GenomeNet

Database: UniProt
Entry: P04424
LinkDB: P04424
Original site: P04424 
ID   ARLY_HUMAN              Reviewed;         464 AA.
AC   P04424; E7EMI0; E9PE48; Q6LDS5; Q96HS2;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 4.
DT   02-JUN-2021, entry version 228.
DE   RecName: Full=Argininosuccinate lyase;
DE            Short=ASAL;
DE            EC=4.3.2.1;
DE   AltName: Full=Arginosuccinase;
GN   Name=ASL;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Liver;
RX   PubMed=3391281; DOI=10.1016/0014-5793(88)80124-8;
RA   Matuo S., Tatsuno M., Kobayashi K., Saheki T., Miyata T.;
RT   "Isolation of cDNA clones of human argininosuccinate lyase and corrected
RT   amino acid sequence.";
RL   FEBS Lett. 234:395-399(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=3463959; DOI=10.1073/pnas.83.19.7211;
RA   O'Brien W.E., McInnes R., Kalumuck K., Adcock M.;
RT   "Cloning and sequence analysis of cDNA for human argininosuccinate lyase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:7211-7215(1986).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=2644168; DOI=10.1016/0888-7543(89)90314-5;
RA   Todd S., McGill J.R., McCombs J.L., Moore C.M., Weider I., Naylor S.L.;
RT   "cDNA sequence, interspecies comparison, and gene mapping analysis of
RT   argininosuccinate lyase.";
RL   Genomics 4:53-59(1989).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Matuo S.;
RT   "Cloning and sequence analysis of cDNA for human argininosuccinate lyase.";
RL   Kagoshima Daigaku Igaku Zasshi 40:147-160(1988).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RA   Linnebank M., Tschiedel E., Koch H.G.;
RT   "Complete sequence of the human ASL gene.";
RL   Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain, and Cervix;
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).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 5-97 (ISOFORM 1/2/3).
RX   PubMed=3368457; DOI=10.1073/pnas.85.10.3479;
RA   Piatigorsky J., O'Brien W.E., Norman B.L., Kalumuck K., Wistow G.J.,
RA   Borras T., Nickerson J.M., Wawrousek E.F.;
RT   "Gene sharing by delta-crystallin and argininosuccinate lyase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 85:3479-3483(1988).
RN   [9]
RP   ACETYLATION AT LYS-69 AND LYS-288, ACTIVITY REGULATION, MUTAGENESIS OF
RP   LYS-288, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=20167786; DOI=10.1126/science.1179689;
RA   Zhao S., Xu W., Jiang W., Yu W., Lin Y., Zhang T., Yao J., Zhou L.,
RA   Zeng Y., Li H., Li Y., Shi J., An W., Hancock S.M., He F., Qin L., Chin J.,
RA   Yang P., Chen X., Lei Q., Xiong Y., Guan K.L.;
RT   "Regulation of cellular metabolism by protein lysine acetylation.";
RL   Science 327:1000-1004(2010).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [11]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (4.2 ANGSTROMS).
RC   TISSUE=Liver;
RX   PubMed=9256435; DOI=10.1073/pnas.94.17.9063;
RA   Turner M.A., Simpson A., McInnes R.R., Howell P.L.;
RT   "Human argininosuccinate lyase: a structural basis for intragenic
RT   complementation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:9063-9068(1997).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF VARIANT ARG-286.
RX   PubMed=11747432; DOI=10.1021/bi011525m;
RA   Sampaleanu L.M., Vallee F., Thompson G.D., Howell P.L.;
RT   "Three-dimensional structure of the argininosuccinate lyase frequently
RT   complementing allele Q286R.";
RL   Biochemistry 40:15570-15580(2001).
RN   [14]
RP   VARIANTS ARGINSA TRP-111; GLN-193 AND ARG-286, AND MUTAGENESIS.
RX   PubMed=1705937;
RA   Barbosa P., Cialkowski M., O'Brien W.E.;
RT   "Analysis of naturally occurring and site-directed mutations in the
RT   argininosuccinate lyase gene.";
RL   J. Biol. Chem. 266:5286-5290(1991).
RN   [15]
RP   VARIANT ARGINSA CYS-95.
