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P0CG47

- UBB_HUMAN

UniProt

P0CG47 - UBB_HUMAN

Protein

Polyubiquitin-B

Gene

UBB

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 46 (01 Oct 2014)
      Sequence version 1 (10 Aug 2010)
      Previous versions | rss
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    Functioni

    Ubiquitin: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei54 – 541Activating enzyme
    Sitei68 – 681Essential for function
    Binding sitei72 – 721Activating enzyme

    GO - Molecular functioni

    1. protein binding Source: IntAct

    GO - Biological processi

    1. activation of MAPK activity Source: Reactome
    2. anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Source: Reactome
    3. antigen processing and presentation of exogenous peptide antigen via MHC class I Source: Reactome
    4. antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent Source: Reactome
    5. antigen processing and presentation of peptide antigen via MHC class I Source: Reactome
    6. apoptotic process Source: Reactome
    7. apoptotic signaling pathway Source: Reactome
    8. carbohydrate metabolic process Source: Reactome
    9. cellular response to hypoxia Source: Reactome
    10. cytokine-mediated signaling pathway Source: Reactome
    11. DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: Reactome
    12. DNA repair Source: Reactome
    13. endosomal transport Source: Reactome
    14. epidermal growth factor receptor signaling pathway Source: Reactome
    15. Fc-epsilon receptor signaling pathway Source: Reactome
    16. fibroblast growth factor receptor signaling pathway Source: Reactome
    17. G1/S transition of mitotic cell cycle Source: Reactome
    18. G2/M transition of mitotic cell cycle Source: Reactome
    19. gene expression Source: Reactome
    20. glucose metabolic process Source: Reactome
    21. glycogen biosynthetic process Source: Reactome
    22. I-kappaB kinase/NF-kappaB signaling Source: Reactome
    23. innate immune response Source: Reactome
    24. intracellular transport of virus Source: Reactome
    25. ion transmembrane transport Source: Reactome
    26. JNK cascade Source: Reactome
    27. membrane organization Source: Reactome
    28. mitotic cell cycle Source: Reactome
    29. mRNA metabolic process Source: Reactome
    30. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
    31. MyD88-independent toll-like receptor signaling pathway Source: Reactome
    32. negative regulation of apoptotic process Source: Reactome
    33. negative regulation of epidermal growth factor receptor signaling pathway Source: Reactome
    34. negative regulation of transcription from RNA polymerase II promoter Source: Reactome
    35. negative regulation of transforming growth factor beta receptor signaling pathway Source: Reactome
    36. negative regulation of type I interferon production Source: Reactome
    37. negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Source: Reactome
    38. neurotrophin TRK receptor signaling pathway Source: Reactome
    39. Notch receptor processing Source: Reactome
    40. Notch signaling pathway Source: Reactome
    41. nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Source: Reactome
    42. nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
    43. positive regulation of apoptotic process Source: Reactome
    44. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Reactome
    45. positive regulation of NF-kappaB transcription factor activity Source: Reactome
    46. positive regulation of transcription from RNA polymerase II promoter Source: Reactome
    47. positive regulation of type I interferon production Source: Reactome
    48. positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Source: Reactome
    49. protein polyubiquitination Source: Reactome
    50. regulation of apoptotic process Source: Reactome
    51. regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: Reactome
    52. regulation of type I interferon production Source: Reactome
    53. regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Source: Reactome
    54. RNA metabolic process Source: Reactome
    55. small molecule metabolic process Source: Reactome
    56. stress-activated MAPK cascade Source: Reactome
    57. T cell receptor signaling pathway Source: Reactome
    58. toll-like receptor 10 signaling pathway Source: Reactome
    59. toll-like receptor 2 signaling pathway Source: Reactome
    60. toll-like receptor 3 signaling pathway Source: Reactome
    61. toll-like receptor 4 signaling pathway Source: Reactome
    62. toll-like receptor 5 signaling pathway Source: Reactome
    63. toll-like receptor 9 signaling pathway Source: Reactome
    64. toll-like receptor signaling pathway Source: Reactome
    65. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
    66. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
    67. transcription, DNA-templated Source: Reactome
    68. transcription initiation from RNA polymerase II promoter Source: Reactome
    69. transforming growth factor beta receptor signaling pathway Source: Reactome
    70. transmembrane transport Source: Reactome
    71. TRIF-dependent toll-like receptor signaling pathway Source: Reactome
    72. viral life cycle Source: Reactome
    73. viral process Source: Reactome
    74. viral protein processing Source: Reactome
    75. virion assembly Source: Reactome

