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. (updated: Dec. 11, 2019)

Protein identification was indicated in the following studies:

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

Publication	Identification ¹	Uniprot mapping ²	Not mapped / Obsolete	TrEMBL	Swiss-Prot
Goodman (2013)	2289 (gene list)	2278	53	20599	2269
Lange (2014)	1234	1234	7	28	1224
Hegedus (2015)	2638	2622	0	235	2387
Wilson (2016)	1658	1528	170	291	1068
d'Alessandro (2017)	1826	1817	2	0	1815
Bryk (2017)	2090	2060	10	108	1942
Chu (2018)	1853	1804	55	362	1387

¹ as available in the article and/or in supplementary material
² uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Protein sequence (FASTA)

Protein coevolution profile (FreeContact)

Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology.

Total structural coverage: 100%

Model score: 99

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Biological Process

Activation of MAPK activity

Aggrephagy

Amyloid fibril formation

Anaphase-promoting complex-dependent catabolic process

Antigen processing and presentation of exogenous peptide antigen via MHC class I

Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent

Antigen processing and presentation of peptide antigen via MHC class I

Apoptotic process

Apoptotic signaling pathway

Carbohydrate metabolic process

Cellular iron ion homeostasis

Cellular protein metabolic process

Cellular response to hypoxia

Circadian rhythm

Cytokine-mediated signaling pathway

Cytoplasmic pattern recognition receptor signaling pathway

DNA damage response, detection of DNA damage

DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest

DNA repair

Endoplasmic reticulum mannose trimming

Endosomal transport

Energy homeostasis

Entry of bacterium into host cell

Epidermal growth factor receptor signaling pathway

ERBB2 signaling pathway

Error-free translesion synthesis

Error-prone translesion synthesis

Fat pad development

Fc-epsilon receptor signaling pathway

Female gonad development

Female meiosis I

Fibroblast growth factor receptor signaling pathway

G1/S transition of mitotic cell cycle

G2/M transition of mitotic cell cycle

Gene expression

Global genome nucleotide-excision repair

Glucose metabolic process

Glycogen biosynthetic process

Hypothalamus gonadotrophin-releasing hormone neuron development

I-kappaB kinase/NF-kappaB signaling

Innate immune response

Interleukin-1-mediated signaling pathway

Interstrand cross-link repair

Intracellular transport of virus

Ion transmembrane transport

JNK cascade

Macroautophagy

Male meiosis I

MAPK cascade

Membrane organization

Mitochondrion transport along microtubule

Mitotic cell cycle

Modification-dependent protein catabolic process

Modulation by symbiont of host defense response

MyD88-dependent toll-like receptor signaling pathway

MyD88-independent toll-like receptor signaling pathway

Negative regulation of apoptotic process

Negative regulation of canonical Wnt signaling pathway

Negative regulation of epidermal growth factor receptor signaling pathway

Negative regulation of G2/M transition of mitotic cell cycle

Negative regulation of Notch signaling pathway

Negative regulation of transcription by RNA polymerase II

Negative regulation of transforming growth factor beta receptor signaling pathway

Negative regulation of type I interferon production

Neuron projection morphogenesis

Neurotrophin TRK receptor signaling pathway

NIK/NF-kappaB signaling

Notch receptor processing

Notch signaling pathway

Nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Nucleotide-binding oligomerization domain containing signaling pathway

Nucleotide-excision repair, DNA damage recognition

Nucleotide-excision repair, DNA duplex unwinding

Nucleotide-excision repair, DNA gap filling

Nucleotide-excision repair, DNA incision

Nucleotide-excision repair, DNA incision, 5'-to lesion

Nucleotide-excision repair, preincision complex assembly

Obsolete negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle

Obsolete positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition

Obsolete regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle

Pathogenesis

Positive regulation of apoptotic process

Positive regulation of canonical Wnt signaling pathway

Positive regulation of epidermal growth factor receptor signaling pathway

Positive regulation of I-kappaB kinase/NF-kappaB signaling

Positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator

Positive regulation of NF-kappaB transcription factor activity

Positive regulation of protein monoubiquitination

Positive regulation of protein ubiquitination

Positive regulation of transcription by RNA polymerase II

Positive regulation of type I interferon production

Pre-replicative complex assembly

Proteasome-mediated ubiquitin-dependent protein catabolic process

Protein deubiquitination

Protein folding

Protein localization

Protein polyubiquitination

Protein targeting to peroxisome

Protein ubiquitination

Protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Regulation of apoptotic process

Regulation of exit from mitosis

Regulation of hematopoietic stem cell differentiation

Regulation of mitochondrial membrane potential

Regulation of mRNA stability

Regulation of necroptotic process

Regulation of neuron death

Regulation of proteasomal protein catabolic process

Regulation of signal transduction by p53 class mediator

Regulation of transcription from RNA polymerase II promoter in response to hypoxia

