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Protein

Isoaspartyl peptidase/L-asparaginase

Gene

ASRGL1

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

Functioni

Has both L-asparaginase and beta-aspartyl peptidase activity. May be involved in the production of L-aspartate, which can act as an excitatory neurotransmitter in some brain regions. Is highly active with L-Asp beta-methyl ester. Besides, has catalytic activity toward beta-aspartyl dipeptides and their methyl esters, including beta-L-Asp-L-Phe, beta-L-Asp-L-Phe methyl ester (aspartame), beta-L-Asp-L-Ala, beta-L-Asp-L-Leu and beta-L-Asp-L-Lys. Does not have aspartylglucosaminidase activity and is inactive toward GlcNAc-L-Asn. Likewise, has no activity toward glutamine.1 Publication

Catalytic activityi

L-asparagine + H2O = L-aspartate + NH3.2 Publications
Cleavage of a beta-linked Asp residue from the N-terminus of a polypeptide.1 Publication

Enzyme regulationi

Glycine accelerates autocleavage into an alpha and beta chain.1 Publication

Kineticsi

  1. KM=3.4 mM for L-asparagine (L-Asn)1 Publication
  2. KM=0.4 mM for L-aspartic acid beta-methyl ester1 Publication
  3. KM=0.4 mM for L-Asp-L-Phe1 Publication
  4. KM=1.0 mM for L-Asp-L-Ala1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei168Nucleophile2 Publications1

    GO - Molecular functioni

    • asparaginase activity Source: UniProtKB
    • beta-aspartyl-peptidase activity Source: UniProtKB

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Protease

    Enzyme and pathway databases

    BioCyciMetaCyc:HS08648-MONOMER.
    ZFISH:HS08648-MONOMER.
    BRENDAi3.4.19.5. 2681.
    ReactomeiR-HSA-71182. Phenylalanine and tyrosine catabolism.

    Protein family/group databases

    MEROPSiT02.002.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Isoaspartyl peptidase/L-asparaginase (EC:3.4.19.51 Publication, EC:3.5.1.12 Publications)
    Alternative name(s):
    Asparaginase-like protein 11 Publication
    Beta-aspartyl-peptidase1 Publication
    Isoaspartyl dipeptidase
    L-asparagine amidohydrolase
    Cleaved into the following 2 chains:
    Gene namesi
    Name:ASRGL1
    Synonyms:ALP, CRASH
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:16448. ASRGL1.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: UniProtKB
    • cytosol Source: Reactome
    • nucleus Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi168T → A or C: Abolishes activation by autocleavage. Abolishes enzyme activity. 2 Publications1
    Mutagenesisi168T → S: Strongly reduced enzyme activity. 2 Publications1

    Organism-specific databases

    DisGeNETi80150.
    OpenTargetsiENSG00000162174.
    PharmGKBiPA25059.

    Chemistry databases

    DrugBankiDB00174. L-Asparagine.
    DB00128. L-Aspartic Acid.

    Polymorphism and mutation databases

    BioMutaiASRGL1.
    DMDMi158706477.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003052041 – 167Isoaspartyl peptidase/L-asparaginase alpha chainAdd BLAST167
    ChainiPRO_0000420556168 – 308Isoaspartyl peptidase/L-asparaginase beta chainAdd BLAST141

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineCombined sources1

    Post-translational modificationi

    Cleaved into an alpha and beta chain by autocatalysis; this activates the enzyme. The N-terminal residue of the beta subunit is responsible for the nucleophile hydrolase activity.2 Publications

    Keywords - PTMi

    Acetylation, Autocatalytic cleavage

    Proteomic databases

    EPDiQ7L266.
    MaxQBiQ7L266.
    PaxDbiQ7L266.
    PeptideAtlasiQ7L266.
    PRIDEiQ7L266.

    2D gel databases

    UCD-2DPAGEQ7L266.

    PTM databases

    iPTMnetiQ7L266.
    PhosphoSitePlusiQ7L266.

    Expressioni

    Tissue specificityi

    Expressed in brain, kidney, testis and tissues of the gastrointestinal tract. Present in sperm (at protein level). Over-expressed in uterine, mammary, prostatic and ovarian carcinoma.2 Publications

    Inductioni

    By 5-alpha-di-hydrotestosterone and progesterone.1 Publication

    Gene expression databases

    BgeeiENSG00000162174.
    CleanExiHS_ASRGL1.
    ExpressionAtlasiQ7L266. baseline and differential.
    GenevisibleiQ7L266. HS.

    Organism-specific databases

    HPAiHPA029725.
    HPA055572.

    Interactioni

    Subunit structurei

    Heterodimer of an alpha and beta chain produced by autocleavage. This heterodimer may then dimerize in turn, giving rise to a heterotetramer.2 Publications

    Protein-protein interaction databases

    BioGridi123142. 6 interactors.
    IntActiQ7L266. 4 interactors.
    STRINGi9606.ENSP00000301776.

    Structurei

    Secondary structure

    1308
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi4 – 8Combined sources5
    Helixi17 – 38Combined sources22
    Turni39 – 41Combined sources3
    Helixi44 – 57Combined sources14
    Beta strandi61 – 64Combined sources4
    Beta strandi71 – 73Combined sources3
    Beta strandi77 – 83Combined sources7
    Turni84 – 86Combined sources3
    Beta strandi89 – 95Combined sources7
    Helixi101 – 111Combined sources11
    Beta strandi115 – 118Combined sources4
    Helixi119 – 128Combined sources10
    Helixi136 – 138Combined sources3
    Helixi142 – 152Combined sources11
    Beta strandi169 – 174Combined sources6
    Beta strandi180 – 186Combined sources7
    Turni203 – 205Combined sources3
    Beta strandi206 – 210Combined sources5
    Turni211 – 213Combined sources3
    Beta strandi214 – 220Combined sources7
    Helixi222 – 228Combined sources7
    Helixi230 – 239Combined sources10
    Helixi244 – 259Combined sources16
    Beta strandi263 – 269Combined sources7
    Beta strandi274 – 282Combined sources9
    Beta strandi285 – 289Combined sources5
    Beta strandi292 – 298Combined sources7
    Beta strandi303 – 306Combined sources4

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3TKJX-ray2.30A/B2-308[»]
    4ET0X-ray3.30A/B2-308[»]
    4O0CX-ray1.50A/B1-308[»]
    4O0DX-ray1.95A/B1-308[»]
    4O0EX-ray1.71A/B1-308[»]
    4O0FX-ray1.92A/B1-308[»]
    4O0GX-ray2.10A/B1-308[»]
    4O0HX-ray1.97A/B1-308[»]
    4OSXX-ray1.95A/B1-308[»]
    4OSYX-ray1.91A/B1-308[»]
    4PVPX-ray1.85A/B1-308[»]
    4PVQX-ray2.13A/B1-308[»]
    4PVRX-ray1.75A/B1-308[»]
    4PVSX-ray1.84A/B1-308[»]
    4ZM9X-ray2.51A/B/C/D2-308[»]
    ProteinModelPortaliQ7L266.
    SMRiQ7L266.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni196 – 199Substrate binding4
    Regioni219 – 222Substrate binding4

    Sequence similaritiesi

    Belongs to the Ntn-hydrolase family.Curated

    Phylogenomic databases

    eggNOGiKOG1592. Eukaryota.
    COG1446. LUCA.
    GeneTreeiENSGT00530000063034.
    HOGENOMiHOG000174613.
    HOVERGENiHBG101662.
    InParanoidiQ7L266.
    KOiK13051.
    OMAiPCVGAGG.
    OrthoDBiEOG091G0CKQ.
    PhylomeDBiQ7L266.
    TreeFamiTF323960.

    Family and domain databases

    CDDicd04702. ASRGL1_like. 1 hit.
    InterProiIPR033844. ASRGL1_meta.
    IPR029055. Ntn_hydrolases_N.
    IPR000246. Peptidase_T2.
    [Graphical view]
    PANTHERiPTHR10188. PTHR10188. 1 hit.
    PfamiPF01112. Asparaginase_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF56235. SSF56235. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q7L266-1) [UniParc]FASTAAdd to basket

    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.

    « Hide

            10         20         30         40         50
    MNPIVVVHGG GAGPISKDRK ERVHQGMVRA ATVGYGILRE GGSAVDAVEG
    60 70 80 90 100
    AVVALEDDPE FNAGCGSVLN TNGEVEMDAS IMDGKDLSAG AVSAVQCIAN
    110 120 130 140 150
    PIKLARLVME KTPHCFLTDQ GAAQFAAAMG VPEIPGEKLV TERNKKRLEK
    160 170 180 190 200
    EKHEKGAQKT DCQKNLGTVG AVALDCKGNV AYATSTGGIV NKMVGRVGDS
    210 220 230 240 250
    PCLGAGGYAD NDIGAVSTTG HGESILKVNL ARLTLFHIEQ GKTVEEAADL
    260 270 280 290 300
    SLGYMKSRVK GLGGLIVVSK TGDWVAKWTS TSMPWAAAKD GKLHFGIDPD

    DTTITDLP
    Length:308
    Mass (Da):32,055
    Last modified:April 3, 2007 - v2
    Checksum:i84E3D6C2D1555B32
    GO
    Isoform 2 (identifier: Q7L266-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-128: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:180
    Mass (Da):18,981
    Checksum:iE21C4620A2261D0C
    GO

    Sequence cautioni

    The sequence BAB15302 differs from that shown. Contaminating sequence.Curated
    The sequence BAB15302 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti181A → T in AAM28434 (PubMed:11984834).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0282871 – 128Missing in isoform 2. 1 PublicationAdd BLAST128

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF411076 mRNA. Translation: AAM28434.1.
    AK025969 mRNA. Translation: BAB15302.1. Different initiation.
    AK091894 mRNA. Translation: BAG52437.1.
    AK313069 mRNA. Translation: BAG35897.1.
    CH471076 Genomic DNA. Translation: EAW74012.1.
    BC021295 mRNA. Translation: AAH21295.3.
    BC064963 mRNA. Translation: AAH64963.1.
    BC093070 mRNA. Translation: AAH93070.1.
    CCDSiCCDS8019.1. [Q7L266-1]
    RefSeqiNP_001077395.1. NM_001083926.1. [Q7L266-1]
    NP_079356.3. NM_025080.3. [Q7L266-1]
    XP_005274362.1. XM_005274305.3. [Q7L266-2]
    XP_005274363.1. XM_005274306.2. [Q7L266-2]
    UniGeneiHs.535326.

    Genome annotation databases

    EnsembliENST00000301776; ENSP00000301776; ENSG00000162174. [Q7L266-1]
    ENST00000415229; ENSP00000400057; ENSG00000162174. [Q7L266-1]
    GeneIDi80150.
    KEGGihsa:80150.
    UCSCiuc001nte.5. human. [Q7L266-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF411076 mRNA. Translation: AAM28434.1.
    AK025969 mRNA. Translation: BAB15302.1. Different initiation.
    AK091894 mRNA. Translation: BAG52437.1.
    AK313069 mRNA. Translation: BAG35897.1.
    CH471076 Genomic DNA. Translation: EAW74012.1.
    BC021295 mRNA. Translation: AAH21295.3.
    BC064963 mRNA. Translation: AAH64963.1.
    BC093070 mRNA. Translation: AAH93070.1.
    CCDSiCCDS8019.1. [Q7L266-1]
    RefSeqiNP_001077395.1. NM_001083926.1. [Q7L266-1]
    NP_079356.3. NM_025080.3. [Q7L266-1]
    XP_005274362.1. XM_005274305.3. [Q7L266-2]
    XP_005274363.1. XM_005274306.2. [Q7L266-2]
    UniGeneiHs.535326.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3TKJX-ray2.30A/B2-308[»]
    4ET0X-ray3.30A/B2-308[»]
    4O0CX-ray1.50A/B1-308[»]
    4O0DX-ray1.95A/B1-308[»]
    4O0EX-ray1.71A/B1-308[»]
    4O0FX-ray1.92A/B1-308[»]
    4O0GX-ray2.10A/B1-308[»]
    4O0HX-ray1.97A/B1-308[»]
    4OSXX-ray1.95A/B1-308[»]
    4OSYX-ray1.91A/B1-308[»]
    4PVPX-ray1.85A/B1-308[»]
    4PVQX-ray2.13A/B1-308[»]
    4PVRX-ray1.75A/B1-308[»]
    4PVSX-ray1.84A/B1-308[»]
    4ZM9X-ray2.51A/B/C/D2-308[»]
    ProteinModelPortaliQ7L266.
    SMRiQ7L266.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi123142. 6 interactors.
    IntActiQ7L266. 4 interactors.
    STRINGi9606.ENSP00000301776.

