ARLY2_ANAPL
ID ARLY2_ANAPL Reviewed; 468 AA.
AC P24058;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 4.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Argininosuccinate lyase;
DE Short=ASAL;
DE EC=4.3.2.1;
DE AltName: Full=Arginosuccinase;
DE AltName: Full=Delta crystallin II;
DE AltName: Full=Delta-2 crystallin;
GN Name=ASL2;
OS Anas platyrhynchos (Mallard) (Anas boschas).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Anseriformes; Anatidae;
OC Anatinae; Anas.
OX NCBI_TaxID=8839;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Lens;
RX PubMed=2269436; DOI=10.1016/0378-1119(90)90262-p;
RA Wistow G.J., Piatigorsky J.;
RT "Gene conversion and splice-site slippage in the argininosuccinate
RT lyases/delta-crystallins of the duck lens: members of an enzyme
RT superfamily.";
RL Gene 96:263-270(1990).
RN [2]
RP SEQUENCE REVISION TO 246-247.
RA Graham C., Wistow G.J.;
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP MUTAGENESIS OF TRP-11 AND ASP-117.
RX PubMed=15966727; DOI=10.1021/bi050346s;
RA Tsai M., Koo J., Howell P.L.;
RT "Recovery of argininosuccinate lyase activity in duck delta1 crystallin.";
RL Biochemistry 44:9034-9044(2005).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF MUTANT ASN-91, FUNCTION, CATALYTIC
RP ACTIVITY, SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=9369472; DOI=10.1021/bi971407s;
RA Abu-Abed M., Turner M.A., Vallee F., Simpson A., Slingsby C., Howell P.L.;
RT "Structural comparison of the enzymatically active and inactive forms of
RT delta crystallin and the role of histidine 91.";
RL Biochemistry 36:14012-14022(1997).
RN [5] {ECO:0007744|PDB:1DCN}
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT ASN-162 IN COMPLEX WITH
RP ARGINOSUCCINATE, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND TISSUE
RP SPECIFICITY.
RX PubMed=10029536; DOI=10.1021/bi982149h;
RA Vallee F., Turner M.A., Lindley P.L., Howell P.L.;
RT "Crystal structure of an inactive duck delta II crystallin mutant with
RT bound argininosuccinate.";
RL Biochemistry 38:2425-2434(1999).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) FUNCTION, CATALYTIC ACTIVITY,
RP SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=11258884; DOI=10.1021/bi002272k;
RA Sampaleanu L.M., Vallee F., Slingsby C., Howell P.L.;
RT "Structural studies of duck delta 1 and delta 2 crystallin suggest
RT conformational changes occur during catalysis.";
RL Biochemistry 40:2732-2742(2001).
RN [7] {ECO:0007744|PDB:1K7W}
RP X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF MUTANT ALA-283 IN COMPLEX WITH
RP ARGINOSUCCINATE, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, TISSUE SPECIFICITY, MUTAGENESIS OF SER-29; ASP-33;
RP ASP-89; ASN-116; THR-161; HIS-162; ARG-238; THR-281; SER-283; ASN-291;
RP ASP-293; GLU-296; LYS-325; ASP-330 AND LYS-331, REACTION MECHANISM, AND
RP ACTIVE SITE.
RX PubMed=11698398; DOI=10.1074/jbc.m107465200;
RA Sampaleanu L.M., Yu B., Howell P.L.;
RT "Mutational analysis of duck delta 2 crystallin and the structure of an
RT inactive mutant with bound substrate provide insight into the enzymatic
RT mechanism of argininosuccinate lyase.";
RL J. Biol. Chem. 277:4166-4175(2002).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF MUTANTS ASP-161 AND SER-161,
RP CATALYTIC ACTIVITY, MUTAGENESIS OF THR-161, FUNCTION, SUBUNIT, AND TISSUE
RP SPECIFICITY.
RX PubMed=15320872; DOI=10.1042/bj20040656;
RA Sampaleanu L.M., Codding P.W., Lobsanov Y.D., Tsai M., Smith G.D.,
RA Horvatin C., Howell P.L.;
RT "Structural studies of duck delta2 crystallin mutants provide insight into
RT the role of Thr161 and the 280s loop in catalysis.";
RL Biochem. J. 384:437-447(2004).
CC -!- FUNCTION: Delta crystallin, the principal crystallin in embryonic lens,
CC is found only in birds and reptiles. This protein also functions as an
CC enzymatically active argininosuccinate lyase.
CC {ECO:0000269|PubMed:10029536, ECO:0000269|PubMed:11698398,
CC ECO:0000269|PubMed:15320872, ECO:0000269|PubMed:9369472}.
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; Evidence={ECO:0000269|PubMed:10029536,
CC ECO:0000269|PubMed:11258884, ECO:0000269|PubMed:11698398,
CC ECO:0000269|PubMed:15320872, ECO:0000269|PubMed:9369472};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.05 mM for N(omega)-(L-arginino)succinate
CC {ECO:0000269|PubMed:11698398};
CC Vmax=1.10 umol/min/mg enzyme {ECO:0000269|PubMed:11698398};
CC -!- PATHWAY: Amino-acid biosynthesis; L-arginine biosynthesis; L-arginine
CC from L-ornithine and carbamoyl phosphate: step 3/3.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:10029536,
CC ECO:0000269|PubMed:11258884, ECO:0000269|PubMed:11698398,
CC ECO:0000269|PubMed:15320872, ECO:0000269|PubMed:9369472}.
CC -!- TISSUE SPECIFICITY: Eye lens. {ECO:0000269|PubMed:10029536,
CC ECO:0000269|PubMed:11258884, ECO:0000269|PubMed:11698398,
CC ECO:0000269|PubMed:15320872, ECO:0000269|PubMed:2269436,
CC ECO:0000269|PubMed:9369472}.
CC -!- MISCELLANEOUS: Each of the four substrate-binding sites present in the
CC homotetrameric assembly are shared between three of the four subunits.
CC -!- SIMILARITY: Belongs to the lyase 1 family. Argininosuccinate lyase
CC subfamily. {ECO:0000305}.
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DR EMBL; M35132; AAC31658.1; -; mRNA.
DR PDB; 1AUW; X-ray; 2.50 A; A/B/C/D=1-468.
DR PDB; 1DCN; X-ray; 2.30 A; A/B/C/D=19-465.
DR PDB; 1HY1; X-ray; 2.30 A; A/B/C/D=1-468.
DR PDB; 1K7W; X-ray; 1.96 A; A/B/C/D=1-468.
DR PDB; 1TJU; X-ray; 2.10 A; A/B/C/D=1-468.
DR PDB; 1TJV; X-ray; 2.00 A; A/B/C/D=1-468.
DR PDB; 1TJW; X-ray; 2.00 A; A/B/C/D=1-468.
DR PDBsum; 1AUW; -.
DR PDBsum; 1DCN; -.
DR PDBsum; 1HY1; -.
DR PDBsum; 1K7W; -.
DR PDBsum; 1TJU; -.
DR PDBsum; 1TJV; -.
DR PDBsum; 1TJW; -.
DR AlphaFoldDB; P24058; -.
DR SMR; P24058; -.
DR MoonProt; P24058; -.
DR SABIO-RK; P24058; -.
DR UniPathway; UPA00068; UER00114.
DR EvolutionaryTrace; P24058; -.
DR GO; GO:0004056; F:argininosuccinate lyase activity; IDA:UniProtKB.
DR GO; GO:0005212; F:structural constituent of eye lens; TAS:UniProtKB.
DR GO; GO:0006526; P:arginine biosynthetic process; TAS:UniProtKB.
DR GO; GO:0042450; P:arginine biosynthetic process via ornithine; IEA:InterPro.
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; Amino-acid biosynthesis; Arginine biosynthesis;
KW Eye lens protein; Lyase.
FT CHAIN 1..468
FT /note="Argininosuccinate lyase"
FT /id="PRO_0000137717"
FT ACT_SITE 162
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:11698398"
FT ACT_SITE 283
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:11698398"
FT BINDING 29
FT /ligand="2-(N(omega)-L-arginino)succinate"
FT /ligand_id="ChEBI:CHEBI:57472"
FT /ligand_note="ligand shared between tetrameric partners"
FT /note="in chain A"
FT /evidence="ECO:0000269|PubMed:11698398,
FT ECO:0007744|PDB:1K7W"
FT BINDING 116
FT /ligand="2-(N(omega)-L-arginino)succinate"
FT /ligand_id="ChEBI:CHEBI:57472"
FT /ligand_note="ligand shared between tetrameric partners"
FT /note="in chain A"
FT /evidence="ECO:0000269|PubMed:11698398,
FT ECO:0007744|PDB:1K7W"
FT BINDING 161
FT /ligand="2-(N(omega)-L-arginino)succinate"
FT /ligand_id="ChEBI:CHEBI:57472"
FT /ligand_note="ligand shared between tetrameric partners"
FT /note="in chain C"
FT /evidence="ECO:0000269|PubMed:10029536,
FT ECO:0000269|PubMed:11698398, ECO:0007744|PDB:1DCN,
FT ECO:0007744|PDB:1K7W"
FT BINDING 291
FT /ligand="2-(N(omega)-L-arginino)succinate"
FT /ligand_id="ChEBI:CHEBI:57472"
FT /ligand_note="ligand shared between tetrameric partners"
FT /note="in chain B"
FT /evidence="ECO:0000269|PubMed:10029536,
FT ECO:0000269|PubMed:11698398, ECO:0007744|PDB:1DCN,
FT ECO:0007744|PDB:1K7W"
FT BINDING 323
FT /ligand="2-(N(omega)-L-arginino)succinate"
FT /ligand_id="ChEBI:CHEBI:57472"
FT /ligand_note="ligand shared between tetrameric partners"
FT /note="in chain A"
FT /evidence="ECO:0000269|PubMed:10029536,
FT ECO:0000269|PubMed:11698398, ECO:0007744|PDB:1DCN,
FT ECO:0007744|PDB:1K7W"
FT BINDING 328
FT /ligand="2-(N(omega)-L-arginino)succinate"
FT /ligand_id="ChEBI:CHEBI:57472"
FT /ligand_note="ligand shared between tetrameric partners"
FT /note="in chain A"
FT /evidence="ECO:0000269|PubMed:10029536,
FT ECO:0007744|PDB:1DCN"
FT BINDING 331
FT /ligand="2-(N(omega)-L-arginino)succinate"
FT /ligand_id="ChEBI:CHEBI:57472"
FT /ligand_note="ligand shared between tetrameric partners"
FT /note="in chain A"
FT /evidence="ECO:0000269|PubMed:10029536,
FT ECO:0000269|PubMed:11698398, ECO:0007744|PDB:1DCN,
FT ECO:0007744|PDB:1K7W"
FT SITE 296
FT /note="Increases basicity of active site His"
FT /evidence="ECO:0000305|PubMed:11698398"
FT MUTAGEN 11
FT /note="W->A: 98% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:15966727"
FT MUTAGEN 11
FT /note="W->F: 90% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:15966727"
FT MUTAGEN 11
FT /note="W->M: 99% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:15966727"
FT MUTAGEN 11
FT /note="W->R: 97% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:15966727"
FT MUTAGEN 11
FT /note="W->Y: 50% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:15966727"
FT MUTAGEN 29
FT /note="S->A: 10% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 33
FT /note="D->N: 99% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 89
FT /note="D->N: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 91
FT /note="H->N: 90% decrease in catalytic activity with 10-
FT fold decrease in substrate affinity."
