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Protein

Aspartoacylase

Gene

ASPA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

Catalytic activityi

N-acyl-L-aspartate + H2O = a carboxylate + L-aspartate.1 Publication

Cofactori

Zn2+2 PublicationsNote: Binds 1 zinc ion per subunit.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi21Zinc1
Metal bindingi24Zinc1
Binding sitei63Substrate1
Metal bindingi116Zinc1
Active sitei1781 Publication1
Binding sitei178Substrate1
Binding sitei288Substrate1

GO - Molecular functioni

GO - Biological processi

  • aspartate catabolic process Source: ProtInc
  • cellular amino acid biosynthetic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS03094-MONOMER.
ZFISH:HS03094-MONOMER.
BRENDAi3.5.1.15. 2681.
ReactomeiR-HSA-70614. Amino acid synthesis and interconversion (transamination).

Names & Taxonomyi

Protein namesi
Recommended name:
Aspartoacylase (EC:3.5.1.15)
Alternative name(s):
Aminoacylase-2
Short name:
ACY-2
Gene namesi
Name:ASPA
Synonyms:ACY2, ASP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:756. ASPA.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Canavan disease (CAND)11 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:271900
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03907916I → T in CAND; <0.5% residual enzyme activity. 2 PublicationsCorresponds to variant rs769653717dbSNPEnsembl.1
Natural variantiVAR_01677821H → P in CAND. 1 Publication1
Natural variantiVAR_01678224E → G in CAND. 1 PublicationCorresponds to variant rs104894551dbSNPEnsembl.1
Natural variantiVAR_03908027G → R in CAND; 3% residual enzyme activity. 2 PublicationsCorresponds to variant rs766328537dbSNPEnsembl.1
Natural variantiVAR_01677957A → T in CAND. 1 Publication1
Natural variantiVAR_01678368D → A in CAND. 1 Publication1
Natural variantiVAR_039081114D → E in CAND; <0.5% residual enzyme activity. 1 Publication1
Natural variantiVAR_016784114D → Y in CAND. 1 Publication1
Natural variantiVAR_039082123G → E in CAND; about 25% residual enzyme activity. 1 Publication1
Natural variantiVAR_004995143I → T in CAND. 1 PublicationCorresponds to variant rs777936704dbSNPEnsembl.1
Natural variantiVAR_004996152C → R in CAND; loss of activity. 1 PublicationCorresponds to variant rs104894548dbSNPEnsembl.1
Natural variantiVAR_016785152C → W in CAND. 1 Publication1
Natural variantiVAR_039083152C → Y in CAND; <0.5% residual enzyme activity. 1 Publication1
Natural variantiVAR_039084168R → C in CAND; undetectable enzyme activity. 1 Publication1
Natural variantiVAR_016780168R → H in CAND. 1 PublicationCorresponds to variant rs770706390dbSNPEnsembl.1
Natural variantiVAR_004997176 – 177Missing in CAND. 1 Publication2
Natural variantiVAR_016781181P → T in CAND. 1 PublicationCorresponds to variant rs786204572dbSNPEnsembl.1
Natural variantiVAR_039085183P → H in CAND. 1 Publication1
Natural variantiVAR_039086186V → F in CAND. 1 Publication1
Natural variantiVAR_039087195M → R in CAND. 1 Publication1
Natural variantiVAR_016786231Y → C in CAND. 1 PublicationCorresponds to variant rs104894550dbSNPEnsembl.1
Natural variantiVAR_016787244H → R in CAND. 1 Publication1
Natural variantiVAR_016788249D → V in CAND. 2 PublicationsCorresponds to variant rs104894552dbSNPEnsembl.1
Natural variantiVAR_004998274G → R in CAND. 2 PublicationsCorresponds to variant rs761064915dbSNPEnsembl.1
Natural variantiVAR_039088280P → L in CAND. 1 Publication1
Natural variantiVAR_039089280P → S in CAND. 1 PublicationCorresponds to variant rs750505963dbSNPEnsembl.1
Natural variantiVAR_004999285E → A in CAND; predominant mutation in Ashkenazi Jewish population; 99% loss of activity. 4 PublicationsCorresponds to variant rs28940279dbSNPEnsembl.1
Natural variantiVAR_039090287A → T in CAND. 1 PublicationCorresponds to variant rs774323189dbSNPEnsembl.1
Natural variantiVAR_005000295F → S in CAND. 2 Publications1
Natural variantiVAR_005001305A → E in CAND; pan-European origin; most prevalent among non-Jewish CAND patients; probably the most ancient mutation; loss of activity. 4 PublicationsCorresponds to variant rs28940574dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi71R → K: Reduces activity by 99%. 1 Publication1
Mutagenesisi164Y → F: Reduces activity by 99%. 1 Publication1
Mutagenesisi168R → K: Reduces activity by 99%. 1 Publication1
Mutagenesisi178E → A: Reduces activity by 99%. 2 Publications1
Mutagenesisi178E → D: Abolishes enzymatic activity. 2 Publications1
Mutagenesisi178E → Q: Abolishes enzymatic activity. 2 Publications1
Mutagenesisi285E → D: 5-fold decrease in activity. 1 Publication1
Mutagenesisi288Y → F: Reduces activity by 99%. 1 Publication1

Keywords - Diseasei

Disease mutation, Leukodystrophy

Organism-specific databases

DisGeNETi443.
MalaCardsiASPA.
MIMi271900. phenotype.
OpenTargetsiENSG00000108381.
Orphaneti314918. Mild Canavan disease.
314911. Severe Canavan disease.
PharmGKBiPA25055.

Chemistry databases

DrugBankiDB00128. L-Aspartic Acid.

Polymorphism and mutation databases

BioMutaiASPA.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002168711 – 313AspartoacylaseAdd BLAST313

Proteomic databases

PaxDbiP45381.
PeptideAtlasiP45381.
PRIDEiP45381.

PTM databases

iPTMnetiP45381.
PhosphoSitePlusiP45381.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000108381.
CleanExiHS_ASPA.
ExpressionAtlasiP45381. baseline and differential.
GenevisibleiP45381. HS.

Organism-specific databases

HPAiHPA022142.
HPA022145.

Interactioni

Subunit structurei

Homodimer.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ACY3Q96HD95EBI-750475,EBI-3916242

Protein-protein interaction databases

BioGridi106935. 5 interactors.
DIPiDIP-60793N.
IntActiP45381. 1 interactor.
MINTiMINT-1440951.
STRINGi9606.ENSP00000263080.

Structurei

Secondary structure

1313
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi14 – 18Combined sources5
Helixi25 – 34Combined sources10
Helixi39 – 41Combined sources3
Beta strandi48 – 53Combined sources6
Helixi55 – 59Combined sources5
Beta strandi65 – 67Combined sources3
Helixi69 – 71Combined sources3
Helixi75 – 78Combined sources4
Beta strandi84 – 86Combined sources3
Helixi88 – 100Combined sources13
Beta strandi105 – 108Combined sources4
Beta strandi110 – 117Combined sources8
Beta strandi119 – 121Combined sources3
Beta strandi123 – 129Combined sources7
Helixi134 – 147Combined sources14
Beta strandi152 – 156Combined sources5
Beta strandi160 – 162Combined sources3
Helixi167 – 170Combined sources4
Beta strandi171 – 181Combined sources11
Helixi189 – 210Combined sources22
Beta strandi218 – 229Combined sources12
Beta strandi237 – 239Combined sources3
Beta strandi241 – 243Combined sources3
Turni245 – 249Combined sources5
Beta strandi259 – 263Combined sources5
Beta strandi269 – 271Combined sources3
Beta strandi274 – 276Combined sources3
Beta strandi278 – 282Combined sources5
Helixi286 – 288Combined sources3
Turni289 – 292Combined sources4
Beta strandi294 – 305Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2I3CX-ray2.80A/B2-313[»]
2O4HX-ray2.70A/B1-313[»]
2O53X-ray2.70A/B1-313[»]
2Q51X-ray2.80A/B2-313[»]
4MRIX-ray2.80A/B1-313[»]
4MXUX-ray2.60A/B1-313[»]
4NFRX-ray3.00A/B1-313[»]
4TNUX-ray2.90A/B1-313[»]
ProteinModelPortaliP45381.
SMRiP45381.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP45381.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni70 – 71Substrate binding2
Regioni164 – 168Substrate binding5

Sequence similaritiesi

Phylogenomic databases

eggNOGiENOG410IERR. Eukaryota.
COG2988. LUCA.
GeneTreeiENSGT00390000001189.
HOGENOMiHOG000232489.
HOVERGENiHBG004172.
InParanoidiP45381.
KOiK01437.
OMAiNFNEGKE.
OrthoDBiEOG091G0BL6.
PhylomeDBiP45381.
TreeFamiTF328708.

Family and domain databases

HAMAPiMF_00704. Aspartoacylase. 1 hit.
InterProiIPR016708. Aspartoacylase.
IPR007036. Aste_AspA.
[Graphical view]
PfamiPF04952. AstE_AspA. 1 hit.
[Graphical view]
PIRSFiPIRSF018001. Aspartoacylase. 1 hit.

Sequencei

Sequence statusi: Complete.

P45381-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTSCHIAEEH IQKVAIFGGT HGNELTGVFL VKHWLENGAE IQRTGLEVKP
60 70 80 90 100
FITNPRAVKK CTRYIDCDLN RIFDLENLGK KMSEDLPYEV RRAQEINHLF
110 120 130 140 150
GPKDSEDSYD IIFDLHNTTS NMGCTLILED SRNNFLIQMF HYIKTSLAPL
160 170 180 190 200
PCYVYLIEHP SLKYATTRSI AKYPVGIEVG PQPQGVLRAD ILDQMRKMIK
210 220 230 240 250
HALDFIHHFN EGKEFPPCAI EVYKIIEKVD YPRDENGEIA AIIHPNLQDQ
260 270 280 290 300
DWKPLHPGDP MFLTLDGKTI PLGGDCTVYP VFVNEAAYYE KKEAFAKTTK
310
LTLNAKSIRC CLH
Length:313
Mass (Da):35,735
Last modified:November 1, 1995 - v1
Checksum:i33C0B9B07839E7F5
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03907916I → T in CAND; <0.5% residual enzyme activity. 2 PublicationsCorresponds to variant rs769653717dbSNPEnsembl.1
Natural variantiVAR_01677821H → P in CAND. 1 Publication1
Natural variantiVAR_01678224E → G in CAND. 1 PublicationCorresponds to variant rs104894551dbSNPEnsembl.1
Natural variantiVAR_03908027G → R in CAND; 3% residual enzyme activity. 2 PublicationsCorresponds to variant rs766328537dbSNPEnsembl.1
Natural variantiVAR_01677957A → T in CAND. 1 Publication1
Natural variantiVAR_01678368D → A in CAND. 1 Publication1
Natural variantiVAR_039081114D → E in CAND; <0.5% residual enzyme activity. 1 Publication1
Natural variantiVAR_016784114D → Y in CAND. 1 Publication1
Natural variantiVAR_039082123G → E in CAND; about 25% residual enzyme activity. 1 Publication1
Natural variantiVAR_004995143I → T in CAND. 1 PublicationCorresponds to variant rs777936704dbSNPEnsembl.1
Natural variantiVAR_004996152C → R in CAND; loss of activity. 1 PublicationCorresponds to variant rs104894548dbSNPEnsembl.1
Natural variantiVAR_016785152C → W in CAND. 1 Publication1
Natural variantiVAR_039083152C → Y in CAND; <0.5% residual enzyme activity. 1 Publication1
Natural variantiVAR_039084168R → C in CAND; undetectable enzyme activity. 1 Publication1
Natural variantiVAR_016780168R → H in CAND. 1 PublicationCorresponds to variant rs770706390dbSNPEnsembl.1
Natural variantiVAR_004997176 – 177Missing in CAND. 1 Publication2
Natural variantiVAR_016781181P → T in CAND. 1 PublicationCorresponds to variant rs786204572dbSNPEnsembl.1
Natural variantiVAR_039085183P → H in CAND. 1 Publication1
Natural variantiVAR_039086186V → F in CAND. 1 Publication1
Natural variantiVAR_039087195M → R in CAND. 1 Publication1
Natural variantiVAR_016786231Y → C in CAND. 1 PublicationCorresponds to variant rs104894550dbSNPEnsembl.1
Natural variantiVAR_016787244H → R in CAND. 1 Publication1
Natural variantiVAR_016788249D → V in CAND. 2 PublicationsCorresponds to variant rs104894552dbSNPEnsembl.1
Natural variantiVAR_004998274G → R in CAND. 2 PublicationsCorresponds to variant rs761064915dbSNPEnsembl.1
Natural variantiVAR_039088280P → L in CAND. 1 Publication1
Natural variantiVAR_039089280P → S in CAND. 1 PublicationCorresponds to variant rs750505963dbSNPEnsembl.1
Natural variantiVAR_004999285E → A in CAND; predominant mutation in Ashkenazi Jewish population; 99% loss of activity. 4 PublicationsCorresponds to variant rs28940279dbSNPEnsembl.1
Natural variantiVAR_039090287A → T in CAND. 1 PublicationCorresponds to variant rs774323189dbSNPEnsembl.1
Natural variantiVAR_005000295F → S in CAND. 2 Publications1
Natural variantiVAR_005001305A → E in CAND; pan-European origin; most prevalent among non-Jewish CAND patients; probably the most ancient mutation; loss of activity. 4 PublicationsCorresponds to variant rs28940574dbSNPEnsembl.1
Natural variantiVAR_039091310C → G.1 PublicationCorresponds to variant rs376854191dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S67156 mRNA. Translation: AAB29190.1.
BC029128 mRNA. Translation: AAH29128.1.
CCDSiCCDS11028.1.
PIRiS38538.
RefSeqiNP_000040.1. NM_000049.2.
NP_001121557.1. NM_001128085.1.
XP_016880150.1. XM_017024661.1.
UniGeneiHs.171142.

Genome annotation databases

EnsembliENST00000263080; ENSP00000263080; ENSG00000108381.
ENST00000456349; ENSP00000409976; ENSG00000108381.
GeneIDi443.
KEGGihsa:443.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S67156 mRNA. Translation: AAB29190.1.
BC029128 mRNA. Translation: AAH29128.1.
CCDSiCCDS11028.1.
PIRiS38538.
RefSeqiNP_000040.1. NM_000049.2.
NP_001121557.1. NM_001128085.1.
XP_016880150.1. XM_017024661.1.
UniGeneiHs.171142.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2I3CX-ray2.80A/B2-313[»]
2O4HX-ray2.70A/B1-313[»]
2O53X-ray2.70A/B1-313[»]
2Q51X-ray2.80A/B2-313[»]
4MRIX-ray2.80A/B1-313[»]
4MXUX-ray2.60A/B1-313[»]
4NFRX-ray3.00A/B1-313[»]
4TNUX-ray2.90A/B1-313[»]
ProteinModelPortaliP45381.
SMRiP45381.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106935. 5 interactors.
DIPiDIP-60793N.
IntActiP45381. 1 interactor.
MINTiMINT-1440951.
STRINGi9606.ENSP00000263080.

Chemistry databases

DrugBankiDB00128. L-Aspartic Acid.

PTM databases

iPTMnetiP45381.
PhosphoSitePlusiP45381.

Polymorphism and mutation databases

BioMutaiASPA.

Proteomic databases

PaxDbiP45381.
PeptideAtlasiP45381.
PRIDEiP45381.

Protocols and materials databases

DNASUi443.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263080; ENSP00000263080; ENSG00000108381.
ENST00000456349; ENSP00000409976; ENSG00000108381.
GeneIDi443.
KEGGihsa:443.

Organism-specific databases

CTDi443.
DisGeNETi443.
GeneCardsiASPA.
GeneReviewsiASPA.
HGNCiHGNC:756. ASPA.
HPAiHPA022142.
HPA022145.
MalaCardsiASPA.
MIMi271900. phenotype.
608034. gene.
neXtProtiNX_P45381.
OpenTargetsiENSG00000108381.
Orphaneti314918. Mild Canavan disease.
314911. Severe Canavan disease.
PharmGKBiPA25055.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IERR. Eukaryota.
COG2988. LUCA.
GeneTreeiENSGT00390000001189.
HOGENOMiHOG000232489.
HOVERGENiHBG004172.
InParanoidiP45381.
KOiK01437.
OMAiNFNEGKE.
OrthoDBiEOG091G0BL6.
PhylomeDBiP45381.
TreeFamiTF328708.

Enzyme and pathway databases

BioCyciMetaCyc:HS03094-MONOMER.
ZFISH:HS03094-MONOMER.
BRENDAi3.5.1.15. 2681.
ReactomeiR-HSA-70614. Amino acid synthesis and interconversion (transamination).

Miscellaneous databases

EvolutionaryTraceiP45381.
GenomeRNAii443.
PROiP45381.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000108381.
CleanExiHS_ASPA.
ExpressionAtlasiP45381. baseline and differential.
GenevisibleiP45381. HS.

Family and domain databases

HAMAPiMF_00704. Aspartoacylase. 1 hit.
InterProiIPR016708. Aspartoacylase.
IPR007036. Aste_AspA.
[Graphical view]
PfamiPF04952. AstE_AspA. 1 hit.
[Graphical view]
PIRSFiPIRSF018001. Aspartoacylase. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiACY2_HUMAN
AccessioniPrimary (citable) accession number: P45381
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 30, 2016
This is version 157 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.