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Q70CQ1

- UBP49_HUMAN

UniProt

Q70CQ1 - UBP49_HUMAN

Protein

Ubiquitin carboxyl-terminal hydrolase 49

Gene

USP49

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 96 (01 Oct 2014)
      Sequence version 1 (05 Jul 2004)
      Previous versions | rss
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    Functioni

    Specifically deubiquitinates histone H2B at 'Lys-120' (H2BK120Ub). H2BK120Ub is a specific tag for epigenetic transcriptional activation and acts as a regulator of mRNA splicing. Deubiquitination is required for efficient cotranscriptional splicing of a large set of exons.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).2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei262 – 2621NucleophileCurated
    Active sitei615 – 6151Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri24 – 8562UBP-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. cysteine-type endopeptidase activity Source: UniProtKB
    2. histone binding Source: UniProtKB
    3. protein binding Source: UniProtKB
    4. ubiquitin-specific protease activity Source: UniProtKB
    5. ubiquitin thiolesterase activity Source: UniProtKB
    6. zinc ion binding Source: InterPro

    GO - Biological processi

    1. histone H2B conserved C-terminal lysine deubiquitination Source: UniProtKB
    2. mRNA splicing, via spliceosome Source: UniProtKB
    3. protein deubiquitination Source: FlyBase
    4. ubiquitin-dependent protein catabolic process Source: InterPro

    Keywords - Molecular functioni

    Chromatin regulator, Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    mRNA processing, mRNA splicing, Ubl conjugation pathway

    Keywords - Ligandi

    Metal-binding, Zinc

    Protein family/group databases

    MEROPSiC19.073.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase 49 (EC:3.4.19.12)
    Alternative name(s):
    Deubiquitinating enzyme 49
    Ubiquitin thioesterase 49
    Ubiquitin-specific-processing protease 49
    Gene namesi
    Name:USP49
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:20078. USP49.

    Subcellular locationi

    Nucleus 1 Publication

    GO - Cellular componenti

    1. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi262 – 2621C → A: Loss of deubiquitinase activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA134954570.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 688688Ubiquitin carboxyl-terminal hydrolase 49PRO_0000080678Add
    BLAST

    Proteomic databases

    PaxDbiQ70CQ1.
    PRIDEiQ70CQ1.

    PTM databases

    PhosphoSiteiQ70CQ1.

    Expressioni

    Gene expression databases

    ArrayExpressiQ70CQ1.
    BgeeiQ70CQ1.
    CleanExiHS_USP49.
    GenevestigatoriQ70CQ1.

    Organism-specific databases

    HPAiHPA030254.
    HPA030255.

    Interactioni

    Subunit structurei

    Component of a complex with RUVBL1 and PSMC5.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    FKBP5Q134512EBI-2511022,EBI-306914

    Protein-protein interaction databases

    BioGridi117382. 38 interactions.
    IntActiQ70CQ1. 48 interactions.
    STRINGi9606.ENSP00000297229.

    Structurei

    3D structure databases

    ProteinModelPortaliQ70CQ1.
    SMRiQ70CQ1. Positions 26-83, 246-655.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini253 – 657405USPAdd
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase C19 family.Curated
    Contains 1 UBP-type zinc finger.PROSITE-ProRule annotation
    Contains 1 USP domain.Curated

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri24 – 8562UBP-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiCOG5077.
    HOGENOMiHOG000015084.
    HOVERGENiHBG018027.
    InParanoidiQ70CQ1.
    KOiK11834.
    OMAiCLECATT.
    OrthoDBiEOG7JX33S.
    PhylomeDBiQ70CQ1.
    TreeFamiTF315281.

