UBP33_BOVIN
ID UBP33_BOVIN Reviewed; 912 AA.
AC A6QNM7;
DT 15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 1.
DT 03-AUG-2022, entry version 101.
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;
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 MRNA].
RC STRAIN=Hereford; TISSUE=Hypothalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUL-2007) 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). Plays a central role in ADRB2 recycling
CC and resensitization after prolonged agonist stimulation by
CC constitutively binding ADRB2, mediating deubiquitination of ADRB2 and
CC inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is
CC probably transferred to the translocated beta-arrestins, leading to
CC beta-arrestins deubiquitination and disengagement from ADRB2. This
CC suggests the existence of a dynamic exchange between the ADRB2 and
CC beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid
CC hormone regulation. Mediates deubiquitination of both 'Lys-48'- and
CC 'Lys-63'-linked polyubiquitin chains (By 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 -!- SUBUNIT: Interacts with VHL, leading to its ubiquitination and
CC subsequent degradation (By similarity). Interacts with ARRB1 and ARRB2
CC (By similarity). Interacts with ADRB2 (By similarity). Interacts with
CC DIO2 (By similarity). Interacts with ROBO1 (By similarity). Interacts
CC with SELENBP1; in a selenium-dependent manner (By similarity).
CC Interacts with CCP110 (By similarity). Interacts with ADRB2 (By
CC similarity). {ECO:0000250|UniProtKB:Q8TEY7}.
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 -!- PTM: Ubiquitinated via a VHL-dependent pathway for proteasomal
CC degradation. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP20/USP33 subfamily.
CC {ECO:0000305}.
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DR EMBL; BC148905; AAI48906.1; -; mRNA.
DR RefSeq; NP_001094609.1; NM_001101139.2.
DR AlphaFoldDB; A6QNM7; -.
DR STRING; 9913.ENSBTAP00000027667; -.
DR MEROPS; C19.037; -.
DR PaxDb; A6QNM7; -.
DR PRIDE; A6QNM7; -.
DR Ensembl; ENSBTAT00000027667; ENSBTAP00000027667; ENSBTAG00000020761.
DR GeneID; 531706; -.
DR KEGG; bta:531706; -.
DR CTD; 23032; -.
DR VEuPathDB; HostDB:ENSBTAG00000020761; -.
DR VGNC; VGNC:36723; USP33.
DR eggNOG; KOG1870; Eukaryota.
DR GeneTree; ENSGT00940000157311; -.
DR HOGENOM; CLU_004896_0_0_1; -.
DR InParanoid; A6QNM7; -.
DR OMA; PSSNCPH; -.
DR OrthoDB; 147564at2759; -.
DR TreeFam; TF352179; -.
DR Proteomes; UP000009136; Chromosome 3.
DR Bgee; ENSBTAG00000020761; Expressed in occipital lobe and 109 other tissues.
DR ExpressionAtlas; A6QNM7; baseline and differential.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005925; C:focal adhesion; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
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:0001664; F:G protein-coupled receptor binding; IEA:Ensembl.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
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:0009267; P:cellular response to starvation; IEA:Ensembl.
DR GO; GO:0051298; P:centrosome duplication; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0032091; P:negative regulation of protein binding; IEA:Ensembl.
DR GO; GO:0032092; P:positive regulation of protein binding; IEA:Ensembl.
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:0050821; P:protein stabilization; IEA:Ensembl.
DR GO; GO:0010506; P:regulation of autophagy; IEA:Ensembl.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.30.2230.10; -; 2.
DR Gene3D; 3.30.40.10; -; 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 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; SSF143791; SSF143791; 2.
DR SUPFAM; SSF54001; SSF54001; 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;
KW Phosphoprotein; Protease; Reference proteome; Repeat; Thiol protease;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..912
FT /note="Ubiquitin carboxyl-terminal hydrolase 33"
FT /id="PRO_0000390423"
FT DOMAIN 154..685
FT /note="USP"
FT DOMAIN 687..780
FT /note="DUSP 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00613"
FT DOMAIN 788..891
FT /note="DUSP 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00613"
FT ZN_FING 6..109
FT /note="UBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT REGION 274..334
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 403..433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 286..323
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 163
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 643
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT BINDING 8
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 10
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 30
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 33
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 43
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 48
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 53
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 60
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 64
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 70
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 83
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 86
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT MOD_RES 346
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TEY7"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TEY7"
SQ SEQUENCE 912 AA; 103323 MW; AF5F91718BA407B4 CRC64;
MSSFRSHCPH LDSVGEITKE DLIQKSHGSC QDCKVRGPNL WACLENRCSY VGCGESQVDH
STIHSQETKH YLTVNLTTLR VWCYACSKEV FLDRKLGTQP SLPHVKPLHQ IQENGVQDFK
IPSNTTLKTP LVAVFDDLDI EVEEEDELKA RGLTGLKNIG NTCYMNAALQ ALSNCPPLTQ
FFLDCGGLAR TDKKPAICKS YLKLMTELWH KSRPGSVVPT TLFQGIKTVN PTFRGYSQQD
AQEFLRCLMD LLHEELKEQV MEVEEDPQTI MTEETMEEDK SQSDVDFQSC ESCSSSDKAE
NENGSRSFSE DNNETTMLIQ DDENNSEMSK DWQKEKMCNK INKVHSEGEL DKDRDSVSET
ADLNNQETVK VQIHSRASEY ITDVHLNDLS TPQILPSNEG VNPRLSASPP KSGNLWPGLP
PTHKKVQSAL SPKRKKQHKK YRSVISDIFD GTIISSVQCL TCDRVSVTLE TFQDLSLPIP
GKEDLAKLHS SSHPTSIVKA GSCGEAYAPQ GWIAFFMEYV KRFVVSCVPS WFWGPVVTLQ
DCLAAFFARD ELKGDNMYSC EKCKKLRNGV KFCKVQKFPE ILCIHLKRFR HELMFSTKIS
THVSFPLEGL DLQPFLAKDS PVQIVTYDLL SVICHHGTAS SGHYIAYCRN NLNNLWYEFD
DQSVTEVSES TVQNAEAYVL FYRKSSEEAQ KERRRISNLL NIMEPSLLQF YISRQWLNKF
KTFAEPGPIS NNDFLCIHGG VPPRKAGYIE DLVLMLPQNI WDNLYSRYGG GPAVNHLYIC
HTCQIEAEKI EKRRKTELEI FIRLNRAFQE EDSPATFYCI SMQWFREWES FVKGKDGDPP
GPIDNTKIAV TKCGNVILRQ GADSGQISEE TWNFLQSIYG GGPEVILRPP VVHVDPDAVQ
AEEKIEVETR SL
