ASL

Protein identityUniProt · HPA

UniProt accession

P04424

Gene

ASL

Ensembl

ENSG00000126522

Chromosome

7

Canonical length

464 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Cytosol

Quaternary structure

Homotetramer

OverviewNCBI Gene

This gene encodes a member of the lyase 1 family. The encoded protein forms a cytosolic homotetramer and primarily catalyzes the reversible hydrolytic cleavage of argininosuccinate into arginine and fumarate, an essential step in the liver in detoxifying ammonia via the urea cycle. Mutations in this gene result in the autosomal recessive disorder argininosuccinic aciduria, or argininosuccinic acid lyase deficiency. A nontranscribed pseudogene is also located on the long arm of chromosome 22. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

464 residues, UniProt reviewed canonical sequence.

>P04424|ASL
     1  MASESGKLWG GRFVGAVDPI MEKFNASIAY DRHLWEVDVQ GSKAYSRGLE KAGLLTKAEM
    61  DQILHGLDKV AEEWAQGTFK LNSNDEDIHT ANERRLKELI GATAGKLHTG RSRNDQVVTD
   121  LRLWMRQTCS TLSGLLWELI RTMVDRAEAE RDVLFPGYTH LQRAQPIRWS HWILSHAVAL
   181  TRDSERLLEV RKRINVLPLG SGAIAGNPLG VDRELLRAEL NFGAITLNSM DATSERDFVA
   241  EFLFWASLCM THLSRMAEDL ILYCTKEFSF VQLSDAYSTG SSLMPQKKNP DSLELIRSKA
   301  GRVFGRCAGL LMTLKGLPST YNKDLQEDKE AVFEVSDTMS AVLQVATGVI STLQIHQENM
   361  GQALSPDMLA TDLAYYLVRK GMPFRQAHEA SGKAVFMAET KGVALNQLSL QELQTISPLF
   421  SGDVICVWDY GHSVEQYGAL GGTARSSVDW QIRQVRALLQ AQQA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ASL can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

356 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ASL.

Disease | AllUniProt

Conditions ASL is implicated in, by any mechanism.

• Argininosuccinic aciduria (ARGINSA) MIM:207900

Disease | GeneticClinVar

239 pathogenic / likely-pathogenic of 964 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Argininosuccinate lyase deficiency
• ASL-related disorder
• Inborn genetic diseases
• Neurodevelopmental disorder
• Acute myeloid leukemia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.94

gnomAD pLI

0

gnomAD missense Z

0.75

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• arginine metabolic process
• L-arginine biosynthetic process
• L-arginine biosynthetic process via ornithine
• locomotory behavior
• positive regulation of nitric oxide biosynthetic process
• post-embryonic development
• urea cycle
• ammonia assimilation cycle

Molecular functions

• identical protein binding
• argininosuccinate lyase activity

Cellular components

• cytoplasm
• cytosol
• extracellular exosome

Protein domainsUniProt · Pfam · InterPro

• Fumarate lyase family
• L-Aspartase-like
• Fumarate lyase, conserved site
• Fumarate lyase, N-terminal
• Fumarase/histidase, N-terminal
• Lyase
• Argininosuccinate lyase
• Argininosuccinate lyase, C-terminal
• Argininosuccinate lyase C-terminal

KeywordsUniProt

• Acetylation
• Amino-acid biosynthesis
• Arginine biosynthesis
• Lyase
• Urea cycle