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Protein

D-3-phosphoglycerate dehydrogenase

Gene

PHGDH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate and the reversible oxidation of (S)-malate to oxaloacetate.2 Publications

Catalytic activityi

3-phospho-D-glycerate + NAD+ = 3-phosphonooxypyruvate + NADH.1 Publication
(R)-2-hydroxyglutarate + NAD+ = 2-oxoglutarate + NADH.1 Publication
(S)-malate + NAD+ = oxaloacetate + NADH.1 Publication

Kineticsi

kcat is 4.5 min(-1) for 3-phosphoglycerate oxidation. kcat is 10.6 min(-1) for oxaloacetate reduction. kcat is 4.7 min(-1) for 2-oxoglutarate reduction.1 Publication
  1. KM=21.6 µM for 3-phosphonooxypyruvate1 Publication
  2. KM=0.26 mM for 3-phosphoglycerate1 Publication
  3. KM=6.5 mM for oxaloacetate1 Publication
  4. KM=10.1 mM for 2-oxoglutarate1 Publication
  5. KM=22 µM for NAD+1 Publication
  6. KM=4 µM for NADH1 Publication
  1. Vmax=35 nmol/min/mg enzyme with 3-phosphohydroxypyruvate as substrate (in patient-derived fibroblasts)1 Publication
  2. Vmax=168 nmol/min/mg enzyme with 3-phosphohydroxypyruvate as substrate (in 3-PGDH overexpressed cells)1 Publication

Pathwayi: L-serine biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes L-serine from 3-phospho-D-glycerate.
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. D-3-phosphoglycerate dehydrogenase (PHGDH), D-3-phosphoglycerate dehydrogenase (HEL-S-113), D-3-phosphoglycerate dehydrogenase (serA), D-3-phosphoglycerate dehydrogenase (PHGDH), D-3-phosphoglycerate dehydrogenase (PHGDH)
  2. Phosphoserine aminotransferase, Phosphoserine aminotransferase (PSAT1), Phosphoserine aminotransferase (PSAT1)
  3. Phosphoserine phosphatase (PSPH)
This subpathway is part of the pathway L-serine biosynthesis, which is itself part of Amino-acid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-serine from 3-phospho-D-glycerate, the pathway L-serine biosynthesis and in Amino-acid biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei78NAD1 Publication1
Binding sitei175NAD1 Publication1
Binding sitei207NAD; via carbonyl oxygen1 Publication1
Active sitei2361
Binding sitei260NAD1 Publication1
Active sitei265By similarity1
Active sitei283Proton donor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi155 – 156NAD1 Publication2
Nucleotide bindingi234 – 236NAD1 Publication3
Nucleotide bindingi283 – 286NAD1 Publication4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
Biological processAmino-acid biosynthesis, Serine biosynthesis
LigandNAD

Enzyme and pathway databases

BioCyciMetaCyc:HS01776-MONOMER
BRENDAi1.1.1.95 2681
ReactomeiR-HSA-977347 Serine biosynthesis
SIGNORiO43175
UniPathwayiUPA00135; UER00196

Names & Taxonomyi

Protein namesi
Recommended name:
D-3-phosphoglycerate dehydrogenase (EC:1.1.1.951 Publication)
Short name:
3-PGDH
Alternative name(s):
2-oxoglutarate reductaseCurated (EC:1.1.1.3991 Publication)
Malate dehydrogenaseCurated (EC:1.1.1.371 Publication)
Gene namesi
Name:PHGDH
Synonyms:PGDH3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000092621.11
HGNCiHGNC:8923 PHGDH
MIMi606879 gene
neXtProtiNX_O43175

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Phosphoglycerate dehydrogenase deficiency (PHGDHD)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive inborn error of L-serine biosynthesis, clinically characterized by congenital microcephaly, psychomotor retardation, and seizures.
See also OMIM:601815
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_059026135R → W in PHGDHD; results in a 2-fold decrease in enzyme activity with 3-phosphohydroxypyruvate, but no change in substrate affinity. 1 PublicationCorresponds to variant dbSNP:rs267606949EnsemblClinVar.1
Natural variantiVAR_059027261V → M in PHGDHD; results in a four-fold decrease in substrate affinity and a slight increase in maximal enzyme activity with 3-phosphohydroxypyruvate. 1 PublicationCorresponds to variant dbSNP:rs267606947EnsemblClinVar.1
Natural variantiVAR_059028373A → T in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 1 Publication1
Natural variantiVAR_059029377G → S in PHGDHD; results in a 2-fold decrease in enzyme activity with 3-phosphohydroxypyruvate, but no change in substrate affinity. 1 PublicationCorresponds to variant dbSNP:rs267606948EnsemblClinVar.1
Natural variantiVAR_013461425V → M in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 2 PublicationsCorresponds to variant dbSNP:rs121907988EnsemblClinVar.1
Natural variantiVAR_059030490V → M in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 3 PublicationsCorresponds to variant dbSNP:rs121907987EnsemblClinVar.1
Neu-Laxova syndrome 1 (NLS1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA lethal, autosomal recessive multiple malformation syndrome characterized by ichthyosis, marked intrauterine growth restriction, microcephaly, short neck, limb deformities, hypoplastic lungs, edema, and central nervous system anomalies including lissencephaly, cerebellar hypoplasia and/or abnormal/agenesis of the corpus callosum. Abnormal facial features include severe proptosis with ectropion, hypertelorism, micrognathia, flattened nose, and malformed ears.
See also OMIM:256520
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071819140G → R in NLS1. 1 PublicationCorresponds to variant dbSNP:rs587777770EnsemblClinVar.1
Natural variantiVAR_071820163R → Q in NLS1. 1 PublicationCorresponds to variant dbSNP:rs587777483EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi26227
MalaCardsiPHGDH
MIMi256520 phenotype
601815 phenotype
OpenTargetsiENSG00000092621
Orphaneti79351 3-phosphoglycerate dehydrogenase deficiency, infantile/juvenile form
2671 Neu-Laxova syndrome
PharmGKBiPA33264

