Reviewed, UniProtKB/Swiss-Prot P04424 (ARLY_HUMAN)

Names and origin

Protein names

Recommended name:
    Argininosuccinate lyase
      Short name=ASAL
    EC=4.3.2.1
Alternative name(s):
    Arginosuccinase

Gene names

Name:

ASL

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	464 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	2-(N(omega)-L-arginino)succinate = fumarate + L-arginine.
Pathway	Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine from L-ornithine and carbamoyl phosphate: step 3/3. Nitrogen metabolism; urea cycle; L-arginine and fumarate from (N(omega)-L-arginino)succinate: step 1/1.
Subunit structure	Homotetramer.
Involvement in disease	Defects in ASL are the cause of arginosuccinicaciduria (ARGINSA) [MIM:207900]. Arginosuccinicaciduria is 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. Ref.10 Ref.11 Ref.12 Ref.14
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.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Arginine biosynthesis Urea cycle
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Molecular function	Lyase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	arginine biosynthetic process via ornithine Inferred from electronic annotation. Source: InterPro arginine catabolic process Traceable author statement. Source: ProtInc urea cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Traceable author statement. Source: ProtInc
Molecular function	argininosuccinate lyase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 464

464

Argininosuccinate lyase

PRO_0000137712

Natural variations

Natural variant

31

1

D → N in ARGINSA. Ref.14

VAR_043106

Natural variant

95

1

R → C in ARGINSA. dbSNP rs28940585. Ref.11

VAR_000676

Natural variant

111

1

R → W in ARGINSA. Ref.10

VAR_000677

Natural variant

113

1

R → Q in ARGINSA. Ref.14

VAR_043107

Natural variant

178

1

V → M in ARGINSA. Ref.12 Ref.14

VAR_017572

Natural variant

181

1

T → S in a breast cancer sample; somatic mutation. Ref.13

VAR_036281

Natural variant

186

1

R → Q in ARGINSA. Ref.14

VAR_043108

Natural variant

193

1

R → Q in ARGINSA. Ref.10

VAR_000678

Natural variant

200

1

G → V in a breast cancer sample; somatic mutation. Ref.13

VAR_036282

Natural variant

236

1

R → W in ARGINSA. Ref.14

VAR_043109

Natural variant

286

1

Q → R in ARGINSA. dbSNP rs28941472. Ref.10 Ref.14 Ref.9

VAR_000679

Natural variant

335

1

V → L in ARGINSA. Ref.14

VAR_043110

Natural variant

379

1

R → C in ARGINSA. Ref.12

VAR_017573

Natural variant

382

1

M → R in ARGINSA. Ref.14

VAR_043111

Natural variant

385

1

R → C in ARGINSA. Ref.12

VAR_017574

Natural variant

456

1

R → W in ARGINSA. Ref.14

VAR_043112

Experimental info

Mutagenesis

51

1

K → N: 2-fold reduction in activity.

Mutagenesis

89

1

H → Q: 10-fold reduction in activity.

Sequence conflict

246

1

A → R in CAA68722. Ref.1

Sequence conflict

246

1

A → R in AAA51786. Ref.2

Sequence conflict

246

1

A → R in AAA51787. Ref.3

Sequence conflict

246

1

A → R in AAA51788. Ref.4

Sequence conflict

246

1

A → R in AAL57276. Ref.5

Sequence conflict

431

1

G → R in CAA68722. Ref.1

Secondary structure

1

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464

Helix Strand Turn

Details...

Helix

19 – 25

7

Helix

28 – 31

4

Helix

32 – 34

3

Helix

35 – 51

17

Helix

57 – 76

20

Helix

88 – 100

13

Helix

101 – 106

6

Turn

107 – 110

4

Helix

113 – 150

38

Beta strand

154 – 159

6

Beta strand

162 – 168

7

Helix

169 – 194

26

Beta strand

195 – 197

3

Turn

202 – 205

4

Helix

213 – 219

7

Beta strand

223 – 225

3

Helix

229 – 232

4

Helix

237 – 264

28

Turn

266 – 268

3

Helix

291 – 314

24

Beta strand

319 – 321

3

Helix

323 – 327

5

Helix

328 – 352

25

Helix

357 – 362

6

Helix

366 – 369

4

Helix

370 – 379

10

Helix

384 – 400

17

Helix

405 – 407

3

Helix

410 – 414

5

Helix

423 – 428

6

Helix

430 – 434

5

Beta strand

442 – 444

3

Helix

445 – 463

19

Sequences

	Sequence		Length	Mass (Da)
	P04424-1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: F751625C1A581883	FASTA	464	51,658
	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