Regulation of tumor necrosis factor-mediated signaling pathway

Regulation of type I interferon production

SCF-dependent proteasomal ubiquitin-dependent protein catabolic process

Seminiferous tubule development

Small molecule metabolic process

Stimulatory C-type lectin receptor signaling pathway

Stress-activated MAPK cascade

T cell receptor signaling pathway

Toll-like receptor 10 signaling pathway

Toll-like receptor 2 signaling pathway

Toll-like receptor 3 signaling pathway

Toll-like receptor 4 signaling pathway

Toll-like receptor 5 signaling pathway

Toll-like receptor 9 signaling pathway

Toll-like receptor signaling pathway

Toll-like receptor TLR1:TLR2 signaling pathway

Toll-like receptor TLR6:TLR2 signaling pathway

Transcription initiation from RNA polymerase II promoter

Transcription, DNA-templated

Transcription-coupled nucleotide-excision repair

Transforming growth factor beta receptor signaling pathway

Translesion synthesis

Transmembrane transport

TRIF-dependent toll-like receptor signaling pathway

Tumor necrosis factor-mediated signaling pathway

Viral life cycle

Viral process

Viral protein processing

Viral translation

Virion assembly

Wnt signaling pathway

Wnt signaling pathway, planar cell polarity pathway

Cellular Component

Cytoplasm

Cytosol

Endocytic vesicle membrane

Endoplasmic reticulum membrane

Endoplasmic reticulum quality control compartment

Endosome membrane

Extracellular exosome

Extracellular space

Host cell

Mitochondrial outer membrane

Mitochondrion

Myelin sheath

Neuron projection

Neuronal cell body

Nucleoplasm

Nucleus

Plasma membrane

Vesicle

Molecular Function

Protein tag

Ubiquitin protein ligase binding

The reference OMIM entry for this protein is 191339

Ubiquitin b; ubb
Polyubiquitin b

DESCRIPTION

Ubiquitin, a small protein consisting of 76 amino acids, has been found in all eukaryotic cells studied. It is one of the most conserved proteins known; the amino acid sequence is identical from insects to humans, and there are only 3 substitutions within the plant and yeast sequences. Two classes of ubiquitin genes are recognized. Class I is a polyubiquitin gene, such as UBB or UBC (191340), encoding a polyprotein of tandemly repeated ubiquitins. The class II genes are fusion products between a single ubiquitin gene and 1 of 2 other possible sequences, either 52 or 76 to 80 predominantly basic amino acids (see UBA52, 191321, and UBA80, 191343, respectively). Ubiquitin is required for ATP-dependent, nonlysosomal intracellular protein degradation, which eliminates most intracellular defective problems as well as normal proteins with a rapid turnover. Degradation involves covalent binding of ubiquitin to the protein to be degraded, through isopeptide bonds from the C-terminal glycine residue to the epsilon-amino groups of lysyl side chains. Presumably, the function of ubiquitin is to label the protein for disposal by intracellular proteases. The most abundant ubiquitin-protein conjugate, however, is ubiquitin-H2A, in which ubiquitin is bound to lys119 in histone H2A; this conjugate is not degraded. Since such ubiquitinated histones are present primarily in actively transcribed chromosomal regions, ubiquitin may play a role in regulation of gene expression (summary by Wiborg et al. (1985) and Baker and Board (1987)).

CLONING

Wiborg et al. (1985) determined that ubiquitin is encoded as a multigene family. Baker and Board (1987) studied cDNA and genomic clones of ubiquitin.

MAPPING

By in situ hybridization, Webb et al. (1990) assigned the 3-coding unit polyubiquitin gene UBB and its nonprocessed pseudogene to chromosome 17p12-p11.1.

GENE FUNCTION

Finley et al. (1989) demonstrated that the basic amino acids fused to ubiquitin in the class II gene products represent ribosomal proteins, and that their fusion to ubiquitin performs a crucial role in ribosome biogenesis in the Saccharomyces cerevisiae. Redman and Rechsteiner (1989) studied these 3-prime in-frame extensions of the ubiquitin genes in mammalian systems and concluded, as did Finley et al. (1989), that the C-terminal extension proteins are ribosomal components. Sutovsky et al. (1999) demonstrated that sperm mitochondria are selectively marked for destruction by a ubiquitin tag. In fertilized eggs from rhesus monkeys and cows the ubiquitination was evident at first mitosis. The signal typically disappeared between the 4-cell and the 8-cell stages of development. This ubiquitination also occurs in the male reproductive tract, but the ubiquitinated sites are masked by disulfide bonds during passage through the epididymis. Conaway et al. (2002) reviewed the role of ubiquitin in transcription regulation in both proteasome-dependent and proteasome-independent mechanisms. Cui et al. (2010) showed that Cif homolog from Burkholderia pseudomallei (CHBP) was a potent inhibitor of the eukaryotic ubiquitination pathway in human cells. CHBP acted as a deamidase that specifically and efficiently deamidated gln40 in ubiquitin and ubiquitin-like protein NEDD8 (603171) both in vitro and during Burkholderia infection. Deamidated ubiquitin was impaired in supporting ubiquitin-chain synthesis. Cif selectively deamidated NEDD8, which abolished the acti ... More on the omim web site

Subscribe to this protein entry history

Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for UBB

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 191339 was added.

Polyubiquitin-B (UBB)