SERA_HUMAN
ID SERA_HUMAN Reviewed; 533 AA.
AC O43175; B2RD08; Q5SZU3; Q9BQ01;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=D-3-phosphoglycerate dehydrogenase;
DE Short=3-PGDH;
DE EC=1.1.1.95 {ECO:0000269|PubMed:11751922};
DE AltName: Full=2-oxoglutarate reductase {ECO:0000305};
DE EC=1.1.1.399 {ECO:0000269|PubMed:25406093};
DE AltName: Full=Malate dehydrogenase {ECO:0000305};
DE EC=1.1.1.37 {ECO:0000269|PubMed:25406093};
GN Name=PHGDH; Synonyms=PGDH3;
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].
RX PubMed=10713460; DOI=10.1016/s0378-1119(00)00009-3;
RA Cho H.M., Jun D.Y., Bae M.A., Ahn J.D., Kim Y.H.;
RT "Nucleotide sequence and differential expression of the human 3-
RT phosphoglycerate dehydrogenase gene.";
RL Gene 245:193-201(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS PHGDHD MET-425 AND MET-490.
RX PubMed=11055895; DOI=10.1086/316886;
RA Klomp L.W.J., de Koning T.J., Malingre H.E.M., van Beurden E.A.C.M.,
RA Brink M., Opdam F.L., Duran M., Jaeken J., Pineda M., van Maldergem L.,
RA Poll-The B.T., van den Berg I.E.T., Berger R.;
RT "Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency
RT -- a neurometabolic disorder associated with reduced L-serine
RT biosynthesis.";
RL Am. J. Hum. Genet. 67:1389-1399(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, 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 [8]
RP PROTEIN SEQUENCE OF 2-54; 59-69; 76-119; 138-155; 237-289; 295-308;
RP 352-380; 385-394; 462-491 AND 523-533, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma, and Ovarian carcinoma;
RA Bienvenut W.V.;
RL Submitted (JAN-2010) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 9-20; 22-33; 76-90; 248-268 AND 271-289.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP CATALYTIC ACTIVITY, AND VARIANT MET-490.
RX PubMed=11751922; DOI=10.1074/jbc.m111419200;
RA Pind S., Slominski E., Mauthe J., Pearlman K., Swoboda K.J., Wilkins J.A.,
RA Sauder P., Natowicz M.R.;
RT "V490M, a common mutation in 3-phosphoglycerate dehydrogenase deficiency,
RT causes enzyme deficiency by decreasing the yield of mature enzyme.";
RL J. Biol. Chem. 277:7136-7143(2002).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INDUCTION BY 17-BETA-ESTRADIOL AND
RP 4-HYDROXYTAMOXIFEN.
RX PubMed=16949628; DOI=10.1016/j.steroids.2006.07.006;
RA Al-Dhaheri M.H., Shah Y.M., Basrur V., Pind S., Rowan B.G.;
RT "Identification of novel proteins induced by estradiol, 4-hydroxytamoxifen
RT and acolbifene in T47D breast cancer cells.";
RL Steroids 71:966-978(2006).
RN [13]
RP INDUCTION BY SP1 AND NF-Y.
RX PubMed=18378410; DOI=10.1016/j.gene.2008.02.018;
RA Jun D.Y., Park H.S., Lee J.Y., Baek J.Y., Park H.-K., Fukui K., Kim Y.H.;
RT "Positive regulation of promoter activity of human 3-phosphoglycerate
RT dehydrogenase (PHGDH) gene is mediated by transcription factors Sp1 and NF-
RT Y.";
RL Gene 414:106-114(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-78, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14 AND THR-78, AND
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 SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-21, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [19]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=25406093; DOI=10.1021/cb500683c;
RA Fan J., Teng X., Liu L., Mattaini K.R., Looper R.E., Vander Heiden M.G.,
RA Rabinowitz J.D.;
RT "Human phosphoglycerate dehydrogenase produces the oncometabolite D-2-
RT hydroxyglutarate.";
RL ACS Chem. Biol. 10:510-516(2015).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 4-314 IN COMPLEX WITH NAD AND
RP SUBSTRATE.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human 3-phosphoglycerate dehydrogenase.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [22]
RP VARIANTS PHGDHD TRP-135; MET-261; THR-373 AND SER-377, CHARACTERIZATION OF
RP VARIANTS PHGDHD TRP-135; MET-261; THR-373; SER-377; MET-425 AND MET-490,
RP AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19235232; DOI=10.1002/humu.20934;
RA Tabatabaie L., de Koning T.J., Geboers A.J.J.M., van den Berg I.E.T.,
RA Berger R., Klomp L.W.J.;
RT "Novel mutations in 3-phosphoglycerate dehydrogenase (PHGDH) are
RT distributed throughout the protein and result in altered enzyme kinetics.";
RL Hum. Mutat. 30:749-756(2009).
RN [23]
RP INVOLVEMENT IN NLS1, AND VARIANTS NLS1 ARG-140 AND GLN-163.
RX PubMed=24836451; DOI=10.1016/j.ajhg.2014.04.015;
RA Shaheen R., Rahbeeni Z., Alhashem A., Faqeih E., Zhao Q., Xiong Y.,
RA Almoisheer A., Al-Qattan S.M., Almadani H.A., Al-Onazi N., Al-Baqawi B.S.,
RA Saleh M.A., Alkuraya F.S.;
RT "Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by
RT mutations in PHGDH.";
RL Am. J. Hum. Genet. 94:898-904(2014).
CC -!- FUNCTION: Catalyzes the reversible oxidation of 3-phospho-D-glycerate
CC to 3-phosphonooxypyruvate, the first step of the phosphorylated L-
CC serine biosynthesis pathway. Also catalyzes the reversible oxidation of
CC 2-hydroxyglutarate to 2-oxoglutarate and the reversible oxidation of
CC (S)-malate to oxaloacetate. {ECO:0000269|PubMed:11751922,
CC ECO:0000269|PubMed:25406093}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R)-3-phosphoglycerate + NAD(+) = 3-phosphooxypyruvate + H(+)
CC + NADH; Xref=Rhea:RHEA:12641, ChEBI:CHEBI:15378, ChEBI:CHEBI:18110,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58272; EC=1.1.1.95;
CC Evidence={ECO:0000269|PubMed:11751922};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-2-hydroxyglutarate + NAD(+) = 2-oxoglutarate + H(+) +
CC NADH; Xref=Rhea:RHEA:49612, ChEBI:CHEBI:15378, ChEBI:CHEBI:15801,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.399; Evidence={ECO:0000269|PubMed:25406093};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-malate + NAD(+) = H(+) + NADH + oxaloacetate;
CC Xref=Rhea:RHEA:21432, ChEBI:CHEBI:15378, ChEBI:CHEBI:15589,
CC ChEBI:CHEBI:16452, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.37;
CC Evidence={ECO:0000269|PubMed:25406093};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=21.6 uM for 3-phosphonooxypyruvate {ECO:0000269|PubMed:19235232};
CC KM=0.26 mM for 3-phosphoglycerate {ECO:0000269|PubMed:25406093};
CC KM=6.5 mM for oxaloacetate {ECO:0000269|PubMed:25406093};
CC KM=10.1 mM for 2-oxoglutarate {ECO:0000269|PubMed:25406093};
CC KM=22 uM for NAD(+) {ECO:0000269|PubMed:25406093};
CC KM=4 uM for NADH {ECO:0000269|PubMed:25406093};
CC Vmax=35 nmol/min/mg enzyme with 3-phosphohydroxypyruvate as substrate
CC (in patient-derived fibroblasts) {ECO:0000269|PubMed:19235232};
CC Vmax=168 nmol/min/mg enzyme with 3-phosphohydroxypyruvate as
CC substrate (in 3-PGDH overexpressed cells)
CC {ECO:0000269|PubMed:19235232};
CC Note=kcat is 4.5 min(-1) for 3-phosphoglycerate oxidation. kcat is
CC 10.6 min(-1) for oxaloacetate reduction. kcat is 4.7 min(-1) for 2-
CC oxoglutarate reduction. {ECO:0000269|PubMed:25406093};
CC -!- PATHWAY: Amino-acid biosynthesis; L-serine biosynthesis; L-serine from
CC 3-phospho-D-glycerate: step 1/3.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:O08651}.
CC -!- INDUCTION: Induced by 17-beta-estradiol (estrogenic ligand) and 4-
CC hydroxytamoxifen (agonist/antagonist ligand). Positively regulated by
CC the transcription factors SP1 and NF-Y. {ECO:0000269|PubMed:16949628,
CC ECO:0000269|PubMed:18378410}.
