SDHL_HUMAN
ID SDHL_HUMAN Reviewed; 328 AA.
AC P20132; A8K9P5;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=L-serine dehydratase/L-threonine deaminase;
DE Short=SDH;
DE EC=4.3.1.17;
DE AltName: Full=L-serine deaminase;
DE AltName: Full=L-threonine dehydratase;
DE Short=TDH;
DE EC=4.3.1.19;
GN Name=SDS; Synonyms=SDH;
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].
RC TISSUE=Liver;
RX PubMed=2674117; DOI=10.1016/s0021-9258(18)71550-0;
RA Ogawa H., Gomi T., Konishi K., Date T., Nakashima H., Nose K., Matsuda Y.,
RA Peraino C., Pitot H.C., Fujioka M.;
RT "Human liver serine dehydratase. cDNA cloning and sequence homology with
RT hydroxyamino acid dehydratases from other sources.";
RL J. Biol. Chem. 264:15818-15823(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [3]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-303, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=18342636; DOI=10.1016/j.bbagen.2008.01.020;
RA Yamada T., Komoto J., Kasuya T., Takata Y., Ogawa H., Mori H.,
RA Takusagawa F.;
RT "A catalytic mechanism that explains a low catalytic activity of serine
RT dehydratase like-1 from human cancer cells: crystal structure and site-
RT directed mutagenesis studies.";
RL Biochim. Biophys. Acta 1780:809-818(2008).
RN [5]
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 [6]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL PHOSPHATE.
RX PubMed=14646100; DOI=10.1107/s0907444903020110;
RA Sun L., Li X., Dong Y., Yang M., Liu Y., Han X., Zhang X., Pang H., Rao Z.;
RT "Crystallization and preliminary crystallographic analysis of human serine
RT dehydratase.";
RL Acta Crystallogr. D 59:2297-2299(2003).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-serine = NH4(+) + pyruvate; Xref=Rhea:RHEA:19169,
CC ChEBI:CHEBI:15361, ChEBI:CHEBI:28938, ChEBI:CHEBI:33384; EC=4.3.1.17;
CC Evidence={ECO:0000269|PubMed:18342636};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-threonine = 2-oxobutanoate + NH4(+); Xref=Rhea:RHEA:22108,
CC ChEBI:CHEBI:16763, ChEBI:CHEBI:28938, ChEBI:CHEBI:57926; EC=4.3.1.19;
CC Evidence={ECO:0000269|PubMed:18342636};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=23 mM for serine {ECO:0000269|PubMed:18342636};
CC KM=31 mM for threonine {ECO:0000269|PubMed:18342636};
CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:14646100}.
CC -!- INTERACTION:
CC P20132; Q8WTU0: DDI1; NbExp=3; IntAct=EBI-17859611, EBI-748248;
CC P20132; O14964: HGS; NbExp=3; IntAct=EBI-17859611, EBI-740220;
CC P20132; Q96PF1: TGM7; NbExp=3; IntAct=EBI-17859611, EBI-12029034;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the serine/threonine dehydratase family.
CC {ECO:0000305}.
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; J05037; AAA36604.1; -; mRNA.
DR EMBL; AK292760; BAF85449.1; -; mRNA.
DR EMBL; CH471054; EAW98054.1; -; Genomic_DNA.
DR CCDS; CCDS9169.1; -.
DR PIR; A34232; DWHUT.
DR RefSeq; NP_006834.2; NM_006843.2.
DR PDB; 1P5J; X-ray; 2.50 A; A=1-328.
DR PDB; 4H27; X-ray; 1.30 A; A=1-328.
DR PDBsum; 1P5J; -.
DR PDBsum; 4H27; -.
DR AlphaFoldDB; P20132; -.
DR SMR; P20132; -.
DR BioGRID; 116189; 8.
DR IntAct; P20132; 3.
DR STRING; 9606.ENSP00000257549; -.
DR DrugBank; DB00114; Pyridoxal phosphate.
DR DrugBank; DB00133; Serine.
DR iPTMnet; P20132; -.
DR PhosphoSitePlus; P20132; -.
DR BioMuta; SDS; -.
DR DMDM; 229462819; -.
DR MassIVE; P20132; -.
DR PaxDb; P20132; -.
DR PeptideAtlas; P20132; -.
DR PRIDE; P20132; -.
DR ProteomicsDB; 53724; -.
DR Antibodypedia; 31269; 264 antibodies from 18 providers.
DR DNASU; 10993; -.
DR Ensembl; ENST00000257549.9; ENSP00000257549.4; ENSG00000135094.11.
DR GeneID; 10993; -.
DR KEGG; hsa:10993; -.
DR MANE-Select; ENST00000257549.9; ENSP00000257549.4; NM_006843.3; NP_006834.2.
DR UCSC; uc001tvg.4; human.
DR CTD; 10993; -.
DR DisGeNET; 10993; -.
DR GeneCards; SDS; -.
DR HGNC; HGNC:10691; SDS.
DR HPA; ENSG00000135094; Tissue enriched (liver).
DR MIM; 182128; gene.
DR neXtProt; NX_P20132; -.
DR OpenTargets; ENSG00000135094; -.
DR PharmGKB; PA35616; -.
DR VEuPathDB; HostDB:ENSG00000135094; -.
DR eggNOG; KOG1250; Eukaryota.
