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Q8N335 (GPD1L_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 108. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glycerol-3-phosphate dehydrogenase 1-like protein

Short name=GPD1-L
EC=1.1.1.8
Gene names
Name:GPD1L
Synonyms:KIAA0089
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length351 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a role in regulating cardiac sodium current; decreased enzymatic activity with resulting increased levels of glycerol 3-phosphate activating the DPD1L-dependent SCN5A phosphorylation pathway, may ultimately lead to decreased sodium current; cardiac sodium current may also be reduced due to alterations of NAD(H) balance induced by DPD1L. Ref.5 Ref.6

Catalytic activity

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

Subunit structure

Interacts with SCN5A. Ref.5

Subcellular location

Cytoplasm. Note: Localized to the region of the plasma membrane. Ref.10

Tissue specificity

Most highly expressed in heart tissue, with lower levels in the skeletal muscle, kidney, lung and other organs. Ref.10

Involvement in disease

Brugada syndrome 2 (BRGDA2) [MIM:611777]: A 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, the individual will faint and may die in a few minutes if the heart is not reset.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.9

Sequence similarities

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

Sequence caution

The sequence BAA07648.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DiseaseBrugada syndrome
Disease mutation
   LigandNAD
   Molecular functionOxidoreductase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNAD metabolic process

Inferred from mutant phenotype Ref.6. Source: BHF-UCL

NADH metabolic process

Inferred from electronic annotation. Source: Ensembl

carbohydrate metabolic process

Inferred from electronic annotation. Source: InterPro

cellular lipid metabolic process

Traceable author statement. Source: Reactome

glycerol-3-phosphate catabolic process

Inferred from electronic annotation. Source: InterPro

glycerophospholipid biosynthetic process

Traceable author statement. Source: Reactome

negative regulation of peptidyl-serine phosphorylation

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

negative regulation of protein kinase C signaling

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

phosphatidic acid biosynthetic process

Traceable author statement. Source: Reactome

phospholipid metabolic process

Traceable author statement. Source: Reactome

positive regulation of protein localization to cell surface

Inferred from mutant phenotype Ref.10Ref.5. Source: BHF-UCL

positive regulation of sodium ion transport

Inferred from mutant phenotype Ref.10Ref.5Ref.6. Source: BHF-UCL

regulation of heart rate

Inferred from mutant phenotype Ref.10Ref.5. Source: BHF-UCL

regulation of sodium ion transmembrane transporter activity

Inferred from mutant phenotype Ref.10Ref.5. Source: BHF-UCL

regulation of ventricular cardiac muscle cell membrane depolarization

Inferred from mutant phenotype Ref.10Ref.5. Source: BHF-UCL

small molecule metabolic process

Traceable author statement. Source: Reactome

triglyceride biosynthetic process

Traceable author statement. Source: Reactome

ventricular cardiac muscle cell action potential

Inferred from mutant phenotype Ref.10Ref.5. Source: BHF-UCL

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

glycerol-3-phosphate dehydrogenase complex

Inferred from electronic annotation. Source: InterPro

plasma membrane

Inferred from direct assay Ref.10. Source: BHF-UCL

   Molecular_functionNAD binding

Inferred from electronic annotation. Source: InterPro

glycerol-3-phosphate dehydrogenase [NAD+] activity

Inferred from electronic annotation. Source: UniProtKB-EC

ion channel binding

Inferred from physical interaction Ref.5. Source: BHF-UCL

sodium channel regulator activity

Inferred from mutant phenotype Ref.10Ref.5. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 351351Glycerol-3-phosphate dehydrogenase 1-like protein
PRO_0000286511

Regions

Nucleotide binding12 – 176NAD
Region271 – 2722Substrate binding

Sites

Active site2061Proton acceptor
Binding site431NAD By similarity
Binding site991NAD By similarity
Binding site1221Substrate By similarity
Binding site1551NAD; via amide nitrogen
Binding site2711NAD By similarity
Binding site2981NAD; via amide nitrogen
Binding site3001NAD By similarity

