ARLY_RAT
ID ARLY_RAT Reviewed; 461 AA.
AC P20673; Q6AZ85;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Argininosuccinate lyase {ECO:0000303|PubMed:2834354};
DE Short=ASAL;
DE EC=4.3.2.1 {ECO:0000250|UniProtKB:P04424};
DE AltName: Full=Arginosuccinase;
GN Name=Asl;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=2834354; DOI=10.1093/oxfordjournals.jbchem.a122227;
RA Amaya Y., Matsubasa T., Takiguchi M., Kobayashi K., Saheki T., Kawamoto S.,
RA Mori M.;
RT "Amino acid sequence of rat argininosuccinate lyase deduced from cDNA.";
RL J. Biochem. 103:177-181(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2789519; DOI=10.1073/pnas.86.2.592;
RA Matsubasa T., Takiguchi M., Amaya Y., Matsuda I., Mori M.;
RT "Structure of the rat argininosuccinate lyase gene: close similarity to
RT chicken delta-crystallin genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:592-596(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=2725197; DOI=10.1016/0169-328x(89)90040-5;
RA Kawamoto S., Kaneko T., Mizuki N., Ohsuga A., Fukushima J., Amaya Y.,
RA Mori M., Okuda K.;
RT "Molecular cloning and nucleotide sequence of rat brain argininosuccinate
RT lyase cDNA with an extremely long 5'-untranslated sequence: evidence for
RT the identity of the brain and liver enzymes.";
RL Brain Res. Mol. Brain Res. 5:235-241(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS CYS-129 AND GLY-301.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=8485149; DOI=10.1016/0167-4781(93)90255-c;
RA Kawamoto S., Amaya Y., Hattori S., Miyagi Y., Onishi H., Okuda K.;
RT "Structural analysis of an extremely long 5'-noncoding region of rat brain
RT argininosuccinate lyase mRNA: presence of multiple B1 repeats and multiple
RT upstream AUG codons, and a possibility of translational control.";
RL Biochim. Biophys. Acta 1173:111-114(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS CYS-129 AND GLY-301.
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
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; D28501; BAA05859.1; -; mRNA.
DR EMBL; M22697; AAA40766.1; -; Genomic_DNA.
DR EMBL; M22682; AAA40766.1; JOINED; Genomic_DNA.
DR EMBL; M22683; AAA40766.1; JOINED; Genomic_DNA.
DR EMBL; M22684; AAA40766.1; JOINED; Genomic_DNA.
DR EMBL; M22685; AAA40766.1; JOINED; Genomic_DNA.
DR EMBL; M22686; AAA40766.1; JOINED; Genomic_DNA.
DR EMBL; M22687; AAA40766.1; JOINED; Genomic_DNA.
DR EMBL; M22688; AAA40766.1; JOINED; Genomic_DNA.
DR EMBL; M22689; AAA40766.1; JOINED; Genomic_DNA.
DR EMBL; M22690; AAA40766.1; JOINED; Genomic_DNA.
DR EMBL; M22691; AAA40766.1; JOINED; Genomic_DNA.
DR EMBL; M22692; AAA40766.1; JOINED; Genomic_DNA.
DR EMBL; M22693; AAA40766.1; JOINED; Genomic_DNA.
DR EMBL; M22694; AAA40766.1; JOINED; Genomic_DNA.
DR EMBL; M22695; AAA40766.1; JOINED; Genomic_DNA.
DR EMBL; M22696; AAA40766.1; JOINED; Genomic_DNA.
DR EMBL; D13978; BAA03088.1; -; mRNA.
DR EMBL; BC078682; AAH78682.1; -; mRNA.
DR PIR; A32188; WZRTRS.
DR RefSeq; NP_067588.2; NM_021577.3.
DR RefSeq; XP_006249307.1; XM_006249245.3.
DR RefSeq; XP_006249309.1; XM_006249247.3.
DR AlphaFoldDB; P20673; -.
DR SMR; P20673; -.
DR STRING; 10116.ENSRNOP00000001211; -.
DR iPTMnet; P20673; -.
DR PhosphoSitePlus; P20673; -.
DR jPOST; P20673; -.
DR PaxDb; P20673; -.
DR PRIDE; P20673; -.
DR GeneID; 59085; -.
DR KEGG; rno:59085; -.
DR CTD; 435; -.
DR RGD; 619974; Asl.
DR eggNOG; KOG1316; Eukaryota.
DR InParanoid; P20673; -.
DR OrthoDB; 1074729at2759; -.
DR PhylomeDB; P20673; -.
DR Reactome; R-RNO-70635; Urea cycle.
DR SABIO-RK; P20673; -.
DR UniPathway; UPA00068; UER00114.
DR UniPathway; UPA00158; UER00273.
DR PRO; PR:P20673; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070852; C:cell body fiber; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0004056; F:argininosuccinate lyase activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0019676; P:ammonia assimilation cycle; ISO:RGD.
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:0006525; P:arginine metabolic process; ISO:RGD.
DR GO; GO:0000053; P:argininosuccinate metabolic process; IDA:RGD.
DR GO; GO:0006520; P:cellular amino acid metabolic process; ISO:RGD.
DR GO; GO:0071242; P:cellular response to ammonium ion; IEP:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR GO; GO:0071377; P:cellular response to glucagon stimulus; IEP:RGD.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEP:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0060539; P:diaphragm development; IEP:RGD.
DR GO; GO:0001822; P:kidney development; IEP:RGD.
DR GO; GO:0001889; P:liver development; IDA:RGD.
DR GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR GO; GO:0007494; P:midgut development; IEP:RGD.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0009791; P:post-embryonic development; ISO:RGD.
DR GO; GO:0014075; P:response to amine; IEP:RGD.
DR GO; GO:0060416; P:response to growth hormone; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0010043; P:response to zinc ion; IEP:RGD.
DR GO; GO:0000050; P:urea cycle; IDA:RGD.
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..461
FT /note="Argininosuccinate lyase"
FT /id="PRO_0000137715"
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"
FT VARIANT 129
FT /note="Y -> C"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8485149"
FT VARIANT 301
FT /note="R -> G"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8485149"
SQ SEQUENCE 461 AA; 51550 MW; 559DF2C59AEDDA8D CRC64;
MASESGKLWG GRFAGSVDPT MDKFNSSIAY DRHLWNVDLQ GSKAYSRGLE KAGLLTKAEM
QQILQGLDKV AEEWAQGIFK LYPNDEDIHT ANERRLKELI GEAAGKLHTG RSRNDQVVTD
LRLWMRQTYS KLSTFLKVLI EAMVDRAEAE CEVLFPGYTH LQRAQPIRWS HWILSHAVAL
TRDLERLKEV QKRINVLPLG SGAIAGNPLG VDREFLCAEL NFGAITLNSM DATSERDFVA
EFLFWASLCM THLSRMAEDL ILYGTKEFNF VQLSDAYSTG SSLMPQKKNP DSLELIRSKA
RRVFGRCAGL LMTLKGLPST YNKDLQEDKE AVFEVSDTMT AVLQVATGVI STLQIHRENM
AQALSPDMLA TDLAYYLVRK GMPFRQAHEA SGKAVVVAEM KGVALNQLSL QELQTVSPLF
SSDVNLVWDY SHSVEQYTAL GGTAQSSVEW QISQVRALLQ M
