UFD1 ubiquitin recognition factor in ER associated degradation 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: UFD1provided by HGNC
Official Full Name: ubiquitin recognition factor in ER associated degradation 1provided by HGNC
Primary source: HGNC:HGNC:12520
See related: Ensembl:ENSG00000070010 MIM:601754; AllianceGenome:HGNC:12520
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: UFD1L
Summary: The protein encoded by this gene forms a complex with two other proteins, nuclear protein localization-4 and valosin-containing protein, and this complex is necessary for the degradation of ubiquitinated proteins. In addition, this complex controls the disassembly of the mitotic spindle and the formation of a closed nuclear envelope after mitosis. Mutations in this gene have been associated with Catch 22 syndrome as well as cardiac and craniofacial defects. Alternative splicing results in multiple transcript variants encoding different isoforms. A related pseudogene has been identified on chromosome 18. [provided by RefSeq, Jun 2009]
Expression: Ubiquitous expression in bone marrow (RPKM 14.2), testis (RPKM 13.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q11.21

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (19449911..19479193, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (19826739..19856026, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (19437434..19466716, complement)

Chromosome 22 - NC_000022.11 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 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?

Structural basis for the interaction between human Npl4 and Npl4-binding motif of human Ufd1.
Title: Structural basis for the interaction between human Npl4 and Npl4-binding motif of human Ufd1.
Multiple UBX proteins reduce the ubiquitin threshold of the mammalian p97-UFD1-NPL4 unfoldase.
Title: Multiple UBX proteins reduce the ubiquitin threshold of the mammalian p97-UFD1-NPL4 unfoldase.
PCBP2 Posttranscriptional Modifications Induce Breast Cancer Progression via Upregulation of UFD1 and NT5E.
Title: PCBP2 Posttranscriptional Modifications Induce Breast Cancer Progression via Upregulation of UFD1 and NT5E.
Involvement of VCP/UFD1/Nucleolin in the viral entry of Enterovirus A species.
Title: Involvement of VCP/UFD1/Nucleolin in the viral entry of Enterovirus A species.
Seesaw conformations of Npl4 in the human p97 complex and the inhibitory mechanism of a disulfiram derivative.
Title: Seesaw conformations of Npl4 in the human p97 complex and the inhibitory mechanism of a disulfiram derivative.
Multisystem proteinopathy mutations in VCP/p97 increase NPLOC4-UFD1L binding and substrate processing.
Title: Multisystem Proteinopathy Mutations in VCP/p97 Increase NPLOC4·UFD1L Binding and Substrate Processing.
results support that Ufd1 S229 phosphorylation status mediated by PKA serves as a key regulatory point for the VCP-Ufd1 interaction and functional ERAD.
Title: Ufd1 phosphorylation at serine 229 negatively regulates endoplasmic reticulum-associated degradation by inhibiting the interaction of Ufd1 with VCP.
CHOP inactivation or BCL2 overexpression is sufficient to rescue tumor cell apoptosis induced by UFD1 knockdown.
Title: UFD1 contributes to MYC-mediated leukemia aggressiveness through suppression of the proapoptotic unfolded protein response.
We demonstrate that WT p97 can unfold proteins and that this activity is dependent on the p97 adaptor NPLOC4-UFD1L, ATP hydrolysis, and substrate ubiquitination, with branched chains providing maximal stimulation.
Title: Ubiquitin- and ATP-dependent unfoldase activity of P97/VCP•NPLOC4•UFD1L is enhanced by a mutation that causes multisystem proteinopathy.
The study revealed a regulatory role of the p97-Npl4-Ufd1 complex in regulating a partial degradation of the NF-kappaB subunit p100.
Title: The Transitional Endoplasmic Reticulum ATPase p97 Regulates the Alternative Nuclear Factor NF-κB Signaling via Partial Degradation of the NF-κB Subunit p100.

