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Details on Person UniProt:P04424 ASL

Class:Id	ReferenceGeneProduct:50291
_chainChangeLog	initiator methionine:1 added on Fri February 6 2015;chain:2-464 added on Fri February 6 2015;initiator methionine:1 for 50291 removed on Fri Nov 03 2023;initiator methionine: for 50291 added on Fri Nov 03 2023;initiator methionine: for 50291 removed on Fri Aug 15 2025;initiator methionine:1 for 50291 added on Fri Aug 15 2025
_displayName	UniProt:P04424 ASL
_timestamp	2025-08-15 20:58:07
chain	initiator methionine:1 chain:2-464
checksum	F751625C1A581883
comment	FUNCTION Catalyzes the reversible cleavage of L-argininosuccinate to fumarate and L-arginine, an intermediate step reaction in the urea cycle mostly providing for hepatic nitrogen detoxification into excretable urea as well as de novo L-arginine synthesis in nonhepatic tissues (PubMed:11747432, PubMed:11747433, PubMed:22081021, PubMed:2263616, PubMed:9045711). Essential regulator of intracellular and extracellular L-arginine pools. As part of citrulline-nitric oxide cycle, forms tissue-specific multiprotein complexes with argininosuccinate synthase ASS1, transport protein SLC7A1 and nitric oxide synthase NOS1, NOS2 or NOS3, allowing for cell-autonomous L-arginine synthesis while channeling extracellular L-arginine to nitric oxide synthesis pathway (PubMed:22081021).CATALYTIC ACTIVITY 2-(N(omega)-L-arginino)succinate = fumarate + L-arginineACTIVITY REGULATION Enzyme activity is regulated by acetylation.BIOPHYSICOCHEMICAL PROPERTIES Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine from L-ornithine and carbamoyl phosphate: step 3/3.PATHWAY Nitrogen metabolism; urea cycle; L-arginine and fumarate from (N(omega)-L-arginino)succinate: step 1/1.SUBUNIT Homotetramer (PubMed:11747433). Forms tissue-specific complexes with ASS1, SLC7A1, HSP90AA1 and nitric oxide synthase NOS1, NOS2 or NOS3; the complex maintenance is independent of ASL catalytic function (By similarity).INTERACTION Acetylation modifies enzyme activity in response to alterations of extracellular nutrient availability. Acetylation increased with trichostin A (TSA) or with nicotinamide (NAM). Glucose increases acetylation by about a factor of 3 with decreasing enzyme activity. Acetylation on Lys-288 is decreased on the addition of extra amino acids resulting in activation of enzyme activity.DISEASE The disease is caused by variants affecting the gene represented in this entry. The phenotype heterogeneity among patients is associated with interallelic complementation resulting in either complete loss of activity or partial regeneration of functional active sites in the heterotetrameric mutant protein.SIMILARITY Belongs to the lyase 1 family. Argininosuccinate lyase subfamily.
description	recommendedName: fullName evidence="15"Argininosuccinate lyase shortName: ASAL ecNumber evidence="3 4 14"4.3.2.1 alternativeName: Arginosuccinase
geneName	ASL
identifier	P04424
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Alternative splicing Amino-acid biosynthesis Arginine biosynthesis Disease variant Lyase Proteomics identification Reference proteome Urea cycle
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15
name	ASL
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:9002806] ENSEMBL:ENSG00000126522 ASL [Homo sapiens]
secondaryIdentifier	ARLY_HUMAN E7EMI0 E9PE48 Q6LDS5 Q96HS2
sequenceLength	464
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:8968678] UniProt:P04424-1 ASL [Homo sapiens] [ReferenceIsoform:8968679] UniProt:P04424-2 ASL [Homo sapiens] [ReferenceIsoform:8968680] UniProt:P04424-3 ASL [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:70570] ASL [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9959319] ASL R95C [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9959321] ASL R12Q [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9959323] ASL R182Q [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9959326] ASL Q354* [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9959327] ASL V178M [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9959329] ASL R297Q [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9959333] ASL D237N [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9959336] ASL R186Q [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9959337] ASL D31N [cytosol] [Homo sapiens] List all 22 refering instances
(referenceSequence)	[ReplacedResidue:9959295] L-methionine 382 replaced with L-arginine [ReplacedResidue:9959296] L-methionine 360 replaced with L-threonine [ReplacedResidue:9959297] L-arginine 379 replaced with L-cysteine [ReplacedResidue:9959298] L-arginine 186 replaced with L-glutamine [ReplacedResidue:9959299] L-glutamic acid 73 replaced with L-lysine [NonsenseMutation:9959300] Nonsense mutation at L-glutamine 354 [ReplacedResidue:9959301] L-glutamine 286 replaced with L-arginine [ReplacedResidue:9959302] L-valine 178 replaced with L-methionine [ReplacedResidue:9959303] L-arginine 113 replaced with L-glutamine [ReplacedResidue:9959304] L-arginine 385 replaced with L-cysteine List all 21 refering instances
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No pathways have been reviewed or authored by UniProt:P04424 ASL (50291)