Ubiquilin-2 (UBQLN2)

The protein contains 624 amino acids for an estimated molecular weight of 65696 Da.

 

Plays an important role in the regulation of different protein degradation mechanisms and pathways including ubiquitin-proteasome system (UPS), autophagy and the endoplasmic reticulum-associated protein degradation (ERAD) pathway. Mediates the proteasomal targeting of misfolded or accumulated proteins for degradation by binding (via UBA domain) to their polyubiquitin chains and by interacting (via ubiquitin-like domain) with the subunits of the proteasome (PubMed:10983987). Plays a role in the ERAD pathway via its interaction with ER-localized proteins FAF2/UBXD8 and HERPUD1 and may form a link between the polyubiquitinated ERAD substrates and the proteasome (PubMed:24215460, PubMed:18307982). Involved in the regulation of macroautophagy and autophagosome formation; required for maturation of autophagy-related protein LC3 from the cytosolic form LC3-I to the membrane-bound form LC3-II and may assist in the maturation of autophagosomes to autolysosomes by mediating autophagosome-lysosome fusion (PubMed:19148225, PubMed:20529957). Negatively regulates the endocytosis of GPCR receptors: AVPR2 and ADRB2, by specifically reducing the rate at which receptor-arrestin complexes concentrate in clathrin-coated pits (CCPs) (PubMed:18199683). (updated: Dec. 20, 2017)

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. 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.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.

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 annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 20%
Model score: 40

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VariantDescription
ALS15
ALS15
dbSNP:rs17002693
Probable disease-associated variant found in a patient with frontotem
ALS15
ALS15
ALS15
ALS15
ALS15
ALS15
ALS15
ALS15

The reference OMIM entry for this protein is 300264

Ubiquilin 2; ubqln2
Plic2, mouse, homolog of; plic2
Chap1

DESCRIPTION

The UBQLN2 gene encodes ubiquilin-2, a member of the ubiquilin family of proteins that regulate the degradation of ubiquitinated proteins by the proteasome. Humans have 4 ubiquilin genes, each encoding a separate protein. Ubiquilins are characterized by the presence of an N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. The middle part of ubiquilins is highly variable. Ubiquilin-2 has a unique repeat region containing 12 PXX tandem repeats (summary by Deng et al., 2011).

CLONING

By performing independent yeast 2-hybrid screens, Kleijnen et al. (2000) isolated cDNAs encoding PLIC1 (UBQLN1; 605046) and PLIC2, homologs of the mouse Plics (proteins linking integrin-associated protein (IAP; 601028) and cytoskeleton) and the yeast Dsk2 protein. The predicted 624-amino acid PLIC2 protein, also called UBQLN2, shares 72% amino acid identity with PLIC1. Two motifs are conserved in the mammalian PLICs and yeast Dsk2, an N-terminal ubiquitin (191339)-like (UBL) domain and a C-terminal ubiquitin-associated (UBA) domain. Unlike ubiquitin, the UBL domain of the PLICs does not have a diglycine motif in its C terminus; the diglycine motif serves as a target site for cellular hydrolases that release ubiquitin from precursor fusion proteins. The absence of a GG sequence suggests that the UBL domain in the PLICs is an integral part of the open reading frame. The UBA domain is a loosely defined sequence motif present in multiple enzyme classes of the ubiquitination machinery. The most notable difference between the mammalian PLICs is the presence of a collagen-like motif in PLIC2 that is absent in PLIC1 and yeast Dsk2. This domain is most homologous to the collagen-like oncoprotein of Herpesvirus saimiri, STP-C488, which is implicated in intracellular signaling via the RAS-RAF pathway (see 190020). The collagen-like domain of PLIC2 contains 8 PXGP motifs that are susceptible to cleavage by collagenase in vitro. Kleijnen et al. (2000) showed that the human PLICs physically associate with both proteasomes and ubiquitin ligases in large complexes. Overexpression of PLICs interfered with the in vivo degradation of 2 unrelated ubiquitin-dependent proteasome substrates, p53 (191170) and I-kappa-B-alpha (NFKBIA; 164008), but not a ubiquitin-independent substrate. These findings raised the possibility that the PLICs, and possibly related ubiquitin-like family members, may functionally link the ubiquitination machinery to the proteasome to affect in vivo protein degradation. By screening a human lung 2-hybrid cDNA library using a pGBT9-STCH (601100) plasmid as bait, Kaye et al. (2000) isolated a cDNA encoding UBQLN2, which they termed CHAP1/DSK2. Mutation analysis determined that the C-terminal Sti1-like repeat sequence, but neither the N-terminal UBL domain nor the C-terminal UBA domain, is required for binding of UBQLN2 to the ATPase domain of STCH.

GENE FUNCTION

The ubiquitin-like domain of the ubiquilins binds to subunits in the proteasome and the ubiquitin-associated domain binds to the polyubiquitin chains that are typically conjugated onto proteins marked for degradation by the proteasome (summary by Deng et al., 2011).

GENE STRUCTURE

The UBQLN2 gene is intronless (Deng et al., 2011).

MAPPING

By radiation hybrid analysis, Kaye and Shows (2000) mapped the UBQLN2 gene to chromosome Xp11.23-p11.1, a location linked to a number of neuropsychiatric disorders.

MOLE ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: 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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300264 was added.

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed