Reviewed, UniProtKB/Swiss-Prot Q8N335 (GPD1L_HUMAN)

Names and origin

Protein names

Recommended name:
    Glycerol-3-phosphate dehydrogenase 1-like protein
    EC=1.1.1.8

Gene names

Name:	GPD1L
Synonyms:	KIAA0089

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	351 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	sn-glycerol 3-phosphate + NAD+ = glycerone phosphate + NADH.
Subcellular location	Cytoplasm. Note: Localized to the region of the plasma membrane. Ref.8
Tissue specificity	Most highly expressed in heart tissue, with lower levels in the skeletal muscle, kidney, lung and other organs. Ref.8
Involvement in disease	Defects in GPD1L are the cause of Brugada syndrome type 2 (BRS2) [MIM:611777]. BRS2 is an autosomal dominant tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs (called ventricular fibrillation), the individual will faint and may die in a few minutes if the heart is not reset. Ref.8 Defects in GPD1L are a cause of sudden infant death syndrome (SIDS) [MIM:272120]. SIDS is the sudden death of an infant younger than 1 year that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of clinical history. Pathophysiologic mechanisms for SIDS may include respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory instability, and inborn errors of metabolism, but definitive pathogenic mechanisms precipitating an infant sudden death remain elusive. Ref.7
Sequence similarities	Belongs to the NAD-dependent glycerol-3-phosphate dehydrogenase family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Brugada syndrome Disease mutation
Ligand	NAD
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro glycerol-3-phosphate catabolic process Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	glycerol-3-phosphate dehydrogenase complex Inferred from electronic annotation. Source: InterPro
Molecular function	NAD or NADH binding Inferred from electronic annotation. Source: InterPro glycerol-3-phosphate dehydrogenase (NAD+) activity Inferred from electronic annotation. Source: EC protein homodimerization activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 351

351

Glycerol-3-phosphate dehydrogenase 1-like protein

PRO_0000286511

Regions

Nucleotide binding

12 – 17

6

NAD

Region

271 – 272

2

Substrate binding

Sites

Active site

206

1

Proton acceptor

Binding site

43

1

NAD By similarity

Binding site

99

1

NAD By similarity

Binding site

122

1

Substrate By similarity

Binding site

155

1

NAD; via amide nitrogen

Binding site

271

1

NAD By similarity

Binding site

298

1

NAD; via amide nitrogen

Binding site

300

1

NAD By similarity

Natural variations

Natural variant

83

1

E → K in SIDS; significant reduction of sodium current when coexpressed with SCN5A in HEK cells. Ref.7

VAR_044044

Natural variant

124

1

I → V in SIDS; significant reduction of sodium current when coexpressed with SCN5A in HEK cells. Ref.7

VAR_044045

Natural variant

178

1

L → F: dbSNP rs35447795.

VAR_032114

Natural variant

273

1

R → C in SIDS; significant reduction of sodium current when coexpressed with SCN5A in HEK cells. Ref.7

VAR_044046

Natural variant

280

1

A → V in BRS2; affects SCN5A membrane expression; reduction of sodium current when coexpressed with SCN5A in HEK cells. Ref.8

VAR_044047

Secondary structure

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351

Helix Strand Turn

Details...

