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Protein

Argininosuccinate lyase

Gene

ASL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

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

Enzyme regulationi

Enzyme activity is regulated by acetylation.By similarity

Pathwayi: L-arginine biosynthesis

This protein is involved in step 3 of the subpathway that synthesizes L-arginine from L-ornithine and carbamoyl phosphate.
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. no protein annotated in this organism
  2. Argininosuccinate synthase (ASS1)
  3. Argininosuccinate lyase (ASL)
This subpathway is part of the pathway L-arginine biosynthesis, which is itself part of Amino-acid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-arginine from L-ornithine and carbamoyl phosphate, the pathway L-arginine biosynthesis and in Amino-acid biosynthesis.

Pathwayi: urea cycle

This protein is involved in step 1 of the subpathway that synthesizes L-arginine and fumarate from (N(omega)-L-arginino)succinate.
Proteins known to be involved in this subpathway in this organism are:
  1. Argininosuccinate lyase (ASL)
This subpathway is part of the pathway urea cycle, which is itself part of Nitrogen metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-arginine and fumarate from (N(omega)-L-arginino)succinate, the pathway urea cycle and in Nitrogen metabolism.

GO - Molecular functioni

GO - Biological processi

  • arginine biosynthetic process Source: GO_Central
  • arginine biosynthetic process via ornithine Source: GO_Central
  • arginine catabolic process Source: ProtInc
  • internal protein amino acid acetylation Source: UniProtKB
  • protein tetramerization Source: GO_Central
  • urea cycle Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

Amino-acid biosynthesis, Arginine biosynthesis, Urea cycle

Enzyme and pathway databases

BioCyciMetaCyc:HS10034-MONOMER.
ZFISH:HS10034-MONOMER.
BRENDAi4.3.2.1. 2681.
ReactomeiR-HSA-70635. Urea cycle.
SABIO-RKP04424.
UniPathwayiUPA00068; UER00114.
UPA00158; UER00273.

