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P04424 (ARLY_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 167. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Argininosuccinate lyase

Short name=ASAL
EC=4.3.2.1
Alternative name(s):
Arginosuccinase
Gene names
Name:ASL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length464 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

2-(N(omega)-L-arginino)succinate = fumarate + L-arginine. HAMAP-Rule MF_00006

Enzyme regulation

Enzyme activity is regulated by acetylation By similarity. Ref.9

Pathway

Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine from L-ornithine and carbamoyl phosphate: step 3/3. HAMAP-Rule MF_00006

Nitrogen metabolism; urea cycle; L-arginine and fumarate from (N(omega)-L-arginino)succinate: step 1/1. HAMAP-Rule MF_00006

Subunit structure

Homotetramer.

Post-translational modification

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. Ref.9

Involvement in disease

Argininosuccinic aciduria (ARGINSA) [MIM:207900]: An autosomal recessive disorder of the urea cycle. The disease is characterized by mental and physical retardation, liver enlargement, skin lesions, dry and brittle hair showing trichorrhexis nodosa microscopically and fluorescing red, convulsions, and episodic unconsciousness.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.14 Ref.15 Ref.17

Sequence similarities

Belongs to the lyase 1 family. Argininosuccinate lyase subfamily.

Sequence caution

The sequence AAA51786.1 differs from that shown. Reason: Frameshift at positions 387 and 452.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P04424-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P04424-2)

The sequence of this isoform differs from the canonical sequence as follows:
     307-326: Missing.
Note: Gene prediction based on EST data.
Isoform 3 (identifier: P04424-3)

The sequence of this isoform differs from the canonical sequence as follows:
     176-201: Missing.
Note: Gene prediction based on EST data.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 464463Argininosuccinate lyase HAMAP-Rule MF_00006
PRO_0000137712

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue71N6-acetyllysine By similarity
Modified residue691N6-acetyllysine Ref.9
Modified residue2881N6-acetyllysine Ref.9

Natural variations

Alternative sequence176 – 20126Missing in isoform 3.
VSP_047255
Alternative sequence307 – 32620Missing in isoform 2.
VSP_047256
Natural variant311D → N in ARGINSA. Ref.17
VAR_043106
Natural variant951R → C in ARGINSA. Ref.14
Corresponds to variant rs28940585 [ dbSNP | Ensembl ].
VAR_000676
Natural variant1111R → W in ARGINSA. Ref.13
VAR_000677
Natural variant1131R → Q in ARGINSA. Ref.17
VAR_043107
Natural variant1781V → M in ARGINSA. Ref.15 Ref.17
Corresponds to variant rs28941473 [ dbSNP | Ensembl ].
VAR_017572
Natural variant1811T → S in a breast cancer sample; somatic mutation. Ref.16
VAR_036281
Natural variant1861R → Q in ARGINSA. Ref.17
VAR_043108
Natural variant1931R → Q in ARGINSA. Ref.13
VAR_000678
Natural variant2001G → V in a breast cancer sample; somatic mutation. Ref.16
VAR_036282
Natural variant2361R → W in ARGINSA. Ref.17
VAR_043109
Natural variant2861Q → R in ARGINSA. Ref.12 Ref.13 Ref.17
Corresponds to variant rs28941472 [ dbSNP | Ensembl ].
VAR_000679
Natural variant3351V → L in ARGINSA. Ref.17
VAR_043110
Natural variant3791R → C in ARGINSA. Ref.15
Corresponds to variant rs28940287 [ dbSNP | Ensembl ].
VAR_017573
Natural variant3821M → R in ARGINSA. Ref.17
VAR_043111
Natural variant3851R → C in ARGINSA. Ref.15
Corresponds to variant rs28940286 [ dbSNP | Ensembl ].
VAR_017574
Natural variant4561R → W in ARGINSA. Ref.17
VAR_043112

Experimental info

Mutagenesis511K → N: 2-fold reduction in activity.
Mutagenesis891H → Q: 10-fold reduction in activity.
Mutagenesis2881K → R: Refractory to inhibition by TSA and NAM and by addition of extra amino acids. No effect on protein structure. Ref.9
Sequence conflict2461A → R in CAA68722. Ref.1
Sequence conflict2461A → R in AAA51786. Ref.2
Sequence conflict2461A → R in AAA51787. Ref.3
Sequence conflict2461A → R in AAA51788. Ref.4
Sequence conflict2461A → R in AAL57276. Ref.5
Sequence conflict4311G → R in CAA68722. Ref.1

Secondary structure

........................................................ 464
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: F751625C1A581883

FASTA46451,658
        10         20         30         40         50         60 
MASESGKLWG GRFVGAVDPI MEKFNASIAY DRHLWEVDVQ GSKAYSRGLE KAGLLTKAEM 

        70         80         90        100        110        120 
DQILHGLDKV AEEWAQGTFK LNSNDEDIHT ANERRLKELI GATAGKLHTG RSRNDQVVTD 

       130        140        150        160        170        180 
LRLWMRQTCS TLSGLLWELI RTMVDRAEAE RDVLFPGYTH LQRAQPIRWS HWILSHAVAL 

       190        200        210        220        230        240 
TRDSERLLEV RKRINVLPLG SGAIAGNPLG VDRELLRAEL NFGAITLNSM DATSERDFVA 

       250        260        270        280        290        300 
EFLFWASLCM THLSRMAEDL ILYCTKEFSF VQLSDAYSTG SSLMPQKKNP DSLELIRSKA 

       310        320        330        340        350        360 
GRVFGRCAGL LMTLKGLPST YNKDLQEDKE AVFEVSDTMS AVLQVATGVI STLQIHQENM 

       370        380        390        400        410        420 
GQALSPDMLA TDLAYYLVRK GMPFRQAHEA SGKAVFMAET KGVALNQLSL QELQTISPLF 

       430        440        450        460 
SGDVICVWDY GHSVEQYGAL GGTARSSVDW QIRQVRALLQ AQQA 

« Hide

Isoform 2 [UniParc].

Checksum: 07114189995B2342
Show »

FASTA44449,509
Isoform 3 [UniParc].

Checksum: C05AA06470444AA4
Show »

FASTA43848,733

References

« Hide 'large scale' references
[1]"Isolation of cDNA clones of human argininosuccinate lyase and corrected amino acid sequence."
Matuo S., Tatsuno M., Kobayashi K., Saheki T., Miyata T.
FEBS Lett. 234:395-399(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[2]"Cloning and sequence analysis of cDNA for human argininosuccinate lyase."
O'Brien W.E., McInnes R., Kalumuck K., Adcock M.
Proc. Natl. Acad. Sci. U.S.A. 83:7211-7215(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"cDNA sequence, interspecies comparison, and gene mapping analysis of argininosuccinate lyase."
Todd S., McGill J.R., McCombs J.L., Moore C.M., Weider I., Naylor S.L.
Genomics 4:53-59(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"Cloning and sequence analysis of cDNA for human argininosuccinate lyase."
Matuo S.
Kagoshima Daigaku Igaku Zasshi 40:147-160(1988)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]"Complete sequence of the human ASL gene."
Linnebank M., Tschiedel E., Koch H.G.
Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[6]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain and Cervix.
[8]"Gene sharing by delta-crystallin and argininosuccinate lyase."
Piatigorsky J., O'Brien W.E., Norman B.L., Kalumuck K., Wistow G.J., Borras T., Nickerson J.M., Wawrousek E.F.
Proc. Natl. Acad. Sci. U.S.A. 85:3479-3483(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 5-97 (ISOFORM 1/2/3).
[9]"Regulation of cellular metabolism by protein lysine acetylation."
Zhao S., Xu W., Jiang W., Yu W., Lin Y., Zhang T., Yao J., Zhou L., Zeng Y., Li H., Li Y., Shi J., An W., Hancock S.M., He F., Qin L., Chin J., Yang P. expand/collapse author list , Chen X., Lei Q., Xiong Y., Guan K.L.
Science 327:1000-1004(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-69 AND LYS-288, ENZYME REGULATION, MUTAGENESIS OF LYS-288, IDENTIFICATION BY MASS SPECTROMETRY.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Human argininosuccinate lyase: a structural basis for intragenic complementation."
Turner M.A., Simpson A., McInnes R.R., Howell P.L.
Proc. Natl. Acad. Sci. U.S.A. 94:9063-9068(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (4.2 ANGSTROMS).
Tissue: Liver.
[12]"Three-dimensional structure of the argininosuccinate lyase frequently complementing allele Q286R."
Sampaleanu L.M., Vallee F., Thompson G.D., Howell P.L.
Biochemistry 40:15570-15580(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF VARIANT ARG-286.
[13]"Analysis of naturally occurring and site-directed mutations in the argininosuccinate lyase gene."
Barbosa P., Cialkowski M., O'Brien W.E.
J. Biol. Chem. 266:5286-5290(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARGINSA TRP-111; GLN-193 AND ARG-286, MUTAGENESIS.
[14]"Molecular analysis of human argininosuccinate lyase: mutant characterization and alternative splicing of the coding region."
Walker D.C., McCloskey D.A., Simard L.R., McInnes R.R.
Proc. Natl. Acad. Sci. U.S.A. 87:9625-9629(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARGINSA CYS-95.
[15]"Clinical, enzymatic, and molecular genetic characterization of a biochemical variant type of argininosuccinic aciduria: prenatal and postnatal diagnosis in five unrelated families."
Kleijer W.J., Garritsen V.H., Linnebank M., Mooyer P., Huijmans J.G.M., Mustonen A., Simola K.O.J., Arslan-Kirchner M., Battini R., Briones P., Cardo E., Mandel H., Tschiedel E., Wanders R.J.A., Koch H.G.
J. Inherit. Metab. Dis. 25:399-410(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARGINSA MET-178; CYS-379 AND CYS-385.
[16]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-181 AND VAL-200.
[17]"Argininosuccinate lyase deficiency: mutational spectrum in Italian patients and identification of a novel ASL pseudogene."
Trevisson E., Salviati L., Baldoin M.C., Toldo I., Casarin A., Sacconi S., Cesaro L., Basso G., Burlina A.B.
Hum. Mutat. 28:694-702(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARGINSA ASN-31; GLN-113; MET-178; GLN-186; TRP-236; ARG-286; LEU-335; ARG-382 AND TRP-456.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y00753 mRNA. Translation: CAA68722.1.
M14218 mRNA. Translation: AAA51786.1. Frameshift.
J03058 mRNA. Translation: AAA51787.1.
M57638 mRNA. Translation: AAA51788.1.
AF376770 Genomic DNA. Translation: AAL57276.1.
AC068533 Genomic DNA. No translation available.
BC008195 mRNA. Translation: AAH08195.1.
BC033146 mRNA. Translation: AAH33146.1.
M21007, M21006 Genomic DNA. Translation: AAA35566.1.
PIRWZHURS. A31658.
RefSeqNP_000039.2. NM_000048.3.
NP_001020114.1. NM_001024943.1.
NP_001020115.1. NM_001024944.1.
NP_001020117.1. NM_001024946.1.
UniGeneHs.632015.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AOSX-ray4.20A/B1-464[»]
1K62X-ray2.65A/B1-464[»]
ProteinModelPortalP04424.
SMRP04424. Positions 6-464.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106927. 15 interactions.
IntActP04424. 5 interactions.
STRING9606.ENSP00000307188.

Chemistry

DrugBankDB00125. L-Arginine.

PTM databases

PhosphoSiteP04424.

Proteomic databases

PaxDbP04424.
PRIDEP04424.

Protocols and materials databases

DNASU435.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000304874; ENSP00000307188; ENSG00000126522. [P04424-1]
ENST00000380839; ENSP00000370219; ENSG00000126522. [P04424-3]
ENST00000395331; ENSP00000378740; ENSG00000126522. [P04424-2]
ENST00000395332; ENSP00000378741; ENSG00000126522. [P04424-1]
GeneID435.
KEGGhsa:435.
UCSCuc003tuo.3. human. [P04424-1]

Organism-specific databases

CTD435.
GeneCardsGC07P065540.
HGNCHGNC:746. ASL.
HPACAB003696.
HPA016646.
MIM207900. phenotype.
608310. gene.
neXtProtNX_P04424.
Orphanet23. Argininosuccinic aciduria.
PharmGKBPA25046.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0165.
HOGENOMHOG000242744.
HOVERGENHBG004281.
InParanoidP04424.
KOK01755.
OMAPTANSLD.
OrthoDBEOG7PS1FN.
PhylomeDBP04424.
TreeFamTF300656.

Enzyme and pathway databases

BioCycMetaCyc:HS10034-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP04424.
UniPathwayUPA00068; UER00114.
UPA00158; UER00273.

Gene expression databases

ArrayExpressP04424.
BgeeP04424.
CleanExHS_ASL.
GenevestigatorP04424.

Family and domain databases

Gene3D1.10.275.10. 1 hit.
HAMAPMF_00006. Arg_succ_lyase.
InterProIPR009049. Argininosuccinate_lyase.
IPR024083. Fumarase/histidase_N.
IPR020557. Fumarate_lyase_CS.
IPR000362. Fumarate_lyase_fam.
IPR022761. Fumarate_lyase_N.
IPR008948. L-Aspartase-like.
[Graphical view]
PANTHERPTHR11444. PTHR11444. 1 hit.
PTHR11444:SF3. PTHR11444:SF3. 1 hit.
PfamPF00206. Lyase_1. 1 hit.
[Graphical view]
PRINTSPR00149. FUMRATELYASE.
SUPFAMSSF48557. SSF48557. 1 hit.
TIGRFAMsTIGR00838. argH. 1 hit.
PROSITEPS00163. FUMARATE_LYASES. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSasl. human.
EvolutionaryTraceP04424.
GenomeRNAi435.
NextBio1821.
PROP04424.
SOURCESearch...

Entry information

Entry nameARLY_HUMAN
AccessionPrimary (citable) accession number: P04424
Secondary accession number(s): E7EMI0 expand/collapse secondary AC list , E9PE48, Q6LDS5, Q96HS2
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 167 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM