UniProtKB - Q96AP4 (ZUP1_HUMAN)
Protein
Zinc finger-containing ubiquitin peptidase 1
Gene
ZUP1
Organism
Homo sapiens (Human)
Status
Functioni
Deubiquitinase with endodeubiquitinase activity that specifically interacts with and cleaves 'Lys-63'-linked long polyubiquitin chains. Shows only weak activity against 'Lys-11' and 'Lys-48'-linked chains (PubMed:29576528, PubMed:29563501, PubMed:29476094). Plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage (PubMed:29576528, PubMed:29576527). Modulates the ubiquitination status of replication protein A (RPA) complex proteins in response to replication stress (PubMed:29563501).4 Publications
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).2 Publications EC:3.4.19.12
Kineticsi
kcat is 4.9 sec(-1) with Arg-Leu-Arg-Gly-Gly-AMC as substrate (PubMed:29476094). kcat is 0.084 sec(-1) with Ub-Rhodamine as substrate (PubMed:29576528).2 Publications
- KM=50.4 µM for Arg-Leu-Arg-Gly-Gly-AMC1 Publication
- KM=4.9 µM for Ub-Rhodamine1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 360 | Nucleophile1 Publication | 1 | |
Sitei | 487 | Involved in the stabilization of negative charge on the oxyanion by the formation of the oxyanion hole1 Publication | 1 | |
Active sitei | 491 | Proton acceptor1 Publication | 1 | |
Active sitei | 512 | By similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 2 – 24 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 29 – 52 | C2H2-type 2; atypical1 PublicationAdd BLAST | 24 | |
Zinc fingeri | 154 – 177 | C2H2-type 3PROSITE-ProRule annotationAdd BLAST | 24 | |
Zinc fingeri | 193 – 215 | C2H2-type 4PROSITE-ProRule annotationAdd BLAST | 23 |
GO - Molecular functioni
- metal ion binding Source: UniProtKB-KW
- thiol-dependent ubiquitin-specific protease activity Source: UniProtKB-EC
GO - Biological processi
- regulation of gene expression Source: GO_Central
Keywordsi
Molecular function | Hydrolase |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q96AP4 |
Names & Taxonomyi
Protein namesi | Recommended name: Zinc finger-containing ubiquitin peptidase 1Curated (EC:3.4.19.121 Publication)Alternative name(s): Lys-63-specific deubiquitinase ZUFSP Short name: DUB Zinc finger with UFM1-specific peptidase domain protein |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:21224, ZUP1 |
neXtProti | NX_Q96AP4 |
VEuPathDBi | HostDB:ENSG00000153975.9 |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 351 | S → A, Q or Y: No effect. 1 Publication | 1 | |
Mutagenesisi | 360 | C → A: Loss of catalytic activity. 4 Publications | 1 | |
Mutagenesisi | 406 | D → A: Loss of catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 428 | E → A: Loss of catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 487 | Q → A: Loss of catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 491 | H → A: Loss of catalytic activity. 3 Publications | 1 | |
Mutagenesisi | 512 | D → A: Loss of catalytic activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 221302 |
OpenTargetsi | ENSG00000153975 |
PharmGKBi | PA162411072 |
Miscellaneous databases
Pharosi | Q96AP4, Tdark |
Genetic variation databases
BioMutai | ZUFSP |
DMDMi | 74762646 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000244336 | 1 – 578 | Zinc finger-containing ubiquitin peptidase 1Add BLAST | 578 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 262 | N6-acetyllysineCombined sources | 1 |
Keywords - PTMi
AcetylationProteomic databases
EPDi | Q96AP4 |
jPOSTi | Q96AP4 |
MassIVEi | Q96AP4 |
MaxQBi | Q96AP4 |
PaxDbi | Q96AP4 |
PeptideAtlasi | Q96AP4 |
PRIDEi | Q96AP4 |
ProteomicsDBi | 75981 [Q96AP4-1] 75982 [Q96AP4-2] |
PTM databases
iPTMneti | Q96AP4 |
PhosphoSitePlusi | Q96AP4 |
Expressioni
Gene expression databases
Bgeei | ENSG00000153975, Expressed in secondary oocyte and 197 other tissues |
ExpressionAtlasi | Q96AP4, baseline and differential |
Genevisiblei | Q96AP4, HS |
Organism-specific databases
HPAi | ENSG00000153975, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with RPA1 and RPA2.