RX   PubMed=2263616; DOI=10.1073/pnas.87.24.9625;
RA   Walker D.C., McCloskey D.A., Simard L.R., McInnes R.R.;
RT   "Molecular analysis of human argininosuccinate lyase: mutant
RT   characterization and alternative splicing of the coding region.";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:9625-9629(1990).
RN   [16]
RP   VARIANTS ARGINSA MET-178; CYS-379 AND CYS-385.
RX   PubMed=12408190; DOI=10.1023/a:1020108002877;
RA   Kleijer W.J., Garritsen V.H., Linnebank M., Mooyer P., Huijmans J.G.M.,
RA   Mustonen A., Simola K.O.J., Arslan-Kirchner M., Battini R., Briones P.,
RA   Cardo E., Mandel H., Tschiedel E., Wanders R.J.A., Koch H.G.;
RT   "Clinical, enzymatic, and molecular genetic characterization of a
RT   biochemical variant type of argininosuccinic aciduria: prenatal and
RT   postnatal diagnosis in five unrelated families.";
RL   J. Inherit. Metab. Dis. 25:399-410(2002).
RN   [17]
RP   VARIANTS [LARGE SCALE ANALYSIS] SER-181 AND VAL-200.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
RN   [18]
RP   VARIANTS ARGINSA ASN-31; GLN-113; MET-178; GLN-186; TRP-236; ARG-286;
RP   LEU-335; ARG-382 AND TRP-456.
RX   PubMed=17326097; DOI=10.1002/humu.20498;
RA   Trevisson E., Salviati L., Baldoin M.C., Toldo I., Casarin A., Sacconi S.,
RA   Cesaro L., Basso G., Burlina A.B.;
RT   "Argininosuccinate lyase deficiency: mutational spectrum in Italian
RT   patients and identification of a novel ASL pseudogene.";
RL   Hum. Mutat. 28:694-702(2007).
RN   [19]
RP   VARIANTS ARGINSA ASN-31; LYS-73; GLN-113; MET-178; GLN-182; GLN-186;
RP   TRP-236; ARG-286; GLN-297; LEU-335; ARG-382 AND TRP-456, AND
RP   CHARACTERIZATION OF VARIANTS ARGINSA ASN-31; LYS-73; GLN-113; MET-178;
RP   GLN-182; GLN-186; TRP-236; ARG-286; GLN-297; LEU-335; ARG-382 AND TRP-456.
RX   PubMed=19703900; DOI=10.1074/jbc.m109.050195;
RA   Trevisson E., Burlina A., Doimo M., Pertegato V., Casarin A., Cesaro L.,
RA   Navas P., Basso G., Sartori G., Salviati L.;
RT   "Functional complementation in yeast allows molecular characterization of
RT   missense argininosuccinate lyase mutations.";
RL   J. Biol. Chem. 284:28926-28934(2009).
RN   [20]
RP   VARIANTS ARGINSA ALA-70; CYS-94; HIS-94; HIS-95; VAL-104; GLU-120; HIS-121;
RP   TRP-126; TRP-146; ARG-156; ASN-160; HIS-166; HIS-168; ASN-170; ARG-180;
RP   GLN-182; TRP-191; TRP-193; VAL-205; GLN-213; PRO-227; ARG-229; THR-229;
RP   GLU-231; ASN-237; THR-256; PRO-262; PRO-295; ARG-301; TRP-306; ALA-324;
RP   LEU-326; PHE-343; PRO-343; VAL-368; GLU-380; HIS-385; LEU-385; GLN-388;
RP   ARG-433; LEU-434; ASN-447 AND GLN-456.
RX   PubMed=24166829; DOI=10.1002/humu.22469;
RA   Balmer C., Pandey A.V., Rufenacht V., Nuoffer J.M., Fang P., Wong L.J.,
RA   Haberle J.;
RT   "Mutations and polymorphisms in the human argininosuccinate lyase (ASL)
RT   gene.";
RL   Hum. Mutat. 35:27-35(2014).
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   -!- ACTIVITY REGULATION: Enzyme activity is regulated by acetylation.
CC       {ECO:0000250}.
CC   -!- PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine
CC       from L-ornithine and carbamoyl phosphate: step 3/3.
CC   -!- PATHWAY: Nitrogen metabolism; urea cycle; L-arginine and fumarate from
CC       (N(omega)-L-arginino)succinate: step 1/1.
CC   -!- SUBUNIT: Homotetramer.
CC   -!- INTERACTION:
CC       P04424; P04424: ASL; NbExp=7; IntAct=EBI-750131, EBI-750131;
CC       P04424; Q9BTE3-2: MCMBP; NbExp=6; IntAct=EBI-750131, EBI-9384556;
CC       P04424; Q96HA8: NTAQ1; NbExp=7; IntAct=EBI-750131, EBI-741158;
CC       P04424; O75382: TRIM3; NbExp=3; IntAct=EBI-750131, EBI-2129889;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P04424-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P04424-2; Sequence=VSP_047256;
CC       Name=3;
CC         IsoId=P04424-3; Sequence=VSP_047255;
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:0000269|PubMed:20167786}.
CC   -!- DISEASE: Argininosuccinic aciduria (ARGINSA) [MIM:207900]: An autosomal
CC       recessive disorder of the urea cycle. The disease is characterized by
CC       mental and physical retardation, liver enlargement, skin lesions, dry
CC       and brittle hair showing trichorrhexis nodosa microscopically and
CC       fluorescing red, convulsions, and episodic unconsciousness.
CC       {ECO:0000269|PubMed:12408190, ECO:0000269|PubMed:1705937,
CC       ECO:0000269|PubMed:17326097, ECO:0000269|PubMed:19703900,
CC       ECO:0000269|PubMed:2263616, ECO:0000269|PubMed:24166829}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the lyase 1 family. Argininosuccinate lyase
CC       subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA51786.1; Type=Frameshift; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; Y00753; CAA68722.1; -; mRNA.
DR   EMBL; M14218; AAA51786.1; ALT_FRAME; mRNA.
DR   EMBL; J03058; AAA51787.1; -; mRNA.
DR   EMBL; M57638; AAA51788.1; -; mRNA.
DR   EMBL; AF376770; AAL57276.1; -; Genomic_DNA.
DR   EMBL; AC068533; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC008195; AAH08195.1; -; mRNA.
DR   EMBL; BC033146; AAH33146.1; -; mRNA.
DR   EMBL; M21007; AAA35566.1; -; Genomic_DNA.
DR   EMBL; M21006; AAA35566.1; JOINED; Genomic_DNA.
DR   CCDS; CCDS47597.1; -. [P04424-2]
DR   CCDS; CCDS47598.1; -. [P04424-3]
DR   CCDS; CCDS5531.1; -. [P04424-1]
DR   PIR; A31658; WZHURS.
DR   RefSeq; NP_000039.2; NM_000048.3. [P04424-1]
DR   RefSeq; NP_001020114.1; NM_001024943.1. [P04424-1]
DR   RefSeq; NP_001020115.1; NM_001024944.1. [P04424-2]
DR   PDB; 1AOS; X-ray; 4.20 A; A/B=1-464.
DR   PDB; 1K62; X-ray; 2.65 A; A/B=1-464.
DR   PDBsum; 1AOS; -.
DR   PDBsum; 1K62; -.
DR   SMR; P04424; -.
DR   BioGRID; 106927; 20.
DR   IntAct; P04424; 8.
DR   STRING; 9606.ENSP00000307188; -.
DR   DrugBank; DB03814; 2-(N-morpholino)ethanesulfonic acid.
DR   DrugBank; DB00125; Arginine.
DR   DrugBank; DB02267; Argininosuccinate.
DR   iPTMnet; P04424; -.
DR   MetOSite; P04424; -.
DR   PhosphoSitePlus; P04424; -.
DR   BioMuta; ASL; -.
DR   EPD; P04424; -.
DR   jPOST; P04424; -.
DR   MassIVE; P04424; -.
DR   MaxQB; P04424; -.
DR   PaxDb; P04424; -.
DR   PeptideAtlas; P04424; -.
DR   PRIDE; P04424; -.
DR   ProteomicsDB; 16946; -.
DR   ProteomicsDB; 19811; -.
DR   ProteomicsDB; 51704; -. [P04424-1]
DR   Antibodypedia; 1530; 296 antibodies.
DR   DNASU; 435; -.
DR   Ensembl; ENST00000304874; ENSP00000307188; ENSG00000126522. [P04424-1]
DR   Ensembl; ENST00000380839; ENSP00000370219; ENSG00000126522. [P04424-3]
DR   Ensembl; ENST00000395331; ENSP00000378740; ENSG00000126522. [P04424-2]
DR   Ensembl; ENST00000395332; ENSP00000378741; ENSG00000126522. [P04424-1]
DR   Ensembl; ENST00000673518; ENSP00000499889; ENSG00000126522. [P04424-3]
DR   GeneID; 435; -.
DR   KEGG; hsa:435; -.
DR   UCSC; uc003tuo.4; human. [P04424-1]
DR   CTD; 435; -.
DR   DisGeNET; 435; -.
DR   GeneCards; ASL; -.
DR   GeneReviews; ASL; -.
DR   HGNC; HGNC:746; ASL.
DR   HPA; ENSG00000126522; Tissue enhanced (liver).
DR   MalaCards; ASL; -.
DR   MIM; 207900; phenotype.
DR   MIM; 608310; gene.
DR   neXtProt; NX_P04424; -.
DR   OpenTargets; ENSG00000126522; -.
DR   Orphanet; 23; Argininosuccinic aciduria.
DR   PharmGKB; PA25046; -.
DR   VEuPathDB; HostDB:ENSG00000126522.16; -.
DR   eggNOG; KOG1316; Eukaryota.
DR   GeneTree; ENSGT00950000183122; -.
DR   HOGENOM; CLU_027272_2_1_1; -.
DR   InParanoid; P04424; -.
DR   OMA; MPGRTHL; -.
DR   PhylomeDB; P04424; -.
DR   TreeFam; TF300656; -.
DR   BioCyc; MetaCyc:HS10034-MONOMER; -.
DR   BRENDA; 4.3.2.1; 2681.
DR   PathwayCommons; P04424; -.
DR   Reactome; R-HSA-70635; Urea cycle.
DR   SABIO-RK; P04424; -.
DR   UniPathway; UPA00068; UER00114.
DR   UniPathway; UPA00158; UER00273.
DR   BioGRID-ORCS; 435; 8 hits in 993 CRISPR screens.
DR   ChiTaRS; ASL; human.
DR   EvolutionaryTrace; P04424; -.
DR   GenomeRNAi; 435; -.
DR   Pharos; P04424; Tbio.
DR   PRO; PR:P04424; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; P04424; protein.
DR   Bgee; ENSG00000126522; Expressed in right lobe of liver and 117 other tissues.
DR   ExpressionAtlas; P04424; baseline and differential.
DR   Genevisible; P04424; HS.
DR   GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0004056; F:argininosuccinate lyase activity; IBA:GO_Central.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0042450; P:arginine biosynthetic process via ornithine; IBA:GO_Central.
DR   GO; GO:0000050; P:urea cycle; TAS:Reactome.
