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Protein

D-3-phosphoglycerate dehydrogenase

Gene

PHGDH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

3-phospho-D-glycerate + NAD+ = 3-phosphonooxypyruvate + NADH.1 Publication
2-hydroxyglutarate + NAD+ = 2-oxoglutarate + NADH.1 Publication

Kineticsi

  1. KM=21.6 µM for 3-phosphohydroxypyruvate1 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 (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

  • electron carrier activity Source: UniProtKB
  • NAD binding Source: InterPro
  • phosphoglycerate dehydrogenase activity Source: Reactome

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Amino-acid biosynthesis, Serine biosynthesis

Keywords - Ligandi

NAD

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
D-3-phosphoglycerate dehydrogenase (EC:1.1.1.95)
Short name:
3-PGDH
Gene namesi
Name:PHGDH
Synonyms:PGDH3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:8923. PHGDH.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • myelin sheath Source: Ensembl
Complete GO annotation...

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 rs267606949dbSNPEnsembl.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 rs267606947dbSNPEnsembl.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 rs267606948dbSNPEnsembl.1
Natural variantiVAR_013461425V → M in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 2 PublicationsCorresponds to variant rs121907988dbSNPEnsembl.1
Natural variantiVAR_059030490V → M in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 3 PublicationsCorresponds to variant rs121907987dbSNPEnsembl.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 rs587777770dbSNPEnsembl.1
Natural variantiVAR_071820163R → Q in NLS1. 1 PublicationCorresponds to variant rs587777483dbSNPEnsembl.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.

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.
TopDownProteomicsiO43175.

PTM databases

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.
ExpressionAtlasiO43175. baseline and differential.
GenevisibleiO43175. HS.

Organism-specific databases

HPAiCAB003681.
CAB068216.
HPA021241.
HPA024031.

Interactioni

Subunit structurei

Homotetramer.By similarity

Protein-protein interaction databases

BioGridi117618. 115 interactors.
IntActiO43175. 40 interactors.
MINTiMINT-4999739.
STRINGi9606.ENSP00000358417.

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
Helixi136 – 138Combined sources3
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
Turni211 – 215Combined sources5
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 – 306Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2G76X-ray1.70A/B4-315[»]
ProteinModelPortaliO43175.
SMRiO43175.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43175.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0068. Eukaryota.
COG0111. LUCA.
GeneTreeiENSGT00840000129939.
HOGENOMiHOG000136693.
HOVERGENiHBG054241.
InParanoidiO43175.
KOiK00058.
OMAiDNTFAQC.
OrthoDBiEOG091G0C5D.
PhylomeDBiO43175.
TreeFamiTF314548.

Family and domain databases

Gene3Di3.30.1330.90. 1 hit.
3.40.50.720. 2 hits.
InterProiIPR029009. ASB_dom.
IPR006139. D-isomer_2_OHA_DH_cat_dom.
IPR029753. D-isomer_DH_CS.
IPR029752. D-isomer_DH_CS1.
IPR006140. D-isomer_DH_NAD-bd.
IPR016040. NAD(P)-bd_dom.
IPR006236. PGDH.
[Graphical view]
PfamiPF00389. 2-Hacid_dh. 1 hit.
PF02826. 2-Hacid_dh_C. 1 hit.
[Graphical view]
SUPFAMiSSF143548. SSF143548. 1 hit.
SSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR01327. PGDH. 1 hit.
PROSITEiPS00065. D_2_HYDROXYACID_DH_1. 1 hit.
PS00670. D_2_HYDROXYACID_DH_2. 1 hit.
PS00671. D_2_HYDROXYACID_DH_3. 1 hit.
[Graphical view]

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 rs267606949dbSNPEnsembl.1
Natural variantiVAR_071819140G → R in NLS1. 1 PublicationCorresponds to variant rs587777770dbSNPEnsembl.1
Natural variantiVAR_071820163R → Q in NLS1. 1 PublicationCorresponds to variant rs587777483dbSNPEnsembl.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 rs267606947dbSNPEnsembl.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 rs267606948dbSNPEnsembl.1
Natural variantiVAR_013461425V → M in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 2 PublicationsCorresponds to variant rs121907988dbSNPEnsembl.1
Natural variantiVAR_059030490V → M in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 3 PublicationsCorresponds to variant rs121907987dbSNPEnsembl.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, AL139251 Genomic DNA. Translation: CAI22407.1.
AL139251, AL589734 Genomic DNA. Translation: CAI22212.1.
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

EnsembliENST00000369409; ENSP00000358417; ENSG00000092621.
GeneIDi26227.
KEGGihsa:26227.
UCSCiuc001ehz.4. human.

