ARLY_BOVIN
ID ARLY_BOVIN Reviewed; 473 AA.
AC Q3SZJ0;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 102.
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;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) 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; BC102831; AAI02832.1; -; mRNA.
DR RefSeq; NP_001029600.1; NM_001034428.1.
DR RefSeq; XP_010817716.1; XM_010819414.2.
DR AlphaFoldDB; Q3SZJ0; -.
DR SMR; Q3SZJ0; -.
DR STRING; 9913.ENSBTAP00000020365; -.
DR iPTMnet; Q3SZJ0; -.
DR PaxDb; Q3SZJ0; -.
DR PeptideAtlas; Q3SZJ0; -.
DR PRIDE; Q3SZJ0; -.
DR Ensembl; ENSBTAT00000020365; ENSBTAP00000020365; ENSBTAG00000015314.
DR Ensembl; ENSBTAT00000076379; ENSBTAP00000056916; ENSBTAG00000015314.
DR GeneID; 512771; -.
DR KEGG; bta:512771; -.
DR CTD; 435; -.
DR VEuPathDB; HostDB:ENSBTAG00000015314; -.
DR eggNOG; KOG1316; Eukaryota.
DR GeneTree; ENSGT00950000183122; -.
DR InParanoid; Q3SZJ0; -.
DR SABIO-RK; Q3SZJ0; -.
DR UniPathway; UPA00068; UER00114.
DR UniPathway; UPA00158; UER00273.
DR Proteomes; UP000009136; Chromosome 25.
DR Bgee; ENSBTAG00000015314; Expressed in liver and 104 other tissues.
DR ExpressionAtlas; Q3SZJ0; baseline and differential.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
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; IBA:GO_Central.
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..473
FT /note="Argininosuccinate lyase"
FT /id="PRO_0000273253"
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 473 AA; 52743 MW; DCF05530CFB06404 CRC64;
MASESGKLWG GRFVGTVDPI MEKFNSSITY DRHLWEADVQ GSKAYSRGLE KAGLLTKAEM
DQILHGLDKV AEEWAQGTFK LNPNDEDIHT ANERRLKELI GETAGKLHTG RSRNDQVVTD
LRLWMRQNCS MLSALLCELI RTMVDRAEAE RDVLFPGYTH LQRAQPIRWS HWILSHAVAL
TRDSERLLEV RKRINVLPLG SGAIAGNPLG VDRELLRAEL DFGAITLNSM DATSERDFVA
EFLFWASLCM THLSRMAEDL ILYGTKEFSF VQLSDAYSTG SSLMPQKKNP DSLELIRSKA
GRVFGRCAGL LMTLKGLPST YNKDLQEDKE AVFEVSDTMS AVLQVATGVI STLQIHRENM
GRALSPDMLA TDLAYYLVRK GMPFRQAHEA SGKAVFMAET KGVALNQLSL QELQTISPLF
SGDVSHVWDY GHSVEQYEAL GGTARSSVDW QIGQLRALLR AQQTESPPHA SPK
