Ubiquitin-like modifier-activating enzyme 6 (UBA6)

The protein contains 1052 amino acids for an estimated molecular weight of 117970 Da.

 

Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Specific for ubiquitin, does not activate ubiquitin-like peptides. Differs from UBE1 in its specificity for substrate E2 charging. Does not charge cell cycle E2s, such as CDC34. Essential for embryonic development. Required for UBD/FAT10 conjugation. Isoform 2 may play a key role in ubiquitin system and may influence spermatogenesis and male fertility. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

This protein is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 95%
Model score: 42

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VariantDescription
dbSNP:rs10010188

The reference OMIM entry for this protein is 611361

Ubiquitin-activating enzyme e1-like 2; ube1l2
Ubiquitin-activating enzyme 6; uba6

DESCRIPTION

Modification of proteins with ubiquitin (UBB; 191339) or ubiquitin-like proteins controls many signaling networks and requires a ubiquitin-activating enzyme (E1), a ubiquitin conjugating enzyme (E2), and a ubiquitin protein ligase (E3). UBE1L2 is an E1 enzyme that initiates the activation and conjugation of ubiquitin-like proteins (Jin et al., 2007).

CLONING

Using the ThiF-homology motif of E1 enzymes as query, Jin et al. (2007) identified UBE1L2, which they called UBA6. The deduced 1,052-amino acid protein contains an N-terminal adenylation domain with 2 ThiF-homology regions, a catalytic cysteine domain, and a C-terminal ubiquitin-fold domain that functions to recruit E2s. UBE1L2 shares approximately 40% overall sequence identity with UBE1 (314370). Database analysis revealed wide expression of UBE1L2 in human tissues and cell lines. Jin et al. (2007) found orthologs of UBE1L2 in vertebrates and the echinoderm sea urchin, but not in insects, worms, fungi, or plants.

GENE FUNCTION

Jin et al. (2007) showed that UBE1L2 activated ubiquitin but not other ubiquitin-like proteins in vitro and in vivo. UBE1L2 charged a number of E2 substrates with ubiquitin, but its substrate specificity was different from that of UBE1. UBA6 specifically charged USE1 (611362), but it did not charge the cell cycle E2s CDC34A and CDC34B (see 116948), which were good substrates for UBE1. The difference in substrate specificity between UBA6 and UBE1 was due to their distinct C-terminal ubiquitin-fold domains. Chiu et al. (2007) showed that E1L2 could activate ubiquitin and transfer ubiquitin to a subset of ubiquitin E2s. E1L2 could also activate FAT10 (UBD; 606050) by forming a thioester between the active-site cysteine of E1L2 and the C-terminal diglycine motif of FAT10. Endogenous E1L2 and FAT10 also formed a thioester in human cells stimulated with TNF-alpha (TNF; 191160) and interferon-gamma (IFNG; 147570). Knockdown of E1L2 by RNA interference significantly reduced FAT10 conjugation in cells.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the UBE1L2 gene to chromosome 4 (TMAP SHGC-52778).

ANIMAL MODEL

Chiu et al. (2007) found that homozygous deletion of E1l2 in mice was embryonic lethal. Heterozygous mice were fertile and developed normally. ... More on the omim web site

Subscribe to this protein entry history

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

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

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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 611361 was added.