    Family and domain databases

    Gene3Di3.30.40.10. 1 hit.
    InterProiIPR018200. Pept_C19ubi-hydrolase_C_CS.
    IPR001394. Peptidase_C19_UCH.
    IPR028889. UCH/PAN2.
    IPR013083. Znf_RING/FYVE/PHD.
    IPR001607. Znf_UBP.
    [Graphical view]
    PfamiPF00443. UCH. 1 hit.
    PF02148. zf-UBP. 1 hit.
    [Graphical view]
    SMARTiSM00290. ZnF_UBP. 1 hit.
    [Graphical view]
    PROSITEiPS00972. USP_1. 1 hit.
    PS00973. USP_2. 1 hit.
    PS50235. USP_3. 1 hit.
    PS50271. ZF_UBP. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q70CQ1-1) [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

    MDRCKHVGRL RLAQDHSILN PQKWCCLECA TTESVWACLK CSHVACGRYI    50
    EDHALKHFEE TGHPLAMEVR DLYVFCYLCK DYVLNDNPEG DLKLLRSSLL 100
    AVRGQKQDTP VRRGRTLRSM ASGEDVVLPQ RAPQGQPQML TALWYRRQRL 150
    LARTLRLWFE KSSRGQAKLE QRRQEEALER KKEEARRRRR EVKRRLLEEL 200
    ASTPPRKSAR LLLHTPRDAG PAASRPAALP TSRRVPAATL KLRRQPAMAP 250
    GVTGLRNLGN TCYMNSILQV LSHLQKFREC FLNLDPSKTE HLFPKATNGK 300
    TQLSGKPTNS SATELSLRND RAEACEREGF CWNGRASISR SLELIQNKEP 350
    SSKHISLCRE LHTLFRVMWS GKWALVSPFA MLHSVWSLIP AFRGYDQQDA 400
    QEFLCELLHK VQQELESEGT TRRILIPFSQ RKLTKQVLKV VNTIFHGQLL 450
    SQVTCISCNY KSNTIEPFWD LSLEFPERYH CIEKGFVPLN QTECLLTEML 500
    AKFTETEALE GRIYACDQCN SKRRKSNPKP LVLSEARKQL MIYRLPQVLR 550
    LHLKRFRWSG RNHREKIGVH VVFDQVLTME PYCCRDMLSS LDKETFAYDL 600
    SAVVMHHGKG FGSGHYTAYC YNTEGGFWVH CNDSKLNVCS VEEVCKTQAY 650
    ILFYTQRTVQ GNARISETHL QAQVQSSNND EGRPQTFS 688
    Length:688
    Mass (Da):79,198
    Last modified:July 5, 2004 - v1
    Checksum:i1DE97A430A636B0B
    GO
    Isoform 2 (identifier: Q70CQ1-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         627-688: FWVHCNDSKL...NDEGRPQTFS → ACALLCGVGDTERG

    Note: No experimental confirmation available.

    Show »
    Length:640
    Mass (Da):73,455
    Checksum:i2476376554DA939E
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei627 – 68862FWVHC…PQTFS → ACALLCGVGDTERG in isoform 2. 1 PublicationVSP_011556Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ586139 mRNA. Translation: CAE51939.1.
    AL365205 Genomic DNA. Translation: CAI13187.1.
    AL365205 Genomic DNA. Translation: CAI13188.1.
    CH471081 Genomic DNA. Translation: EAX04065.1.
    BC014176 mRNA. Translation: AAH14176.1.
    CCDSiCCDS4861.1. [Q70CQ1-2]
    CCDS69111.1. [Q70CQ1-1]
    RefSeqiNP_001273483.1. NM_001286554.1. [Q70CQ1-1]
    NP_061031.2. NM_018561.4. [Q70CQ1-2]
    UniGeneiHs.593575.
    Hs.665742.

    Genome annotation databases

    EnsembliENST00000373006; ENSP00000362097; ENSG00000164663. [Q70CQ1-2]
    ENST00000373009; ENSP00000362100; ENSG00000164663. [Q70CQ1-1]
    ENST00000394253; ENSP00000377797; ENSG00000164663. [Q70CQ1-1]
    GeneIDi25862.
    KEGGihsa:25862.
    UCSCiuc003ori.3. human. [Q70CQ1-2]

    Polymorphism databases

    DMDMi52000871.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ586139 mRNA. Translation: CAE51939.1 .
    AL365205 Genomic DNA. Translation: CAI13187.1 .
    AL365205 Genomic DNA. Translation: CAI13188.1 .
    CH471081 Genomic DNA. Translation: EAX04065.1 .
    BC014176 mRNA. Translation: AAH14176.1 .
    CCDSi CCDS4861.1. [Q70CQ1-2 ]
    CCDS69111.1. [Q70CQ1-1 ]
    RefSeqi NP_001273483.1. NM_001286554.1. [Q70CQ1-1 ]
    NP_061031.2. NM_018561.4. [Q70CQ1-2 ]
    UniGenei Hs.593575.
    Hs.665742.

