PROSITE documentation PDOC00271
Ubiquitin domain signature and profile


Ubiquitin [1,2,3] is a protein of seventy six amino acid residues, found in all eukaryotic cells and whose sequence is extremely well conserved from protozoan to vertebrates. It plays a key role in a variety of cellular processes, such as ATP-dependent selective degradation of cellular proteins, maintenance of chromatin structure, regulation of gene expression, stress response and ribosome biogenesis.

In most species, there are many genes coding for ubiquitin. However they can be classified into two classes. The first class produces polyubiquitin molecules consisting of exact head to tail repeats of ubiquitin. The number of repeats is variable (up to twelve in a Xenopus gene). In the majority of polyubiquitin precursors, there is a final amino-acid after the last repeat. The second class of genes produces precursor proteins consisting of a single copy of ubiquitin fused to a C-terminal extension protein (CEP). There are two types of CEP proteins and both seem to be ribosomal proteins.

Ubiquitin is a globular protein, the last four C-terminal residues (Leu-Arg-Gly-Gly) extending from the compact structure to form a 'tail', important for its function. The latter is mediated by the covalent conjugation of ubiquitin to target proteins, by an isopeptide linkage between the C-terminal glycine and the epsilon amino group of lysine residues in the target proteins.

There are a number of proteins which are evolutionary related to ubiquitin:

  • Ubiquitin-like proteins from baculoviruses as well as in some strains of bovine viral diarrhea viruses (BVDV). These proteins are highly similar to their eukaryotic counterparts.
  • Mammalian protein GDX [4]. GDX is composed of two domains, a N-terminal ubiquitin-like domain of 74 residues and a C-terminal domain of 83 residues with some similarity with the thyroglobulin hormonogenic site.
  • Mammalian protein FAU [5]. FAU is a fusion protein which consist of a N-terminal ubiquitin-like protein of 74 residues fused to ribosomal protein S30.
  • Mouse protein NEDD-8 [6], a ubiquitin-like protein of 81 residues.
  • Human protein BAT3, a large fusion protein of 1132 residues that contains a N-terminal ubiquitin-like domain.
  • Caenorhabditis elegans protein ubl-1 [7]. Ubl-1 is a fusion protein which consist of a N-terminal ubiquitin-like protein of 70 residues fused to ribosomal protein S27A.
  • Yeast DNA repair protein RAD23 [8]. RAD23 contains a N-terminal domain that seems to be distantly, yet significantly, related to ubiquitin.
  • Mammalian RAD23-related proteins RAD23A and RAD23B.
  • Mammalian BCL-2 binding athanogene-1 (BAG-1). BAG-1 is a protein of 274 residues that contains a central ubiquitin-like domain.
  • Human spliceosome associated protein 114 (SAP 114 or SF3A120).
  • Yeast protein DSK2, a protein involved in spindle pole body duplication and which contains a N-terminal ubiquitin-like domain.
  • Human protein CKAP1/TFCB, Schizosaccharomyces pombe protein alp11 and Caenorhabditis elegans hypothetical protein F53F4.3. These proteins contain a N-terminal ubiquitin domain and a C-terminal CAP-Gly domain (see <PDOC00660>).
  • Schizosaccharomyces pombe hypothetical protein SpAC26A3.16. This protein contains a N-terminal ubiquitin domain.
  • Yeast protein SMT3.
  • Human ubiquitin-like proteins SMT3A and SMT3B.
  • Human ubiquitin-like protein SMT3C (also known as PIC1; Ubl1, Sumo-1; Gmp-1 or Sentrin). This protein is involved in targeting ranGAP1 to the nuclear pore complex protein ranBP2.
  • SMT3-like proteins in plants and Caenorhabditis elegans.

To identify ubiquitin and related proteins we have developed a pattern based on conserved positions in the central section of the sequence. A profile was also developed that spans the complete length of the ubiquitin domain.

Last update:

December 2004 / Pattern and text revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

UBIQUITIN_2, PS50053; Ubiquitin domain profile  (MATRIX)

UBIQUITIN_1, PS00299; Ubiquitin domain signature  (PATTERN)


1AuthorsJentsch S. Seufert W. Hauser H.-P.
TitleGenetic analysis of the ubiquitin system.
SourceBiochim. Biophys. Acta 1089:127-139(1991).
PubMed ID1647207

2AuthorsMonia B.P. Ecker D.J. Croke S.T.
SourceBio/Technology 8:209-215(1990).

3AuthorsFinley D. Varshavsky A.
SourceTrends Biochem. Sci. 10:343-347(1985).

4AuthorsFilippi M. Tribioli C. Toniolo D.
TitleLinkage and sequence conservation of the X-linked genes DXS253E (P3) and DXS254E (GdX) in mouse and man.
SourceGenomics 7:453-457(1990).
PubMed ID1973144

5AuthorsOlvera J. Wool I.G.
TitleThe carboxyl extension of a ubiquitin-like protein is rat ribosomal protein S30.
SourceJ. Biol. Chem. 268:17967-17974(1993).
PubMed ID8394356

6AuthorsKumar S. Yoshida Y. Noda M.
TitleCloning of a cDNA which encodes a novel ubiquitin-like protein.
SourceBiochem. Biophys. Res. Commun. 195:393-399(1993).
PubMed ID8395831

7AuthorsJones D. Candido E.P.
TitleNovel ubiquitin-like ribosomal protein fusion genes from the nematodes Caenorhabditis elegans and Caenorhabditis briggsae.
SourceJ. Biol. Chem. 268:19545-19551(1993).
PubMed ID7690036

8AuthorsMelnick L. Sherman F.
TitleThe gene clusters ARC and COR on chromosomes 5 and 10, respectively, of Saccharomyces cerevisiae share a common ancestry.
SourceJ. Mol. Biol. 233:372-388(1993).
PubMed ID8411151

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