Reviewed, UniProtKB/Swiss-Prot P22061 (PIMT_HUMAN)

Names and origin

Protein names

Recommended name:
    Protein-L-isoaspartate(D-aspartate) O-methyltransferase
      Short name=PIMT
    EC=2.1.1.77
Alternative name(s):
    Protein-beta-aspartate methyltransferase
    Protein L-isoaspartyl/D-aspartyl methyltransferase
    L-isoaspartyl protein carboxyl methyltransferase

Gene names

Name:

PCMT1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	227 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the methyl esterification of L-isoaspartyl and D-aspartyl residues in peptides and proteins that result from spontaneous decomposition of normal L-aspartyl and L-asparaginyl residues. It plays a role in the repair and/or degradation of damaged proteins. Acts on microtubule-associated protein 2, calreticulin, clathrin light chains a and b, Ubiquitin carboxyl-terminal hydrolase isozyme L1, phosphatidylethanolamine-binding protein 1, stathmin, beta-synuclein and alpha-synuclein By similarity.
Catalytic activity	S-adenosyl-L-methionine + protein L-isoaspartate = S-adenosyl-L-homocysteine + protein L-isoaspartate alpha-methyl ester.
Subunit structure	Monomer.
Subcellular location	Cytoplasm.
Polymorphism	The allele frequencies for the polymorphism at codon 120 differ between ethnic groups; in the Caucasian population Ile-120 is present at a frequency of 0.45, while it is found at a frequency of 0.88 and 0.81 in the Asian and the African populations respectively. Val-120 is found at a frequency of 0.55 in the Caucasians, 0.12 and 0.19 in the Asian and African populations respectively. The Ile-120 variant has higher specific activity and thermostability than the Val-120 variant. The Val-120 variant has a higher affinity for protein substrates.
Sequence similarities	Belongs to the L-isoaspartyl/D-aspartyl protein methyltransferase family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
PTM	Acetylation Disulfide bond
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	protein amino acid methylation Traceable author statement. Source: ProtInc protein repair Ref.11 Traceable author statement. Source: UniProtKB
Cellular component	endoplasmic reticulum Ref.2 Traceable author statement. Source: ProtInc
Molecular function	identical protein binding Inferred from physical interaction. Source: IntAct protein-L-isoaspartate (D-aspartate) O-methyltransferase activity Ref.11 Traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-353343,EBI-353343
EIF1B	O60739	1	EBI-353343,EBI-1043343
VHL	P40337	1	EBI-353343,EBI-301246

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P22061-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P22061-2)

The sequence of this isoform differs from the canonical sequence as follows:
     226-227: WK → DEL

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 227

226

Protein-L-isoaspartate(D-aspartate) O-methyltransferase

PRO_0000111875

Sites

Active site

60

1

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.1

Disulfide bond

43 ↔ 95

By similarity

Natural variations

Alternative sequence

226 – 227

2

WK → DEL in isoform 2.

VSP_004716

Natural variant

120

1

I → V: dbSNP rs4816. Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.9 Ref.11 Ref.14

VAR_006173

Experimental info

Sequence conflict

19

1

K → G AA sequence Ref.9

Sequence conflict

23

1

I → L AA sequence Ref.1

Sequence conflict

60

1

S → A AA sequence Ref.9

Sequence conflict

102

1

C → Q AA sequence Ref.1

Sequence conflict

168

1

A → P AA sequence Ref.9

Sequence conflict

206

1

K → R in AAA90933. Ref.2

Secondary structure

1

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227

Helix Strand Turn

Details...