1 PublicationBinary interactionsi
Hide detailsQ96AP4
With | #Exp. | IntAct |
---|---|---|
ARHGAP45 [Q92619] | 3 | EBI-744706,EBI-2825900 |
MMP14 [P50281] | 3 | EBI-744706,EBI-992788 |
RPS21 [Q8WVC2] | 3 | EBI-744706,EBI-10276945 |
Protein-protein interaction databases
BioGRIDi | 128708, 171 interactors |
IntActi | Q96AP4, 6 interactors |
MINTi | Q96AP4 |
STRINGi | 9606.ENSP00000357565 |
Miscellaneous databases
RNActi | Q96AP4, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q96AP4 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 226 – 248 | MIU2 PublicationsAdd BLAST | 23 | |
Regioni | 249 – 274 | zUBD/ZHA2 PublicationsAdd BLAST | 26 |
Domaini
The motif interacting with ubiquitin (MIU) and ZUFSP ubiquitin-binding domain (zUBD, also called ZUFSP helical arm ZHA) are responsible for binding the distal (outgoing) ubiquitin units S1 and S2 respectively.2 Publications1 Publication
C2H2-type zinc finger 4 is a ubiquitin-binding zinc finger (UBZ) and required for polyubiquitin binding, possibly binding the proximal ubiqutin, and for catalytic activity (PubMed:29576528) (Probable). C2H2-type zinc fingers 1-3 are required for localization to sites of DNA damage (PubMed:29576528).1 Publication1 Publication
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 2 – 24 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 29 – 52 | C2H2-type 2; atypical1 PublicationAdd BLAST | 24 | |
Zinc fingeri | 154 – 177 | C2H2-type 3PROSITE-ProRule annotationAdd BLAST | 24 | |
Zinc fingeri | 193 – 215 | C2H2-type 4PROSITE-ProRule annotationAdd BLAST | 23 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | KOG4696, Eukaryota |
GeneTreei | ENSGT00390000008232 |
HOGENOMi | CLU_017060_1_1_1 |
InParanoidi | Q96AP4 |
OMAi | EYHKRKA |
PhylomeDBi | Q96AP4 |
TreeFami | TF323699 |
Family and domain databases
InterProi | View protein in InterPro IPR012462, Peptidase_C78_UfSP1/2 IPR013087, Znf_C2H2_type |
Pfami | View protein in Pfam PF07910, Peptidase_C78, 1 hit |
SMARTi | View protein in SMART SM00355, ZnF_C2H2, 4 hits |
PROSITEi | View protein in PROSITE PS00028, ZINC_FINGER_C2H2_1, 2 hits PS50157, ZINC_FINGER_C2H2_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: Q96AP4-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MLSCNICGET VTSEPDMKAH LIVHMESEII CPFCKLSGVN YDEMCFHIET
60 70 80 90 100
AHFEQNTLER NFERINTVQY GTSDNKKDNT LQCGMEVNSS ILSGCASNHP
110 120 130 140 150
KNSAQNLTKD STLKHEGFYS ENLTESRKFL KSREKQSSLT EIKGSVYETT
160 170 180 190 200
YSPPECPFCG KIEEHSEDME THVKTKHANL LDIPLEDCDQ PLYDCPMCGL
210 220 230 240 250
ICTNYHILQE HVDLHLEENS FQQGMDRVQC SGDLQLAHQL QQEEDRKRRS
260 270 280 290 300
EESRQEIEEF QKLQRQYGLD NSGGYKQQQL RNMEIEVNRG RMPPSEFHRR
310 320 330 340 350
KADMMESLAL GFDDGKTKTS GIIEALHRYY QNAATDVRRV WLSSVVDHFH
360 370 380 390 400
SSLGDKGWGC GYRNFQMLLS SLLQNDAYND CLKGMLIPCI PKIQSMIEDA
410 420 430 440 450
WKEGFDPQGA SQLNNRLQGT KAWIGACEVY ILLTSLRVKC HIVDFHKSTG
460 470 480 490 500
PLGTHPRLFE WILNYYSSEG EGSPKVVCTS KPPIYLQHQG HSRTVIGIEE
510 520 530 540 550
KKNRTLCLLI LDPGCPSREM QKLLKQDIEA SSLKQLRKSM GNLKHKQYQI
560 570
LAVEGALSLE EKLARRQASQ VFTAEKIP
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketX6R6X3 | X6R6X3_HUMAN | Zinc finger-containing ubiquitin pe... | ZUP1 | 280 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_026889 | 379 | N → D1 PublicationCorresponds to variant dbSNP:rs4946188Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_019533 | 1 – 519 | Missing in isoform 2. 1 PublicationAdd BLAST | 519 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK054582 mRNA Translation: BAB70765.1 BX537872 mRNA Translation: CAD97873.1 AL132795 Genomic DNA No translation available. BC015420 mRNA Translation: AAH15420.1 BC016879 mRNA Translation: AAH16879.1 |
CCDSi | CCDS5110.1 [Q96AP4-1] |
RefSeqi | NP_659499.2, NM_145062.2 [Q96AP4-1] XP_011533867.1, XM_011535565.2 |
Genome annotation databases
Ensembli | ENST00000368576; ENSP00000357565; ENSG00000153975 [Q96AP4-1] |
GeneIDi | 221302 |
KEGGi | hsa:221302 |
UCSCi | uc003pxf.3, human [Q96AP4-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK054582 mRNA Translation: BAB70765.1 BX537872 mRNA Translation: CAD97873.1 AL132795 Genomic DNA No translation available. BC015420 mRNA Translation: AAH15420.1 BC016879 mRNA Translation: AAH16879.1 |
CCDSi | CCDS5110.1 [Q96AP4-1] |
RefSeqi | NP_659499.2, NM_145062.2 [Q96AP4-1] XP_011533867.1, XM_011535565.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6EI1 | X-ray | 1.73 | A | 232-578 | [»] | |
6FGE | X-ray | 1.74 | A | 231-578 | [»] | |
SMRi | Q96AP4 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 128708, 171 interactors |
IntActi | Q96AP4, 6 interactors |
MINTi | Q96AP4 |
STRINGi | 9606.ENSP00000357565 |
PTM databases
iPTMneti | Q96AP4 |
PhosphoSitePlusi | Q96AP4 |
Genetic variation databases
BioMutai | ZUFSP |
DMDMi | 74762646 |
Proteomic databases
EPDi | Q96AP4 |
jPOSTi | Q96AP4 |
MassIVEi | Q96AP4 |
MaxQBi | Q96AP4 |
PaxDbi | Q96AP4 |
PeptideAtlasi | Q96AP4 |
PRIDEi | Q96AP4 |
ProteomicsDBi | 75981 [Q96AP4-1] 75982 [Q96AP4-2] |
Protocols and materials databases
Antibodypediai | 32518, 109 antibodies |
Genome annotation databases
Ensembli | ENST00000368576; ENSP00000357565; ENSG00000153975 [Q96AP4-1] |
GeneIDi | 221302 |
KEGGi | hsa:221302 |
UCSCi | uc003pxf.3, human [Q96AP4-1] |
Organism-specific databases
CTDi | 221302 |
DisGeNETi | 221302 |
GeneCardsi | ZUP1 |
HGNCi | HGNC:21224, ZUP1 |
HPAi | ENSG00000153975, Low tissue specificity |
neXtProti | NX_Q96AP4 |
OpenTargetsi | ENSG00000153975 |
PharmGKBi | PA162411072 |
VEuPathDBi | HostDB:ENSG00000153975.9 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4696, Eukaryota |
GeneTreei | ENSGT00390000008232 |
HOGENOMi | CLU_017060_1_1_1 |
InParanoidi | Q96AP4 |
OMAi | EYHKRKA |
PhylomeDBi | Q96AP4 |
TreeFami | TF323699 |
Enzyme and pathway databases
PathwayCommonsi | Q96AP4 |
Miscellaneous databases
BioGRID-ORCSi | 221302, 5 hits in 881 CRISPR screens |
GenomeRNAii | 221302 |
Pharosi | Q96AP4, Tdark |
PROi | PR:Q96AP4 |
RNActi | Q96AP4, protein |
Gene expression databases
Bgeei | ENSG00000153975, Expressed in secondary oocyte and 197 other tissues |
ExpressionAtlasi | Q96AP4, baseline and differential |
Genevisiblei | Q96AP4, HS |
Family and domain databases
InterProi | View protein in InterPro IPR012462, Peptidase_C78_UfSP1/2 IPR013087, Znf_C2H2_type |
Pfami | View protein in Pfam PF07910, Peptidase_C78, 1 hit |
SMARTi | View protein in SMART SM00355, ZnF_C2H2, 4 hits |
PROSITEi | View protein in PROSITE PS00028, ZINC_FINGER_C2H2_1, 2 hits PS50157, ZINC_FINGER_C2H2_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ZUP1_HUMAN | |
Accessioni | Q96AP4Primary (citable) accession number: Q96AP4 Secondary accession number(s): Q5TD92, Q6PJH7, Q96NV6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 27, 2006 |
Last sequence update: | December 1, 2001 | |
Last modified: | February 10, 2021 | |
This is version 156 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Peptidase families
Classification of peptidase families and list of entries