ID   UBP16_BOVIN             Reviewed;         826 AA.
AC   Q08DA3; F1N2B1;
DT   24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT   11-DEC-2013, sequence version 2.
DT   02-SEP-2026, entry version 128.
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};
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 GENOMIC DNA].
RC   STRAIN=Hereford;
RX   PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA   Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA   Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA   Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT   "A whole-genome assembly of the domestic cow, Bos taurus.";
RL   Genome Biol. 10:R42.01-R42.10(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Fetal muscle;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (SEP-2006) 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. Also mediates
CC       deubiquitination of tektin proteins (TEKT1, TEKT2, TEK3, TEKT4 and
CC       TEKT5), promoting their stability. {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       Interacts with CEP78; promoting deubiquitination of tektins.
CC       {ECO:0000255|HAMAP-Rule:MF_03062}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03062}.
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}.
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DR   EMBL; DAAA02000172; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; DAAA02000173; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC123861; AAI23862.1; -; mRNA.
DR   RefSeq; NP_001070335.1; NM_001076867.1.
DR   AlphaFoldDB; Q08DA3; -.
DR   SMR; Q08DA3; -.
DR   FunCoup; Q08DA3; 4690.
DR   STRING; 9913.ENSBTAP00000026801; -.
DR   GlyGen; Q08DA3; 1 site.
DR   PaxDb; 9913-ENSBTAP00000026801; -.
DR   GeneID; 519992; -.
DR   KEGG; bta:519992; -.
DR   CTD; 10600; -.
DR   VGNC; VGNC:52842; USP16.
DR   eggNOG; KOG1873; Eukaryota.
DR   HOGENOM; CLU_007938_1_0_1; -.
DR   InParanoid; Q08DA3; -.
DR   OrthoDB; 2020758at2759; -.
DR   Proteomes; UP000009136; 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: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:0051289; P:protein homotetramerization; ISS:UniProtKB.
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   FunFam; 3.30.40.10:FF:000147; Ubiquitin carboxyl-terminal hydrolase 16; 1.
DR   FunFam; 3.90.70.10:FF:000045; Ubiquitin carboxyl-terminal hydrolase 16; 1.
DR   FunFam; 3.90.70.10:FF:000082; Ubiquitin carboxyl-terminal hydrolase 16; 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; IPR050164; Peptidase_C19.
DR   InterPro; IPR001394; Peptidase_C19_UCH.
DR   InterPro; IPR030849; UBP16.
DR   InterPro; IPR028889; USP.
DR   InterPro; IPR018200; USP_CS.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   InterPro; IPR001607; Znf_UBP.
DR   PANTHER; PTHR24006; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR24006:SF852; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 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; Cell cycle; Cell division; Chromatin regulator; Hydrolase;
KW   Isopeptide bond; Metal-binding; Mitosis; Nucleus; Phosphoprotein; Protease;
KW   Reference proteome; Thiol protease; Transcription;
KW   Transcription regulation; Ubl conjugation; Ubl conjugation pathway; Zinc;
KW   Zinc-finger.
FT   CHAIN           1..826
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 16"
FT                   /id="PRO_0000367501"
FT   DOMAIN          195..825
FT                   /note="USP"
FT   ZN_FING         22..142
FT                   /note="UBP-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT   REGION          144..189
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          393..458
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        158..180
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        393..407
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        408..419
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        420..429
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        437..457
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        204
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03062"
FT   ACT_SITE        760
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         188
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y5T5"
FT   MOD_RES         414
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y5T5"
FT   MOD_RES         530
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q99LG0"
FT   MOD_RES         551
FT                   /note="Phosphoserine"
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   CONFLICT        771
FT                   /note="S -> N (in Ref. 2; AAI23862)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   826 AA;  94050 MW;  54A141CB98B711CE CRC64;
     MGKKRTKGKT VPIDDSSESL EPVCRHIRKG LEQGNLKKAL VNVEWNICQD CKTDNKVKDK
     SEEETEENPS VWLCLKCGHQ GCGRNSQEQH ALKHYMKPRS EPHCLVLSLD NWSVWCYLCD
     DEVHYCNSNR LGQVVDYVRK QAGNTTPESA EDNGNIELEN KKLEKESKNE QEREKKENMA
     RENPSMNSTS QITVKGLSNL GNTCFFNAVM QNLSQTPVLR ELLKEVKMSG TIVKIEPPDL
     ALTEPLEINL EPPGPLTLAM SQFLNEMQET KKGIVTPREL FSQVCKKAVR FKGYQQQDSQ
     ELLRYLLDGM RAEEHQRVSK GILKAFDNST EKVDEELKNK VKEYEKKKSV PSFVDRIFGG
     ELTSTIMCDE CRTVSLVHES FLDLSLPVLD DQSGKKSIND KNLKKTMEDE DKDSEEEKDN
     DSYLKERNDI PSGTSKHLQK KAKKQAKKQA KNQRRQQKIQ GKVLHLNDVY AIDHPEDNEC
     EVEMSLQREA DIKSNHISQE EVAPKEYCVN QKDLNGHEKM IESITDNQKS TEEAAMKNVS
     VDNDLEVLAS SATECPRNLN GAYLKEGSNG EVDISSGFEN LNLNAALQPD EINIEILDDD
     PTPGTKVYEV VNEDPETAFC TLANREAFNT DECSVQHCLY QFTRNEKLRD ANKLLCEVCT
     RRQYSGPKAN MKGERKHIYT NAKKQMLISL APPVLTLHFK RFQQAGFNLR KVNKHIKFPE
     ILDLAPFCTL KCKNVAEEHT RVLYSLYGVV EHSGTMRSGH YTAYAKTRTA STHLSNLVLH
     GDIPQDFEME STKGQWFHIS DTHVQAVPTT KVLSSQAYLL FYERIL
//