UBE2Z

Last updated
UBE2Z
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases UBE2Z , USE1, HOYS7, ubiquitin conjugating enzyme E2 Z
External IDs OMIM: 611362 MGI: 1343160 HomoloGene: 11319 GeneCards: UBE2Z
Orthologs
SpeciesHumanMouse
Entrez

65264

268470

Ensembl

ENSG00000159202

ENSMUSG00000014349

UniProt

Q9H832

Q3UE37

RefSeq (mRNA)

NM_023079

NM_172300

RefSeq (protein)

NP_075567

NP_758504

Location (UCSC) Chr 17: 48.91 – 48.93 Mb Chr 11: 95.94 – 95.96 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Ubiquitin conjugating enzyme E2 Z (UBE2Z), also known as UBA6-specific E2 enzyme 1 (USE1), is an enzyme that in humans is encoded by the UBE2Z gene on chromosome 17. [5] [6] It is ubiquitously expressed in many tissues and cell types. [7] UBE2Z is an E2 ubiquitin conjugating enzyme and participates in the second step of protein ubiquitination during proteolysis. [8] A genome-wide association study (GWAS) revealed the UBE2Z gene to be associated with chronic kidney disease. [9] The UBE2Z gene also contains one of 27 SNPs associated with increased risk of coronary artery disease. [10]

Contents

Structure

Gene

The UBE2Z gene resides on chromosome 17 at the band 17q21.32 and contains 7 exons. [5] This gene produces 2 isoforms through alternative splicing. [11] The UBE2Z cDNA spans a length of 3,054 base pairs. [12]

Protein

This protein belongs to the ubiquitin conjugating enzyme family and is one of the E2 enzymes. [11] UBE2Z spans 246 amino acids, 150 of which encode a conserved 16–18 kDa ubiquitin conjugating enzyme E2 domain (UBC domain) that is located at the enzyme’s N-terminal and responsible for the enzyme’s catalytic function. This UBC domain has a relatively inflexible β-sheet structure with flanking helices and contains a highly conserved cysteine residue, Cys80, which functions as an active site for the thiol ester formation with ubiquitin. UBE2Z also contains a C-terminal extension, suggested to participate in substrate binding, which is characteristic of a class II E2 ubiquitin conjugating enzyme. [12]

Function

The UBE2Z gene is ubiquitously expressed in human tissues, and its expression is relatively high in placenta, pancreas, spleen and testis. Notably, its expression in cancer tissues is much higher than in relevant normal tissues, especially in kidney, lymph node, colon and ovary cancer. [12] As an E2 member of the ubiquitin-conjugating enzyme family, UBE2Z mainly participates in the second step of protein ubiquitination, which is a major component of protein degradation machinery. [8] Specifically, UBE2Z receives ubiquitin (Ub) from ubiquitin-activating enzyme (E1), mediates the transfer of Ub from E2 to substrate, directly or indirectly with the help of ligase enzyme (E3), which interacts with the substrate and E2-Ub complex. UBE2Z could only be charged by Ub or FAT10 from UBA6 instead of UBA1, distinguishing it from other E2s. [13] [14]

Clinical significance

A study in genetic variants that regulate lipid metabolism and determine the susceptibility to dyslipidemia in Japanese individuals revealed that UBE2Z, together with ZPR1 and Interleukin-6R, may be important loci for hypertriglyceridemia. [15] Moreover, in a GWAS among 2247 Japanese individuals, 29 polymorphisms that were previously identified as susceptible loci for coronary artery disease were investigated to identify a correlation of these loci to chronic kidney disease. [9] This GWAS meta-analysis revealed through a chi-square test that rs46522 on the UBE2Z gene was significantly related to chronic kidney disease. [9]

Clinical marker

A multi-locus genetic risk score study based on a combination of 27 loci, including the UBE2Z gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22). [10]

Related Research Articles

<span class="mw-page-title-main">UBA1</span> Protein-coding gene in the species Homo sapiens

Ubiquitin-like modifier activating enzyme 1 (UBA1) is an enzyme which in humans is encoded by the UBA1 gene. UBA1 participates in ubiquitination and the NEDD8 pathway for protein folding and degradation, among many other biological processes. This protein has been linked to X-linked spinal muscular atrophy type 2, neurodegenerative diseases, and cancers.

<span class="mw-page-title-main">UBE3A</span> Protein-coding gene in Homo sapiens

Ubiquitin-protein ligase E3A (UBE3A) also known as E6AP ubiquitin-protein ligase (E6AP) is an enzyme that in humans is encoded by the UBE3A gene. This enzyme is involved in targeting proteins for degradation within cells.

<span class="mw-page-title-main">Ubiquitin-activating enzyme</span> Class of enzymes

Ubiquitin-activating enzymes, also known as E1 enzymes, catalyze the first step in the ubiquitination reaction, which can target a protein for degradation via a proteasome. This covalent bond of ubiquitin or ubiquitin-like proteins to targeted proteins is a major mechanism for regulating protein function in eukaryotic organisms. Many processes such as cell division, immune responses and embryonic development are also regulated by post-translational modification by ubiquitin and ubiquitin-like proteins.

<span class="mw-page-title-main">NEDD8</span>

NEDD8 is a protein that in humans is encoded by the NEDD8 gene. This ubiquitin-like (UBL) protein becomes covalently conjugated to a limited number of cellular proteins, in a process called NEDDylation similar to ubiquitination. Human NEDD8 shares 60% amino acid sequence identity to ubiquitin. The primary known substrates of NEDD8 modification are the cullin subunits of cullin-based E3 ubiquitin ligases, which are active only when NEDDylated. Their NEDDylation is critical for the recruitment of E2 to the ligase complex, thus facilitating ubiquitin conjugation. NEDD8 modification has therefore been implicated in cell cycle progression and cytoskeletal regulation.

<span class="mw-page-title-main">UBE2L3</span> Protein-coding gene in humans

Ubiquitin-conjugating enzyme E2 L3 (UBE2L3), also called UBCH7, is a protein that in humans is encoded by the UBE2L3 gene. As an E2 enzyme, UBE2L3 participates in ubiquitination to target proteins for degradation. The role of UBE2L3 in the ubiquitination of the NF-κB precursor implicated it in various major autoimmune diseases, including rheumatoid arthritis (RA), celiac disease, Crohn's disease (CD), and systemic lupus erythematosus.

<span class="mw-page-title-main">UBE2G2</span> Protein-coding gene in the species Homo sapiens

Ubiquitin-conjugating enzyme E2 G2 is a protein that in humans is encoded by the UBE2G2 gene.

<span class="mw-page-title-main">UBE2V2</span> Protein-coding gene in the species Homo sapiens

Ubiquitin-conjugating enzyme E2 variant 2 is a protein that in humans is encoded by the UBE2V2 gene. Ubiquitin-conjugating enzyme E2 variant proteins constitute a distinct subfamily within the E2 protein family.

<span class="mw-page-title-main">UBE1C</span> Protein-coding gene in the species Homo sapiens

NEDD8-activating enzyme E1 catalytic subunit is a protein that in humans is encoded by the UBA3 gene.

<span class="mw-page-title-main">UBE2L6</span> Protein-coding gene in the species Homo sapiens

Ubiquitin/ISG15-conjugating enzyme E2 L6 is a protein that in humans is encoded by the UBE2L6 gene.

<span class="mw-page-title-main">UBE2A</span> Protein-coding gene in the species Homo sapiens

Ubiquitin-conjugating enzyme E2 A is a protein that in humans is encoded by the UBE2A gene.

<span class="mw-page-title-main">UBE2B</span> Protein-coding gene in the species Homo sapiens

Ubiquitin-conjugating enzyme E2 B is a protein that in humans is encoded by the UBE2B gene.

<span class="mw-page-title-main">UBE2C</span> Protein-coding gene in the species Homo sapiens

Ubiquitin-conjugating enzyme E2 C is a protein that in humans is encoded by the UBE2C gene.

<span class="mw-page-title-main">UBE1L2</span> Protein-coding gene in the species Homo sapiens

Ubiquitin-like modifier-activating enzyme 6 is a protein that in humans is encoded by the UBA6 gene.

<span class="mw-page-title-main">UBE2G1</span> Protein-coding gene in the species Homo sapiens

Ubiquitin-conjugating enzyme E2 G1 is a protein that in humans is encoded by the UBE2G1 gene.

<span class="mw-page-title-main">UBE1L</span> Protein-coding gene in the species Homo sapiens

Ubiquitin-like modifier-activating enzyme 7 is a protein that in humans is encoded by the UBA7 gene.

<span class="mw-page-title-main">UBE2E1</span>

Ubiquitin-conjugating enzyme E2 E1 is a protein that in humans is encoded by the UBE2E1 gene.

