ID   UBP4_KLULA              Reviewed;         796 AA.
AC   Q9HFS7; Q6CNS6;
DT   16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   03-AUG-2022, entry version 115.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 4;
DE            EC=3.4.19.12;
DE   AltName: Full=Deubiquitinating enzyme 4;
DE   AltName: Full=Ubiquitin thioesterase 4;
DE   AltName: Full=Ubiquitin-specific-processing protease 4;
GN   Name=DOA4; Synonyms=UBP4; OrderedLocusNames=KLLA0E10275g;
OS   Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 /
OS   NRRL Y-1140 / WM37) (Yeast) (Candida sphaerica).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Kluyveromyces.
OX   NCBI_TaxID=284590;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=11076031; DOI=10.1515/bc.2000.121;
RA   Amerik A.Y., Li S.J., Hochstrasser M.;
RT   "Analysis of the deubiquitinating enzymes of the yeast Saccharomyces
RT   cerevisiae.";
RL   Biol. Chem. 381:981-992(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37;
RX   PubMed=15229592; DOI=10.1038/nature02579;
RA   Dujon B., Sherman D., Fischer G., Durrens P., Casaregola S., Lafontaine I.,
RA   de Montigny J., Marck C., Neuveglise C., Talla E., Goffard N., Frangeul L.,
RA   Aigle M., Anthouard V., Babour A., Barbe V., Barnay S., Blanchin S.,
RA   Beckerich J.-M., Beyne E., Bleykasten C., Boisrame A., Boyer J.,
RA   Cattolico L., Confanioleri F., de Daruvar A., Despons L., Fabre E.,
RA   Fairhead C., Ferry-Dumazet H., Groppi A., Hantraye F., Hennequin C.,
RA   Jauniaux N., Joyet P., Kachouri R., Kerrest A., Koszul R., Lemaire M.,
RA   Lesur I., Ma L., Muller H., Nicaud J.-M., Nikolski M., Oztas S.,
RA   Ozier-Kalogeropoulos O., Pellenz S., Potier S., Richard G.-F.,
RA   Straub M.-L., Suleau A., Swennen D., Tekaia F., Wesolowski-Louvel M.,
RA   Westhof E., Wirth B., Zeniou-Meyer M., Zivanovic Y., Bolotin-Fukuhara M.,
RA   Thierry A., Bouchier C., Caudron B., Scarpelli C., Gaillardin C.,
RA   Weissenbach J., Wincker P., Souciet J.-L.;
RT   "Genome evolution in yeasts.";
RL   Nature 430:35-44(2004).
CC   -!- FUNCTION: Ubiquitin thioesterase that acts at the late
CC       endosome/prevacuolar compartment to recover ubiquitin from
CC       ubiquitinated membrane proteins en route to the vacuole. Removes also
CC       ubiquitin from soluble proteins targeted to proteasomes. Is essential
CC       to maintain a normal level of free ubiquitin. Required for promoting
CC       coordination of DNA replication and avoids DNA overreplication (By
CC       similarity). {ECO:0000250}.
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;
CC   -!- ACTIVITY REGULATION: RFU1 is an inhibitor of deubiquitination activity.
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Late endosome membrane
CC       {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR   EMBL; AF303215; AAG17929.1; -; Genomic_DNA.
DR   EMBL; CR382125; CAG99500.1; -; Genomic_DNA.
DR   RefSeq; XP_454413.1; XM_454413.1.
DR   AlphaFoldDB; Q9HFS7; -.
DR   SMR; Q9HFS7; -.
DR   STRING; 28985.XP_454413.1; -.
DR   EnsemblFungi; CAG99500; CAG99500; KLLA0_E10275g.
DR   GeneID; 2894137; -.
DR   KEGG; kla:KLLA0_E10275g; -.
DR   eggNOG; KOG1868; Eukaryota.
DR   HOGENOM; CLU_005922_1_0_1; -.
DR   InParanoid; Q9HFS7; -.
DR   OMA; KFFIDNR; -.
DR   Proteomes; UP000000598; Chromosome E.
DR   GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0000502; C:proteasome complex; IEA:EnsemblFungi.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IEA:UniProtKB-EC.
DR   GO; GO:1904669; P:ATP export; IEA:EnsemblFungi.
DR   GO; GO:0006897; P:endocytosis; IEA:EnsemblFungi.
DR   GO; GO:0010995; P:free ubiquitin chain depolymerization; IEA:EnsemblFungi.
DR   GO; GO:0070676; P:intralumenal vesicle formation; IEA:EnsemblFungi.
DR   GO; GO:0016579; P:protein deubiquitination; IEA:InterPro.
DR   GO; GO:0006275; P:regulation of DNA replication; IEA:EnsemblFungi.
DR   GO; GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IEA:EnsemblFungi.
DR   Gene3D; 3.40.250.10; -; 1.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR001394; Peptidase_C19_UCH.
DR   InterPro; IPR001763; Rhodanese-like_dom.
DR   InterPro; IPR036873; Rhodanese-like_dom_sf.
DR   InterPro; IPR018200; USP_CS.
DR   InterPro; IPR028889; USP_dom.
DR   Pfam; PF00581; Rhodanese; 1.
DR   Pfam; PF00443; UCH; 1.
DR   SMART; SM00450; RHOD; 1.
DR   SUPFAM; SSF52821; SSF52821; 1.
DR   SUPFAM; SSF54001; SSF54001; 1.
DR   PROSITE; PS50206; RHODANESE_3; 1.
DR   PROSITE; PS00972; USP_1; 1.
DR   PROSITE; PS00973; USP_2; 1.
DR   PROSITE; PS50235; USP_3; 1.
PE   3: Inferred from homology;
KW   Cytoplasm; Endosome; Hydrolase; Membrane; Protease; Reference proteome;
KW   Thiol protease; Ubl conjugation pathway.
FT   CHAIN           1..796
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 4"
FT                   /id="PRO_0000376820"
FT   DOMAIN          170..294
FT                   /note="Rhodanese"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00173"
FT   DOMAIN          432..794
FT                   /note="USP"
FT   ACT_SITE        441
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   ACT_SITE        752
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
SQ   SEQUENCE   796 AA;  90929 MW;  09A9F905579C14B2 CRC64;
     MLEHNSKLFC KSLSQLSAVA SKVVAEDVEG EHFKQLLAKC IDTLSIYKSE LRKLSCASKD
     TPPSQIYQLN ETLYVYYKIV SQIASQVIPG LAEFQQIKMN SKKDSKDKEL LEIYSRLVSA
     LANDKQIGEV KRFIKNHSEE AAHDGTQHSY ENGEFVSISQ LHSLIRHDND SSGILLVDIR
     PRMDFNDGHI KHNNVICIEP ISFKESYTDS DILRKSLITA SDREVDLFKN RDKFRLIVLY
     TDTDEHTKYY WQQLEVLQDI LCNRSFDKPL HHTKVIVLQN GVNAWKEKYP MELKKIMESA
     ISDIRTKPVE HNFHPMALSN NNNIEKANSP SHSQTTSFTH YPDAPFLTNG ASIKTAGLVP
     NQLLPSTSNL TKALQQNDEG NSEPYKLQPN GIKNHRQESN NHANGTNCIV SSNGNNSVAK
     SGHPSINLDF AIGLVNLGNS CYLNCIIQCL LGCHELSYIF LTNSYRKHVN VNSRLGSKGL
     LANYFSQLVQ KMYQQGKLQA YNNTNMESTA VHPTQFKLAC GSINSLFKGK QQQDCQEFCQ
     FLLDGLHEDL NQCGTNPPLK ELSPEAEKMR ETMPMRIASA IEWERYLTTD FSVIVDLFQG
     QYASQLRCKI CAHTSTTYQA FSVLSVPVPR ARSCTIYDCF KEFTKLETLE KDELWYCPYC
     KQRQPSTKQI IITRLPNNLI IHLKRFDNMM NKNNVFVNYP NELDLTGFWI DDYNGEMPKD
     NGVSLPLRGQ KPPFNYRLFA VASHSGTLYG GHYTSFVDKG RVGWCSFDDV SWRKIRRKDE
     YITPNAYVLF YRRVNM