    Chemistry databases

    DrugBankiDB00174. L-Asparagine.
    DB00128. L-Aspartic Acid.

    Protein family/group databases

    MEROPSiT02.002.

    PTM databases

    iPTMnetiQ7L266.
    PhosphoSitePlusiQ7L266.

    Polymorphism and mutation databases

    BioMutaiASRGL1.
    DMDMi158706477.

    2D gel databases

    UCD-2DPAGEQ7L266.

    Proteomic databases

    EPDiQ7L266.
    MaxQBiQ7L266.
    PaxDbiQ7L266.
    PeptideAtlasiQ7L266.
    PRIDEiQ7L266.

    Protocols and materials databases

    DNASUi80150.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000301776; ENSP00000301776; ENSG00000162174. [Q7L266-1]
    ENST00000415229; ENSP00000400057; ENSG00000162174. [Q7L266-1]
    GeneIDi80150.
    KEGGihsa:80150.
    UCSCiuc001nte.5. human. [Q7L266-1]

    Organism-specific databases

    CTDi80150.
    DisGeNETi80150.
    GeneCardsiASRGL1.
    HGNCiHGNC:16448. ASRGL1.
    HPAiHPA029725.
    HPA055572.
    MIMi609212. gene.
    neXtProtiNX_Q7L266.
    OpenTargetsiENSG00000162174.
    PharmGKBiPA25059.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1592. Eukaryota.
    COG1446. LUCA.
    GeneTreeiENSGT00530000063034.
    HOGENOMiHOG000174613.
    HOVERGENiHBG101662.
    InParanoidiQ7L266.
    KOiK13051.
    OMAiPCVGAGG.
    OrthoDBiEOG091G0CKQ.
    PhylomeDBiQ7L266.
    TreeFamiTF323960.

    Enzyme and pathway databases

    BioCyciMetaCyc:HS08648-MONOMER.
    ZFISH:HS08648-MONOMER.
    BRENDAi3.4.19.5. 2681.
    ReactomeiR-HSA-71182. Phenylalanine and tyrosine catabolism.

    Miscellaneous databases

    ChiTaRSiASRGL1. human.
    GeneWikiiASRGL1.
    GenomeRNAii80150.
    PROiQ7L266.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000162174.
    CleanExiHS_ASRGL1.
    ExpressionAtlasiQ7L266. baseline and differential.
    GenevisibleiQ7L266. HS.

    Family and domain databases

    CDDicd04702. ASRGL1_like. 1 hit.
    InterProiIPR033844. ASRGL1_meta.
    IPR029055. Ntn_hydrolases_N.
    IPR000246. Peptidase_T2.
    [Graphical view]
    PANTHERiPTHR10188. PTHR10188. 1 hit.
    PfamiPF01112. Asparaginase_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF56235. SSF56235. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiASGL1_HUMAN
    AccessioniPrimary (citable) accession number: Q7L266
    Secondary accession number(s): B2R7Q0
    , Q567Q4, Q6P1P0, Q8NI34, Q9H6F7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 2, 2007
    Last sequence update: April 3, 2007
    Last modified: November 30, 2016
    This is version 119 of the entry and version 2 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 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. 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.