Full text data of GPD2
GPD2
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Glycerol-3-phosphate dehydrogenase, mitochondrial; GPD-M; GPDH-M; 1.1.5.3 (mtGPD; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Glycerol-3-phosphate dehydrogenase, mitochondrial; GPD-M; GPDH-M; 1.1.5.3 (mtGPD; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Comments
Isoform P43304-2 was detected.
Isoform P43304-2 was detected.
UniProt
P43304
ID GPDM_HUMAN Reviewed; 727 AA.
AC P43304; A8K4V0; B3KSA9; Q59FR1; Q9HAP9;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-MAY-2009, sequence version 3.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=Glycerol-3-phosphate dehydrogenase, mitochondrial;
DE Short=GPD-M;
DE Short=GPDH-M;
DE EC=1.1.5.3;
DE AltName: Full=mtGPD;
DE Flags: Precursor;
GN Name=GPD2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS HIS-264 AND
RP HIS-525.
RX PubMed=7821823; DOI=10.1016/0378-1119(94)90469-3;
RA Lehn D.A., Brown L.J., Simonson G.D., Moran S.M., McDonald M.J.;
RT "The sequence of a human mitochondrial glycerol-3-phosphate
RT dehydrogenase-encoding cDNA.";
RL Gene 150:417-418(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT HIS-264.
RX PubMed=8549872; DOI=10.2337/diab.45.2.262;
RA Ferrer J., Aoki M., Behn P., Nestorowicz A., Riggs A., Permutt M.A.;
RT "Mitochondrial glycerol-3-phosphate dehydrogenase. Cloning of an
RT alternatively spliced human islet-cell cDNA, tissue distribution,
RT physical mapping, and identification of a polymorphic genetic
RT marker.";
RL Diabetes 45:262-266(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-264.
RX PubMed=8682323; DOI=10.1016/0378-1119(96)00019-4;
RA Brown L.J., Stoffel M., Moran S.M., Fernald A.A., Lehn D.A.,
RA LeBeau M.M., MacDonald M.J.;
RT "Structural organization and mapping of the human mitochondrial
RT glycerol phosphate dehydrogenase-encoding gene and pseudogene.";
RL Gene 172:309-312(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS HIS-264 AND
RP HIS-525.
RC TISSUE=Testis;
RA Yin L.L., Li J.M., Sha J.H.;
RT "A novel glycerol-3-phosphate dehydrogenase 3 from adult testis.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP HIS-264.
RC TISSUE=Testis, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP HIS-264.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT HIS-264.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-408, AND VARIANT HIS-264.
RC TISSUE=Brain;
RX PubMed=9110174;
RA Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W.,
RA Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.;
RT "Large-scale concatenation cDNA sequencing.";
RL Genome Res. 7:353-358(1997).
RN [10]
RP PROTEIN SEQUENCE OF 212-227 AND 558-572, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [11]
RP PROTEIN SEQUENCE OF 340-348; 410-418; 526-538; 558-572 AND 715-722,
RP AND MASS SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (JAN-2006) to UniProtKB.
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- CATALYTIC ACTIVITY: sn-glycerol 3-phosphate + a quinone =
CC glycerone phosphate + a quinol.
CC -!- COFACTOR: FAD.
CC -!- ENZYME REGULATION: Calcium-binding enhance the activity of the
CC enzyme.
CC -!- PATHWAY: Polyol metabolism; glycerol degradation via glycerol
CC kinase pathway; glycerone phosphate from sn-glycerol 3-phosphate
CC (anaerobic route): step 1/1.
CC -!- SUBCELLULAR LOCATION: Mitochondrion.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P43304-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P43304-2; Sequence=VSP_017134;
CC -!- SIMILARITY: Belongs to the FAD-dependent glycerol-3-phosphate
CC dehydrogenase family.
CC -!- SIMILARITY: Contains 2 EF-hand domains.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92636.1; Type=Erroneous initiation;
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DR EMBL; U12424; AAA65701.1; -; mRNA.
DR EMBL; U36310; AAB60403.1; -; mRNA.
DR EMBL; U40367; AAC50556.1; -; Genomic_DNA.
DR EMBL; U40353; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40354; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40355; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40357; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40358; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40359; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40360; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40361; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40362; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40363; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40364; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40365; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; AF311325; AAG33851.1; -; mRNA.
DR EMBL; AK093198; BAG52671.1; -; mRNA.
DR EMBL; AK291065; BAF83754.1; -; mRNA.
DR EMBL; AK292817; BAF85506.1; -; mRNA.
DR EMBL; AB209399; BAD92636.1; ALT_INIT; mRNA.
DR EMBL; AC011308; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092686; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471058; EAX11453.1; -; Genomic_DNA.
DR EMBL; U79250; AAB50200.1; -; mRNA.
DR PIR; G02093; G02093.
DR RefSeq; NP_000399.3; NM_000408.4.
DR RefSeq; NP_001076581.2; NM_001083112.2.
DR RefSeq; XP_005246526.1; XM_005246469.1.
DR UniGene; Hs.512382; -.
DR ProteinModelPortal; P43304; -.
DR SMR; P43304; 63-693.
DR IntAct; P43304; 1.
DR MINT; MINT-4530883; -.
DR STRING; 9606.ENSP00000308610; -.
DR PhosphoSite; P43304; -.