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   1: Evidence at protein level;
KW   3D-structure; Acetylation; Alternative splicing; Amino-acid biosynthesis;
KW   Arginine biosynthesis; Disease variant; Lyase; Reference proteome;
KW   Urea cycle.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:Q91YI0"
FT   CHAIN           2..464
FT                   /note="Argininosuccinate lyase"
FT                   /id="PRO_0000137712"
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:0000269|PubMed:20167786"
FT   MOD_RES         288
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000269|PubMed:20167786"
FT   VAR_SEQ         176..201
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_047255"
FT   VAR_SEQ         307..326
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_047256"
FT   VARIANT         31
FT                   /note="D -> N (in ARGINSA; reduction of argininosuccinate
FT                   lyase activity; no effect on protein expression;
FT                   dbSNP:rs754995756)"
FT                   /evidence="ECO:0000269|PubMed:17326097,
FT                   ECO:0000269|PubMed:19703900"
FT                   /id="VAR_043106"
FT   VARIANT         70
FT                   /note="V -> A (in ARGINSA; dbSNP:rs1027739421)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072186"
FT   VARIANT         73
FT                   /note="E -> K (in ARGINSA; complete loss of
FT                   argininosuccinate lyase activity; abolishes protein
FT                   expression)"
FT                   /evidence="ECO:0000269|PubMed:19703900"
FT                   /id="VAR_075551"
FT   VARIANT         94
FT                   /note="R -> C (in ARGINSA; severe; dbSNP:rs374304304)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072187"
FT   VARIANT         94
FT                   /note="R -> H (in ARGINSA; dbSNP:rs777437569)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072188"
FT   VARIANT         95
FT                   /note="R -> C (in ARGINSA; dbSNP:rs28940585)"
FT                   /evidence="ECO:0000269|PubMed:2263616"
FT                   /id="VAR_000676"
FT   VARIANT         95
FT                   /note="R -> H (in ARGINSA; dbSNP:rs150244667)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072189"
FT   VARIANT         104
FT                   /note="A -> V (in ARGINSA)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072190"
FT   VARIANT         111
FT                   /note="R -> W (in ARGINSA; dbSNP:rs138310841)"
FT                   /evidence="ECO:0000269|PubMed:1705937"
FT                   /id="VAR_000677"
FT   VARIANT         113
FT                   /note="R -> Q (in ARGINSA; complete loss of
FT                   argininosuccinate lyase activity; no effect on protein
FT                   expression; dbSNP:rs752783461)"
FT                   /evidence="ECO:0000269|PubMed:17326097,
FT                   ECO:0000269|PubMed:19703900"
FT                   /id="VAR_043107"
FT   VARIANT         120
FT                   /note="D -> E (in ARGINSA; severe)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072191"
FT   VARIANT         121
FT                   /note="L -> H (in ARGINSA)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072192"
FT   VARIANT         126
FT                   /note="R -> W (in ARGINSA; dbSNP:rs201962738)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072193"
FT   VARIANT         146
FT                   /note="R -> W (in ARGINSA; dbSNP:rs199938613)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072194"
FT   VARIANT         156
FT                   /note="P -> R (in ARGINSA; dbSNP:rs769017508)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072195"
FT   VARIANT         160
FT                   /note="H -> N (in ARGINSA)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072196"
FT   VARIANT         166
FT                   /note="P -> H (in ARGINSA)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072197"
FT   VARIANT         168
FT                   /note="R -> H (in ARGINSA; dbSNP:rs727503811)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072198"
FT   VARIANT         170
FT                   /note="S -> N (in ARGINSA; dbSNP:rs1180650883)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072199"
FT   VARIANT         178
FT                   /note="V -> M (in ARGINSA; reduction of argininosuccinate
FT                   lyase activity; no effect on protein expression;
FT                   dbSNP:rs28941473)"
FT                   /evidence="ECO:0000269|PubMed:12408190,
FT                   ECO:0000269|PubMed:17326097, ECO:0000269|PubMed:19703900"
FT                   /id="VAR_017572"
FT   VARIANT         180
FT                   /note="L -> R (in ARGINSA; dbSNP:rs1057141162)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072200"
FT   VARIANT         181
FT                   /note="T -> S (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036281"
FT   VARIANT         182
FT                   /note="R -> Q (in ARGINSA; reduction of argininosuccinate
FT                   lyase activity; reduces protein expression;
FT                   dbSNP:rs751590073)"
FT                   /evidence="ECO:0000269|PubMed:19703900,
FT                   ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072201"
FT   VARIANT         186
FT                   /note="R -> Q (in ARGINSA; reduction of argininosuccinate
FT                   lyase activity; reduces protein expression;
FT                   dbSNP:rs752397242)"
