 220 230 240 LRALGAEIVR TPTNARFDSP ESHVGVAWRL KNEIPNSHIL DQYRNASNPL AHYDTTADEI 250 260 270 280 290 300 LQQCDGKLDM LVASVGTGGT ITGIARKLKE KCPGCRIIGV DPEGSILAEP EELNQTEQTT 310 320 330 340 350 360 YEVEGIGYDF IPTVLDRTVV DKWFKSNDEE AFTFARMLIA QEGLLCGGSA GSTVAVAVKA 370 380 390 400 410 420 AQELQEGQRC VVILPDSVRN YMTKFLSDRW MLQKGFLKEE DLTEKKPWWW HLRVQELGLS 430 440 450 460 470 480 APLTVLPTIT CGHTIEILRE KGFDQAPVVD EAGVILGMVT LGNMLSSLLA GKVQPSDQVG 490 500 510 520 530 540 KVIYKQFKQI RLTDTLGRLS HILEMDHFAL VVHEQIQSQD QAWAGVVGGP ADHSTGKSSQ 550 560 RQMVFGVVTA IDLLNFVAAQ ERDQK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human cystathionine beta-synthase cDNA: sequence, alternative splicing and expression in cultured cells." Kraus J.P., Le K., Swaroop M., Ohura T., Tahara T., Rosenberg L.E., Roper M.D., Kozich V. Hum. Mol. Genet. 2:1633-1638(1993) [PubMed: 7903580] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Genomic organization of the human cystathionine beta-synthase gene: evidence for various cDNAs." Chasse J.-F., Paly E., Paris D., Paul V., Sinet P.-M., Kamoun P., London J. Biochem. Biophys. Res. Commun. 211:826-832(1995) [PubMed: 7598711] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"A yeast system for expression of human cystathionine beta-synthase: structural and functional conservation of the human and yeast genes." Kruger W.D., Cox D.R. Proc. Natl. Acad. Sci. U.S.A. 91:6614-6618(1994) [PubMed: 8022826] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Human cystathionine beta-synthase: gene organization and expression of different 5' alternative splicing." Chasse J.-F., Paul V., Escanez R., Kamoun P., London J. Mamm. Genome 8:917-921(1997) [PubMed: 9383285] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms." Kraus J.P., Oliveriusova J., Sokolova J., Kraus E., Vlcek C., de Franchis R., Maclean K.N., Bao L., Bukovska G., Patterson D., Paces V., Ansorge W., Kozich V. Genomics 52:312-324(1998) [PubMed: 9790750] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-69. Tissue: Brain, Eye, Lung and Muscle.
[8]	"Purification and properties of cystathionine beta-synthase from human liver. Evidence for identical subunits." Kraus J.P., Packman S., Fowler B., Rosenberg L.E. J. Biol. Chem. 253:6523-6528(1978) [PubMed: 681363] [Abstract] Cited for: CHARACTERIZATION.
[9]	"Human cystathionine beta-synthase is a target for sumoylation." Kabil O., Zhou Y., Banerjee R. Biochemistry 45:13528-13536(2006) [PubMed: 17087506] [Abstract] Cited for: SUMOYLATION AT LYS-211, SUBCELLULAR LOCATION.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]	"Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein." Meier M., Janosik M., Kery V., Kraus J.P., Burkhard P. EMBO J. 20:3910-3916(2001) [PubMed: 11483494] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-413 IN COMPLEX WITH PYRIDOXAL PHOSPHATE AND IRON, SUBUNIT.
[12]	"Human cystathionine beta-synthase is a heme sensor protein. Evidence that the redox sensor is heme and not the vicinal cysteines in the CXXC motif seen in the crystal structure of the truncated enzyme." Taoka S., Lepore B.W., Kabil O., Ojha S., Ringe D., Banerjee R. Biochemistry 41:10454-10461(2002) [PubMed: 12173932] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 45-406 IN COMPLEX WITH PYRIDOXAL PHOSPHATE AND IRON, ALLOSTERIC ACTIVATOR ADOMET, MUTAGENESIS OF CYS-272 AND CYS-275.
