Ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5)

The protein contains 329 amino acids for an estimated molecular weight of 37607 Da.

 

Protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. Deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome. Putative regulatory component of the INO80 complex; however is inactive in the INO80 complex and is activated by a transient interaction of the INO80 complex with the proteasome via ADRM1. (updated: March 4, 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. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

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.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 100%
Model score: 100
No model available.

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VariantDescription
empty

The reference OMIM entry for this protein is 610667

Ubiquitin carboxyl-terminal hydrolase l5; uchl5
Uch37

CLONING

Using yeast 2-hybrid analysis of a mouse brain library with the N-terminal region of Smad3 (603109) as bait, Wicks et al. (2005) identified mouse Uchl5. They stated that mouse Uchl5 and human UCH37 (UCHL5) are 99% identical. UCHL5 is a member of the UCH enzyme family and contains a conserved catalytic domain and a nonconserved extended C-terminal tail.

GENE FUNCTION

Lam et al. (1997, 1997) originally identified bovine UCHL5 as a component of the 26S proteasome and showed that it functions in editing polyubiquitinated protein substrates. Wicks et al. (2005) reported that proteasome-associated UCHL5 sequentially removes ubiquitin from the distal end of the lys48-linked polyubiquitin chain and has the potential to rescue ubiquitinated substrates from proteasomal degradation. Using a variety of immunoprecipitation assays, they found that mouse Uchl5 binds strongly to Smad7 (602932) and weakly to Smad2 (601366) and Smad3. Deletion constructs showed that Uchl5 binding does not require the Smurf-binding PY motif of Smad7. Transfection experiments with transforming growth factor-beta receptor-1 (Tgfbr1; 190181), Smad7, Smurf2 (605532), and Uchl5 showed that Uchl5 deubiquitinates and stabilizes TGFBR1. Using a luciferase reporter construct in HEK-293 cells, Wicks et al. (2005) showed that Uchl5 overexpression increases Tgfbr1-dependent transcription. Knockdown of Uchl5 expression by RNA interference abrogated Tgf-beta-dependent transcription. Rolen et al. (2006) reported that deregulation of some ubiquitin-specific proteases (USPs) affect tumor growth. Using a functional proteomics assay in which tagged probes target the active sites of USPs, they investigated the activity of USPs in human HPV-carrying cervical carcinoma biopsies relative to adjacent normal tissue. The activity of UCHL5 was significantly increased in 76% of the tumors analyzed. UCHL5 was active in 92% (24 of 26) of the cervical carcinoma biopsies, and in 100% of 8 cervical carcinoma cell lines, of which 6 were HPV-positive and 2 were HPV-negative. UCHL5 activity level did not correlate with the clinical stage of the tumors or the presence of metastases.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the UCHL5 gene to chromosome 1 (TMAP WI-14924). ... 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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610667 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed