RIR1_ECOLI
ID RIR1_ECOLI Reviewed; 761 AA.
AC P00452; P78088; P78177;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Ribonucleoside-diphosphate reductase 1 subunit alpha;
DE EC=1.17.4.1;
DE AltName: Full=Protein B1;
DE AltName: Full=Ribonucleoside-diphosphate reductase 1 R1 subunit;
DE AltName: Full=Ribonucleotide reductase 1;
GN Name=nrdA; Synonyms=dnaF; OrderedLocusNames=b2234, JW2228;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6087316; DOI=10.1073/pnas.81.14.4294;
RA Carlson J., Fuchs J.A., Messing J.;
RT "Primary structure of the Escherichia coli ribonucleoside diphosphate
RT reductase operon.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:4294-4297(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=3287341; DOI=10.1093/nar/16.9.4174;
RA Nilsson O., Aaberg A., Lundqvist T., Sjoeberg B.-M.;
RT "Nucleotide sequence of the gene coding for the large subunit of
RT ribonucleotide reductase of Escherichia coli. Correction.";
RL Nucleic Acids Res. 16:4174-4174(1988).
RN [3]
RP SEQUENCE REVISION TO 526-527.
RA Sjoeberg B.-M.;
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=9205837; DOI=10.1093/dnares/4.2.91;
RA Yamamoto Y., Aiba H., Baba T., Hayashi K., Inada T., Isono K., Itoh T.,
RA Kimura S., Kitagawa M., Makino K., Miki T., Mitsuhashi N., Mizobuchi K.,
RA Mori H., Nakade S., Nakamura Y., Nashimoto H., Oshima T., Oyama S.,
RA Saito N., Sampei G., Satoh Y., Sivasundaram S., Tagami H., Takahashi H.,
RA Takeda J., Takemoto K., Uehara K., Wada C., Yamagata S., Horiuchi T.;
RT "Construction of a contiguous 874-kb sequence of the Escherichia coli-K12
RT genome corresponding to 50.0-68.8 min on the linkage map and analysis of
RT its sequence features.";
RL DNA Res. 4:91-113(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [7]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=3894026; DOI=10.1111/j.1432-1033.1985.tb09037.x;
RA Sjoeberg B.-M., Eriksson S., Joernvall H., Carlquist M., Eklund H.;
RT "Protein B1 of ribonucleotide reductase. Direct analytical data and
RT comparisons with data indirectly deduced from the nucleotide sequence of
RT the Escherichia coli nrdA gene.";
RL Eur. J. Biochem. 150:423-427(1985).
RN [8]
RP ACTIVE SITES.
RX PubMed=2663852; DOI=10.1016/s0021-9258(18)63849-9;
RA Aaberg A., Hahne S., Karlsson M., Larsson A., Ormoe M., Aahgren A.,
RA Sjoeberg B.-M.;
RT "Evidence for two different classes of redox-active cysteines in
RT ribonucleotide reductase of Escherichia coli.";
RL J. Biol. Chem. 264:12249-12252(1989).
RN [9]
RP ACTIVE SITES, AND MUTAGENESIS OF TYR-730 AND TYR-731.
RX PubMed=8702814; DOI=10.1074/jbc.271.34.20655;
RA Ekberg M., Sahlin M., Eriksson M., Sjoberg B.M.;
RT "Two conserved tyrosine residues in protein R1 participate in an
RT intermolecular electron transfer in ribonucleotide reductase.";
RL J. Biol. Chem. 271:20655-20659(1996).
RN [10]
RP ACTIVITY REGULATION, AND INDUCTION BY HYDROXYUREA.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=20005847; DOI=10.1016/j.molcel.2009.11.024;
RA Davies B.W., Kohanski M.A., Simmons L.A., Winkler J.A., Collins J.J.,
RA Walker G.C.;
RT "Hydroxyurea induces hydroxyl radical-mediated cell death in Escherichia
RT coli.";
RL Mol. Cell 36:845-860(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-283, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=K12 / JW1106, and K12 / MG1655 / ATCC 47076;
RX PubMed=18723842; DOI=10.1074/mcp.m800187-mcp200;
RA Zhang J., Sprung R., Pei J., Tan X., Kim S., Zhu H., Liu C.F.,
RA Grishin N.V., Zhao Y.;
RT "Lysine acetylation is a highly abundant and evolutionarily conserved
RT modification in Escherichia coli.";
RL Mol. Cell. Proteomics 8:215-225(2009).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=8052308; DOI=10.1038/370533a0;
RA Uhlin U., Eklund H.;
RT "Structure of ribonucleotide reductase protein R1.";
RL Nature 370:533-539(1994).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF MUTANTS ALA-441; ASP-441 AND
RP GLN-441, DISULFIDE BOND, SUBUNIT, ACTIVE SITE, ACTIVITY REGULATION, ENZYME
RP MECHANISM, AND MUTAGENESIS OF GLU-441.
RX PubMed=9395490; DOI=10.1074/jbc.272.50.31533;
RA Persson A.L., Eriksson M., Katterle B., Potsch S., Sahlin M., Sjoberg B.M.;
RT "A new mechanism-based radical intermediate in a mutant R1 protein
RT affecting the catalytically essential Glu441 in Escherichia coli
RT ribonucleotide reductase.";
RL J. Biol. Chem. 272:31533-31541(1997).
RN [14] {ECO:0007744|PDB:1R1R, ECO:0007744|PDB:2R1R, ECO:0007744|PDB:3R1R, ECO:0007744|PDB:4R1R}
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEXES WITH ATP; GDP AND DTTP,
RP DISULFIDE BOND, SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=9309223; DOI=10.1016/s0969-2126(97)00259-1;
RA Eriksson M., Uhlin U., Ramaswamy S., Ekberg M., Regnstroem K.,
RA Sjoeberg B.-M., Eklund H.;
RT "Binding of allosteric effectors to ribonucleotide reductase protein R1:
RT reduction of active-site cysteines promotes substrate binding.";
RL Structure 5:1077-1092(1997).
RN [15]
RP STRUCTURE BY NMR OF 737-761, AND BINDING SITES.
RX PubMed=10493864; DOI=10.1006/jmbi.1999.3067;
RA Berardi M.J., Bushweller J.H.;
RT "Binding specificity and mechanistic insight into glutaredoxin-catalyzed
RT protein disulfide reduction.";
RL J. Mol. Biol. 292:151-161(1999).
CC -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC Catalyzes the biosynthesis of deoxyribonucleotides from the
CC corresponding ribonucleotides. R1 contains the binding sites for both
CC substrates and allosteric effectors and carries out the actual
CC reduction of the ribonucleotide. It also provides redox-active
CC cysteines.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thioredoxin]-disulfide + a 2'-deoxyribonucleoside 5'-
CC diphosphate + H2O = [thioredoxin]-dithiol + a ribonucleoside 5'-
CC diphosphate; Xref=Rhea:RHEA:23252, Rhea:RHEA-COMP:10698, Rhea:RHEA-
CC COMP:10700, ChEBI:CHEBI:15377, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:73316; EC=1.17.4.1;
CC -!- ACTIVITY REGULATION: Under complex allosteric control mediated by
CC deoxynucleoside triphosphates and ATP binding to separate specificity
CC and activation sites on the alpha subunit. The type of nucleotide bound
CC at the specificity site determines substrate preference. It seems
CC probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP
CC reduction and dTTP favors GDP reduction. Stimulated by ATP and
CC inhibited by dATP binding to the activity site. In vitro, its activity
CC is increased by dithiothreitol (DTT) or thioredoxins (non-specific).
CC Inhibited by hydroxyurea, leads to dNTP depletion, replication fork
CC arrest and genomic instability (PubMed:20005847).
CC {ECO:0000269|PubMed:9309223, ECO:0000269|PubMed:9395490,
CC ECO:0000305|PubMed:20005847}.
CC -!- PATHWAY: Genetic information processing; DNA replication.
CC -!- SUBUNIT: Tetramer of two alpha (R1) and two beta (R2) subunits. The B1
CC protein is a dimer of alpha subunits. A radical transfer pathway occurs
CC between 'Tyr-122' of R2 and R1. {ECO:0000269|PubMed:9309223,
CC ECO:0000269|PubMed:9395490}.
CC -!- INTERACTION:
CC P00452; P00452: nrdA; NbExp=3; IntAct=EBI-370018, EBI-370018;
CC P00452; P69924: nrdB; NbExp=11; IntAct=EBI-370018, EBI-555196;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Alpha;
CC IsoId=P00452-1; Sequence=Displayed;
CC Name=Alpha';
CC IsoId=P00452-2; Sequence=VSP_018871, VSP_018872;
CC -!- INDUCTION: Induced 5-fold by hydroxyurea (at protein level).
CC {ECO:0000269|PubMed:20005847}.
CC -!- PTM: Binding of the substrate occurs primarily when the active-site
CC cysteines are reduced.
CC -!- MISCELLANEOUS: E.coli produces two separate class I enzymes. This one
CC is the functional enzyme during growth.
CC -!- MISCELLANEOUS: Two distinct regulatory sites have been defined: one
CC controls substrate specificity and the other regulates the overall
CC catalytic activity. A substrate-binding catalytic site, located on R1,
CC is formed only in the presence of the second subunit R2.
CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC chain family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA24223.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
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DR EMBL; K02672; AAA24223.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X06999; CAA30056.2; -; Genomic_DNA.
DR EMBL; U00096; AAC75294.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA16053.1; -; Genomic_DNA.
DR PIR; H64993; RDEC1R.
DR RefSeq; NP_416737.1; NC_000913.3.
DR RefSeq; WP_001075164.1; NZ_STEB01000002.1.
DR PDB; 1QFN; NMR; -; B=737-761.
DR PDB; 1R1R; X-ray; 2.90 A; A/B/C=1-761.
DR PDB; 1RLR; X-ray; 2.50 A; A=1-761.
DR PDB; 2R1R; X-ray; 3.00 A; A/B/C=1-761.
DR PDB; 2X0X; X-ray; 2.30 A; A/B/C=1-761.
DR PDB; 2XAK; X-ray; 2.80 A; A/B/C=1-761.
DR PDB; 2XAP; X-ray; 2.10 A; A/B/C=1-761.
DR PDB; 2XAV; X-ray; 2.80 A; A/B/C=1-761.
DR PDB; 2XAW; X-ray; 3.10 A; A/B/C=1-761.
DR PDB; 2XAX; X-ray; 2.75 A; A/B/C=1-761.
DR PDB; 2XAY; X-ray; 2.65 A; A/B/C=1-761.
DR PDB; 2XAZ; X-ray; 2.60 A; A/B/C=1-761.
DR PDB; 2XO4; X-ray; 2.50 A; A/B/C=1-761.
DR PDB; 2XO5; X-ray; 2.70 A; A/B/C=1-761.
DR PDB; 3R1R; X-ray; 3.00 A; A/B/C=1-761.
DR PDB; 3UUS; X-ray; 5.65 A; A/B/C/D=1-761.
DR PDB; 4ERM; X-ray; 3.95 A; A/B/C/D=1-761.
DR PDB; 4ERP; X-ray; 4.45 A; A/B/C/D=1-761.
DR PDB; 4R1R; X-ray; 3.20 A; A/B/C=1-761.
DR PDB; 5CNS; X-ray; 2.98 A; A/B/C/D=1-761.
DR PDB; 5CNT; X-ray; 3.25 A; A/B/C/D=1-761.
DR PDB; 5CNU; X-ray; 3.40 A; A/B/C/D=1-761.
DR PDB; 5CNV; X-ray; 3.20 A; A/B/C/D=1-761.
DR PDB; 5R1R; X-ray; 3.10 A; A/B/C=1-761.
DR PDB; 6R1R; X-ray; 3.10 A; A/B/C=1-761.
DR PDB; 6W4X; EM; 3.60 A; A/B=1-761.
DR PDB; 7R1R; X-ray; 3.10 A; A/B/C=1-761.
DR PDBsum; 1QFN; -.
DR PDBsum; 1R1R; -.