DR DMDM; 229462943; -.
DR REPRODUCTION-2DPAGE; IPI00017895; -.
DR UCD-2DPAGE; P43304; -.
DR PaxDb; P43304; -.
DR PRIDE; P43304; -.
DR Ensembl; ENST00000310454; ENSP00000308610; ENSG00000115159.
DR Ensembl; ENST00000409674; ENSP00000386425; ENSG00000115159.
DR Ensembl; ENST00000409861; ENSP00000386626; ENSG00000115159.
DR Ensembl; ENST00000438166; ENSP00000409708; ENSG00000115159.
DR GeneID; 2820; -.
DR KEGG; hsa:2820; -.
DR UCSC; uc002tzd.4; human.
DR CTD; 2820; -.
DR GeneCards; GC02P157291; -.
DR H-InvDB; HIX0002519; -.
DR HGNC; HGNC:4456; GPD2.
DR HPA; HPA008012; -.
DR MIM; 138430; gene.
DR neXtProt; NX_P43304; -.
DR PharmGKB; PA28837; -.
DR eggNOG; COG0578; -.
DR HOGENOM; HOG000004813; -.
DR HOVERGEN; HBG005897; -.
DR InParanoid; P43304; -.
DR KO; K00111; -.
DR OMA; SYFLTKS; -.
DR OrthoDB; EOG74TWZ2; -.
DR PhylomeDB; P43304; -.
DR BioCyc; MetaCyc:HS03841-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR UniPathway; UPA00618; UER00673.
DR GenomeRNAi; 2820; -.
DR NextBio; 11111; -.
DR PRO; PR:P43304; -.
DR ArrayExpress; P43304; -.
DR Bgee; P43304; -.
DR CleanEx; HS_GPD2; -.
DR Genevestigator; P43304; -.
DR GO; GO:0009331; C:glycerol-3-phosphate dehydrogenase complex; IEA:InterPro.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR GO; GO:0004368; F:glycerol-3-phosphate dehydrogenase activity; TAS:ProtInc.
DR GO; GO:0052591; F:sn-glycerol-3-phosphate:ubiquinone-8 oxidoreductase activity; IEA:UniProtKB-EC.
DR GO; GO:0044255; P:cellular lipid metabolic process; TAS:Reactome.
DR GO; GO:0006094; P:gluconeogenesis; IEA:Ensembl.
DR GO; GO:0019563; P:glycerol catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006072; P:glycerol-3-phosphate metabolic process; IEA:Ensembl.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 1.10.238.10; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR006076; FAD-dep_OxRdtase.
DR InterPro; IPR000447; G3P_DH_FAD-dep.
DR Pfam; PF01266; DAO; 1.
DR Pfam; PF13499; EF-hand_7; 1.
DR PRINTS; PR01001; FADG3PDH.
DR SMART; SM00054; EFh; 2.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 2.
DR PROSITE; PS00977; FAD_G3PDH_1; 1.
DR PROSITE; PS00978; FAD_G3PDH_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Complete proteome;
KW Direct protein sequencing; FAD; Flavoprotein; Metal-binding;
KW Mitochondrion; Oxidoreductase; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Transit peptide.
FT TRANSIT 1 42 Mitochondrion (By similarity).
FT CHAIN 43 727 Glycerol-3-phosphate dehydrogenase,
FT mitochondrial.
FT /FTId=PRO_0000010429.
FT DOMAIN 623 658 EF-hand 1.
FT DOMAIN 659 694 EF-hand 2.
FT NP_BIND 71 99 FAD (Potential).
FT CA_BIND 672 683 Potential.
FT MOD_RES 601 601 Phosphotyrosine (By similarity).
FT VAR_SEQ 1 126 Missing (in isoform 2).
FT /FTId=VSP_017134.
FT VARIANT 264 264 R -> H (in dbSNP:rs2116665).
FT /FTId=VAR_049113.
FT VARIANT 453 453 K -> Q (in dbSNP:rs35096779).
FT /FTId=VAR_049114.
FT VARIANT 525 525 R -> H (in dbSNP:rs1051916).
FT /FTId=VAR_025215.
SQ SEQUENCE 727 AA; 80853 MW; 70D8B4E5CB4F2EFD CRC64;
MAFQKAVKGT ILVGGGALAT VLGLSQFAHY RRKQMNLAYV KAADCISEPV NREPPSREAQ
LLTLQNTSEF DILVIGGGAT GSGCALDAVT RGLKTALVER DDFSSGTSSR STKLIHGGVR
YLQKAIMKLD IEQYRMVKEA LHERANLLEI APHLSAPLPI MLPVYKWWQL PYYWVGIKLY
DLVAGSNCLK SSYVLSKSRA LEHFPMLQKD KLVGAIVYYD GQHNDARMNL AIALTAARYG
AATANYMEVV SLLKKTDPQT GKVRVSGARC KDVLTGQEFD VRAKCVINAT GPFTDSVRKM
DDKDAAAICQ PSAGVHIVMP GYYSPESMGL LDPATSDGRV IFFLPWQKMT IAGTTDTPTD
VTHHPIPSEE DINFILNEVR NYLSCDVEVR RGDVLAAWSG IRPLVTDPKS ADTQSISRNH
VVDISESGLI TIAGGKWTTY RSMAEDTINA AVKTHNLKAG PSRTVGLFLQ GGKDWSPTLY
IRLVQDYGLE SEVAQHLAAT YGDKAFEVAK MASVTGKRWP IVGVRLVSEF PYIEAEVKYG
IKEYACTAVD MISRRTRLAF LNVQAAEEAL PRIVELMGRE LNWDDYKKQE QLETARKFLY
YEMGYKSRSE QLTDRSEISL LPSDIDRYKK RFHKFDADQK GFITIVDVQR VLESINVQMD
ENTLHEILNE VDLNKNGQVE LNEFLQLMSA IQKGRVSGSR LAILMKTAEE NLDRRVPIPV
DRSCGGL
//
ID GPDM_HUMAN Reviewed; 727 AA.