Helix

10 – 19

10

Helix

26 – 33

8

Helix

37 – 39

3

Beta strand

47 – 49

3

Beta strand

51 – 54

4

Beta strand

57 – 59

3

Helix

62 – 71

10

Turn

72 – 75

4

Beta strand

81 – 85

5

Helix

91 – 100

10

Beta strand

105 – 111

7

Helix

113 – 126

14

Helix

129 – 132

4

Beta strand

134 – 141

8

Helix

143 – 145

3

Helix

148 – 150

3

Beta strand

153 – 158

6

Beta strand

160 – 164

5

Helix

167 – 171

5

Beta strand

173 – 184

12

Beta strand

190 – 197

8

Beta strand

203 – 211

9

Helix

219 – 222

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 987D63EA48422CA8	FASTA	227	24,650
	10 20 30 40 50 60 MAWKSGGASH SELIHNLRKN GIIKTDKVFE VMLATDRSHY AKCNPYMDSP QSIGFQATIS 70 80 90 100 110 120 APHMHAYALE LLFDQLHEGA KALDVGSGSG ILTACFARMV GCTGKVIGID HIKELVDDSI 130 140 150 160 170 180 NNVRKDDPTL LSSGRVQLVV GDGRMGYAEE APYDAIHVGA AAPVVPQALI DQLKPGGRLI 190 200 210 220 LPVGPAGGNQ MLEQYDKLQD GSIKMKPLMG VIYVPLTDKE KQWSRWK
	Isoform 2. Checksum: 845044B3EA48422C	FASTA	228	24,693
	10 20 30 40 50 60 MAWKSGGASH SELIHNLRKN GIIKTDKVFE VMLATDRSHY AKCNPYMDSP QSIGFQATIS 70 80 90 100 110 120 APHMHAYALE LLFDQLHEGA KALDVGSGSG ILTACFARMV GCTGKVIGID HIKELVDDSI 130 140 150 160 170 180 NNVRKDDPTL LSSGRVQLVV GDGRMGYAEE APYDAIHVGA AAPVVPQALI DQLKPGGRLI 190 200 210 220 LPVGPAGGNQ MLEQYDKLQD GSIKMKPLMG VIYVPLTDKE KQWSRDEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of the D-aspartyl/L-isoaspartyl protein methyltransferase from human erythrocytes. Common sequence motifs for protein, DNA, RNA, and small molecule S-adenosylmethionine-dependent methyltransferases." Ingrosso D., Fowler A.V., Bleibaum J., Clarke S. J. Biol. Chem. 264:20131-20139(1989) [PubMed: 2684970] [Abstract] Cited for: PROTEIN SEQUENCE (ISOFORM 1). Tissue: Erythrocyte.
[2]	"Alternative splicing of the human isoaspartyl protein carboxyl methyltransferase RNA leads to the generation of a C-terminal -RDEL sequence in isozyme II." Maclaren D.C., Kagan R.M., Clarke S. Biochem. Biophys. Res. Commun. 185:277-283(1992) [PubMed: 1339271] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT VAL-120. Tissue: Brain cortex.
[3]	"Characterization of three cDNAs encoding two isozymes of an isoaspartyl protein carboxyl methyltransferase from human erythroid leukemia cells." Takeda R., Mizobuchi M., Murao K., Sato M., Takahara J. J. Biochem. 117:683-685(1995) [PubMed: 7592526] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT VAL-120.
[4]	"Gene expression of carboxyl methyltransferase is altered in Alzheimer's disease and the product is localized to neurofibrillary tangles." Shirasawa T., Takahashi H., Endoh R., Sakamoto K., Hirokawa K., Mori H. Submitted (APR-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT VAL-120. Tissue: Brain.
[5]	"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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-120. Tissue: Brain.
[6]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT VAL-120.
[7]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT VAL-120. Tissue: Muscle and Skin.
[8]	"Structure of the human gene encoding the protein repair L-isoaspartyl (D-aspartyl) O-methyltransferase." Devry C.G., Tsai W., Clarke S. Arch. Biochem. Biophys. 335:321-332(1996) [PubMed: 8914929] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-18. Tissue: Foreskin.
[9]	"Purification of homologous protein carboxyl methyltransferase isozymes from human and bovine erythrocytes." Gilbert J.M., Fowler A., Bleibaum J., Clarke S. Biochemistry 27:5227-5233(1988) [PubMed: 3167043] [Abstract] Cited for: PROTEIN SEQUENCE OF 5-19; 44-60; 106-170; 179-198 AND 205-220, VARIANT VAL-120.
[10]	Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 5-18; 25-37; 82-98; 114-144 AND 179-221, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[11]	"Amino acid polymorphisms of the human L-isoaspartyl/D-aspartyl methyltransferase involved in protein repair." Tsai W., Clarke S. Biochem. Biophys. Res. Commun. 203:491-497(1994) [PubMed: 8074695] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 20-53; 100-139 AND 169-224, VARIANT VAL-120.
[12]	"Distinct C-terminal sequences of isozymes I and II of the human erythrocyte L-isoaspartyl/D-aspartyl protein methyltransferase." Ingrosso D., Kagan R.M., Clarke S. Biochem. Biophys. Res. Commun. 175:351-358(1991) [PubMed: 1998518] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE (ISOFORM 2). Tissue: Erythrocyte.
[13]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[14]	"Polymorphic forms of the protein L-isoaspartate (D-aspartate) O-methyltransferase involved in the repair of age-damaged proteins." DeVry C.G., Clarke S. J. Hum. Genet. 44:275-288(1999) [PubMed: 10496068] [Abstract] Cited for: VARIANT VAL-120.
[15]	"Crystal structure of human L-isoaspartyl methyltransferase." Ryttersgaard C., Griffith S.C., Sawaya M.R., MacLaren D.C., Clarke S., Yeates T.O. J. Biol. Chem. 277:10642-10646(2002) [PubMed: 11792715] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[16]	"Crystal structure of human L-isoaspartyl-O-methyl-transferase with S-adenosyl homocysteine at 1.6-A resolution and modeling of an isoaspartyl-containing peptide at the active site." Smith C.D., Carson M., Friedman A.M., Skinner M.M., Delucas L., Chantalat L., Weise L., Shirasawa T., Chattopadhyay D. Protein Sci. 11:625-635(2002) [PubMed: 11847284] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M93008 mRNA. Translation: AAA90934.1.
M93009 mRNA. Translation: AAA90933.1.
D25545 mRNA. Translation: BAA05028.1.
D25546 mRNA. Translation: BAA05029.1.
D25547 mRNA. Translation: BAA05030.1.
D13892 mRNA. Translation: BAA02991.1.
AL355312 Genomic DNA. Translation: CAH72862.1.
AK289724 mRNA. Translation: BAF82413.1.
AL355312 Genomic DNA. Translation: CAH72863.1.
BC007501 mRNA. Translation: AAH07501.1.
BC008748 mRNA. Translation: AAH08748.1.
U49740 Genomic DNA. Translation: AAB38386.1.
S73902 Genomic DNA. Translation: AAC60639.2.
S73903 Genomic DNA. Translation: AAC60640.1.
S73905 Genomic DNA. Translation: AAC60641.2.