FT MUTAGEN 116
FT /note="N->D: 99% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 117
FT /note="D->A: 55% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:15966727"
FT MUTAGEN 117
FT /note="D->E: 58% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:15966727"
FT MUTAGEN 161
FT /note="T->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11698398,
FT ECO:0000269|PubMed:15320872"
FT MUTAGEN 161
FT /note="T->D: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11698398,
FT ECO:0000269|PubMed:15320872"
FT MUTAGEN 161
FT /note="T->S: 30% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:11698398,
FT ECO:0000269|PubMed:15320872"
FT MUTAGEN 161
FT /note="T->V: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11698398,
FT ECO:0000269|PubMed:15320872"
FT MUTAGEN 162
FT /note="H->E: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 238
FT /note="R->Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 281
FT /note="T->V: 80% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 283
FT /note="S->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 283
FT /note="S->C: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 283
FT /note="S->D: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 283
FT /note="S->H: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 283
FT /note="S->T: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 291
FT /note="N->L: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 293
FT /note="D->N: 99% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 296
FT /note="E->D: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 325
FT /note="K->N: 99% decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 330
FT /note="D->N: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11698398"
FT MUTAGEN 331
FT /note="K->Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11698398"
FT HELIX 21..27
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 30..33
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 34..36
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 37..53
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 59..77
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 90..102
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 104..110
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 115..151
FT /evidence="ECO:0007829|PDB:1K7W"
FT TURN 152..154
FT /evidence="ECO:0007829|PDB:1K7W"
FT STRAND 156..161
FT /evidence="ECO:0007829|PDB:1K7W"
FT STRAND 164..170
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 171..196
FT /evidence="ECO:0007829|PDB:1K7W"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:1K7W"
FT TURN 204..207
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 215..222
FT /evidence="ECO:0007829|PDB:1K7W"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 231..236
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 239..265
FT /evidence="ECO:0007829|PDB:1K7W"
FT TURN 268..270
FT /evidence="ECO:0007829|PDB:1K7W"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:1TJV"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:1K7W"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:1K7W"
FT STRAND 286..291
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 293..316
FT /evidence="ECO:0007829|PDB:1K7W"
FT STRAND 321..323
FT /evidence="ECO:0007829|PDB:1TJV"
FT HELIX 325..329
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 330..354
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 359..364
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 368..371
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 372..380
FT /evidence="ECO:0007829|PDB:1K7W"
FT TURN 381..383
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 386..401
FT /evidence="ECO:0007829|PDB:1K7W"
FT TURN 402..404
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 407..409
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 412..418
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 424..429
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 432..436
FT /evidence="ECO:0007829|PDB:1K7W"
FT STRAND 444..446
FT /evidence="ECO:0007829|PDB:1K7W"
FT HELIX 447..465
FT /evidence="ECO:0007829|PDB:1K7W"
SQ SEQUENCE 468 AA; 51710 MW; FBFD26EDC762E7BC CRC64;
MASEARGDKL WGGRFSGSTD PIMEKLNSSI AYDQRLSEVD IQGSMAYAKA LEKAGILTKT
ELEKILSGLE KISEEWSKGV FVVKQSDEDI HTANERRLKE LIGDIAGKLH TGRSRNDQVV
TDLKLFMKNS LSIISTHLLQ LIKTLVERAA IEIDVILPGY THLQKAQPIR WSQFLLSHAV
ALTRDSERLG EVKKRINVLP LGSGALAGNP LDIDREMLRS ELEFASISLN SMDAISERDF
VVEFLSFATL LMIHLSKMAE DLIIYSTSEF GFLTLSDAFS TGSSLMPQKK NPDSLELIRS
KAGRVFGRLA SILMVLKGLP STYNKDLQED KEAVFDVVDT LTAVLQVATG VISTLQISKE
NMEKALTPEM LATDLALYLV RKGVPFRQAH TASGKAVHLA ETKGITINKL SLEDLKSISP
QFSSDVSQVF NFVNSVEQYT ALAGTAKSSV TTQIEQLREL MKKQKEQA