AC P43304; A8K4V0; B3KSA9; Q59FR1; Q9HAP9;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-MAY-2009, sequence version 3.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=Glycerol-3-phosphate dehydrogenase, mitochondrial;
DE Short=GPD-M;
DE Short=GPDH-M;
DE EC=1.1.5.3;
DE AltName: Full=mtGPD;
DE Flags: Precursor;
GN Name=GPD2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS HIS-264 AND
RP HIS-525.
RX PubMed=7821823; DOI=10.1016/0378-1119(94)90469-3;
RA Lehn D.A., Brown L.J., Simonson G.D., Moran S.M., McDonald M.J.;
RT "The sequence of a human mitochondrial glycerol-3-phosphate
RT dehydrogenase-encoding cDNA.";
RL Gene 150:417-418(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT HIS-264.
RX PubMed=8549872; DOI=10.2337/diab.45.2.262;
RA Ferrer J., Aoki M., Behn P., Nestorowicz A., Riggs A., Permutt M.A.;
RT "Mitochondrial glycerol-3-phosphate dehydrogenase. Cloning of an
RT alternatively spliced human islet-cell cDNA, tissue distribution,
RT physical mapping, and identification of a polymorphic genetic
RT marker.";
RL Diabetes 45:262-266(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-264.
RX PubMed=8682323; DOI=10.1016/0378-1119(96)00019-4;
RA Brown L.J., Stoffel M., Moran S.M., Fernald A.A., Lehn D.A.,
RA LeBeau M.M., MacDonald M.J.;
RT "Structural organization and mapping of the human mitochondrial
RT glycerol phosphate dehydrogenase-encoding gene and pseudogene.";
RL Gene 172:309-312(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS HIS-264 AND
RP HIS-525.
RC TISSUE=Testis;
RA Yin L.L., Li J.M., Sha J.H.;
RT "A novel glycerol-3-phosphate dehydrogenase 3 from adult testis.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP HIS-264.
RC TISSUE=Testis, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP HIS-264.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT HIS-264.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-408, AND VARIANT HIS-264.
RC TISSUE=Brain;
RX PubMed=9110174;
RA Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W.,
RA Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.;
RT "Large-scale concatenation cDNA sequencing.";
RL Genome Res. 7:353-358(1997).
RN [10]
RP PROTEIN SEQUENCE OF 212-227 AND 558-572, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [11]
RP PROTEIN SEQUENCE OF 340-348; 410-418; 526-538; 558-572 AND 715-722,
RP AND MASS SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (JAN-2006) to UniProtKB.
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- CATALYTIC ACTIVITY: sn-glycerol 3-phosphate + a quinone =
CC glycerone phosphate + a quinol.
CC -!- COFACTOR: FAD.
CC -!- ENZYME REGULATION: Calcium-binding enhance the activity of the
CC enzyme.
CC -!- PATHWAY: Polyol metabolism; glycerol degradation via glycerol
CC kinase pathway; glycerone phosphate from sn-glycerol 3-phosphate
CC (anaerobic route): step 1/1.
CC -!- SUBCELLULAR LOCATION: Mitochondrion.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P43304-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P43304-2; Sequence=VSP_017134;
CC -!- SIMILARITY: Belongs to the FAD-dependent glycerol-3-phosphate
CC dehydrogenase family.
CC -!- SIMILARITY: Contains 2 EF-hand domains.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92636.1; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; U12424; AAA65701.1; -; mRNA.
DR EMBL; U36310; AAB60403.1; -; mRNA.
DR EMBL; U40367; AAC50556.1; -; Genomic_DNA.
DR EMBL; U40353; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40354; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40355; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40357; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40358; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40359; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40360; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40361; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40362; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40363; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40364; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; U40365; AAC50556.1; JOINED; Genomic_DNA.
DR EMBL; AF311325; AAG33851.1; -; mRNA.
DR EMBL; AK093198; BAG52671.1; -; mRNA.
DR EMBL; AK291065; BAF83754.1; -; mRNA.
DR EMBL; AK292817; BAF85506.1; -; mRNA.
DR EMBL; AB209399; BAD92636.1; ALT_INIT; mRNA.
DR EMBL; AC011308; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092686; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471058; EAX11453.1; -; Genomic_DNA.
DR EMBL; U79250; AAB50200.1; -; mRNA.
DR PIR; G02093; G02093.
DR RefSeq; NP_000399.3; NM_000408.4.
DR RefSeq; NP_001076581.2; NM_001083112.2.
DR RefSeq; XP_005246526.1; XM_005246469.1.
DR UniGene; Hs.512382; -.
DR ProteinModelPortal; P43304; -.
DR SMR; P43304; 63-693.
DR IntAct; P43304; 1.
DR MINT; MINT-4530883; -.
DR STRING; 9606.ENSP00000308610; -.
DR PhosphoSite; P43304; -.
DR DMDM; 229462943; -.
DR REPRODUCTION-2DPAGE; IPI00017895; -.
DR UCD-2DPAGE; P43304; -.
DR PaxDb; P43304; -.
DR PRIDE; P43304; -.
DR Ensembl; ENST00000310454; ENSP00000308610; ENSG00000115159.
DR Ensembl; ENST00000409674; ENSP00000386425; ENSG00000115159.
DR Ensembl; ENST00000409861; ENSP00000386626; ENSG00000115159.
DR Ensembl; ENST00000438166; ENSP00000409708; ENSG00000115159.
DR GeneID; 2820; -.
DR KEGG; hsa:2820; -.
DR UCSC; uc002tzd.4; human.
DR CTD; 2820; -.
DR GeneCards; GC02P157291; -.
DR H-InvDB; HIX0002519; -.
DR HGNC; HGNC:4456; GPD2.
DR HPA; HPA008012; -.
DR MIM; 138430; gene.
DR neXtProt; NX_P43304; -.
DR PharmGKB; PA28837; -.
DR eggNOG; COG0578; -.
DR HOGENOM; HOG000004813; -.
DR HOVERGEN; HBG005897; -.
DR InParanoid; P43304; -.
DR KO; K00111; -.
DR OMA; SYFLTKS; -.
DR OrthoDB; EOG74TWZ2; -.
DR PhylomeDB; P43304; -.
DR BioCyc; MetaCyc:HS03841-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR UniPathway; UPA00618; UER00673.
DR GenomeRNAi; 2820; -.
DR NextBio; 11111; -.
DR PRO; PR:P43304; -.
DR ArrayExpress; P43304; -.
DR Bgee; P43304; -.
DR CleanEx; HS_GPD2; -.
DR Genevestigator; P43304; -.
DR GO; GO:0009331; C:glycerol-3-phosphate dehydrogenase complex; IEA:InterPro.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR GO; GO:0004368; F:glycerol-3-phosphate dehydrogenase activity; TAS:ProtInc.
DR GO; GO:0052591; F:sn-glycerol-3-phosphate:ubiquinone-8 oxidoreductase activity; IEA:UniProtKB-EC.
DR GO; GO:0044255; P:cellular lipid metabolic process; TAS:Reactome.
DR GO; GO:0006094; P:gluconeogenesis; IEA:Ensembl.
DR GO; GO:0019563; P:glycerol catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006072; P:glycerol-3-phosphate metabolic process; IEA:Ensembl.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 1.10.238.10; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR006076; FAD-dep_OxRdtase.
DR InterPro; IPR000447; G3P_DH_FAD-dep.
DR Pfam; PF01266; DAO; 1.
DR Pfam; PF13499; EF-hand_7; 1.
DR PRINTS; PR01001; FADG3PDH.
DR SMART; SM00054; EFh; 2.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 2.
DR PROSITE; PS00977; FAD_G3PDH_1; 1.
DR PROSITE; PS00978; FAD_G3PDH_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Complete proteome;
KW Direct protein sequencing; FAD; Flavoprotein; Metal-binding;
KW Mitochondrion; Oxidoreductase; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Transit peptide.
FT TRANSIT 1 42 Mitochondrion (By similarity).
FT CHAIN 43 727 Glycerol-3-phosphate dehydrogenase,
FT mitochondrial.
FT /FTId=PRO_0000010429.
FT DOMAIN 623 658 EF-hand 1.
FT DOMAIN 659 694 EF-hand 2.
FT NP_BIND 71 99 FAD (Potential).
FT CA_BIND 672 683 Potential.
FT MOD_RES 601 601 Phosphotyrosine (By similarity).
FT VAR_SEQ 1 126 Missing (in isoform 2).
FT /FTId=VSP_017134.
FT VARIANT 264 264 R -> H (in dbSNP:rs2116665).
FT /FTId=VAR_049113.
FT VARIANT 453 453 K -> Q (in dbSNP:rs35096779).
FT /FTId=VAR_049114.
FT VARIANT 525 525 R -> H (in dbSNP:rs1051916).
FT /FTId=VAR_025215.