[13]	"Cystathionine beta-synthase mutations in homocystinuria." Kraus J.P., Janosik M., Kozich V., Mandell R., Shih V.E., Sperandeo M.P., Sebastio G., de Franchis R., Andria G., Kluijtmans L.A.J., Blom H.J., Boers G.H.J., Gordon R.B., Kamoun P., Tsai M.Y., Kruger W.D., Koch H.G., Ohura T., Gaustadnes M. Hum. Mutat. 13:362-375(1999) [PubMed: 10338090] [Abstract] Cited for: REVIEW ON CBSD VARIANTS.
[14]	"Screening for mutations by expressing patient cDNA segments in E. coli: homocystinuria due to cystathionine beta-synthase deficiency." Kozich V., Kraus J.P. Hum. Mutat. 1:113-123(1992) [PubMed: 1301198] [Abstract] Cited for: VARIANT CBSD THR-278.
[15]	"Molecular defect in a patient with pyridoxine-responsive homocystinuria." Kozich V., de Franchis R., Kraus J.P. Hum. Mol. Genet. 2:815-816(1993) [PubMed: 8353501] [Abstract] Cited for: VARIANTS CBSD VAL-114 AND LEU-145.
[16]	"Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria." Hu F.L., Gu Z., Kozich V., Kraus J.P., Ramesh V., Shih V.E. Hum. Mol. Genet. 2:1857-1860(1993) [PubMed: 7506602] [Abstract] Cited for: VARIANTS CBSD THR-278 AND SER-307.
[17]	"Identical genotypes in siblings with different homocystinuric phenotypes: identification of three mutations in cystathionine beta-synthase using an improved bacterial expression system." de Franchis R., Kozich V., McInnes R., Kraus J.P. Hum. Mol. Genet. 3:1103-1108(1994) [PubMed: 7981678] [Abstract] Cited for: VARIANTS CBSD ARG-78 AND ASN-102.
[18]	"Characterization of a cystathionine beta-synthase allele with three mutations in cis in a patient with B6 nonresponsive homocystinuria." Marble M., Geraghty M.T., de Franchis R., Kraus J.P., Valle D. Hum. Mol. Genet. 3:1883-1886(1994) [PubMed: 7849717] [Abstract] Cited for: VARIANTS CBSD GLN-125 AND ASP-131.
[19]	"Komrower Lecture. Molecular basis of phenotype expression in homocystinuria." Kraus J.P. J. Inherit. Metab. Dis. 17:383-390(1994) [PubMed: 7967489] [Abstract] Cited for: VARIANTS CBSD.
[20]	"A missense mutation (I278T) in the cystathionine beta-synthase gene prevalent in pyridoxine-responsive homocystinuria and associated with mild clinical phenotype." Shih V.E., Fringer J.M., Mandell R., Kraus J.P., Berry G.T., Heidenreich R.A., Korson M.S., Levy H.L., Ramesh V. Am. J. Hum. Genet. 57:34-39(1995) [PubMed: 7611293] [Abstract] Cited for: VARIANTS CBSD ARG-139; LYS-144 AND THR-278.
[21]	"The molecular basis of homocystinuria due to cystathionine beta-synthase deficiency in Italian families, and report of four novel mutations." Sebastio G., Sperandeo M.P., Panico M., de Franchis R., Kraus J.P., Andria G. Am. J. Hum. Genet. 56:1324-1333(1995) [PubMed: 7762555] [Abstract] Cited for: VARIANTS CBSD SER-88; GLN-125 AND MET-257.
[22]	"Two novel missense mutations in the cystathionine beta-synthase gene in homocystinuric patients." Kluijtmans L.A.J., Blom H.J., Boers G.H.J., van Oost B.A., Trijbels F.J.M., van den Heuvel L.P.W.J. Hum. Genet. 96:249-250(1995) [PubMed: 7635485] [Abstract] Cited for: VARIANTS CBSD TYR-165 AND MET-371.