DR PDBsum; 1RLR; -.
DR PDBsum; 2R1R; -.
DR PDBsum; 2X0X; -.
DR PDBsum; 2XAK; -.
DR PDBsum; 2XAP; -.
DR PDBsum; 2XAV; -.
DR PDBsum; 2XAW; -.
DR PDBsum; 2XAX; -.
DR PDBsum; 2XAY; -.
DR PDBsum; 2XAZ; -.
DR PDBsum; 2XO4; -.
DR PDBsum; 2XO5; -.
DR PDBsum; 3R1R; -.
DR PDBsum; 3UUS; -.
DR PDBsum; 4ERM; -.
DR PDBsum; 4ERP; -.
DR PDBsum; 4R1R; -.
DR PDBsum; 5CNS; -.
DR PDBsum; 5CNT; -.
DR PDBsum; 5CNU; -.
DR PDBsum; 5CNV; -.
DR PDBsum; 5R1R; -.
DR PDBsum; 6R1R; -.
DR PDBsum; 6W4X; -.
DR PDBsum; 7R1R; -.
DR AlphaFoldDB; P00452; -.
DR SMR; P00452; -.
DR BioGRID; 4262130; 184.
DR ComplexPortal; CPX-1075; Ribonucleoside-diphosphate reductase 1 complex.
DR DIP; DIP-584N; -.
DR IntAct; P00452; 10.
DR STRING; 511145.b2234; -.
DR iPTMnet; P00452; -.
DR jPOST; P00452; -.
DR PaxDb; P00452; -.
DR PRIDE; P00452; -.
DR EnsemblBacteria; AAC75294; AAC75294; b2234.
DR EnsemblBacteria; BAA16053; BAA16053; BAA16053.
DR GeneID; 58461287; -.
DR GeneID; 946612; -.
DR KEGG; ecj:JW2228; -.
DR KEGG; eco:b2234; -.
DR PATRIC; fig|1411691.4.peg.1; -.
DR EchoBASE; EB0654; -.
DR eggNOG; COG0209; Bacteria.
DR HOGENOM; CLU_000404_3_0_6; -.
DR InParanoid; P00452; -.
DR OMA; RGSIQNI; -.
DR PhylomeDB; P00452; -.
DR BioCyc; EcoCyc:NRDA-MON; -.
DR BioCyc; MetaCyc:NRDA-MON; -.
DR BRENDA; 1.17.4.1; 2026.
DR SABIO-RK; P00452; -.
DR UniPathway; UPA00326; -.
DR EvolutionaryTrace; P00452; -.
DR PRO; PR:P00452; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; IDA:EcoliWiki.
DR GO; GO:0005524; F:ATP binding; IDA:EcoliWiki.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IDA:EcoCyc.
DR GO; GO:0009265; P:2'-deoxyribonucleotide biosynthetic process; IDA:ComplexPortal.
DR GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; IDA:EcoliWiki.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-UniPathway.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; IDA:EcoliWiki.
DR GO; GO:0009185; P:ribonucleoside diphosphate metabolic process; IDA:ComplexPortal.
DR DisProt; DP02715; -.
DR InterPro; IPR005144; ATP-cone_dom.
DR InterPro; IPR013346; NrdE_NrdA.
DR InterPro; IPR000788; RNR_lg_C.
DR InterPro; IPR013509; RNR_lsu_N.
DR InterPro; IPR008926; RNR_R1-su_N.
DR InterPro; IPR039718; Rrm1.
DR PANTHER; PTHR11573; PTHR11573; 1.
DR Pfam; PF03477; ATP-cone; 1.
DR Pfam; PF02867; Ribonuc_red_lgC; 1.
DR Pfam; PF00317; Ribonuc_red_lgN; 1.
DR PRINTS; PR01183; RIBORDTASEM1.
DR SUPFAM; SSF48168; SSF48168; 1.
DR TIGRFAMs; TIGR02506; NrdE_NrdA; 1.
DR PROSITE; PS51161; ATP_CONE; 1.
DR PROSITE; PS00089; RIBORED_LARGE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Allosteric enzyme; Alternative initiation;
KW ATP-binding; Deoxyribonucleotide synthesis; Direct protein sequencing;
KW Disulfide bond; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..761
FT /note="Ribonucleoside-diphosphate reductase 1 subunit
FT alpha"
FT /id="PRO_0000030596"
FT DOMAIN 5..95
FT /note="ATP-cone"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00492"
FT ACT_SITE 437
FT /note="Proton acceptor"
FT ACT_SITE 439
FT /note="Cysteine radical intermediate"
FT ACT_SITE 441
FT /note="Proton acceptor"
FT BINDING 9
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:9309223,
FT ECO:0007744|PDB:3R1R"
FT BINDING 15..21
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:9309223,
FT ECO:0007744|PDB:3R1R"
FT BINDING 55
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:9309223,
FT ECO:0007744|PDB:3R1R"
FT BINDING 91
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:9309223,
FT ECO:0007744|PDB:3R1R"
FT BINDING 209
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000269|PubMed:9309223,
FT ECO:0007744|PDB:4R1R"
FT BINDING 232..234
FT /ligand="dTTP"
FT /ligand_id="ChEBI:CHEBI:37568"
FT /ligand_note="allosteric effector that controls substrate
FT specificity"
FT /evidence="ECO:0000269|PubMed:9309223,
FT ECO:0007744|PDB:4R1R"
FT BINDING 262
FT /ligand="dTTP"
FT /ligand_id="ChEBI:CHEBI:37568"
FT /ligand_note="allosteric effector that controls substrate
FT specificity"
FT /evidence="ECO:0000269|PubMed:9309223,
FT ECO:0007744|PDB:4R1R"
FT BINDING 269
FT /ligand="dTTP"
FT /ligand_id="ChEBI:CHEBI:37568"
FT /ligand_note="allosteric effector that controls substrate
FT specificity"
FT /evidence="ECO:0000269|PubMed:9309223,
FT ECO:0007744|PDB:4R1R"
FT BINDING 437
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000269|PubMed:9309223,
FT ECO:0007744|PDB:4R1R"
FT BINDING 441
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000269|PubMed:9309223,
FT ECO:0007744|PDB:4R1R"
FT BINDING 623..625
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000269|PubMed:9309223,
FT ECO:0007744|PDB:4R1R"
FT SITE 225
FT /note="Important for hydrogen atom transfer"
FT SITE 462
FT /note="Important for hydrogen atom transfer"
FT SITE 730
FT /note="Important for electron transfer"
FT SITE 731
FT /note="Important for electron transfer"
FT SITE 754
FT /note="Interacts with thioredoxin/glutaredoxin"
FT SITE 759
FT /note="Interacts with thioredoxin/glutaredoxin"
FT MOD_RES 283
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:18723842"
FT DISULFID 225..462
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:9309223,
FT ECO:0000269|PubMed:9395490"
FT VAR_SEQ 1..25
FT /note="Missing (in isoform Alpha')"
FT /evidence="ECO:0000305"
FT /id="VSP_018871"
FT VAR_SEQ 26
FT /note="L -> M (in isoform Alpha')"
FT /evidence="ECO:0000305"
FT /id="VSP_018872"
FT VARIANT 1..2
FT /note="Missing (in 15% of the chains)"
FT VARIANT 1
FT /note="Missing (in 30% of the chains)"
FT MUTAGEN 441
FT /note="E->A,Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:9395490"
FT MUTAGEN 441
FT /note="E->D: Decrease in activity."
FT /evidence="ECO:0000269|PubMed:9395490"
FT MUTAGEN 730
FT /note="Y->F: Loss of activity."
FT /evidence="ECO:0000269|PubMed:8702814"
FT MUTAGEN 731
FT /note="Y->F: Loss of activity."