Names & Taxonomyi

Protein namesi
Recommended name:
Argininosuccinate lyase (EC:4.3.2.1)
Short name:
ASAL
Alternative name(s):
Arginosuccinase
Gene namesi
Name:ASL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:746. ASL.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: ProtInc
  • cytosol Source: GO_Central
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Argininosuccinic aciduria (ARGINSA)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:207900
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04310631D → N in ARGINSA; reduction of argininosuccinate lyase activity; no effect on protein expression. 2 PublicationsCorresponds to variant rs754995756dbSNPEnsembl.1
Natural variantiVAR_07218670V → A in ARGINSA. 1 Publication1
Natural variantiVAR_07555173E → K in ARGINSA; complete loss of argininosuccinate lyase activity; abolishes protein expression. 1 Publication1
Natural variantiVAR_07218794R → C in ARGINSA; severe. 1 PublicationCorresponds to variant rs374304304dbSNPEnsembl.1
Natural variantiVAR_07218894R → H in ARGINSA. 1 PublicationCorresponds to variant rs777437569dbSNPEnsembl.1
Natural variantiVAR_00067695R → C in ARGINSA. 1 PublicationCorresponds to variant rs28940585dbSNPEnsembl.1
Natural variantiVAR_07218995R → H in ARGINSA. 1 PublicationCorresponds to variant rs150244667dbSNPEnsembl.1
Natural variantiVAR_072190104A → V in ARGINSA. 1 Publication1
Natural variantiVAR_000677111R → W in ARGINSA. 1 PublicationCorresponds to variant rs138310841dbSNPEnsembl.1
Natural variantiVAR_043107113R → Q in ARGINSA; complete loss of argininosuccinate lyase activity; no effect on protein expression. 2 PublicationsCorresponds to variant rs752783461dbSNPEnsembl.1
Natural variantiVAR_072191120D → E in ARGINSA; severe. 1 Publication1
Natural variantiVAR_072192121L → H in ARGINSA. 1 Publication1
Natural variantiVAR_072193126R → W in ARGINSA. 1 PublicationCorresponds to variant rs201962738dbSNPEnsembl.1
Natural variantiVAR_072194146R → W in ARGINSA. 1 PublicationCorresponds to variant rs199938613dbSNPEnsembl.1
Natural variantiVAR_072195156P → R in ARGINSA. 1 PublicationCorresponds to variant rs769017508dbSNPEnsembl.1
Natural variantiVAR_072196160H → N in ARGINSA. 1 Publication1
Natural variantiVAR_072197166P → H in ARGINSA. 1 Publication1
Natural variantiVAR_072198168R → H in ARGINSA. 1 PublicationCorresponds to variant rs727503811dbSNPEnsembl.1
Natural variantiVAR_072199170S → N in ARGINSA. 1 Publication1
Natural variantiVAR_017572178V → M in ARGINSA; reduction of argininosuccinate lyase activity; no effect on protein expression. 3 PublicationsCorresponds to variant rs28941473dbSNPEnsembl.1
Natural variantiVAR_072200180L → R in ARGINSA. 1 Publication1
Natural variantiVAR_072201182R → Q in ARGINSA; reduction of argininosuccinate lyase activity; reduces protein expression. 2 PublicationsCorresponds to variant rs751590073dbSNPEnsembl.1
Natural variantiVAR_043108186R → Q in ARGINSA; reduction of argininosuccinate lyase activity; reduces protein expression. 2 PublicationsCorresponds to variant rs752397242dbSNPEnsembl.1
Natural variantiVAR_072202191R → W in ARGINSA. 1 PublicationCorresponds to variant rs143508372dbSNPEnsembl.1
Natural variantiVAR_000678193R → Q in ARGINSA. 1 PublicationCorresponds to variant rs373697663dbSNPEnsembl.1
Natural variantiVAR_072203193R → W in ARGINSA. 1 Publication1
Natural variantiVAR_072204205A → V in ARGINSA. 1 PublicationCorresponds to variant rs796051925dbSNPEnsembl.1
Natural variantiVAR_072205213R → Q in ARGINSA. 1 Publication1
Natural variantiVAR_072206227L → P in ARGINSA. 1 Publication1
Natural variantiVAR_072207229S → R in ARGINSA. 1 Publication1
Natural variantiVAR_072208229S → T in ARGINSA. 1 Publication1
Natural variantiVAR_072209231D → E in ARGINSA. 1 Publication1
Natural variantiVAR_043109236R → W in ARGINSA; complete loss of argininosuccinate lyase activity; no effect on protein expression. 2 PublicationsCorresponds to variant rs761268464dbSNPEnsembl.1
Natural variantiVAR_072210237D → N in ARGINSA; severe. 1 PublicationCorresponds to variant rs552951774dbSNPEnsembl.1
Natural variantiVAR_072211256M → T in ARGINSA. 1 PublicationCorresponds to variant rs149057077dbSNPEnsembl.1
Natural variantiVAR_072212262L → P in ARGINSA. 1 Publication1
Natural variantiVAR_000679286Q → R in ARGINSA; complete loss of argininosuccinate lyase activity; no effect on protein expression. 4 PublicationsCorresponds to variant rs28941472dbSNPEnsembl.1
Natural variantiVAR_072213295L → P in ARGINSA. 1 Publication1
Natural variantiVAR_075552297R → Q in ARGINSA; reduction of argininosuccinate lyase activity; no effect on protein expression. 1 PublicationCorresponds to variant rs750431938dbSNPEnsembl.1
Natural variantiVAR_072214301G → R in ARGINSA. 1 Publication1
Natural variantiVAR_072215306R → W in ARGINSA; severe. 1 Publication1
Natural variantiVAR_072216324D → A in ARGINSA. 1 Publication1
Natural variantiVAR_072217326Q → L in ARGINSA; severe. 1 Publication1
Natural variantiVAR_043110335V → L in ARGINSA; reduction of argininosuccinate lyase activity; no effect on protein expression. 2 Publications1
Natural variantiVAR_072218343L → F in ARGINSA. 1 Publication1
Natural variantiVAR_072219343L → P in ARGINSA. 1 Publication1
Natural variantiVAR_072220368M → V in ARGINSA. 1 Publication1
Natural variantiVAR_017573379R → C in ARGINSA. 1 PublicationCorresponds to variant rs28940287dbSNPEnsembl.1
Natural variantiVAR_072221380K → E in ARGINSA. 1 Publication1
Natural variantiVAR_043111382M → R in ARGINSA; reduction of argininosuccinate lyase activity; reduces protein expression. 2 Publications1
Natural variantiVAR_017574385R → C in ARGINSA. 1 PublicationCorresponds to variant rs28940286dbSNPEnsembl.1
Natural variantiVAR_072222385R → H in ARGINSA. 1 PublicationCorresponds to variant rs746120802dbSNPEnsembl.1
Natural variantiVAR_072223385R → L in ARGINSA; severe. 1 Publication1
Natural variantiVAR_072224388H → Q in ARGINSA; severe. 1 Publication1
Natural variantiVAR_072225433S → R in ARGINSA. 1 PublicationCorresponds to variant rs796051928dbSNPEnsembl.1
Natural variantiVAR_072226434V → L in ARGINSA. 1 PublicationCorresponds to variant rs773071023dbSNPEnsembl.1
Natural variantiVAR_072227447S → N in ARGINSA. 1 PublicationCorresponds to variant rs373519615dbSNPEnsembl.1
Natural variantiVAR_072228456R → Q in ARGINSA. 1 PublicationCorresponds to variant rs767271619dbSNPEnsembl.1
Natural variantiVAR_043112456R → W in ARGINSA; reduction of argininosuccinate lyase activity; reduces protein expression. 2 PublicationsCorresponds to variant rs759396688dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi51K → N: 2-fold reduction in activity. 1 Publication1
Mutagenesisi89H → Q: 10-fold reduction in activity. 1 Publication1
Mutagenesisi288K → R: Refractory to inhibition by TSA and NAM and by addition of extra amino acids. No effect on protein structure. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi435.
MalaCardsiASL.
MIMi207900. phenotype.
OpenTargetsiENSG00000126522.
Orphaneti23. Argininosuccinic aciduria.
PharmGKBiPA25046.