    Enzyme and pathway databases

    ReactomeiREACT_111080. Spry regulation of FGF signaling.
    REACT_111178. ER-Phagosome pathway.
    REACT_111184. Negative regulation of FGFR signaling.
    REACT_1156. Orc1 removal from chromatin.
    REACT_115662. Downregulation of ERBB2:ERBB3 signaling.
    REACT_115755. Signaling by ERBB2.
    REACT_115828. Downregulation of ERBB4 signaling.
    REACT_115831. ISG15 antiviral mechanism.
    REACT_115852. Signaling by constitutively active EGFR.
    REACT_115893. Membrane binding and targetting of GAG proteins.
    REACT_1181. Association of licensing factors with the pre-replicative complex.
    REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_118656. Activation of NF-kappaB in B cells.
    REACT_118780. NOTCH1 Intracellular Domain Regulates Transcription.
    REACT_120726. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
    REACT_120727. Downregulation of TGF-beta receptor signaling.
    REACT_120734. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
    REACT_120916. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
    REACT_121111. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
    REACT_1221. CDK-mediated phosphorylation and removal of Cdc6.
    REACT_12484. EGFR downregulation.
    REACT_12555. Downstream TCR signaling.
    REACT_13415. p75NTR recruits signalling complexes.
    REACT_13464. Regulation of activated PAK-2p34 by proteasome mediated degradation.
    REACT_13643. NRIF signals cell death from the nucleus.
    REACT_13696. NF-kB is activated and signals survival.
    REACT_150471. Separation of Sister Chromatids.
    REACT_160089. Constitutive Signaling by NOTCH1 HD Domain Mutants.
    REACT_160189. Stimuli-sensing channels.
    REACT_160205. NOTCH2 Activation and Transmission of Signal to the Nucleus.
    REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
    REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
    REACT_160315. Regulation of PLK1 Activity at G2/M Transition.
    REACT_1614. Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
    REACT_163977. Regulation of innate immune responses to cytosolic DNA.
    REACT_163994. FCERI mediated NF-kB activation.
    REACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169208. Glycogen synthesis.
    REACT_169325. Oncogene Induced Senescence.
    REACT_169436. Oxidative Stress Induced Senescence.
    REACT_172638. Asymmetric localization of PCP proteins.
    REACT_18265. Regulation of the Fanconi anemia pathway.
    REACT_18410. Fanconi Anemia pathway.
    REACT_1949. CDT1 association with the CDC6:ORC:origin complex.
    REACT_199384. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_200716. regulation of FZD by ubiquitination.
    REACT_200731. deactivation of the beta-catenin transactivating complex.
    REACT_200766. degradation of AXIN.
    REACT_200777. TCF dependent signaling in response to WNT.
    REACT_200783. Myoclonic epilepsy of Lafora.
    REACT_200841. degradation of DVL.
    REACT_20549. Autodegradation of the E3 ubiquitin ligase COP1.
    REACT_21281. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
    REACT_21368. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
    REACT_21399. activated TAK1 mediates p38 MAPK activation.
    REACT_22442. Interleukin-1 signaling.
    REACT_225574. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_23787. Regulation of signaling by CBL.
    REACT_24918. IRAK1 recruits IKK complex.
    REACT_24941. Circadian Clock.
    REACT_25018. IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
    REACT_25120. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
    REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
    REACT_25271. Negative regulators of RIG-I/MDA5 signaling.
    REACT_25325. AUF1 (hnRNP D0) destabilizes mRNA.
    REACT_25351. TRAF6 mediated induction of TAK1 complex.
    REACT_25354. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
    REACT_25359. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.
    REACT_25374. IKK complex recruitment mediated by RIP1.
    REACT_25380. IRAK2 mediated activation of TAK1 complex.
    REACT_27258. Endosomal Sorting Complex Required For Transport (ESCRT).
    REACT_4. Ubiquitin-dependent degradation of Cyclin D1.
    REACT_6359. Budding and maturation of HIV virion.
    REACT_6761. APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
    REACT_6785. Autodegradation of Cdh1 by Cdh1:APC/C.
    REACT_6818. Assembly Of The HIV Virion.
    REACT_6820. APC/C:Cdc20 mediated degradation of Cyclin B.
    REACT_6821. SCF-beta-TrCP mediated degradation of Emi1.
    REACT_6871. APC/C:Cdc20 mediated degradation of Securin.
    REACT_75776. NOD1/2 Signaling Pathway.
    REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
    REACT_821. Cyclin D associated events in G1.
    REACT_9003. SCF(Skp2)-mediated degradation of p27/p21.
    REACT_9031. Vpu mediated degradation of CD4.
    REACT_9453. Vif-mediated degradation of APOBEC3G.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Polyubiquitin-B
    Cleaved into the following chain:
    Gene namesi
    Name:UBB
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:12463. UBB.