Chemistry databases

ChEMBLiCHEMBL2311243
DrugBankiDB00157 NADH

Polymorphism and mutation databases

BioMutaiPHGDH

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000760122 – 533D-3-phosphoglycerate dehydrogenaseAdd BLAST532

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine1 Publication1
Modified residuei14PhosphoserineCombined sources1
Modified residuei21N6-acetyllysine; alternateBy similarity1
Cross-linki21Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
Cross-linki21Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei58N6-acetyllysineBy similarity1
Modified residuei78PhosphothreonineCombined sources1

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO43175
MaxQBiO43175
PaxDbiO43175
PeptideAtlasiO43175
PRIDEiO43175
ProteomicsDBi48792
TopDownProteomicsiO43175

PTM databases

CarbonylDBiO43175
iPTMnetiO43175
PhosphoSitePlusiO43175
SwissPalmiO43175

Expressioni

Inductioni

Induced by 17-beta-estradiol (estrogenic ligand) and 4-hydroxytamoxifen (agonist/antagonist ligand). Positively regulated by the transcription factors SP1 and NF-Y.2 Publications

Gene expression databases

BgeeiENSG00000092621
CleanExiHS_PHGDH
GenevisibleiO43175 HS

Organism-specific databases

HPAiCAB003681
CAB068216
HPA021241
HPA024031

Interactioni

Subunit structurei

Homotetramer.By similarity

Protein-protein interaction databases

BioGridi117618, 122 interactors
IntActiO43175, 46 interactors
MINTiO43175
STRINGi9606.ENSP00000358417

Chemistry databases

BindingDBiO43175

Structurei

Secondary structure

1533
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi8 – 11Combined sources4
Helixi18 – 26Combined sources9
Beta strandi29 – 32Combined sources4
Helixi38 – 44Combined sources7
Helixi45 – 47Combined sources3
Beta strandi49 – 53Combined sources5
Beta strandi55 – 57Combined sources3
Helixi61 – 66Combined sources6
Beta strandi72 – 79Combined sources8
Helixi85 – 91Combined sources7
Beta strandi94 – 96Combined sources3
Helixi103 – 119Combined sources17
Helixi121 – 129Combined sources9
Turni135 – 138Combined sources4
Beta strandi147 – 151Combined sources5
Helixi155 – 165Combined sources11
Turni166 – 168Combined sources3
Beta strandi170 – 174Combined sources5
Beta strandi176 – 178Combined sources3
Helixi180 – 185Combined sources6
Helixi193 – 196Combined sources4
Helixi197 – 199Combined sources3
Beta strandi201 – 205Combined sources5
Helixi211 – 213Combined sources3
Beta strandi216 – 218Combined sources3
Helixi219 – 222Combined sources4
Beta strandi229 – 233Combined sources5
Helixi242 – 251Combined sources10
Beta strandi252 – 260Combined sources9
Beta strandi263 – 266Combined sources4
Helixi271 – 274Combined sources4
Beta strandi278 – 280Combined sources3
Helixi289 – 292Combined sources4

3D structure databases

ProteinModelPortaliO43175
SMRiO43175
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43175

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0068 Eukaryota
COG0111 LUCA
GeneTreeiENSGT00530000063021
HOGENOMiHOG000136693
HOVERGENiHBG054241
InParanoidiO43175
KOiK00058
OMAiNIAGMQV
OrthoDBiEOG091G0C5D
PhylomeDBiO43175
TreeFamiTF314548

