ID CBS_HUMAN Reviewed; 551 AA. AC P35520; B2R993; D3DSK4; Q99425; Q9BWC5; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 27-MAR-2024, entry version 246. DE RecName: Full=Cystathionine beta-synthase {ECO:0000305}; DE EC=4.2.1.22 {ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:23974653, ECO:0000269|PubMed:23981774, ECO:0000269|PubMed:25044645}; DE AltName: Full=Beta-thionase; DE AltName: Full=Serine sulfhydrase; GN Name=CBS; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=7903580; DOI=10.1093/hmg/2.10.1633; RA Kraus J.P., Le K., Swaroop M., Ohura T., Tahara T., Rosenberg L.E., RA Roper M.D., Kozich V.; RT "Human cystathionine beta-synthase cDNA: sequence, alternative splicing and RT expression in cultured cells."; RL Hum. Mol. Genet. 2:1633-1638(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=7598711; DOI=10.1006/bbrc.1995.1886; RA Chasse J.-F., Paly E., Paris D., Paul V., Sinet P.-M., Kamoun P., RA London J.; RT "Genomic organization of the human cystathionine beta-synthase gene: RT evidence for various cDNAs."; RL Biochem. Biophys. Res. Commun. 211:826-832(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8022826; DOI=10.1073/pnas.91.14.6614; RA Kruger W.D., Cox D.R.; RT "A yeast system for expression of human cystathionine beta-synthase: RT structural and functional conservation of the human and yeast genes."; RL Proc. Natl. Acad. Sci. U.S.A. 91:6614-6618(1994). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9383285; DOI=10.1007/s003359900611; RA Chasse J.-F., Paul V., Escanez R., Kamoun P., London J.; RT "Human cystathionine beta-synthase: gene organization and expression of RT different 5' alternative splicing."; RL Mamm. Genome 8:917-921(1997). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING. RX PubMed=9790750; DOI=10.1006/geno.1998.5437; RA Kraus J.P., Oliveriusova J., Sokolova J., Kraus E., Vlcek C., RA de Franchis R., Maclean K.N., Bao L., Bukovska G., Patterson D., Paces V., RA Ansorge W., Kozich V.; RT "The human cystathionine beta-synthase (CBS) gene: complete sequence, RT alternative splicing, and polymorphisms."; RL Genomics 52:312-324(1998). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10830953; DOI=10.1038/35012518; RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U., RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.; RT "The DNA sequence of human chromosome 21."; RL Nature 405:311-319(2000). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-69. RC TISSUE=Brain, Eye, Lung, and Muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP CHARACTERIZATION. RX PubMed=681363; DOI=10.1016/s0021-9258(19)46963-9; RA Kraus J.P., Packman S., Fowler B., Rosenberg L.E.; RT "Purification and properties of cystathionine beta-synthase from human RT liver. Evidence for identical subunits."; RL J. Biol. Chem. 253:6523-6528(1978). RN [12] RP SUMOYLATION AT LYS-211, AND SUBCELLULAR LOCATION. RX PubMed=17087506; DOI=10.1021/bi0615644; RA Kabil O., Zhou Y., Banerjee R.; RT "Human cystathionine beta-synthase is a target for sumoylation."; RL Biochemistry 45:13528-13536(2006). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-199, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP CHARACTERIZATION OF VARIANTS CBSD LEU-49; ARG-65; ARG-78; ASN-102; VAL-114; RP GLN-125; LYS-144; ARG-148; TYR-165; LYS-176; ALA-180; MET-191; LYS-228; RP ARG-262; LYS-266; THR-278; LYS-302; ARG-305; SER-307; CYS-369; LEU-422; RP THR-435; GLN-439; ASN-444; LEU-466 AND SER-539, FUNCTION, CATALYTIC RP ACTIVITY, PATHWAY, ACTIVITY REGULATION, AND SUBUNIT. RX PubMed=20506325; DOI=10.1002/humu.21273; RA Kozich V., Sokolova J., Klatovska V., Krijt J., Janosik M., Jelinek K., RA Kraus J.P.; RT "Cystathionine beta-synthase mutations: effect of mutation topology on RT folding and activity."; RL Hum. Mutat. 31:809-819(2010). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-413 IN COMPLEX WITH PYRIDOXAL RP PHOSPHATE AND IRON, SUBUNIT, ACTIVITY REGULATION, AND REGION. RX PubMed=11483494; DOI=10.1093/emboj/20.15.3910; RA Meier M., Janosik M., Kery V., Kraus J.P., Burkhard P.; RT "Structure of human cystathionine beta-synthase: a unique pyridoxal 5'- RT phosphate-dependent heme protein."; RL EMBO J. 20:3910-3916(2001). RN [20] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 45-406 IN COMPLEX WITH PYRIDOXAL RP PHOSPHATE AND IRON, ALLOSTERIC ACTIVATOR ADOMET, MUTAGENESIS OF CYS-272 AND RP CYS-275, AND REGION. RX PubMed=12173932; DOI=10.1021/bi026052d; RA Taoka S., Lepore B.W., Kabil O., Ojha S., Ringe D., Banerjee R.; RT "Human cystathionine beta-synthase is a heme sensor protein. Evidence that RT the redox sensor is heme and not the vicinal cysteines in the CXXC motif RT seen in the crystal structure of the truncated enzyme."; RL Biochemistry 41:10454-10461(2002). RN [21] RP REVIEW ON CBSD VARIANTS. RX PubMed=10338090; RX DOI=10.1002/(sici)1098-1004(1999)13:5<362::aid-humu4>3.0.co;2-k; RA Kraus J.P., Janosik M., Kozich V., Mandell R., Shih V.E., Sperandeo M.P., RA Sebastio G., de Franchis R., Andria G., Kluijtmans L.A.J., Blom H.J., RA Boers G.H.J., Gordon R.B., Kamoun P., Tsai M.Y., Kruger W.D., Koch H.G., RA Ohura T., Gaustadnes M.; RT "Cystathionine beta-synthase mutations in homocystinuria."; RL Hum. Mutat. 13:362-375(1999). RN [22] RP VARIANT CBSD THR-278. RX PubMed=1301198; DOI=10.1002/humu.1380010206; RA Kozich V., Kraus J.P.; RT "Screening for mutations by expressing patient cDNA segments in E. coli: RT homocystinuria due to cystathionine beta-synthase deficiency."; RL Hum. Mutat. 1:113-123(1992). RN [23] RP VARIANTS CBSD VAL-114 AND LEU-145. RX PubMed=8353501; DOI=10.1093/hmg/2.6.815; RA Kozich V., de Franchis R., Kraus J.P.; RT "Molecular defect in a patient with pyridoxine-responsive homocystinuria."; RL Hum. Mol. Genet. 2:815-816(1993). RN [24] RP VARIANTS CBSD THR-278 AND SER-307. RX PubMed=7506602; DOI=10.1093/hmg/2.11.1857; RA Hu F.L., Gu Z., Kozich V., Kraus J.P., Ramesh V., Shih V.E.; RT "Molecular basis of cystathionine beta-synthase deficiency in pyridoxine RT responsive and nonresponsive homocystinuria."; RL Hum. Mol. Genet. 2:1857-1860(1993). RN [25] RP VARIANTS CBSD ARG-78 AND ASN-102. RX PubMed=7981678; DOI=10.1093/hmg/3.7.1103; RA de Franchis R., Kozich V., McInnes R., Kraus J.P.; RT "Identical genotypes in siblings with different homocystinuric phenotypes: RT identification of three mutations in cystathionine beta-synthase using an RT improved bacterial expression system."; RL Hum. Mol. Genet. 3:1103-1108(1994). RN [26] RP VARIANTS CBSD GLN-125 AND ASP-131. RX PubMed=7849717; DOI=10.1093/hmg/3.10.1883; RA Marble M., Geraghty M.T., de Franchis R., Kraus J.P., Valle D.; RT "Characterization of a cystathionine beta-synthase allele with three RT mutations in cis in a patient with B6 nonresponsive homocystinuria."; RL Hum. Mol. Genet. 3:1883-1886(1994). RN [27] RP VARIANTS CBSD. RX PubMed=7967489; DOI=10.1007/bf00711354; RA Kraus J.P.; RT "Komrower Lecture. Molecular basis of phenotype expression in RT homocystinuria."; RL J. Inherit. Metab. Dis. 17:383-390(1994). RN [28] RP VARIANTS CBSD ARG-139; LYS-144 AND THR-278. RX PubMed=7611293; RA Shih V.E., Fringer J.M., Mandell R., Kraus J.P., Berry G.T., RA Heidenreich R.A., Korson M.S., Levy H.L., Ramesh V.; RT "A missense mutation (I278T) in the cystathionine beta-synthase gene RT prevalent in pyridoxine-responsive homocystinuria and associated with mild RT clinical phenotype."; RL Am. J. Hum. Genet. 57:34-39(1995). RN [29] RP VARIANTS CBSD SER-88; GLN-125 AND MET-257. RX PubMed=7762555; RA Sebastio G., Sperandeo M.P., Panico M., de Franchis R., Kraus J.P., RA Andria G.; RT "The molecular basis of homocystinuria due to cystathionine beta-synthase RT deficiency in Italian families, and report of four novel mutations."; RL Am. J. Hum. Genet. 56:1324-1333(1995). RN [30] RP VARIANTS CBSD TYR-165 AND MET-371. RX PubMed=7635485; DOI=10.1007/bf00207394; RA Kluijtmans L.A.J., Blom H.J., Boers G.H.J., van Oost B.A., Trijbels F.J.M., RA van den Heuvel L.P.W.J.; RT "Two novel missense mutations in the cystathionine beta-synthase gene in RT homocystinuric patients."; RL Hum. Genet. 96:249-250(1995). RN [31] RP VARIANTS CBSD MET-168; HIS-224; THR-278; SER-307; VAL-331 AND GLU-454. RX PubMed=8528202; DOI=10.1093/hmg/4.7.1155; RA Kruger W.D., Cox D.R.; RT "A yeast assay for functional detection of mutations in the human RT cystathionine beta-synthase gene."; RL Hum. Mol. Genet. 4:1155-1161(1995). RN [32] RP VARIANT CBSD LEU-290. RX PubMed=7564249; DOI=10.1007/bf00711769; RA Sperandeo M.P., Panico M., Pepe A., Candito M., de Franchis R., Kraus J.P., RA Andria G., Sebastio G.; RT "Molecular analysis of patients affected by homocystinuria due to RT cystathionine beta-synthase deficiency: report of a new mutation in exon 8 RT and a deletion in intron 11."; RL J. Inherit. Metab. Dis. 18:211-214(1995). RN [33] RP VARIANT CBSD ASN-444, AND CHARACTERIZATION OF VARIANT CBSD ASN-444. RX PubMed=8755636; DOI=10.1172/jci118791; RA Kluijtmans L.A.J., Boers G.H.J., Stevens E.M.B., Renier W.O., Kraus J.P., RA Trijbels F.J.M., van den Heuvel L.P.W.J., Blom H.J.; RT "Defective cystathionine beta-synthase regulation by S-adenosylmethionine RT in a partially pyridoxine responsive homocystinuria patient."; RL J. Clin. Invest. 98:285-289(1996). RN [34] RP VARIANTS CBSD ARG-116; THR-278 AND LEU-290. RX PubMed=8803779; DOI=10.1007/bf01799266; RA Sperandeo M.P., Candito M., Sebastio G., Rolland M.O., Turc-Carel C., RA Giudicelli H., Dellamonica P., Andria G.; RT "Homocysteine response to methionine challenge in four obligate RT heterozygotes for homocystinuria and relationship with cystathionine beta- RT synthase mutations."; RL J. Inherit. Metab. Dis. 19:351-356(1996). RN [35] RP VARIANTS CBSD LYS-144; THR-278; GLU-331; MET-353 AND GLN-439. RX PubMed=9156316; RA Dawson P.A., Cox A.J., Emmerson B.T., Dudman N.P.B., Kraus J.P., RA Gordon R.B.; RT "Characterisation of five missense mutations in the cystathionine beta- RT synthase gene from three patients with B6-nonresponsive homocystinuria."; RL Eur. J. Hum. Genet. 5:15-21(1997). RN [36] RP VARIANTS CBSD MET-262; LYS-266; THR-278; SER-307; ALA-320 AND CYS-369. RX PubMed=9361025; DOI=10.1093/hmg/6.13.2213; RA Kim C.E., Gallagher P.M., Guttormsen A.B., Refsum H., Ueland P.M., Ose L., RA Foelling I., Whitehead A.S., Tsai M.Y., Kruger W.D.; RT "Functional modeling of vitamin responsiveness in yeast: a common RT pyridoxine-responsive cystathionine beta-synthase mutation in RT homocystinuria."; RL Hum. Mol. Genet. 6:2213-2221(1997). RN [37] RP VARIANTS CBSD GLU-384 AND SER-539. RX PubMed=8990018; RX DOI=10.1002/(sici)1098-1004(1997)9:1<81::aid-humu18>3.0.co;2-l; RA Aral B., Coude M., London J., Aupetit J., Chasse J.-F., Zabot M.-T., RA Chadefaux-Vekemans B., Kamoun P.; RT "Two novel mutations (K384E and L539S) in the C-terminal moiety of the RT cystathionine beta-synthase protein in two French pyridoxine-responsive RT homocystinuria patients."; RL Hum. Mutat. 9:81-82(1997). RN [38] RP VARIANTS CBSD LYS-176; THR-278 AND SER-307. RX PubMed=9266356; DOI=10.1023/a:1005325911665; RA Kozich V., Janosik M., Sokolova J., Oliveriusova J., Orendac M., RA Kraus J.P., Elleder D.; RT "Analysis of CBS alleles in Czech and Slovak patients with homocystinuria: RT report on three novel mutations E176K, W409X and 1223 + 37 del99."; RL J. Inherit. Metab. Dis. 20:363-366(1997). RN [39] RP VARIANTS CBSD TYR-370 AND GLN-439. RX PubMed=10462600; DOI=10.1054/modi00200129; RA Tsai M.Y., Wong P.W.K., Garg U., Hanson N.Q., Schwichtenberg K.; RT "Two novel mutations in the cystathionine beta-synthase gene of RT homocystinuric patients."; RL Mol. Diagn. 2:129-133(1997). RN [40] RP VARIANTS CBSD LYS-144 AND TYR-165. RX PubMed=10215408; RX DOI=10.1002/(sici)1098-1004(1998)11:4<332::aid-humu16>3.0.co;2-p; RA Gordon R.B., Cox A.J., Dawson P.A., Emmerson B.T., Kraus J.P., Dudman N.P.; RT "Mutational analysis of the cystathionine beta-synthase gene: a splicing RT mutation, two missense mutations and an insertion in patients with RT homocystinuria."; RL Hum. Mutat. 11:332-332(1998). RN [41] RP VARIANTS CBSD PRO-101; LYS-228; MET-262; THR-278; SER-307 AND PRO-355. RX PubMed=9889017; DOI=10.1006/mgme.1998.2771; RA Gallagher P.M., Naughten E., Hanson N.Q., Schwichtenberg K., Bignell M., RA Yuan M., Ward P., Yap S., Whitehead A.S., Tsai M.Y.; RT "Characterization of mutations in the cystathionine beta-synthase gene in RT Irish patients with homocystinuria."; RL Mol. Genet. Metab. 65:298-302(1998). RN [42] RP VARIANTS CBSD TRP-58; VAL-126; LYS-302 AND CYS-336. RX PubMed=10408774; RX DOI=10.1002/(sici)1098-1004(1999)13:6<453::aid-humu4>3.0.co;2-k; RA de Franchis R., Kraus E., Kozich V., Sebastio G., Kraus J.P.; RT "Four novel mutations in the cystathionine beta-synthase gene: effect of a RT second linked mutation on the severity of the homocystinuric phenotype."; RL Hum. Mutat. 13:453-457(1999). RN [43] RP VARIANTS CBSD ARG-262 AND THR-278, AND VARIANT GLN-102. RX PubMed=11013450; RX DOI=10.1002/1098-1004(200010)16:4<372::aid-humu12>3.0.co;2-j; RA Gat-Yablonski G., Mandel H., Fowler B., Taleb O., Sela B.-A.; RT "Homocystinuria in the Arab population of Israel: identification of two RT novel mutations using DGGE analysis."; RL Hum. Mutat. 16:372-372(2000). RN [44] RP VARIANTS CBSD ARG-65; VAL-114; LYS-144; THR-155; TYR-165; LYS-176 AND RP THR-278, AND CHARACTERIZATION OF VARIANTS CBSD VAL-114; LYS-144; THR-155; RP TYR-165; LYS-176 AND THR-278. RX PubMed=11359213; DOI=10.1086/320597; RA Janosik M., Oliveriusova J., Janosikova B., Sokolova J., Kraus E., RA Kraus J.P., Kozich V.; RT "Impaired heme binding and aggregation of mutant cystathionine beta- RT synthase subunits in homocystinuria."; RL Am. J. Hum. Genet. 68:1506-1513(2001). RN [45] RP VARIANTS CBSD PRO-125 AND THR-361. RX PubMed=11553052; DOI=10.1034/j.1399-0004.2001.600212.x; RA Castro R., Heil S.G., Rivera I., Jakobs C., de Almeida I.T., Blom H.J.; RT "Molecular genetic analysis of the cystathionine beta-synthase gene in RT Portuguese homocystinuria patients: three novel mutations."; RL Clin. Genet. 60:161-163(2001). RN [46] RP VARIANTS CBSD ARG-85; THR-278; LEU-422; THR-435; ASN-444 AND LEU-466, AND RP CHARACTERIZATION OF VARIANTS CBSD ARG-85; LEU-422; THR-435 AND LEU-466. RX PubMed=12007221; DOI=10.1002/humu.10089; RA Maclean K.N., Gaustadnes M., Oliveriusova J., Janosik M., Kraus E., RA Kozich V., Kery V., Skovby F., Ruediger N., Ingerslev J., Stabler S.P., RA Allen R.H., Kraus J.P.; RT "High homocysteine and thrombosis without connective tissue disorders are RT associated with a novel class of cystathionine beta-synthase (CBS) RT mutations."; RL Hum. Mutat. 19:641-655(2002). RN [47] RP VARIANTS CBSD LEU-49; PRO-101; ARG-109; GLN-125; LYS-144; TYR-165; LYS-228; RP THR-278; LYS-302; SER-307; GLU-331; CYS-336; SER-347; MET-353; CYS-369; RP MET-371 AND GLN-439, AND CHARACTERIZATION OF VARIANTS CBSD PRO-101; RP ARG-109; LYS-228 AND SER-347. RX PubMed=12124992; DOI=10.1002/humu.10104; RA Gaustadnes M., Wilcken B., Oliveriusova J., McGill J., Fletcher J., RA Kraus J.P., Wilcken D.E.; RT "The molecular basis of cystathionine beta-synthase deficiency in RT Australian patients: genotype-phenotype correlations and response to RT treatment."; RL Hum. Mutat. 20:117-126(2002). RN [48] RP VARIANTS CBSD TRP-125; MET-191; TYR-275; CYS-336; PRO-338; ASN-349; GLN-379 RP AND PRO-456. RX PubMed=12815602; DOI=10.1002/humu.9153; RA Urreizti R., Balcells S., Rodes M., Vilarinho L., Baldellou A., Couce M.L., RA Munoz C., Campistol J., Pinto X., Vilaseca M.A., Grinberg D.; RT "Spectrum of CBS mutations in 16 homocystinuric patients from the iberian RT peninsula: high prevalence of T191M and absence of I278T or G307S."; RL Hum. Mutat. 22:103-103(2003). RN [49] RP VARIANTS CBSD PRO-101; THR-226; SER-228; PRO-231; THR-278; SER-307; RP ALA-320; MET-353; ASN-376 AND LYS-526, AND CHARACTERIZATION OF VARIANTS RP CBSD PRO-101; THR-226; SER-228; PRO-231; THR-278; SER-307; ALA-320; RP MET-353; ASN-376 AND LYS-526. RX PubMed=14635102; DOI=10.1002/humu.10290; RA Kruger W.D., Wang L., Jhee K.H., Singh R.H., Elsas L.J. II; RT "Cystathionine beta-synthase deficiency in Georgia (USA): correlation of RT clinical and biochemical phenotype with genotype."; RL Hum. Mutat. 22:434-441(2003). RN [50] RP VARIANTS CBSD MET-143; ARG-148; LYS-228 AND THR-278, AND CHARACTERIZATION RP OF VARIANTS CBSD MET-143 AND ARG-148. RX PubMed=15146473; DOI=10.1002/humu.9249; RA Orendac M., Pronicka E., Kubalska J., Janosik M., Sokolova J., RA Linnebank M., Koch H.G., Kozich V.; RT "Identification and functional analysis of two novel mutations in the CBS RT gene in Polish patients with homocystinuria."; RL Hum. Mutat. 23:631-631(2004). RN [51] RP VARIANTS CBSD 247-LYS--GLY-256 DEL; PRO-288 AND TRP-379. RX PubMed=15365998; DOI=10.1002/humu.9280; RA Linnebank M., Janosik M., Kozich V., Pronicka E., Kubalska J., Sokolova J., RA Linnebank A., Schmidt E., Leyendecker C., Klockgether T., Kraus J.P., RA Koch H.G.; RT "The cystathionine beta-synthase (CBS) mutation c.1224-2A>C in Central RT Europe: vitamin B6 nonresponsiveness and a common ancestral haplotype."; RL Hum. Mutat. 24:352-353(2004). RN [52] RP VARIANTS CBSD ALA-168; MET-191 AND THR-278. RX PubMed=15993874; DOI=10.1016/j.cccn.2005.05.030; RA Porto M.P.R., Galdieri L.C., Pereira V.G., Vergani N., da Rocha J.C.C., RA Micheletti C., Martins A.M., Perez A.B.A., Almeida V.D.; RT "Molecular analysis of homocystinuria in Brazilian patients."; RL Clin. Chim. Acta 362:71-78(2005). RN [53] RP VARIANTS CBSD GLN-154; VAL-155; ASP-234 DEL; MET-257; THR-288; CYS-336; RP SER-347 AND MET-353, VARIANT CYS-18, CHARACTERIZATION OF VARIANTS CBSD RP GLN-154; VAL-155; ASP-234 DEL; MET-257; THR-288; CYS-336; SER-347 AND RP MET-353, AND CHARACTERIZATION OF VARIANT CYS-18. RX PubMed=16205833; DOI=10.1007/s10038-005-0312-2; RA Lee S.-J., Lee D.H., Yoo H.-W., Koo S.K., Park E.-S., Park J.-W., Lim H.G., RA Jung S.-C.; RT "Identification and functional analysis of cystathionine beta-synthase gene RT mutations in patients with homocystinuria."; RL J. Hum. Genet. 50:648-654(2005). RN [54] RP CHARACTERIZATION OF VARIANTS CBSD TRP-125; ARG-148; VAL-173; MET-191; RP THR-226; TYR-275; CYS-336; HIS-336; PRO-338; ASN-349; GLN-379 AND PRO-456, RP AND CHARACTERIZATION OF VARIANT GLN-548. RX PubMed=16429402; DOI=10.1002/humu.9395; RA Urreizti R., Asteggiano C., Cozar M., Frank N., Vilaseca M.A., Grinberg D., RA Balcells S.; RT "Functional assays testing pathogenicity of 14 cystathionine-beta synthase RT mutations."; RL Hum. Mutat. 27:211-211(2006). RN [55] RP VARIANTS CBSD MET-173 DEL; LEU-200; SER-278; ASN-281; VAL-321 AND SER-446, RP AND CHARACTERIZATION OF VARIANTS CBSD MET-173 DEL; SER-278; ASN-281 AND RP VAL-321. RX PubMed=21520339; DOI=10.1002/humu.21514; RA Cozar M., Urreizti R., Vilarinho L., Grosso C., Dodelson de Kremer R., RA Asteggiano C.G., Dalmau J., Garcia A.M., Vilaseca M.A., Grinberg D., RA Balcells S.; RT "Identification and functional analyses of CBS alleles in Spanish and RT Argentinian homocystinuric patients."; RL Hum. Mutat. 32:835-842(2011). RN [56] RP VARIANTS CBSD THR-278 AND CYS-336. RX PubMed=21240075; DOI=10.1097/pat.0b013e3283419dbb; RA Kwok J.S., Fung S.L., Lui G.C., Law E.L., Chan M.H., Leung C.B., Tang N.L.; RT "CBS gene mutations found in a Chinese pyridoxine-responsive homocystinuria RT patient."; RL Pathology 43:81-83(2011). RN [57] RP VARIANT CBSD LYS-266, CHARACTERIZATION OF VARIANT CBSD LYS-266, AND RP ACTIVITY REGULATION. RX PubMed=22738154; DOI=10.1021/bi300421z; RA Smith A.T., Su Y., Stevens D.J., Majtan T., Kraus J.P., Burstyn J.N.; RT "Effect of the disease-causing R266K mutation on the heme and PLP RT environments of human cystathionine beta-synthase."; RL Biochemistry 51:6360-6370(2012). RN [58] RP VARIANTS CBSD ARG-85; ASN-87 AND ASN-234, CHARACTERIZATION OF VARIANTS CBSD RP ASN-87 AND ASN-234, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, COFACTOR, RP SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=23981774; DOI=10.1016/j.gene.2013.08.021; RA Casique L., Kabil O., Banerjee R., Martinez J.C., De Lucca M.; RT "Characterization of two pathogenic mutations in cystathionine beta- RT synthase: different intracellular locations for wild-type and mutant RT proteins."; RL Gene 531:117-124(2013). RN [59] RP VARIANT CBSD GLY-449, CHARACTERIZATION OF VARIANTS CBSD LEU-427; ASN-444; RP GLY-449; LEU-500 AND GLN-540, AND CATALYTIC ACTIVITY. RX PubMed=25044645; DOI=10.1002/humu.22616; RA Mendes M.I., Santos A.S., Smith D.E., Lino P.R., Colaco H.G., RA de Almeida I.T., Vicente J.B., Salomons G.S., Rivera I., Blom H.J., RA Leandro P.; RT "Insights into the regulatory domain of cystathionine Beta-synthase: RT characterization of six variant proteins."; RL Hum. Mutat. 35:1195-1202(2014). RN [60] RP VARIANTS CBSD LEU-49; LYS-269 DEL; THR-278; HIS-336; LEU-427; ASN-444; RP LEU-500 AND GLN-540, CHARACTERIZATION OF VARIANTS CBSD LEU-49; LYS-269 DEL; RP THR-278; HIS-336; LEU-427; ASN-444; LEU-500 AND GLN-540, FUNCTION, RP CATALYTIC ACTIVITY, PATHWAY, AND ACTIVITY REGULATION. RX PubMed=23974653; DOI=10.1007/s10545-013-9647-6; RA Mendes M.I., Colaco H.G., Smith D.E., Ramos R.J., Pop A., van Dooren S.J., RA Tavares de Almeida I., Kluijtmans L.A., Janssen M.C., Rivera I., RA Salomons G.S., Leandro P., Blom H.J.; RT "Reduced response of Cystathionine Beta-Synthase (CBS) to S- RT Adenosylmethionine (SAM): Identification and functional analysis of CBS RT gene mutations in Homocystinuria patients."; RL J. Inherit. Metab. Dis. 37:245-254(2014). CC -!- FUNCTION: Hydro-lyase catalyzing the first step of the transsulfuration CC pathway, where the hydroxyl group of L-serine is displaced by L- CC homocysteine in a beta-replacement reaction to form L-cystathionine, CC the precursor of L-cysteine. This catabolic route allows the CC elimination of L-methionine and the toxic metabolite L-homocysteine CC (PubMed:23981774, PubMed:20506325, PubMed:23974653). Also involved in CC the production of hydrogen sulfide, a gasotransmitter with signaling CC and cytoprotective effects on neurons (By similarity). CC {ECO:0000250|UniProtKB:P32232, ECO:0000269|PubMed:20506325, CC ECO:0000269|PubMed:23974653, ECO:0000269|PubMed:23981774}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-homocysteine + L-serine = H2O + L,L-cystathionine; CC Xref=Rhea:RHEA:10112, ChEBI:CHEBI:15377, ChEBI:CHEBI:33384, CC ChEBI:CHEBI:58161, ChEBI:CHEBI:58199; EC=4.2.1.22; CC Evidence={ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:23974653, CC ECO:0000269|PubMed:23981774, ECO:0000269|PubMed:25044645}; CC -!- COFACTOR: CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; CC Evidence={ECO:0000269|PubMed:23981774}; CC -!- ACTIVITY REGULATION: Allosterically activated by S-adenosyl- CC methionine/AdoMet. Activated by S-adenosylhomocysteine/AdoHcy CC (PubMed:20506325). Binds non-covalently to a heme group that may CC control the redox sensitivity of the enzyme (PubMed:11483494, CC PubMed:12173932, PubMed:22738154). {ECO:0000269|PubMed:11483494, CC ECO:0000269|PubMed:12173932, ECO:0000269|PubMed:20506325, CC ECO:0000269|PubMed:22738154, ECO:0000269|PubMed:23974653}. CC -!- PATHWAY: Amino-acid biosynthesis; L-cysteine biosynthesis; L-cysteine CC from L-homocysteine and L-serine: step 1/2. CC {ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:23974653, CC ECO:0000269|PubMed:23981774}. CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:11483494, CC ECO:0000269|PubMed:12173932, ECO:0000269|PubMed:20506325, CC ECO:0000269|PubMed:23981774}. CC -!- INTERACTION: CC P35520; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-740135, EBI-1383687; CC P35520; P35520: CBS; NbExp=6; IntAct=EBI-740135, EBI-740135; CC P35520; P35222: CTNNB1; NbExp=3; IntAct=EBI-740135, EBI-491549; CC P35520; Q15438: CYTH1; NbExp=3; IntAct=EBI-740135, EBI-997830; CC P35520; Q08426: EHHADH; NbExp=4; IntAct=EBI-740135, EBI-2339219; CC P35520; O75344: FKBP6; NbExp=3; IntAct=EBI-740135, EBI-744771; CC P35520; P51116: FXR2; NbExp=3; IntAct=EBI-740135, EBI-740459; CC P35520; P06241: FYN; NbExp=3; IntAct=EBI-740135, EBI-515315; CC P35520; P22466: GAL; NbExp=3; IntAct=EBI-740135, EBI-6624768; CC P35520; P42858: HTT; NbExp=12; IntAct=EBI-740135, EBI-466029; CC P35520; Q92993-2: KAT5; NbExp=3; IntAct=EBI-740135, EBI-20795332; CC P35520; O75928-2: PIAS2; NbExp=3; IntAct=EBI-740135, EBI-348567; CC P35520; Q13526: PIN1; NbExp=4; IntAct=EBI-740135, EBI-714158; CC P35520; P17612: PRKACA; NbExp=3; IntAct=EBI-740135, EBI-476586; CC P35520; P54619: PRKAG1; NbExp=3; IntAct=EBI-740135, EBI-1181439; CC P35520; P25786: PSMA1; NbExp=4; IntAct=EBI-740135, EBI-359352; CC P35520; P57075: UBASH3A; NbExp=4; IntAct=EBI-740135, EBI-2105393; CC P35520; Q7KZS0: UBE2I; NbExp=6; IntAct=EBI-740135, EBI-10180829; CC P35520; Q9UJ78-2: ZMYM5; NbExp=3; IntAct=EBI-740135, EBI-17634549; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17087506, CC ECO:0000269|PubMed:23981774}. Nucleus {ECO:0000269|PubMed:17087506}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=Major; CC IsoId=P35520-1; Sequence=Displayed; CC Name=2; Synonyms=Minor; CC IsoId=P35520-2; Sequence=VSP_001217; CC -!