Cross-referencesi

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, AL139251 Genomic DNA. Translation: CAI22407.1.
AL139251, AL589734 Genomic DNA. Translation: CAI22212.1.
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2G76X-ray1.70A/B4-315[»]
ProteinModelPortaliO43175.
SMRiO43175.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117618. 115 interactors.
IntActiO43175. 40 interactors.
MINTiMINT-4999739.
STRINGi9606.ENSP00000358417.

Chemistry databases

ChEMBLiCHEMBL2311243.

PTM databases

iPTMnetiO43175.
PhosphoSitePlusiO43175.
SwissPalmiO43175.

Polymorphism and mutation databases

BioMutaiPHGDH.

Proteomic databases

EPDiO43175.
MaxQBiO43175.
PaxDbiO43175.
PeptideAtlasiO43175.
PRIDEiO43175.
TopDownProteomicsiO43175.

Protocols and materials databases

DNASUi26227.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000369409; ENSP00000358417; ENSG00000092621.
GeneIDi26227.
KEGGihsa:26227.
UCSCiuc001ehz.4. human.

Organism-specific databases

CTDi26227.
DisGeNETi26227.
GeneCardsiPHGDH.
HGNCiHGNC:8923. PHGDH.
HPAiCAB003681.
CAB068216.
HPA021241.
HPA024031.
MalaCardsiPHGDH.
MIMi256520. phenotype.
601815. phenotype.
606879. gene.
neXtProtiNX_O43175.
OpenTargetsiENSG00000092621.
Orphaneti79351. 3-phosphoglycerate dehydrogenase deficiency, infantile/juvenile form.
2671. Neu-Laxova syndrome.
PharmGKBiPA33264.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0068. Eukaryota.
COG0111. LUCA.
GeneTreeiENSGT00840000129939.
HOGENOMiHOG000136693.
HOVERGENiHBG054241.
InParanoidiO43175.
KOiK00058.
OMAiDNTFAQC.
OrthoDBiEOG091G0C5D.
PhylomeDBiO43175.
TreeFamiTF314548.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiPHGDH. human.
EvolutionaryTraceiO43175.
GeneWikiiPhosphoglycerate_dehydrogenase.
GenomeRNAii26227.
PROiO43175.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000092621.
CleanExiHS_PHGDH.
ExpressionAtlasiO43175. baseline and differential.
GenevisibleiO43175. HS.

Family and domain databases

Gene3Di3.30.1330.90. 1 hit.
3.40.50.720. 2 hits.
InterProiIPR029009. ASB_dom.
IPR006139. D-isomer_2_OHA_DH_cat_dom.
IPR029753. D-isomer_DH_CS.
IPR029752. D-isomer_DH_CS1.
IPR006140. D-isomer_DH_NAD-bd.
IPR016040. NAD(P)-bd_dom.
IPR006236. PGDH.
[Graphical view]
PfamiPF00389. 2-Hacid_dh. 1 hit.
PF02826. 2-Hacid_dh_C. 1 hit.
[Graphical view]
SUPFAMiSSF143548. SSF143548. 1 hit.
SSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR01327. PGDH. 1 hit.
PROSITEiPS00065. D_2_HYDROXYACID_DH_1. 1 hit.
PS00670. D_2_HYDROXYACID_DH_2. 1 hit.
PS00671. D_2_HYDROXYACID_DH_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSERA_HUMAN
AccessioniPrimary (citable) accession number: O43175
Secondary accession number(s): B2RD08, Q5SZU3, Q9BQ01
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 175 of the entry and version 4 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.