    Subcellular locationi

    Chain Ubiquitin : Cytoplasm By similarity. Nucleus By similarity

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. endocytic vesicle membrane Source: Reactome
    3. endosome membrane Source: Reactome
    4. nucleoplasm Source: Reactome
    5. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi48 – 481K → R: No effect on HLTF-mediated polyubiquitination of PCNA. 1 Publication
    Mutagenesisi63 – 631K → R: Abolishes HLTF-mediated polyubiquitination of PCNA. 1 Publication
    Mutagenesisi65 – 651S → A: Prevents phosphorylation in case of mitophagy. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 7676UbiquitinPRO_0000396174Add
    BLAST
    Chaini77 – 15276UbiquitinPRO_0000396175Add
    BLAST
    Chaini153 – 22876UbiquitinPRO_0000396176Add
    BLAST
    Propeptidei229 – 2291PRO_0000396177

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Cross-linki6 – 6Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Cross-linki11 – 11Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)2 Publications
    Cross-linki27 – 27Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Cross-linki29 – 29Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Cross-linki33 – 33Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki48 – 48Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)3 Publications
    Cross-linki63 – 63Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)2 Publications
    Modified residuei65 – 651Phosphoserine; by PINK11 Publication
    Cross-linki76 – 76Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins)

    Post-translational modificationi

    Ubiquitin: Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PARK2), triggering mitophagy.6 Publications

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP0CG47.
    PRIDEiP0CG47.

    PTM databases

    PhosphoSiteiP0CG47.

    Expressioni

    Gene expression databases

    ArrayExpressiP0CG47.
    BgeeiP0CG47.

    Organism-specific databases

    HPAiCAB013048.
    HPA041344.
    HPA049132.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CCDC50Q8IVM02EBI-413034,EBI-723996
    DUSP1P285622EBI-413034,EBI-975493
    GGA1Q9UJY53EBI-413034,EBI-447141
    GGA3Q9NZ522EBI-413034,EBI-447404
    Mast2Q605922EBI-413034,EBI-493888From a different organism.
    MCM7P339932EBI-413034,EBI-355924
    NPQ9DLK62EBI-413034,EBI-8433218From a different organism.
    Pax3P246102EBI-413034,EBI-1208116From a different organism.
    RABGEF1Q9UJ416EBI-413034,EBI-913954
    RNF11Q9Y3C52EBI-413034,EBI-396669
    RNF43Q68DV72EBI-413034,EBI-1647060
    SMURF2Q9HAU44EBI-413034,EBI-396727

    Protein-protein interaction databases

    BioGridi113162. 59 interactions.
    IntActiP0CG47. 66 interactions.
    MINTiMINT-8084593.

    Structurei

    3D structure databases

    ProteinModelPortaliP0CG47.
    SMRiP0CG47. Positions 1-227.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini1 – 7676Ubiquitin-like 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini77 – 15276Ubiquitin-like 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini153 – 22876Ubiquitin-like 3PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the ubiquitin family.Curated
    Contains 3 ubiquitin-like domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    KOiK04551.
    OMAiLTHRIKM.
    PhylomeDBiP0CG47.
    TreeFamiTF300820.

