UniProt Accession

 G3P_HUMAN; P04406; E7EUT4; P00354; Q53X65 

Genbank Protein ID

 X01677; M17851; M33197; J02642; J04038; X53778; AF261085; AY007133; AB062273; BT006893; AY340484; CR407671; AC006064; CH471116; BC001601; BC004109; BC009081; BC013310; BC023632; BC025925; BC026907; BC029618; BC083511 

Genbank Nucleotide ID

 CAA25833.1; AAA86283.1; AAA52518.1; AAA52496.1; AAA53191.1; CAA37794.1; AAF99678.1; AAG01996.1; BAB93466.1; AAP35539.1; AAP88932.1; CAG28599.1; EAW88787.1; AAH01601.1; AAH04109.1; AAH09081.1; AAH13310.1; AAH23632.1; AAH25925.1; AAH26907.1; AAH29618.1; AAH83511.1 

Protein Name

 Glyceraldehyde-3-phosphate dehydrogenase 

Protein Synonyms/Alias

 GAPDH; Peptidyl-cysteine S-nitrosylase GAPDH 

Gene Name

 GAPDH 

Gene Synonyms/Alias

 GAPD; CDABP0047; OK/SW-cl.12 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
5	***MGKVKVGVNGFG	methylation	[1]
5	***MGKVKVGVNGFG	ubiquitination	[2, 3, 4, 5, 6, 7]
27	RAAFNSGKVDIVAIN	acetylation	[8]
27	RAAFNSGKVDIVAIN	phosphoglycerylation	[9]
55	QYDSTHGKFHGTVKA	acetylation	[8]
61	GKFHGTVKAENGKLV	acetylation	[7, 8, 10, 11, 12]
61	GKFHGTVKAENGKLV	ubiquitination	[2, 3, 4, 5, 6, 7, 13, 14, 15, 16, 17]
66	TVKAENGKLVINGNP	acetylation	[7]
66	TVKAENGKLVINGNP	methylation	[1]
66	TVKAENGKLVINGNP	ubiquitination	[2, 4, 6, 7, 13, 17]
84	FQERDPSKIKWGDAG	acetylation	[7, 10, 11, 12]
84	FQERDPSKIKWGDAG	ubiquitination	[2, 3, 4, 5, 6, 7, 16, 18]
86	ERDPSKIKWGDAGAE	ubiquitination	[2, 3, 4, 5, 6, 7, 16]
107	GVFTTMEKAGAHLQG	ubiquitination	[3, 4, 5]
117	AHLQGGAKRVIISAP	acetylation	[19]
117	AHLQGGAKRVIISAP	ubiquitination	[3, 5, 16]
139	VMGVNHEKYDNSLKI	acetylation	[10]
139	VMGVNHEKYDNSLKI	ubiquitination	[2, 3, 4, 5, 6, 17]
145	EKYDNSLKIISNASC	ubiquitination	[2, 3, 4, 6, 14, 16]
162	NCLAPLAKVIHDNFG	acetylation	[20]
186	HAITATQKTVDGPSG	acetylation	[10, 21, 22]
186	HAITATQKTVDGPSG	ubiquitination	[3, 4, 5, 6, 18]
194	TVDGPSGKLWRDGRG	acetylation	[10]
194	TVDGPSGKLWRDGRG	malonylation	[23]
194	TVDGPSGKLWRDGRG	methylation	[1]
194	TVDGPSGKLWRDGRG	ubiquitination	[2, 3, 4, 5, 6, 14, 18, 24]
215	PASTGAAKAVGKVIP	malonylation	[23]
215	PASTGAAKAVGKVIP	methylation	[1]
215	PASTGAAKAVGKVIP	ubiquitination	[2, 3, 4, 5, 6, 14, 16, 17, 18, 24]
219	GAAKAVGKVIPELNG	acetylation	[10]
219	GAAKAVGKVIPELNG	ubiquitination	[2, 3, 4, 5, 6, 24]
227	VIPELNGKLTGMAFR	acetylation	[10, 19]
227	VIPELNGKLTGMAFR	methylation	[1]
227	VIPELNGKLTGMAFR	ubiquitination	[2, 3, 4, 5, 6, 14]
251	DLTCRLEKPAKYDDI	acetylation	[19]
251	DLTCRLEKPAKYDDI	ubiquitination	[3, 4, 16, 17]
254	CRLEKPAKYDDIKKV	acetylation	[10, 25]
254	CRLEKPAKYDDIKKV	ubiquitination	[3, 4, 5, 16]
259	PAKYDDIKKVVKQAS	ubiquitination	[3, 5, 16]
260	AKYDDIKKVVKQASE	methylation	[1]
260	AKYDDIKKVVKQASE	ubiquitination	[4]
263	DDIKKVVKQASEGPL	methylation	[1]
263	DDIKKVVKQASEGPL	ubiquitination	[2, 3, 4, 5, 6, 14, 18]
271	QASEGPLKGILGYTE	ubiquitination	[3]
334	LMAHMASKE******	methylation	[1]
334	LMAHMASKE******	ubiquitination	[3, 4, 5, 14, 16]

Reference

 [1] Update on activities at the Universal Protein Resource (UniProt) in 2013.
 e="String">UniProt Consortium.
 Nucleic Acids Res. 2013 Jan;41(Database issue):D43-7. [PMID: 23161681]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [7] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [8] Monoclonal antibody cocktail as an enrichment tool for acetylome analysis.
 Shaw PG, Chaerkady R, Zhang Z, Davidson NE, Pandey A.
 Anal Chem. 2011 May 15;83(10):3623-6. [PMID: 21466224]
 [9] Functional lysine modification by an intrinsically reactive primary glycolytic metabolite.
 Moellering RE, Cravatt BF.
 Science. 2013 Aug 2;341(6145):549-53. [PMID: 23908237]
 [10] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [11] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [12] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [13] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [14] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [15] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [16] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [17] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [18] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [19] Nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase is regulated by acetylation.
 Ventura M, Mateo F, Serratosa J, Salaet I, Carujo S, Bachs O, Pujol MJ.
 Int J Biochem Cell Biol. 2010 Oct;42(10):1672-80. [PMID: 20601085]
 [20] Nitric oxide-induced nuclear GAPDH activates p300/CBP and mediates apoptosis.
 Sen N, Hara MR, Kornberg MD, Cascio MB, Bae BI, Shahani N, Thomas B, Dawson TM, Dawson VL, Snyder SH, Sawa A.
 Nat Cell Biol. 2008 Jul;10(7):866-73. [PMID: 18552833]
 [21] The enzymatic significance of S-acetylation and N-acetylation of 3-phosphoglyceraldehyde dehydrogenase.
 Mathew E, Meriwether BP, Park JH.
 J Biol Chem. 1967 Nov 10;242(21):5024-33. [PMID: 4293781]
 [22] S-N transfer and dual acetylation in the S-acetylation and N-acetylation of 3-phosphoglyceraldehyde dehydrogenase by substrates.
 Park JH, Agnello CF, Mathew E.
 J Biol Chem. 1966 Feb 10;241(3):769-71. [PMID: 5908143]
 [23] The first identification of lysine malonylation substrates and its regulatory enzyme.
 Peng C, Lu Z, Xie Z, Cheng Z, Chen Y, Tan M, Luo H, Zhang Y, He W, Yang K, Zwaans BM, Tishkoff D, Ho L, Lombard D, He TC, Dai J, Verdin E, Ye Y, Zhao Y.
 Mol Cell Proteomics. 2011 Dec;10(12):M111.012658. [PMID: 21908771]
 [24] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [25] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786] 

Functional Description

 Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D- glyceroyl phosphate. Component of the GAIT (gamma interferon- activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation. 

