ID   UBP33_DANRE             Reviewed;         897 AA.
AC   A5PMR2; Q6NYK6;
DT   15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT   10-JUL-2007, sequence version 1.
DT   27-MAR-2024, entry version 103.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 33;
DE            EC=3.4.19.12;
DE   AltName: Full=Deubiquitinating enzyme 33;
DE   AltName: Full=Ubiquitin thioesterase 33;
DE   AltName: Full=Ubiquitin-specific-processing protease 33;
GN   Name=usp33; ORFNames=ch211-284g18.1;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
RX   PubMed=23594743; DOI=10.1038/nature12111;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA   Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA   Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA   Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA   Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA   Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA   Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA   McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA   Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA   Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA   Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA   Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA   Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA   Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA   Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA   Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA   Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA   Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA   Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA   Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA   de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA   Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Deubiquitinating enzyme involved in various processes such as
CC       centrosome duplication, cellular migration and beta-2 adrenergic
CC       receptor/ADRB2 recycling. Involved in regulation of centrosome
CC       duplication by mediating deubiquitination of ccp110 in S and G2/M
CC       phase, leading to stabilize ccp110 during the period which centrioles
CC       duplicate and elongate. Involved in cell migration via its interaction
CC       with intracellular domain of robo1, leading to regulate the Slit
CC       signaling. Plays a role in commissural axon guidance cross the ventral
CC       midline of the neural tube in a Slit-dependent manner, possibly by
CC       mediating the deubiquitination of robo1. Acts as a regulator of G-
CC       protein coupled receptor (GPCR) signaling by mediating the
CC       deubiquitination of beta-arrestins (arrb1 and arrb2) and beta-2
CC       adrenergic receptor (adrb2). Deubiquitinates dio2, thereby regulating
CC       thyroid hormone regulation. Mediates deubiquitination of both 'Lys-
CC       48'- and 'Lys-63'-linked polyubiquitin chains (By similarity).
CC       {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   -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC       {ECO:0000250|UniProtKB:Q8TEY7}. Cytoplasm, cytoskeleton, microtubule
CC       organizing center, centrosome {ECO:0000250|UniProtKB:Q8TEY7}.
CC       Note=Associates with centrosomes predominantly in S and G2 phases but
CC       less in G1 phase (By similarity). {ECO:0000250|UniProtKB:Q8TEY7}.
CC   -!- DOMAIN: The UBP-type zinc finger binds 3 zinc ions. However, it does
CC       not bind ubiquitin, probably because the conserved Arg in position 55
CC       is replaced by a Glu residue (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. USP20/USP33 subfamily.
CC       {ECO:0000305}.
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DR   EMBL; BX649634; CAN88027.1; -; Genomic_DNA.
DR   EMBL; BC066557; AAH66557.1; -; mRNA.
DR   RefSeq; NP_998392.1; NM_213227.1.
DR   AlphaFoldDB; A5PMR2; -.
DR   STRING; 7955.ENSDARP00000014516; -.
DR   MEROPS; C19.037; -.
DR   PaxDb; 7955-ENSDARP00000014516; -.
DR   GeneID; 406508; -.
DR   KEGG; dre:406508; -.
DR   AGR; ZFIN:ZDB-GENE-040426-2323; -.
DR   CTD; 23032; -.
DR   ZFIN; ZDB-GENE-040426-2323; usp33.
DR   eggNOG; KOG1870; Eukaryota.
DR   HOGENOM; CLU_004896_0_0_1; -.
DR   InParanoid; A5PMR2; -.
DR   OMA; LCSVICH; -.
DR   OrthoDB; 227085at2759; -.
DR   PhylomeDB; A5PMR2; -.
DR   TreeFam; TF352179; -.
DR   Reactome; R-DRE-5689880; Ub-specific processing proteases.
DR   Reactome; R-DRE-9010553; Regulation of expression of SLITs and ROBOs.
DR   PRO; PR:A5PMR2; -.
DR   Proteomes; UP000000437; Chromosome 2.
DR   Bgee; ENSDARG00000016163; Expressed in cleaving embryo and 26 other cell types or tissues.
DR   ExpressionAtlas; A5PMR2; baseline and differential.
DR   GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR   GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
DR   GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR   GO; GO:0051298; P:centrosome duplication; ISS:UniProtKB.
DR   GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR   GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR   GO; GO:0071108; P:protein K48-linked deubiquitination; ISS:UniProtKB.
DR   GO; GO:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR   CDD; cd02674; Peptidase_C19R; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 2.
