P21695 (GPDA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glycerol-3-phosphate dehydrogenase [NAD(+)], cytoplasmic
Short name=GPD-C
Short name=GPDH-C
EC=1.1.1.8

Gene names

Name:

GPD1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	349 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	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 component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	NAD
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	NADH oxidation Inferred from electronic annotation. Source: Compara cellular response to cAMP Inferred from electronic annotation. Source: Compara cellular response to tumor necrosis factor Inferred from electronic annotation. Source: Compara gluconeogenesis Inferred from electronic annotation. Source: Compara glycerol-3-phosphate catabolic process Inferred from electronic annotation. Source: InterPro phosphatidic acid biosynthetic process Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome triglyceride biosynthetic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome glycerol-3-phosphate dehydrogenase complex Inferred from electronic annotation. Source: InterPro mitochondrion Inferred from electronic annotation. Source: Compara
Molecular_function	NAD binding Inferred from electronic annotation. Source: Compara glycerol-3-phosphate dehydrogenase [NAD+] activity Traceable author statement Ref.1. Source: ProtInc glycerol-3-phosphate dehydrogenase activity Inferred from electronic annotation. Source: Compara
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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 349

348

Glycerol-3-phosphate dehydrogenase [NAD(+)], cytoplasmic

PRO_0000138079

Regions

Nucleotide binding

10 – 15

6

NAD

Region

269 – 270

2

Substrate binding

Sites

Active site

204

1

Proton acceptor Probable

Binding site

41

1

NAD

Binding site

97

1

NAD

Binding site

120

1

Substrate

Binding site

153

1

NAD; via amide nitrogen

Binding site

269

1

NAD

Binding site

296

1

NAD; via amide nitrogen

Binding site

298

1

NAD

Natural variations

Alternative sequence

74 – 96

23

Missing in isoform 2.

VSP_045999

Natural variant

54

1

I → V. Ref.7
Corresponds to variant rs2232202 [ dbSNP | Ensembl ].

VAR_029492

Natural variant

113

1

A → P. Ref.1
Corresponds to variant rs1128867 [ dbSNP | Ensembl ].

VAR_029493

Natural variant

124

1

E → K. Ref.7
Corresponds to variant rs34783513 [ dbSNP | Ensembl ].

VAR_067425

Natural variant

197

1

V → A. Ref.7
Corresponds to variant rs2232207 [ dbSNP | Ensembl ].

VAR_049220

Natural variant

223

1

T → I. Ref.7

VAR_067426

Secondary structure

1

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349

Helix Strand Turn

Details...

Beta strand

4 – 9

6

Helix

13 – 28

16

Beta strand

32 – 39

8

Beta strand

44 – 49

6

Helix

50 – 57

8

Turn

61 – 63

3

Beta strand

73 – 78

6

Helix

79 – 83

5

Beta strand

87 – 91

5

Helix

95 – 97

3

Helix

98 – 105

8

Beta strand

114 – 117

4

Beta strand

124 – 128

5

Helix

132 – 140

9

Beta strand

144 – 148

5

Helix

153 – 157

5

Beta strand

162 – 167

6

Helix

171 – 181

11

Beta strand

186 – 192

7

Helix

194 – 216

23

Helix

221 – 242

22

Beta strand

243 – 245

3

Helix

249 – 253

5

Turn

255 – 257

3

Helix

258 – 267

10

Helix

269 – 280

12

Helix

284 – 291

8

Helix

298 – 313

16

Helix

316 – 318

3

Helix

320 – 330

11

Helix

335 – 338

4

Helix

339 – 343

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 20, 2007. Version 4. Checksum: CE7B7681103076EF	FASTA	349	37,568
	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
	Isoform 2 [UniParc]. Checksum: 61562929C503DB70	FASTA	326	35,140
	10 20 30 40 50 60 MASKKVCIVG SGNWGSAIAK IVGGNAAQLA QFDPRVTMWV FEEDIGGKKL TEIINTQHEN 70 80 90 100 110 120 VKYLPGHKLP PNVFIGKICD QLKGHLKANA TGISLIKGVD EGPNGLKLIS EVIGERLGIP 130 140 150 160 170 180 MSVLMGANIA SEVADEKFCE TTIGCKDPAQ GQLLKELMQT PNFRITVVQE VDTVEICGAL 190 200 210 220 230 240 KNVVAVGAGF CDGLGFGDNT KAAVIRLGLM EMIAFAKLFC SGPVSSATFL ESCGVADLIT 250 260 270 280 290 300 TCYGGRNRKV AEAFARTGKS IEQLEKELLN GQKLQGPETA RELYSILQHK GLVDKFPLFM 310 320 AVYKVCYEGQ PVGEFIHCLQ NHPEHM

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

IPI

IPI00295777.
IPI01020783.

PIR

S55920.

RefSeq

NP_001244128.1. NM_001257199.1.
NP_005267.2. NM_005276.3.

UniGene

Hs.524418.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WPQ	X-ray	2.50	A/B	1-349	[»]
1X0V	X-ray	2.30	A/B	1-349	[»]
1X0X	X-ray	2.75	A	1-349	[»]

ProteinModelPortal

P21695.

ModBase

Search...

Protein-protein interaction databases

IntAct

P21695. 3 interactions.

MINT

MINT-1429375.

STRING

9606.ENSP00000301149.

PTM databases

PhosphoSite

P21695.

Polymorphism databases

DMDM

134047785.

Proteomic databases

PaxDb

P21695.

PRIDE

P21695.

Protocols and materials databases

DNASU

2819.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000301149; ENSP00000301149; ENSG00000167588.
ENST00000548814; ENSP00000446768; ENSG00000167588.

GeneID

2819.

KEGG

hsa:2819.

UCSC

uc001rvz.3. human.

Organism-specific databases

CTD

2819.

GeneCards

GC12P050497.

HGNC

HGNC:4455. GPD1.

HPA

HPA044620.

MIM

138420. gene.
614480. phenotype.

neXtProt

NX_P21695.

Orphanet

300293. Infantile regressive hypertriglyceridemia and hepatosteatosis.

PharmGKB

PA28836.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0240.

HOGENOM

HOG000246855.

HOVERGEN

HBG003669.

InParanoid

P21695.

KO

K00006.

OMA

PVGEFIH.

OrthoDB

EOG4WQ12X.

Enzyme and pathway databases

BioCyc

MetaCyc:HS09586-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P21695.

Gene expression databases

ArrayExpress

P21695.

Bgee

P21695.

CleanEx

HS_GPD1.

Genevestigator

P21695.

GermOnline

ENSG00000167588. Homo sapiens.

Family and domain databases

Gene3D

1.10.1040.10. 1 hit.
3.40.50.720. 1 hit.

InterPro

IPR008927. 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]

PANTHER

PTHR11728. PTHR11728. 1 hit.

Pfam

PF07479. NAD_Gly3P_dh_C. 1 hit.
PF01210. NAD_Gly3P_dh_N. 1 hit.
[Graphical view]

PIRSF

PIRSF000114. Glycerol-3-P_dh. 1 hit.

PRINTS

PR00077. GPDHDRGNASE.

SUPFAM

SSF48179. 6DGDH_C_like. 1 hit.

TIGRFAMs

TIGR03376. glycerol3P_DH. 1 hit.

PROSITE

PS00957. NAD_G3PDH. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00157. NADH.

EvolutionaryTrace

P21695.

GenomeRNAi

2819.

NextBio

11107.

SOURCE

Search...

Entry information

Entry name

GPDA_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 130 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.