<span class="mw-page-title-main">UBE2M</span> Protein-coding gene in the species Homo sapiens

NEDD8-conjugating enzyme Ubc12 is a protein that in humans is encoded by the UBE2M gene.

<span class="mw-page-title-main">UFM1</span> Protein-coding gene in the species Homo sapiens

Ubiquitin-fold modifier 1, also known as UFM1, is a protein which in humans is encoded by the UFM1 gene.

<span class="mw-page-title-main">UBE2O</span> Protein-coding gene in the species Homo sapiens

Ubiquitin-conjugating enzyme E2 O is a protein that in humans is encoded by the UBE2O gene.

<span class="mw-page-title-main">Ubiquitin conjugating enzyme e2 q2</span> Protein-coding gene in the species Homo sapiens

Ubiquitin conjugating enzyme E2 Q2 is a protein that in humans is encoded by the UBE2Q2 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000159202 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000014349 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 "UBE2Z ubiquitin conjugating enzyme E2 Z [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 10 October 2016.
  6. ↑ Bialas J, Groettrup M, Aichem A (1 January 2015). "Conjugation of the ubiquitin activating enzyme UBE1 with the ubiquitin-like modifier FAT10 targets it for proteasomal degradation". PLOS ONE. 10 (3): e0120329. Bibcode:2015PLoSO..1020329B. doi: 10.1371/journal.pone.0120329 . PMC   4359146 . PMID   25768649.
  7. ↑ "BioGPS - your Gene Portal System". biogps.org. Retrieved 10 October 2016.
  8. 1 2 Baarends WM, Roest HP, Grootegoed JA (May 1999). "The ubiquitin system in gametogenesis". Molecular and Cellular Endocrinology. 151 (1–2): 5–16. doi:10.1016/s0303-7207(99)00060-x. PMID   10411315. S2CID   8632308.
  9. 1 2 3 Horibe H, Fujimaki T, Oguri M, Kato K, Matsuoka R, Abe S, Tokoro F, Arai M, Noda T, Watanabe S, Yamada Y (April 2015). "Association of a polymorphism of the interleukin 6 receptor gene with chronic kidney disease in Japanese individuals". Nephrology. 20 (4): 273–8. doi:10.1111/nep.12381. PMID   25524550. S2CID   11292241.
  10. 1 2 Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, Nordio F, Hyde CL, Cannon CP, Sacks FM, Poulter NR, Sever PS, Ridker PM, Braunwald E, Melander O, Kathiresan S, Sabatine MS (June 2015). "Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials". Lancet. 385 (9984): 2264–71. doi:10.1016/S0140-6736(14)61730-X. PMC   4608367 . PMID   25748612.
  11. 1 2 "UBE2Z - Ubiquitin-conjugating enzyme E2 Z - Homo sapiens (Human) - UBE2Z gene & protein". UniProt . Retrieved 10 October 2016.
  12. 1 2 3 Gu X, Zhao F, Zheng M, Fei X, Chen X, Huang S, Xie Y, Mao Y (September 2007). "Cloning and characterization of a gene encoding the human putative ubiquitin conjugating enzyme E2Z (UBE2Z)". Molecular Biology Reports. 34 (3): 183–8. doi:10.1007/s11033-006-9033-7. PMID   17160626. S2CID   27210618.
  13. ↑ Jin J, Li X, Gygi SP, Harper JW (June 2007). "Dual E1 activation systems for ubiquitin differentially regulate E2 enzyme charging". Nature. 447 (7148): 1135–8. Bibcode:2007Natur.447.1135J. doi:10.1038/nature05902. PMID   17597759. S2CID   4337767.
  14. ↑ Aichem A, Pelzer C, Lukasiak S, Kalveram B, Sheppard PW, Rani N, Schmidtke G, Groettrup M (4 May 2010). "USE1 is a bispecific conjugating enzyme for ubiquitin and FAT10, which FAT10ylates itself in cis". Nature Communications. 1 (2): 13. Bibcode:2010NatCo...1...13A. doi: 10.1038/ncomms1012 . PMID   20975683.
  15. ↑ Abe S, Tokoro F, Matsuoka R, Arai M, Noda T, Watanabe S, Horibe H, Fujimaki T, Oguri M, Kato K, Minatoguchi S, Yamada Y (October 2015). "Association of genetic variants with dyslipidemia". Molecular Medicine Reports. 12 (4): 5429–36. doi: 10.3892/mmr.2015.4081 . PMID   26238946.

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