- TISSUE SPECIFICITY: In the adult strongly expressed in liver and CC pancreas, some expression in heart and brain, weak expression in lung CC and kidney. In the fetus, expressed in brain, liver and kidney. CC -!- DISEASE: Cystathionine beta-synthase deficiency (CBSD) [MIM:236200]: An CC enzymatic deficiency resulting in altered sulfur metabolism and CC homocystinuria. The clinical features of untreated homocystinuria due CC to CBS deficiency include myopia, ectopia lentis, intellectual CC disability, skeletal anomalies resembling Marfan syndrome, and CC thromboembolic events. Light skin and hair can also be present. CC Biochemical features include increased urinary homocystine and CC methionine. {ECO:0000269|PubMed:10215408, ECO:0000269|PubMed:10408774, CC ECO:0000269|PubMed:10462600, ECO:0000269|PubMed:11013450, CC ECO:0000269|PubMed:11359213, ECO:0000269|PubMed:11553052, CC ECO:0000269|PubMed:12007221, ECO:0000269|PubMed:12124992, CC ECO:0000269|PubMed:12815602, ECO:0000269|PubMed:1301198, CC ECO:0000269|PubMed:14635102, ECO:0000269|PubMed:15146473, CC ECO:0000269|PubMed:15365998, ECO:0000269|PubMed:15993874, CC ECO:0000269|PubMed:16205833, ECO:0000269|PubMed:16429402, CC ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:21240075, CC ECO:0000269|PubMed:21520339, ECO:0000269|PubMed:22738154, CC ECO:0000269|PubMed:23974653, ECO:0000269|PubMed:23981774, CC ECO:0000269|PubMed:25044645, ECO:0000269|PubMed:7506602, CC ECO:0000269|PubMed:7564249, ECO:0000269|PubMed:7611293, CC ECO:0000269|PubMed:7635485, ECO:0000269|PubMed:7762555, CC ECO:0000269|PubMed:7849717, ECO:0000269|PubMed:7967489, CC ECO:0000269|PubMed:7981678, ECO:0000269|PubMed:8353501, CC ECO:0000269|PubMed:8528202, ECO:0000269|PubMed:8755636, CC ECO:0000269|PubMed:8803779, ECO:0000269|PubMed:8990018, CC ECO:0000269|PubMed:9156316, ECO:0000269|PubMed:9266356, CC ECO:0000269|PubMed:9361025, ECO:0000269|PubMed:9889017}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the cysteine synthase/cystathionine beta- CC synthase family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=CBS mutation database; CC URL="https://databases.lovd.nl/shared/genes/CBS"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L19501; AAA19874.1; -; mRNA. DR EMBL; X82166; CAA57656.1; -; mRNA. DR EMBL; L14577; AAA98524.1; -; mRNA. DR EMBL; X88562; CAA61252.1; -; Genomic_DNA. DR EMBL; X91910; CAA61252.1; JOINED; Genomic_DNA. DR EMBL; X98811; CAA61252.1; JOINED; Genomic_DNA. DR EMBL; X98812; CAA61252.1; JOINED; Genomic_DNA. DR EMBL; X98813; CAA61252.1; JOINED; Genomic_DNA. DR EMBL; X98814; CAA61252.1; JOINED; Genomic_DNA. DR EMBL; X98815; CAA61252.1; JOINED; Genomic_DNA. DR EMBL; X98816; CAA61252.1; JOINED; Genomic_DNA. DR EMBL; X98817; CAA61252.1; JOINED; Genomic_DNA. DR EMBL; X98818; CAA61252.1; JOINED; Genomic_DNA. DR EMBL; X98819; CAA61252.1; JOINED; Genomic_DNA. DR EMBL; X98820; CAA61252.1; JOINED; Genomic_DNA. DR EMBL; X98821; CAA61252.1; JOINED; Genomic_DNA. DR EMBL; X98822; CAA61252.1; JOINED; Genomic_DNA. DR EMBL; X98823; CAA61252.1; JOINED; Genomic_DNA. DR EMBL; AF042836; AAC64684.1; -; Genomic_DNA. DR EMBL; AF042836; AAC64683.1; -; Genomic_DNA. DR EMBL; BT007154; AAP35818.1; -; mRNA. DR EMBL; AK313691; BAG36440.1; -; mRNA. DR EMBL; AP001630; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471079; EAX09508.1; -; Genomic_DNA. DR EMBL; CH471079; EAX09509.1; -; Genomic_DNA. DR EMBL; CH471079; EAX09510.1; -; Genomic_DNA. DR EMBL; CH471079; EAX09511.1; -; Genomic_DNA. DR EMBL; CH471079; EAX09515.1; -; Genomic_DNA. DR EMBL; BC000440; AAH00440.1; -; mRNA. DR EMBL; BC007257; AAH07257.1; -; mRNA. DR EMBL; BC010242; AAH10242.1; -; mRNA. DR EMBL; BC011381; AAH11381.1; -; mRNA. DR CCDS; CCDS13693.1; -. [P35520-1] DR PIR; A55760; A55760. DR RefSeq; NP_000062.1; NM_000071.2. [P35520-1] DR RefSeq; NP_001171479.1; NM_001178008.2. [P35520-1] DR RefSeq; NP_001171480.1; NM_001178009.2. [P35520-1] DR RefSeq; NP_001307227.1; NM_001320298.1. [P35520-1] DR RefSeq; NP_001308002.1; NM_001321073.1. [P35520-1] DR RefSeq; XP_011528079.1; XM_011529777.1. [P35520-2] DR RefSeq; XP_011528083.1; XM_011529781.1. DR RefSeq; XP_011528084.1; XM_011529782.1. DR RefSeq; XP_011544396.1; XM_011546094.1. DR RefSeq; XP_011544397.1; XM_011546095.2. DR RefSeq; XP_011544399.1; XM_011546097.2. DR RefSeq; XP_011544400.1; XM_011546098.1. DR RefSeq; XP_011544401.1; XM_011546099.1. DR RefSeq; XP_016883700.1; XM_017028211.1. DR RefSeq; XP_016883701.1; XM_017028212.1. DR RefSeq; XP_016883702.1; XM_017028213.1. DR RefSeq; XP_016883703.1; XM_017028214.1. DR RefSeq; XP_016883704.1; XM_017028215.1. DR RefSeq; XP_016883705.1; XM_017028216.1. DR RefSeq; XP_016883706.1; XM_017028217.1. DR RefSeq; XP_016883707.1; XM_017028218.1. DR RefSeq; XP_016883978.1; XM_017028489.1. DR RefSeq; XP_016883979.1; XM_017028490.1. DR RefSeq; XP_016883980.1; XM_017028491.1. [P35520-1] DR RefSeq; XP_016883981.1; XM_017028492.1. DR PDB; 1JBQ; X-ray; 2.60 A; A/B/C/D/E/F=2-413. DR PDB; 1M54; X-ray; 2.90 A; A/B/C/D/E/F=44-406. DR PDB; 4COO; X-ray; 2.00 A; A/B=1-551. DR PDB; 4L0D; X-ray; 2.97 A; A/B=1-551. DR PDB; 4L27; X-ray; 3.39 A; A/B/C/D=2-551. DR PDB; 4L28; X-ray; 2.63 A; A/B/C/D=2-551. DR PDB; 4L3V; X-ray; 3.63 A; A/B/C=2-551. DR PDB; 4PCU; X-ray; 3.58 A; A/B=1-551. DR PDB; 4UUU; X-ray; 1.71 A; A/B=406-547. DR PDB; 5MMS; X-ray; 2.80 A; A/B/C/D/E/F=1-408. DR PDB; 7QGT; X-ray; 2.69 A; A/B=1-551. DR PDB; 8STW; X-ray; 2.40 A; A/B/C/D/E/F=44-406. DR PDBsum; 1JBQ; -. DR PDBsum; 1M54; -. DR PDBsum; 4COO; -. DR PDBsum; 4L0D; -. DR PDBsum; 4L27; -. DR PDBsum; 4L28; -. DR PDBsum; 4L3V; -. DR PDBsum; 4PCU; -. DR PDBsum; 4UUU; -. DR PDBsum; 5MMS; -. DR PDBsum; 7QGT; -. DR PDBsum; 8STW; -. DR AlphaFoldDB; P35520; -. DR SMR; P35520; -. DR BioGRID; 107321; 146. DR BioGRID; 3195666; 12. DR IntAct; P35520; 53. DR MINT; P35520; -. DR BindingDB; P35520; -. DR ChEMBL; CHEMBL3399911; -. DR DrugBank; DB00118; Ademetionine. DR DrugBank; DB00151; Cysteine. DR DrugBank; DB00114; Pyridoxal phosphate. DR DrugBank; DB00133; Serine. DR DrugCentral; P35520; -. DR GuidetoPHARMACOLOGY; 1443; -. DR GlyCosmos; P35520; 1 site, 1 glycan. DR GlyGen; P35520; 2 sites, 2 O-linked glycans (2 sites). DR iPTMnet; P35520; -. DR PhosphoSitePlus; P35520; -. DR SwissPalm; P35520; -. DR BioMuta; CBS; -. DR DMDM; 543959; -. DR EPD; P35520; -. DR jPOST; P35520; -. DR MassIVE; P35520; -. DR MaxQB; P35520; -. DR PeptideAtlas; P35520; -. DR ProteomicsDB; 55074; -. [P35520-1] DR ProteomicsDB; 55075; -. [P35520-2] DR Pumba; P35520; -. DR Antibodypedia; 768; 526 antibodies from 37 providers. DR DNASU; 875; -. DR Ensembl; ENST00000352178.9; ENSP00000344460.5; ENSG00000160200.18. [P35520-1] DR Ensembl; ENST00000359624.7; ENSP00000352643.3; ENSG00000160200.18. [P35520-1] DR Ensembl; ENST00000398158.5; ENSP00000381225.1; ENSG00000160200.18. [P35520-1] DR Ensembl; ENST00000398165.8; ENSP00000381231.4; ENSG00000160200.18. [P35520-1] DR GeneID; 102724560; -. DR GeneID; 875; -. DR KEGG; hsa:102724560; -. DR KEGG; hsa:875; -. DR MANE-Select; ENST00000398165.8; ENSP00000381231.4; NM_000071.3; NP_000062.1. DR UCSC; uc002zct.3; human. [P35520-1] DR AGR; HGNC:1550; -. DR CTD; 875; -. DR DisGeNET; 102724560; -. DR DisGeNET; 875; -. DR GeneCards; CBS; -. DR GeneReviews; CBS; -. DR HGNC; HGNC:1550; CBS. DR HPA; ENSG00000160200; Group enriched (brain, liver, pancreas). DR MalaCards; CBS; -. DR MIM; 236200; phenotype. DR MIM; 613381; gene. DR neXtProt; NX_P35520; -. DR OpenTargets; ENSG00000160200; -. DR Orphanet; 394; Homocystinuria due to cystathionine beta-synthase deficiency. DR PharmGKB; PA26123; -. DR VEuPathDB; HostDB:ENSG00000160200; -. DR GeneTree; ENSGT00510000047027; -. DR HOGENOM; CLU_021018_0_0_1; -. DR InParanoid; P35520; -. DR OMA; KFADDEW; -. DR OrthoDB; 5487987at2759; -. DR PhylomeDB; P35520; -. DR TreeFam; TF300784; -. DR BioCyc; MetaCyc:HS08461-MONOMER; -. DR BRENDA; 4.2.1.22; 2681. DR PathwayCommons; P35520; -. DR Reactome; R-HSA-1614603; Cysteine formation from homocysteine. DR Reactome; R-HSA-2408508; Metabolism of ingested SeMet, Sec, MeSec into H2Se. DR SABIO-RK; P35520; -. DR SignaLink; P35520; -. DR SIGNOR; P35520; -. DR UniPathway; UPA00136; UER00201. DR BioGRID-ORCS; 102724560; 0 hits in 17 CRISPR screens. DR BioGRID-ORCS; 875; 11 hits in 1154 CRISPR screens. DR ChiTaRS; CBS; human. DR EvolutionaryTrace; P35520; -. DR GeneWiki; Cystathionine_beta_synthase; -. DR Pharos; P35520; Tchem. DR PRO; PR:P35520; -. DR Proteomes; UP000005640; Chromosome 21. DR RNAct; P35520; Protein. DR Bgee; ENSG00000160200; Expressed in right lobe of liver and 97 other cell types or tissues. DR ExpressionAtlas; P35520; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; HDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0070025; F:carbon monoxide binding; IDA:BHF-UCL. DR GO; GO:0004122; F:cystathionine beta-synthase activity; IDA:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0020037; F:heme binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0072341; F:modified amino acid binding; IDA:UniProtKB. DR GO; GO:0070026; F:nitric oxide binding; IDA:BHF-UCL. DR GO; GO:0050421; F:nitrite reductase (NO-forming) activity; IDA:BHF-UCL. DR GO; GO:0019825; F:oxygen binding; IDA:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:UniProtKB. DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; IDA:BHF-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0097746; P:blood vessel diameter maintenance; IEA:Ensembl. DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl. DR GO; GO:0060351; P:cartilage development involved in endochondral bone morphogenesis; IEA:Ensembl. DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl. DR GO; GO:0021587; P:cerebellum morphogenesis; IEA:Ensembl. DR GO; GO:0019344; P:cysteine biosynthetic process; IDA:BHF-UCL. DR GO; GO:0006535; P:cysteine biosynthetic process from serine; IBA:GO_Central. DR GO; GO:0019343; P:cysteine biosynthetic process via cystathionine; IEA:InterPro. DR GO; GO:0042262; P:DNA protection; IMP:BHF-UCL. DR GO; GO:0001958; P:endochondral ossification; IEA:Ensembl. DR GO; GO:0043418; P:homocysteine catabolic process; IDA:UniProtKB. DR GO; GO:0050667; P:homocysteine metabolic process; IDA:UniProtKB. DR GO; GO:0070814; P:hydrogen sulfide biosynthetic process; IDA:UniProtKB. DR GO; GO:0019448; P:L-cysteine catabolic process; IDA:UniProtKB. DR GO; GO:0006565; P:L-serine catabolic process; IDA:UniProtKB. DR GO; GO:0006563; P:L-serine metabolic process; IDA:UniProtKB. DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0010749; P:regulation of nitric oxide mediated signal transduction; IEA:Ensembl. DR GO; GO:0051593; P:response to folic acid; IEA:Ensembl. DR GO; GO:0006801; P:superoxide metabolic process; IEA:Ensembl. DR GO; GO:0019346; P:transsulfuration; IEA:Ensembl. DR CDD; cd01561; CBS_like; 1. DR CDD; cd04608; CBS_pair_CBS; 1. DR DisProt; DP01976; -. DR Gene3D; 3.40.50.1100; -; 2. DR Gene3D; 3.10.580.10; CBS-domain; 1. DR InterPro; IPR046353; CBS_C. DR InterPro; IPR000644; CBS_dom. DR InterPro; IPR046342; CBS_dom_sf. DR InterPro; IPR005857; Cysta_beta_synth. DR InterPro; IPR001216; P-phosphate_BS. DR InterPro; IPR001926; TrpB-like_PALP. DR InterPro; IPR036052; TrpB-like_PALP_sf. DR NCBIfam; TIGR01137; cysta_beta; 1. DR PANTHER; PTHR10314; CYSTATHIONINE BETA-SYNTHASE; 1. DR PANTHER; PTHR10314:SF194; CYSTATHIONINE BETA-SYNTHASE; 1. DR Pfam; PF00571; CBS; 1. DR Pfam; PF00291; PALP; 1. DR SMART; SM00116; CBS; 1. DR SUPFAM; SSF54631; CBS-domain pair; 1. DR SUPFAM; SSF53686; Tryptophan synthase beta subunit-like PLP-dependent enzymes; 1. DR PROSITE; PS51371; CBS; 1. DR PROSITE; PS00901; CYS_SYNTHASE; 1. DR Genevisible; P35520; HS. PE 1: Evidence at protein level; KW 3D-structure; Allosteric enzyme; Alternative splicing; KW Amino-acid biosynthesis; CBS domain; Cysteine biosynthesis; Cytoplasm; KW Disease variant; Heme; Iron; Isopeptide bond; Lyase; Metal-binding; KW Nucleus; Phosphoprotein; Pyridoxal phosphate; Reference proteome; KW Ubl conjugation. FT CHAIN 1..551 FT /note="Cystathionine beta-synthase" FT /id="PRO_0000167133" FT DOMAIN 418..476 FT /note="CBS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703" FT REGION 1..74 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 28..44 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 52 FT /ligand="heme" FT /ligand_id="ChEBI:CHEBI:30413" FT /ligand_part="Fe" FT /ligand_part_id="ChEBI:CHEBI:18248" FT /note="axial binding residue" FT /evidence="ECO:0000269|PubMed:11483494, FT ECO:0000269|PubMed:12173932" FT BINDING 65 FT /ligand="heme" FT /ligand_id="ChEBI:CHEBI:30413" FT /ligand_part="Fe" FT /ligand_part_id="ChEBI:CHEBI:18248" FT /note="axial binding residue" FT /evidence="ECO:0000269|PubMed:11483494, FT ECO:0000269|PubMed:12173932" FT BINDING 149 FT /ligand="pyridoxal 5'-phosphate" FT /ligand_id="ChEBI:CHEBI:597326" FT /evidence="ECO:0000269|PubMed:11483494, FT ECO:0000269|PubMed:12173932" FT BINDING 256..260 FT /ligand="pyridoxal 5'-phosphate" FT /ligand_id="ChEBI:CHEBI:597326" FT /evidence="ECO:0000269|PubMed:11483494, FT ECO:0000269|PubMed:12173932" FT BINDING 349 FT /ligand="pyridoxal 5'-phosphate" FT /ligand_id="ChEBI:CHEBI:597326" FT /evidence="ECO:0000269|PubMed:11483494, FT ECO:0000269|PubMed:12173932" FT MOD_RES 27 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 119 FT /note="N6-(pyridoxal phosphate)lysine" FT /evidence="ECO:0000269|PubMed:11483494, FT ECO:0000269|PubMed:12173932" FT MOD_RES 199 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 211 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:17087506" FT VAR_SEQ 518 FT /note="Y -> SQDQAWAGVVGGPAD (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_001217" FT VARIANT 18 FT /note="R -> C (results in 1/3 to 2/3 the enzyme activity of FT the wild-type; dbSNP:rs201827340)" FT /evidence="ECO:0000269|PubMed:16205833" FT /id="VAR_046921" FT VARIANT 49 FT /note="P -> L (in CBSD; decreased expression; no effect on FT cystathionine beta-synthase activity; increased FT homotetramer formation; dbSNP:rs148865119)" FT /evidence="ECO:0000269|PubMed:12124992, FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:23974653" FT /id="VAR_008049" FT VARIANT 58 FT /note="R -> W (in CBSD; linked with V-114; 18% of activity; FT dbSNP:rs555959266)" FT /evidence="ECO:0000269|PubMed:10408774" FT /id="VAR_008050" FT VARIANT 65 FT /note="H -> R (in CBSD; decreased cystathionine FT beta-synthase activity; inhibited by AdoMet and AdoHcy; FT decreased homotetramer formation; dbSNP:rs1191141364)" FT /evidence="ECO:0000269|PubMed:11359213, FT ECO:0000269|PubMed:20506325" FT /id="VAR_021790" FT VARIANT 69 FT /note="A -> P (in dbSNP:rs17849313)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_046922" FT VARIANT 78 FT /note="P -> R (in CBSD; severe form; associated in cis with FT N-102; decreased cystathionine beta-synthase activity; FT decreased homotetramer formation; dbSNP:rs786204608)" FT /evidence="ECO:0000269|PubMed:20506325, FT ECO:0000269|PubMed:7981678" FT /id="VAR_002171" FT VARIANT 85 FT /note="G -> R (in CBSD; loss of cystathionine beta-synthase FT activity; dbSNP:rs863223435)" FT /evidence="ECO:0000269|PubMed:12007221, FT ECO:0000269|PubMed:23981774" FT /id="VAR_008051" FT VARIANT 87 FT /note="T -> N (in CBSD; decreased cystathionine FT beta-synthase activity; increased aggregation)" FT /evidence="ECO:0000269|PubMed:23981774" FT /id="VAR_074590" FT VARIANT 88 FT /note="P -> S (in CBSD)" FT /evidence="ECO:0000269|PubMed:7762555" FT /id="VAR_002172" FT VARIANT 101 FT /note="L -> P (in CBSD; common mutation in Irish FT population; loss of activity; dbSNP:rs786204757)" FT /evidence="ECO:0000269|PubMed:12124992, FT ECO:0000269|PubMed:14635102, ECO:0000269|PubMed:9889017" FT /id="VAR_021791" FT VARIANT 102 FT /note="K -> N (in CBSD; associated in cis with R-78; FT decreased cystathionine beta-synthase activity; decreased FT homotetramer formation; dbSNP:rs786204609)" FT /evidence="ECO:0000269|PubMed:20506325, FT ECO:0000269|PubMed:7981678" FT /id="VAR_002173" FT VARIANT 102 FT /note="K -> Q (in dbSNP:rs34040148)" FT /evidence="ECO:0000269|PubMed:11013450" FT /id="VAR_008052" FT VARIANT 109 FT /note="C -> R (in CBSD; loss of activity; FT dbSNP:rs778220779)" FT /evidence="ECO:0000269|PubMed:12124992" FT /id="VAR_021792" FT VARIANT 114 FT /note="A -> V (in CBSD; mild form; when linked with W-58 FT severe form; decreased cystathionine beta-synthase FT activity; decreases homotetramer formation by promoting FT formation of larger aggregates; dbSNP:rs121964964)" FT /evidence="ECO:0000269|PubMed:11359213, FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:8353501" FT /id="VAR_002174" FT VARIANT 116 FT /note="G -> R (in CBSD; dbSNP:rs760214620)" FT /evidence="ECO:0000269|PubMed:8803779" FT /id="VAR_008053" FT VARIANT 121 FT /note="R -> C (in CBSD; dbSNP:rs775992753)" FT /id="VAR_008054" FT VARIANT 121 FT /note="R -> H (in CBSD; dbSNP:rs770095972)" FT /id="VAR_008055" FT VARIANT 121 FT /note="R -> L (in CBSD; mild form; dbSNP:rs770095972)" FT /id="VAR_008056" FT VARIANT 125 FT /note="R -> P (in CBSD)" FT /evidence="ECO:0000269|PubMed:11553052" FT /id="VAR_046923" FT VARIANT 125 FT /note="R -> Q (in CBSD; severe form; when linked with D-131 FT moderate form; loss of cystathionine beta-synthase FT activity; decreased homotetramer formation; FT dbSNP:rs781444670)" FT /evidence="ECO:0000269|PubMed:12124992, FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:7762555, FT ECO:0000269|PubMed:7849717" FT /id="VAR_002175" FT VARIANT 125 FT /note="R -> W (in CBSD; exhibits an activity lower than 4% FT of the wild-type enzyme; absent capacity to form multimeric FT quaternary structure; dbSNP:rs886057100)" FT /evidence="ECO:0000269|PubMed:12815602, FT ECO:0000269|PubMed:16429402" FT /id="VAR_008057" FT VARIANT 126 FT /note="M -> V (in CBSD; loss of activity)" FT /evidence="ECO:0000269|PubMed:10408774" FT /id="VAR_008058" FT VARIANT 128 FT /note="E -> D (in CBSD; dbSNP:rs374593242)" FT /id="VAR_008059" FT VARIANT 131 FT /note="E -> D (in CBSD; linked with Q-125; loss of FT activity; dbSNP:rs1555875351)" FT /evidence="ECO:0000269|PubMed:7849717" FT /id="VAR_002176" FT VARIANT 139 FT /note="G -> R (in CBSD; mild form; dbSNP:rs121964965)" FT /evidence="ECO:0000269|PubMed:7611293" FT /id="VAR_008060" FT VARIANT 143 FT /note="I -> M (in CBSD; 4% of activity; stable; FT dbSNP:rs370167302)" FT /evidence="ECO:0000269|PubMed:15146473" FT /id="VAR_021793" FT VARIANT 144 FT /note="E -> K (in CBSD; loss of cystathionine beta-synthase FT activity; impaired stimulation by AdoMet and AdoHcy; FT decreased homotetramer formation; dbSNP:rs121964966)" FT /evidence="ECO:0000269|PubMed:10215408, FT ECO:0000269|PubMed:11359213, ECO:0000269|PubMed:12124992, FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:7611293, FT ECO:0000269|PubMed:9156316" FT /id="VAR_002177" FT VARIANT 145 FT /note="P -> L (in CBSD; dbSNP:rs121964963)" FT /evidence="ECO:0000269|PubMed:8353501" FT /id="VAR_002178" FT VARIANT 148 FT /note="G -> R (in CBSD; loss of cystathionine beta-synthase FT activity; impaired stimulation by AdoMet and AdoHcy; loss FT of homotetramer formation; dbSNP:rs755952006)" FT /evidence="ECO:0000269|PubMed:15146473, FT ECO:0000269|PubMed:16429402, ECO:0000269|PubMed:20506325" FT /id="VAR_008061" FT VARIANT 151..159 FT /note="Missing (in CBSD)" FT /id="VAR_008063" FT VARIANT 151 FT /note="G -> R (in CBSD; dbSNP:rs373782713)" FT /id="VAR_008062" FT VARIANT 152 FT /note="I -> M (in CBSD; severe form)" FT /id="VAR_008064" FT VARIANT 154 FT /note="L -> Q (in CBSD; protein expression is comparable to FT wild-type; significant decrease of enzyme activity)" FT /evidence="ECO:0000269|PubMed:16205833" FT /id="VAR_046924" FT VARIANT 155 FT /note="A -> T (in CBSD; complete loss of activity; severely FT affects homotetramer formation by promoting formation of FT larger aggregates; dbSNP:rs1429138569)" FT /evidence="ECO:0000269|PubMed:11359213" FT /id="VAR_008065" FT VARIANT 155 FT /note="A -> V (in CBSD; protein expression is comparable to FT wild-type; significant decrease of enzyme activity)" FT /evidence="ECO:0000269|PubMed:16205833" FT /id="VAR_046925" FT VARIANT 165 FT /note="C -> Y (in CBSD; severe form; protein expression is FT comparable to wild-type; loss of cystathionine FT beta-synthase activity; no effect on homotetramer FT formation; dbSNP:rs1347651454)" FT /evidence="ECO:0000269|PubMed:10215408, FT ECO:0000269|PubMed:11359213, ECO:0000269|PubMed:12124992, FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:7635485" FT /id="VAR_002179" FT VARIANT 168 FT /note="V -> A (in CBSD)" FT /evidence="ECO:0000269|PubMed:15993874" FT /id="VAR_046926" FT VARIANT 168 FT /note="V -> M (in CBSD; dbSNP:rs121964970)" FT /evidence="ECO:0000269|PubMed:8528202" FT /id="VAR_002180" FT VARIANT 173 FT /note="M -> V (in CBSD; presents 40% of the wild-type FT activity; highly reduced capacity to form multimeric FT quaternary structure)" FT /evidence="ECO:0000269|PubMed:16429402" FT /id="VAR_046927" FT VARIANT 173 FT /note="Missing (in CBSD; loss of activity)" FT /evidence="ECO:0000269|PubMed:21520339" FT /id="VAR_066098" FT VARIANT 176 FT /note="E -> K (in CBSD; severe form; loss of cystathionine FT beta-synthase activity; inhibited by AdoMet; severely FT decreases homotetramer formation by promoting formation of FT larger aggregates; dbSNP:rs762065361)" FT /evidence="ECO:0000269|PubMed:11359213, FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:9266356" FT /id="VAR_008066" FT VARIANT 180 FT /note="V -> A (in CBSD; decreased cystathionine FT beta-synthase activity; decreases homotetramer formation; FT dbSNP:rs1555875010)" FT /evidence="ECO:0000269|PubMed:20506325" FT /id="VAR_008067" FT VARIANT 191 FT /note="T -> M (in CBSD; moderate and severe forms; loss of FT cystathionine beta-synthase activity; absent capacity to FT form multimeric quaternary structure; dbSNP:rs121964973)" FT /evidence="ECO:0000269|PubMed:12815602, FT ECO:0000269|PubMed:15993874, ECO:0000269|PubMed:16429402, FT ECO:0000269|PubMed:20506325" FT /id="VAR_008068" FT VARIANT 198 FT /note="D -> V (in CBSD)" FT /id="VAR_008069" FT VARIANT 200 FT /note="P -> L (in CBSD; dbSNP:rs758712880)" FT /evidence="ECO:0000269|PubMed:21520339" FT /id="VAR_066099" FT VARIANT 224 FT /note="R -> H (in CBSD; dbSNP:rs761647392)" FT /evidence="ECO:0000269|PubMed:8528202" FT /id="VAR_002181" FT VARIANT 226 FT /note="A -> T (in CBSD; presents 20% of the wild-type FT activity; dramatically reduced capacity to form multimeric FT quaternary structure; dbSNP:rs763835246)" FT /evidence="ECO:0000269|PubMed:14635102, FT ECO:0000269|PubMed:16429402" FT /id="VAR_008070" FT VARIANT 228 FT /note="N -> K (in CBSD; loss of cystathionine beta-synthase FT activity; decreased homotetramer formation; FT dbSNP:rs1464223176)" FT /evidence="ECO:0000269|PubMed:12124992, FT ECO:0000269|PubMed:15146473, ECO:0000269|PubMed:20506325, FT ECO:0000269|PubMed:9889017" FT /id="VAR_021794" FT VARIANT 228 FT /note="N -> S (in CBSD; has significantly decreased levels FT of enzyme activity; dbSNP:rs1555874803)" FT /evidence="ECO:0000269|PubMed:14635102" FT /id="VAR_046928" FT VARIANT 231 FT /note="A -> P (in CBSD; has significantly decreased levels FT of enzyme activity)" FT /evidence="ECO:0000269|PubMed:14635102" FT /id="VAR_046929" FT VARIANT 234 FT /note="D -> N (in CBSD; decreased cystathionine FT beta-synthase activity; changed localization; decreased FT interaction with pyridoxal 5'-phosphate; no effect on FT homotetramer formation; dbSNP:rs773734233)" FT /evidence="ECO:0000269|PubMed:23981774" FT /id="VAR_008071" FT VARIANT 234 FT /note="Missing (in CBSD; protein expression is comparable FT to wild-type; significant decrease of enzyme activity)" FT /evidence="ECO:0000269|PubMed:16205833" FT /id="VAR_046930" FT VARIANT 239 FT /note="E -> K (in CBSD)" FT /id="VAR_002182" FT VARIANT 247..256 FT /note="Missing (in CBSD)" FT /evidence="ECO:0000269|PubMed:15365998" FT /id="VAR_046931" FT VARIANT 257 FT /note="T -> M (in CBSD; moderate to severe form; protein FT expression is comparable to wild-type; significant decrease FT of enzyme activity; dbSNP:rs758236584)" FT /evidence="ECO:0000269|PubMed:16205833, FT ECO:0000269|PubMed:7762555" FT /id="VAR_002183" FT VARIANT 262 FT /note="T -> M (in CBSD; moderate form; dbSNP:rs149119723)" FT /evidence="ECO:0000269|PubMed:9361025, FT ECO:0000269|PubMed:9889017" FT /id="VAR_008072" FT VARIANT 262 FT /note="T -> R (in CBSD; severe form; loss of cystathionine FT beta-synthase activity; loss of homotetramer formation)" FT /evidence="ECO:0000269|PubMed:11013450, FT ECO:0000269|PubMed:20506325" FT /id="VAR_021795" FT VARIANT 266 FT /note="R -> G (in CBSD)" FT /id="VAR_008073" FT VARIANT 266 FT /note="R -> K (in CBSD; mild form; decreased cystathionine FT beta-synthase activity; decreased homotetramer formation; FT no effect on heme-binding; decreased stability; FT dbSNP:rs121964969)" FT /evidence="ECO:0000269|PubMed:20506325, FT ECO:0000269|PubMed:22738154, ECO:0000269|PubMed:9361025" FT /id="VAR_008074" FT VARIANT 269 FT /note="Missing (in CBSD; loss of expression)" FT /evidence="ECO:0000269|PubMed:23974653" FT /id="VAR_074591" FT VARIANT 270 FT /note="Missing (in CBSD)" FT /id="VAR_008075" FT VARIANT 275 FT /note="C -> Y (in CBSD; severe form; exhibits an activity FT lower than 4% of the wild-type enzyme; absent capacity to FT form multimeric quaternary structure)" FT /evidence="ECO:0000269|PubMed:12815602, FT ECO:0000269|PubMed:16429402" FT /id="VAR_021796" FT VARIANT 278 FT /note="I -> S (in CBSD; loss of activity)" FT /evidence="ECO:0000269|PubMed:21520339" FT /id="VAR_066100" FT VARIANT 278 FT /note="I -> T (in CBSD; mild to severe form; common FT mutation; decreased expression; loss of cystathionine FT beta-synthase activity; impaired stimulation by AdoMet and FT AdoHcy; severely affects homotetramer formation by FT promoting formation of larger aggregates; dbSNP:rs5742905)" FT /evidence="ECO:0000269|PubMed:11013450, FT ECO:0000269|PubMed:11359213, ECO:0000269|PubMed:12007221, FT ECO:0000269|PubMed:12124992, ECO:0000269|PubMed:1301198, FT ECO:0000269|PubMed:14635102, ECO:0000269|PubMed:15146473, FT ECO:0000269|PubMed:15993874, ECO:0000269|PubMed:20506325, FT ECO:0000269|PubMed:21240075, ECO:0000269|PubMed:23974653, FT ECO:0000269|PubMed:7506602, ECO:0000269|PubMed:7611293, FT ECO:0000269|PubMed:8528202, ECO:0000269|PubMed:8803779, FT ECO:0000269|PubMed:9156316, ECO:0000269|PubMed:9266356, FT ECO:0000269|PubMed:9361025, ECO:0000269|PubMed:9889017" FT /id="VAR_002184" FT VARIANT 281 FT /note="D -> N (in CBSD; loss of activity)" FT /evidence="ECO:0000269|PubMed:21520339" FT /id="VAR_066101" FT VARIANT 288 FT /note="A -> P (in CBSD)" FT /evidence="ECO:0000269|PubMed:15365998" FT /id="VAR_046932" FT VARIANT 288 FT /note="A -> T (in CBSD; protein expression is comparable to FT wild-type; significant decrease of enzyme activity; FT dbSNP:rs141502207)" FT /evidence="ECO:0000269|PubMed:16205833" FT /id="VAR_046933" FT VARIANT 290 FT /note="P -> L (in CBSD; dbSNP:rs760912339)" FT /evidence="ECO:0000269|PubMed:7564249, FT ECO:0000269|PubMed:8803779" FT /id="VAR_002185" FT VARIANT 302 FT /note="E -> K (in CBSD; no effect on cystathionine FT beta-synthase activity; inhibited by AdoHcy and impaired FT activation by AdoMet; no effect on homotetramer formation; FT dbSNP:rs779270933)" FT /evidence="ECO:0000269|PubMed:10408774, FT ECO:0000269|PubMed:12124992, ECO:0000269|PubMed:20506325" FT /id="VAR_008076" FT VARIANT 305 FT /note="G -> R (in CBSD; loss of cystathionine beta-synthase FT activity; no effect on homotetramer formation)" FT /evidence="ECO:0000269|PubMed:20506325" FT /id="VAR_008077" FT VARIANT 307 FT /note="G -> S (in CBSD; moderate to severe form; linked FT with D-534; common mutation; loss of cystathionine FT beta-synthase activity; impaired stimulation by AdoMet and FT AdoHcy; no effect on homotetramer formation; FT dbSNP:rs121964962)" FT /evidence="ECO:0000269|PubMed:12124992, FT ECO:0000269|PubMed:14635102, ECO:0000269|PubMed:20506325, FT ECO:0000269|PubMed:7506602, ECO:0000269|PubMed:8528202, FT ECO:0000269|PubMed:9266356, ECO:0000269|PubMed:9361025, FT ECO:0000269|PubMed:9889017" FT /id="VAR_002186" FT VARIANT 320 FT /note="V -> A (in CBSD; has 36% of wild-type enzyme FT activity; dbSNP:rs781567152)" FT /evidence="ECO:0000269|PubMed:14635102, FT ECO:0000269|PubMed:9361025" FT /id="VAR_008078" FT VARIANT 321 FT /note="D -> V (in CBSD; loss of activity)" FT /evidence="ECO:0000269|PubMed:21520339" FT /id="VAR_066102" FT VARIANT 331 FT /note="A -> E (in CBSD; dbSNP:rs777919630)" FT /evidence="ECO:0000269|PubMed:12124992, FT ECO:0000269|PubMed:9156316" FT /id="VAR_008079" FT VARIANT 331 FT /note="A -> V (in CBSD; dbSNP:rs777919630)" FT /evidence="ECO:0000269|PubMed:8528202" FT /id="VAR_002187" FT VARIANT 336 FT /note="R -> C (in CBSD; protein expression is comparable to FT wild-type; loss of activity; absent capacity to form FT multimeric quaternary structure; dbSNP:rs398123151)" FT /evidence="ECO:0000269|PubMed:10408774, FT ECO:0000269|PubMed:12124992, ECO:0000269|PubMed:12815602, FT ECO:0000269|PubMed:16205833, ECO:0000269|PubMed:16429402, FT ECO:0000269|PubMed:21240075" FT /id="VAR_002188" FT VARIANT 336 FT /note="R -> H (in CBSD; mild form; no effect on expression; FT exhibits an activity lower than 4% of the wild-type enzyme; FT altered stimulation by AdoMet; absent capacity to form FT multimeric quaternary structure; dbSNP:rs760417941)" FT /evidence="ECO:0000269|PubMed:16429402, FT ECO:0000269|PubMed:23974653" FT /id="VAR_008080" FT VARIANT 338 FT /note="L -> P (in CBSD; severe form; exhibits an activity FT lower than 4% of the wild-type enzyme; absent capacity to FT form multimeric quaternary structure)" FT /evidence="ECO:0000269|PubMed:12815602, FT ECO:0000269|PubMed:16429402" FT /id="VAR_021797" FT VARIANT 347 FT /note="G -> S (in CBSD; protein expression is comparable to FT wild-type; loss of activity; dbSNP:rs771298943)" FT /evidence="ECO:0000269|PubMed:12124992, FT ECO:0000269|PubMed:16205833" FT /id="VAR_021798" FT VARIANT 349 FT /note="S -> N (in CBSD; severe form; exhibits an activity FT lower than 4% of the wild-type enzyme; absent capacity to FT form multimeric quaternary structure)" FT /evidence="ECO:0000269|PubMed:12815602, FT ECO:0000269|PubMed:16429402" FT /id="VAR_021799" FT VARIANT 352 FT /note="S -> N (in CBSD)" FT /id="VAR_008081" FT VARIANT 353 FT /note="T -> M (in CBSD; protein expression is comparable to FT wild-type; significant decrease of enzyme activity; FT dbSNP:rs121964972)" FT /evidence="ECO:0000269|PubMed:12124992, FT ECO:0000269|PubMed:14635102, ECO:0000269|PubMed:16205833, FT ECO:0000269|PubMed:9156316" FT /id="VAR_008082" FT VARIANT 354 FT /note="V -> M (in CBSD; dbSNP:rs267606146)" FT /id="VAR_008083" FT VARIANT 355 FT /note="A -> P (in CBSD; dbSNP:rs1192581453)" FT /evidence="ECO:0000269|PubMed:9889017" FT /id="VAR_021800" FT VARIANT 361 FT /note="A -> T (in CBSD; dbSNP:rs745764562)" FT /evidence="ECO:0000269|PubMed:11553052" FT /id="VAR_046934" FT VARIANT 369 FT /note="R -> C (in CBSD; when linked with C-491 severe form; FT decreased cystathionine beta-synthase activity; decreased FT homotetramer formation; dbSNP:rs117687681)" FT /evidence="ECO:0000269|PubMed:12124992, FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:9361025" FT /id="VAR_008084" FT VARIANT 369 FT /note="R -> H (in CBSD; dbSNP:rs11700812)" FT /id="VAR_002189" FT VARIANT 370 FT /note="C -> Y (in CBSD; dbSNP:rs757920190)" FT /evidence="ECO:0000269|PubMed:10462600" FT /id="VAR_008085" FT VARIANT 371 FT /note="V -> M (in CBSD; dbSNP:rs372010465)" FT /evidence="ECO:0000269|PubMed:12124992, FT ECO:0000269|PubMed:7635485" FT /id="VAR_002190" FT VARIANT 376 FT /note="D -> N (in CBSD; has significantly decreased levels FT of enzyme activity; dbSNP:rs1170128038)" FT /evidence="ECO:0000269|PubMed:14635102" FT /id="VAR_046935" FT VARIANT 379 FT /note="R -> Q (in CBSD; exhibits an activity lower than 4% FT of the wild-type enzyme; absent capacity to form multimeric FT quaternary structure; dbSNP:rs763036586)" FT /evidence="ECO:0000269|PubMed:12815602, FT ECO:0000269|PubMed:16429402" FT /id="VAR_021801" FT VARIANT 379 FT /note="R -> W (in CBSD; dbSNP:rs769080151)" FT /evidence="ECO:0000269|PubMed:15365998" FT /id="VAR_046936" FT VARIANT 384 FT /note="K -> E (in CBSD; severe form; dbSNP:rs121964967)" FT /evidence="ECO:0000269|PubMed:8990018" FT /id="VAR_002191" FT VARIANT 384 FT /note="K -> N (in CBSD; moderate form)" FT /id="VAR_008086" FT VARIANT 391 FT /note="M -> I (in CBSD)" FT /id="VAR_008087" FT VARIANT 422 FT /note="P -> L (in CBSD; changed cystathionine beta-synthase FT activity; impaired stimulation by AdoMet; does not affect FT homotetramer formation; dbSNP:rs28934892)" FT /evidence="ECO:0000269|PubMed:12007221, FT ECO:0000269|PubMed:20506325" FT /id="VAR_021802" FT VARIANT 427 FT /note="P -> L (in CBSD; no effect on cystathionine FT beta-synthase activity; altered stimulation by AdoMet; FT dbSNP:rs863223434)" FT /evidence="ECO:0000269|PubMed:23974653, FT ECO:0000269|PubMed:25044645" FT /id="VAR_074592" FT VARIANT 434 FT /note="T -> N (in CBSD; dbSNP:rs1555872506)" FT /id="VAR_008088" FT VARIANT 435 FT /note="I -> T (in CBSD; no effect on cystathionine FT beta-synthase activity; impaired stimulation by AdoMet and FT AdoHcy; does not affect homotetramer formation)" FT /evidence="ECO:0000269|PubMed:12007221, FT ECO:0000269|PubMed:20506325" FT /id="VAR_008089" FT VARIANT 439 FT /note="R -> Q (in CBSD; no effect on cystathionine FT beta-synthase activity; increased homotetramer formation; FT dbSNP:rs756467921)" FT /evidence="ECO:0000269|PubMed:10462600, FT ECO:0000269|PubMed:12124992, ECO:0000269|PubMed:20506325, FT ECO:0000269|PubMed:9156316" FT /id="VAR_008090" FT VARIANT 444 FT /note="D -> N (in CBSD; decreased expression; no effect on FT cystathionine beta-synthase activity; altered stimulation FT by AdoMet; increased homotetramer formation; FT dbSNP:rs28934891)" FT /evidence="ECO:0000269|PubMed:12007221, FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:23974653, FT ECO:0000269|PubMed:25044645, ECO:0000269|PubMed:8755636" FT /id="VAR_002192" FT VARIANT 446 FT /note="A -> S (in CBSD)" FT /evidence="ECO:0000269|PubMed:21520339" FT /id="VAR_066103" FT VARIANT 449 FT /note="V -> G (in CBSD; no effect on cystathionine FT beta-synthase activity; altered stimulation by AdoMet)" FT /evidence="ECO:0000269|PubMed:25044645" FT /id="VAR_074593" FT VARIANT 454 FT /note="V -> E (in CBSD)" FT /evidence="ECO:0000269|PubMed:8528202" FT /id="VAR_002193" FT VARIANT 456 FT /note="L -> P (in CBSD; severe; exhibits an activity lower FT than 4% of the wild-type enzyme; absent capacity to form FT multimeric quaternary structure)" FT /evidence="ECO:0000269|PubMed:12815602, FT ECO:0000269|PubMed:16429402" FT /id="VAR_021803" FT VARIANT 466 FT /note="S -> L (in CBSD; increased cystathionine FT beta-synthase activity; impaired stimulation by AdoMet and FT AdoHcy; decreased homotetramer formation; FT dbSNP:rs121964971)" FT /evidence="ECO:0000269|PubMed:12007221, FT ECO:0000269|PubMed:20506325" FT /id="VAR_008091" FT VARIANT 491 FT /note="R -> C (in CBSD; linked with C-369; FT dbSNP:rs1339830457)" FT /id="VAR_008092" FT VARIANT 500 FT /note="S -> L (in CBSD; no effect on cystathionine FT beta-synthase activity; altered stimulation by AdoMet; FT dbSNP:rs755106884)" FT /evidence="ECO:0000269|PubMed:23974653, FT ECO:0000269|PubMed:25044645" FT /id="VAR_074594" FT VARIANT 526 FT /note="Q -> K (in CBSD; has significantly decreased levels FT of enzyme activity)" FT /evidence="ECO:0000269|PubMed:14635102" FT /id="VAR_046937" FT VARIANT 534 FT /note="V -> D (in CBSD; linked with S-307)" FT /id="VAR_008093" FT VARIANT 539 FT /note="L -> S (in CBSD; loss of cystathionine beta-synthase FT activity; impaired stimulation by AdoMet and AdoHcy; loss FT of homotetramer formation; dbSNP:rs121964968)" FT /evidence="ECO:0000269|PubMed:20506325, FT ECO:0000269|PubMed:8990018" FT /id="VAR_002194" FT VARIANT 540 FT /note="L -> Q (in CBSD; no effect on cystathionine FT beta-synthase activity; altered stimulation by AdoMet)" FT /evidence="ECO:0000269|PubMed:23974653, FT ECO:0000269|PubMed:25044645" FT /id="VAR_074595" FT VARIANT 548 FT /note="R -> Q (presents 60% of the wild-type activity; FT highly reduced capacity to form multimeric quaternary FT structure; dbSNP:rs150828989)" FT /evidence="ECO:0000269|PubMed:16429402" FT /id="VAR_046938" FT MUTAGEN 272 FT /note="C->A: Reduced heme content and cystathionine FT beta-synthase activity." FT /evidence="ECO:0000269|PubMed:12173932" FT MUTAGEN 275 FT /note="C->S: Reduced heme content and cystathionine FT beta-synthase activity." FT /evidence="ECO:0000269|PubMed:12173932" FT CONFLICT 58 FT /note="R -> P (in Ref. 4; CAA61252)" FT /evidence="ECO:0000305" FT HELIX 60..62 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 75..79 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 80..82 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 83..85 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 89..91 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 95..98 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 103..109 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 110..112 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 113..117 FT /evidence="ECO:0007829|PDB:4L0D" FT HELIX 119..132 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 141..145 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 149..161 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 164..170 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 175..183 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 187..191 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 193..195 FT /evidence="ECO:0007829|PDB:5MMS" FT STRAND 197..199 FT /evidence="ECO:0007829|PDB:4L27" FT HELIX 203..213 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 217..219 FT /evidence="ECO:0007829|PDB:4L28" FT TURN 222..224 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 227..234 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 236..243 FT /evidence="ECO:0007829|PDB:4COO" FT TURN 244..246 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 249..254 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 256..258 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 259..271 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 272..274 FT /evidence="ECO:0007829|PDB:1M54" FT STRAND 276..282 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 288..290 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 291..294 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 317..319 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 322..326 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 328..342 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 348..360 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 361..363 FT /evidence="ECO:0007829|PDB:4COO" FT STRAND 369..374 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 378..381 FT /evidence="ECO:0007829|PDB:4COO" FT TURN 382..386 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 388..393 FT /evidence="ECO:0007829|PDB:4COO" FT HELIX 399..404 FT /evidence="ECO:0007829|PDB:4COO" FT TURN 408..411 FT /evidence="ECO:0007829|PDB:4UUU" FT HELIX 414..417 FT /evidence="ECO:0007829|PDB:4UUU" FT HELIX 431..441 FT /evidence="ECO:0007829|PDB:4UUU" FT STRAND 444..449 FT /evidence="ECO:0007829|PDB:4UUU" FT STRAND 455..460 FT /evidence="ECO:0007829|PDB:4UUU" FT HELIX 461..469 FT /evidence="ECO:0007829|PDB:4UUU" FT HELIX 479..482 FT /evidence="ECO:0007829|PDB:4UUU" FT STRAND 489..491 FT /evidence="ECO:0007829|PDB:4UUU" FT HELIX 496..505 FT /evidence="ECO:0007829|PDB:4UUU" FT STRAND 509..515 FT /evidence="ECO:0007829|PDB:4UUU" FT STRAND 526..534 FT /evidence="ECO:0007829|PDB:4UUU" FT HELIX 536..544 FT /evidence="ECO:0007829|PDB:4UUU" SQ SEQUENCE 551 AA; 60587 MW; F89E69C67BDE6701 CRC64; MPSETPQAEV GPTGCPHRSG PHSAKGSLEK GSPEDKEAKE PLWIRPDAPS RCTWQLGRPA SESPHHHTAP AKSPKILPDI LKKIGDTPMV RINKIGKKFG LKCELLAKCE FFNAGGSVKD RISLRMIEDA ERDGTLKPGD TIIEPTSGNT GIGLALAAAV RGYRCIIVMP EKMSSEKVDV LRALGAEIVR TPTNARFDSP ESHVGVAWRL KNEIPNSHIL DQYRNASNPL AHYDTTADEI LQQCDGKLDM LVASVGTGGT ITGIARKLKE KCPGCRIIGV DPEGSILAEP EELNQTEQTT YEVEGIGYDF IPTVLDRTVV DKWFKSNDEE AFTFARMLIA QEGLLCGGSA GSTVAVAVKA AQELQEGQRC VVILPDSVRN YMTKFLSDRW MLQKGFLKEE DLTEKKPWWW HLRVQELGLS APLTVLPTIT CGHTIEILRE KGFDQAPVVD EAGVILGMVT LGNMLSSLLA GKVQPSDQVG KVIYKQFKQI RLTDTLGRLS HILEMDHFAL VVHEQIQYHS TGKSSQRQMV FGVVTAIDLL NFVAAQERDQ K //