Chemistry databases

DrugBankiDB00125. L-Arginine.

Polymorphism and mutation databases

BioMutaiASL.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001377122 – 464Argininosuccinate lyaseAdd BLAST463

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei7N6-acetyllysineBy similarity1
Modified residuei69N6-acetyllysine1 Publication1
Modified residuei288N6-acetyllysine1 Publication1

Post-translational modificationi

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.1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP04424.
MaxQBiP04424.
PaxDbiP04424.
PeptideAtlasiP04424.
PRIDEiP04424.

PTM databases

iPTMnetiP04424.
PhosphoSitePlusiP04424.

Expressioni

Gene expression databases

BgeeiENSG00000126522.
CleanExiHS_ASL.
ExpressionAtlasiP04424. baseline and differential.
GenevisibleiP04424. HS.

Organism-specific databases

HPAiCAB003696.
HPA016646.

Interactioni

Subunit structurei

Homotetramer.

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-750131,EBI-750131
WDYHV1Q96HA85EBI-750131,EBI-741158

Protein-protein interaction databases

BioGridi106927. 17 interactors.
IntActiP04424. 8 interactors.
STRINGi9606.ENSP00000307188.

Structurei

Secondary structure

1464
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi19 – 25Combined sources7
Helixi28 – 31Combined sources4
Helixi32 – 34Combined sources3
Helixi35 – 51Combined sources17
Helixi57 – 76Combined sources20
Helixi88 – 100Combined sources13
Helixi101 – 106Combined sources6
Turni107 – 110Combined sources4
Helixi113 – 150Combined sources38
Beta strandi154 – 159Combined sources6
Beta strandi162 – 168Combined sources7
Helixi169 – 194Combined sources26
Beta strandi195 – 197Combined sources3
Turni202 – 205Combined sources4
Helixi213 – 219Combined sources7
Beta strandi223 – 225Combined sources3
Helixi229 – 232Combined sources4
Helixi237 – 264Combined sources28
Turni266 – 268Combined sources3
Helixi291 – 314Combined sources24
Helixi323 – 327Combined sources5
Helixi328 – 352Combined sources25
Helixi357 – 362Combined sources6
Helixi366 – 369Combined sources4
Helixi370 – 379Combined sources10
Helixi384 – 400Combined sources17
Helixi405 – 407Combined sources3
Helixi410 – 414Combined sources5
Helixi423 – 428Combined sources6
Helixi430 – 434Combined sources5
Beta strandi442 – 444Combined sources3
Helixi445 – 463Combined sources19

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AOSX-ray4.20A/B1-464[»]
1K62X-ray2.65A/B1-464[»]
ProteinModelPortaliP04424.
SMRiP04424.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04424.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1316. Eukaryota.
COG0165. LUCA.
GeneTreeiENSGT00390000014045.
HOGENOMiHOG000242744.
HOVERGENiHBG004281.
InParanoidiP04424.
KOiK01755.
OMAiAHHLMAY.
OrthoDBiEOG091G0AJA.
PhylomeDBiP04424.
TreeFamiTF300656.

