Reviewed, UniProtKB/Swiss-Prot O43175 (SERA_HUMAN)

Names and origin

Protein names

Recommended name:
    D-3-phosphoglycerate dehydrogenase
      Short name=3-PGDH
    EC=1.1.1.95

Gene names

Name:	PHGDH
Synonyms:	PGDH3

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	533 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	3-phospho-D-glycerate + NAD+ = 3-phosphonooxypyruvate + NADH. Ref.10 2-hydroxyglutarate + NAD+ = 2-oxoglutarate + NADH. Ref.10
Pathway	Amino-acid biosynthesis; L-serine biosynthesis; L-serine from 3-phospho-D-glycerate: step 1/3.
Subunit structure	Homotetramer By similarity.
Induction	Induced by 17-beta-estradiol (estrogenic ligand) and 4-hydroxytamoxifen (agonist/antagonist ligand). Positively regulated by the transcription factors SP1 and NF-Y. Ref.11 Ref.12
Involvement in disease	Defects in PHGDH are the cause of phosphoglycerate dehydrogenase deficiency (PHGDH deficiency) [MIM:601815]. It is characterized by congenital microcephaly, psychomotor retardation, and seizures.
Sequence similarities	Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.
Biophysicochemical properties	Kinetic parameters: KM=21.6 µM for 3-phosphohydroxypyruvate Vmax=35 nmol/min/mg enzyme with 3-phosphohydroxypyruvate as substrate (in patient-derived fibroblasts) Vmax=168 nmol/min/mg enzyme with 3-phosphohydroxypyruvate as substrate (in 3-PGDH overexpressed cells)

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Serine biosynthesis
Disease	Disease mutation
Ligand	NAD
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	L-serine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW brain development Traceable author statement. Source: ProtInc oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	NAD or NADH binding Inferred from electronic annotation. Source: InterPro electron carrier activity Traceable author statement. Source: UniProtKB phosphoglycerate dehydrogenase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8

Chain

2 – 533

532

D-3-phosphoglycerate dehydrogenase

PRO_0000076012

Regions

Nucleotide binding

155 – 156

2

NAD

Nucleotide binding

234 – 236

3

NAD

Nucleotide binding

283 – 286

4

NAD

Sites

Active site

236

1

Active site

265

1

By similarity

Active site

283

1

Proton donor

Binding site

78

1

NAD

Binding site

175

1

NAD

Binding site

207

1

NAD; via carbonyl oxygen

Binding site

260

1

NAD

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.8

Modified residue

371

1

Phosphoserine Ref.13

Natural variations

Natural variant

135

1

R → W in PHGDH deficiency; results in a 2-fold decrease in enzyme activity with 3-phosphohydroxypyruvate, but no change in substrate affinity. Ref.16

VAR_059026

Natural variant

261

1

V → M in PHGDH deficiency; results in a four-fold decrease in substrate affinity and a slight increase in maximal enzyme activity with 3-phosphohydroxypyruvate. Ref.16

VAR_059027

Natural variant

373

1

A → T in PHGDH deficiency; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. Ref.16

VAR_059028

Natural variant

377

1

G → S in PHGDH deficiency; results in a 2-fold decrease in enzyme activity with 3-phosphohydroxypyruvate, but no change in substrate affinity. Ref.16

VAR_059029

Natural variant

425

1

V → M in PHGDH deficiency; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. Ref.16 Ref.2

VAR_013461

Natural variant

490

1

V → M in PHGDH deficiency; results in almost undetectable enzyme activity with 3-phosphohydroxypyruvate. Ref.10 Ref.16 Ref.2

VAR_059030

Experimental info

Sequence conflict

25

1

D → E in AAB88664. Ref.1

Sequence conflict

25

1

D → E in AAD51415. Ref.1

Secondary structure

1

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533

Helix Strand Turn

Details...