IPI

IPI00411680.
IPI00828189.

PIR

A34489.
JH0624.

UniGene

Hs.279257

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1I1N	X-ray	1.50	A	2-227	[»]
1KR5	X-ray	2.10	A	2-227	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P22061. 21 interactions.

2-D gel databases

OGP

P22061.

REPRODUCTION-2DPAGE

IPI00411680.

Proteomic databases

PRIDE

P22061.

Genome annotation databases

Ensembl

ENSG00000120265. Homo sapiens. [Contig view]

KEGG

hsa:5110.

Organism-specific databases

GeneCards

GC06P150112.

H-InvDB

HIX0006288.

HGNC

HGNC:8728. PCMT1.

HPA

HPA003239.

MIM

176851. gene.

PharmGKB

PA262.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P22061.

Enzyme and pathway databases

BRENDA

2.1.1.77. 247.

Gene expression databases

ArrayExpress

P22061.

Bgee

P22061.

GermOnline

ENSG00000120265. Homo sapiens.

Family and domain databases

InterPro

IPR000682. PCMT.
[Graphical view]

PANTHER

PTHR11579. PCMT. 1 hit.

Pfam

PF01135. PCMT. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00080. pimt. 1 hit.

PROSITE

PS01279. PCMT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

19718.

SOURCE

Search...

Entry information

Entry name

PIMT_HUMAN

Accession

Primary (citable) accession number: P22061
Secondary accession number(s): A8K109 , Q14661, Q16556, Q5VYC1, Q5VYC2, Q93061, Q96II9, Q99625, Q9BQV7, Q9BQV8, Q9NP03

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	January 23, 2007
Last modified:	May 26, 2009
This is version 106 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)