Family and domain databases

CDDicd01359. Argininosuccinate_lyase. 1 hit.
Gene3Di1.10.275.10. 1 hit.
HAMAPiMF_00006. Arg_succ_lyase. 1 hit.
InterProiIPR029419. Arg_succ_lyase_C.
IPR009049. Argininosuccinate_lyase.
IPR024083. Fumarase/histidase_N.
IPR020557. Fumarate_lyase_CS.
IPR000362. Fumarate_lyase_fam.
IPR022761. Fumarate_lyase_N.
IPR008948. L-Aspartase-like.
[Graphical view]
PANTHERiPTHR11444. PTHR11444. 1 hit.
PTHR11444:SF3. PTHR11444:SF3. 1 hit.
PfamiPF14698. ASL_C2. 1 hit.
PF00206. Lyase_1. 1 hit.
[Graphical view]
PRINTSiPR00149. FUMRATELYASE.
SUPFAMiSSF48557. SSF48557. 1 hit.
TIGRFAMsiTIGR00838. argH. 1 hit.
PROSITEiPS00163. FUMARATE_LYASES. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P04424-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MASESGKLWG GRFVGAVDPI MEKFNASIAY DRHLWEVDVQ GSKAYSRGLE
60 70 80 90 100
KAGLLTKAEM DQILHGLDKV AEEWAQGTFK LNSNDEDIHT ANERRLKELI
110 120 130 140 150
GATAGKLHTG RSRNDQVVTD LRLWMRQTCS TLSGLLWELI RTMVDRAEAE
160 170 180 190 200
RDVLFPGYTH LQRAQPIRWS HWILSHAVAL TRDSERLLEV RKRINVLPLG
210 220 230 240 250
SGAIAGNPLG VDRELLRAEL NFGAITLNSM DATSERDFVA EFLFWASLCM
260 270 280 290 300
THLSRMAEDL ILYCTKEFSF VQLSDAYSTG SSLMPQKKNP DSLELIRSKA
310 320 330 340 350
GRVFGRCAGL LMTLKGLPST YNKDLQEDKE AVFEVSDTMS AVLQVATGVI
360 370 380 390 400
STLQIHQENM GQALSPDMLA TDLAYYLVRK GMPFRQAHEA SGKAVFMAET
410 420 430 440 450
KGVALNQLSL QELQTISPLF SGDVICVWDY GHSVEQYGAL GGTARSSVDW
460
QIRQVRALLQ AQQA
Length:464
Mass (Da):51,658
Last modified:January 23, 2007 - v4
Checksum:iF751625C1A581883
GO
Isoform 2 (identifier: P04424-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     307-326: Missing.

Note: Gene prediction based on EST data.
Show »
Length:444
Mass (Da):49,509
Checksum:i07114189995B2342
GO
Isoform 3 (identifier: P04424-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     176-201: Missing.