    3D structure databases

    ProteinModelPortali Q70CQ1.
    SMRi Q70CQ1. Positions 26-83, 246-655.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 117382. 38 interactions.
    IntActi Q70CQ1. 48 interactions.
    STRINGi 9606.ENSP00000297229.

    Protein family/group databases

    MEROPSi C19.073.

    PTM databases

    PhosphoSitei Q70CQ1.

    Polymorphism databases

    DMDMi 52000871.

    Proteomic databases

    PaxDbi Q70CQ1.
    PRIDEi Q70CQ1.

    Protocols and materials databases

    DNASUi 25862.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000373006 ; ENSP00000362097 ; ENSG00000164663 . [Q70CQ1-2 ]
    ENST00000373009 ; ENSP00000362100 ; ENSG00000164663 . [Q70CQ1-1 ]
    ENST00000394253 ; ENSP00000377797 ; ENSG00000164663 . [Q70CQ1-1 ]
    GeneIDi 25862.
    KEGGi hsa:25862.
    UCSCi uc003ori.3. human. [Q70CQ1-2 ]

    Organism-specific databases

    CTDi 25862.
    GeneCardsi GC06M041787.
    H-InvDB HIX0164985.
    HGNCi HGNC:20078. USP49.
    HPAi HPA030254.
    HPA030255.
    neXtProti NX_Q70CQ1.
    PharmGKBi PA134954570.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5077.
    HOGENOMi HOG000015084.
    HOVERGENi HBG018027.
    InParanoidi Q70CQ1.
    KOi K11834.
    OMAi CLECATT.
    OrthoDBi EOG7JX33S.
    PhylomeDBi Q70CQ1.
    TreeFami TF315281.

    Miscellaneous databases

    GenomeRNAii 25862.
    NextBioi 47231.
    PROi Q70CQ1.

    Gene expression databases

    ArrayExpressi Q70CQ1.
    Bgeei Q70CQ1.
    CleanExi HS_USP49.
    Genevestigatori Q70CQ1.

    Family and domain databases

    Gene3Di 3.30.40.10. 1 hit.
    InterProi IPR018200. Pept_C19ubi-hydrolase_C_CS.
    IPR001394. Peptidase_C19_UCH.
    IPR028889. UCH/PAN2.
    IPR013083. Znf_RING/FYVE/PHD.
    IPR001607. Znf_UBP.
    [Graphical view ]
    Pfami PF00443. UCH. 1 hit.
    PF02148. zf-UBP. 1 hit.
    [Graphical view ]
    SMARTi SM00290. ZnF_UBP. 1 hit.
    [Graphical view ]
    PROSITEi PS00972. USP_1. 1 hit.
    PS00973. USP_2. 1 hit.
    PS50235. USP_3. 1 hit.
    PS50271. ZF_UBP. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases."
      Quesada V., Diaz-Perales A., Gutierrez-Fernandez A., Garabaya C., Cal S., Lopez-Otin C.
      Biochem. Biophys. Res. Commun. 314:54-62(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME ACTIVITY.
    2. "The DNA sequence and analysis of human chromosome 6."
      Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
      , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
      Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Eye.
    5. "USP49 deubiquitinates histone H2B and regulates cotranscriptional pre-mRNA splicing."
      Zhang Z., Jones A., Joo H.Y., Zhou D., Cao Y., Chen S., Erdjument-Bromage H., Renfrow M., He H., Tempst P., Townes T.M., Giles K.E., Ma L., Wang H.
      Genes Dev. 27:1581-1595(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH RUVBL1 AND PSMC5, MUTAGENESIS OF CYS-262.

    Entry informationi

    Entry nameiUBP49_HUMAN
    AccessioniPrimary (citable) accession number: Q70CQ1
    Secondary accession number(s): Q5T3D9, Q5T3E0, Q96CK4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 13, 2004
    Last sequence update: July 5, 2004
    Last modified: October 1, 2014
    This is version 96 of the entry and version 1 of the sequence. [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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 6
      Human chromosome 6: entries, gene names and cross-references to MIM
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3