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	PROSITE documentation PDOC00463

Ubiquitin-activating enzyme (E1 enzyme) [1,2] activates ubiquitin by first adenylating with ATP its C-terminal glycine residue and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding an ubiquitin-E1 thiolester and free AMP. Later the ubiquitin moiety is transferred to a cysteine residue on one of the many forms of ubiquitin-conjugating enzymes (E2).

E1 is a large monomeric protein of about 110 to 115 Kd (about 1000 residues). In yeast there are two forms (UBA1 and UBA2) [3], while in plants and mammals multiple forms exist including a form which is Y-linked in mouse and some other mammals and which may be involved in spermatogenesis.

It has been shown [4] that the last of the five cysteines that are conserved in the sequence of E1 from various species is the one that binds ubiquitin. We have developed two patterns specific for E1, the first pattern contains the second of the five conserved cysteines while the second pattern includes the active site cysteine.

Last update:

December 2004 / Patterns and text revised.

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

UBIQUITIN_ACTIVAT_1, PS00536; Ubiquitin-activating enzyme signature 1  (PATTERN)

• Consensus pattern:
  K-[AI]-[CL]-S-G-K-[FI]-x-[PQ]
• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 31
  • detected by PS00536: 15 (true positives)
  • undetected by PS00536: 16 (14 false negatives and 2 'partials')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS00536:
  NONE.
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00536
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00536
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS00536
• View ligand binding statistics of PS00536
• Matching PDB structures: 1Y8Q 1Y8R 3CMM 3KYC ... [ALL]

UBIQUITIN_ACTIVAT_2, PS00865; Ubiquitin-activating enzyme active site  (PATTERN)

• Consensus pattern:
  P-[LIVMG]-C-T-[LIVM]-[KRHA]-x-[FTNM]-P
  C is the active site residue
• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 39
  • detected by PS00865: 36 (true positives)
  • undetected by PS00865: 3 (3 false negatives and 0 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS00865:
  NONE.
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00865
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00865
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS00865
• View ligand binding statistics of PS00865
• Matching PDB structures: 1TT5 1YOV 1Z7L 2NVU ... [ALL]

1	Authors	Jentsch S., Seufert W., Hauser H.-P.
	Title	Genetic analysis of the ubiquitin system.
	Source	Biochim. Biophys. Acta 1089:127-139(1991).
	PubMed ID	1647207

2	Authors	Hershko A.
	Title	The ubiquitin pathway for protein degradation.
	Source	Trends Biochem. Sci. 16:265-268(1991).
	PubMed ID	1656558

3	Authors	Dohmen R.J., Stappen R., McGrath J.P., Forrova H., Kolarov J., Goffeau A., Varshavsky A.
	Title	An essential yeast gene encoding a homolog of ubiquitin-activating enzyme.
	Source	J. Biol. Chem. 270:18099-18109(1995).
	PubMed ID	7629121

4	Authors	Hatfield P.M., Vierstra R.D.
	Title	Multiple forms of ubiquitin-activating enzyme E1 from wheat. Identification of an essential cysteine by in vitro mutagenesis.
	Source	J. Biol. Chem. 267:14799-14803(1992).
	PubMed ID	1634524

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