Note: Gene prediction based on EST data.
Show »
Length:438
Mass (Da):48,733
Checksum:iC05AA06470444AA4
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti246A → R in CAA68722 (PubMed:3391281).Curated1
Sequence conflicti246A → R in AAA51786 (PubMed:3463959).Curated1
Sequence conflicti246A → R in AAA51787 (PubMed:2644168).Curated1
Sequence conflicti246A → R in AAA51788 (Ref. 4) Curated1
Sequence conflicti246A → R in AAL57276 (Ref. 5) Curated1
Sequence conflicti431G → R in CAA68722 (PubMed:3391281).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04310631D → N in ARGINSA; reduction of argininosuccinate lyase activity; no effect on protein expression. 2 PublicationsCorresponds to variant rs754995756dbSNPEnsembl.1
Natural variantiVAR_07218670V → A in ARGINSA. 1 Publication1
Natural variantiVAR_07555173E → K in ARGINSA; complete loss of argininosuccinate lyase activity; abolishes protein expression. 1 Publication1
Natural variantiVAR_07218794R → C in ARGINSA; severe. 1 PublicationCorresponds to variant rs374304304dbSNPEnsembl.1
Natural variantiVAR_07218894R → H in ARGINSA. 1 PublicationCorresponds to variant rs777437569dbSNPEnsembl.1
Natural variantiVAR_00067695R → C in ARGINSA. 1 PublicationCorresponds to variant rs28940585dbSNPEnsembl.1
Natural variantiVAR_07218995R → H in ARGINSA. 1 PublicationCorresponds to variant rs150244667dbSNPEnsembl.1
Natural variantiVAR_072190104A → V in ARGINSA. 1 Publication1
Natural variantiVAR_000677111R → W in ARGINSA. 1 PublicationCorresponds to variant rs138310841dbSNPEnsembl.1
Natural variantiVAR_043107113R → Q in ARGINSA; complete loss of argininosuccinate lyase activity; no effect on protein expression. 2 PublicationsCorresponds to variant rs752783461dbSNPEnsembl.1
Natural variantiVAR_072191120D → E in ARGINSA; severe. 1 Publication1
Natural variantiVAR_072192121L → H in ARGINSA. 1 Publication1
Natural variantiVAR_072193126R → W in ARGINSA. 1 PublicationCorresponds to variant rs201962738dbSNPEnsembl.1
Natural variantiVAR_072194146R → W in ARGINSA. 1 PublicationCorresponds to variant rs199938613dbSNPEnsembl.1
Natural variantiVAR_072195156P → R in ARGINSA. 1 PublicationCorresponds to variant rs769017508dbSNPEnsembl.1
Natural variantiVAR_072196160H → N in ARGINSA. 1 Publication1
Natural variantiVAR_072197166P → H in ARGINSA. 1 Publication1
Natural variantiVAR_072198168R → H in ARGINSA. 1 PublicationCorresponds to variant rs727503811dbSNPEnsembl.1
Natural variantiVAR_072199170S → N in ARGINSA. 1 Publication1
Natural variantiVAR_017572178V → M in ARGINSA; reduction of argininosuccinate lyase activity; no effect on protein expression. 3 PublicationsCorresponds to variant rs28941473dbSNPEnsembl.1
Natural variantiVAR_072200180L → R in ARGINSA. 1 Publication1
Natural variantiVAR_036281181T → S in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_072201182R → Q in ARGINSA; reduction of argininosuccinate lyase activity; reduces protein expression. 2 PublicationsCorresponds to variant rs751590073dbSNPEnsembl.1
Natural variantiVAR_043108186R → Q in ARGINSA; reduction of argininosuccinate lyase activity; reduces protein expression. 2 PublicationsCorresponds to variant rs752397242dbSNPEnsembl.1
Natural variantiVAR_072202191R → W in ARGINSA. 1 PublicationCorresponds to variant rs143508372dbSNPEnsembl.1
Natural variantiVAR_000678193R → Q in ARGINSA. 1 PublicationCorresponds to variant rs373697663dbSNPEnsembl.1
Natural variantiVAR_072203193R → W in ARGINSA. 1 Publication1
Natural variantiVAR_036282200G → V in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_072204205A → V in ARGINSA. 1 PublicationCorresponds to variant rs796051925dbSNPEnsembl.1
Natural variantiVAR_072205213R → Q in ARGINSA. 1 Publication1
Natural variantiVAR_072206227L → P in ARGINSA. 1 Publication1
Natural variantiVAR_072207229S → R in ARGINSA. 1 Publication1
Natural variantiVAR_072208229S → T in ARGINSA. 1 Publication1
Natural variantiVAR_072209231D → E in ARGINSA. 1 Publication1
Natural variantiVAR_043109236R → W in ARGINSA; complete loss of argininosuccinate lyase activity; no effect on protein expression. 2 PublicationsCorresponds to variant rs761268464dbSNPEnsembl.1
Natural variantiVAR_072210237D → N in ARGINSA; severe. 1 PublicationCorresponds to variant rs552951774dbSNPEnsembl.1
Natural variantiVAR_072211256M → T in ARGINSA. 1 PublicationCorresponds to variant rs149057077dbSNPEnsembl.1
Natural variantiVAR_072212262L → P in ARGINSA. 1 Publication1
Natural variantiVAR_000679286Q → R in ARGINSA; complete loss of argininosuccinate lyase activity; no effect on protein expression. 4 PublicationsCorresponds to variant rs28941472dbSNPEnsembl.1
Natural variantiVAR_072213295L → P in ARGINSA. 1 Publication1
Natural variantiVAR_075552297R → Q in ARGINSA; reduction of argininosuccinate lyase activity; no effect on protein expression. 1 PublicationCorresponds to variant rs750431938dbSNPEnsembl.1
Natural variantiVAR_072214301G → R in ARGINSA. 1 Publication1
Natural variantiVAR_072215306R → W in ARGINSA; severe. 1 Publication1
Natural variantiVAR_072216324D → A in ARGINSA. 1 Publication1
Natural variantiVAR_072217326Q → L in ARGINSA; severe. 1 Publication1
Natural variantiVAR_043110335V → L in ARGINSA; reduction of argininosuccinate lyase activity; no effect on protein expression. 2 Publications1
Natural variantiVAR_072218343L → F in ARGINSA. 1 Publication1
Natural variantiVAR_072219343L → P in ARGINSA. 1 Publication1
Natural variantiVAR_072220368M → V in ARGINSA. 1 Publication1
Natural variantiVAR_017573379R → C in ARGINSA. 1 PublicationCorresponds to variant rs28940287dbSNPEnsembl.1
Natural variantiVAR_072221380K → E in ARGINSA. 1 Publication1
Natural variantiVAR_043111382M → R in ARGINSA; reduction of argininosuccinate lyase activity; reduces protein expression. 2 Publications1
Natural variantiVAR_017574385R → C in ARGINSA. 1 PublicationCorresponds to variant rs28940286dbSNPEnsembl.1
Natural variantiVAR_072222385R → H in ARGINSA. 1 PublicationCorresponds to variant rs746120802dbSNPEnsembl.1
Natural variantiVAR_072223385R → L in ARGINSA; severe. 1 Publication1
Natural variantiVAR_072224388H → Q in ARGINSA; severe. 1 Publication1
Natural variantiVAR_072225433S → R in ARGINSA. 1 PublicationCorresponds to variant rs796051928dbSNPEnsembl.1
Natural variantiVAR_072226434V → L in ARGINSA. 1 PublicationCorresponds to variant rs773071023dbSNPEnsembl.1
Natural variantiVAR_072227447S → N in ARGINSA. 1 PublicationCorresponds to variant rs373519615dbSNPEnsembl.1
Natural variantiVAR_072228456R → Q in ARGINSA. 1 PublicationCorresponds to variant rs767271619dbSNPEnsembl.1
Natural variantiVAR_043112456R → W in ARGINSA; reduction of argininosuccinate lyase activity; reduces protein expression. 2 PublicationsCorresponds to variant rs759396688dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_047255176 – 201Missing in isoform 3. CuratedAdd BLAST26
Alternative sequenceiVSP_047256307 – 326Missing in isoform 2. CuratedAdd BLAST20

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS47597.1. [P04424-2]
CCDS47598.1. [P04424-3]
CCDS5531.1. [P04424-1]
PIRiA31658. WZHURS.
RefSeqiNP_000039.2. NM_000048.3. [P04424-1]
NP_001020114.1. NM_001024943.1. [P04424-1]
NP_001020115.1. NM_001024944.1. [P04424-2]
UniGeneiHs.632015.

Genome annotation databases

EnsembliENST00000304874; ENSP00000307188; ENSG00000126522. [P04424-1]
ENST00000380839; ENSP00000370219; ENSG00000126522. [P04424-3]
ENST00000395331; ENSP00000378740; ENSG00000126522. [P04424-2]
ENST00000395332; ENSP00000378741; ENSG00000126522. [P04424-1]
GeneIDi435.
KEGGihsa:435.
UCSCiuc003tuo.4. human. [P04424-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS47597.1. [P04424-2]
CCDS47598.1. [P04424-3]
CCDS5531.1. [P04424-1]
PIRiA31658. WZHURS.
RefSeqiNP_000039.2. NM_000048.3. [P04424-1]
NP_001020114.1. NM_001024943.1. [P04424-1]
NP_001020115.1. NM_001024944.1. [P04424-2]
UniGeneiHs.632015.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AOSX-ray4.20A/B1-464[»]
1K62X-ray2.65A/B1-464[»]
ProteinModelPortaliP04424.
SMRiP04424.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106927. 17 interactors.
IntActiP04424. 8 interactors.
STRINGi9606.ENSP00000307188.

Chemistry databases

DrugBankiDB00125. L-Arginine.

PTM databases

iPTMnetiP04424.
PhosphoSitePlusiP04424.

Polymorphism and mutation databases

BioMutaiASL.

Proteomic databases

EPDiP04424.
MaxQBiP04424.
PaxDbiP04424.
PeptideAtlasiP04424.
PRIDEiP04424.

Protocols and materials databases

DNASUi435.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000304874; ENSP00000307188; ENSG00000126522. [P04424-1]
ENST00000380839; ENSP00000370219; ENSG00000126522. [P04424-3]
ENST00000395331; ENSP00000378740; ENSG00000126522. [P04424-2]
ENST00000395332; ENSP00000378741; ENSG00000126522. [P04424-1]
GeneIDi435.
KEGGihsa:435.
UCSCiuc003tuo.4. human. [P04424-1]

Organism-specific databases

CTDi435.
DisGeNETi435.
GeneCardsiASL.
GeneReviewsiASL.
HGNCiHGNC:746. ASL.
HPAiCAB003696.
HPA016646.
MalaCardsiASL.
MIMi207900. phenotype.
608310. gene.
neXtProtiNX_P04424.
OpenTargetsiENSG00000126522.
Orphaneti23. Argininosuccinic aciduria.
PharmGKBiPA25046.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1316. Eukaryota.
COG0165. LUCA.
GeneTreeiENSGT00390000014045.
HOGENOMiHOG000242744.
HOVERGENiHBG004281.
InParanoidiP04424.
KOiK01755.
OMAiAHHLMAY.
OrthoDBiEOG091G0AJA.
PhylomeDBiP04424.
TreeFamiTF300656.

Enzyme and pathway databases

UniPathwayiUPA00068; UER00114.
UPA00158; UER00273.
BioCyciMetaCyc:HS10034-MONOMER.
ZFISH:HS10034-MONOMER.
BRENDAi4.3.2.1. 2681.
ReactomeiR-HSA-70635. Urea cycle.
SABIO-RKP04424.

Miscellaneous databases

ChiTaRSiASL. human.
EvolutionaryTraceiP04424.
GenomeRNAii435.
PROiP04424.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000126522.
CleanExiHS_ASL.
ExpressionAtlasiP04424. baseline and differential.
GenevisibleiP04424. HS.

Family and domain databases

CDDicd01359. Argininosuccinate_lyase. 1 hit.
Gene3Di1.10.275.10. 1 hit.
HAMAPiMF_00006. Arg_succ_lyase. 1 hit.
InterProiIPR029419. Arg_succ_lyase_C.
IPR009049. Argininosuccinate_lyase.
IPR024083. Fumarase/histidase_N.
IPR020557. Fumarate_lyase_CS.
IPR000362. Fumarate_lyase_fam.
IPR022761. Fumarate_lyase_N.
IPR008948. L-Aspartase-like.
[Graphical view]
PANTHERiPTHR11444. PTHR11444. 1 hit.
PTHR11444:SF3. PTHR11444:SF3. 1 hit.
PfamiPF14698. ASL_C2. 1 hit.
PF00206. Lyase_1. 1 hit.
[Graphical view]
PRINTSiPR00149. FUMRATELYASE.
SUPFAMiSSF48557. SSF48557. 1 hit.
TIGRFAMsiTIGR00838. argH. 1 hit.
PROSITEiPS00163. FUMARATE_LYASES. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiARLY_HUMAN
AccessioniPrimary (citable) accession number: P04424
Secondary accession number(s): E7EMI0
, E9PE48, Q6LDS5, Q96HS2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 195 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.