ID AMPL_BOVIN Reviewed; 519 AA. AC P00727; Q2HJH5; Q2PC24; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 188. DE RecName: Full=Cytosol aminopeptidase {ECO:0000305}; DE EC=3.4.11.1 {ECO:0000269|PubMed:14583094}; DE AltName: Full=Cysteinylglycine-S-conjugate dipeptidase {ECO:0000305|PubMed:14583094}; DE EC=3.4.13.23 {ECO:0000269|PubMed:14583094}; DE AltName: Full=Leucine aminopeptidase 3 {ECO:0000250|UniProtKB:P28838}; DE Short=LAP-3; DE AltName: Full=Leucyl aminopeptidase {ECO:0000303|PubMed:14583094}; DE Short=LAP {ECO:0000303|PubMed:14583094}; DE AltName: Full=Peptidase S {ECO:0000250|UniProtKB:P28838}; DE AltName: Full=Proline aminopeptidase {ECO:0000250|UniProtKB:P28839}; DE EC=3.4.11.5 {ECO:0000250|UniProtKB:P28839}; DE AltName: Full=Prolyl aminopeptidase {ECO:0000250|UniProtKB:P28838}; GN Name=LAP3 {ECO:0000250|UniProtKB:P28838}; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Hereford; RX PubMed=19390049; DOI=10.1126/science.1169588; RG The bovine genome sequencing and analysis consortium; RT "The genome sequence of taurine cattle: a window to ruminant biology and RT evolution."; RL Science 324:522-528(2009). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Kidney; RX PubMed=8369298; DOI=10.1021/bi00087a006; RA Wallner B.P., Hession C., Tizard R., Frey A.Z., Zuliani A., Mura C., RA Jahngen-Hodge J., Taylor A.; RT "Isolation of bovine kidney leucine aminopeptidase cDNA: comparison with RT the lens enzyme and tissue-specific expression of two mRNAs."; RL Biochemistry 32:9296-9301(1993). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 11-519 (ISOFORM 1). RC STRAIN=Hereford; TISSUE=Hypothalamus; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP PROTEIN SEQUENCE (ISOFORM 3), AND CLEAVAGE OF INITIATOR METHIONINE (ISOFORM RP 3). RC TISSUE=Lens; RX PubMed=7085616; DOI=10.1016/s0021-9258(18)34539-3; RA Cuypers H.T., van Loon-Klaassen L.A.H., Vree Egberts W.T.M., de Jong W.W., RA Bloemendal H.; RT "The primary structure of leucine aminopeptidase from bovine eye lens."; RL J. Biol. Chem. 257:7077-7085(1982). RN [5] RP PROTEIN SEQUENCE (ISOFORM 3), AND CLEAVAGE OF INITIATOR METHIONINE (ISOFORM RP 3). RX PubMed=7085617; DOI=10.1016/s0021-9258(18)34540-x; RA Cuypers H.T., van Loon-Klaassen L.A.H., Vree Egberts W.T.M., de Jong W.W., RA Bloemendal H.; RT "Sulfhydryl content of bovine eye lens leucine aminopeptidase. RT Determination of the reactivity of the sulfhydryl groups of the zinc RT metalloenzyme, of the enzyme activated by Mg2+, Mn2+, and Co2+, and of the RT metal-free apoenzyme."; RL J. Biol. Chem. 257:7086-7091(1982). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 431-478. RC STRAIN=Holstein; RA Seroussi E.; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=14583094; DOI=10.1042/bj20031336; RA Cappiello M., Lazzarotti A., Buono F., Scaloni A., D'Ambrosio C., RA Amodeo P., Mendez B.L., Pelosi P., Del Corso A., Mura U.; RT "New role for leucyl aminopeptidase in glutathione turnover."; RL Biochem. J. 378:35-44(2004). RN [8] {ECO:0007744|PDB:1LAP} RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) (ISOFORM 3) IN COMPLEX WITH ZINC, AND RP CLEAVAGE OF INITIATOR METHIONINE (ISOFORM 3). RX PubMed=2395881; DOI=10.1073/pnas.87.17.6878; RA Burley S.K., David P.R., Taylor A., Lipscomb W.N.; RT "Molecular structure of leucine aminopeptidase at 2.7-A resolution."; RL Proc. Natl. Acad. Sci. U.S.A. 87:6878-6882(1990). RN [9] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) (ISOFORM 3) IN COMPLEX WITH BESTATIN, RP AND CLEAVAGE OF INITIATOR METHIONINE (ISOFORM 3). RX PubMed=1548695; DOI=10.1016/0022-2836(92)90580-d; RA Burley S.K., David P.R., Sweet R.M., Taylor A., Lipscomb W.N.; RT "Structure determination and refinement of bovine lens leucine RT aminopeptidase and its complex with bestatin."; RL J. Mol. Biol. 224:113-140(1992). RN [10] {ECO:0007744|PDB:1BLL} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 33-519 IN COMPLEX WITH ZINC AND RP AMASTATIN. RX PubMed=8357796; DOI=10.1021/bi00084a011; RA Kim H., Lipscomb W.N.; RT "X-ray crystallographic determination of the structure of bovine lens RT leucine aminopeptidase complexed with amastatin: formulation of a catalytic RT mechanism featuring a gem-diolate transition state."; RL Biochemistry 32:8465-8478(1993). RN [11] {ECO:0007744|PDB:1BPM, ECO:0007744|PDB:1BPN} RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 33-519 IN COMPLEX WITH MAGNESIUM RP AND ZINC. RX PubMed=8506345; DOI=10.1073/pnas.90.11.5006; RA Kim H., Lipscomb W.N.; RT "Differentiation and identification of the two catalytic metal binding RT sites in bovine lens leucine aminopeptidase by x-ray crystallography."; RL Proc. Natl. Acad. Sci. U.S.A. 90:5006-5010(1993). RN [12] {ECO:0007744|PDB:1LAM, ECO:0007744|PDB:1LAN} RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) (ISOFORM 3) IN COMPLEX WITH ZINC AND RP LEUCINE, CLEAVAGE OF INITIATOR METHIONINE (ISOFORM 3), AND ACTIVE SITE. RX PubMed=7578088; DOI=10.1021/bi00045a021; RA Straeter N., Lipscomb W.N.; RT "Two-metal ion mechanism of bovine lens leucine aminopeptidase: active site RT solvent structure and binding mode of L-leucinal, a gem-diolate transition RT state analogue, by X-ray crystallography."; RL Biochemistry 34:14792-14800(1995). RN [13] {ECO:0007744|PDB:1LCP} RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 33-516 IN COMPLEX WITH LEUCINE RP PHOSPHONIC ACID AND ZINC. RX PubMed=7619821; DOI=10.1021/bi00028a033; RA Strater N., Lipscomb W.N.; RT "Transition state analogue L-leucinephosphonic acid bound to bovine lens RT leucine aminopeptidase: X-ray structure at 1.65 A resolution in a new RT crystal form."; RL Biochemistry 34:9200-9210(1995). RN [14] {ECO:0007744|PDB:2EWB} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 33-518 IN COMPLEX WITH ZINC AND RP ZOFENOPRILAT, FUNCTION, COFACTOR, ACTIVITY REGULATION, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=16519517; DOI=10.1021/bi052069v; RA Cappiello M., Alterio V., Amodeo P., Del Corso A., Scaloni A., Pedone C., RA Moschini R., De Donatis G.M., De Simone G., Mura U.; RT "Metal ion substitution in the catalytic site greatly affects the binding RT of sulfhydryl-containing compounds to leucyl aminopeptidase."; RL Biochemistry 45:3226-3234(2006). RN [15] {ECO:0007744|PDB:2J9A} RP X-RAY CRYSTALLOGRAPHY (1.73 ANGSTROMS) OF 33-519 IN COMPLEX WITH ZINC AND RP MICROGININ FR1. RX PubMed=17157838; DOI=10.1016/j.febslet.2006.11.060; RA Kraft M., Schleberger C., Weckesser J., Schulz G.E.; RT "Binding structure of the leucine aminopeptidase inhibitor microginin RT FR1."; RL FEBS Lett. 580:6943-6947(2006). CC -!- FUNCTION: Cytosolic metallopeptidase that catalyzes the removal of CC unsubstituted N-terminal hydrophobic amino acids from various peptides CC (PubMed:14583094, PubMed:16519517). The presence of Zn(2+) ions is CC essential for the peptidase activity, and the association with other CC cofactors can modulate the substrate spectificity of the enzyme CC (PubMed:16519517). For instance, in the presence of Mn(2+), it displays CC a specific Cys-Gly hydrolyzing activity of Cys-Gly-S-conjugates CC (PubMed:16519517). Involved in the metabolism of glutathione and in the CC degradation of glutathione S-conjugates, which may play a role in the CC control of the cell redox status (PubMed:14583094). CC {ECO:0000269|PubMed:14583094, ECO:0000269|PubMed:16519517}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Release of an N-terminal amino acid, Xaa-|-Yaa-, in which Xaa CC is preferably Leu, but may be other amino acids including Pro CC although not Arg or Lys, and Yaa may be Pro. Amino acid amides and CC methyl esters are also readily hydrolyzed, but rates on arylamides CC are exceedingly low.; EC=3.4.11.1; CC Evidence={ECO:0000269|PubMed:14583094}; CC -!- CATALYTIC ACTIVITY: CC Reaction=an S-substituted L-cysteinylglycine + H2O = an S-substituted CC L-cysteine + glycine; Xref=Rhea:RHEA:60444, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:57305, ChEBI:CHEBI:58717, ChEBI:CHEBI:143103; CC EC=3.4.13.23; Evidence={ECO:0000269|PubMed:14583094}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60445; CC Evidence={ECO:0000305|PubMed:14583094}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + L-cysteinylglycine = glycine + L-cysteine; CC Xref=Rhea:RHEA:28783, ChEBI:CHEBI:15377, ChEBI:CHEBI:35235, CC ChEBI:CHEBI:57305, ChEBI:CHEBI:61694; CC Evidence={ECO:0000269|PubMed:14583094}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28784; CC Evidence={ECO:0000305|PubMed:14583094}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + S-benzyl-L-cysteinylglycine = glycine + S-benzyl-L- CC cysteine; Xref=Rhea:RHEA:62568, ChEBI:CHEBI:15377, ChEBI:CHEBI:57305, CC ChEBI:CHEBI:145802, ChEBI:CHEBI:145803; CC Evidence={ECO:0000250|UniProtKB:Q68FS4}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62569; CC Evidence={ECO:0000250|UniProtKB:Q68FS4}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Release of N-terminal proline from a peptide.; EC=3.4.11.5; CC Evidence={ECO:0000250|UniProtKB:P28839}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:16519517}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000269|PubMed:16519517}; CC Note=Binds two metal ions per subunit. Two metal binding sites with CC different affinities are located in the enzyme active site and can be CC occupied in vitro by different metals: site 1 is occupied by Zn(2+), CC Mn(2+), Mg(2+) or Co(2+), while the tight binding site 2 can be CC occupied by only Zn(2+) or Co(2+) (PubMed:16519517). One Zn(2+) ion is CC tightly bound to site 2 and essential for enzyme activity in vivo, CC while site 1 can be occupied by different metals to give different CC enzymatic activities (PubMed:16519517). Mn(2+) is required for Cys-Gly CC hydrolysis activity (PubMed:16519517). A third metal binding site may CC serve a structural role, possibly stabilizing part of the interface CC between the N-terminal and the catalytic domain (PubMed:7619821). CC {ECO:0000269|PubMed:16519517, ECO:0000269|PubMed:7619821, CC ECO:0000303|PubMed:16519517}; CC -!- ACTIVITY REGULATION: Zofenoprilat inhibits Cys-Gly hydrolysis activity. CC {ECO:0000269|PubMed:16519517}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.42 mM for Cys-Gly (at pH 6.9 and 25 degrees Celsius) CC {ECO:0000269|PubMed:14583094}; CC KM=2.3 mM for Leu-Gly (at pH 6.9 and 25 degrees Celsius) CC {ECO:0000269|PubMed:14583094}; CC KM=2.8 mM for Met-Gly (at pH 6.9 and 25 degrees Celsius) CC {ECO:0000269|PubMed:14583094}; CC KM=0.57 mM for Cys-Gly (at pH 7.4 and 25 degrees Celsius) CC {ECO:0000269|PubMed:14583094}; CC KM=2.5 mM for Leu-Gly (at pH 7.4 and 25 degrees Celsius) CC {ECO:0000269|PubMed:14583094}; CC KM=1.5 mM for Met-Gly (at pH 7.4 and 25 degrees Celsius) CC {ECO:0000269|PubMed:14583094}; CC KM=5.2 mM for Ser-Gly (at pH 7.4 and 25 degrees Celsius) CC {ECO:0000269|PubMed:14583094}; CC KM=0.59 mM for Cys-Gly (at pH 8.3 and 25 degrees Celsius) CC {ECO:0000269|PubMed:14583094}; CC KM=1.5 mM for Leu-Gly (at pH 8.3 and 25 degrees Celsius) CC {ECO:0000269|PubMed:14583094}; CC KM=1.3 mM for Met-Gly (at pH 8.3 and 25 degrees Celsius) CC {ECO:0000269|PubMed:14583094}; CC KM=5 mM for Ser-Gly (at pH 8.3 and 25 degrees Celsius) CC {ECO:0000269|PubMed:14583094}; CC Note=kcat is 3400 min(-1) for Cys-Gly hydrolysis activity (at pH 6.9 CC and 25 degrees Celsius). kcat is 11500 min(-1) for Leu-Gly hydrolysis CC activity (at pH 6.9 and 25 degrees Celsius). kcat is 8150 min(-1) for CC Met-Gly hydrolysis activity (at pH 6.9 and 25 degrees Celsius) CC (PubMed:14583094). kcat is 6000 min(-1) for Cys-Gly hydrolysis CC activity (at pH 7.4 and 25 degrees Celsius). kcat is 24000 min(-1) CC for Leu-Gly hydrolysis activity (at pH 7.4 and 25 degrees Celsius). CC kcat is 28100 min(-1) for Met-Gly hydrolysis activity (at pH 7.4 and CC 25 degrees Celsius). kcat is 1000 min(-1) for Ser-Gly hydrolysis CC activity (at pH 7.4 and 25 degrees Celsius) (PubMed:14583094). kcat CC is 7100 min(-1) for Cys-Gly hydrolysis activity (at pH 8.3 and 25 CC degrees Celsius). kcat is 40500 min(-1) for Leu-Gly hydrolysis CC activity (at pH 8.3 and 25 degrees Celsius). kcat is 59300 min(-1) CC for Met-Gly hydrolysis activity (at pH 8.3 and 25 degrees Celsius). CC kcat is 2500 min(-1) for Ser-Gly hydrolysis activity (at pH 8.3 and CC 25 degrees Celsius) (PubMed:14583094). {ECO:0000269|PubMed:14583094}; CC -!- SUBUNIT: Homohexamer. {ECO:0000269|PubMed:14583094}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q68FS4}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=3; CC Name=1; CC IsoId=P00727-1; Sequence=Displayed; CC Name=2; CC IsoId=P00727-2; Sequence=VSP_022634; CC Name=3; CC IsoId=P00727-3; Sequence=VSP_058150; CC -!- SIMILARITY: Belongs to the peptidase M17 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB28170.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; S65367; AAB28170.1; ALT_INIT; mRNA. DR EMBL; BC105385; AAI05386.1; -; mRNA. DR EMBL; AJ871963; CAI44744.1; -; Genomic_DNA. DR PIR; A54338; APBOL. DR RefSeq; NP_776523.2; NM_174098.3. [P00727-1] DR PDB; 1BLL; X-ray; 2.40 A; E=33-519. DR PDB; 1BPM; X-ray; 2.90 A; A=33-519. DR PDB; 1BPN; X-ray; 2.90 A; A=33-519. DR PDB; 1LAM; X-ray; 1.60 A; A=33-516. DR PDB; 1LAN; X-ray; 1.90 A; A=33-516. DR PDB; 1LAP; X-ray; 2.70 A; A=33-519. DR PDB; 1LCP; X-ray; 1.65 A; A/B=33-516. DR PDB; 2EWB; X-ray; 1.85 A; A=33-518. DR PDB; 2J9A; X-ray; 1.73 A; A=33-519. DR PDBsum; 1BLL; -. DR PDBsum; 1BPM; -. DR PDBsum; 1BPN; -. DR PDBsum; 1LAM; -. DR PDBsum; 1LAN; -. DR PDBsum; 1LAP; -. DR PDBsum; 1LCP; -. DR PDBsum; 2EWB; -. DR PDBsum; 2J9A; -. DR AlphaFoldDB; P00727; -. DR SMR; P00727; -. DR STRING; 9913.ENSBTAP00000007860; -. DR