Sequence Annotation

 NP_BIND 13 14 NAD.
 REGION 2 148 Interaction with WARS.
 REGION 151 153 Glyceraldehyde 3-phosphate binding (By
 REGION 211 212 Glyceraldehyde 3-phosphate binding (By
 ACT_SITE 152 152 Nucleophile.
 BINDING 35 35 NAD.
 BINDING 80 80 NAD; via carbonyl oxygen.
 BINDING 122 122 NAD.
 BINDING 182 182 Glyceraldehyde 3-phosphate (By
 BINDING 234 234 Glyceraldehyde 3-phosphate (By
 BINDING 316 316 NAD.
 MOD_RES 5 5 N6,N6-dimethyllysine.
 MOD_RES 9 9 Deamidated asparagine.
 MOD_RES 42 42 Phosphotyrosine.
 MOD_RES 61 61 N6-acetyllysine.
 MOD_RES 64 64 Deamidated asparagine.
 MOD_RES 66 66 N6,N6-dimethyllysine.
 MOD_RES 70 70 Deamidated asparagine.
 MOD_RES 75 75 Phosphothreonine.
 MOD_RES 83 83 Phosphoserine.
 MOD_RES 122 122 Phosphoserine.
 MOD_RES 148 148 Phosphoserine.
 MOD_RES 149 149 Deamidated asparagine.
 MOD_RES 151 151 Phosphoserine.
 MOD_RES 152 152 ADP-ribosylcysteine; by autocatalysis; in
 MOD_RES 152 152 Cysteine persulfide (By similarity).
 MOD_RES 152 152 S-nitrosocysteine; in reversibly
 MOD_RES 155 155 Deamidated asparagine.
 MOD_RES 184 184 Phosphothreonine.
 MOD_RES 194 194 N6,N6-dimethyllysine; alternate.
 MOD_RES 194 194 N6-acetyllysine; alternate.
 MOD_RES 194 194 N6-malonyllysine; alternate.
 MOD_RES 211 211 Phosphothreonine.
 MOD_RES 215 215 N6,N6-dimethyllysine; alternate.
 MOD_RES 215 215 N6-malonyllysine; alternate.
 MOD_RES 219 219 N6-acetyllysine.
 MOD_RES 225 225 Deamidated asparagine.
 MOD_RES 227 227 N6,N6-dimethyllysine; alternate.
 MOD_RES 227 227 N6-acetyllysine; alternate.
 MOD_RES 229 229 Phosphothreonine.
 MOD_RES 237 237 Phosphothreonine.
 MOD_RES 254 254 N6-acetyllysine.
 MOD_RES 260 260 N6,N6-dimethyllysine.
 MOD_RES 263 263 N6,N6-dimethyllysine.
 MOD_RES 312 312 Phosphoserine.
 MOD_RES 314 314 Phosphotyrosine (By similarity).
 MOD_RES 316 316 Deamidated asparagine.
 MOD_RES 320 320 Phosphotyrosine (By similarity).
 MOD_RES 334 334 N6,N6-dimethyllysine.  

Keyword

 3D-structure; Acetylation; ADP-ribosylation; Alternative splicing; Apoptosis; Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing; Glycolysis; Membrane; Methylation; NAD; Nucleus; Oxidoreductase; Phosphoprotein; Polymorphism; Reference proteome; S-nitrosylation; Transferase; Translation regulation; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 335 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; ISS:UniProtKB.
 GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
 GO:0005811; C:lipid particle; IDA:UniProtKB.
 GO:0015630; C:microtubule cytoskeleton; ISS:UniProtKB.
 GO:0005634; C:nucleus; ISS:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
 GO:0005886; C:plasma membrane; IDA:HPA.
 GO:0030529; C:ribonucleoprotein complex; IDA:UniProtKB.
 GO:0004365; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity; ISS:UniProtKB.
 GO:0008017; F:microtubule binding; ISS:UniProtKB.
 GO:0051287; F:NAD binding; IEA:InterPro.
 GO:0050661; F:NADP binding; IEA:InterPro.
 GO:0035605; F:peptidyl-cysteine S-nitrosylase activity; ISS:UniProtKB.
 GO:0071346; P:cellular response to interferon-gamma; IDA:UniProtKB.
 GO:0006094; P:gluconeogenesis; TAS:Reactome.
 GO:0006096; P:glycolysis; NAS:UniProtKB.
 GO:0000226; P:microtubule cytoskeleton organization; ISS:UniProtKB.
 GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
 GO:0051402; P:neuron apoptotic process; ISS:UniProtKB.
 GO:0035606; P:peptidyl-cysteine S-trans-nitrosylation; ISS:UniProtKB.
 GO:0050821; P:protein stabilization; ISS:UniProtKB.
 GO:0044281; P:small molecule metabolic process; TAS:Reactome. 

Interpro

 IPR020831; GlycerAld/Erythrose_P_DH.
 IPR020830; GlycerAld_3-P_DH_AS.
 IPR020829; GlycerAld_3-P_DH_cat.
 IPR020828; GlycerAld_3-P_DH_NAD(P)-bd.
 IPR006424; Glyceraldehyde-3-P_DH_1.
 IPR016040; NAD(P)-bd_dom. 

Pfam

 PF02800; Gp_dh_C
 PF00044; Gp_dh_N 

SMART

 SM00846; Gp_dh_N 

PROSITE

 PS00071; GAPDH 

PRINTS

 PR00078; G3PDHDRGNASE.