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.
22  structures 5605  species 0  interactions 12362  sequences 112  architectures

Family: PCMT (PF01135)

Summary: Protein-L-isoaspartate(D-aspartate) O-methyltransferase (PCMT)

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 "L-isoaspartyl methyltransferase". More...

L-isoaspartyl methyltransferase Edit Wikipedia article

Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PIMT, PCMT)
Human L-Isoaspartyl Methyltransferase - PDB id 1KR5.jpg
Crystallographic structure of Human L-isoaspartyl methyltransferase.[1]
EC number2.1.1.77
CAS number105638-50-4
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Protein-L-isoaspartate(D-aspartate) O-methyltransferase

Protein L-isoaspartyl methyltransferase (PIMT, PCMT), also called S-adenosyl-L-methionine:protein-L-isoaspartate O-methyltransferase, is an enzyme which recognizes and catalyzes the repair of damaged L-isoaspartyl and D-aspartyl groups in proteins. It is a highly conserved enzyme which is present in nearly all eukaryotes, archaebacteria, and Gram-negative eubacteria.[1]


PIMT acts to transfer methyl groups from S-adenosyl-L-methionine to the alpha side chain carboxyl groups of damaged L-isoaspartyl and D-aspartyl amino acids. The enzyme takes the end methyl residue from the methionine side chain and adds it to the side chain carboxyl group of L-isoaspartate or D-aspartate to create a methyl ester. Subsequent nonenzymatic reactions result in a rapid transformation to L-succinimide, which is a precursor to aspartate and isoaspartate. The L-succinimide can then undergo nonenzymatic hydrolysis, which generates some repaired L-aspartyl residues as well as some L-isoaspartyl residues, which can then enter the cycle again for eventual conversion to the normal peptide linkage.

PIMT tends to act on proteins that have been non-enzymatically damaged due to age. By performing this repair mechanism, the enzyme helps to maintain overall protein integrity. This mechanism has been observed by several groups, and has been confirmed through experimental testing. In one report, PIMT was inhibited by adenosine dialdehyde. The results supported the proposed function of the enzyme, as the amount of abnormal L-aspartate residues increased when cells were treated with the indirect inhibitor, adenosine dialdehyde.[2] Additionally, S-adenosylhomocysteine is known to be a competitive inhibitor of PIMT.[2] When PIMT is not present in cells, the abnormal aspartyl residues accumulate, creating abnormal proteins that have been known to cause fatal progressive epilepsy in mice.[3] It has been suggested that calmodulin may play a role in stimulating the function of PIMT, although the relationship between these two molecules has not been thoroughly explored.[4] In addition to calmodulin, guanosine 5'-O-[gamma-thio]triphosphate (GTPgammaS) has been found to stimulate PIMT activity.[5]


The enzyme is present in human cytosol in two forms due to alternative splicing and differs among individuals in the population due to a single polymorphism at protein 119, either valine or isoleucine. The enzyme structure is described as a “doubly wound alpha/beta/alpha sandwich structure” which is quite consistent in all species analyzed thus far.[1] If there is any difference in the sequences between different organisms it occurs in the regions connecting the three motifs in the sandwich structure, but the sequence of the individual motifs tends to be highly conserved. Researchers have found the active site to be in the loop between the beta structure and the second alpha helix and have determined it to be highly specific for isoaspartyl residues. For example, the residues found at the C-terminus of drosophila PIMT (dPIMT) are rotated 90 degrees so as to allow more space for a substrate to interact with the enzyme. In fact, dPIMT appears to alternate between this unique open conformation and the less open conformation common of PIMT in other organisms. Although possibly unrelated to this, increased levels of dPIMT in drosophila have been correlated with increase life expectancy in these organisms due to their importance in protein repair.[6]


Reaction catalysed by PIMT

See also

External links


  1. ^ a b c PDB: 1KR5​; Ryttersgaard C, Griffith SC, Sawaya MR, MacLaren DC, Clarke S, Yeates TO (March 2002). "Crystal structure of human L-isoaspartyl methyltransferase". J. Biol. Chem. 277 (12): 10642–6. doi:10.1074/jbc.M200229200. PMID 11792715.
  2. ^ a b Johnson BA, Najbauer J, Aswad DW (March 1993). "Accumulation of substrates for protein L-isoaspartyl methyltransferase in adenosine dialdehyde-treated PC12 cells". J. Biol. Chem. 268 (9): 6174–81. PMID 8454593.
  3. ^ Yamamoto A, Takagi H, Kitamura D, Tatsuoka H, Nakano H, Kawano H, Kuroyanagi H, Yahagi Y, Kobayashi S, Koizumi K, Sakai T, Saito K, Chiba T, Kawamura K, Suzuki K, Watanabe T, Mori H, Shirasawa T (March 1998). "Deficiency in protein L-isoaspartyl methyltransferase results in a fatal progressive epilepsy". J. Neurosci. 18 (6): 2063–74. PMID 9482793.
  4. ^ O'Connor MB, O'Connor CM (May 1998). "Complex interactions of the protein L-isoaspartyl methyltransferase and calmodulin revealed with the yeast two-hybrid system". J. Biol. Chem. 273 (21): 12909–13. doi:10.1074/jbc.273.21.12909. PMID 9582322.
  5. ^ Bilodeau D, Béliveau R (January 1999). "Inhibition of GTPgammaS-dependent L-isoaspartyl protein methylation by tyrosine kinase inhibitors in kidney". Cell. Signal. 11 (1): 45–52. doi:10.1016/S0898-6568(98)00030-8. PMID 10206344.
  6. ^ Bennett EJ, Bjerregaard J, Knapp JE, Chavous DA, Friedman AM, Royer WE, O'Connor CM (November 2003). "Catalytic implications from the Drosophila protein L-isoaspartyl methyltransferase structure and site-directed mutagenesis". Biochemistry. 42 (44): 12844–53. doi:10.1021/bi034891+. PMID 14596598.

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

This tab holds annotation information from the InterPro database.

No InterPro data for this Pfam family.

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 206 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 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 DUF2431 DUF268 DUF2855 DUF3410 DUF364 DUF43 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 K_oxygenase KR LCM Ldh_1_N LpxI_N Lycopene_cycl 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 MOLO1 Mqo MT-A70 MTS Mur_ligase N2227 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 Orbi_VP4 PALP PARP_regulatory PCMT PDH 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 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


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.

Representative proteomes UniProt
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

Representative proteomes UniProt

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.

Representative proteomes UniProt
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...


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: Prosite
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Finn RD , Bateman A
Number in seed: 9
Number in full: 12362
Average length of the domain: 188.40 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 66.57 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.3 20.3
Trusted cut-off 20.3 20.3
Noise cut-off 20.2 20.2
Model length: 210
Family (HMM) version: 21
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

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


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


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


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.


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 PCMT domain has been found. There are 22 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...