    Family and domain databases

    InterProiIPR019956. Ubiquitin.
    IPR000626. Ubiquitin-like.
    IPR029071. Ubiquitin-rel_dom.
    IPR019954. Ubiquitin_CS.
    [Graphical view]
    PfamiPF00240. ubiquitin. 3 hits.
    [Graphical view]
    PRINTSiPR00348. UBIQUITIN.
    SMARTiSM00213. UBQ. 3 hits.
    [Graphical view]
    SUPFAMiSSF54236. SSF54236. 3 hits.
    PROSITEiPS00299. UBIQUITIN_1. 3 hits.
    PS50053. UBIQUITIN_2. 3 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P0CG47-1 [UniParc]FASTAAdd to Basket

    « Hide

    MQIFVKTLTG KTITLEVEPS DTIENVKAKI QDKEGIPPDQ QRLIFAGKQL    50
    EDGRTLSDYN IQKESTLHLV LRLRGGMQIF VKTLTGKTIT LEVEPSDTIE 100
    NVKAKIQDKE GIPPDQQRLI FAGKQLEDGR TLSDYNIQKE STLHLVLRLR 150
    GGMQIFVKTL TGKTITLEVE PSDTIENVKA KIQDKEGIPP DQQRLIFAGK 200
    QLEDGRTLSD YNIQKESTLH LVLRLRGGC 229
    Length:229
    Mass (Da):25,762
    Last modified:August 10, 2010 - v1
    Checksum:i33011162F1C48BB1
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti76 – 229154GMQIF…LRGGC → YADLREDPDRQDHHPGSGAQ in UBB(+1); loss of polyubiquitination; impairs the ubiquitin-proteasome pathway; refractory to disassembly by DUBs; slow degradation by UCHL3.
    VAR_066248Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X04803 Genomic DNA. Translation: CAA28495.1.
    AB089617 Genomic DNA. Translation: BAC56955.1.
    AC093484 Genomic DNA. No translation available.
    BC000379 mRNA. Translation: AAH00379.1.
    BC009301 mRNA. Translation: AAH09301.1.
    BC015127 mRNA. Translation: AAH15127.1.
    BC026301 mRNA. Translation: AAH26301.1.
    BC031027 mRNA. Translation: AAH31027.1.
    BC046123 mRNA. Translation: AAH46123.1.
    CCDSiCCDS11177.1.
    PIRiA26437. UQHUB.
    RefSeqiNP_001268645.1. NM_001281716.1.
    NP_001268646.1. NM_001281717.1.
    NP_001268647.1. NM_001281718.1.
    NP_001268648.1. NM_001281719.1.
    NP_001268649.1. NM_001281720.1.
    NP_061828.1. NM_018955.3.
    UniGeneiHs.356190.
    Hs.730603.
    Hs.741549.

    Genome annotation databases

    EnsembliENST00000302182; ENSP00000304697; ENSG00000170315.
    ENST00000395837; ENSP00000379178; ENSG00000170315.
    ENST00000395839; ENSP00000379180; ENSG00000170315.
    GeneIDi7314.
    KEGGihsa:7314.
    UCSCiuc002gpx.3. human.

    Polymorphism databases

    DMDMi302595875.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X04803 Genomic DNA. Translation: CAA28495.1 .
    AB089617 Genomic DNA. Translation: BAC56955.1 .
    AC093484 Genomic DNA. No translation available.
    BC000379 mRNA. Translation: AAH00379.1 .
    BC009301 mRNA. Translation: AAH09301.1 .
    BC015127 mRNA. Translation: AAH15127.1 .
    BC026301 mRNA. Translation: AAH26301.1 .
    BC031027 mRNA. Translation: AAH31027.1 .
    BC046123 mRNA. Translation: AAH46123.1 .
    CCDSi CCDS11177.1.
    PIRi A26437. UQHUB.
    RefSeqi NP_001268645.1. NM_001281716.1.
    NP_001268646.1. NM_001281717.1.
    NP_001268647.1. NM_001281718.1.
    NP_001268648.1. NM_001281719.1.
    NP_001268649.1. NM_001281720.1.
    NP_061828.1. NM_018955.3.
    UniGenei Hs.356190.
    Hs.730603.
    Hs.741549.

    3D structure databases

    ProteinModelPortali P0CG47.
    SMRi P0CG47. Positions 1-227.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 113162. 59 interactions.
    IntActi P0CG47. 66 interactions.
    MINTi MINT-8084593.

    PTM databases

    PhosphoSitei P0CG47.

    Polymorphism databases

    DMDMi 302595875.

    Proteomic databases

    MaxQBi P0CG47.
    PRIDEi P0CG47.

    Protocols and materials databases

    DNASUi 7314.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000302182 ; ENSP00000304697 ; ENSG00000170315 .
    ENST00000395837 ; ENSP00000379178 ; ENSG00000170315 .
    ENST00000395839 ; ENSP00000379180 ; ENSG00000170315 .
    GeneIDi 7314.
    KEGGi hsa:7314.
    UCSCi uc002gpx.3. human.

    Organism-specific databases

    CTDi 7314.
    GeneCardsi GC17P016301.
    HGNCi HGNC:12463. UBB.
    HPAi CAB013048.
    HPA041344.
    HPA049132.
    MIMi 191339. gene.
    neXtProti NX_P0CG47.
    GenAtlasi Search...

    Phylogenomic databases

    KOi K04551.
    OMAi LTHRIKM.
    PhylomeDBi P0CG47.
    TreeFami TF300820.

    Enzyme and pathway databases

    Reactomei REACT_111080. Spry regulation of FGF signaling.
    REACT_111178. ER-Phagosome pathway.
    REACT_111184. Negative regulation of FGFR signaling.
    REACT_1156. Orc1 removal from chromatin.
    REACT_115662. Downregulation of ERBB2:ERBB3 signaling.
    REACT_115755. Signaling by ERBB2.
    REACT_115828. Downregulation of ERBB4 signaling.
    REACT_115831. ISG15 antiviral mechanism.
    REACT_115852. Signaling by constitutively active EGFR.
    REACT_115893. Membrane binding and targetting of GAG proteins.
    REACT_1181. Association of licensing factors with the pre-replicative complex.
    REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_118656. Activation of NF-kappaB in B cells.
    REACT_118780. NOTCH1 Intracellular Domain Regulates Transcription.
    REACT_120726. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
    REACT_120727. Downregulation of TGF-beta receptor signaling.
    REACT_120734. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
    REACT_120916. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
    REACT_121111. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
    REACT_1221. CDK-mediated phosphorylation and removal of Cdc6.
    REACT_12484. EGFR downregulation.
    REACT_12555. Downstream TCR signaling.
    REACT_13415. p75NTR recruits signalling complexes.
    REACT_13464. Regulation of activated PAK-2p34 by proteasome mediated degradation.
    REACT_13643. NRIF signals cell death from the nucleus.
    REACT_13696. NF-kB is activated and signals survival.
    REACT_150471. Separation of Sister Chromatids.
    REACT_160089. Constitutive Signaling by NOTCH1 HD Domain Mutants.
    REACT_160189. Stimuli-sensing channels.
    REACT_160205. NOTCH2 Activation and Transmission of Signal to the Nucleus.
    REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
    REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
    REACT_160315. Regulation of PLK1 Activity at G2/M Transition.
    REACT_1614. Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
    REACT_163977. Regulation of innate immune responses to cytosolic DNA.
    REACT_163994. FCERI mediated NF-kB activation.
    REACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169208. Glycogen synthesis.
    REACT_169325. Oncogene Induced Senescence.
    REACT_169436. Oxidative Stress Induced Senescence.
    REACT_172638. Asymmetric localization of PCP proteins.
    REACT_18265. Regulation of the Fanconi anemia pathway.
    REACT_18410. Fanconi Anemia pathway.
    REACT_1949. CDT1 association with the CDC6:ORC:origin complex.
    REACT_199384. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_200716. regulation of FZD by ubiquitination.
    REACT_200731. deactivation of the beta-catenin transactivating complex.
    REACT_200766. degradation of AXIN.
    REACT_200777. TCF dependent signaling in response to WNT.
    REACT_200783. Myoclonic epilepsy of Lafora.
    REACT_200841. degradation of DVL.
    REACT_20549. Autodegradation of the E3 ubiquitin ligase COP1.
    REACT_21281. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
    REACT_21368. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
    REACT_21399. activated TAK1 mediates p38 MAPK activation.
    REACT_22442. Interleukin-1 signaling.
    REACT_225574. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_23787. Regulation of signaling by CBL.
    REACT_24918. IRAK1 recruits IKK complex.
    REACT_24941. Circadian Clock.
    REACT_25018. IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
    REACT_25120. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
    REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
    REACT_25271. Negative regulators of RIG-I/MDA5 signaling.
    REACT_25325. AUF1 (hnRNP D0) destabilizes mRNA.
    REACT_25351. TRAF6 mediated induction of TAK1 complex.
    REACT_25354. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
    REACT_25359. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.
    REACT_25374. IKK complex recruitment mediated by RIP1.
    REACT_25380. IRAK2 mediated activation of TAK1 complex.
    REACT_27258. Endosomal Sorting Complex Required For Transport (ESCRT).
    REACT_4. Ubiquitin-dependent degradation of Cyclin D1.
    REACT_6359. Budding and maturation of HIV virion.
    REACT_6761. APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
    REACT_6785. Autodegradation of Cdh1 by Cdh1:APC/C.
    REACT_6818. Assembly Of The HIV Virion.
    REACT_6820. APC/C:Cdc20 mediated degradation of Cyclin B.
    REACT_6821. SCF-beta-TrCP mediated degradation of Emi1.
    REACT_6871. APC/C:Cdc20 mediated degradation of Securin.
    REACT_75776. NOD1/2 Signaling Pathway.
    REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
    REACT_821. Cyclin D associated events in G1.
    REACT_9003. SCF(Skp2)-mediated degradation of p27/p21.
    REACT_9031. Vpu mediated degradation of CD4.
    REACT_9453. Vif-mediated degradation of APOBEC3G.

    Miscellaneous databases

    ChiTaRSi UBB. human.
    GeneWikii Ubiquitin_B.
    GenomeRNAii 7314.
    NextBioi 28592.
    PROi P0CG47.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P0CG47.
    Bgeei P0CG47.

    Family and domain databases

    InterProi IPR019956. Ubiquitin.
    IPR000626. Ubiquitin-like.
    IPR029071. Ubiquitin-rel_dom.
    IPR019954. Ubiquitin_CS.
    [Graphical view ]
    Pfami PF00240. ubiquitin. 3 hits.
    [Graphical view ]
    PRINTSi PR00348. UBIQUITIN.
    SMARTi SM00213. UBQ. 3 hits.
    [Graphical view ]
    SUPFAMi SSF54236. SSF54236. 3 hits.
    PROSITEi PS00299. UBIQUITIN_1. 3 hits.
    PS50053. UBIQUITIN_2. 3 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The human ubiquitin gene family: structure of a gene and pseudogenes from the Ub B subfamily."
      Baker R.T., Board P.G.
      Nucleic Acids Res. 15:443-463(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Blood.
    2. "Lineage-specific homogenization of the polyubiquitin gene among human and great apes."
      Tachikui H., Saitou N., Nakajima T., Hayasaka I., Ishida T., Inoue I.
      J. Mol. Evol. 57:737-744(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
      Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
      , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
      Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
      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].
      Tissue: Brain, Liver and Lung.
    5. Lubec G., Chen W.-Q., Sun Y.
      Submitted (DEC-2008) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 1-27; 30-42 AND 55-72, IDENTIFICATION BY MASS SPECTROMETRY.
      Tissue: Fetal brain cortex.
    6. "Molecular conservation of 74 amino acid sequence of ubiquitin between cattle and man."
      Schlesinger D.H., Goldstein G.
      Nature 255:423-424(1975) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1-74.
    7. "Alzheimer disease-specific conformation of hyperphosphorylated paired helical filament-tau is polyubiquitinated through Lys-48, Lys-11, and Lys-6 ubiquitin conjugation."
      Cripps D., Thomas S.N., Jeng Y., Yang F., Davies P., Yang A.J.
      J. Biol. Chem. 281:10825-10838(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1-27 AND 43-54, UBIQUITINATION AT LYS-6; LYS-11 AND LYS-48, IDENTIFICATION BY MASS SPECTROMETRY.
    8. "Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain."
      Huang F., Kirkpatrick D., Jiang X., Gygi S.P., Sorkin A.
      Mol. Cell 21:737-748(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, UBIQUITINATION AT LYS-11; LYS-29; LYS-48 AND LYS-63, IDENTIFICATION BY MASS SPECTROMETRY.
    9. "Functional regulation of FEZ1 by the U-box-type ubiquitin ligase E4B contributes to neuritogenesis."
      Okumura F., Hatakeyama S., Matsumoto M., Kamura T., Nakayama K.
      J. Biol. Chem. 279:53533-53543(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION AT LYS-27.
    10. "The proteomic reactor facilitates the analysis of affinity-purified proteins by mass spectrometry: application for identifying ubiquitinated proteins in human cells."
      Vasilescu J., Zweitzig D.R., Denis N.J., Smith J.C., Ethier M., Haines D.S., Figeys D.
      J. Proteome Res. 6:298-305(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-48.
      Tissue: Lung adenocarcinoma.
    11. "Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks."
      Motegi A., Liaw H.-J., Lee K.-Y., Roest H.P., Maas A., Wu X., Moinova H., Markowitz S.D., Ding H., Hoeijmakers J.H.J., Myung K.
      Proc. Natl. Acad. Sci. U.S.A. 105:12411-12416(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION AT LYS-63, MUTAGENESIS OF LYS-48 AND LYS-63.
    12. "The emerging complexity of protein ubiquitination."
      Komander D.
      Biochem. Soc. Trans. 37:937-953(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW, FUNCTION.
    13. "Mutant ubiquitin (UBB(+1)) associated with neurodegenerative disorders is hydrolyzed by ubiquitin C-terminal hydrolase L3 (UCH-L3)."
      Dennissen F.J., Kholod N., Hermes D.J., Kemmerling N., Steinbusch H.W., Dantuma N.P., van Leeuwen F.W.
      FEBS Lett. 585:2568-2574(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: CLEAVAGE BY UCHL3 (VARIANT UBB(+1)).
    14. Cited for: IDENTIFICATION OF VARIANT UBB(+1).
    15. "Disease-specific accumulation of mutant ubiquitin as a marker for proteasomal dysfunction in the brain."
      Fischer D.F., De Vos R.A., Van Dijk R., De Vrij F.M., Proper E.A., Sonnemans M.A., Verhage M.C., Sluijs J.A., Hobo B., Zouambia M., Steur E.N., Kamphorst W., Hol E.M., Van Leeuwen F.W.
      FASEB J. 17:2014-2024(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY (VARIANT UBB(+1)).
    16. Cited for: PHOSPHORYLATION AT SER-65, MUTAGENESIS OF SER-65.

    Entry informationi

    Entry nameiUBB_HUMAN
    AccessioniPrimary (citable) accession number: P0CG47
    Secondary accession number(s): P02248
    , P02249, P02250, P62988, Q29120, Q6LBL4, Q6LDU5, Q8WYN8, Q91887, Q91888, Q9BWD6, Q9BX98, Q9UEF2, Q9UEG1, Q9UEK8, Q9UPK7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 10, 2010
    Last sequence update: August 10, 2010
    Last modified: October 1, 2014
    This is version 46 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

    Miscellaneous

    Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.
    The mRNA encoding variant UBB(+1) is produced by an unknown mechanism involving the deletion of a GT dinucleotide in the close proximity of a GAGAG motif (PubMed:9422699). This variant mRNA is found in normal brain, but the encoded protein accumulates only in brain neurofibrillary tangles and neuritic plaques in Alzheimer disease and other tauopathies, as well as polyglutaminopathies (PubMed:14597671). UBB(+1) variant cannot be used for polyubiquitination, is not effectively degraded by the proteasome when ubiquitinated and ubiquitinated UBB(+1) is refractory to disassembly by deubiquitinating enzymes (DUBs). In healthy brain, UBB(+1) C-terminus can be cleaved by UCHL3 (PubMed:21762696).3 Publications
    For a better understanding, features related to ubiquitin are only indicated for the first chain.

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: 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. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3