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Protein

Ubiquitin carboxyl-terminal hydrolase 16

Gene

USP16

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Specifically deubiquitinates 'Lys-120' of histone H2A (H2AK119Ub), a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Deubiquitination of histone H2A is a prerequisite for subsequent phosphorylation at 'Ser-11' of histone H3 (H3S10ph), and is required for chromosome segregation when cells enter into mitosis. In resting B- and T-lymphocytes, phosphorylation by AURKB leads to enhance its activity, thereby maintaining transcription in resting lymphocytes. Regulates Hox gene expression via histone H2A deubiquitination. Prefers nucleosomal substrates. Does not deubiquitinate histone H2B.UniRule annotation2 Publications

Miscellaneous

USP16 may contribute to somatic stem cell defects observed in Down syndrome. USP16 is triplicated in Down syndrome and its overexpression may contribute to proliferation defects in stem cells. Reduction of USP16 levels results in increased proliferation capacity of Down syndrome fibroblasts (PubMed:24025767).1 Publication

Catalytic activityi

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).UniRule annotation1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi24Zinc 11
Metal bindingi26Zinc 11
Metal bindingi48Zinc 21
Metal bindingi51Zinc 21
Metal bindingi74Zinc 31
Metal bindingi77Zinc 31
Metal bindingi82Zinc 21
Metal bindingi90Zinc 21
Metal bindingi94Zinc 31
Metal bindingi103Zinc 31
Metal bindingi116Zinc 11
Metal bindingi119Zinc 11
Active sitei205Nucleophile1
Active sitei758Proton acceptorUniRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri60 – 125UBP-typeUniRule annotationAdd BLAST66

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: UniProtKB
  • histone binding Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
  • thiol-dependent ubiquitinyl hydrolase activity Source: UniProtKB
  • transcription coactivator activity Source: UniProtKB
  • ubiquitin binding Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: UniProtKB
  • histone deubiquitination Source: UniProtKB
  • histone H2A K63-linked deubiquitination Source: UniProtKB
  • mitotic cell cycle Source: UniProtKB
  • monoubiquitinated histone H2A deubiquitination Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • positive regulation of translational elongation Source: UniProtKB
  • protein deubiquitination Source: Reactome
  • protein homotetramerization Source: UniProtKB
  • regulation of cell cycle Source: InterPro
  • regulation of transcription by RNA polymerase II Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • ubiquitin-dependent protein catabolic process Source: InterPro

Keywordsi

Molecular functionActivator, Chromatin regulator, Hydrolase, Protease, Thiol protease
Biological processCell cycle, Cell division, Mitosis, Transcription, Transcription regulation, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5689880 Ub-specific processing proteases
SIGNORiQ9Y5T5

Protein family/group databases

MEROPSiC19.021

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 16UniRule annotation (EC:3.4.19.12UniRule annotation)
Alternative name(s):
Deubiquitinating enzyme 16UniRule annotation
Ubiquitin thioesterase 16UniRule annotation
Ubiquitin-processing protease UBP-M
Ubiquitin-specific-processing protease 16UniRule annotation
Gene namesi
Name:USP16UniRule annotation
ORF Names:MSTP039
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

EuPathDBiHostDB:ENSG00000156256.14
HGNCiHGNC:12614 USP16
MIMi604735 gene
neXtProtiNX_Q9Y5T5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving USP16 is a cause of Chronic myelomonocytic leukemia. Inversion inv(21) (q21;q22) with RUNX1/AML1.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi205C → S: Loss of enzyme activity. 3 Publications1

Organism-specific databases

DisGeNETi10600
OpenTargetsiENSG00000156256
PharmGKBiPA37240

Polymorphism and mutation databases

BioMutaiUSP16
DMDMi6686071

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806431 – 823Ubiquitin carboxyl-terminal hydrolase 16Add BLAST823

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki140Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei189PhosphoserineCombined sources1
Modified residuei415PhosphoserineCombined sources1
Modified residuei531PhosphoserineBy similarity1
Modified residuei552PhosphoserineCombined sources1
Modified residuei554PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated at the onset of mitosis and dephosphorylated during the metaphase/anaphase transition. Phosphorylation by AURKB enhances the deubiquitinase activity.UniRule annotation1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9Y5T5
PaxDbiQ9Y5T5
PeptideAtlasiQ9Y5T5
PRIDEiQ9Y5T5
ProteomicsDBi86497
86498 [Q9Y5T5-2]
86499 [Q9Y5T5-3]
86500 [Q9Y5T5-4]
86501 [Q9Y5T5-5]

PTM databases

iPTMnetiQ9Y5T5
PhosphoSitePlusiQ9Y5T5

Expressioni

Tissue specificityi

Present in all the tissues examined including fetal brain, lung, liver, kidney, and adult heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.1 Publication