Natural variations

Natural variant831E → K in SIDS; decreased enzymatic activity and significant reduction of sodium current when coexpressed with SCN5A in HEK cells. Ref.5 Ref.9
VAR_044044
Natural variant1241I → V in SIDS; significant reduction of sodium current when coexpressed with SCN5A in HEK cells. Ref.9
Corresponds to variant rs72552293 [ dbSNP | Ensembl ].
VAR_044045
Natural variant1781L → F.
Corresponds to variant rs35447795 [ dbSNP | Ensembl ].
VAR_032114
Natural variant2731R → C in SIDS; significant reduction of sodium current when coexpressed with SCN5A in HEK cells. Ref.9
VAR_044046
Natural variant2801A → V in BRGDA2; decreased enzymatic activity; affects SCN5A membrane expression; reduction of sodium current when coexpressed with SCN5A in HEK cells. Ref.5 Ref.6 Ref.10
VAR_044047

Secondary structure

........................................................... 351
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8N335 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 74C3B27EEB41DE89

FASTA35138,419
        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 

« Hide

References

« Hide '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] [Europe PMC] [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. 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].
[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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain and Placenta.
[5]"GPD1L links redox state to cardiac excitability by PKC-dependent phosphorylation of the sodium channel SCN5A."
Valdivia C.R., Ueda K., Ackerman M.J., Makielski J.C.
Am. J. Physiol. 297:H1446-H1452(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS LYS-83 AND VAL-280, INTERACTION WITH SCN5A.
[6]"Cardiac Na+ current regulation by pyridine nucleotides."
Liu M., Sanyal S., Gao G., Gurung I.S., Zhu X., Gaconnet G., Kerchner L.J., Shang L.L., Huang C.L., Grace A., London B., Dudley S.C. Jr.
Circ. Res. 105:737-745(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CHARACTERIZATION OF VARIANT VAL-280.
[7]"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].
[8]"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.
[9]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS SIDS LYS-83; VAL-124 AND CYS-273, CHARACTERIZATION OF VARIANTS SIDS LYS-83; VAL-124 AND CYS-273.
[10]"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] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, VARIANT BRGDA2 VAL-280, CHARACTERIZATION OF VARIANT BRGDA2 VAL-280.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_055956.1. NM_015141.3.
UniGeneHs.82432.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2PLAX-ray2.51A/B1-349[»]
ProteinModelPortalQ8N335.
SMRQ8N335. Positions 4-346.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116783. 3 interactions.
STRING9606.ENSP00000282541.

PTM databases

PhosphoSiteQ8N335.

Polymorphism databases

DMDM74750945.

Proteomic databases

PaxDbQ8N335.
PeptideAtlasQ8N335.
PRIDEQ8N335.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000282541; ENSP00000282541; ENSG00000152642.
GeneID23171.
KEGGhsa:23171.
UCSCuc003cew.3. human.

Organism-specific databases

CTD23171.
GeneCardsGC03P032123.
HGNCHGNC:28956. GPD1L.
HPAHPA035284.
MIM272120. phenotype.
611777. phenotype.
611778. gene.
neXtProtNX_Q8N335.
Orphanet130. Brugada syndrome.
PharmGKBPA134986345.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0240.
HOGENOMHOG000246855.
HOVERGENHBG003669.
InParanoidQ8N335.
KOK00006.
OMAKIFCKGQ.
PhylomeDBQ8N335.
TreeFamTF300836.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ8N335.
BgeeQ8N335.
CleanExHS_GPD1L.
GenevestigatorQ8N335.

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.
ProtoNetSearch...

Other

ChiTaRSGPD1L. human.
EvolutionaryTraceQ8N335.
GenomeRNAi23171.
NextBio44579.
PROQ8N335.
SOURCESearch...

Entry information

Entry nameGPD1L_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 108 of the entry and version 1 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 3

Human chromosome 3: entries, gene names and cross-references to MIM