FT                   /evidence="ECO:0000269|PubMed:17326097,
FT                   ECO:0000269|PubMed:19703900"
FT                   /id="VAR_043108"
FT   VARIANT         191
FT                   /note="R -> W (in ARGINSA; dbSNP:rs143508372)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072202"
FT   VARIANT         193
FT                   /note="R -> Q (in ARGINSA; dbSNP:rs373697663)"
FT                   /evidence="ECO:0000269|PubMed:1705937"
FT                   /id="VAR_000678"
FT   VARIANT         193
FT                   /note="R -> W (in ARGINSA; dbSNP:rs1428029508)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072203"
FT   VARIANT         200
FT                   /note="G -> V (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036282"
FT   VARIANT         205
FT                   /note="A -> V (in ARGINSA; dbSNP:rs796051925)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072204"
FT   VARIANT         213
FT                   /note="R -> Q (in ARGINSA; dbSNP:rs1449589636)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072205"
FT   VARIANT         227
FT                   /note="L -> P (in ARGINSA)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072206"
FT   VARIANT         229
FT                   /note="S -> R (in ARGINSA)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072207"
FT   VARIANT         229
FT                   /note="S -> T (in ARGINSA; dbSNP:rs1554327272)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072208"
FT   VARIANT         231
FT                   /note="D -> E (in ARGINSA)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072209"
FT   VARIANT         236
FT                   /note="R -> W (in ARGINSA; complete loss of
FT                   argininosuccinate lyase activity; no effect on protein
FT                   expression; dbSNP:rs761268464)"
FT                   /evidence="ECO:0000269|PubMed:17326097,
FT                   ECO:0000269|PubMed:19703900"
FT                   /id="VAR_043109"
FT   VARIANT         237
FT                   /note="D -> N (in ARGINSA; severe; dbSNP:rs552951774)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072210"
FT   VARIANT         256
FT                   /note="M -> T (in ARGINSA; dbSNP:rs149057077)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072211"
FT   VARIANT         262
FT                   /note="L -> P (in ARGINSA; dbSNP:rs1554327586)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072212"
FT   VARIANT         286
FT                   /note="Q -> R (in ARGINSA; complete loss of
FT                   argininosuccinate lyase activity; no effect on protein
FT                   expression; dbSNP:rs28941472)"
FT                   /evidence="ECO:0000269|PubMed:11747432,
FT                   ECO:0000269|PubMed:1705937, ECO:0000269|PubMed:17326097,
FT                   ECO:0000269|PubMed:19703900"
FT                   /id="VAR_000679"
FT   VARIANT         295
FT                   /note="L -> P (in ARGINSA; dbSNP:rs1369337876)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072213"
FT   VARIANT         297
FT                   /note="R -> Q (in ARGINSA; reduction of argininosuccinate
FT                   lyase activity; no effect on protein expression;
FT                   dbSNP:rs750431938)"
FT                   /evidence="ECO:0000269|PubMed:19703900"
FT                   /id="VAR_075552"
FT   VARIANT         301
FT                   /note="G -> R (in ARGINSA; dbSNP:rs1161412459)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072214"
FT   VARIANT         306
FT                   /note="R -> W (in ARGINSA; severe; dbSNP:rs868834862)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072215"
FT   VARIANT         324
FT                   /note="D -> A (in ARGINSA)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072216"
FT   VARIANT         326
FT                   /note="Q -> L (in ARGINSA; severe)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072217"
FT   VARIANT         335
FT                   /note="V -> L (in ARGINSA; reduction of argininosuccinate
FT                   lyase activity; no effect on protein expression)"
FT                   /evidence="ECO:0000269|PubMed:17326097,
FT                   ECO:0000269|PubMed:19703900"
FT                   /id="VAR_043110"
FT   VARIANT         343
FT                   /note="L -> F (in ARGINSA)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072218"
FT   VARIANT         343
FT                   /note="L -> P (in ARGINSA)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072219"
FT   VARIANT         368
FT                   /note="M -> V (in ARGINSA; dbSNP:rs1554328202)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072220"
FT   VARIANT         379
FT                   /note="R -> C (in ARGINSA; dbSNP:rs28940287)"
FT                   /evidence="ECO:0000269|PubMed:12408190"
FT                   /id="VAR_017573"
FT   VARIANT         380
FT                   /note="K -> E (in ARGINSA)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072221"
FT   VARIANT         382
FT                   /note="M -> R (in ARGINSA; reduction of argininosuccinate
FT                   lyase activity; reduces protein expression)"
FT                   /evidence="ECO:0000269|PubMed:17326097,
FT                   ECO:0000269|PubMed:19703900"
FT                   /id="VAR_043111"
FT   VARIANT         385
FT                   /note="R -> C (in ARGINSA; dbSNP:rs28940286)"