CC -!- DISEASE: Phosphoglycerate dehydrogenase deficiency (PHGDHD)
CC [MIM:601815]: An autosomal recessive inborn error of L-serine
CC biosynthesis, clinically characterized by congenital microcephaly,
CC psychomotor retardation, and seizures. {ECO:0000269|PubMed:11055895,
CC ECO:0000269|PubMed:19235232}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Neu-Laxova syndrome 1 (NLS1) [MIM:256520]: A lethal, autosomal
CC recessive multiple malformation syndrome characterized by ichthyosis,
CC marked intrauterine growth restriction, microcephaly, short neck, limb
CC deformities, hypoplastic lungs, edema, and central nervous system
CC anomalies including lissencephaly, cerebellar hypoplasia and/or
CC abnormal/agenesis of the corpus callosum. Abnormal facial features
CC include severe proptosis with ectropion, hypertelorism, micrognathia,
CC flattened nose, and malformed ears. {ECO:0000269|PubMed:24836451}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; AF006043; AAB88664.1; -; mRNA.
DR EMBL; AF171237; AAD51415.1; -; mRNA.
DR EMBL; CR456795; CAG33076.1; -; mRNA.
DR EMBL; AK315360; BAG37755.1; -; mRNA.
DR EMBL; AL589734; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139251; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56708.1; -; Genomic_DNA.
DR EMBL; BC000303; AAH00303.1; -; mRNA.
DR EMBL; BC001349; AAH01349.1; -; mRNA.
DR EMBL; BC011262; AAH11262.1; -; mRNA.
DR CCDS; CCDS904.1; -.
DR RefSeq; NP_006614.2; NM_006623.3.
DR PDB; 2G76; X-ray; 1.70 A; A/B=4-315.
DR PDB; 5N53; X-ray; 1.48 A; A/B=100-294.
DR PDB; 5N6C; X-ray; 2.30 A; A/B=8-306.
DR PDB; 5NZO; X-ray; 1.29 A; A/B=100-294.
DR PDB; 5NZP; X-ray; 1.30 A; A/B=96-299.
DR PDB; 5NZQ; X-ray; 1.50 A; A/B=93-315.
DR PDB; 5OFM; X-ray; 1.50 A; A/B=93-315.
DR PDB; 5OFV; X-ray; 1.50 A; A/B=93-315.
DR PDB; 5OFW; X-ray; 1.50 A; A/B=93-315.
DR PDB; 6CWA; X-ray; 1.77 A; A/B=4-315.
DR PDB; 6PLF; X-ray; 1.70 A; A/B=4-315.
DR PDB; 6PLG; X-ray; 2.93 A; A/B/C/D/E/F/G/H=4-315.
DR PDB; 6RIH; X-ray; 2.15 A; A/B=4-315.
DR PDB; 6RJ2; X-ray; 2.00 A; A/B=4-315.
DR PDB; 6RJ3; X-ray; 1.42 A; A/B=4-315.
DR PDB; 6RJ5; X-ray; 1.89 A; A/B=4-315.
DR PDB; 6RJ6; X-ray; 1.98 A; A/B=4-315.
DR PDB; 7CVP; X-ray; 2.50 A; A/B=4-315.
DR PDB; 7DKM; X-ray; 1.70 A; A/B=3-308.
DR PDBsum; 2G76; -.
DR PDBsum; 5N53; -.
DR PDBsum; 5N6C; -.
DR PDBsum; 5NZO; -.
DR PDBsum; 5NZP; -.
DR PDBsum; 5NZQ; -.
DR PDBsum; 5OFM; -.
DR PDBsum; 5OFV; -.
DR PDBsum; 5OFW; -.
DR PDBsum; 6CWA; -.
DR PDBsum; 6PLF; -.
DR PDBsum; 6PLG; -.
DR PDBsum; 6RIH; -.
DR PDBsum; 6RJ2; -.
DR PDBsum; 6RJ3; -.
DR PDBsum; 6RJ5; -.
DR PDBsum; 6RJ6; -.
DR PDBsum; 7CVP; -.
DR PDBsum; 7DKM; -.
DR AlphaFoldDB; O43175; -.
DR SMR; O43175; -.
DR BioGRID; 117618; 247.
DR IntAct; O43175; 68.
DR MINT; O43175; -.
DR STRING; 9606.ENSP00000358417; -.
