Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Adenylosuccinate synthetase isozyme 1

Gene

Adssl1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of the purine nucleotide cycle (PNC), which interconverts IMP and AMP to regulate the nucleotide levels in various tissues, and which contributes to glycolysis and ammoniagenesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP.1 Publication

Catalytic activityi

GTP + IMP + L-aspartate = GDP + phosphate + N(6)-(1,2-dicarboxyethyl)-AMP.UniRule annotation

Cofactori

Mg2+Note: Binds 1 Mg2+ ion per subunit.

Enzyme regulationi

Weakly inhibited by AMP non-competitively to all substrates. Inhibited by IMP non-competitively with respect to GTP. Inhibited by fructose 1,6-bisphosphate competitively with respect to IMP.

Kineticsi

  1. KM=12 µM for GTP1 Publication
  2. KM=45 µM for IMP1 Publication
  3. KM=140 µM for L-aspartate1 Publication

    pH dependencei

    Optimum pH is 6.6-6.9.1 Publication

    Pathwayi: AMP biosynthesis via de novo pathway

    This protein is involved in step 1 of the subpathway that synthesizes AMP from IMP.UniRule annotation
    Proteins known to be involved in the 2 steps of the subpathway in this organism are:
    1. Adenylosuccinate synthetase isozyme 1 (Adssl1), Adenylosuccinate synthetase isozyme 1 (Adssl1), Adenylosuccinate synthetase (Adss), Adenylosuccinate synthetase isozyme 2 (Adss), Adenylosuccinate synthetase isozyme 2 (Adss), Adenylosuccinate synthetase isozyme 1 (Adssl1)
    2. Adenylosuccinate lyase (Adsl), Adenylosuccinate lyase (Adsl), Adenylosuccinate lyase (Adsl)
    This subpathway is part of the pathway AMP biosynthesis via de novo pathway, which is itself part of Purine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes AMP from IMP, the pathway AMP biosynthesis via de novo pathway and in Purine metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei43 – 431Proton acceptorUniRule annotation
    Metal bindingi43 – 431Magnesium
    Binding sitei43 – 431Substrate
    Metal bindingi70 – 701Magnesium; via carbonyl oxygen
    Active sitei71 – 711Proton donorUniRule annotation
    Binding sitei163 – 1631IMPUniRule annotation1 Publication
    Binding sitei177 – 1771IMP; shared with dimeric partnerUniRule annotation1 Publication
    Binding sitei256 – 2561IMPUniRule annotation1 Publication
    Binding sitei271 – 2711IMPUniRule annotation1 Publication
    Binding sitei335 – 3351IMPUniRule annotation1 Publication
    Binding sitei337 – 3371GTPUniRule annotation1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi42 – 487GTPUniRule annotation1 Publication
    Nucleotide bindingi70 – 723GTPUniRule annotation1 Publication
    Nucleotide bindingi363 – 3653GTPUniRule annotation1 Publication
    Nucleotide bindingi445 – 4484GTPUniRule annotation1 Publication

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Purine biosynthesis

    Keywords - Ligandi

    GTP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi6.3.4.4. 3474.
    ReactomeiR-MMU-73817. Purine ribonucleoside monophosphate biosynthesis.
    UniPathwayiUPA00075; UER00335.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Adenylosuccinate synthetase isozyme 1UniRule annotation (EC:6.3.4.4UniRule annotation)
    Short name:
    AMPSase 1UniRule annotation
    Short name:
    AdSS 1UniRule annotation
    Alternative name(s):
    Adenylosuccinate synthetase, basic isozymeUniRule annotation
    Adenylosuccinate synthetase, muscle isozymeUniRule annotation
    Short name:
    M-type adenylosuccinate synthetaseUniRule annotation
    IMP--aspartate ligase 1UniRule annotation
    Gene namesi
    Name:Adssl1
    Synonyms:Adss1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 12

    Organism-specific databases

    MGIiMGI:87947. Adssl1.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: MGI
    • membrane Source: UniProtKB-SubCell
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 457457Adenylosuccinate synthetase isozyme 1PRO_0000095133Add
    BLAST

    Proteomic databases

    EPDiP28650.
    PaxDbiP28650.
    PRIDEiP28650.

    PTM databases

    iPTMnetiP28650.
    PhosphoSiteiP28650.