SQ SEQUENCE 727 AA; 80853 MW; 70D8B4E5CB4F2EFD CRC64;
MAFQKAVKGT ILVGGGALAT VLGLSQFAHY RRKQMNLAYV KAADCISEPV NREPPSREAQ
LLTLQNTSEF DILVIGGGAT GSGCALDAVT RGLKTALVER DDFSSGTSSR STKLIHGGVR
YLQKAIMKLD IEQYRMVKEA LHERANLLEI APHLSAPLPI MLPVYKWWQL PYYWVGIKLY
DLVAGSNCLK SSYVLSKSRA LEHFPMLQKD KLVGAIVYYD GQHNDARMNL AIALTAARYG
AATANYMEVV SLLKKTDPQT GKVRVSGARC KDVLTGQEFD VRAKCVINAT GPFTDSVRKM
DDKDAAAICQ PSAGVHIVMP GYYSPESMGL LDPATSDGRV IFFLPWQKMT IAGTTDTPTD
VTHHPIPSEE DINFILNEVR NYLSCDVEVR RGDVLAAWSG IRPLVTDPKS ADTQSISRNH
VVDISESGLI TIAGGKWTTY RSMAEDTINA AVKTHNLKAG PSRTVGLFLQ GGKDWSPTLY
IRLVQDYGLE SEVAQHLAAT YGDKAFEVAK MASVTGKRWP IVGVRLVSEF PYIEAEVKYG
IKEYACTAVD MISRRTRLAF LNVQAAEEAL PRIVELMGRE LNWDDYKKQE QLETARKFLY
YEMGYKSRSE QLTDRSEISL LPSDIDRYKK RFHKFDADQK GFITIVDVQR VLESINVQMD
ENTLHEILNE VDLNKNGQVE LNEFLQLMSA IQKGRVSGSR LAILMKTAEE NLDRRVPIPV
DRSCGGL
//
MIM
138430
*RECORD*
*FIELD* NO
138430
*FIELD* TI
*138430 GLYCEROL-3-PHOSPHATE DEHYDROGENASE 2; GPD2
;;GLYCEROPHOSPHATE DEHYDROGENASE-2 Ca(2+)-RESPONSIVE MITOCHONDRIAL FAD-LINKED;;
read moreGPD, MITOCHONDRIAL; GPDM;;
GDH2
*FIELD* TX
DESCRIPTION
Mitochondrial glycerophosphate dehydrogenase (EC 1.1.99.5), or GPD2, is
located on the outer surface of the inner mitochondrial membrane and
catalyzes the unidirectional conversion of glycerol-3-phosphate (G-3-P)
to dihydroxyacetone phosphate (DHAP) with concomitant reduction of the
enzyme-bound FAD. Together with a cytosolic NAD-linked GPD (GPD1;
138420), GPD2 forms the glycerol phosphate shuttle, which uses the
interconversion of G-3-P and DHAP to transfer reducing equivalents into
mitochondria, resulting in the reoxidation of NADH formed during
glycolysis.
CLONING
Shaw et al. (1982) determined that GPDM is widely distributed in adult
and fetal tissues. Activity was also detected in cultured lymphoblastoid
cells and fibroblasts, but not in red cells. Brown et al. (1996) cloned
the human GPDM gene. The deduced protein contains a leader peptide,
followed by a FAD-binding domain, 2 central conserved regions postulated
to play a role in glycerol phosphate binding, and 2 C-terminal
calcium-binding domains. The calcium-binding region shows greatest
homology with the calmodulin (see 114180) and troponin-C (see 191039)
subfamilies of the EF-hand family of proteins.
Ferrer et al. (1996) identified 2 mitochondrial GPD variants with
different 5-prime ends. RT-PCR detected both transcripts in purified
native human pancreatic islets and other tissues. Northern blot analysis
detected a major 6.5-kb transcript in RNA from human and rat pancreatic
islets, with lower expression in other human tissues.
GENE FUNCTION
The Goto-Kakizaki (GK) rat is a genetic model for noninsulin-dependent
diabetes (124853). By biochemical assay and Western blot analysis,
MacDonald et al. (1996) found that GPD2 enzymatic activity and protein
level were about 35 to 40% of normal in GK rats. The activity of
pyruvate carboxylase (608786) was also reduced, but other enzyme
activities were within the normal range. Normalization of GK rat blood
sugars with insulin treatment for 14 days corrected the enzyme deficits.
MacDonald et al. (1996) concluded that decreased Gpd2 and pyruvate
carboxylase in the islets of GK rats was a secondary feature of
diabetes.
Gong et al. (2000) determined that the GPD2 promoter A was 10% as active
as promoter B in a rat beta-cell line (INS-1) and in HeLa cells.
Deletion and mutation analysis indicated that NRF2 (GABPA; 600609)- and
E2F (see 189971)-binding sites were important regulatory cis elements in
promoter B. Exposing INS-1 cells to high glucose for 7 days decreased
Gpd2 activity by 53% and promoter B activity by 60%. Promoter B activity
was unchanged or slightly increased in a human hepatoma cell line and
HeLa cells exposed to high glucose. Gong et al. (2000) concluded that
beta cells may regulate GPD2 transcription differently than other cells.
GENE STRUCTURE
Brown et al. (1996) determined that the GPD2 gene contains 17 exons and
spans more than 83 kb. Introns interrupt the 5-prime untranslated region
and the sequences encoding the leader peptide, FAD-binding domain, and
putative catalytic site.
Gong et al. (2000) determined that the 5-prime flanking region of the
GPD2 gene contains 2 alternative first exons, 1A and 1B, and 2
promoters, A and B. Exon 1A contains 3 transcription start sites, and
exon 1B contains 4 transcription start sites. Promoter A contains
several repetitive elements. Promoter B has no TATA box, but it is GC
rich and contains putative transcription factor-binding sites for SP1
(189906), AP1 (see JUN; 165160), AP2 (107589), E2F, and NRF2.
MAPPING
Ferrer et al. (1996) mapped the human GPD2 gene to chromosome 2 by PCR
analysis of genomic DNA from human-rodent somatic cell hybrids, and
identified 5 independent overlapping YAC clones containing the GPD2
sequence in the CEPH YAC library. Analysis of these YACs identified a
highly polymorphic chromosome 2q21-q33 dinucleotide repeat genetic
marker (D2S141) physically linked to the GPD2 gene. By fluorescence in
situ hybridization, Brown et al. (1996) mapped the GPD2 gene to
chromosome 2q24.1. They mapped a retropseudogene (processed pseudogene)
to chromosome 17.
MOLECULAR GENETICS
Mitochondrial glycerophosphate dehydrogenase represents a key component
of the pancreatic B-cell glucose-sensing device. Deficiency of this
enzyme appears to contribute to the impairment of glucose-stimulated
insulin release in several animal models of noninsulin-dependent
diabetes mellitus. Novials et al. (1997) reported a mutation in the GDH2
gene in a patient with type II diabetes mellitus and his
glucose-intolerant half sister. Single-strand conformation polymorphism
analysis (SSCP) revealed an abnormal mobility. Sequencing revealed a
missense mutation predicted to lead to a phe635-to-ser amino acid
substitution (138430.0001).
ANIMAL MODEL
Brown et al. (2002) found that mice lacking mitochondrial Gpd showed a
50% reduction in viability compared with wildtype littermates. Pups
lacking mitochondrial Gpd had decreased liver ATP and slightly increased
liver glycerol phosphate, but uncoupling protein-1 (UCP1; 113730) mRNA
levels were normal. Adult animals had normal liver and muscle
metabolites and normal cold tolerance. However, they had lower body mass
index, a 40% reduction in the weight of white adipose tissue, and
slightly lower fasting blood glucose than controls.
Brown et al. (2002) found that mice lacking both cytosolic and
mitochondrial Gpd were active and nursed well for several days, but they
failed to grow and usually died within the first week. These mice shared
some features of both glycerol kinase deficiency and hereditary fructose
intolerance, suggesting the phenotype resulted from the combined effects
of the loss of gluconeogenic substrate, the osmotic effects of glycerol,
and the metabolic effects of accumulated phosphorylated metabolites.
*FIELD* AV
.0001
DIABETES MELLITUS, TYPE II
GPD2, PHE635SER
In a man in whom a diagnosis of type II diabetes mellitus (125853) had
been made at the age of 53 years, Novials et al. (1997) found an
abnormally low activity of mitochondrial GDH in a CD3(+) T-lymphocyte
homogenate. SSCP analysis showed an abnormality of the PCR products
derived from the GDH2 gene; sequencing revealed a TTT-to-TCT transition
predicted to result in a change of codon 635 from phenylalanine to
serine.
*FIELD* RF
1. Brown, L. J.; Koza, R. A.; Everett, C.; Reitman, M. L.; Marshall,
L.; Fahien, L. A.; Kozak, L. P.; MacDonald, M. J.: Normal thyroid
thermogenesis but reduced viability and adiposity in mice lacking
the mitochondrial glycerol phosphate dehydrogenase. J. Biol. Chem. 277:
32892-32898, 2002.
2. Brown, L. J.; Koza, R. A.; Marshall, L.; Kozak, L. P.; MacDonald,
M. J.: Lethal hypoglycemic ketosis and glyceroluria in mice lacking
both the mitochondrial and the cytosolic glycerol phosphate dehydrogenases. J.
Biol. Chem. 277: 32899-32904, 2002.
3. Brown, L. J.; Stoffel, M.; Moran, S. M.; Fernald, A. A.; Lehn,
D. A.; LeBeau, M. M.; MacDonald, M. J.: Structural organization and
mapping of the human mitochondrial glycerol phosphate dehydrogenase-encoding
gene and pseudogene. Gene 172: 309-312, 1996.
4. Ferrer, J.; Aoki, M.; Behn, P.; Nestorowicz, A.; Riggs, A.; Permutt,
M. A.: Mitochondrial glycerol-3-phosphate dehydrogenase: cloning
of an alternatively spliced human islet-cell cDNA, tissue distribution,
physical mapping, and identification of a polymorphic genetic marker. Diabetes 45:
262-266, 1996.
5. Gong, Q.; Brown, L. J.; MacDonald, M. J.: Functional analysis
of two promoters for the human mitochondrial glycerol phosphate dehydrogenase
gene. J. Biol. Chem. 275: 38012-38021, 2000.
6. MacDonald, M. J.; Efendic, S.; Ostenson, C.-G.: Normalization
by insulin treatment of low mitochondrial glycerol phosphate dehydrogenase
and pyruvate carboxylase in pancreatic islets of the GK rat. Diabetes 45:
886-890, 1996.
7. Novials, A.; Vidal, J.; Franco, C.; Ribera, F.; Sener, A.; Malaisse,
W. J.; Gomis, R.: Mutation in the calcium-binding domain of the mitochondrial
glycerophosphate dehydrogenase gene in a family of diabetic subjects. Biochem.
Biophys. Res. Commun. 231: 570-572, 1997.
8. Shaw, M.-A.; Edwards, Y. H.; Hopkinson, D. A.: Human mitochondrial
glycerol phosphate dehydrogenase (GPD-M) isozymes. Ann. Hum. Genet. 46:
11-23, 1982.