Gene expression databases

BgeeiENSG00000156256
CleanExiHS_USP16
ExpressionAtlasiQ9Y5T5 baseline and differential
GenevisibleiQ9Y5T5 HS

Organism-specific databases

HPAiHPA021140

Interactioni

Subunit structurei

Homotetramer.UniRule annotation1 Publication

GO - Molecular functioni

  • histone binding Source: UniProtKB
  • ubiquitin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115848, 31 interactors
DIPiDIP-53761N
IntActiQ9Y5T5, 6 interactors
STRINGi9606.ENSP00000334808

Structurei

Secondary structure

1823
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi27 – 30Combined sources4
Helixi33 – 40Combined sources8
Beta strandi45 – 47Combined sources3
Helixi49 – 52Combined sources4
Turni63 – 65Combined sources3
Beta strandi71 – 74Combined sources4
Turni75 – 77Combined sources3
Beta strandi80 – 82Combined sources3
Beta strandi86 – 88Combined sources3
Helixi90 – 96Combined sources7
Beta strandi105 – 108Combined sources4
Turni109 – 111Combined sources3
Beta strandi114 – 116Combined sources3
Turni117 – 120Combined sources4
Beta strandi121 – 123Combined sources3
Helixi130 – 142Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2I50NMR-A22-143[»]
ProteinModelPortaliQ9Y5T5
SMRiQ9Y5T5
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y5T5

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini196 – 822USPAdd BLAST627

Domaini

The UBP-type zinc finger binds 3 zinc ions that form a pair of cross-braced ring fingers encapsulated within a third zinc finger in the primary structure. It recognizes the C-terminal tail of free ubiquitin.1 Publication

Sequence similaritiesi

Belongs to the peptidase C19 family. USP16 subfamily.UniRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri60 – 125UBP-typeUniRule annotationAdd BLAST66

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG1873 Eukaryota
COG5560 LUCA
GeneTreeiENSGT00860000133682
HOVERGENiHBG062704
InParanoidiQ9Y5T5
KOiK11844
OMAiFHISDTS
OrthoDBiEOG091G01WT
PhylomeDBiQ9Y5T5
TreeFamiTF326075

Family and domain databases

Gene3Di3.30.40.10, 1 hit
HAMAPiMF_03062 UBP16, 1 hit
InterProiView protein in InterPro
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR030849 UBP16
IPR018200 USP_CS
IPR028889 USP_dom
IPR013083 Znf_RING/FYVE/PHD
IPR001607 Znf_UBP
PfamiView protein in Pfam
PF00443 UCH, 1 hit
PF02148 zf-UBP, 1 hit
SMARTiView protein in SMART
SM00290 ZnF_UBP, 1 hit
SUPFAMiSSF54001 SSF54001, 2 hits
PROSITEiView protein in PROSITE
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit
PS50271 ZF_UBP, 1 hit

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y5T5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGKKRTKGKT VPIDDSSETL EPVCRHIRKG LEQGNLKKAL VNVEWNICQD
60 70 80 90 100
CKTDNKVKDK AEEETEEKPS VWLCLKCGHQ GCGRNSQEQH ALKHYLTPRS
110 120 130 140 150
EPHCLVLSLD NWSVWCYVCD NEVQYCSSNQ LGQVVDYVRK QASITTPKPA
160 170 180 190 200
EKDNGNIELE NKKLEKESKN EQEREKKENM AKENPPMNSP CQITVKGLSN
210 220 230 240 250
LGNTCFFNAV MQNLSQTPVL RELLKEVKMS GTIVKIEPPD LALTEPLEIN
260 270 280 290 300
LEPPGPLTLA MSQFLNEMQE TKKGVVTPKE LFSQVCKKAV RFKGYQQQDS
310 320 330 340 350
QELLRYLLDG MRAEEHQRVS KGILKAFGNS TEKLDEELKN KVKDYEKKKS
360 370 380 390 400
MPSFVDRIFG GELTSMIMCD QCRTVSLVHE SFLDLSLPVL DDQSGKKSVN
410 420 430 440 450
DKNLKKTVED EDQDSEEEKD NDSYIKERSD IPSGTSKHLQ KKAKKQAKKQ
460 470 480 490 500
AKNQRRQQKI QGKVLHLNDI CTIDHPEDSE YEAEMSLQGE VNIKSNHISQ
510 520 530 540 550
EGVMHKEYCV NQKDLNGQAK MIESVTDNQK STEEVDMKNI NMDNDLEVLT
560 570 580 590 600
SSPTRNLNGA YLTEGSNGEV DISNGFKNLN LNAALHPDEI NIEILNDSHT
610 620 630 640 650
PGTKVYEVVN EDPETAFCTL ANREVFNTDE CSIQHCLYQF TRNEKLRDAN
660 670 680 690 700
KLLCEVCTRR QCNGPKANIK GERKHVYTNA KKQMLISLAP PVLTLHLKRF
710 720 730 740 750
QQAGFNLRKV NKHIKFPEIL DLAPFCTLKC KNVAEENTRV LYSLYGVVEH
760 770 780 790 800
SGTMRSGHYT AYAKARTANS HLSNLVLHGD IPQDFEMESK GQWFHISDTH
810 820
VQAVPTTKVL NSQAYLLFYE RIL
Length:823
Mass (Da):93,570
Last modified:November 1, 1999 - v1
Checksum:iC7D4175649BA3E31
GO
Isoform 2 (identifier: Q9Y5T5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     150-150: Missing.

Show »
Length:822
Mass (Da):93,499
Checksum:i36FD67E22FA078AB
GO
Isoform 3 (identifier: Q9Y5T5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: MGKKRTKGKTVPIDDSSETL → MGSVAV
     150-150: Missing.

Note: No experimental confirmation available.
Show »
Length:808
Mass (Da):91,870
Checksum:iE4528720234CB7B7
GO
Isoform 4 (identifier: Q9Y5T5-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-310: Missing.

Note: No experimental confirmation available.
Show »
Length:513
Mass (Da):58,397
Checksum:i9AD260CF2FE530A9
GO
Isoform 5 (identifier: Q9Y5T5-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     394-823: SGKKSVNDKN...AYLLFYERIL → VRLLNLFYSSRFFFL

Show »
Length:408
Mass (Da):46,599
Checksum:i5B3EB300F72F4E04
GO

Sequence cautioni

The sequence AAG39290 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAG51175 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti141Q → E in AAG39290 (Ref. 8) Curated1
Sequence conflicti297Q → R in BAG51175 (PubMed:14702039).Curated1
Sequence conflicti348K → E in BAD96604 (Ref. 4) Curated1
Sequence conflicti350S → P in BAD96401 (Ref. 4) Curated1
Sequence conflicti480 – 481EY → DN in AAH30777 (PubMed:15489334).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_020388141Q → H2 PublicationsCorresponds to variant dbSNP:rs2274802Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0367131 – 310Missing in isoform 4. 1 PublicationAdd BLAST310
Alternative sequenceiVSP_0367141 – 20MGKKR…SSETL → MGSVAV in isoform 3. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_036715150Missing in isoform 2 and isoform 3. 2 Publications1
Alternative sequenceiVSP_036716394 – 823SGKKS…YERIL → VRLLNLFYSSRFFFL in isoform 5. 1 PublicationAdd BLAST430

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF126736 mRNA Translation: AAD20949.1
AY333928 mRNA Translation: AAR13293.1
AK023247 mRNA Translation: BAG51175.1 Different initiation.
AK302247 mRNA Translation: BAG63599.1
AK294284 mRNA Translation: BAG57569.1
AK222681 mRNA Translation: BAD96401.1
AK222884 mRNA Translation: BAD96604.1
AL163249 Genomic DNA Translation: CAB90432.1
AF129075 Genomic DNA No translation available.
CH471079 Genomic DNA Translation: EAX09927.1
CH471079 Genomic DNA Translation: EAX09929.1
BC030777 mRNA Translation: AAH30777.1
AF113219 mRNA Translation: AAG39290.1 Different initiation.
CCDSiCCDS13583.1 [Q9Y5T5-1]
CCDS42912.1 [Q9Y5T5-2]
RefSeqiNP_001001992.1, NM_001001992.1 [Q9Y5T5-2]
NP_001027582.1, NM_001032410.1 [Q9Y5T5-1]
NP_006438.1, NM_006447.2 [Q9Y5T5-1]
XP_016883746.1, XM_017028257.1 [Q9Y5T5-1]
XP_016883747.1, XM_017028258.1 [Q9Y5T5-2]
XP_016883748.1, XM_017028259.1 [Q9Y5T5-2]
XP_016883749.1, XM_017028260.1 [Q9Y5T5-4]
XP_016883750.1, XM_017028261.1 [Q9Y5T5-4]
UniGeneiHs.99819

Genome annotation databases

EnsembliENST00000334352; ENSP00000334808; ENSG00000156256 [Q9Y5T5-1]
ENST00000399975; ENSP00000382857; ENSG00000156256 [Q9Y5T5-2]
ENST00000399976; ENSP00000382858; ENSG00000156256 [Q9Y5T5-1]
GeneIDi10600
KEGGihsa:10600
UCSCiuc002ymw.4 human [Q9Y5T5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiUBP16_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5T5
Secondary accession number(s): A8MU43
, B3KN13, B4DFV8, B4DY37, D3DSD9, Q53GP7, Q53HA0, Q5VKN8, Q8NEL3, Q9H3E6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1999
Last modified: June 20, 2018
This is version 167 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

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