[23]	"A yeast assay for functional detection of mutations in the human cystathionine beta-synthase gene." Kruger W.D., Cox D.R. Hum. Mol. Genet. 4:1155-1161(1995) [PubMed: 8528202] [Abstract] Cited for: VARIANTS CBSD MET-168; HIS-224; THR-278; SER-307; VAL-331 AND GLU-454.
[24]	"Molecular analysis of patients affected by homocystinuria due to cystathionine beta-synthase deficiency: report of a new mutation in exon 8 and a deletion in intron 11." Sperandeo M.P., Panico M., Pepe A., Candito M., de Franchis R., Kraus J.P., Andria G., Sebastio G. J. Inherit. Metab. Dis. 18:211-214(1995) [PubMed: 7564249] [Abstract] Cited for: VARIANT CBSD LEU-290.
[25]	"Defective cystathionine beta-synthase regulation by S-adenosylmethionine in a partially pyridoxine responsive homocystinuria patient." Kluijtmans L.A.J., Boers G.H.J., Stevens E.M.B., Renier W.O., Kraus J.P., Trijbels F.J.M., van den Heuvel L.P.W.J., Blom H.J. J. Clin. Invest. 98:285-289(1996) [PubMed: 8755636] [Abstract] Cited for: VARIANT CBSD ASN-444, CHARACTERIZATION OF VARIANT CBSD ASN-444.
[26]	"Homocysteine response to methionine challenge in four obligate heterozygotes for homocystinuria and relationship with cystathionine beta-synthase mutations." Sperandeo M.P., Candito M., Sebastio G., Rolland M.O., Turc-Carel C., Giudicelli H., Dellamonica P., Andria G. J. Inherit. Metab. Dis. 19:351-356(1996) [PubMed: 8803779] [Abstract] Cited for: VARIANTS CBSD ARG-116; THR-278 AND LEU-290.
[27]	"Characterisation of five missense mutations in the cystathionine beta-synthase gene from three patients with B6-nonresponsive homocystinuria." Dawson P.A., Cox A.J., Emmerson B.T., Dudman N.P.B., Kraus J.P., Gordon R.B. Eur. J. Hum. Genet. 5:15-21(1997) [PubMed: 9156316] [Abstract] Cited for: VARIANTS CBSD LYS-144; THR-278; GLU-331; MET-353 AND GLN-439.
[28]	"Functional modeling of vitamin responsiveness in yeast: a common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria." Kim C.E., Gallagher P.M., Guttormsen A.B., Refsum H., Ueland P.M., Ose L., Foelling I., Whitehead A.S., Tsai M.Y., Kruger W.D. Hum. Mol. Genet. 6:2213-2221(1997) [PubMed: 9361025] [Abstract] Cited for: VARIANTS CBSD MET-262; LYS-266; THR-278; SER-307; ALA-320 AND CYS-369.
[29]	"Two novel mutations (K384E and L539S) in the C-terminal moiety of the cystathionine beta-synthase protein in two French pyridoxine-responsive homocystinuria patients." Aral B., Coude M., London J., Aupetit J., Chasse J.-F., Zabot M.-T., Chadefaux-Vekemans B., Kamoun P. Hum. Mutat. 9:81-82(1997) [PubMed: 8990018] [Abstract] Cited for: VARIANTS CBSD GLU-384 AND SER-539.
[30]	"Analysis of CBS alleles in Czech and Slovak patients with homocystinuria: report on three novel mutations E176K, W409X and 1223 + 37 del99." Kozich V., Janosik M., Sokolova J., Oliveriusova J., Orendac M., Kraus J.P., Elleder D. J. Inherit. Metab. Dis. 20:363-366(1997) [PubMed: 9266356] [Abstract] Cited for: VARIANTS CBSD LYS-176; THR-278 AND SER-307.
[31]	"Two novel mutations in the cystathionine beta-synthase gene of homocystinuric patients." Tsai M.Y., Wong P.W.K., Garg U., Hanson N.Q., Schwichtenberg K. Mol. Diagn. 2:129-133(1997) [PubMed: 10462600] [Abstract] Cited for: VARIANTS CBSD TYR-370 AND GLN-439.
[32]	"Mutational analysis of the cystathionine beta-synthase gene: a splicing mutation, two missense mutations and an insertion in patients with homocystinuria." Gordon R.B., Cox A.J., Dawson P.A., Emmerson B.T., Kraus J.P., Dudman N.P. Hum. Mutat. 11:332-332(1998) [PubMed: 10215408] [Abstract] Cited for: VARIANTS CBSD LYS-144 AND TYR-165.
[33]	"Characterization of mutations in the cystathionine beta-synthase gene in Irish patients with homocystinuria." Gallagher P.M., Naughten E., Hanson N.Q., Schwichtenberg K., Bignell M., Yuan M., Ward P., Yap S., Whitehead A.S., Tsai M.Y. Mol. Genet. Metab. 65:298-302(1998) [PubMed: 9889017] [Abstract] Cited for: VARIANTS CBSD PRO-101; LYS-228; MET-262; THR-278; SER-307 AND PRO-355.
[34]	"Four novel mutations in the cystathionine beta-synthase gene: effect of a second linked mutation on the severity of the homocystinuric phenotype." de Franchis R., Kraus E., Kozich V., Sebastio G., Kraus J.P. Hum. Mutat. 13:453-457(1999) [PubMed: 10408774] [Abstract] Cited for: VARIANTS CBSD TRP-58; VAL-126; LYS-302 AND CYS-336.
[35]	"Homocystinuria in the Arab population of Israel: identification of two novel mutations using DGGE analysis." Gat-Yablonski G., Mandel H., Fowler B., Taleb O., Sela B.-A. Hum. Mutat. 16:372-372(2000) [PubMed: 11013450] [Abstract] Cited for: VARIANTS CBSD GLN-102; ARG-262 AND THR-278.
[36]	"Impaired heme binding and aggregation of mutant cystathionine beta-synthase subunits in homocystinuria." Janosik M., Oliveriusova J., Janosikova B., Sokolova J., Kraus E., Kraus J.P., Kozich V. Am. J. Hum. Genet. 68:1506-1513(2001) [PubMed: 11359213] [Abstract] Cited for: VARIANTS CBSD ARG-65; VAL-114; LYS-144; THR-155; TYR-165; LYS-176 AND THR-278, CHARACTERIZATION OF VARIANTS CBSD VAL-114; LYS-144; THR-155; TYR-165; LYS-176 AND THR-278.
[37]	"Molecular genetic analysis of the cystathionine beta-synthase gene in Portuguese homocystinuria patients: three novel mutations." Castro R., Heil S.G., Rivera I., Jakobs C., de Almeida I.T., Blom H.J. Clin. Genet. 60:161-163(2001) [PubMed: 11553052] [Abstract] Cited for: VARIANTS CBSD PRO-125 AND THR-361.
[38]	"High homocysteine and thrombosis without connective tissue disorders are associated with a novel class of cystathionine beta-synthase (CBS) mutations." Maclean K.N., Gaustadnes M., Oliveriusova J., Janosik M., Kraus E., Kozich V., Kery V., Skovby F., Ruediger N., Ingerslev J., Stabler S.P., Allen R.H., Kraus J.P. Hum. Mutat. 19:641-655(2002) [PubMed: 12007221] [Abstract] Cited for: VARIANTS CBSD ARG-85; THR-278; LEU-422; THR-435; ASN-444 AND LEU-466, CHARACTERIZATION OF VARIANTS CBSD ARG-85; LEU-422; THR-435 AND LEU-466.
[39]	"The molecular basis of cystathionine beta-synthase deficiency in Australian patients: genotype-phenotype correlations and response to treatment." Gaustadnes M., Wilcken B., Oliveriusova J., McGill J., Fletcher J., Kraus J.P., Wilcken D.E. Hum. Mutat. 20:117-126(2002) [PubMed: 12124992] [Abstract] Cited for: VARIANTS CBSD LEU-49; PRO-101; ARG-109; GLN-125; LYS-144; TYR-165; LYS-228; THR-278; LYS-302; SER-307; GLU-331; CYS-336; SER-347; MET-353; CYS-369; MET-371 AND GLN-439, CHARACTERIZATION OF VARIANTS CBSD PRO-101; ARG-109; LYS-228 AND SER-347.
