ID   ARLY_MACFA              Reviewed;         464 AA.
AC   Q60HH3;
DT   12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   23-NOV-2004, sequence version 1.
DT   03-AUG-2022, entry version 78.
DE   RecName: Full=Argininosuccinate lyase;
DE            Short=ASAL;
DE            EC=4.3.2.1 {ECO:0000250|UniProtKB:P04424};
DE   AltName: Full=Arginosuccinase;
GN   Name=ASL; ORFNames=QccE-15270;
OS   Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9541;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain cortex;
RA   Kusuda J., Osada N., Tanuma R., Hirata M., Sugano S., Hashimoto K.;
RT   "Isolation and characterization of cDNA for macaque neurological disease
RT   genes.";
RL   Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Catalyzes the reversible cleavage of L-argininosuccinate to
CC       fumarate and L-arginine, an intermediate step reaction in the urea
CC       cycle mostly providing for hepatic nitrogen detoxification into
CC       excretable urea as well as de novo L-arginine synthesis in nonhepatic
CC       tissues (By similarity). Essential regulator of intracellular and
CC       extracellular L-arginine pools. As part of citrulline-nitric oxide
CC       cycle, forms tissue-specific multiprotein complexes with
CC       argininosuccinate synthase ASS1, transport protein SLC7A1 and nitric
CC       oxide synthase NOS1, NOS2 or NOS3, allowing for cell-autonomous L-
CC       arginine synthesis while channeling extracellular L-arginine to nitric
CC       oxide synthesis pathway (By similarity).
CC       {ECO:0000250|UniProtKB:P04424}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-(N(omega)-L-arginino)succinate = fumarate + L-arginine;
CC         Xref=Rhea:RHEA:24020, ChEBI:CHEBI:29806, ChEBI:CHEBI:32682,
CC         ChEBI:CHEBI:57472; EC=4.3.2.1;
CC         Evidence={ECO:0000250|UniProtKB:P04424};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24021;
CC         Evidence={ECO:0000250|UniProtKB:P04424};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24022;
CC         Evidence={ECO:0000250|UniProtKB:P04424};
CC   -!- ACTIVITY REGULATION: Enzyme activity is regulated by acetylation.
CC       {ECO:0000250|UniProtKB:P04424}.
CC   -!- PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine
CC       from L-ornithine and carbamoyl phosphate: step 3/3.
CC       {ECO:0000250|UniProtKB:P04424}.
CC   -!- PATHWAY: Nitrogen metabolism; urea cycle; L-arginine and fumarate from
CC       (N(omega)-L-arginino)succinate: step 1/1.
CC       {ECO:0000250|UniProtKB:P04424}.
CC   -!- SUBUNIT: Homotetramer (By similarity). Forms tissue-specific complexes
CC       with ASS1, SLC7A1, HSP90AA1 and nitric oxide synthase NOS1, NOS2 or
CC       NOS3; the complex maintenance is independent of ASL catalytic function
CC       (By similarity). {ECO:0000250|UniProtKB:P04424,
CC       ECO:0000250|UniProtKB:Q91YI0}.
CC   -!- PTM: Acetylation modifies enzyme activity in response to alterations of
CC       extracellular nutrient availability. Acetylation increased with
CC       trichostin A (TSA) or with nicotinamide (NAM). Glucose increases
CC       acetylation by about a factor of 3 with decreasing enzyme activity.
CC       Acetylation on Lys-288 is decreased on the addition of extra amino
CC       acids resulting in activation of enzyme activity.
CC       {ECO:0000250|UniProtKB:P04424}.
CC   -!- SIMILARITY: Belongs to the lyase 1 family. Argininosuccinate lyase
CC       subfamily. {ECO:0000305}.
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DR   EMBL; AB125154; BAD51942.1; -; mRNA.
DR   AlphaFoldDB; Q60HH3; -.
DR   SMR; Q60HH3; -.
DR   STRING; 9541.XP_005549580.1; -.
DR   UniPathway; UPA00068; UER00114.
DR   UniPathway; UPA00158; UER00273.
DR   Proteomes; UP000233100; Unplaced.
DR   GO; GO:0004056; F:argininosuccinate lyase activity; ISS:UniProtKB.
DR   GO; GO:0006526; P:arginine biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0042450; P:arginine biosynthetic process via ornithine; IEA:InterPro.
DR   GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0000050; P:urea cycle; IEA:UniProtKB-UniPathway.
DR   CDD; cd01359; Argininosuccinate_lyase; 1.
DR   Gene3D; 1.10.275.10; -; 1.
DR   HAMAP; MF_00006; Arg_succ_lyase; 1.
DR   InterPro; IPR029419; Arg_succ_lyase_C.
DR   InterPro; IPR009049; Argininosuccinate_lyase.
DR   InterPro; IPR024083; Fumarase/histidase_N.
DR   InterPro; IPR020557; Fumarate_lyase_CS.
DR   InterPro; IPR000362; Fumarate_lyase_fam.
DR   InterPro; IPR022761; Fumarate_lyase_N.
DR   InterPro; IPR008948; L-Aspartase-like.
DR   PANTHER; PTHR43814; PTHR43814; 1.
DR   Pfam; PF14698; ASL_C2; 1.
DR   Pfam; PF00206; Lyase_1; 1.
DR   PRINTS; PR00149; FUMRATELYASE.
DR   SUPFAM; SSF48557; SSF48557; 1.
DR   TIGRFAMs; TIGR00838; argH; 1.
DR   PROSITE; PS00163; FUMARATE_LYASES; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; Amino-acid biosynthesis; Arginine biosynthesis; Lyase;
KW   Reference proteome; Urea cycle.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:Q91YI0"
FT   CHAIN           2..464
FT                   /note="Argininosuccinate lyase"
FT                   /id="PRO_0000137713"
FT   ACT_SITE        160
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P24058"
FT   ACT_SITE        281
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P24058"
FT   BINDING         27
FT                   /ligand="2-(N(omega)-L-arginino)succinate"
FT                   /ligand_id="ChEBI:CHEBI:57472"
FT                   /ligand_note="ligand shared between tetrameric partners"
FT                   /note="in chain A"
FT                   /evidence="ECO:0000250|UniProtKB:P24058"
FT   BINDING         114
FT                   /ligand="2-(N(omega)-L-arginino)succinate"
FT                   /ligand_id="ChEBI:CHEBI:57472"
FT                   /ligand_note="ligand shared between tetrameric partners"
FT                   /note="in chain A"
FT                   /evidence="ECO:0000250|UniProtKB:P24058"
FT   BINDING         159
FT                   /ligand="2-(N(omega)-L-arginino)succinate"
FT                   /ligand_id="ChEBI:CHEBI:57472"
FT                   /ligand_note="ligand shared between tetrameric partners"
FT                   /note="in chain C"
FT                   /evidence="ECO:0000250|UniProtKB:P24058"
FT   BINDING         289
FT                   /ligand="2-(N(omega)-L-arginino)succinate"
FT                   /ligand_id="ChEBI:CHEBI:57472"
FT                   /ligand_note="ligand shared between tetrameric partners"
FT                   /note="in chain B"
FT                   /evidence="ECO:0000250|UniProtKB:P24058"
FT   BINDING         321
FT                   /ligand="2-(N(omega)-L-arginino)succinate"
FT                   /ligand_id="ChEBI:CHEBI:57472"
FT                   /ligand_note="ligand shared between tetrameric partners"
FT                   /note="in chain A"
FT                   /evidence="ECO:0000250|UniProtKB:P24058"
FT   BINDING         326
FT                   /ligand="2-(N(omega)-L-arginino)succinate"
FT                   /ligand_id="ChEBI:CHEBI:57472"
FT                   /ligand_note="ligand shared between tetrameric partners"
FT                   /note="in chain A"
FT                   /evidence="ECO:0000250|UniProtKB:P24058"
FT   BINDING         329
FT                   /ligand="2-(N(omega)-L-arginino)succinate"
FT                   /ligand_id="ChEBI:CHEBI:57472"
FT                   /ligand_note="ligand shared between tetrameric partners"
FT                   /note="in chain A"
FT                   /evidence="ECO:0000250|UniProtKB:P24058"
FT   SITE            294
FT                   /note="Increases basicity of active site His"
FT                   /evidence="ECO:0000250|UniProtKB:P24058"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:Q91YI0"
FT   MOD_RES         7
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q91YI0"
FT   MOD_RES         69
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P04424"
FT   MOD_RES         288
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P04424"
SQ   SEQUENCE   464 AA;  51808 MW;  189BB25E67A0A982 CRC64;
     MASESGKLWG GRFVGAVDPI MEKFNASIAY DRHLWEVDVQ GSKAYSRGLE KAGLLTKAEM
     DQILHGLDKV AEEWAQCTFK LSPNDEDIHT ANERRLKELI GETAGKLHTG RSRNDQVVTD
     LRLWMRQTCS TLSGLLWELI RTMVDRAEAE RDVLFPGYTH LQRAQPIRWS HWILSHAVAL
     TRDSERLLEV RKRINVLPLG SGAIAGNPLS VDRELLRAEL NFGAITLNSM DATSERDFVA
     EFLFWASLCM THLSRMAEDL ILYCTKEFSF VQLSDAYSTG SSLMPQKKNP DSLELIRSKA
     GRVFGRCAGL LMTLKGLPST YNKDLQEDKE AVFEVSDTMS AVLQVATGVI STLQIHRENM
     GQALSPDMLA TDLAYYLVRK GMPFRQAHEA SGKAVFMAET KGVALNELSL QELQTISPLF
     SGDVSCVWDY GHSVEQYGAL GGTARSSVDW QIRQVRALLQ TQQA