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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei78 – 781NAD1 Publication
Binding sitei175 – 1751NAD1 Publication
Binding sitei207 – 2071NAD; via carbonyl oxygen1 Publication
Active sitei236 – 2361
Binding sitei260 – 2601NAD1 Publication
Active sitei265 – 2651By similarity
Active sitei283 – 2831Proton donor

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi155 – 1562NAD1 Publication
Nucleotide bindingi234 – 2363NAD1 Publication
Nucleotide bindingi283 – 2864NAD1 Publication

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.
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti135 – 1351R → W in PHGDHD; results in a 2-fold decrease in enzyme activity with 3-phosphohydroxypyruvate, but no change in substrate affinity. 1 Publication
Corresponds to variant rs267606949 [ dbSNP | Ensembl ].
VAR_059026
Natural varianti261 – 2611V → M in PHGDHD; results in a four-fold decrease in substrate affinity and a slight increase in maximal enzyme activity with 3-phosphohydroxypyruvate. 1 Publication
Corresponds to variant rs267606947 [ dbSNP | Ensembl ].
VAR_059027
Natural varianti373 – 3731A → T in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 1 Publication
VAR_059028
Natural varianti377 – 3771G → S in PHGDHD; results in a 2-fold decrease in enzyme activity with 3-phosphohydroxypyruvate, but no change in substrate affinity. 1 Publication
Corresponds to variant rs267606948 [ dbSNP | Ensembl ].
VAR_059029
Natural varianti425 – 4251V → M in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 2 Publications
Corresponds to variant rs121907988 [ dbSNP | Ensembl ].
VAR_013461
Natural varianti490 – 4901V → M in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 3 Publications
Corresponds to variant rs121907987 [ dbSNP | Ensembl ].
VAR_059030
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti140 – 1401G → R in NLS1. 1 Publication
Corresponds to variant rs587777770 [ dbSNP | Ensembl ].
VAR_071819
Natural varianti163 – 1631R → Q in NLS1. 1 Publication
Corresponds to variant rs587777483 [ dbSNP | Ensembl ].
VAR_071820

Keywords - Diseasei

Disease mutation

Organism-specific databases

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

Chemistry

ChEMBLiCHEMBL2311243.

Polymorphism and mutation databases

BioMutaiPHGDH.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved1 Publication
Chaini2 – 533532D-3-phosphoglycerate dehydrogenasePRO_0000076012Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine1 Publication
Modified residuei14 – 141PhosphoserineCombined sources
Modified residuei21 – 211N6-acetyllysine; alternateBy similarity
Cross-linki21 – 21Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
Cross-linki21 – 21Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei58 – 581N6-acetyllysineBy similarity
Modified residuei78 – 781PhosphothreonineCombined sources

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

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

PTM databases

iPTMnetiO43175.
PhosphoSiteiO43175.
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 interactions.
IntActiO43175. 40 interactions.
MINTiMINT-4999739.
STRINGi9606.ENSP00000358417.

Structurei

Secondary structure

1
533
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi8 – 114Combined sources
Helixi18 – 269Combined sources
Beta strandi29 – 324Combined sources
Helixi38 – 447Combined sources
Helixi45 – 473Combined sources
Beta strandi49 – 535Combined sources
Beta strandi55 – 573Combined sources
Helixi61 – 666Combined sources
Beta strandi72 – 798Combined sources
Helixi85 – 917Combined sources
Beta strandi94 – 963Combined sources
Helixi103 – 11917Combined sources
Helixi121 – 1299Combined sources
Helixi136 – 1383Combined sources
Beta strandi147 – 1515Combined sources
Helixi155 – 16511Combined sources
Turni166 – 1683Combined sources
Beta strandi170 – 1745Combined sources
Beta strandi176 – 1783Combined sources
Helixi180 – 1856Combined sources
Helixi193 – 1964Combined sources
Helixi197 – 1993Combined sources
Beta strandi201 – 2055Combined sources
Turni211 – 2155Combined sources
Helixi219 – 2224Combined sources
Beta strandi229 – 2335Combined sources
Helixi242 – 25110Combined sources
Beta strandi252 – 2609Combined sources
Beta strandi263 – 2664Combined sources
Helixi271 – 2744Combined sources
Beta strandi278 – 2803Combined sources
Helixi289 – 30618Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2G76X-ray1.70A/B4-315[»]
ProteinModelPortaliO43175.
SMRiO43175. Positions 6-307.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti25 – 251D → E in AAB88664 (PubMed:10713460).Curated
Sequence conflicti25 – 251D → E in AAD51415 (PubMed:10713460).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti135 – 1351R → W in PHGDHD; results in a 2-fold decrease in enzyme activity with 3-phosphohydroxypyruvate, but no change in substrate affinity. 1 Publication
Corresponds to variant rs267606949 [ dbSNP | Ensembl ].
VAR_059026
Natural varianti140 – 1401G → R in NLS1. 1 Publication
Corresponds to variant rs587777770 [ dbSNP | Ensembl ].
VAR_071819
Natural varianti163 – 1631R → Q in NLS1. 1 Publication
Corresponds to variant rs587777483 [ dbSNP | Ensembl ].
VAR_071820
Natural varianti261 – 2611V → M in PHGDHD; results in a four-fold decrease in substrate affinity and a slight increase in maximal enzyme activity with 3-phosphohydroxypyruvate. 1 Publication
Corresponds to variant rs267606947 [ dbSNP | Ensembl ].
VAR_059027
Natural varianti373 – 3731A → T in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 1 Publication
VAR_059028
Natural varianti377 – 3771G → S in PHGDHD; results in a 2-fold decrease in enzyme activity with 3-phosphohydroxypyruvate, but no change in substrate affinity. 1 Publication
Corresponds to variant rs267606948 [ dbSNP | Ensembl ].
VAR_059029
Natural varianti425 – 4251V → M in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 2 Publications
Corresponds to variant rs121907988 [ dbSNP | Ensembl ].
VAR_013461
Natural varianti490 – 4901V → M in PHGDHD; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. 3 Publications
Corresponds to variant rs121907987 [ dbSNP | Ensembl ].
VAR_059030

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
EntryMethodResolution (Å)ChainPositionsPDBsum
2G76X-ray1.70A/B4-315[»]
ProteinModelPortaliO43175.
SMRiO43175. Positions 6-307.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry

ChEMBLiCHEMBL2311243.

PTM databases

iPTMnetiO43175.
PhosphoSiteiO43175.
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.
GeneCardsiPHGDH.
HGNCiHGNC:8923. PHGDH.
HPAiCAB003681.
CAB068216.
HPA021241.
HPA024031.
MalaCardsiPHGDH.
MIMi256520. phenotype.
601815. phenotype.
606879. gene.
neXtProtiNX_O43175.
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.
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: September 7, 2016
This is version 173 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.