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P21695 (GPDA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glycerol-3-phosphate dehydrogenase [NAD(+)], cytoplasmic

Short name=GPD-C
Short name=GPDH-C
EC=1.1.1.8
Gene names
Name:GPD1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length349 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

sn-glycerol 3-phosphate + NAD+ = glycerone phosphate + NADH.

Enzyme regulation

Inhibited by zinc ions and sulfate. Ref.8

Subunit structure

Homodimer. Ref.8

Subcellular location

Cytoplasm.

Involvement in disease

Hypertriglyceridemia, transient infantile (HTGTI) [MIM:614480]: An autosomal recessive disorder characterized by onset of moderate to severe transient hypertriglyceridemia in infancy that normalizes with age. The hypertriglyceridemia is associated with hepatomegaly, moderately elevated transaminases, persistent fatty liver, and the development of hepatic fibrosis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Belongs to the NAD-dependent glycerol-3-phosphate dehydrogenase family.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandNAD
   Molecular functionOxidoreductase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNADH oxidation

Inferred from electronic annotation. Source: Ensembl

cellular lipid metabolic process

Traceable author statement. Source: Reactome

cellular response to cAMP

Inferred from electronic annotation. Source: Ensembl

cellular response to tumor necrosis factor

Inferred from electronic annotation. Source: Ensembl

gluconeogenesis

Inferred from electronic annotation. Source: Ensembl

glycerol-3-phosphate catabolic process

Inferred from electronic annotation. Source: InterPro

glycerophospholipid biosynthetic process

Traceable author statement. Source: Reactome

phosphatidic acid biosynthetic process

Traceable author statement. Source: Reactome

phospholipid metabolic process

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

triglyceride biosynthetic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

glycerol-3-phosphate dehydrogenase complex

Inferred from electronic annotation. Source: InterPro

mitochondrion

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionNAD binding

Inferred from electronic annotation. Source: Ensembl

glycerol-3-phosphate dehydrogenase [NAD+] activity

Traceable author statement Ref.1. Source: ProtInc

glycerol-3-phosphate dehydrogenase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P21695-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P21695-2)

The sequence of this isoform differs from the canonical sequence as follows:
     74-96: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 349349Glycerol-3-phosphate dehydrogenase [NAD(+)], cytoplasmic
PRO_0000138079

Regions

Nucleotide binding10 – 156NAD
Region269 – 2702Substrate binding

Sites

Active site2041Proton acceptor Probable
Binding site411NAD
Binding site971NAD
Binding site1201Substrate
Binding site1531NAD; via amide nitrogen
Binding site2691NAD
Binding site2961NAD; via amide nitrogen
Binding site2981NAD

Amino acid modifications

Modified residue2891N6-succinyllysine By similarity

Natural variations

Alternative sequence74 – 9623Missing in isoform 2.
VSP_045999
Natural variant541I → V. Ref.7
Corresponds to variant rs2232202 [ dbSNP | Ensembl ].
VAR_029492
Natural variant1131A → P. Ref.1
Corresponds to variant rs1128867 [ dbSNP | Ensembl ].
VAR_029493
Natural variant1241E → K. Ref.7
Corresponds to variant rs34783513 [ dbSNP | Ensembl ].
VAR_067425
Natural variant1971V → A. Ref.7
Corresponds to variant rs2232207 [ dbSNP | Ensembl ].
VAR_049220
Natural variant2231T → I. Ref.7
VAR_067426

Secondary structure

........................................................... 349
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 20, 2007. Version 4.
Checksum: CE7B7681103076EF

FASTA34937,568
        10         20         30         40         50         60 
MASKKVCIVG SGNWGSAIAK IVGGNAAQLA QFDPRVTMWV FEEDIGGKKL TEIINTQHEN 

        70         80         90        100        110        120 
VKYLPGHKLP PNVVAVPDVV QAAEDADILI FVVPHQFIGK ICDQLKGHLK ANATGISLIK 

       130        140        150        160        170        180 
GVDEGPNGLK LISEVIGERL GIPMSVLMGA NIASEVADEK FCETTIGCKD PAQGQLLKEL 

       190        200        210        220        230        240 
MQTPNFRITV VQEVDTVEIC GALKNVVAVG AGFCDGLGFG DNTKAAVIRL GLMEMIAFAK 

       250        260        270        280        290        300 
LFCSGPVSSA TFLESCGVAD LITTCYGGRN RKVAEAFART GKSIEQLEKE LLNGQKLQGP 

       310        320        330        340 
ETARELYSIL QHKGLVDKFP LFMAVYKVCY EGQPVGEFIH CLQNHPEHM 

« Hide

Isoform 2 [UniParc].