Beta strand

8 – 11

4

Helix

18 – 26

9

Beta strand

29 – 32

4

Helix

38 – 44

7

Helix

45 – 47

3

Beta strand

49 – 53

5

Beta strand

55 – 57

3

Helix

61 – 66

6

Beta strand

72 – 79

8

Helix

85 – 91

7

Beta strand

94 – 96

3

Helix

103 – 119

17

Helix

121 – 129

9

Helix

136 – 138

3

Beta strand

147 – 151

5

Helix

155 – 165

11

Turn

166 – 168

3

Beta strand

170 – 174

5

Beta strand

176 – 178

3

Helix

180 – 185

6

Helix

193 – 196

4

Helix

197 – 199

3

Beta strand

201 – 205

5

Turn

211 – 215

5

Helix

219 – 222

4

Beta strand

229 – 233

5

Helix

242 – 251

10

Beta strand

252 – 260

9

Beta strand

263 – 266

4

Helix

271 – 274

4

Beta strand

278 – 280

3

Helix

289 – 306

18

Sequences

	Sequence		Length	Mass (Da)
	O43175-1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: C58EB72275C45B35	FASTA	533	56,651
	10 20 30 40 50 60 MAFANLRKVL ISDSLDPCCR KILQDGGLQV VEKQNLSKEE LIAELQDCEG LIVRSATKVT 70 80 90 100 110 120 ADVINAAEKL QVVGRAGTGV DNVDLEAATR KGILVMNTPN GNSLSAAELT CGMIMCLARQ 130 140 150 160 170 180 IPQATASMKD GKWERKKFMG TELNGKTLGI LGLGRIGREV ATRMQSFGMK TIGYDPIISP 190 200 210 220 230 240 EVSASFGVQQ LPLEEIWPLC DFITVHTPLL PSTTGLLNDN TFAQCKKGVR VVNCARGGIV 250 260 270 280 290 300 DEGALLRALQ SGQCAGAALD VFTEEPPRDR ALVDHENVIS CPHLGASTKE AQSRCGEEIA 310 320 330 340 350 360 VQFVDMVKGK SLTGVVNAQA LTSAFSPHTK PWIGLAEALG TLMRAWAGSP KGTIQVITQG 370 380 390 400 410 420 TSLKNAGNCL SPAVIVGLLK EASKQADVNL VNAKLLVKEA GLNVTTSHSP AAPGEQGFGE 430 440 450 460 470 480 CLLAVALAGA PYQAVGLVQG TTPVLQGLNG AVFRPEVPLR RDLPLLLFRT QTSDPAMLPT 490 500 510 520 530 MIGLLAEAGV RLLSYQTSLV SDGETWHVMG ISSLLPSLEA WKQHVTEAFQ FHF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence and differential expression of the human 3-phosphoglycerate dehydrogenase gene." Cho H.M., Jun D.Y., Bae M.A., Ahn J.D., Kim Y.H. Gene 245:193-201(2000) [PubMed: 10713460] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency -- a neurometabolic disorder associated with reduced L-serine biosynthesis." Klomp L.W.J., de Koning T.J., Malingre H.E.M., van Beurden E.A.C.M., Brink M., Opdam F.L., Duran M., Jaeken J., Pineda M., van Maldergem L., Poll-The B.T., van den Berg I.E.T., Berger R. Am. J. Hum. Genet. 67:1389-1399(2000) [PubMed: 11055895] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS PHGDH DEFICIENCY MET-425 AND MET-490.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Lung and Muscle.
[8]	Bienvenut W.V. Submitted (JAN-2010) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-54; 59-69; 76-119; 138-155; 237-289; 295-308; 352-380; 385-394; 462-491 AND 523-533, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: B-cell lymphoma and Ovarian carcinoma.
[9]	Lubec G., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 9-20; 22-33; 76-90; 248-268 AND 271-289. Tissue: Fetal brain cortex.
[10]	"V490M, a common mutation in 3-phosphoglycerate dehydrogenase deficiency, causes enzyme deficiency by decreasing the yield of mature enzyme." Pind S., Slominski E., Mauthe J., Pearlman K., Swoboda K.J., Wilkins J.A., Sauder P., Natowicz M.R. J. Biol. Chem. 277:7136-7143(2002) [PubMed: 11751922] [Abstract] Cited for: CATALYTIC ACTIVITY, VARIANT MET-490.
[11]	"Identification of novel proteins induced by estradiol, 4-hydroxytamoxifen and acolbifene in T47D breast cancer cells." Al-Dhaheri M.H., Shah Y.M., Basrur V., Pind S., Rowan B.G. Steroids 71:966-978(2006) [PubMed: 16949628] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, INDUCTION BY 17-BETA-ESTRADIOL AND 4-HYDROXYTAMOXIFEN.
[12]	"Positive regulation of promoter activity of human 3-phosphoglycerate dehydrogenase (PHGDH) gene is mediated by transcription factors Sp1 and NF-Y." Jun D.Y., Park H.S., Lee J.Y., Baek J.Y., Park H.-K., Fukui K., Kim Y.H. Gene 414:106-114(2008) [PubMed: 18378410] [Abstract] Cited for: INDUCTION BY SP1 AND NF-Y.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-371, MASS SPECTROMETRY.
[14]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[15]	"Crystal structure of human 3-phosphoglycerate dehydrogenase." Structural genomics consortium (SGC) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 4-314 IN COMPLEX WITH NAD AND SUBSTRATE.
[16]	"Novel mutations in 3-phosphoglycerate dehydrogenase (PHGDH) are distributed throughout the protein and result in altered enzyme kinetics." Tabatabaie L., de Koning T.J., Geboers A.J.J.M., van den Berg I.E.T., Berger R., Klomp L.W.J. Hum. Mutat. 30:749-756(2009) [PubMed: 19235232] [Abstract] Cited for: VARIANTS PHGDH DEFICIENCY TRP-135; MET-261; THR-373 AND SER-377, CHARACTERIZATION OF VARIANTS PHGDH DEFICIENCY TRP-135; MET-261; THR-373; SER-377; MET-425 AND MET-490, BIOPHYSICOCHEMICAL PROPERTIES.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00011200.

RefSeq

NP_006614.2.

UniGene

Hs.487296

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2G76	X-ray	1.70	A/B	4-314	[»]

SMR

O43175. Positions 7-516.

ModBase

Search...

Protein-protein interaction databases

IntAct

O43175. 5 interactions.

STRING

O43175.

PTM databases

PhosphoSite

O43175.

Proteomic databases

PeptideAtlas

O43175.

PRIDE

O43175.

Genome annotation databases

Ensembl

ENST00000369409; ENSP00000358417; ENSG00000092621; Homo sapiens. [Genome view]

GeneID

26227.

KEGG

hsa:26227.

NMPDR

fig|9606.3.peg.1817.

UCSC

uc001ehz.1. human.

Organism-specific databases

CTD

26227.

GeneCards

GC01P119966.

H-InvDB

HIX0000952.

HGNC

HGNC:8923. PHGDH.

HPA

CAB003681.
HPA021241.
HPA024031.

MIM

601815. phenotype.
606879. gene.

Orphanet

79351. 3-Phosphoglycerate dehydrogenase deficiency.
35705. Neurometabolic disorder due to serine deficiency.

PharmGKB

PA33264.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13949.

HOGENOM

HBG731446.

HOVERGEN

O43175.

InParanoid

O43175.

OMA

NDNTFAQ.

OrthoDB

EOG93N9ZD.

PhylomeDB

O43175.

Enzyme and pathway databases

BRENDA

1.1.1.95. 247.

Gene expression databases

ArrayExpress

O43175.

Bgee

O43175.

CleanEx

HS_PHGDH.

Genevestigator

O43175.

GermOnline

ENSG00000092621. Homo sapiens.

Family and domain databases

InterPro

IPR006236. D-3-Phosphoglycerate_DH.
IPR006139. D-isomer_2_OHA_DH_cat_dom.
IPR006140. D-isomer_2_OHA_DH_NAD-bd.
IPR015508. D3PG_DH.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

PANTHER

PTHR10996:SF20. D3PG_Deh. 1 hit.

Pfam

PF00389. 2-Hacid_dh. 1 hit.
PF02826. 2-Hacid_dh_C. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01327. PGDH. 1 hit.

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.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00157. NADH.

NextBio

48383.

SOURCE

Search...

Entry information

Entry name

SERA_HUMAN

Accession

Primary (citable) accession number: O43175
Secondary accession number(s): B2RD08, Q5SZU3, Q9BQ01

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 106 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.