P24058 (ARLY2_ANAPL) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Argininosuccinate lyase
Short name=ASAL
EC=4.3.2.1

Alternative name(s):
Arginosuccinase
Delta crystallin II
Delta-2 crystallin

Gene names

Name:

ASL2

Organism

Anas platyrhynchos (Domestic duck) (Anas boschas)

Taxonomic identifier

8839 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Sauropsida › Sauria › Archosauria › Dinosauria › Saurischia › Theropoda › Coelurosauria › Aves › Neognathae › Anseriformes › Anatidae › Anas

Protein attributes

Sequence length	468 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Delta crystallin, the principal crystallin in embryonic lens, is found only in birds and reptiles. This protein also functions as an enzymatically active argininosuccinate lyase. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8
Catalytic activity	2-(N(omega)-L-arginino)succinate = fumarate + L-arginine. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8
Pathway	Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine from L-ornithine and carbamoyl phosphate: step 3/3.
Subunit structure	Homotetramer. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8
Tissue specificity	Eye lens. Ref.1 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8
Miscellaneous	Each of the four substrate binding sites present in the homotetrameric assembly are shared between three of the four subunits.
Sequence similarities	Belongs to the lyase 1 family. Argininosuccinate lyase subfamily.
Biophysicochemical properties	Kinetic parameters: KM=0.05 mM for N(omega)-(L-arginino)succinate Ref.7 Vmax=1.10 µmol/min/mg enzyme

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Arginine biosynthesis
Molecular function	Eye lens protein Lyase
Technical term	3D-structure
Gene Ontology (GO)
Biological_process	arginine biosynthetic process Traceable author statement Ref.8. Source: UniProtKB arginine biosynthetic process via ornithine Inferred from electronic annotation. Source: InterPro
Molecular_function	argininosuccinate lyase activity Inferred from direct assay Ref.8. Source: UniProtKB structural constituent of eye lens Traceable author statement Ref.7. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 468

468

Argininosuccinate lyase

PRO_0000137717

Regions

Region

114 – 116

3

Substrate binding

Sites

Active site

162

1

Proton acceptor; shared with tetrameric partner 2

Active site

283

1

Proton acceptor; shared with tetrameric partner 1

Active site

296

1

Charge relay system; shared with tetrameric partner 1

Binding site

29

1

Substrate

Binding site

91

1

Substrate

Binding site

161

1

Substrate; shared with tetrameric partner 2

Binding site

289

1

Substrate; shared with tetrameric partner 1

Binding site

323

1

Substrate

Binding site

328

1

Substrate

Binding site

331

1

Substrate

Experimental info

Mutagenesis

11

1

W → A: 98% decrease in catalytic efficiency. Ref.3

Mutagenesis

11

1

W → F: 90% decrease in catalytic efficiency. Ref.3

Mutagenesis

11

1

W → M: 99% decrease in catalytic efficiency. Ref.3

Mutagenesis

11

1

W → R: 97% decrease in catalytic efficiency. Ref.3

Mutagenesis

11

1

W → Y: 50% decrease in catalytic efficiency. Ref.3

Mutagenesis

29

1

S → A: 10% decrease in catalytic efficiency. Ref.7

Mutagenesis

33

1

D → N: 99% decrease in catalytic efficiency. Ref.7

Mutagenesis

89

1

D → N: Loss of activity. Ref.7

Mutagenesis

91

1

H → N: 90% decrease in catalytic activity with 10-fold decrease in substrate affinity.