Checksum: 61562929C503DB70
Show »

FASTA32635,140

References

« Hide 'large scale' references
[1]"Molecular cloning, sequencing and expression of a cDNA encoding a human liver NAD-dependent alpha-glycerol-3-phosphate dehydrogenase."
Menaya J., Gonzalez-Manchon C., Parrilla R., Ayuso M.S.
Biochim. Biophys. Acta 1262:91-94(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT PRO-113.
Tissue: Liver.
[2]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Macrophage.
[3]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Pancreas.
[5]"Sequence conservation and structural organization of the glycerol-3-phosphate dehydrogenase promoter in mice and humans."
Gwynn B., Lyford K.L., Birkenmeier E.H.
Mol. Cell. Biol. 10:5244-5256(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-14.
Tissue: Fetal liver.
[6]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"Transient infantile hypertriglyceridemia, fatty liver, and hepatic fibrosis caused by mutated GPD1, encoding glycerol-3-phosphate dehydrogenase 1."
Basel-Vanagaite L., Zevit N., Zahav A.H., Guo L., Parathath S., Pasmanik-Chor M., McIntyre A.D., Wang J., Albin-Kaplanski A., Hartman C., Marom D., Zeharia A., Badir A., Shoerman O., Simon A.J., Rechavi G., Shohat M., Hegele R.A., Fisher E.A., Shamir R.
Am. J. Hum. Genet. 90:49-60(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN HTGTI, VARIANTS VAL-54; LYS-124; ALA-197 AND ILE-223.
[8]"Crystal structures of human glycerol 3-phosphate dehydrogenase 1 (GPD1)."
Ou X., Ji C., Han X., Zhao X., Li X., Mao Y., Wong L.-L., Bartlam M., Rao Z.
J. Mol. Biol. 357:858-869(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH NAD, SUBUNIT, ENZYME REGULATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L34041 mRNA. Translation: AAA92863.1.
AK130162 mRNA. No translation available.
AC025154 Genomic DNA. No translation available.
BC032234 mRNA. Translation: AAH32234.1.
M36917 Genomic DNA. Translation: AAA35925.1.
PIRS55920.
RefSeqNP_001244128.1. NM_001257199.1.
NP_005267.2. NM_005276.3.
UniGeneHs.524418.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WPQX-ray2.50A/B1-349[»]
1X0VX-ray2.30A/B1-349[»]
1X0XX-ray2.75A1-349[»]
ProteinModelPortalP21695.
SMRP21695. Positions 1-349.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109080. 2 interactions.
IntActP21695. 3 interactions.
MINTMINT-1429375.
STRING9606.ENSP00000301149.

Chemistry

DrugBankDB00157. NADH.

PTM databases

PhosphoSiteP21695.

Polymorphism databases

DMDM134047785.

Proteomic databases

PaxDbP21695.
PRIDEP21695.

Protocols and materials databases

DNASU2819.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000301149; ENSP00000301149; ENSG00000167588. [P21695-1]
ENST00000548814; ENSP00000446768; ENSG00000167588. [P21695-2]
GeneID2819.
KEGGhsa:2819.
UCSCuc001rvz.4. human. [P21695-1]

Organism-specific databases

CTD2819.
GeneCardsGC12P050497.
HGNCHGNC:4455. GPD1.
HPAHPA044620.
MIM138420. gene.
614480. phenotype.
neXtProtNX_P21695.
Orphanet300293. Infantile regressive hypertriglyceridemia and hepatosteatosis.
PharmGKBPA28836.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0240.
HOGENOMHOG000246855.
HOVERGENHBG003669.
InParanoidP21695.
KOK00006.
OMAHILPFAR.
OrthoDBEOG7ZKSBS.
PhylomeDBP21695.
TreeFamTF300836.

Enzyme and pathway databases

BioCycMetaCyc:HS09586-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP21695.

Gene expression databases

ArrayExpressP21695.
BgeeP21695.
CleanExHS_GPD1.
GenevestigatorP21695.

Family and domain databases

Gene3D1.10.1040.10. 1 hit.
3.40.50.720. 1 hit.
InterProIPR008927. 6-PGluconate_DH_C-like.
IPR013328. DH_multihelical.
IPR006168. G3P_DH_NAD-dep.
IPR006109. G3P_DH_NAD-dep_C.
IPR017751. G3P_DH_NAD-dep_euk.
IPR011128. G3P_DH_NAD-dep_N.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PANTHERPTHR11728. PTHR11728. 1 hit.
PfamPF07479. NAD_Gly3P_dh_C. 1 hit.
PF01210. NAD_Gly3P_dh_N. 1 hit.
[Graphical view]
PIRSFPIRSF000114. Glycerol-3-P_dh. 1 hit.
PRINTSPR00077. GPDHDRGNASE.
SUPFAMSSF48179. SSF48179. 1 hit.
TIGRFAMsTIGR03376. glycerol3P_DH. 1 hit.
PROSITEPS00957. NAD_G3PDH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP21695.
GenomeRNAi2819.
NextBio11107.
PROP21695.
SOURCESearch...

Entry information

Entry nameGPDA_HUMAN
AccessionPrimary (citable) accession number: P21695
Secondary accession number(s): F8W1L5, Q8N1B0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: March 20, 2007
Last modified: April 16, 2014
This is version 140 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM