UBP33_PONAB
ID UBP33_PONAB Reviewed; 914 AA.
AC Q5REG5; Q5R7L1;
DT 15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 90.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart, and Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-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). 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; CR857564; CAH89842.1; -; mRNA.
DR EMBL; CR860104; CAH92249.1; -; mRNA.
DR RefSeq; NP_001124855.1; NM_001131383.1.
DR AlphaFoldDB; Q5REG5; -.
DR STRING; 9601.ENSPPYP00000001418; -.
DR MEROPS; C19.037; -.
DR GeneID; 100171716; -.
DR KEGG; pon:100171716; -.
DR CTD; 23032; -.
DR eggNOG; KOG1870; Eukaryota.
DR InParanoid; Q5REG5; -.
DR OrthoDB; 147564at2759; -.
DR Proteomes; UP000001595; Unplaced.
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: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..914
FT /note="Ubiquitin carboxyl-terminal hydrolase 33"
FT /id="PRO_0000390425"
FT DOMAIN 154..683
FT /note="USP"
FT DOMAIN 685..778
FT /note="DUSP 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00613"
FT DOMAIN 786..893
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 266..313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 387..437
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 285..313
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 387..408
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 641
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 345
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TEY7"
FT MOD_RES 407
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TEY7"
FT CONFLICT 27
FT /note="Q -> H (in Ref. 1; CAH92249)"
FT /evidence="ECO:0000305"
FT CONFLICT 63
FT /note="I -> V (in Ref. 1; CAH92249)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="S -> R (in Ref. 1; CAH92249)"
FT /evidence="ECO:0000305"
FT CONFLICT 787
FT /note="E -> K (in Ref. 1; CAH92249)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 914 AA; 103637 MW; DD772E64F42C0829 CRC64;
MSAFRNHCPH LDSVGEITKE DLIQKSQGTC QDCKVRGPNL WACLENRCSY VGCGESQVDH
STIHSQETKH YLTVNLTTLR VWCYACSKEV FLDRKLGTQP SLPHVRQPHQ IQENSVQDFK
IPSNTTLKTP LVAVFDDLDI EVDEEDELRA RGLTGLKNIG NTCYMNAALQ ALSNCPPLTQ
FFLDCGGLAR TDKKPAICKS YLKLMTELWH KSRPGSVVPT NLFQGIKTVN PTFRGYSQQD
AQEFLRCLMD LLHEELKEQV MEVEDPQTIT TEETMEEDKS QSDVDFQSCE SCSNSDKAEN
ENGSSCFSED NNETTMLIQD DENNSEMSKD WQKEKMCNKI NKVNSEGELD KDRDSISETV
DLNNQETVKV QIHSRASEYI TDVHSNDLST PQILPSNESI NPRLSASPPK SGNLWPGLAP
PHKKAQSASP KRKKQHKKYR SVISDIFDGT IISSVQCLTC DRVSVTLETF QDLSLPIPGK
EDLAKLHSSS HPTSIVKAGS CGEAYAPQGW IAFFMEYVKR FVVSCVPSWF WGPVVTLQDC
LAAFFARDEL KGDNMYSCEK CKKLRNGVKF CKVQKFPEIL CIHLKRFRHE LMFSTKISTH
VSFPLEGLDL QPFLAKDSPA QIVTYDLLSV ICHHGTASSG HYIAYCRNNL NNLWYEFDDQ
SVTEVSESTV QNAEAYVLFY RKSSEEAQKE RRRISNLLNI MEPSLLQFYI SRQWLNKFKT
FAEPGPISNN DFLCIHGGVP PRKAGYIEDL VLMLPQNIWD NLYSRYGGGP AVNHLYICHT
CQIEAEEIEK KKKNRRKTEL EIFIRLNRAF QKEDSPATFY CISMQWFREW ESFVKGKDGD
PPGPIDNTKI AVTKCGSVML RQGADSGQIS EETWNFLQSI YGGGPEVILR PPVVHVDPDI
LQAEEKIEVE TRSL