Mutagenesis

116

1

N → D: 99% decrease in catalytic efficiency. Ref.7

Mutagenesis

117

1

D → A: 55% decrease in catalytic efficiency. Ref.3

Mutagenesis

117

1

D → E: 58% decrease in catalytic efficiency. Ref.3

Mutagenesis

161

1

T → A: Loss of activity. Ref.7 Ref.8

Mutagenesis

161

1

T → D: Loss of activity. Ref.7 Ref.8

Mutagenesis

161

1

T → S: 30% decrease in catalytic efficiency. Ref.7 Ref.8

Mutagenesis

161

1

T → V: Loss of activity. Ref.7 Ref.8

Mutagenesis

162

1

H → E: Loss of activity. Ref.7

Mutagenesis

238

1

R → Q: Loss of activity. Ref.7

Mutagenesis

281

1

T → V: 80% decrease in catalytic efficiency. Ref.7

Mutagenesis

283

1

S → A: Loss of activity. Ref.7

Mutagenesis

283

1

S → C: Loss of activity. Ref.7

Mutagenesis

283

1

S → D: Loss of activity. Ref.7

Mutagenesis

283

1

S → H: Loss of activity. Ref.7

Mutagenesis

283

1

S → T: Loss of activity. Ref.7

Mutagenesis

291

1

N → L: Loss of activity. Ref.7

Mutagenesis

293

1

D → N: 99% decrease in catalytic efficiency. Ref.7

Mutagenesis

296

1

E → D: Loss of activity. Ref.7

Mutagenesis

325

1

K → N: 99% decrease in catalytic efficiency. Ref.7

Mutagenesis

330

1

D → N: Loss of activity. Ref.7

Mutagenesis

331

1

K → Q: Loss of activity. Ref.7

Secondary structure

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468

Helix Strand Turn

Details...

Helix

21 – 27

7

Helix

30 – 33

4

Helix

34 – 36

3

Helix

37 – 53

17

Helix

59 – 77

19

Helix

90 – 102

13

Helix

104 – 110

7

Helix

115 – 151

37

Turn

152 – 154

3

Beta strand

156 – 161

6

Beta strand

164 – 170

7

Helix

171 – 196

26

Beta strand

197 – 199

3

Turn

204 – 207

4

Helix

215 – 222

8

Beta strand

225 – 227

3

Helix

231 – 236

6

Helix

239 – 265

27

Turn

268 – 270

3

Beta strand

272 – 274

3

Helix

277 – 279

3

Beta strand

281 – 283

3

Beta strand

286 – 291

6

Helix

293 – 316

24

Beta strand

321 – 323

3

Helix

325 – 329

5

Helix

330 – 354

25

Helix

359 – 364

6

Helix

368 – 371

4

Helix

372 – 380

9

Turn

381 – 383

3

Helix

386 – 401

16

Turn

402 – 404

3

Helix

407 – 409

3

Helix

412 – 418

7

Helix

424 – 429

6

Helix

432 – 436

5

Beta strand

444 – 446

3

Helix

447 – 465

19

Sequences

	Sequence		Length	Mass (Da)
	P24058 [UniParc]. Last modified May 30, 2000. Version 4. Checksum: FBFD26EDC762E7BC	FASTA	468	51,710
	10 20 30 40 50 60 MASEARGDKL WGGRFSGSTD PIMEKLNSSI AYDQRLSEVD IQGSMAYAKA LEKAGILTKT 70 80 90 100 110 120 ELEKILSGLE KISEEWSKGV FVVKQSDEDI HTANERRLKE LIGDIAGKLH TGRSRNDQVV 130 140 150 160 170 180 TDLKLFMKNS LSIISTHLLQ LIKTLVERAA IEIDVILPGY THLQKAQPIR WSQFLLSHAV 190 200 210 220 230 240 ALTRDSERLG EVKKRINVLP LGSGALAGNP LDIDREMLRS ELEFASISLN SMDAISERDF 250 260 270 280 290 300 VVEFLSFATL LMIHLSKMAE DLIIYSTSEF GFLTLSDAFS TGSSLMPQKK NPDSLELIRS 310 320 330 340 350 360 KAGRVFGRLA SILMVLKGLP STYNKDLQED KEAVFDVVDT LTAVLQVATG VISTLQISKE 370 380 390 400 410 420 NMEKALTPEM LATDLALYLV RKGVPFRQAH TASGKAVHLA ETKGITINKL SLEDLKSISP 430 440 450 460 QFSSDVSQVF NFVNSVEQYT ALAGTAKSSV TTQIEQLREL MKKQKEQA