BindingDB; P00727; -. DR ChEMBL; CHEMBL1671610; -. DR DrugCentral; P00727; -. DR MEROPS; M17.001; -. DR PaxDb; 9913-ENSBTAP00000007860; -. DR PeptideAtlas; P00727; -. DR Ensembl; ENSBTAT00000007860.6; ENSBTAP00000007860.5; ENSBTAG00000005989.6. [P00727-1] DR GeneID; 781648; -. DR KEGG; bta:781648; -. DR CTD; 51056; -. DR VEuPathDB; HostDB:ENSBTAG00000005989; -. DR eggNOG; KOG2597; Eukaryota. DR GeneTree; ENSGT00530000063255; -. DR InParanoid; P00727; -. DR OMA; MVTMKAD; -. DR OrthoDB; 2899215at2759; -. DR TreeFam; TF314954; -. DR BRENDA; 3.4.11.1; 908. DR SABIO-RK; P00727; -. DR EvolutionaryTrace; P00727; -. DR Proteomes; UP000009136; Chromosome 6. DR Bgee; ENSBTAG00000005989; Expressed in caput epididymis and 102 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IDA:CAFA. DR GO; GO:0005739; C:mitochondrion; ISS:AgBase. DR GO; GO:0004180; F:carboxypeptidase activity; IEA:RHEA. DR GO; GO:0016805; F:dipeptidase activity; IEA:UniProtKB-KW. DR GO; GO:0097718; F:disordered domain specific binding; IPI:CAFA. DR GO; GO:0030145; F:manganese ion binding; IEA:InterPro. DR GO; GO:0070006; F:metalloaminopeptidase activity; IEA:InterPro. DR GO; GO:0008233; F:peptidase activity; ISS:AgBase. DR GO; GO:0006508; P:proteolysis; IBA:GO_Central. DR CDD; cd00433; Peptidase_M17; 1. DR Gene3D; 3.40.220.10; Leucine Aminopeptidase, subunit E, domain 1; 1. DR Gene3D; 3.40.630.10; Zn peptidases; 1. DR HAMAP; MF_00181; Cytosol_peptidase_M17; 1. DR InterPro; IPR011356; Leucine_aapep/pepB. DR InterPro; IPR043472; Macro_dom-like. DR InterPro; IPR000819; Peptidase_M17_C. DR InterPro; IPR023042; Peptidase_M17_leu_NH2_pept. DR InterPro; IPR008283; Peptidase_M17_N. DR PANTHER; PTHR11963:SF52; CYTOSOL AMINOPEPTIDASE; 1. DR PANTHER; PTHR11963; LEUCINE AMINOPEPTIDASE-RELATED; 1. DR Pfam; PF00883; Peptidase_M17; 1. DR Pfam; PF02789; Peptidase_M17_N; 1. DR PRINTS; PR00481; LAMNOPPTDASE. DR SUPFAM; SSF52949; Macro domain-like; 1. DR SUPFAM; SSF53187; Zn-dependent exopeptidases; 1. DR PROSITE; PS00631; CYTOSOL_AP; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative initiation; Aminopeptidase; Cobalt; KW Cytoplasm; Dipeptidase; Direct protein sequencing; Hydrolase; Magnesium; KW Manganese; Metal-binding; Phosphoprotein; Protease; Reference proteome; KW Zinc. FT CHAIN 1..519 FT /note="Cytosol aminopeptidase" FT /id="PRO_0000165824" FT ACT_SITE 294 FT /evidence="ECO:0000269|PubMed:7578088" FT ACT_SITE 368 FT /evidence="ECO:0000269|PubMed:7578088" FT BINDING 202 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /ligand_note="structural" FT /evidence="ECO:0000305|PubMed:7619821, FT ECO:0007744|PDB:1LCP" FT BINDING 203 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /ligand_note="structural" FT /evidence="ECO:0000305|PubMed:7619821, FT ECO:0007744|PDB:1LCP" FT BINDING 205 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /ligand_note="structural" FT /evidence="ECO:0000305|PubMed:7619821, FT ECO:0007744|PDB:1LCP" FT BINDING 282 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:7578088, FT ECO:0000269|PubMed:7619821, ECO:0007744|PDB:1LAN, FT ECO:0007744|PDB:1LCP" FT BINDING 282 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:16519517, FT ECO:0000269|PubMed:17157838, ECO:0007744|PDB:2EWB, FT ECO:0007744|PDB:2J9A" FT BINDING 287 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:8506345, FT ECO:0007744|PDB:1BPM" FT BINDING 287 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:7578088, FT ECO:0000269|PubMed:7619821, ECO:0007744|PDB:1LAN, FT ECO:0007744|PDB:1LCP" FT BINDING 287 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:16519517, FT ECO:0000269|PubMed:17157838, ECO:0000269|PubMed:8506345, FT ECO:0007744|PDB:2EWB, ECO:0007744|PDB:2J9A" FT BINDING 287 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:16519517, FT ECO:0000269|PubMed:17157838, ECO:0007744|PDB:2EWB, FT ECO:0007744|PDB:2J9A" FT BINDING 292 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:7619821, FT ECO:0007744|PDB:1LCP" FT BINDING 294 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:7578088, FT ECO:0000269|PubMed:7619821, ECO:0007744|PDB:1LAN, FT ECO:0007744|PDB:1LCP" FT BINDING 303 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /ligand_note="structural" FT /evidence="ECO:0000305|PubMed:7619821, FT ECO:0007744|PDB:1LCP" FT BINDING 305 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:7578088, FT ECO:0007744|PDB:1LAN" FT BINDING 305 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:16519517, FT ECO:0000269|PubMed:17157838, ECO:0007744|PDB:2EWB, FT ECO:0007744|PDB:2J9A" FT BINDING 364 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:8506345, FT ECO:0007744|PDB:1BPM" FT BINDING 364 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:7619821, FT ECO:0007744|PDB:1LCP" FT BINDING 364 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:16519517, FT ECO:0000269|PubMed:17157838, ECO:0000269|PubMed:8506345, FT ECO:0007744|PDB:2EWB, ECO:0007744|PDB:2J9A" FT BINDING 366 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:8506345, FT ECO:0007744|PDB:1BPM" FT BINDING 366 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:16519517, FT ECO:0000269|PubMed:17157838, ECO:0000269|PubMed:8506345, FT ECO:0007744|PDB:2EWB, ECO:0007744|PDB:2J9A" FT BINDING 366 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:16519517, FT ECO:0000269|PubMed:17157838, ECO:0000269|PubMed:8506345, FT ECO:0007744|PDB:1BPM, ECO:0007744|PDB:2EWB, FT ECO:0007744|PDB:2J9A" FT MOD_RES 42 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q68FS4" FT MOD_RES 45 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9CPY7" FT MOD_RES 54 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q68FS4" FT MOD_RES 61 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9CPY7" FT MOD_RES 103 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9CPY7" FT MOD_RES 180 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9CPY7" FT MOD_RES 194 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P28838" FT MOD_RES 238 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P28838" FT MOD_RES 455 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9CPY7" FT MOD_RES 455 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9CPY7" FT MOD_RES 476 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9CPY7" FT MOD_RES 489 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9CPY7" FT MOD_RES 489 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9CPY7" FT VAR_SEQ 1..31 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_058150" FT VAR_SEQ 11..31 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8369298" FT /id="VSP_022634" FT CONFLICT 77 FT /note="P -> S (in Ref. 2; AAB28170)" FT /evidence="ECO:0000305" FT CONFLICT 414..415 FT /note="LW -> M (in Ref. 4; AA sequence and 5; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 506..513 FT /note="Missing (in Ref. 4; AA sequence and 5; AA sequence)" FT /evidence="ECO:0000305" FT STRAND 34..40 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 47..49 FT /evidence="ECO:0007829|PDB:1BPM" FT HELIX 54..62 FT /evidence="ECO:0007829|PDB:1LAM" FT TURN 63..65 FT /evidence="ECO:0007829|PDB:1LAM" FT HELIX 66..73 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 83..90 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 93..100 FT /evidence="ECO:0007829|PDB:1LAM" FT TURN 110..113 FT /evidence="ECO:0007829|PDB:1LAM" FT HELIX 116..134 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 138..142 FT /evidence="ECO:0007829|PDB:1LAM" FT HELIX 148..159 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 174..181 FT /evidence="ECO:0007829|PDB:1LAM" FT HELIX 183..204 FT /evidence="ECO:0007829|PDB:1LAM" FT TURN 207..209 FT /evidence="ECO:0007829|PDB:1LAM" FT HELIX 212..226 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 228..235 FT /evidence="ECO:0007829|PDB:1LAM" FT HELIX 237..242 FT /evidence="ECO:0007829|PDB:1LAM" FT HELIX 246..252 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 255..257 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 260..267 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 269..271 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 277..281 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 283..287 FT /evidence="ECO:0007829|PDB:1LAM" FT HELIX 299..304 FT /evidence="ECO:0007829|PDB:1LAM" FT HELIX 307..321 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 325..337 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 348..351 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 357..361 FT /evidence="ECO:0007829|PDB:1LAM" FT TURN 363..366 FT /evidence="ECO:0007829|PDB:1BPN" FT HELIX 367..379 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 384..390 FT /evidence="ECO:0007829|PDB:1LAM" FT HELIX 394..400 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 405..410 FT /evidence="ECO:0007829|PDB:1LAM" FT HELIX 412..425 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 429..431 FT /evidence="ECO:0007829|PDB:1LAM" FT HELIX 436..443 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 446..453 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 455..457 FT /evidence="ECO:0007829|PDB:1LAM" FT HELIX 460..469 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 475..481 FT /evidence="ECO:0007829|PDB:1LAM" FT HELIX 483..485 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 486..492 FT /evidence="ECO:0007829|PDB:1LAM" FT STRAND 497..499 FT /evidence="ECO:0007829|PDB:1LAM" FT HELIX 504..515 FT /evidence="ECO:0007829|PDB:1LAM" FT INIT_MET P00727-3:1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:1548695, FT ECO:0000269|PubMed:2395881, ECO:0000269|PubMed:7085616, FT ECO:0000269|PubMed:7085617, ECO:0000269|PubMed:7578088" SQ SEQUENCE 519 AA; 56289 MW; CDA6AED4D937F624 CRC64; MFLLPLPAAA RVAVRHLSVK RLWAPGPAAA DMTKGLVLGI YSKEKEEDEP QFTSAGENFN KLVSGKLREI LNISGPPLKA GKTRTFYGLH EDFPSVVVVG LGKKTAGIDE QENWHEGKEN IRAAVAAGCR QIQDLEIPSV EVDPCGDAQA AAEGAVLGLY EYDDLKQKRK VVVSAKLHGS EDQEAWQRGV LFASGQNLAR RLMETPANEM TPTKFAEIVE ENLKSASIKT DVFIRPKSWI EEQEMGSFLS VAKGSEEPPV FLEIHYKGSP NASEPPLVFV GKGITFDSGG ISIKAAANMD LMRADMGGAA TICSAIVSAA KLDLPINIVG LAPLCENMPS GKANKPGDVV RARNGKTIQV DNTDAEGRLI LADALCYAHT FNPKVIINAA TLTGAMDIAL GSGATGVFTN SSWLWNKLFE ASIETGDRVW RMPLFEHYTR QVIDCQLADV NNIGKYRSAG ACTAAAFLKE FVTHPKWAHL DIAGVMTNKD EVPYLRKGMA GRPTRTLIEF LFRFSQDSA //