Family and domain databases

Gene3Di3.30.1330.90, 1 hit
InterProiView protein in InterPro
IPR029009 ASB_dom_sf
IPR006139 D-isomer_2_OHA_DH_cat_dom
IPR029753 D-isomer_DH_CS
IPR029752 D-isomer_DH_CS1
IPR006140 D-isomer_DH_NAD-bd
IPR036291 NAD(P)-bd_dom_sf
IPR006236 PGDH
PfamiView protein in Pfam
PF00389 2-Hacid_dh, 1 hit
PF02826 2-Hacid_dh_C, 1 hit
SUPFAMiSSF143548 SSF143548, 1 hit
SSF51735 SSF51735, 1 hit
TIGRFAMsiTIGR01327 PGDH, 1 hit
PROSITEiView protein in PROSITE
PS00065 D_2_HYDROXYACID_DH_1, 1 hit
PS00670 D_2_HYDROXYACID_DH_2, 1 hit
PS00671 D_2_HYDROXYACID_DH_3, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O43175-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAFANLRKVL ISDSLDPCCR KILQDGGLQV VEKQNLSKEE LIAELQDCEG
60 70 80 90 100
LIVRSATKVT ADVINAAEKL QVVGRAGTGV DNVDLEAATR KGILVMNTPN
110 120 130 140 150
GNSLSAAELT CGMIMCLARQ IPQATASMKD GKWERKKFMG TELNGKTLGI
160 170 180 190 200
LGLGRIGREV ATRMQSFGMK TIGYDPIISP EVSASFGVQQ LPLEEIWPLC
210 220 230 240 250
DFITVHTPLL PSTTGLLNDN TFAQCKKGVR VVNCARGGIV DEGALLRALQ
260 270 280 290 300
SGQCAGAALD VFTEEPPRDR ALVDHENVIS CPHLGASTKE AQSRCGEEIA
310 320 330 340 350
VQFVDMVKGK SLTGVVNAQA LTSAFSPHTK PWIGLAEALG TLMRAWAGSP
360 370 380 390 400
KGTIQVITQG TSLKNAGNCL SPAVIVGLLK EASKQADVNL VNAKLLVKEA
410 420 430 440 450
GLNVTTSHSP AAPGEQGFGE CLLAVALAGA PYQAVGLVQG TTPVLQGLNG
460 470 480 490 500
AVFRPEVPLR RDLPLLLFRT QTSDPAMLPT MIGLLAEAGV RLLSYQTSLV
510 520 530
SDGETWHVMG ISSLLPSLEA WKQHVTEAFQ FHF
Length:533
Mass (Da):56,651
Last modified:January 23, 2007 - v4
Checksum:iC58EB72275C45B35
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti25D → E in AAB88664 (PubMed:10713460).Curated1
Sequence conflicti25D → E in AAD51415 (PubMed:10713460).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_059026135R → W in PHGDHD; results in a 2-fold decrease in enzyme activity with 3-phosphohydroxypyruvate, but no change in substrate affinity. 1 PublicationCorresponds to variant dbSNP:rs267606949EnsemblClinVar.1
Natural variantiVAR_071819140G → R in NLS1. 1 PublicationCorresponds to variant dbSNP:rs587777770EnsemblClinVar.1
Natural variantiVAR_071820163R → Q in NLS1. 1 PublicationCorresponds to variant dbSNP:rs587777483EnsemblClinVar.1
Natural variantiVAR_059027261V → M in PHGDHD; results in a four-fold decrease in substrate affinity and a slight increase in maximal enzyme activity with 3-phosphohydroxypyruvate. 1 PublicationCorresponds to variant dbSNP:rs267606947EnsemblClinVar.1
Natural variantiVAR_059028373A → T in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 1 Publication1
Natural variantiVAR_059029377G → S in PHGDHD; results in a 2-fold decrease in enzyme activity with 3-phosphohydroxypyruvate, but no change in substrate affinity. 1 PublicationCorresponds to variant dbSNP:rs267606948EnsemblClinVar.1
Natural variantiVAR_013461425V → M in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 2 PublicationsCorresponds to variant dbSNP:rs121907988EnsemblClinVar.1
Natural variantiVAR_059030490V → M in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 3 PublicationsCorresponds to variant dbSNP:rs121907987EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF006043 mRNA Translation: AAB88664.1
AF171237 mRNA Translation: AAD51415.1
CR456795 mRNA Translation: CAG33076.1
AK315360 mRNA Translation: BAG37755.1
AL589734 Genomic DNA No translation available.
AL139251 Genomic DNA No translation available.
CH471122 Genomic DNA Translation: EAW56708.1
BC000303 mRNA Translation: AAH00303.1
BC001349 mRNA Translation: AAH01349.1
BC011262 mRNA Translation: AAH11262.1
CCDSiCCDS904.1
RefSeqiNP_006614.2, NM_006623.3
UniGeneiHs.487296

Genome annotation databases

EnsembliENST00000641023; ENSP00000493175; ENSG00000092621
ENST00000641597; ENSP00000493382; ENSG00000092621
GeneIDi26227
KEGGihsa:26227
UCSCiuc001ehz.4 human

Similar proteinsi

Entry informationi

Entry nameiSERA_HUMAN
AccessioniPrimary (citable) accession number: O43175
Secondary accession number(s): B2RD08, Q5SZU3, Q9BQ01
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 23, 2007
Last modified: July 18, 2018
This is version 194 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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