References

	« Hide 'large scale' referencesShow '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: 3391281] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. 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: 3463959] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 2644168] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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].
[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].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Cervix.
[7]	"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: 3368457] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 5-97.
[8]	"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: 9256435] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (4.2 ANGSTROMS). Tissue: Liver.
[9]	"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: 11747432] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF VARIANT ARG-286.
[10]	"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: 1705937] [Abstract] Cited for: VARIANTS ARGINSA TRP-111; GLN-193 AND ARG-286, MUTAGENESIS.
[11]	"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: 2263616] [Abstract] Cited for: VARIANT ARGINSA CYS-95.
[12]	"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: 12408190] [Abstract] Cited for: VARIANTS ARGINSA MET-178; CYS-379 AND CYS-385.
[13]	"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. , 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: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-181 AND VAL-200.
[14]	"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: 17326097] [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

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.
BC008195 mRNA. Translation: AAH08195.1.
BC033146 mRNA. Translation: AAH33146.1.
M21007, M21006 Genomic DNA. Translation: AAA35566.1.

IPI

IPI00220267.

PIR

WZHURS. A31658.

RefSeq

NP_000039.2.
NP_001020114.1.

UniGene

Hs.632015

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AOS	X-ray	4.20	A/B	1-464	[»]
1K62	X-ray	2.65	A/B	1-464	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P04424. 1 interaction.

STRING

P04424.

Proteomic databases

PRIDE

P04424.

Genome annotation databases

Ensembl

ENST00000304874; ENSP00000307188; ENSG00000126522; Homo sapiens. [Genome view]
ENST00000338592; ENSP00000340044; ENSG00000126522; Homo sapiens. [Genome view]
ENST00000360415; ENSP00000353589; ENSG00000126522; Homo sapiens. [Genome view]
ENST00000362000; ENSP00000354710; ENSG00000126522; Homo sapiens. [Genome view]
ENST00000380839; ENSP00000370219; ENSG00000126522; Homo sapiens. [Genome view]
ENST00000395326; ENSP00000378736; ENSG00000126522; Homo sapiens. [Genome view]
ENST00000395331; ENSP00000378740; ENSG00000126522; Homo sapiens. [Genome view]
ENST00000395332; ENSP00000378741; ENSG00000126522; Homo sapiens. [Genome view]
ENST00000398684; ENSP00000381674; ENSG00000126522; Homo sapiens. [Genome view]
ENST00000415001; ENSP00000398605; ENSG00000126522; Homo sapiens. [Genome view]
ENST00000419250; ENSP00000413883; ENSG00000126522; Homo sapiens. [Genome view]
ENST00000422170; ENSP00000394411; ENSG00000126522; Homo sapiens. [Genome view]
ENST00000431089; ENSP00000388653; ENSG00000126522; Homo sapiens. [Genome view]
ENST00000450043; ENSP00000396527; ENSG00000126522; Homo sapiens. [Genome view]

GeneID

435.

KEGG

hsa:435.

UCSC

uc003tuo.1. human.

Organism-specific databases

CTD

435.

GeneCards

GC07P065178.

HGNC

HGNC:746. ASL.

HPA

CAB003696.
HPA016646.

MIM

207900. phenotype.
608310. gene.

Orphanet

23. Argininosuccinicaciduria.

PharmGKB

PA25046.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P04424.

HOVERGEN

P04424.

Enzyme and pathway databases

BioCyc

MetaCyc:MON-11324.

BRENDA

4.3.2.1. 247.

Reactome

REACT_13. Metabolism of amino acids.

Gene expression databases

ArrayExpress

P04424.

Bgee

P04424.

CleanEx

HS_ASL.

Genevestigator

P04424.

GermOnline

ENSG00000169910. Homo sapiens.

Family and domain databases

InterPro

IPR009049. Argininosuccinate_lyase.
IPR003031. D_crystallin.
IPR000362. Fumarate_lyase.
IPR020557. Fumarate_lyase_CS.
[Graphical view]

PANTHER

PTHR11444:SF3. argH. 1 hit.

Pfam

PF00206. Lyase_1. 1 hit.
[Graphical view]

PRINTS

PR00145. ARGSUCLYASE.
PR00149. FUMRATELYASE.

TIGRFAMs

TIGR00838. argH. 1 hit.

PROSITE

PS00163. FUMARATE_LYASES. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00125. L-Arginine.

NextBio

1821.

SOURCE

Search...

Entry information

Entry name

ARLY_HUMAN

Accession

Primary (citable) accession number: P04424
Secondary accession number(s): Q6LDS5, Q96HS2

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 23, 2007
Last modified:	October 13, 2009
This is version 124 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.