Reactome | UniProt:P04424 ASL

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.
crossReference	[DatabaseIdentifier:11445274] ENSEMBL:ENSG00000126522 [DatabaseIdentifier:12310886] RefSeq:NP_000039.2 [DatabaseIdentifier:12310887] RefSeq:NP_001020115.1 [DatabaseIdentifier:12310888] RefSeq:NP_001020114.1 [DatabaseIdentifier:12310885] RefSeq:NP_001020117.1 [DatabaseIdentifier:12281854] Pharos - Targets:P04424 [DatabaseIdentifier:12239388] PRO:P04424 [DatabaseIdentifier:12154689] PDB:1K62 [DatabaseIdentifier:12154690] PDB:1AOS [DatabaseIdentifier:12136251] Orphanet:ASL [DatabaseIdentifier:12121529] OpenTargets:ENSG00000126522 [DatabaseIdentifier:11837042] HPA:ENSG00000126522-ASL [DatabaseIdentifier:11831367] HMDB Protein:HMDBP00697 [DatabaseIdentifier:11783938] GeneCards:ASL [DatabaseIdentifier:11654758] ENSEMBL:ENST00000380839 [DatabaseIdentifier:11654757] ENSEMBL:ENST00000395331 [DatabaseIdentifier:11654759] ENSEMBL:ENST00000395332 [DatabaseIdentifier:11654756] ENSEMBL:ENST00000673518 [DatabaseIdentifier:11654760] ENSEMBL:ENST00000304874 [DatabaseIdentifier:11532057] ENSEMBL:ENSP00000499889 [DatabaseIdentifier:11532059] ENSEMBL:ENSP00000378740 [DatabaseIdentifier:11532060] ENSEMBL:ENSP00000378741 [DatabaseIdentifier:11532058] ENSEMBL:ENSP00000370219 [DatabaseIdentifier:11532061] ENSEMBL:ENSP00000307188
databaseName	UniProt
dbId	50291
description	recommendedName: fullName evidence="15"Argininosuccinate lyase shortName: ASAL ecNumber evidence="3 4 14"4.3.2.1 alternativeName: Arginosuccinase
displayName	UniProt:P04424 ASL
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:9963647] Weiser, Joel, 2025-08-15
moleculeType	Protein
name	ASL
otherIdentifier	11720822_a_at 11740232_x_at 11742937_x_at 11746742_a_at 11760562_at 17046601 204608_PM_at 204608_at 3005364 3005365 3005366 3005367 3005368 3005372 3005373 3005374 3005375 3005376 3005377 3005378 3005379 3005380 3005381 3005382 3005383 3005385 3005386 3005387 3005388 3005389 3005390 3005391 3005392 3005393 3005394 3005395 3005396 3005397 3005399 3005401 3005403 3005404 3005405 3005406 3005407 3005408 3005409 3005410 3005411 3005417 3052703 36528_at 435 8133122 89775_r_at A_23_P26223 GE57826 GO:0000050 GO:0003824 GO:0004056 GO:0005515 GO:0005737 GO:0005829 GO:0006520 GO:0006525 GO:0006526 GO:0007626 GO:0008652 GO:0009791 GO:0016829 GO:0019676 GO:0042450 GO:0042802 GO:0045429 GO:0070062 GO:0071941 GO:0170033 HMNXSV003015004 ILMN_1685037 ILMN_1685142 ILMN_2379393 M14218_at PH_hs_0025846 PH_hs_0033478 TC07003307.hg g4502256_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-70570] ASL [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959350] ASL A398D [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959326] ASL Q354* [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959355] ASL E73K [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959323] ASL R182Q [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959352] ASL M360T [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959333] ASL D237N [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959329] ASL R297Q [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959361] ASL R456W [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959360] ASL R113Q [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959343] ASL M382R [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959340] ASL D87G [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959339] ASL R236W [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959336] ASL R186Q [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959319] ASL R95C [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959347] ASL V335L [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959346] ASL Q286R [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959327] ASL V178M [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959341] ASL R385C [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959321] ASL R12Q [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959337] ASL D31N [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9959353] ASL R379C [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:11426769] dbSNP Gene:435 ASL [ReferenceDNASequence:12670237] UCSC:P04424 ASL [ReferenceDNASequence:12107216] OMIM:608310 ASL [ReferenceDNASequence:12024829] NCBI Gene:435 ASL [ReferenceDNASequence:11940736] Monarch:435 ASL [ReferenceDNASequence:11854628] KEGG:hsa:435 ASL [ReferenceDNASequence:11815562] HGNC:746 ASL [ReferenceDNASequence:ensembl:ENSG00000126522] ENSEMBL:ENSG00000126522 ASL [ReferenceDNASequence:11310947] BioGPS Gene:435 ASL [ReferenceDNASequence:11391183] COSMIC - genes:ASL ASL [ReferenceDNASequence:11407710] CTD Gene:435 ASL
referenceTranscript	[ReferenceRNASequence:12492965] RefSeq:NM_001024944.2 ASL [ReferenceRNASequence:12492964] RefSeq:NM_001024943.2 ASL [ReferenceRNASequence:12492963] RefSeq:NM_000048.3 ASL [ReferenceRNASequence:12492966] RefSeq:NM_001024946.2 ASL
schemaClass	ReferenceGeneProduct
secondaryIdentifier	ARLY_HUMAN E7EMI0 E9PE48 Q6LDS5 Q96HS2
sequenceLength	464
species	[Species:48887] Homo sapiens
stId	uniprot:P04424
url	http://purl.uniprot.org/uniprot/P04424

UniProt:P04424 ASL Show undefined attributes

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