Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P45381 (ACY2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Aspartoacylase

EC=3.5.1.15
Alternative name(s):
Aminoacylase-2
Short name=ACY-2
Gene names
Name:ASPA
Synonyms:ACY2, ASP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length313 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate. NAA occurs in high concentration in brain and its hydrolysis NAA plays a significant part in the maintenance of intact white matter. In other tissues it act as a scavenger of NAA from body fluids. HAMAP-Rule MF_00704

Catalytic activity

N-acyl-L-aspartate + H2O = a carboxylate + L-aspartate. Ref.4

Cofactor

Binds 1 zinc ion per subunit. Ref.5 Ref.6

Subunit structure

Homodimer Probable. Ref.5 Ref.6

Subcellular location

Cytoplasm. Nucleus By similarity HAMAP-Rule MF_00704.

Tissue specificity

Brain white matter, skeletal muscle, kidney, adrenal glands, lung and liver.

Involvement in disease

Canavan disease (CAND) [MIM:271900]: A rare neurodegenerative condition of infancy or childhood characterized by white matter vacuolization and demyelination that gives rise to a spongy appearance. The clinical features are onset in early infancy, atonia of neck muscles, hypotonia, hyperextension of legs and flexion of arms, blindness, severe mental defect, megalocephaly, and death by 18 months on the average.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.3 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16

Sequence similarities

Belongs to the AspA/AstE family. Aspartoacylase subfamily.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 313313Aspartoacylase HAMAP-Rule MF_00704
PRO_0000216871

Regions

Region70 – 712Substrate binding HAMAP-Rule MF_00704
Region164 – 1685Substrate binding HAMAP-Rule MF_00704

Sites

Active site1781 Ref.4
Metal binding211Zinc
Metal binding241Zinc
Metal binding1161Zinc
Binding site631Substrate
Binding site1781Substrate
Binding site2881Substrate

Natural variations

Natural variant161I → T in CAND; <0.5% residual enzyme activity. Ref.10 Ref.13
VAR_039079
Natural variant211H → P in CAND. Ref.14
VAR_016778
Natural variant241E → G in CAND. Ref.15
VAR_016782
Natural variant271G → R in CAND; 3% residual enzyme activity. Ref.10 Ref.13
VAR_039080
Natural variant571A → T in CAND. Ref.14
VAR_016779
Natural variant681D → A in CAND. Ref.15
VAR_016783
Natural variant1141D → E in CAND; <0.5% residual enzyme activity. Ref.10
VAR_039081
Natural variant1141D → Y in CAND. Ref.16
VAR_016784
Natural variant1231G → E in CAND; about 25% residual enzyme activity. Ref.10
VAR_039082
Natural variant1431I → T in CAND; in a Japanese patient. Ref.11
VAR_004995
Natural variant1521C → R in CAND; loss of activity. Ref.9
VAR_004996
Natural variant1521C → W in CAND. Ref.15
VAR_016785
Natural variant1521C → Y in CAND; <0.5% residual enzyme activity. Ref.10
VAR_039083
Natural variant1681R → C in CAND; undetectable enzyme activity. Ref.10
VAR_039084
Natural variant1681R → H in CAND. Ref.14
VAR_016780
Natural variant176 – 1772Missing in CAND.
VAR_004997
Natural variant1811P → T in CAND. Ref.14
VAR_016781
Natural variant1831P → H in CAND. Ref.13
VAR_039085
Natural variant1861V → F in CAND. Ref.13
VAR_039086
Natural variant1951M → R in CAND. Ref.13
VAR_039087
Natural variant2311Y → C in CAND. Ref.12
VAR_016786
Natural variant2441H → R in CAND. Ref.15
VAR_016787
Natural variant2491D → V in CAND. Ref.15 Ref.16
VAR_016788
Natural variant2741G → R in CAND. Ref.8 Ref.13
VAR_004998
Natural variant2801P → L in CAND. Ref.13
VAR_039088
Natural variant2801P → S in CAND. Ref.13
VAR_039089
Natural variant2851E → A in CAND; predominant mutation in Ashkenazi Jewish population; 99% loss of activity. Ref.1 Ref.3 Ref.7 Ref.10
Corresponds to variant rs28940279 [ dbSNP | Ensembl ].
VAR_004999
Natural variant2871A → T in CAND. Ref.13
VAR_039090
Natural variant2951F → S in CAND. Ref.8 Ref.13
VAR_005000
Natural variant3051A → E in CAND; loss of activity; pan-European origin; most prevalent among non-Jewish CAND patients; probably the most ancient mutation. Ref.7 Ref.8 Ref.10 Ref.13
Corresponds to variant rs28940574 [ dbSNP | Ensembl ].
VAR_005001
Natural variant3101C → G. Ref.10
VAR_039091

