P0CG47 · UBB_HUMAN
- ProteinPolyubiquitin-B
- GeneUBB
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids229 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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 proteotoxic stress response and cell cycle; 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.
Miscellaneous
Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins eL40 and eS31, 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).
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).
For a better understanding, features related to ubiquitin are only indicated for the first chain.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 54 | Interacts with activating enzyme | ||||
Sequence: R | ||||||
Site | 68 | Essential for function | ||||
Sequence: H | ||||||
Site | 72 | Interacts with activating enzyme | ||||
Sequence: R |
GO annotations
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended namePolyubiquitin-B
- Cleaved into 1 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP0CG47
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Ubiquitin
Mitochondrion outer membrane ; Peripheral membrane protein
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 48 | No effect on HLTF-mediated polyubiquitination of PCNA. | ||||
Sequence: K → R | ||||||
Mutagenesis | 63 | Abolishes HLTF-mediated polyubiquitination of PCNA. | ||||
Sequence: K → R | ||||||
Mutagenesis | 65 | Prevents phosphorylation in case of mitophagy. Decreased localization of PRKN to mitochondria. | ||||
Sequence: S → A | ||||||
Mutagenesis | 65 | Phosphomimetic mutant that binds and activates PRKN. | ||||
Sequence: S → D | ||||||
Mutagenesis | 65 | Phosphomimetic mutant that binds and activates PRKN. | ||||
Sequence: S → E | ||||||
Mutagenesis | 68 | Loss of DTX3L-mediated polyubiquitination of histone H3 and H4. | ||||
Sequence: H → G | ||||||
Mutagenesis | 72 | No effect on ADP-ribosylation. | ||||
Sequence: R → G | ||||||
Mutagenesis | 72 | No effect on ADP-ribosylation, when associated with K-74. | ||||
Sequence: R → K | ||||||
Mutagenesis | 74 | No effect on ADP-ribosylation. | ||||
Sequence: R → G | ||||||
Mutagenesis | 74 | No effect on ADP-ribosylation, when associated with K-72. | ||||
Sequence: R → K | ||||||
Mutagenesis | 76 | Loss of ADP-ribosylation. | ||||
Sequence: G → A | ||||||
Natural variant | VAR_066248 | 76-229 | in UBB(+1); loss of polyubiquitination; impairs the ubiquitin-proteasome pathway; refractory to disassembly by DUBs; slow degradation by UCHL3 | |||
Sequence: GMQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGGMQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGGC → YADLREDPDRQDHHPGSGAQ |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 162 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, cross-link, modified residue (large scale data), modified residue, propeptide.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000396174 | 1-76 | UniProt | Ubiquitin | |||
Sequence: MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG | |||||||
Cross-link | 6 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Cross-link | 11 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 12 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 14 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 20 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 22 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Cross-link | 27 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Cross-link | 29 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Cross-link | 33 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Cross-link | 48 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 55 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 57 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 63 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Modified residue | 65 | UniProt | Phosphoserine; by PINK1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 65 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 66 | UniProt | (Microbial infection) ADP-ribosylthreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 66 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 76 | UniProt | ADP-ribosylglycine | ||||
Sequence: G | |||||||
Cross-link | 76 | UniProt | Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins) | ||||
Sequence: G | |||||||
Chain | PRO_0000396175 | 77-152 | UniProt | Ubiquitin | |||
Sequence: MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG | |||||||
Modified residue (large scale data) | 88 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 90 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 96 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 98 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 131 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 133 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 141 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 142 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Chain | PRO_0000396176 | 153-228 | UniProt | Ubiquitin | |||
Sequence: MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG | |||||||
Modified residue (large scale data) | 164 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 166 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 172 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 174 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 207 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 209 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 217 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 218 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Propeptide | PRO_0000396177 | 229 | UniProt | ||||
Sequence: C |
Post-translational modification
Ubiquitin
Phosphorylated at Ser-65 by PINK1 during mitophagy (PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25527291, PubMed:26161729).
Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy (PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25527291, PubMed:26161729).
Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30 (PubMed:25527291).
Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy (PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25527291, PubMed:26161729).
Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30 (PubMed:25527291).
Ubiquitin
Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones.
Ubiquitin
(Microbial infection) Mono-ADP-ribosylated at Thr-66 by the C.violaceum CteC virulence factor. ADP-ribosylation causes the shutdown of polyubiquitin synthesis and disrupts the recognition and reversal of polyubiquitin.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Interacts with SKP1-KMD2A and SKP1-KMD2B complexes.
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1-76 | Ubiquitin-like 1 | ||||
Sequence: MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG | ||||||
Domain | 77-152 | Ubiquitin-like 2 | ||||
Sequence: MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG | ||||||
Domain | 153-228 | Ubiquitin-like 3 | ||||
Sequence: MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG |
Sequence similarities
Belongs to the ubiquitin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length229
- Mass (Da)25,762
- Last updated2010-08-10 v1
- Checksum33011162F1C48BB1
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X04803 EMBL· GenBank· DDBJ | CAA28495.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AB089617 EMBL· GenBank· DDBJ | BAC56955.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC093484 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC000379 EMBL· GenBank· DDBJ | AAH00379.1 EMBL· GenBank· DDBJ | mRNA | ||
BC009301 EMBL· GenBank· DDBJ | AAH09301.1 EMBL· GenBank· DDBJ | mRNA | ||
BC015127 EMBL· GenBank· DDBJ | AAH15127.1 EMBL· GenBank· DDBJ | mRNA | ||
BC026301 EMBL· GenBank· DDBJ | AAH26301.1 EMBL· GenBank· DDBJ | mRNA | ||
BC031027 EMBL· GenBank· DDBJ | AAH31027.1 EMBL· GenBank· DDBJ | mRNA | ||
BC046123 EMBL· GenBank· DDBJ | AAH46123.1 EMBL· GenBank· DDBJ | mRNA |