ID   UBP16_MACFA             Reviewed;         826 AA.
AC   Q4R6X7; Q4R6G7;
DT   24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT   24-MAR-2009, sequence version 2.
DT   27-MAR-2024, entry version 92.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 16 {ECO:0000255|HAMAP-Rule:MF_03062};
DE            EC=3.4.19.12 {ECO:0000255|HAMAP-Rule:MF_03062};
DE   AltName: Full=Deubiquitinating enzyme 16 {ECO:0000255|HAMAP-Rule:MF_03062};
DE   AltName: Full=Ubiquitin thioesterase 16 {ECO:0000255|HAMAP-Rule:MF_03062};
DE   AltName: Full=Ubiquitin-specific-processing protease 16 {ECO:0000255|HAMAP-Rule:MF_03062};
GN   Name=USP16 {ECO:0000255|HAMAP-Rule:MF_03062};
GN   ORFNames=QtsA-16913, QtsA-18064;
OS   Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9541;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Testis;
RG   International consortium for macaque cDNA sequencing and analysis;
RT   "DNA sequences of macaque genes expressed in brain or testis and its
RT   evolutionary implications.";
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Specifically deubiquitinates 'Lys-120' of histone H2A
CC       (H2AK119Ub), a specific tag for epigenetic transcriptional repression,
CC       thereby acting as a coactivator. Deubiquitination of histone H2A is a
CC       prerequisite for subsequent phosphorylation at 'Ser-11' of histone H3
CC       (H3S10ph), and is required for chromosome segregation when cells enter
CC       into mitosis. In resting B- and T-lymphocytes, phosphorylation by AURKB
CC       leads to enhance its activity, thereby maintaining transcription in
CC       resting lymphocytes. Regulates Hox gene expression via histone H2A
CC       deubiquitination. Prefers nucleosomal substrates. Does not
CC       deubiquitinate histone H2B. Also deubiquitinates non-histone proteins,
CC       such as ribosomal protein RPS27A: deubiquitination of monoubiquitinated
CC       RPS27A promotes maturation of the 40S ribosomal subunit.
CC       {ECO:0000255|HAMAP-Rule:MF_03062}.
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:0000255|HAMAP-Rule:MF_03062};
CC   -!- SUBUNIT: Homotetramer. Associates with late pre-40S ribosomes.
CC       {ECO:0000255|HAMAP-Rule:MF_03062}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03062}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q4R6X7-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q4R6X7-2; Sequence=VSP_036723, VSP_036724;
CC   -!- DOMAIN: The UBP-type zinc finger binds 3 zinc ions that form a pair of
CC       cross-braced ring fingers encapsulated within a third zinc finger in
CC       the primary structure. It recognizes the C-terminal tail of free
CC       ubiquitin. {ECO:0000255|HAMAP-Rule:MF_03062}.
CC   -!- PTM: Phosphorylated at the onset of mitosis and dephosphorylated during
CC       the metaphase/anaphase transition. Phosphorylation by AURKB enhances
CC       the deubiquitinase activity. {ECO:0000255|HAMAP-Rule:MF_03062}.
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. USP16 subfamily.
CC       {ECO:0000255|HAMAP-Rule:MF_03062}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAE01308.1; Type=Frameshift; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AB169053; BAE01147.1; -; mRNA.
DR   EMBL; AB169216; BAE01308.1; ALT_FRAME; mRNA.
DR   AlphaFoldDB; Q4R6X7; -.
DR   BMRB; Q4R6X7; -.
DR   STRING; 9541.ENSMFAP00000026358; -.
DR   eggNOG; KOG1873; Eukaryota.
DR   Proteomes; UP000233100; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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:0042393; F:histone binding; ISS:UniProtKB.
DR   GO; GO:0140950; F:histone H2A deubiquitinase activity; ISS:UniProtKB.
DR   GO; GO:0043024; F:ribosomal small subunit binding; ISS:UniProtKB.
DR   GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR   GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR   GO; GO:0006974; P:DNA damage response; ISS:UniProtKB.
DR   GO; GO:0016578; P:histone deubiquitination; IEA:UniProtKB-UniRule.
DR   GO; GO:0140014; P:mitotic nuclear division; IEA:UniProtKB-UniRule.
DR   GO; GO:0035520; P:monoubiquitinated protein deubiquitination; ISS:UniProtKB.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB.
DR   GO; GO:0090070; P:positive regulation of ribosome biogenesis; ISS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR   GO; GO:0045901; P:positive regulation of translational elongation; ISS:UniProtKB.
DR   GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0051726; P:regulation of cell cycle; IEA:InterPro.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR   CDD; cd02667; Peptidase_C19K; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 2.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR   HAMAP; MF_03062; UBP16; 1.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR001394; Peptidase_C19_UCH.
DR   InterPro; IPR030849; UBP16.
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:SF12; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 16; 1.
DR   Pfam; PF00443; UCH; 1.
DR   Pfam; PF02148; zf-UBP; 1.
DR   SMART; SM00290; ZnF_UBP; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   SUPFAM; SSF57850; RING/U-box; 1.
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   Activator; Alternative splicing; Cell cycle; Cell division;
KW   Chromatin regulator; Hydrolase; Isopeptide bond; Metal-binding; Mitosis;
KW   Nucleus; Phosphoprotein; Protease; Reference proteome; Thiol protease;
KW   Transcription; Transcription regulation; Ubl conjugation;
KW   Ubl conjugation pathway; Zinc; Zinc-finger.
FT   CHAIN           1..826
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 16"
FT                   /id="PRO_0000367502"
FT   DOMAIN          196..825
FT                   /note="USP"
FT   ZN_FING         22..142
FT                   /note="UBP-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   REGION          146..190
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          394..460
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        153..182
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        395..412
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        419..437
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        438..456
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        205
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03062"
FT   ACT_SITE        761
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03062"
FT   BINDING         24
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         26
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         48
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         51
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         74
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         77
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         82
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         90
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         94
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         103
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         116
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   BINDING         119
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   MOD_RES         189
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y5T5"
FT   MOD_RES         415
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y5T5"
FT   MOD_RES         552
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y5T5"
FT   MOD_RES         557
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y5T5"
FT   CROSSLNK        140
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y5T5"
FT   VAR_SEQ         150
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.1"
FT                   /id="VSP_036723"
FT   VAR_SEQ         735..826
FT                   /note="NVAEENTRVLYSLYGVVEHSGTMRSGHYTAYAKARTANSHLSNLVLHGDIPQ
FT                   DFEMESKGQWFHISDTHVQAVPTTKVLNSQAYLLFYERIL -> ILKWNQKGSGFTSAT
FT                   HMCKLCLQLKY (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.1"
FT                   /id="VSP_036724"
FT   CONFLICT        55
FT                   /note="N -> D (in Ref. 1; BAE01308)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        128
FT                   /note="S -> P (in Ref. 1; BAE01308)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        136
FT                   /note="D -> E (in Ref. 1; BAE01308)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        143
FT                   /note="S -> G (in Ref. 1; BAE01147)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        208
FT                   /note="N -> D (in Ref. 1; BAE01308)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        531
FT                   /note="P -> S (in Ref. 1; BAE01147)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   826 AA;  94059 MW;  EEBDB3D17A4CD634 CRC64;
     MGKKRTKGKT VPIDDSSETL EPMCRHIRKG LEQGNLKKAL VNVEWNICQD CKTDNKVKDK
     AEEETEEKPS VWLCLKCGHQ GCGRNSQEQH ALKHYLTPRS EPHCLVLSLD NWSVWCYICD
     NEVQYCSSNQ LGQVVDYVRK QASITTPKPA EKDNGNIELE NKKLEKESKN EQEREKKENM
     AKENPPMNSP SQITVKGLSN LGNTCFFNAV MQNLSQTPVL RELLKEVKMS GTIVKIEPPD
     LALTEPLEIN LEPPGPLTLA MSQFLNEMQE TKKGIVTPKE LFSQVCKKAV RFKGYQQQDS
     QELLRYLLDG MRAEEHQRVS KGILKAFGNS TEKLDEELKN KVKDYEKKKS IPSFVDRIFG
     GELTSTIMCD QCRTVSLVHE SFLDLSLPVL DDQSGKKSVN DKNLKKTMED EDQDSEEEKD
     NDSYIKERSD IPSGTSKHLQ KKAKKQAKKQ AKNQRRQQKI QGKVLHLNDI CTIDHPEDNE
     YEAEMSLQGE VNIKSNHISQ EGVMHKEYCV NQKDLNGQEK MIESVTDNQK PTEEVDMKNI
     NMDNDLEVLT SSPTECTRNL NGAYLTEASN GEVDISNGFK NLNLNAALHP DEINIEILND
     SHTPGTKVYE VVNEDPETAF CTLANREVFN TDECSIQHCL YQFTRNEKLR DANKLLCEVC
     TRRQCNGPKA NMKGERKHVY TNAKKQMLIS LAPPVLTLHL KRFQQAGFNL RKVNKHIKFP
     EILDLAPFCT LKCKNVAEEN TRVLYSLYGV VEHSGTMRSG HYTAYAKART ANSHLSNLVL
     HGDIPQDFEM ESKGQWFHIS DTHVQAVPTT KVLNSQAYLL FYERIL
//