*FIELD* CN
Patricia A. Hartz - updated: 4/7/2006
Patricia A. Hartz - updated: 5/26/2005
Victor A. McKusick - updated: 6/20/1997
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
mgross: 04/12/2006
mgross: 4/12/2006
terry: 4/7/2006
wwang: 6/15/2005
wwang: 6/7/2005
terry: 5/26/2005
terry: 2/2/2005
terry: 6/2/2004
alopez: 6/4/2001
dkim: 12/9/1998
dkim: 7/2/1998
joanna: 8/12/1997
terry: 6/23/1997
joanna: 6/20/1997
terry: 12/3/1996
terry: 11/8/1996
terry: 11/2/1995
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988
reenie: 6/4/1986
*RECORD*
*FIELD* NO
138430
*FIELD* TI
*138430 GLYCEROL-3-PHOSPHATE DEHYDROGENASE 2; GPD2
;;GLYCEROPHOSPHATE DEHYDROGENASE-2 Ca(2+)-RESPONSIVE MITOCHONDRIAL FAD-LINKED;;
read moreGPD, MITOCHONDRIAL; GPDM;;
GDH2
*FIELD* TX
DESCRIPTION
Mitochondrial glycerophosphate dehydrogenase (EC 1.1.99.5), or GPD2, is
located on the outer surface of the inner mitochondrial membrane and
catalyzes the unidirectional conversion of glycerol-3-phosphate (G-3-P)
to dihydroxyacetone phosphate (DHAP) with concomitant reduction of the
enzyme-bound FAD. Together with a cytosolic NAD-linked GPD (GPD1;
138420), GPD2 forms the glycerol phosphate shuttle, which uses the
interconversion of G-3-P and DHAP to transfer reducing equivalents into
mitochondria, resulting in the reoxidation of NADH formed during
glycolysis.
CLONING
Shaw et al. (1982) determined that GPDM is widely distributed in adult
and fetal tissues. Activity was also detected in cultured lymphoblastoid
cells and fibroblasts, but not in red cells. Brown et al. (1996) cloned
the human GPDM gene. The deduced protein contains a leader peptide,
followed by a FAD-binding domain, 2 central conserved regions postulated
to play a role in glycerol phosphate binding, and 2 C-terminal
calcium-binding domains. The calcium-binding region shows greatest
homology with the calmodulin (see 114180) and troponin-C (see 191039)
subfamilies of the EF-hand family of proteins.
Ferrer et al. (1996) identified 2 mitochondrial GPD variants with
different 5-prime ends. RT-PCR detected both transcripts in purified
native human pancreatic islets and other tissues. Northern blot analysis
detected a major 6.5-kb transcript in RNA from human and rat pancreatic
islets, with lower expression in other human tissues.
GENE FUNCTION
The Goto-Kakizaki (GK) rat is a genetic model for noninsulin-dependent
diabetes (124853). By biochemical assay and Western blot analysis,
MacDonald et al. (1996) found that GPD2 enzymatic activity and protein
level were about 35 to 40% of normal in GK rats. The activity of
pyruvate carboxylase (608786) was also reduced, but other enzyme
activities were within the normal range. Normalization of GK rat blood
sugars with insulin treatment for 14 days corrected the enzyme deficits.
MacDonald et al. (1996) concluded that decreased Gpd2 and pyruvate
carboxylase in the islets of GK rats was a secondary feature of
diabetes.
Gong et al. (2000) determined that the GPD2 promoter A was 10% as active
as promoter B in a rat beta-cell line (INS-1) and in HeLa cells.
Deletion and mutation analysis indicated that NRF2 (GABPA; 600609)- and
E2F (see 189971)-binding sites were important regulatory cis elements in
promoter B. Exposing INS-1 cells to high glucose for 7 days decreased
Gpd2 activity by 53% and promoter B activity by 60%. Promoter B activity
was unchanged or slightly increased in a human hepatoma cell line and
HeLa cells exposed to high glucose. Gong et al. (2000) concluded that
beta cells may regulate GPD2 transcription differently than other cells.
GENE STRUCTURE
Brown et al. (1996) determined that the GPD2 gene contains 17 exons and
spans more than 83 kb. Introns interrupt the 5-prime untranslated region
and the sequences encoding the leader peptide, FAD-binding domain, and
putative catalytic site.
Gong et al. (2000) determined that the 5-prime flanking region of the
GPD2 gene contains 2 alternative first exons, 1A and 1B, and 2
promoters, A and B. Exon 1A contains 3 transcription start sites, and
exon 1B contains 4 transcription start sites. Promoter A contains
several repetitive elements. Promoter B has no TATA box, but it is GC
rich and contains putative transcription factor-binding sites for SP1
(189906), AP1 (see JUN; 165160), AP2 (107589), E2F, and NRF2.
MAPPING
Ferrer et al. (1996) mapped the human GPD2 gene to chromosome 2 by PCR
analysis of genomic DNA from human-rodent somatic cell hybrids, and
identified 5 independent overlapping YAC clones containing the GPD2
sequence in the CEPH YAC library. Analysis of these YACs identified a
highly polymorphic chromosome 2q21-q33 dinucleotide repeat genetic
marker (D2S141) physically linked to the GPD2 gene. By fluorescence in
situ hybridization, Brown et al. (1996) mapped the GPD2 gene to
chromosome 2q24.1. They mapped a retropseudogene (processed pseudogene)
to chromosome 17.