FT /evidence="ECO:0000269|PubMed:8702814"
FT STRAND 6..8
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 10..12
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 19..30
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 38..46
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 55..68
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 77..94
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 102..111
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 118..122
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 125..134
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 137..142
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 145..154
FT /evidence="ECO:0007829|PDB:2XAP"
FT TURN 160..162
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 169..180
FT /evidence="ECO:0007829|PDB:2XAP"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:2XAP"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 189..201
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 204..206
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 209..214
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:5CNS"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 234..248
FT /evidence="ECO:0007829|PDB:2XAP"
FT TURN 249..251
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 253..257
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:1RLR"
FT HELIX 274..276
FT /evidence="ECO:0007829|PDB:5R1R"
FT HELIX 278..289
FT /evidence="ECO:0007829|PDB:2XAP"
FT TURN 290..292
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 296..299
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 301..307
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 313..317
FT /evidence="ECO:0007829|PDB:2XAP"
FT TURN 318..320
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 322..324
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 326..328
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 333..339
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 341..349
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 352..356
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 358..360
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 364..370
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 372..384
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 386..388
FT /evidence="ECO:0007829|PDB:2XAX"
FT STRAND 391..394
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 395..409
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 412..416
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 419..422
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 423..426
FT /evidence="ECO:0007829|PDB:2XAP"
FT TURN 428..430
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 438..440
FT /evidence="ECO:0007829|PDB:5CNS"
FT STRAND 463..468
FT /evidence="ECO:0007829|PDB:2XAP"
FT TURN 469..471
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 475..477
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 478..495
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 501..510
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 513..518
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 520..526
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 531..534
FT /evidence="ECO:0007829|PDB:2X0X"
FT HELIX 537..562
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 568..570
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 573..575
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 579..582
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 585..589
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 599..609
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 612..614
FT /evidence="ECO:0007829|PDB:2XO5"
FT HELIX 624..628
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 639..645
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 648..650
FT /evidence="ECO:0007829|PDB:5CNS"
FT STRAND 652..655
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 659..662
FT /evidence="ECO:0007829|PDB:2XAP"
FT TURN 663..665
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 669..671
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 672..675
FT /evidence="ECO:0007829|PDB:2XAK"
FT HELIX 676..686
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 697..699
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 701..703
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 705..707
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 711..723
FT /evidence="ECO:0007829|PDB:2XAP"
FT STRAND 732..734
FT /evidence="ECO:0007829|PDB:2XAP"
FT HELIX 738..741
FT /evidence="ECO:0007829|PDB:1RLR"
SQ SEQUENCE 761 AA; 85775 MW; 7E034F154567C3FC CRC64;
MNQNLLVTKR DGSTERINLD KIHRVLDWAA EGLHNVSISQ VELRSHIQFY DGIKTSDIHE
TIIKAAADLI SRDAPDYQYL AARLAIFHLR KKAYGQFEPP ALYDHVVKMV EMGKYDNHLL
EDYTEEEFKQ MDTFIDHDRD MTFSYAAVKQ LEGKYLVQNR VTGEIYESAQ FLYILVAACL
FSNYPRETRL QYVKRFYDAV STFKISLPTP IMSGVRTPTR QFSSCVLIEC GDSLDSINAT
SSAIVKYVSQ RAGIGINAGR IRALGSPIRG GEAFHTGCIP FYKHFQTAVK SCSQGGVRGG
AATLFYPMWH LEVESLLVLK NNRGVEGNRV RHMDYGVQIN KLMYTRLLKG EDITLFSPSD
VPGLYDAFFA DQEEFERLYT KYEKDDSIRK QRVKAVELFS LMMQERASTG RIYIQNVDHC
NTHSPFDPAI APVRQSNLCL EIALPTKPLN DVNDENGEIA LCTLSAFNLG AINNLDELEE
LAILAVRALD ALLDYQDYPI PAAKRGAMGR RTLGIGVINF AYYLAKHGKR YSDGSANNLT
HKTFEAIQYY LLKASNELAK EQGACPWFNE TTYAKGILPI DTYKKDLDTI ANEPLHYDWE
ALRESIKTHG LRNSTLSALM PSETSSQISN ATNGIEPPRG YVSIKASKDG ILRQVVPDYE
HLHDAYELLW EMPGNDGYLQ LVGIMQKFID QSISANTNYD PSRFPSGKVP MQQLLKDLLT
AYKFGVKTLY YQNTRDGAED AQDDLVPSIQ DDGCESGACK I