DR BindingDB; O43175; -.
DR ChEMBL; CHEMBL2311243; -.
DR DrugBank; DB00157; NADH.
DR CarbonylDB; O43175; -.
DR GlyGen; O43175; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O43175; -.
DR MetOSite; O43175; -.
DR PhosphoSitePlus; O43175; -.
DR SwissPalm; O43175; -.
DR BioMuta; PHGDH; -.
DR CPTAC; CPTAC-109; -.
DR CPTAC; CPTAC-110; -.
DR EPD; O43175; -.
DR jPOST; O43175; -.
DR MassIVE; O43175; -.
DR MaxQB; O43175; -.
DR PaxDb; O43175; -.
DR PeptideAtlas; O43175; -.
DR PRIDE; O43175; -.
DR ProteomicsDB; 48792; -.
DR TopDownProteomics; O43175; -.
DR Antibodypedia; 3291; 484 antibodies from 35 providers.
DR DNASU; 26227; -.
DR Ensembl; ENST00000641023.2; ENSP00000493175.1; ENSG00000092621.13.
DR Ensembl; ENST00000641597.1; ENSP00000493382.1; ENSG00000092621.13.
DR GeneID; 26227; -.
DR KEGG; hsa:26227; -.
DR MANE-Select; ENST00000641023.2; ENSP00000493175.1; NM_006623.4; NP_006614.2.
DR UCSC; uc001ehz.4; human.
DR CTD; 26227; -.
DR DisGeNET; 26227; -.
DR GeneCards; PHGDH; -.
DR HGNC; HGNC:8923; PHGDH.
DR HPA; ENSG00000092621; Low tissue specificity.
DR MalaCards; PHGDH; -.
DR MIM; 256520; phenotype.
DR MIM; 601815; phenotype.
DR MIM; 606879; gene.
DR neXtProt; NX_O43175; -.
DR OpenTargets; ENSG00000092621; -.
DR Orphanet; 79351; 3-phosphoglycerate dehydrogenase deficiency, infantile/juvenile form.
DR Orphanet; 583607; Neu-laxova syndrome due to 3-phosphoglycerate dehydrogenase deficiency.
DR PharmGKB; PA33264; -.
DR VEuPathDB; HostDB:ENSG00000092621; -.
DR eggNOG; KOG0068; Eukaryota.
DR GeneTree; ENSGT00940000155863; -.
DR HOGENOM; CLU_019796_8_1_1; -.
DR InParanoid; O43175; -.
DR OMA; NIAGMQV; -.
DR OrthoDB; 911009at2759; -.
DR PhylomeDB; O43175; -.
DR TreeFam; TF314548; -.
DR BioCyc; MetaCyc:HS01776-MON; -.
DR BRENDA; 1.1.1.95; 2681.
DR PathwayCommons; O43175; -.
DR Reactome; R-HSA-977347; Serine biosynthesis.
DR SABIO-RK; O43175; -.
DR SignaLink; O43175; -.
DR SIGNOR; O43175; -.
DR UniPathway; UPA00135; UER00196.
DR BioGRID-ORCS; 26227; 16 hits in 1089 CRISPR screens.
DR ChiTaRS; PHGDH; human.
DR EvolutionaryTrace; O43175; -.
DR GeneWiki; Phosphoglycerate_dehydrogenase; -.
DR GenomeRNAi; 26227; -.
DR Pharos; O43175; Tchem.
DR PRO; PR:O43175; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O43175; protein.
DR Bgee; ENSG00000092621; Expressed in ventricular zone and 192 other tissues.
DR ExpressionAtlas; O43175; baseline and differential.
DR Genevisible; O43175; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
DR GO; GO:0030060; F:L-malate dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0004617; F:phosphoglycerate dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; TAS:ProtInc.
DR GO; GO:0070314; P:G1 to G0 transition; IEA:Ensembl.
DR GO; GO:0009448; P:gamma-aminobutyric acid metabolic process; IEA:Ensembl.
DR GO; GO:0021782; P:glial cell development; IEA:Ensembl.
DR GO; GO:0006541; P:glutamine metabolic process; IEA:Ensembl.
DR GO; GO:0006544; P:glycine metabolic process; IEA:Ensembl.
DR GO; GO:0006564; P:L-serine biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0021915; P:neural tube development; IEA:Ensembl.
