UCHL3_PLAF7
ID UCHL3_PLAF7 Reviewed; 232 AA.
AC Q8IKM8;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase UCHL3 {ECO:0000305};
DE EC=3.4.19.12 {ECO:0000269|PubMed:17371404, ECO:0000269|PubMed:19047059, ECO:0000269|PubMed:20042598, ECO:0000269|PubMed:31658303};
DE AltName: Full=PfUCHL3 {ECO:0000303|PubMed:17371404};
GN Name=UCHL3 {ECO:0000303|PubMed:17371404};
GN ORFNames=PF3D7_1460400 {ECO:0000312|EMBL:CZU00300.1};
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329 {ECO:0000312|Proteomes:UP000001450};
RN [1] {ECO:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-92.
RX PubMed=17371404; DOI=10.1111/j.1462-5822.2007.00896.x;
RA Frickel E.M., Quesada V., Muething L., Gubbels M.J., Spooner E., Ploegh H.,
RA Artavanis-Tsakonas K.;
RT "Apicomplexan UCHL3 retains dual specificity for ubiquitin and Nedd8
RT throughout evolution.";
RL Cell. Microbiol. 9:1601-1610(2007).
RN [3] {ECO:0000305}
RP CATALYTIC ACTIVITY.
RX PubMed=19047059; DOI=10.1074/jbc.m807172200;
RA Popp M.W., Artavanis-Tsakonas K., Ploegh H.L.;
RT "Substrate filtering by the active site crossover loop in UCHL3 revealed by
RT sortagging and gain-of-function mutations.";
RL J. Biol. Chem. 284:3593-3602(2009).
RN [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, DEVELOPMENTAL STAGE, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND MUTAGENESIS OF ASN-13 AND ASP-33.
RX PubMed=31658303; DOI=10.1371/journal.ppat.1008086;
RA Karpiyevich M., Adjalley S., Mol M., Ascher D.B., Mason B.,
RA van der Heden van Noort G.J., Laman H., Ovaa H., Lee M.C.S.,
RA Artavanis-Tsakonas K.;
RT "Nedd8 hydrolysis by UCH proteases in Plasmodium parasites.";
RL PLoS Pathog. 15:e1008086-e1008086(2019).
RN [5] {ECO:0007744|PDB:2WDT, ECO:0007744|PDB:2WE6}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH UBIQUITIN ANALOG,
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVE
RP SITE.
RX PubMed=20042598; DOI=10.1074/jbc.m109.072405;
RA Artavanis-Tsakonas K., Weihofen W.A., Antos J.M., Coleman B.I.,
RA Comeaux C.A., Duraisingh M.T., Gaudet R., Ploegh H.L.;
RT "Characterization and structural studies of the Plasmodium falciparum
RT ubiquitin and Nedd8 hydrolase UCHL3.";
RL J. Biol. Chem. 285:6857-6866(2010).
CC -!- FUNCTION: Thiol protease that recognizes and hydrolyzes a peptide bond
CC at the C-terminal glycine of either ubiquitin or NEDD8
CC (PubMed:17371404, PubMed:31658303, PubMed:20042598). Essential for
CC parasite blood stage survival (PubMed:20042598).
CC {ECO:0000269|PubMed:17371404, ECO:0000269|PubMed:20042598,
CC ECO:0000269|PubMed:31658303}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:17371404,
CC ECO:0000269|PubMed:19047059, ECO:0000269|PubMed:20042598,
CC ECO:0000269|PubMed:31658303};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=301 nM for ubiquitin-AMC {ECO:0000269|PubMed:20042598};
CC Note=kcat is 3.2 sec(-1) with ubiquitin-AMC as substrate.
CC {ECO:0000269|PubMed:20042598};
CC -!- DEVELOPMENTAL STAGE: Expressed during the parasite blood stage, in
CC schizonts (at protein level). {ECO:0000269|PubMed:31658303}.
CC -!- SIMILARITY: Belongs to the peptidase C12 family. {ECO:0000305}.
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DR EMBL; LN999946; CZU00300.1; -; Genomic_DNA.
DR RefSeq; XP_001348750.2; XM_001348714.2.
DR PDB; 2WDT; X-ray; 2.30 A; A/C=1-232.
DR PDB; 2WE6; X-ray; 2.42 A; A/B=1-232.
DR PDBsum; 2WDT; -.
DR PDBsum; 2WE6; -.
DR AlphaFoldDB; Q8IKM8; -.
DR SMR; Q8IKM8; -.
DR STRING; 5833.PF14_0576; -.
DR MEROPS; C12.010; -.
DR PRIDE; Q8IKM8; -.
DR EnsemblProtists; CZU00300; CZU00300; PF3D7_1460400.
DR GeneID; 812158; -.
DR KEGG; pfa:PF3D7_1460400; -.
DR VEuPathDB; PlasmoDB:PF3D7_1460400; -.
DR HOGENOM; CLU_054406_0_2_1; -.
DR InParanoid; Q8IKM8; -.
DR OMA; YVCFVKG; -.
DR PhylomeDB; Q8IKM8; -.
DR Reactome; R-PFA-5689603; UCH proteinases.
DR Reactome; R-PFA-8951664; Neddylation.
DR EvolutionaryTrace; Q8IKM8; -.
DR Proteomes; UP000001450; Chromosome 14.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:GeneDB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0019784; F:deNEDDylase activity; IDA:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IDA:GeneDB.
DR GO; GO:0000338; P:protein deneddylation; IDA:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:GeneDB.
DR Gene3D; 3.40.532.10; -; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001578; Peptidase_C12_UCH.
DR InterPro; IPR036959; Peptidase_C12_UCH_sf.
DR PANTHER; PTHR10589; PTHR10589; 1.
DR Pfam; PF01088; Peptidase_C12; 1.
DR PRINTS; PR00707; UBCTHYDRLASE.
DR SUPFAM; SSF54001; SSF54001; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation pathway.
FT CHAIN 1..232
FT /note="Ubiquitin carboxyl-terminal hydrolase UCHL3"
FT /id="PRO_0000451572"
FT REGION 10..14
FT /note="Interaction with ubiquitin"
FT /evidence="ECO:0000269|PubMed:20042598"
FT REGION 151..159
FT /note="Crossover loop which restricts access of large
FT ubiquitin adducts to the active site"
FT /evidence="ECO:0000269|PubMed:19047059"
FT REGION 163..165
FT /note="Interaction with ubiquitin"
FT /evidence="ECO:0000269|PubMed:20042598"
FT ACT_SITE 92
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:20042598"
FT ACT_SITE 164
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P09936"
FT SITE 33
FT /note="Interaction with ubiquitin"
FT /evidence="ECO:0000269|PubMed:20042598"
FT SITE 157
FT /note="Interaction with ubiquitin"
FT /evidence="ECO:0000269|PubMed:20042598"
FT SITE 179
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:P09936"
FT SITE 219
FT /note="Interaction with ubiquitin"
FT /evidence="ECO:0000269|PubMed:20042598"
FT MUTAGEN 13
FT /note="N->D: Small increase in deubiquitinating and
FT deneddylating activities. Small reduction in
FT deubiquitinating and deneddylating activities; when
FT associated with E-33."
FT /evidence="ECO:0000269|PubMed:31658303"
FT MUTAGEN 33
FT /note="D->E: Small reduction in deubiquitinating and
FT deneddylating activities. Small reduction in
FT deubiquitinating and deneddylating activities; when
FT associated with D-13."
FT /evidence="ECO:0000269|PubMed:31658303"
FT MUTAGEN 92
FT /note="C->A: Complete loss of deubiquitinating and
FT deneddylating activities."
FT /evidence="ECO:0000269|PubMed:17371404"
FT HELIX 14..24
FT /evidence="ECO:0007829|PDB:2WDT"
FT STRAND 28..33
FT /evidence="ECO:0007829|PDB:2WDT"
FT HELIX 39..42
FT /evidence="ECO:0007829|PDB:2WDT"
FT STRAND 51..57
FT /evidence="ECO:0007829|PDB:2WDT"
FT HELIX 92..103
FT /evidence="ECO:0007829|PDB:2WDT"
FT TURN 105..107
FT /evidence="ECO:0007829|PDB:2WDT"
FT HELIX 115..122
FT /evidence="ECO:0007829|PDB:2WDT"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:2WDT"
FT HELIX 128..137
FT /evidence="ECO:0007829|PDB:2WDT"
FT HELIX 139..145
FT /evidence="ECO:0007829|PDB:2WDT"
FT HELIX 155..159
FT /evidence="ECO:0007829|PDB:2WDT"
FT STRAND 163..178
FT /evidence="ECO:0007829|PDB:2WDT"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:2WDT"
FT STRAND 186..190
FT /evidence="ECO:0007829|PDB:2WDT"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:2WDT"
FT HELIX 196..207
FT /evidence="ECO:0007829|PDB:2WDT"
FT TURN 208..211
FT /evidence="ECO:0007829|PDB:2WDT"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:2WE6"
FT STRAND 219..225
FT /evidence="ECO:0007829|PDB:2WDT"
SQ SEQUENCE 232 AA; 26899 MW; 8B2720342B644DFF CRC64;
MAKNDIWTPL ESNPDSLYLY SCKLGQSKLK FVDIYGFNND LLDMIPQPVQ AVIFLYPVND
NIVSENNTND KHNLKENFDN VWFIKQYIPN SCGTIALLHL YGNLRNKFEL DKDSVLDDFF
NKVNEMSAEK RGQELKNNKS IENLHHEFCG QVENRDDILD VDTHFIVFVQ IEGKIIELDG
RKDHPTVHCF TNGDNFLYDT GKIIQDKFIE KCKDDLRFSA LAVIPNDNFD II
