CDC34 cell division cycle 34, ubiqiutin conjugating enzyme [Homo sapiens (human)] - Gene

Summary

Official Symbol: CDC34provided by HGNC
Official Full Name: cell division cycle 34, ubiqiutin conjugating enzymeprovided by HGNC
Primary source: HGNC:HGNC:1734
See related: Ensembl:ENSG00000099804 MIM:116948; AllianceGenome:HGNC:1734
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: UBC3; UBCH3; UBE2R1; E2-CDC34
Summary: The protein encoded by this gene is a member of the ubiquitin-conjugating enzyme family. Ubiquitin-conjugating enzyme catalyzes the covalent attachment of ubiquitin to other proteins. This protein is a part of the large multiprotein complex, which is required for ubiquitin-mediated degradation of cell cycle G1 regulators, and for the initiation of DNA replication. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in testis (RPKM 23.4), placenta (RPKM 14.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.3

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (531760..542087)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (485161..495858)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (531760..542087)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Targeting CDC34 E2 ubiquitin conjugating enzyme for lung cancer therapy.
Title: Targeting CDC34 E2 ubiquitin conjugating enzyme for lung cancer therapy.
Systematic identification of CDC34 that functions to stabilize EGFR and promote lung carcinogenesis.
Title: Systematic identification of CDC34 that functions to stabilize EGFR and promote lung carcinogenesis.
UBE2R2 alone had negligible ubiquitylation activity at physiological concentrations and the ablation of UBE2R1/2 had no effect on the stability of SCF substrates in cells. A genome-wide CRISPR screen revealed that an additional E2 enzyme, UBE2G1, buffers against the loss of UBE2R1/2.
Title: Robust cullin-RING ligase function is established by a multiplicity of poly-ubiquitylation pathways.
study finds that mutation of the catalytically active cysteine to serine (C93S) results in the reduced ubiquitination, increased stability, and attenuated degradation rate of CDC34; Through semi-quantitative proteomics, identified the CDC34-interacting proteins and discovered that the wild-type and mutant proteins have many differentially interacted proteins
Title: The Catalytically Inactive Mutation of the Ubiquitin-Conjugating Enzyme CDC34 Affects its Stability and Cell Proliferation.
Study shows that Ube2R1/2 forms a salt bridge interaction between a conserved Asp residue on Ube2R1/2 and acceptor ubiquitin residue Arg 54 and that perturbation of this interaction leads to the severe loss of UbeR2 activity. Results also provide new insight into how the Ube2R1/2 acidic loop may participate in catalysis.
Title: Mechanism of Lysine 48 Selectivity during Polyubiquitin Chain Formation by the Ube2R1/2 Ubiquitin-Conjugating Enzyme.
ubiquitin binding by the acidic loops of Ube2g1 and Ube2r1 enzymes distinguishes their Lys-48-ubiquitylation activities
Title: Differential ubiquitin binding by the acidic loops of Ube2g1 and Ube2r1 enzymes distinguishes their Lys-48-ubiquitylation activities.
We discuss how these results can explain the rapid association of Cdc34 and SCF.
Title: Ubiquitin-conjugating enzyme Cdc34 and ubiquitin ligase Skp1-cullin-F-box ligase (SCF) interact through multiple conformations.
Here we have investigated how the acidic loop in human Cdc34 promotes ubiquitination, identifying two key molecular events during which the acidic loop exerts its influence
Title: Multimodal mechanism of action for the Cdc34 acidic loop: a case study for why ubiquitin-conjugating enzymes have loops and tails.
These data suggest that FBXO15 and Ube2r1 regulate P-gp expression through the ubiquitin-proteasome pathway.
Title: FBXO15 regulates P-glycoprotein/ABCB1 expression through the ubiquitin--proteasome pathway in cancer cells.
Tristetraprolin promotes an increase in expression of mature let-7, which leads to the inhibition of let-7 target gene CDC34 expression and suppresses cell growth.
Title: Ectopic over-expression of tristetraprolin in human cancer cells promotes biogenesis of let-7 by down-regulation of Lin28.

Submit: New GeneRIF Correction See all GeneRIFs (28)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vif	vif	CUL5/RBX2/ELOB/ELOC/Vif/CBF-beta complex catalyzes polyubiquitin chain formation on A3G in the presence of ubiquitin E2 UBE2R1 (CDC34) or UBCH5b (UBE2D2)	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D19S236E (e-PCR)
- UniSTS:147533

RH79792 (e-PCR)
- UniSTS:92805

D19S236E (e-PCR)
- UniSTS:147453

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin conjugating enzyme activity	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin conjugating enzyme activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin-protein transferase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin-protein transferase activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA replication initiation	NAS Non-traceable Author Statement more info	PubMed
involved_in G1/S transition of mitotic cell cycle	NAS Non-traceable Author Statement more info	PubMed
involved_in cellular response to interferon-beta	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cAMP-mediated signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of inclusion body assembly	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in protein K48-linked ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein modification process	NAS Non-traceable Author Statement more info	PubMed
involved_in protein polyubiquitination	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein polyubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	NAS Non-traceable Author Statement more info	PubMed
involved_in response to growth factor	IEA Inferred from Electronic Annotation more info
involved_in ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in nuclear speck	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: ubiquitin-conjugating enzyme E2 R1

Names: (E3-independent) E2 ubiquitin-conjugating enzyme R1; E2 ubiquitin-conjugating enzyme R1; cell division cycle 34 homolog; ubiquitin carrier protein; ubiquitin-conjugating enzyme E2-32 KDA complementing; ubiquitin-conjugating enzyme E2-CDC34; ubiquitin-protein ligase R1

NP_004350.1

EC 2.3.2.23

EC 2.3.2.24

XP_005259747.1

EC 2.3.2.23

EC 2.3.2.24

XP_006723015.1

EC 2.3.2.23

EC 2.3.2.24

XP_054178773.1

EC 2.3.2.23

EC 2.3.2.24

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_004359.2 → NP_004350.1 ubiquitin-conjugating enzyme E2 R1

See identical proteins and their annotated locations for NP_004350.1

Status: REVIEWED

Source sequence(s)

AC011531, AC011556

Consensus CDS

CCDS12030.1

UniProtKB/Swiss-Prot

A8K689, P49427

Related

ENSP00000215574.2, ENST00000215574.9

Conserved Domains (1) summary

cd00195
Location:11 → 162

UBCc; Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain. This is part of the ubiquitin-mediated protein degradation pathway in which a thiol-ester linkage forms between a conserved cysteine and the C-terminus of ubiquitin and complexes with ubiquitin ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

531760..542087

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006722952.3 → XP_006723015.1 ubiquitin-conjugating enzyme E2 R1 isoform X2

UniProtKB/TrEMBL

U3KPV8

Related

ENSP00000475282.3, ENST00000586283.6

Conserved Domains (2) summary

COG5078
Location:6 → 162

COG5078; Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones]

cd00195
Location:11 → 162

UBCc; Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain. This is part of the ubiquitin-mediated protein degradation pathway in which a thiol-ester linkage forms between a conserved cysteine and the C-terminus of ubiquitin and complexes with ubiquitin ...
XM_005259690.4 → XP_005259747.1 ubiquitin-conjugating enzyme E2 R1 isoform X1

Conserved Domains (2) summary

COG5078
Location:6 → 162

COG5078; Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones]

cd00195
Location:11 → 162

UBCc; Ubiquitin-conjugating enzyme E2, catalytic (UBCc) domain. This is part of the ubiquitin-mediated protein degradation pathway in which a thiol-ester linkage forms between a conserved cysteine and the C-terminus of ubiquitin and complexes with ubiquitin ...