Beta strand

8 – 11

4

Helix

15 – 28

14

Beta strand

38 – 41

4

Helix

52 – 59

8

Turn

63 – 65

3

Beta strand

75 – 79

5

Helix

81 – 85

5

Beta strand

89 – 93

5

Helix

97 – 99

3

Helix

100 – 107

8

Beta strand

116 – 119

4

Beta strand

124 – 127

4

Beta strand

130 – 133

4

Helix

134 – 142

9

Beta strand

144 – 152

9

Helix

155 – 159

5

Beta strand

164 – 169

6

Helix

173 – 183

11

Beta strand

188 – 194

7

Helix

196 – 218

23

Helix

223 – 244

22

Beta strand

245 – 247

3

Helix

251 – 254

4

Turn

257 – 259

3

Helix

260 – 269

10

Helix

271 – 282

12

Helix

286 – 294

9

Helix

301 – 315

15

Helix

318 – 320

3

Helix

322 – 332

11

Helix

339 – 345

7

Sequences

	Sequence		Length	Mass (Da)
	Q8N335-1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 74C3B27EEB41DE89	FASTA	351	38,419
	10 20 30 40 50 60 MAAAPLKVCI VGSGNWGSAV AKIIGNNVKK LQKFASTVKM WVFEETVNGR KLTDIINNDH 70 80 90 100 110 120 ENVKYLPGHK LPENVVAMSN LSEAVQDADL LVFVIPHQFI HRICDEITGR VPKKALGITL 130 140 150 160 170 180 IKGIDEGPEG LKLISDIIRE KMGIDISVLM GANIANEVAA EKFCETTIGS KVMENGLLFK 190 200 210 220 230 240 ELLQTPNFRI TVVDDADTVE LCGALKNIVA VGAGFCDGLR CGDNTKAAVI RLGLMEMIAF 250 260 270 280 290 300 ARIFCKGQVS TATFLESCGV ADLITTCYGG RNRRVAEAFA RTGKTIEELE KEMLNGQKLQ 310 320 330 340 350 GPQTSAEVYR ILKQKGLLDK FPLFTAVYQI CYESRPVQEM LSCLQSHPEH T

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1." Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S., Tabata S., Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N. DNA Res. 2:37-43(1995) [PubMed: 7788527] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow.
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	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].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Placenta.
[5]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[6]	"Crystal structure of human glycerol-3-phosphate dehydrogenase 1-like protein." Structural genomics consortium (SGC) Submitted (MAY-2007) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 1-349 IN COMPLEX WITH NAD AND PHOSPHATE IONS.
[7]	"Molecular and functional characterization of novel glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) mutations in sudden infant death syndrome." Van Norstrand D.W., Valdivia C.R., Tester D.J., Ueda K., London B., Makielski J.C., Ackerman M.J. Circulation 116:2253-2259(2007) [PubMed: 17967976] [Abstract] Cited for: VARIANTS SIDS LYS-83; VAL-124 AND CYS-273, CHARACTERIZATION OF VARIANTS SIDS LYS-83; VAL-124 AND CYS-273.
[8]	"Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias." London B., Michalec M., Mehdi H., Zhu X., Kerchner L., Sanyal S., Viswanathan P.C., Pfahnl A.E., Shang L.L., Madhusudanan M., Baty C.J., Lagana S., Aleong R., Gutmann R., Ackerman M.J., McNamara D.M., Weiss R., Dudley S.C. Jr. Circulation 116:2260-2268(2007) [PubMed: 17967977] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, VARIANT BRS2 VAL-280, CHARACTERIZATION OF VARIANT BRS2 VAL-280.

Cross-references

Sequence databases

EMBLGenBankDDBJ

D42047 mRNA. Translation: BAA07648.1. Different initiation.
AK292808 mRNA. Translation: BAF85497.1.
CH471055 Genomic DNA. Translation: EAW64422.1.
BC006168 mRNA. Translation: AAH06168.1.
BC028726 mRNA. Translation: AAH28726.1.

IPI

IPI00032959.

RefSeq

NP_055956.1.

UniGene

Hs.82432

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2PLA	X-ray	2.51	A/B	1-349	[»]

ModBase

Search...

Proteomic databases

PeptideAtlas

Q8N335.

PRIDE

Q8N335.

Genome annotation databases

Ensembl

ENSG00000152642. Homo sapiens. [Contig view]

GeneID

23171.

KEGG

hsa:23171.

NMPDR

fig|9606.3.peg.22252.

UCSC

uc003cew.1. human.

Organism-specific databases

GeneCards

GC03P032123.

HGNC

HGNC:28956. GPD1L.

MIM

272120. phenotype.
611777. phenotype.
611778. gene.

PharmGKB

PA134986345.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q8N335.

OMA

Q8N335. AKIFCKG.

Enzyme and pathway databases

BRENDA

1.1.1.8. 247.

Gene expression databases

ArrayExpress

Q8N335.

Bgee

Q8N335.

CleanEx

HS_GPD1L.

Family and domain databases

InterPro

IPR013328. DH_multihelical.
IPR016040. NAD(P)-bd_dom.
IPR006168. NAD-dep_Gly3P_DH.
IPR017751. NAD-dep_Gly3P_DH_euk.
IPR011128. NAD-dep_Gly3P_DH_N.
IPR006109. NAD_Gly3P_DH_C.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
G3DSA:1.10.1040.10. Opine_DH. 1 hit.

PANTHER

PTHR11728. NAD_Gly3P_DH. 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.

ProDom

PD001278. NAD_Gly3P_C. 1 hit.
[Graphical view] [Entries sharing at least one domain]

TIGRFAMs

TIGR03376. glycerol3P_DH. 1 hit.

PROSITE

PS00957. NAD_G3PDH. False negative.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

44579.

SOURCE

Search...

Entry information

Entry name

GPD1L_HUMAN

Accession

Primary (citable) accession number: Q8N335
Secondary accession number(s): A8K9U3, Q14702, Q9BRM5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 15, 2007
Last sequence update:	October 1, 2002
Last modified:	July 7, 2009
This is version 61 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)