[40]	"Spectrum of CBS mutations in 16 homocystinuric patients from the iberian peninsula: high prevalence of T191M and absence of I278T or G307S." Urreizti R., Balcells S., Rodes M., Vilarinho L., Baldellou A., Couce M.L., Munoz C., Campistol J., Pinto X., Vilaseca M.A., Grinberg D. Hum. Mutat. 22:103-103(2003) [PubMed: 12815602] [Abstract] Cited for: VARIANTS CBSD TRP-125; MET-191; TYR-275; CYS-336; PRO-338; ASN-349; GLN-379 AND PRO-456.
[41]	"Cystathionine beta-synthase deficiency in Georgia (USA): correlation of clinical and biochemical phenotype with genotype." Kruger W.D., Wang L., Jhee K.H., Singh R.H., Elsas L.J. II Hum. Mutat. 22:434-441(2003) [PubMed: 14635102] [Abstract] Cited for: VARIANTS CBSD PRO-101; THR-226; SER-228; PRO-231; THR-278; SER-307; ALA-320; MET-353; ASN-376 AND LYS-526, CHARACTERIZATION OF VARIANTS CBSD PRO-101; THR-226; SER-228; PRO-231; THR-278; SER-307; ALA-320; MET-353; ASN-376 AND LYS-526.
[42]	"Identification and functional analysis of two novel mutations in the CBS gene in Polish patients with homocystinuria." Orendac M., Pronicka E., Kubalska J., Janosik M., Sokolova J., Linnebank M., Koch H.G., Kozich V. Hum. Mutat. 23:631-631(2004) [PubMed: 15146473] [Abstract] Cited for: VARIANTS CBSD MET-143; ARG-148; LYS-228 AND THR-278, CHARACTERIZATION OF VARIANTS CBSD MET-143 AND ARG-148.
[43]	"The cystathionine beta-synthase (CBS) mutation c.1224-2A>C in Central Europe: vitamin B6 nonresponsiveness and a common ancestral haplotype." Linnebank M., Janosik M., Kozich V., Pronicka E., Kubalska J., Sokolova J., Linnebank A., Schmidt E., Leyendecker C., Klockgether T., Kraus J.P., Koch H.G. Hum. Mutat. 24:352-353(2004) [PubMed: 15365998] [Abstract] Cited for: VARIANTS CBSD 247-LYS--GLY-256 DEL; PRO-288 AND TRP-379.
[44]	"Molecular analysis of homocystinuria in Brazilian patients." Porto M.P.R., Galdieri L.C., Pereira V.G., Vergani N., da Rocha J.C.C., Micheletti C., Martins A.M., Perez A.B.A., Almeida V.D. Clin. Chim. Acta 362:71-78(2005) [PubMed: 15993874] [Abstract] Cited for: VARIANTS CBSD ALA-168; MET-191 AND THR-278.
[45]	"Identification and functional analysis of cystathionine beta-synthase gene mutations in patients with homocystinuria." Lee S.-J., Lee D.H., Yoo H.-W., Koo S.K., Park E.-S., Park J.-W., Lim H.G., Jung S.-C. J. Hum. Genet. 50:648-654(2005) [PubMed: 16205833] [Abstract] Cited for: VARIANTS CBSD GLN-154; VAL-155; ASP-234 DEL; MET-257; THR-288; CYS-336; SER-347 AND MET-353, VARIANT CYS-18, CHARACTERIZATION OF VARIANTS CBSD GLN-154; VAL-155; ASP-234 DEL; MET-257; THR-288; CYS-336; SER-347 AND MET-353, CHARACTERIZATION OF VARIANT CYS-18.
[46]	"Functional assays testing pathogenicity of 14 cystathionine-beta synthase mutations." Urreizti R., Asteggiano C., Cozar M., Frank N., Vilaseca M.A., Grinberg D., Balcells S. Hum. Mutat. 27:211-211(2006) [PubMed: 16429402] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS CBSD TRP-125; ARG-148; VAL-173; MET-191; THR-226; TYR-275; CYS-336; HIS-336; PRO-338; ASN-349; GLN-379 AND PRO-456, CHARACTERIZATION OF VARIANT GLN-548.
+	Additional computationally mapped references.

Web resources

CBS mutation database

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

L19501 mRNA. Translation: AAA19874.1.
X82166 mRNA. Translation: CAA57656.1.
L14577 mRNA. Translation: AAA98524.1.
X88562 , X91910, X98811, X98812, X98813, X98814, X98815, X98816, X98817, X98818, X98819, X98820, X98821, X98822, X98823 Genomic DNA. Translation: CAA61252.1.
AF042836 Genomic DNA. Translation: AAC64684.1.
AF042836 Genomic DNA. Translation: AAC64683.1.
BT007154 mRNA. Translation: AAP35818.1.
BC000440 mRNA. Translation: AAH00440.1.
BC007257 mRNA. Translation: AAH07257.1.
BC010242 mRNA. Translation: AAH10242.1.
BC011381 mRNA. Translation: AAH11381.1.

IPI

IPI00219352.
IPI00219649.

PIR

A55760.

RefSeq

NP_000062.1.

UniGene

Hs.533013

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JBQ	X-ray	2.60	A/B/C/D/E/F	2-413	[»]
1M54	X-ray	2.90	A/B/C/D/E/F	45-406	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P35520. 4 interactions.

Proteomic databases

PRIDE

P35520.

Genome annotation databases

Ensembl

ENSG00000160200. Homo sapiens. [Contig view]

GeneID

875.

KEGG

hsa:875.

Organism-specific databases

GeneCards

GC21M043346.

H-InvDB

HIX0016150.

HGNC

HGNC:1550. CBS.

HPA

HPA001223.

MIM

236200. gene+phenotype.
603174. phenotype.

Orphanet

394. Homocystinuria due to cystathionine beta-synthase deficiency.

PharmGKB

PA26123.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P35520.

OMA

P35520. FLSDRWM.

Enzyme and pathway databases

BRENDA

4.2.1.22. 247.

Gene expression databases

ArrayExpress

P35520.

Bgee

P35520.

CleanEx

HS_CBS.

GermOnline

ENSG00000160200. Homo sapiens.

Family and domain databases

InterPro

IPR001216. Cys_synth_BS.
IPR005857. Cysta_beta_synth.
IPR000644. Cysta_beta_synth_core.
IPR001926. PyrdxlP-dep_enz_bsu.
[Graphical view]

Pfam

PF00571. CBS. 1 hit.
PF00291. PALP. 1 hit.
[Graphical view]

SMART

SM00116. CBS. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01137. cysta_beta. 1 hit.

PROSITE

PS51371. CBS. 1 hit.
PS00901. CYS_SYNTHASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00151. L-Cysteine.
DB00133. L-Serine.
DB00114. Pyridoxal Phosphate.
DB00165. Pyridoxine.
DB00118. S-Adenosylmethionine.

NextBio

3642.

SOURCE

Search...

Entry information

Entry name

CBS_HUMAN

Accession

Primary (citable) accession number: P35520
Secondary accession number(s): Q99425, Q9BWC5

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)