DR GeneTree; ENSGT00940000160172; -.
DR HOGENOM; CLU_021152_3_0_1; -.
DR InParanoid; P20132; -.
DR OMA; AEQGCEH; -.
DR OrthoDB; 1199679at2759; -.
DR PhylomeDB; P20132; -.
DR TreeFam; TF329014; -.
DR BioCyc; MetaCyc:HS05952-MON; -.
DR BRENDA; 4.3.1.17; 2681.
DR PathwayCommons; P20132; -.
DR Reactome; R-HSA-8849175; Threonine catabolism.
DR SABIO-RK; P20132; -.
DR SignaLink; P20132; -.
DR UniPathway; UPA00138; -.
DR BioGRID-ORCS; 10993; 13 hits in 1077 CRISPR screens.
DR ChiTaRS; SDS; human.
DR EvolutionaryTrace; P20132; -.
DR GenomeRNAi; 10993; -.
DR Pharos; P20132; Tbio.
DR PRO; PR:P20132; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P20132; protein.
DR Bgee; ENSG00000135094; Expressed in right lobe of liver and 108 other tissues.
DR ExpressionAtlas; P20132; baseline and differential.
DR Genevisible; P20132; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0003941; F:L-serine ammonia-lyase activity; IDA:UniProtKB.
DR GO; GO:0004794; F:L-threonine ammonia-lyase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:UniProtKB.
DR GO; GO:0006094; P:gluconeogenesis; IEA:UniProtKB-UniPathway.
DR GO; GO:0009097; P:isoleucine biosynthetic process; IBA:GO_Central.
DR GO; GO:0006565; P:L-serine catabolic process; IDA:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0042866; P:pyruvate biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006567; P:threonine catabolic process; IBA:GO_Central.
DR Gene3D; 3.40.50.1100; -; 2.
DR InterPro; IPR001926; PLP-dep.
DR InterPro; IPR000634; Ser/Thr_deHydtase_PyrdxlP-BS.
DR InterPro; IPR036052; Trypto_synt_PLP_dependent.
DR Pfam; PF00291; PALP; 1.
DR SUPFAM; SSF53686; SSF53686; 1.
DR PROSITE; PS00165; DEHYDRATASE_SER_THR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Gluconeogenesis; Lipid metabolism; Lyase;
KW Pyridoxal phosphate; Reference proteome.
FT CHAIN 1..328
FT /note="L-serine dehydratase/L-threonine deaminase"
FT /id="PRO_0000185594"
FT MOD_RES 41
FT /note="N6-(pyridoxal phosphate)lysine"
FT MUTAGEN 303
FT /note="C->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:18342636"
FT CONFLICT 89
FT /note="S -> G (in Ref. 1; AAA36604)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="V -> C (in Ref. 1; AAA36604)"
FT /evidence="ECO:0000305"
FT CONFLICT 183
FT /note="V -> C (in Ref. 1; AAA36604)"
FT /evidence="ECO:0000305"
FT CONFLICT 230
FT /note="A -> S (in Ref. 1; AAA36604)"
FT /evidence="ECO:0000305"
FT CONFLICT 270
FT /note="C -> W (in Ref. 1; AAA36604)"
FT /evidence="ECO:0000305"
FT STRAND 13..16
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 17..23
FT /evidence="ECO:0007829|PDB:4H27"
FT STRAND 25..31
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 32..34
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 36..38
FT /evidence="ECO:0007829|PDB:1P5J"
FT HELIX 43..54
FT /evidence="ECO:0007829|PDB:4H27"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 67..79
FT /evidence="ECO:0007829|PDB:4H27"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 93..101
FT /evidence="ECO:0007829|PDB:4H27"
FT STRAND 105..109
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 115..126
FT /evidence="ECO:0007829|PDB:4H27"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 139..145
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 147..155
FT /evidence="ECO:0007829|PDB:4H27"
FT STRAND 161..166
FT /evidence="ECO:0007829|PDB:4H27"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 171..182
FT /evidence="ECO:0007829|PDB:4H27"
FT STRAND 190..195
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 200..207
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 221..223
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 230..236
FT /evidence="ECO:0007829|PDB:4H27"
FT STRAND 241..246
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 248..262
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 268..278
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 281..287
FT /evidence="ECO:0007829|PDB:4H27"
FT STRAND 297..302
FT /evidence="ECO:0007829|PDB:4H27"
FT HELIX 310..319
FT /evidence="ECO:0007829|PDB:4H27"
SQ SEQUENCE 328 AA; 34625 MW; F6E9AB01D6308C83 CRC64;
MMSGEPLHVK TPIRDSMALS KMAGTSVYLK MDSAQPSGSF KIRGIGHFCK RWAKQGCAHF
VCSSAGNAGM AAAYAARQLG VPATIVVPST TPALTIERLK NEGATVKVVG ELLDEAFELA
KALAKNNPGW VYIPPFDDPL IWEGHASIVK ELKETLWEKP GAIALSVGGG GLLCGVVQGL
QEVGWGDVPV IAMETFGAHS FHAATTAGKL VSLPKITSVA KALGVKTVGA QALKLFQEHP
IFSEVISDQE AVAAIEKFVD DEKILVEPAC GAALAAVYSH VIQKLQLEGN LRTPLPSLVV
IVCGGSNISL AQLRALKEQL GMTNRLPK