DR GO; GO:0031175; P:neuron projection development; IEA:Ensembl.
DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR GO; GO:0021510; P:spinal cord development; IEA:Ensembl.
DR GO; GO:0019530; P:taurine metabolic process; IEA:Ensembl.
DR GO; GO:0006566; P:threonine metabolic process; IEA:Ensembl.
DR Gene3D; 3.30.1330.90; -; 1.
DR InterPro; IPR029009; ASB_dom_sf.
DR InterPro; IPR006139; D-isomer_2_OHA_DH_cat_dom.
DR InterPro; IPR029753; D-isomer_DH_CS.
DR InterPro; IPR029752; D-isomer_DH_CS1.
DR InterPro; IPR006140; D-isomer_DH_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR006236; PGDH.
DR InterPro; IPR045626; PGDH_ASB_dom.
DR Pfam; PF00389; 2-Hacid_dh; 1.
DR Pfam; PF02826; 2-Hacid_dh_C; 1.
DR Pfam; PF19304; PGDH_inter; 1.
DR SUPFAM; SSF143548; SSF143548; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01327; PGDH; 1.
DR PROSITE; PS00065; D_2_HYDROXYACID_DH_1; 1.
DR PROSITE; PS00670; D_2_HYDROXYACID_DH_2; 1.
DR PROSITE; PS00671; D_2_HYDROXYACID_DH_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Amino-acid biosynthesis;
KW Direct protein sequencing; Disease variant; Isopeptide bond; NAD;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Serine biosynthesis;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.8"
FT CHAIN 2..533
FT /note="D-3-phosphoglycerate dehydrogenase"
FT /id="PRO_0000076012"
FT ACT_SITE 236
FT ACT_SITE 265
FT /evidence="ECO:0000250"
FT ACT_SITE 283
FT /note="Proton donor"
FT BINDING 78
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.21"
FT BINDING 155..156
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.21"
FT BINDING 175
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.21"
FT BINDING 207
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.21"
FT BINDING 234..236
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.21"
FT BINDING 260
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.21"
FT BINDING 283..286
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.21"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.8"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 21
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q61753"
FT MOD_RES 58
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q61753"
FT MOD_RES 78
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT CROSSLNK 21
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 21
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT VARIANT 135
FT /note="R -> W (in PHGDHD; results in a 2-fold decrease in
FT enzyme activity with 3-phosphohydroxypyruvate, but no
FT change in substrate affinity; dbSNP:rs267606949)"
FT /evidence="ECO:0000269|PubMed:19235232"
FT /id="VAR_059026"
FT VARIANT 140
FT /note="G -> R (in NLS1; dbSNP:rs587777770)"
FT /evidence="ECO:0000269|PubMed:24836451"
FT /id="VAR_071819"
FT VARIANT 163
FT /note="R -> Q (in NLS1; dbSNP:rs587777483)"
FT /evidence="ECO:0000269|PubMed:24836451"
FT /id="VAR_071820"
FT VARIANT 261
FT /note="V -> M (in PHGDHD; results in a four-fold decrease
FT in substrate affinity and a slight increase in maximal
FT enzyme activity with 3-phosphohydroxypyruvate;
FT dbSNP:rs267606947)"
FT /evidence="ECO:0000269|PubMed:19235232"
FT /id="VAR_059027"
FT VARIANT 373
FT /note="A -> T (in PHGDHD; results in almost undetectable
FT enzyme activity with 3-phosphohydroxypyruvate;
FT dbSNP:rs201553627)"
FT /evidence="ECO:0000269|PubMed:19235232"
FT /id="VAR_059028"
FT VARIANT 377
FT /note="G -> S (in PHGDHD; results in a 2-fold decrease in
FT enzyme activity with 3-phosphohydroxypyruvate, but no
FT change in substrate affinity; dbSNP:rs267606948)"
FT /evidence="ECO:0000269|PubMed:19235232"
FT /id="VAR_059029"
FT VARIANT 425
FT /note="V -> M (in PHGDHD; results in almost undetectable
FT enzyme activity with 3-phosphohydroxypyruvate;
FT dbSNP:rs121907988)"
FT /evidence="ECO:0000269|PubMed:11055895,
FT ECO:0000269|PubMed:19235232"
FT /id="VAR_013461"
FT VARIANT 490
FT /note="V -> M (in PHGDHD; results in almost undetectable
FT enzyme activity with 3-phosphohydroxypyruvate;
FT dbSNP:rs121907987)"
FT /evidence="ECO:0000269|PubMed:11055895,
FT ECO:0000269|PubMed:11751922, ECO:0000269|PubMed:19235232"
FT /id="VAR_059030"
FT CONFLICT 25
FT /note="D -> E (in Ref. 1; AAB88664/AAD51415)"
FT /evidence="ECO:0000305"
FT STRAND 8..11
FT /evidence="ECO:0007829|PDB:6RJ3"
FT HELIX 18..25
FT /evidence="ECO:0007829|PDB:6RJ3"
FT STRAND 29..32
FT /evidence="ECO:0007829|PDB:6RJ3"
FT HELIX 38..45
FT /evidence="ECO:0007829|PDB:6RJ3"
FT STRAND 49..53
FT /evidence="ECO:0007829|PDB:6RJ3"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:6RJ3"
FT HELIX 61..66
FT /evidence="ECO:0007829|PDB:6RJ3"
FT STRAND 72..78
FT /evidence="ECO:0007829|PDB:6RJ3"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:6RJ5"
FT HELIX 85..90
FT /evidence="ECO:0007829|PDB:6RJ3"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:6RJ3"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:6RJ3"
FT HELIX 103..119
FT /evidence="ECO:0007829|PDB:5NZO"
FT HELIX 121..129
FT /evidence="ECO:0007829|PDB:5NZO"
FT TURN 135..138
FT /evidence="ECO:0007829|PDB:5NZO"
FT STRAND 147..151
FT /evidence="ECO:0007829|PDB:5NZO"
FT HELIX 155..165
FT /evidence="ECO:0007829|PDB:5NZO"
FT TURN 166..168
FT /evidence="ECO:0007829|PDB:5NZO"
FT STRAND 170..174
FT /evidence="ECO:0007829|PDB:5NZO"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:5NZO"
FT HELIX 180..185
FT /evidence="ECO:0007829|PDB:5NZO"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:6PLF"
FT HELIX 193..196
FT /evidence="ECO:0007829|PDB:5NZO"
FT HELIX 197..199
FT /evidence="ECO:0007829|PDB:5NZO"
FT STRAND 201..205
FT /evidence="ECO:0007829|PDB:5NZO"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:5NZO"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:5NZO"
FT HELIX 219..222
FT /evidence="ECO:0007829|PDB:5NZO"
FT STRAND 229..233
FT /evidence="ECO:0007829|PDB:5NZO"
FT HELIX 242..251
FT /evidence="ECO:0007829|PDB:5NZO"
FT STRAND 252..260
FT /evidence="ECO:0007829|PDB:5NZO"
FT STRAND 263..266
FT /evidence="ECO:0007829|PDB:5NZO"
FT HELIX 271..274
FT /evidence="ECO:0007829|PDB:5NZO"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:5NZO"
FT HELIX 289..292
FT /evidence="ECO:0007829|PDB:5NZO"
SQ SEQUENCE 533 AA; 56651 MW; C58EB72275C45B35 CRC64;
MAFANLRKVL ISDSLDPCCR KILQDGGLQV VEKQNLSKEE LIAELQDCEG LIVRSATKVT
ADVINAAEKL QVVGRAGTGV DNVDLEAATR KGILVMNTPN GNSLSAAELT CGMIMCLARQ
IPQATASMKD GKWERKKFMG TELNGKTLGI LGLGRIGREV ATRMQSFGMK TIGYDPIISP
EVSASFGVQQ LPLEEIWPLC DFITVHTPLL PSTTGLLNDN TFAQCKKGVR VVNCARGGIV
DEGALLRALQ SGQCAGAALD VFTEEPPRDR ALVDHENVIS CPHLGASTKE AQSRCGEEIA
VQFVDMVKGK SLTGVVNAQA LTSAFSPHTK PWIGLAEALG TLMRAWAGSP KGTIQVITQG
TSLKNAGNCL SPAVIVGLLK EASKQADVNL VNAKLLVKEA GLNVTTSHSP AAPGEQGFGE
CLLAVALAGA PYQAVGLVQG TTPVLQGLNG AVFRPEVPLR RDLPLLLFRT QTSDPAMLPT
MIGLLAEAGV RLLSYQTSLV SDGETWHVMG ISSLLPSLEA WKQHVTEAFQ FHF