Experimental info

Mutagenesis711R → K: Reduces activity by 99%. Ref.5
Mutagenesis1641Y → F: Reduces activity by 99%. Ref.5
Mutagenesis1681R → K: Reduces activity by 99%. Ref.5
Mutagenesis1781E → A: Reduces activity by 99%. Ref.4 Ref.5
Mutagenesis1781E → D: Abolishes enzymatic activity. Ref.4 Ref.5
Mutagenesis1781E → Q: Abolishes enzymatic activity. Ref.4 Ref.5
Mutagenesis2851E → D: 5-fold decrease in activity. Ref.3
Mutagenesis2881Y → F: Reduces activity by 99%. Ref.5

Secondary structure

........................................................... 313
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P45381 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 33C0B9B07839E7F5

FASTA31335,735
        10         20         30         40         50         60 
MTSCHIAEEH IQKVAIFGGT HGNELTGVFL VKHWLENGAE IQRTGLEVKP FITNPRAVKK 

        70         80         90        100        110        120 
CTRYIDCDLN RIFDLENLGK KMSEDLPYEV RRAQEINHLF GPKDSEDSYD IIFDLHNTTS 

       130        140        150        160        170        180 
NMGCTLILED SRNNFLIQMF HYIKTSLAPL PCYVYLIEHP SLKYATTRSI AKYPVGIEVG 

       190        200        210        220        230        240 
PQPQGVLRAD ILDQMRKMIK HALDFIHHFN EGKEFPPCAI EVYKIIEKVD YPRDENGEIA 

       250        260        270        280        290        300 
AIIHPNLQDQ DWKPLHPGDP MFLTLDGKTI PLGGDCTVYP VFVNEAAYYE KKEAFAKTTK 

       310 
LTLNAKSIRC CLH 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease."
Kaul R., Gao G.P., Balamurugan K., Matalon R.
Nat. Genet. 5:118-123(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CAND ALA-285.
Tissue: Kidney.
[2]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]"Purification and preliminary characterization of brain aspartoacylase."
Moore R.A., Le Coq J., Faehnle C.R., Viola R.E.
Arch. Biochem. Biophys. 413:1-8(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION, CHARACTERIZATION OF VARIANT CAND ALA-285, MUTAGENESIS OF GLU-285.
Tissue: Brain.
[4]"Identification of the zinc binding ligands and the catalytic residue in human aspartoacylase, an enzyme involved in Canavan disease."
Herga S., Berrin J.G., Perrier J., Puigserver A., Giardina T.
FEBS Lett. 580:5899-5904(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, ZINC-BINDING SITES, ACTIVE SITE, MUTAGENESIS OF GLU-178.
[5]"Examination of the mechanism of human brain aspartoacylase through the binding of an intermediate analogue."
Le Coq J., Pavlovsky A., Malik R., Sanishvili R., Xu C., Viola R.E.
Biochemistry 47:3484-3492(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEXES WITH ZINC IONS; PHOSPHATE AND N-PHOSPHONOMETHYL-L-ASPARTATE, COFACTOR, SUBUNIT, MUTAGENESIS OF ARG-71; TYR-164; ARG-168; GLU-178 AND TYR-288.
[6]"Structure of aspartoacylase, the brain enzyme impaired in Canavan disease."
Bitto E., Bingman C.A., Wesenberg G.E., McCoy J.G., Phillips G.N. Jr.
Proc. Natl. Acad. Sci. U.S.A. 104:456-461(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH ZINC IONS, SUBUNIT, COFACTOR.
[7]"Canavan disease: mutations among Jewish and non-Jewish patients."
Kaul R., Gao G.P., Aloya M., Balamurugan K., Petrosky A., Michals K., Matalon R.
Am. J. Hum. Genet. 55:34-41(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CAND ALA-285 AND GLU-305.
[8]"The molecular basis of canavan (aspartoacylase deficiency) disease in European non-Jewish patients."
Shaag A., Anikster Y., Christensen E., Glustein J.Z., Fois A., Michelakakis H., Nigro F., Pronicka E., Ribes A., Zabot M.-T., Elpeleg O.N.
Am. J. Hum. Genet. 57:572-580(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CAND 176-GLY-ILE-177 DEL; ARG-274; SER-295 AND GLU-305.
[9]"Novel (Cys152 > Arg) missense mutation in an Arab patient with Canavan disease."
Kaul R., Gao G.P., Michals K., Whelan D.T., Levin S., Matalon R.
Hum. Mutat. 5:269-271(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CAND ARG-152.
[10]"Identification and expression of eight novel mutations among non-Jewish patients with Canavan disease."
Kaul R., Gao G.P., Matalon R., Aloya M., Su Q., Jin M., Johnson A.B., Schutgens R.B.H., Clarke J.T.R.
Am. J. Hum. Genet. 59:95-102(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CAND THR-16; ARG-27; GLU-114; GLU-123; TYR-152; CYS-168; ALA-285 AND GLU-305, VARIANT GLY-310, CHARACTERIZATION OF VARIANTS CAND THR-16; ARG-27; GLU-114; GLU-123; TYR-152 AND CYS-168.
[11]"Missense mutation (I143T) in a Japanese patient with Canavan disease."
Kobayashi K., Tsujino S., Ezoe T., Hamaguchi H., Nihei K., Sakuragawa N.
Hum. Mutat. Suppl. 1:S308-S309(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CAND THR-143.
[12]"Novel missense mutation (Y231C) in a Turkish patient with Canavan disease."
Rady P.L., Vargas T., Tyring S.K., Matalon R., Langenbeck U.
Am. J. Med. Genet. 87:273-275(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CAND CYS-231.
[13]"The spectrum of mutations of the aspartoacylase gene in Canavan disease in non-Jewish patients."
Elpeleg O.N., Shaag A.
J. Inherit. Metab. Dis. 22:531-534(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CAND THR-16; ARG-27; HIS-183; PHE-186; ARG-195; ARG-274; SER-280; LEU-280; THR-287; SER-295 AND GLU-305.
[14]"Mutation detection in the aspartoacylase gene in 17 patients with Canavan disease: four new mutations in the non-Jewish population."
Sistermans E.A., de Coo R.F., van Beerendonk H.M., Poll-The B.T., Kleijer W.J., van Oost B.A.
Eur. J. Hum. Genet. 8:557-560(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CAND PRO-21; THR-57; HIS-168 AND THR-181.
[15]"Identification and characterization of novel mutations of the aspartoacylase gene in non-Jewish patients with Canavan disease."
Zeng B.J., Wang Z.H., Ribeiro L.A., Leone P., De Gasperi R., Kim S.J., Raghavan S., Ong E., Pastores G.M., Kolodny E.H.
J. Inherit. Metab. Dis. 25:557-570(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CAND GLY-24; ALA-68; TRP-152; ARG-244 AND VAL-249.
[16]"Two novel aspartoacylase gene (ASPA) missense mutations specific to Norwegian and Swedish patients with Canavan disease."
Olsen T.R., Tranebjaerg L., Kvittingen E.A., Hagenfeldt L., Moller C., Nilssen O.
J. Med. Genet. 39:E55-E55(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CAND TYR-114 AND VAL-249.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S67156 mRNA. Translation: AAB29190.1.
BC029128 mRNA. Translation: AAH29128.1.
CCDSCCDS11028.1.
PIRS38538.
RefSeqNP_000040.1. NM_000049.2.
NP_001121557.1. NM_001128085.1.
XP_006721590.1. XM_006721527.1.
UniGeneHs.171142.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2I3CX-ray2.80A/B2-313[»]
2O4HX-ray2.70A/B1-313[»]
2O53X-ray2.70A/B1-313[»]
2Q51X-ray2.80A/B2-313[»]
ProteinModelPortalP45381.
SMRP45381. Positions 9-310.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106935. 1 interaction.
DIPDIP-60793N.
MINTMINT-1440951.
STRING9606.ENSP00000263080.