DR   Gene3D; 3.30.2230.10; DUSP-like; 2.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR   InterPro; IPR035927; DUSP-like_sf.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR006615; Pept_C19_DUSP.
DR   InterPro; IPR001394; Peptidase_C19_UCH.
DR   InterPro; IPR018200; USP_CS.
DR   InterPro; IPR028889; USP_dom.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   InterPro; IPR001607; Znf_UBP.
DR   PANTHER; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR21646:SF32; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 33; 1.
DR   Pfam; PF06337; DUSP; 2.
DR   Pfam; PF00443; UCH; 1.
DR   Pfam; PF02148; zf-UBP; 1.
DR   SMART; SM00695; DUSP; 2.
DR   SMART; SM00290; ZnF_UBP; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   SUPFAM; SSF143791; DUSP-like; 2.
DR   SUPFAM; SSF57850; RING/U-box; 1.
DR   PROSITE; PS51283; DUSP; 2.
DR   PROSITE; PS00972; USP_1; 1.
DR   PROSITE; PS00973; USP_2; 1.
DR   PROSITE; PS50235; USP_3; 1.
DR   PROSITE; PS50271; ZF_UBP; 1.
PE   2: Evidence at transcript level;
KW   Cytoplasm; Cytoskeleton; Endocytosis; Hydrolase; Metal-binding; Protease;
KW   Reference proteome; Repeat; Thiol protease; Ubl conjugation pathway; Zinc;
KW   Zinc-finger.
FT   CHAIN           1..897
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 33"
FT                   /id="PRO_0000390426"
FT   DOMAIN          156..670
FT                   /note="USP"
FT   DOMAIN          672..765
FT                   /note="DUSP 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00613"
FT   DOMAIN          773..876
FT                   /note="DUSP 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00613"
FT   ZN_FING         7..110
FT                   /note="UBP-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   REGION          261..308
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          343..420
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          875..897
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        357..420
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        882..897
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        165
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   ACT_SITE        628
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   BINDING         9
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         11
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         31
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         34
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         44
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         49
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         54
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         61
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         65
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         71
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         84
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         87
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   CONFLICT        207
FT                   /note="I -> V (in Ref. 2; AAH66557)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        217
FT                   /note="A -> S (in Ref. 2; AAH66557)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        732
FT                   /note="A -> T (in Ref. 2; AAH66557)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   897 AA;  100655 MW;  19103583F04B4315 CRC64;
     MSGVSSNDCP HLECVGEITK EELIQKSHGQ CQDCKVGGPN LWACLENGCS YVGCGESHAD
     HSTVHSQETR HNLTVNLTTL RVWCYACTKE VFLERKLGPH KQLPNAAKAV SPVQTPCQDL
     NTPGSPTSLR VPSAGTCDDL DMETEEEDEL RTRGLTGLKN IGNTCYMNAA LQALSNCPPL
     TQFFLECGGL VKTDKKPALC KSYQKLITDL WHKNRNAYVV PTNLFQGIKA VNPMFRGYSQ
     QDSQEFLRCL MDQLHEELKE LIPEPEDPNQ AVAMDDSPDE DNHSQSDDFQ SCESCGSSDR
     ADNEGPRVPE DINEAEMLMP EQNQNNRDWQ KEKNLINNLY RAGSHGDLDK DVDTTSDSRP
     IISSQGAIKA QGRTSDSEIQ VSSTVRPQSP TGNEGITSRL SSSPPKSSAW PNLSSTHKKV
     PMFTPTKTKR QRKYHSIISE VFDGTIVSSV QCLTCDRVSV TLENFQDISL PIPGKEDLAK
     LHSSSHQTAL VKAGSCGEAY APQGWIAFVM EYIKSWFWGP VVTLQDCLAA FFARDELKGD
     NMYSCEKCKK LRNGVKFCKV QSLPEILCIH LKRFRHELMF STKIGTHVSF PLEGLEMQPF
     LAKDSSALTT TYDLLSVICH HGTASSGHYI AYCRNELNQL WYEFDDQSVT EVSESCVQNA
     EAYVLFYKKS NDETQKERRK VTSLFNMMEP SLLQFYVSRQ WLNKFKTFAE PGPISNHDFL
     CAHGGIPPNK AAYIDDLVLM IPQNVWDHLY SRYGGGPAVN HLYVCHTCQN EIEKLEKRRK
     NELDMFVRLN KAFQEEESPV VIYCISMQWF REWESFVKGK DIDPPGPIDN SKIAVNKNGH
     ITLKPGADSG QISEETWNFL HNIHGGGPVV TVRPSVSHQE SETSQSEEKI EVETRTV
//