References

[1]	"Gene conversion and splice-site slippage in the argininosuccinate lyases/delta-crystallins of the duck lens: members of an enzyme superfamily." Wistow G.J., Piatigorsky J. Gene 96:263-270(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Lens.
[2]	Graham C., Wistow G.J. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 246-247.
[3]	"Recovery of argininosuccinate lyase activity in duck delta1 crystallin." Tsai M., Koo J., Howell P.L. Biochemistry 44:9034-9044(2005) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TRP-11 AND ASP-117.
[4]	"Structural comparison of the enzymatically active and inactive forms of delta crystallin and the role of histidine 91." Abu-Abed M., Turner M.A., Vallee F., Simpson A., Slingsby C., Howell P.L. Biochemistry 36:14012-14022(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF MUTANT ASN-91, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, TISSUE SPECIFICITY.
[5]	"Crystal structure of an inactive duck delta II crystallin mutant with bound argininosuccinate." Vallee F., Turner M.A., Lindley P.L., Howell P.L. Biochemistry 38:2425-2434(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT ASN-162 IN COMPLEX WITH ARGINOSUCCINATE, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, TISSUE SPECIFICITY.
[6]	"Structural studies of duck delta 1 and delta 2 crystallin suggest conformational changes occur during catalysis." Sampaleanu L.M., Vallee F., Slingsby C., Howell P.L. Biochemistry 40:2732-2742(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, TISSUE SPECIFICITY.
[7]	"Mutational analysis of duck delta 2 crystallin and the structure of an inactive mutant with bound substrate provide insight into the enzymatic mechanism of argininosuccinate lyase." Sampaleanu L.M., Yu B., Howell P.L. J. Biol. Chem. 277:4166-4175(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF MUTANT ALA-283 IN COMPLEX WITH ARGINOSUCCINATE, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, TISSUE SPECIFICITY, MUTAGENESIS OF SER-29; ASP-33; ASP-89; ASN-116; THR-161; HIS-162; ARG-238; THR-281; SER-283; ASN-291; ASP-293; GLU-296; LYS-325; ASP-330 AND LYS-331.
[8]	"Structural studies of duck delta2 crystallin mutants provide insight into the role of Thr161 and the 280s loop in catalysis." Sampaleanu L.M., Codding P.W., Lobsanov Y.D., Tsai M., Smith G.D., Horvatin C., Howell P.L. Biochem. J. 384:437-447(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF MUTANTS ASP-161 AND SER-161, CATALYTIC ACTIVITY, MUTAGENESIS OF THR-161, FUNCTION, SUBUNIT, TISSUE SPECIFICITY.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M35132 mRNA. Translation: AAC31658.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AUW	X-ray	2.50	A/B/C/D	1-468	[»]
1DCN	X-ray	2.30	A/B/C/D	19-465	[»]
1HY1	X-ray	2.30	A/B/C/D	1-468	[»]
1K7W	X-ray	1.96	A/B/C/D	1-468	[»]
1TJU	X-ray	2.10	A/B/C/D	1-468	[»]
1TJV	X-ray	2.00	A/B/C/D	1-468	[»]
1TJW	X-ray	2.00	A/B/C/D	1-468	[»]

ProteinModelPortal

P24058.

SMR

P24058. Positions 19-467.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Phylogenomic databases

HOVERGEN

HBG004281.

Enzyme and pathway databases

SABIO-RK

P24058.

UniPathway

UPA00068; UER00114.

Family and domain databases

Gene3D

1.10.275.10. 1 hit.

InterPro

IPR009049. Argininosuccinate_lyase.
IPR003031. D_crystallin.
IPR024083. Fumarase/histidase_N.
IPR000362. Fumarate_lyase.
IPR020557. Fumarate_lyase_CS.
IPR022761. Fumarate_lyase_N.
IPR008948. L-Aspartase-like.
[Graphical view]

PANTHER

PTHR11444:SF3. PTHR11444:SF3. 1 hit.

Pfam

PF00206. Lyase_1. 1 hit.
[Graphical view]

PRINTS

PR00145. ARGSUCLYASE.
PR00149. FUMRATELYASE.

SUPFAM

SSF48557. L-Aspartase-like. 1 hit.

TIGRFAMs

TIGR00838. argH. 1 hit.

PROSITE

PS00163. FUMARATE_LYASES. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P24058.

Entry information

Entry name

ARLY2_ANAPL

Accession

Primary (citable) accession number: P24058

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	May 30, 2000
Last modified:	April 3, 2013
This is version 93 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program