Submit: New GeneRIF Correction See all GeneRIFs (27)

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
Vpu	vpu	The VCP-UFD1L-NPL4 complex is required for HIV-1 Vpu-induced CD4 degradation in the ER-associated degradation pathway. The ATPase activity of VCP and ubiquitin binding to UFD1L are important for CD4 degradation by Vpu	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

D8S2279 (e-PCR)
- UniSTS:473907

RH75489 (e-PCR)
- UniSTS:84533

D10S16 (e-PCR)
- UniSTS:155756

D18S1297 (e-PCR)
- UniSTS:18820

SHGC-67307 (e-PCR)
- UniSTS:89991

RH18339 (e-PCR)
- UniSTS:90616

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables K48-linked polyubiquitin modification-dependent protein binding	IEA Inferred from Electronic Annotation more info
enables cysteine-type deubiquitinase activity	TAS Traceable Author Statement more info	PubMed
enables polyubiquitin modification-dependent protein binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in ERAD pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in ERAD pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ERAD pathway	ISO Inferred from Sequence Orthology more info
involved_in cellular response to misfolded protein	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of RIG-I signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of type I interferon production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in retrograde protein transport, ER to cytosol	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in retrograde protein transport, ER to cytosol	ISO Inferred from Sequence Orthology more info
involved_in skeletal system development	TAS Traceable Author Statement more info	PubMed
involved_in ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of UFD1-NPL4 complex	IPI Inferred from Physical Interaction more info	PubMed
part_of VCP-NPL4-UFD1 AAA ATPase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of VCP-NPL4-UFD1 AAA ATPase complex	IDA Inferred from Direct Assay more info	PubMed
part_of VCP-NPL4-UFD1 AAA ATPase complex	IPI Inferred from Physical Interaction more info	PubMed
part_of VCP-NPL4-UFD1 AAA ATPase complex	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	TAS Traceable Author Statement more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	HDA more info	PubMed

General protein information

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Preferred Names: ubiquitin recognition factor in ER-associated degradation protein 1

Names: UB fusion protein 1; ubiquitin fusion degradation 1 like; ubiquitin fusion degradation protein 1 homolog

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_001035247.3 → NP_001030324.2 ubiquitin recognition factor in ER-associated degradation protein 1 isoform B

See identical proteins and their annotated locations for NP_001030324.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region that results in a frameshift, compared to variant 1. The encoded isoform (B) has a distinct C-terminus and is shorter than isoform A.

Source sequence(s)

AC000068, AK225877, AW131352, CB128364, DB496066, DB570679

Consensus CDS

CCDS33600.2

UniProtKB/TrEMBL

B4E3I3

Related

ENSP00000382439.1, ENST00000399523.5

Conserved Domains (1) summary

pfam03152
Location:19 → 193

UFD1; Ubiquitin fusion degradation protein UFD1
NM_001362910.2 → NP_001349839.1 ubiquitin recognition factor in ER-associated degradation protein 1 isoform C

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice site in the 5' region and is predicted to use a downstream start codon compared to variant 1. The encoded isoform (C) has a shorter N-terminus compared to isoform A.

Source sequence(s)

AC000068, AC000087

UniProtKB/TrEMBL

B4E3I3

Conserved Domains (1) summary

pfam03152
Location:14 → 188

UFD1; Ubiquitin fusion degradation protein UFD1
NM_005659.7 → NP_005650.2 ubiquitin recognition factor in ER-associated degradation protein 1 isoform A

See identical proteins and their annotated locations for NP_005650.2

Status: REVIEWED

Description

Transcript Variant: This variant (1)encodes the longest isoform (A).

Source sequence(s)

AC000068, AW131352, BC005087, CB128364, DB570679

Consensus CDS

CCDS13761.1

UniProtKB/Swiss-Prot

A8MW31, Q92890, Q9Y5N0

UniProtKB/TrEMBL

B4E3I3, Q541A5

Related

ENSP00000263202.9, ENST00000263202.15

Conserved Domains (1) summary

pfam03152
Location:19 → 193

UFD1; Ubiquitin fusion degradation protein UFD1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000022.11 Reference GRCh38.p14 Primary Assembly

Range

19449911..19479193 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047441488.1 → XP_047297444.1 ubiquitin recognition factor in ER-associated degradation protein 1 isoform X3
XM_047441487.1 → XP_047297443.1 ubiquitin recognition factor in ER-associated degradation protein 1 isoform X2
XM_047441486.1 → XP_047297442.1 ubiquitin recognition factor in ER-associated degradation protein 1 isoform X1

Alternate T2T-CHM13v2.0

Genomic

NC_060946.1 Alternate T2T-CHM13v2.0

Range

19826739..19856026 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054325901.1 → XP_054181876.1 ubiquitin recognition factor in ER-associated degradation protein 1 isoform X3
XM_054325900.1 → XP_054181875.1 ubiquitin recognition factor in ER-associated degradation protein 1 isoform X2
XM_054325899.1 → XP_054181874.1 ubiquitin recognition factor in ER-associated degradation protein 1 isoform X1