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Protein

Isoaspartyl peptidase/L-asparaginase

Gene

ASRGL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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
    • hydrolase activity Source: GO_Central

    GO - Biological processi

    Keywordsi

    Molecular functionHydrolase, Protease

    Enzyme and pathway databases

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

    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

    EuPathDBiHostDB:ENSG00000162174.12
    HGNCiHGNC:16448 ASRGL1
    MIMi609212 gene
    neXtProtiNX_Q7L266

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    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
    ProteomicsDBi68755
    68756 [Q7L266-2]

    2D gel databases

    UCD-2DPAGEiQ7L266

    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 Expressed in 205 organ(s), highest expression level in endometrium
    CleanExiHS_ASRGL1
    ExpressionAtlasiQ7L266 baseline and differential
    GenevisibleiQ7L266 HS

    Organism-specific databases

    HPAiCAB070192
    HPA029725
    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, 7 interactors
    IntActiQ7L266, 4 interactors
    MINTiQ7L266
    STRINGi9606.ENSP00000301776

    Structurei

    Secondary structure

    1308
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    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
    OMAiGITGKWP
    OrthoDBiEOG091G0CKQ
    PhylomeDBiQ7L266
    TreeFamiTF323960

    Family and domain databases

    CDDicd04702 ASRGL1_like, 1 hit
    InterProiView protein in InterPro
    IPR033844 ASRGL1_meta
    IPR029055 Ntn_hydrolases_N
    IPR000246 Peptidase_T2
    PANTHERiPTHR10188 PTHR10188, 1 hit
    PfamiView protein in Pfam
    PF01112 Asparaginase_2, 1 hit
    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

    This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

    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

    Computationally mapped potential isoform sequencesi

    There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    E9PJK6E9PJK6_HUMAN
    Isoaspartyl peptidase/L-asparaginas...
    ASRGL1
    70Annotation score:
    A0A087WUG3A0A087WUG3_HUMAN
    Isoaspartyl peptidase/L-asparaginas...
    ASRGL1
    164Annotation score:
    A0A087WZI5A0A087WZI5_HUMAN
    Isoaspartyl peptidase/L-asparaginas...
    ASRGL1
    133Annotation score:
    A0A087X1T8A0A087X1T8_HUMAN
    Isoaspartyl peptidase/L-asparaginas...
    ASRGL1
    56Annotation score:

    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

    Similar proteinsi

    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, 7 interactors
    IntActiQ7L266, 4 interactors
    MINTiQ7L266
    STRINGi9606.ENSP00000301776

    Chemistry databases

    DrugBankiDB00174 L-Asparagine
    DB00128 L-Aspartic Acid

    PTM databases

    iPTMnetiQ7L266
    PhosphoSitePlusiQ7L266

    Polymorphism and mutation databases

    BioMutaiASRGL1
    DMDMi158706477

    2D gel databases

    UCD-2DPAGEiQ7L266

    Proteomic databases

    EPDiQ7L266
    MaxQBiQ7L266
    PaxDbiQ7L266
    PeptideAtlasiQ7L266
    PRIDEiQ7L266
    ProteomicsDBi68755
    68756 [Q7L266-2]

    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
    EuPathDBiHostDB:ENSG00000162174.12
    GeneCardsiASRGL1
    HGNCiHGNC:16448 ASRGL1
    HPAiCAB070192
    HPA029725
    HPA055572
    MIMi609212 gene
    neXtProtiNX_Q7L266
    OpenTargetsiENSG00000162174
    PharmGKBiPA25059
    GenAtlasiSearch...

    Phylogenomic databases

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

    Enzyme and pathway databases

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

    Miscellaneous databases

    ChiTaRSiASRGL1 human
    GeneWikiiASRGL1
    GenomeRNAii80150
    PROiPR:Q7L266
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000162174 Expressed in 205 organ(s), highest expression level in endometrium
    CleanExiHS_ASRGL1
    ExpressionAtlasiQ7L266 baseline and differential
    GenevisibleiQ7L266 HS

    Family and domain databases

    CDDicd04702 ASRGL1_like, 1 hit
    InterProiView protein in InterPro
    IPR033844 ASRGL1_meta
    IPR029055 Ntn_hydrolases_N
    IPR000246 Peptidase_T2
    PANTHERiPTHR10188 PTHR10188, 1 hit
    PfamiView protein in Pfam
    PF01112 Asparaginase_2, 1 hit
    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 historyiIntegrated into UniProtKB/Swiss-Prot: October 2, 2007
    Last sequence update: April 3, 2007
    Last modified: November 7, 2018
    This is version 129 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
      Index of protein domains and families
    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. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
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