FT                   /evidence="ECO:0000269|PubMed:12408190"
FT                   /id="VAR_017574"
FT   VARIANT         385
FT                   /note="R -> H (in ARGINSA; dbSNP:rs746120802)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072222"
FT   VARIANT         385
FT                   /note="R -> L (in ARGINSA; severe)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072223"
FT   VARIANT         388
FT                   /note="H -> Q (in ARGINSA; severe)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072224"
FT   VARIANT         433
FT                   /note="S -> R (in ARGINSA; dbSNP:rs796051928)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072225"
FT   VARIANT         434
FT                   /note="V -> L (in ARGINSA; dbSNP:rs773071023)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072226"
FT   VARIANT         447
FT                   /note="S -> N (in ARGINSA; dbSNP:rs373519615)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072227"
FT   VARIANT         456
FT                   /note="R -> Q (in ARGINSA; dbSNP:rs767271619)"
FT                   /evidence="ECO:0000269|PubMed:24166829"
FT                   /id="VAR_072228"
FT   VARIANT         456
FT                   /note="R -> W (in ARGINSA; reduction of argininosuccinate
FT                   lyase activity; reduces protein expression;
FT                   dbSNP:rs759396688)"
FT                   /evidence="ECO:0000269|PubMed:17326097,
FT                   ECO:0000269|PubMed:19703900"
FT                   /id="VAR_043112"
FT   MUTAGEN         51
FT                   /note="K->N: 2-fold reduction in activity."
FT                   /evidence="ECO:0000269|PubMed:1705937"
FT   MUTAGEN         89
FT                   /note="H->Q: 10-fold reduction in activity."
FT                   /evidence="ECO:0000269|PubMed:1705937"
FT   MUTAGEN         288
FT                   /note="K->R: Refractory to inhibition by TSA and NAM and by
FT                   addition of extra amino acids. No effect on protein
FT                   structure."
FT                   /evidence="ECO:0000269|PubMed:20167786"
FT   CONFLICT        246
FT                   /note="A -> R (in Ref. 1; CAA68722, 2; AAA51786, 3;
FT                   AAA51787, 4; AAA51788 and 5; AAL57276)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        431
FT                   /note="G -> R (in Ref. 1; CAA68722)"
FT                   /evidence="ECO:0000305"
FT   HELIX           19..25
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           28..31
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           32..34
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           35..51
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           57..76
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           88..100
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           101..106
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   TURN            107..110
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           113..150
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   STRAND          154..159
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   STRAND          162..168
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           169..194
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   STRAND          195..197
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   TURN            202..205
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           213..219
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   STRAND          223..225
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           229..232
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           237..264
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   TURN            266..268
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           291..314
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           323..327
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           328..352
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           357..362
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           366..369
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           370..379
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           384..400
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           405..407
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           410..414
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           423..428
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           430..434
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   STRAND          442..444
FT                   /evidence="ECO:0007829|PDB:1K62"
FT   HELIX           445..463
FT                   /evidence="ECO:0007829|PDB:1K62"
SQ   SEQUENCE   464 AA;  51658 MW;  F751625C1A581883 CRC64;
     MASESGKLWG GRFVGAVDPI MEKFNASIAY DRHLWEVDVQ GSKAYSRGLE KAGLLTKAEM
     DQILHGLDKV AEEWAQGTFK LNSNDEDIHT ANERRLKELI GATAGKLHTG RSRNDQVVTD
     LRLWMRQTCS TLSGLLWELI RTMVDRAEAE RDVLFPGYTH LQRAQPIRWS HWILSHAVAL
     TRDSERLLEV RKRINVLPLG SGAIAGNPLG VDRELLRAEL NFGAITLNSM DATSERDFVA
     EFLFWASLCM THLSRMAEDL ILYCTKEFSF VQLSDAYSTG SSLMPQKKNP DSLELIRSKA
     GRVFGRCAGL LMTLKGLPST YNKDLQEDKE AVFEVSDTMS AVLQVATGVI STLQIHQENM
     GQALSPDMLA TDLAYYLVRK GMPFRQAHEA SGKAVFMAET KGVALNQLSL QELQTISPLF
     SGDVICVWDY GHSVEQYGAL GGTARSSVDW QIRQVRALLQ AQQA
//
DBGET integrated database retrieval system