    Expressioni

    Tissue specificityi

    High levels in muscle.

    Gene expression databases

    BgeeiP28650.
    CleanExiMM_ADSSL1.
    ExpressionAtlasiP28650. baseline and differential.
    GenevisibleiP28650. MM.

    Interactioni

    Subunit structurei

    Homodimer.UniRule annotation1 Publication

    Protein-protein interaction databases

    BioGridi198010. 1 interaction.
    IntActiP28650. 2 interactions.
    MINTiMINT-4109247.
    STRINGi10090.ENSMUSP00000021726.

    Structurei

    Secondary structure

    1
    457
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni27 – 293Combined sources
    Beta strandi33 – 4210Combined sources
    Helixi46 – 549Combined sources
    Beta strandi58 – 625Combined sources
    Beta strandi71 – 744Combined sources
    Beta strandi79 – 857Combined sources
    Helixi87 – 904Combined sources
    Beta strandi94 – 985Combined sources
    Beta strandi102 – 1043Combined sources
    Helixi106 – 11712Combined sources
    Turni118 – 1203Combined sources
    Helixi124 – 1263Combined sources
    Beta strandi127 – 1315Combined sources
    Helixi139 – 15517Combined sources
    Beta strandi164 – 1663Combined sources
    Helixi167 – 1759Combined sources
    Helixi182 – 1854Combined sources
    Helixi189 – 20517Combined sources
    Helixi214 – 22815Combined sources
    Helixi229 – 2313Combined sources
    Helixi235 – 24410Combined sources
    Beta strandi250 – 2534Combined sources
    Helixi258 – 2603Combined sources
    Turni262 – 2643Combined sources
    Helixi278 – 2847Combined sources
    Helixi288 – 2903Combined sources
    Beta strandi291 – 30414Combined sources
    Beta strandi306 – 3083Combined sources
    Helixi317 – 3259Combined sources
    Turni331 – 3333Combined sources
    Beta strandi338 – 3403Combined sources
    Helixi344 – 35411Combined sources
    Beta strandi357 – 3626Combined sources
    Helixi364 – 3674Combined sources
    Beta strandi371 – 38111Combined sources
    Beta strandi384 – 3885Combined sources
    Helixi395 – 3984Combined sources
    Beta strandi400 – 4078Combined sources
    Helixi419 – 4213Combined sources
    Helixi424 – 43714Combined sources
    Beta strandi441 – 4455Combined sources
    Beta strandi447 – 4493Combined sources
    Turni450 – 4523Combined sources
    Beta strandi453 – 4553Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1IWEX-ray2.10A/B1-457[»]
    1J4BX-ray2.50A1-457[»]
    1LNYX-ray2.20A/B1-457[»]
    1LONX-ray2.10A1-457[»]
    1LOOX-ray2.20A1-457[»]
    1MEZX-ray2.40A1-457[»]
    1MF0X-ray2.50A1-457[»]
    1MF1X-ray2.70A1-457[»]
    2DGNX-ray2.40A1-457[»]
    ProteinModelPortaliP28650.
    SMRiP28650. Positions 27-457.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP28650.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni43 – 464IMP binding
    Regioni68 – 714IMP binding
    Regioni331 – 3377Substrate binding

    Sequence similaritiesi

    Belongs to the adenylosuccinate synthetase family.UniRule annotation

    Phylogenomic databases

    eggNOGiKOG1355. Eukaryota.
    COG0104. LUCA.
    HOGENOMiHOG000260959.
    HOVERGENiHBG053768.
    InParanoidiP28650.
    KOiK01939.
    PhylomeDBiP28650.

    Family and domain databases

    HAMAPiMF_00011. Adenylosucc_synth.
    MF_03126. Adenylosucc_synth_vert_basic.
    InterProiIPR018220. Adenylosuccin_syn_GTP-bd.
    IPR033128. Adenylosuccin_syn_Lys_AS.
    IPR001114. Adenylosuccinate_synthetase.
    IPR027509. AdSS_1_vert.
    IPR027417. P-loop_NTPase.
    [Graphical view]
    PANTHERiPTHR11846. PTHR11846. 1 hit.
    PfamiPF00709. Adenylsucc_synt. 1 hit.
    [Graphical view]
    SMARTiSM00788. Adenylsucc_synt. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 1 hit.
    TIGRFAMsiTIGR00184. purA. 1 hit.
    PROSITEiPS01266. ADENYLOSUCCIN_SYN_1. 1 hit.
    PS00513. ADENYLOSUCCIN_SYN_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

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

    Isoform 1 (identifier: P28650-1) [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
    MSGTRASNDR PPGTGGVKRG RLQQEAAATG SRVTVVLGAQ WGDEGKGKVV
    60 70 80 90 100
    DLLATDADIV SRCQGGNNAG HTVVVDGKEY DFHLLPSGII NTKAVSFIGN
    110 120 130 140 150
    GVVIHLPGLF EEAEKNEKKG LKDWEKRLII SDRAHLVFDF HQAVDGLQEV
    160 170 180 190 200
    QRQAQEGKNI GTTKKGIGPT YSSKAARTGL RICDLLSDFD EFSARFKNLA
    210 220 230 240 250
    HQHQSMFPTL EIDVEGQLKR LKGFAERIRP MVRDGVYFMY EALHGPPKKV
    260 270 280 290 300
    LVEGANAALL DIDFGTYPFV TSSNCTVGGV CTGLGIPPQN IGDVYGVVKA
    310 320 330 340 350
    YTTRVGIGAF PTEQINEIGD LLQNRGHEWG VTTGRKRRCG WLDLMILRYA
    360 370 380 390 400
    HMVNGFTALA LTKLDILDVL SEIKVGISYK LNGKRIPYFP ANQEILQKVE
    410 420 430 440 450
    VEYETLPGWK ADTTGARKWE DLPPQAQSYV RFVENHMGVA VKWVGVGKSR

    ESMIQLF
    Length:457
    Mass (Da):50,254
    Last modified:February 1, 1996 - v2
    Checksum:iEBEC85BF907B7FED
    GO
    Isoform 2 (identifier: P28650-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         136-136: L → LENEVPHEPLPSASLLPMCWLLAP

    Note: No experimental confirmation available.
    Show »
    Length:480
    Mass (Da):52,780
    Checksum:i875588460688208D
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei136 – 1361L → LENEVPHEPLPSASLLPMCW LLAP in isoform 2. 1 PublicationVSP_008422

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M74495 mRNA. Translation: AAA82870.1.
    BC039943 mRNA. Translation: AAH39943.1.
    CCDSiCCDS26192.1. [P28650-1]
    PIRiA39317. AJMSDS.
    RefSeqiNP_031447.1. NM_007421.2. [P28650-1]
    UniGeneiMm.3440.

    Genome annotation databases

    EnsembliENSMUST00000021726; ENSMUSP00000021726; ENSMUSG00000011148. [P28650-1]
    GeneIDi11565.
    KEGGimmu:11565.
    UCSCiuc007peu.2. mouse. [P28650-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M74495 mRNA. Translation: AAA82870.1.
    BC039943 mRNA. Translation: AAH39943.1.
    CCDSiCCDS26192.1. [P28650-1]
    PIRiA39317. AJMSDS.
    RefSeqiNP_031447.1. NM_007421.2. [P28650-1]
    UniGeneiMm.3440.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1IWEX-ray2.10A/B1-457[»]
    1J4BX-ray2.50A1-457[»]
    1LNYX-ray2.20A/B1-457[»]
    1LONX-ray2.10A1-457[»]
    1LOOX-ray2.20A1-457[»]
    1MEZX-ray2.40A1-457[»]
    1MF0X-ray2.50A1-457[»]
    1MF1X-ray2.70A1-457[»]
    2DGNX-ray2.40A1-457[»]
    ProteinModelPortaliP28650.
    SMRiP28650. Positions 27-457.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi198010. 1 interaction.
    IntActiP28650. 2 interactions.
    MINTiMINT-4109247.
    STRINGi10090.ENSMUSP00000021726.

    PTM databases

    iPTMnetiP28650.
    PhosphoSiteiP28650.

    Proteomic databases

    EPDiP28650.
    PaxDbiP28650.
    PRIDEiP28650.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000021726; ENSMUSP00000021726; ENSMUSG00000011148. [P28650-1]
    GeneIDi11565.
    KEGGimmu:11565.
    UCSCiuc007peu.2. mouse. [P28650-1]

    Organism-specific databases

    CTDi122622.
    MGIiMGI:87947. Adssl1.

    Phylogenomic databases

    eggNOGiKOG1355. Eukaryota.
    COG0104. LUCA.
    HOGENOMiHOG000260959.
    HOVERGENiHBG053768.
    InParanoidiP28650.
    KOiK01939.
    PhylomeDBiP28650.

    Enzyme and pathway databases

    UniPathwayiUPA00075; UER00335.
    BRENDAi6.3.4.4. 3474.
    ReactomeiR-MMU-73817. Purine ribonucleoside monophosphate biosynthesis.

    Miscellaneous databases

    ChiTaRSiAdssl1. mouse.
    EvolutionaryTraceiP28650.
    NextBioi279066.
    PROiP28650.
    SOURCEiSearch...

    Gene expression databases

    BgeeiP28650.
    CleanExiMM_ADSSL1.
    ExpressionAtlasiP28650. baseline and differential.
    GenevisibleiP28650. MM.

    Family and domain databases

    HAMAPiMF_00011. Adenylosucc_synth.
    MF_03126. Adenylosucc_synth_vert_basic.
    InterProiIPR018220. Adenylosuccin_syn_GTP-bd.
    IPR033128. Adenylosuccin_syn_Lys_AS.
    IPR001114. Adenylosuccinate_synthetase.
    IPR027509. AdSS_1_vert.
    IPR027417. P-loop_NTPase.
    [Graphical view]
    PANTHERiPTHR11846. PTHR11846. 1 hit.
    PfamiPF00709. Adenylsucc_synt. 1 hit.
    [Graphical view]
    SMARTiSM00788. Adenylsucc_synt. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 1 hit.
    TIGRFAMsiTIGR00184. purA. 1 hit.
    PROSITEiPS01266. ADENYLOSUCCIN_SYN_1. 1 hit.
    PS00513. ADENYLOSUCCIN_SYN_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Molecular cloning and expression of a mouse muscle cDNA encoding adenylosuccinate synthetase."
      Guicherit O.M., Rudolph F.B., Kellems R.E., Cooper B.F.
      J. Biol. Chem. 266:22582-22587(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Muscle.
    2. "Amplification of an adenylosuccinate synthetase gene in alanosine-resistant murine T-lymphoma cells. Molecular cloning of a cDNA encoding the 'non-muscle' isozyme."
      Guicherit O.M., Cooper B.F., Rudolph F.B., Kellems R.E.
      J. Biol. Chem. 269:4488-4496(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: SEQUENCE REVISION.
    3. "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] (ISOFORM 2).
      Strain: Czech II.
      Tissue: Mammary tumor.
    4. "Variations in the response of mouse isozymes of adenylosuccinate synthetase to inhibitors of physiological relevance."
      Borza T., Iancu C.V., Pike E., Honzatko R.B., Fromm H.J.
      J. Biol. Chem. 278:6673-6679(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
    5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung and Spleen.
    6. "Recombinant mouse muscle adenylosuccinate synthetase: overexpression, kinetics, and crystal structure."
      Iancu C.V., Borza T., Choe J.Y., Fromm H.J., Honzatko R.B.
      J. Biol. Chem. 276:42146-42152(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS).
    7. "IMP, GTP, and 6-phosphoryl-IMP complexes of recombinant mouse muscle adenylosuccinate synthetase."
      Iancu C.V., Borza T., Fromm H.J., Honzatko R.B.
      J. Biol. Chem. 277:26779-26787(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH IMP AND GTP.
    8. "Feedback inhibition and product complexes of recombinant mouse muscle adenylosuccinate synthetase."
      Iancu C.V., Borza T., Fromm H.J., Honzatko R.B.
      J. Biol. Chem. 277:40536-40543(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS).
    9. "Cavitation as a mechanism of substrate discrimination by adenylosuccinate synthetases."
      Iancu C.V., Zhou Y., Borza T., Fromm H.J., Honzatko R.B.
      Biochemistry 45:11703-11711(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS).

    Entry informationi

    Entry nameiPURA1_MOUSE
    AccessioniPrimary (citable) accession number: P28650
    Secondary accession number(s): Q8CHQ1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 1992
    Last sequence update: February 1, 1996
    Last modified: May 11, 2016
    This is version 151 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    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.