MOLECULAR GENETICS
Mitochondrial glycerophosphate dehydrogenase represents a key component
of the pancreatic B-cell glucose-sensing device. Deficiency of this
enzyme appears to contribute to the impairment of glucose-stimulated
insulin release in several animal models of noninsulin-dependent
diabetes mellitus. Novials et al. (1997) reported a mutation in the GDH2
gene in a patient with type II diabetes mellitus and his
glucose-intolerant half sister. Single-strand conformation polymorphism
analysis (SSCP) revealed an abnormal mobility. Sequencing revealed a
missense mutation predicted to lead to a phe635-to-ser amino acid
substitution (138430.0001).
ANIMAL MODEL
Brown et al. (2002) found that mice lacking mitochondrial Gpd showed a
50% reduction in viability compared with wildtype littermates. Pups
lacking mitochondrial Gpd had decreased liver ATP and slightly increased
liver glycerol phosphate, but uncoupling protein-1 (UCP1; 113730) mRNA
levels were normal. Adult animals had normal liver and muscle
metabolites and normal cold tolerance. However, they had lower body mass
index, a 40% reduction in the weight of white adipose tissue, and
slightly lower fasting blood glucose than controls.
Brown et al. (2002) found that mice lacking both cytosolic and
mitochondrial Gpd were active and nursed well for several days, but they
failed to grow and usually died within the first week. These mice shared
some features of both glycerol kinase deficiency and hereditary fructose
intolerance, suggesting the phenotype resulted from the combined effects
of the loss of gluconeogenic substrate, the osmotic effects of glycerol,
and the metabolic effects of accumulated phosphorylated metabolites.
*FIELD* AV
.0001
DIABETES MELLITUS, TYPE II
GPD2, PHE635SER
In a man in whom a diagnosis of type II diabetes mellitus (125853) had
been made at the age of 53 years, Novials et al. (1997) found an
abnormally low activity of mitochondrial GDH in a CD3(+) T-lymphocyte
homogenate. SSCP analysis showed an abnormality of the PCR products
derived from the GDH2 gene; sequencing revealed a TTT-to-TCT transition
predicted to result in a change of codon 635 from phenylalanine to
serine.
*FIELD* RF
1. Brown, L. J.; Koza, R. A.; Everett, C.; Reitman, M. L.; Marshall,
L.; Fahien, L. A.; Kozak, L. P.; MacDonald, M. J.: Normal thyroid
thermogenesis but reduced viability and adiposity in mice lacking
the mitochondrial glycerol phosphate dehydrogenase. J. Biol. Chem. 277:
32892-32898, 2002.
2. Brown, L. J.; Koza, R. A.; Marshall, L.; Kozak, L. P.; MacDonald,
M. J.: Lethal hypoglycemic ketosis and glyceroluria in mice lacking
both the mitochondrial and the cytosolic glycerol phosphate dehydrogenases. J.
Biol. Chem. 277: 32899-32904, 2002.
3. Brown, L. J.; Stoffel, M.; Moran, S. M.; Fernald, A. A.; Lehn,
D. A.; LeBeau, M. M.; MacDonald, M. J.: Structural organization and
mapping of the human mitochondrial glycerol phosphate dehydrogenase-encoding
gene and pseudogene. Gene 172: 309-312, 1996.
4. Ferrer, J.; Aoki, M.; Behn, P.; Nestorowicz, A.; Riggs, A.; Permutt,
M. A.: Mitochondrial glycerol-3-phosphate dehydrogenase: cloning
of an alternatively spliced human islet-cell cDNA, tissue distribution,
physical mapping, and identification of a polymorphic genetic marker. Diabetes 45:
262-266, 1996.
5. Gong, Q.; Brown, L. J.; MacDonald, M. J.: Functional analysis
of two promoters for the human mitochondrial glycerol phosphate dehydrogenase
gene. J. Biol. Chem. 275: 38012-38021, 2000.
6. MacDonald, M. J.; Efendic, S.; Ostenson, C.-G.: Normalization
by insulin treatment of low mitochondrial glycerol phosphate dehydrogenase
and pyruvate carboxylase in pancreatic islets of the GK rat. Diabetes 45:
886-890, 1996.
7. Novials, A.; Vidal, J.; Franco, C.; Ribera, F.; Sener, A.; Malaisse,
W. J.; Gomis, R.: Mutation in the calcium-binding domain of the mitochondrial
glycerophosphate dehydrogenase gene in a family of diabetic subjects. Biochem.
Biophys. Res. Commun. 231: 570-572, 1997.
8. Shaw, M.-A.; Edwards, Y. H.; Hopkinson, D. A.: Human mitochondrial
glycerol phosphate dehydrogenase (GPD-M) isozymes. Ann. Hum. Genet. 46:
11-23, 1982.
*FIELD* CN
Patricia A. Hartz - updated: 4/7/2006
Patricia A. Hartz - updated: 5/26/2005
Victor A. McKusick - updated: 6/20/1997
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
mgross: 04/12/2006
mgross: 4/12/2006
terry: 4/7/2006
wwang: 6/15/2005
wwang: 6/7/2005
terry: 5/26/2005
terry: 2/2/2005
terry: 6/2/2004
alopez: 6/4/2001
dkim: 12/9/1998
dkim: 7/2/1998
joanna: 8/12/1997
terry: 6/23/1997
joanna: 6/20/1997
terry: 12/3/1996
terry: 11/8/1996
terry: 11/2/1995
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988
reenie: 6/4/1986