!!

Powering down the Pfam website
On October 5th, we will start redirecting the traffic from Pfam (pfam.xfam.org) to InterPro (www.ebi.ac.uk/interpro). The Pfam website will be available at legacy.pfam.xfam.org until January 2023, when it will be decommissioned. You can read more about the sunset period in our blog post.

Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
767  structures 8657  species 0  interactions 18775  sequences 99  architectures

Family: Gp_dh_N (PF00044)

Summary: Glyceraldehyde 3-phosphate dehydrogenase, NAD binding domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Glyceraldehyde 3-phosphate dehydrogenase". More...

Glyceraldehyde 3-phosphate dehydrogenase Edit Wikipedia article

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is an important enzyme used in reaction 6 of glycolysis. It oxidizes glyceraldehyde-3-phosphate at the 1-carbon position, converting an aldehyde to a carboxylic acid, and simultaneously adding a phosphate. The product is 1,3-bisphosphoglycerate.

Sources

Voet, D. and Voet, J. G. (2004) Biochemistry, Third Edition. J. Wiley & Sons, Hoboken, NJ.

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Glyceraldehyde 3-phosphate dehydrogenase, NAD binding domain Provide feedback

GAPDH is a tetrameric NAD-binding enzyme involved in glycolysis and glyconeogenesis. N-terminal domain is a Rossmann NAD(P) binding fold.

Literature references

  1. Kim H, Feil IK, Verlinde CL, Petra PH, Hol WG; , Biochemistry 1995;34:14975-14986.: Crystal structure of glycosomal glyceraldehyde-3-phosphate dehydrogenase from Leishmania mexicana: implications for structure-based drug design and a new position for the inorganic phosphate binding site. PUBMED:7578111 EPMC:7578111


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR020828

This entry represents the N-terminal domain which is a Rossmann NAD(P) binding fold.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in glycolysis and gluconeogenesis [ PUBMED:2716055 ] by reversibly catalysing the oxidation and phosphorylation of D-glyceraldehyde-3-phosphate to 1,3-diphospho-glycerate. The enzyme exists as a tetramer of identical subunits, each containing 2 conserved functional domains: an NAD-binding domain, and a highly conserved catalytic domain [ PUBMED:6303388 ]. The enzyme has been found to bind to actin and tropomyosin, and may thus have a role in cytoskeleton assembly. Alternatively, the cytoskeleton may provide a framework for precise positioning of the glycolytic enzymes, thus permitting efficient passage of metabolites from enzyme to enzyme [ PUBMED:6303388 ].

GAPDH displays diverse non-glycolytic functions as well, its role depending upon its subcellular location. For instance, the translocation of GAPDH to the nucleus acts as a signalling mechanism for programmed cell death, or apoptosis [ PUBMED:10740219 ]. The accumulation of GAPDH within the nucleus is involved in the induction of apoptosis, where GAPDH functions in the activation of transcription. The presence of GAPDH is associated with the synthesis of pro-apoptotic proteins like BAX, c-JUN and GAPDH itself.

GAPDH has been implicated in certain neurological diseases: GAPDH is able to bind to the gene products from neurodegenerative disorders such as Huntington's disease, Alzheimer's disease, Parkinson's disease and Machado-Joseph disease through stretches encoded by their CAG repeats. Abnormal neuronal apoptosis is associated with these diseases. Propargylamines such as deprenyl increase neuronal survival by interfering with apoptosis signalling pathways via their binding to GAPDH, which decreases the synthesis of pro-apoptotic proteins [ PUBMED:12721812 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan NADP_Rossmann (CL0063), which has the following description:

A class of redox enzymes are two domain proteins. One domain, termed the catalytic domain, confers substrate specificity and the precise reaction of the enzyme. The other domain, which is common to this class of redox enzymes, is a Rossmann-fold domain. The Rossmann domain binds nicotinamide adenine dinucleotide (NAD+) and it is this cofactor that reversibly accepts a hydride ion, which is lost or gained by the substrate in the redox reaction. Rossmann domains have an alpha/beta fold, which has a central beta sheet, with approximately five alpha helices found surrounding the beta sheet.The strands forming the beta sheet are found in the following characteristic order 654123. The inter sheet crossover of the stands in the sheet form the NAD+ binding site [1]. In some more distantly relate Rossmann domains the NAD+ cofactor is replaced by the functionally similar cofactor FAD.

The clan contains the following 209 members:

2-Hacid_dh_C 3Beta_HSD 3HCDH_N 3HCDH_RFF adh_short adh_short_C2 ADH_zinc_N ADH_zinc_N_2 AdoHcyase_NAD AdoMet_MTase AlaDh_PNT_C Amino_oxidase ApbA AviRa B12-binding Bac_GDH Bin3 Bmt2 BMT5-like BpsA_C CARME CbiJ CheR CMAS CmcI CoA_binding CoA_binding_2 CoA_binding_3 Cons_hypoth95 CoV_ExoN CoV_Methyltr_2 DAO DapB_N DFP DNA_methylase DOT1 DRE2_N DREV DUF1442 DUF1611_N DUF166 DUF1776 DUF268 DUF2855 DUF3410 DUF364 DUF5129 DUF5130 DUF6094 DUF938 DXP_reductoisom DXPR_C Eco57I ELFV_dehydrog Eno-Rase_FAD_bd Eno-Rase_NADH_b Enoyl_reductase Epimerase F420_oxidored FAD_binding_2 FAD_binding_3 FAD_oxidored Fibrillarin FMO-like FmrO FtsJ fvmX7 G6PD_N GCD14 GDI GDP_Man_Dehyd GFO_IDH_MocA GIDA GidB GLF Glu_dehyd_C Glyco_hydro_4 Glyco_tran_WecG GMC_oxred_N Gp_dh_N GRAS GRDA HcgC HI0933_like HIM1 IlvN ISPD_C KR LCM Ldh_1_N LpxI_N Lycopene_cycl Lys_Orn_oxgnase Malic_M Mannitol_dh MCRA Met_10 Methyltr_RsmB-F Methyltr_RsmF_N Methyltrans_Mon Methyltrans_SAM Methyltransf_10 Methyltransf_11 Methyltransf_12 Methyltransf_14 Methyltransf_15 Methyltransf_16 Methyltransf_17 Methyltransf_18 Methyltransf_19 Methyltransf_2 Methyltransf_20 Methyltransf_21 Methyltransf_22 Methyltransf_23 Methyltransf_24 Methyltransf_25 Methyltransf_28 Methyltransf_29 Methyltransf_3 Methyltransf_30 Methyltransf_31 Methyltransf_32 Methyltransf_33 Methyltransf_34 Methyltransf_4 Methyltransf_5 Methyltransf_7 Methyltransf_8 Methyltransf_9 Methyltransf_PK MethyltransfD12 MetW Mg-por_mtran_C MmeI_Mtase MOLO1 Mqo MT-A70 MTS Mur_ligase N6-adenineMlase N6_Mtase N6_N4_Mtase NAD_binding_10 NAD_binding_2 NAD_binding_3 NAD_binding_4 NAD_binding_5 NAD_binding_7 NAD_binding_8 NAD_binding_9 NAD_Gly3P_dh_N NAS NmrA NNMT_PNMT_TEMT NodS OCD_Mu_crystall OpcA_G6PD_assem Orbi_VP4 PALP PARP_regulatory PCMT PDH_N PglD_N Polysacc_syn_2C Polysacc_synt_2 Pox_MCEL Pox_mRNA-cap Prenylcys_lyase PrmA PRMT5 Pyr_redox Pyr_redox_2 Pyr_redox_3 Reovirus_L2 RmlD_sub_bind Rossmann-like rRNA_methylase RrnaAD Rsm22 RsmJ Sacchrp_dh_NADP SAM_MT SE Semialdhyde_dh Shikimate_DH Spermine_synth SRR1 TehB THF_DHG_CYH_C Thi4 ThiF TPM_phosphatase TPMT TrkA_N TRM TRM13 TrmK tRNA_U5-meth_tr Trp_halogenase TylF Ubie_methyltran UDPG_MGDP_dh_N UPF0020 UPF0146 Urocanase V_cholerae_RfbT XdhC_C YjeF_N

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(74)
Full
(18775)
Representative proteomes UniProt
(82487)
RP15
(2505)
RP35
(8618)
RP55
(18195)
RP75
(30276)
Jalview View  View  View  View  View  View  View 
HTML View             
PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(74)
Full
(18775)
Representative proteomes UniProt
(82487)
RP15
(2505)
RP35
(8618)
RP55
(18195)
RP75
(30276)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(74)
Full
(18775)
Representative proteomes UniProt
(82487)
RP15
(2505)
RP35
(8618)
RP55
(18195)
RP75
(30276)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Overington
Previous IDs: gpdh;
Type: Domain
Sequence Ontology: SO:0000417
Author: Eddy SR , Griffiths-Jones SR
Number in seed: 74
Number in full: 18775
Average length of the domain: 101.8 aa
Average identity of full alignment: 42 %
Average coverage of the sequence by the domain: 29.03 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 31.7 31.7
Trusted cut-off 31.8 31.7
Noise cut-off 31.6 31.6
Model length: 101
Family (HMM) version: 27
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Gp_dh_N domain has been found. There are 767 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

Loading structure mapping...

AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A044R9M9 View 3D Structure Click here
A0A077ZHV3 View 3D Structure Click here
A0A077ZJ41 View 3D Structure Click here
A0A077ZMJ5 View 3D Structure Click here
A0A0D2F5D8 View 3D Structure Click here
A0A0G2JYY8 View 3D Structure Click here
A0A0G2K3I6 View 3D Structure Click here
A0A0G2K7M1 View 3D Structure Click here
A0A0G2K8S2 View 3D Structure Click here
A0A0H3GN34 View 3D Structure Click here
A0A0H3GNE5 View 3D Structure Click here
A0A0H3GSZ3 View 3D Structure Click here
A0A0H3GWR1 View 3D Structure Click here
A0A0J9XXG7 View 3D Structure Click here
A0A0K0E472 View 3D Structure Click here
A0A0K0EQF8 View 3D Structure Click here
A0A0K0ESW0 View 3D Structure Click here
A0A0N4UDR2 View 3D Structure Click here
A0A0R0FQX0 View 3D Structure Click here
A0A0R0KA84 View 3D Structure Click here
A0A158N7S3 View 3D Structure Click here
A0A1C1C7G6 View 3D Structure Click here
A0A1D5RLD8 View 3D Structure Click here
A0A1D6E965 View 3D Structure Click here
A0A1D6H1J5 View 3D Structure Click here
A0A1D6HCF4 View 3D Structure Click here
A0A1D6I150 View 3D Structure Click here
A0A1D6J815 View 3D Structure Click here
A0A1D6J820 View 3D Structure Click here
A0A1D6LZD5 View 3D Structure Click here
A0A1D6NHJ0 View 3D Structure Click here
A0A1D6QSB3 View 3D Structure Click here
A0A3P7DIY7 View 3D Structure Click here
A0A3P7E6M6 View 3D Structure Click here
A0KGD2 View 3D Structure Click here
A0QWW2 View 3D Structure Click here
A1S9A4 View 3D Structure Click here
A1SVN9 View 3D Structure Click here
A2YQT7 View 3D Structure Click here
A3FKF7 View 3D Structure Click here