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Protein

Zinc finger-containing ubiquitin peptidase 1

Gene

ZUP1

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

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

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
  1. KM=50.4 µM for Arg-Leu-Arg-Gly-Gly-AMC1 Publication
  2. KM=4.9 µM for Ub-Rhodamine1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei360Nucleophile1 Publication1
    Sitei487Involved in the stabilization of negative charge on the oxyanion by the formation of the oxyanion hole1 Publication1
    Active sitei491Proton acceptor1 Publication1
    Active sitei512By similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Zinc fingeri2 – 24C2H2-type 1PROSITE-ProRule annotationAdd BLAST23
    Zinc fingeri29 – 52C2H2-type 2; atypical1 PublicationAdd BLAST24
    Zinc fingeri154 – 177C2H2-type 3PROSITE-ProRule annotationAdd BLAST24
    Zinc fingeri193 – 215C2H2-type 4PROSITE-ProRule annotationAdd BLAST23

    GO - Molecular functioni

    Keywordsi

    Molecular functionHydrolase
    LigandMetal-binding, Zinc

    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
    Name:ZUP1Imported
    Synonyms:C6orf113, ZUFSPImported
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 6

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000153975.9
    HGNCiHGNC:21224 ZUP1
    neXtProtiNX_Q96AP4

    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

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi351S → A, Q or Y: No effect. 1 Publication1
    Mutagenesisi360C → A: Loss of catalytic activity. 4 Publications1
    Mutagenesisi406D → A: Loss of catalytic activity. 1 Publication1
    Mutagenesisi428E → A: Loss of catalytic activity. 1 Publication1
    Mutagenesisi487Q → A: Loss of catalytic activity. 1 Publication1
    Mutagenesisi491H → A: Loss of catalytic activity. 3 Publications1
    Mutagenesisi512D → A: Loss of catalytic activity. 1 Publication1

    Organism-specific databases

    OpenTargetsiENSG00000153975
    PharmGKBiPA162411072

    Polymorphism and mutation databases

    BioMutaiZUFSP
    DMDMi74762646

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002443361 – 578Zinc finger-containing ubiquitin peptidase 1Add BLAST578

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei262N6-acetyllysineCombined sources1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiQ96AP4
    MaxQBiQ96AP4
    PaxDbiQ96AP4
    PeptideAtlasiQ96AP4
    PRIDEiQ96AP4
    ProteomicsDBi75981
    75982 [Q96AP4-2]

    PTM databases

    iPTMnetiQ96AP4
    PhosphoSitePlusiQ96AP4

    Expressioni

    Gene expression databases

    BgeeiENSG00000153975 Expressed in 184 organ(s), highest expression level in secondary oocyte
    CleanExiHS_ZUFSP
    ExpressionAtlasiQ96AP4 baseline and differential
    GenevisibleiQ96AP4 HS

    Organism-specific databases

    HPAiHPA044426

    Interactioni

    Subunit structurei

    Interacts with RPA1 and RPA2.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    RPS21Q8WVC23EBI-744706,EBI-10276945

    Protein-protein interaction databases

    BioGridi128708, 7 interactors
    IntActiQ96AP4, 5 interactors
    MINTiQ96AP4
    STRINGi9606.ENSP00000357565

    Structurei

    Secondary structure

    1578
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliQ96AP4
    SMRiQ96AP4
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni226 – 248MIU2 PublicationsAdd BLAST23
    Regioni249 – 274zUBD/ZHA2 PublicationsAdd BLAST26

    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

    Belongs to the peptidase C78 family. ZUFSP subfamily.Curated

    Zinc finger

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Zinc fingeri2 – 24C2H2-type 1PROSITE-ProRule annotationAdd BLAST23
    Zinc fingeri29 – 52C2H2-type 2; atypical1 PublicationAdd BLAST24
    Zinc fingeri154 – 177C2H2-type 3PROSITE-ProRule annotationAdd BLAST24
    Zinc fingeri193 – 215C2H2-type 4PROSITE-ProRule annotationAdd BLAST23

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiKOG4696 Eukaryota
    ENOG410XRQT LUCA
    GeneTreeiENSGT00390000008232
    HOGENOMiHOG000155812
    HOVERGENiHBG055781
    InParanoidiQ96AP4
    OMAiQEHVELH
    OrthoDBiEOG091G09EG
    PhylomeDBiQ96AP4
    TreeFamiTF323699

    Family and domain databases

    InterProiView protein in InterPro
    IPR012462 Peptidase_C78_UfSP1/2
    IPR013087 Znf_C2H2_type
    PfamiView protein in Pfam
    PF07910 Peptidase_C78, 1 hit
    SMARTiView protein in SMART
    SM00355 ZnF_C2H2, 4 hits
    PROSITEiView protein in PROSITE
    PS00028 ZINC_FINGER_C2H2_1, 2 hits
    PS50157 ZINC_FINGER_C2H2_2, 1 hit

    Sequences (2+)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.iShow all

    Isoform 1 (identifier: Q96AP4-1) [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
    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
    Length:578
    Mass (Da):65,959
    Last modified:December 1, 2001 - v1
    Checksum:i8590426B41F2C9A0
    GO
    Isoform 2 (identifier: Q96AP4-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-519: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:59
    Mass (Da):6,724
    Checksum:iE71C39FE59D781BC
    GO

    Computationally mapped potential isoform sequencesi

    There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    X6R6X3X6R6X3_HUMAN
    Zinc finger-containing ubiquitin pe...
    ZUP1
    280Annotation score:

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_026889379N → D1 PublicationCorresponds to variant dbSNP:rs4946188Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0195331 – 519Missing in isoform 2. 1 PublicationAdd BLAST519

    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
    CCDSiCCDS5110.1 [Q96AP4-1]
    RefSeqiNP_659499.2, NM_145062.2 [Q96AP4-1]
    XP_011533867.1, XM_011535565.2 [Q96AP4-1]
    UniGeneiHs.29857

    Genome annotation databases

    EnsembliENST00000368576; ENSP00000357565; ENSG00000153975 [Q96AP4-1]
    GeneIDi221302
    KEGGihsa:221302
    UCSCiuc003pxf.3 human [Q96AP4-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiZUP1_HUMAN
    AccessioniPrimary (citable) accession number: Q96AP4
    Secondary accession number(s): Q5TD92, Q6PJH7, Q96NV6
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 27, 2006
    Last sequence update: December 1, 2001
    Last modified: September 12, 2018
    This is version 138 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
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    Main funding by: National Institutes of Health

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