Chemistry

DrugBankDB00128. L-Aspartic Acid.

PTM databases

PhosphoSiteP45381.

Proteomic databases

PaxDbP45381.
PRIDEP45381.

Protocols and materials databases

DNASU443.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263080; ENSP00000263080; ENSG00000108381.
ENST00000456349; ENSP00000409976; ENSG00000108381.
GeneID443.
KEGGhsa:443.
UCSCuc002fvq.3. human.

Organism-specific databases

CTD443.
GeneCardsGC17P003326.
GeneReviewsASPA.
HGNCHGNC:756. ASPA.
HPAHPA022142.
HPA022145.
MIM271900. phenotype.
608034. gene.
neXtProtNX_P45381.
Orphanet314918. Mild Canavan disease.
314911. Severe Canavan disease.
PharmGKBPA25055.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2988.
HOGENOMHOG000232489.
HOVERGENHBG004172.
InParanoidP45381.
KOK01437.
OMATTRSVAK.
PhylomeDBP45381.
TreeFamTF328708.

Enzyme and pathway databases

BioCycMetaCyc:HS03094-MONOMER.

Gene expression databases

ArrayExpressP45381.
BgeeP45381.
CleanExHS_ASPA.
GenevestigatorP45381.

Family and domain databases

HAMAPMF_00704. Aspartoacylase.
InterProIPR016708. Aspartoacylase.
IPR007036. Aste_AspA.
[Graphical view]
PfamPF04952. AstE_AspA. 1 hit.
[Graphical view]
PIRSFPIRSF018001. Aspartoacylase. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP45381.
GenomeRNAi443.
NextBio1855.
PROP45381.
SOURCESearch...

Entry information

Entry nameACY2_HUMAN
AccessionPrimary (citable) accession number: P45381
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM