NPLOC4 NPL4 homolog, ubiquitin recognition factor [Homo sapiens (human)] - Gene

Summary

Official Symbol: NPLOC4provided by HGNC
Official Full Name: NPL4 homolog, ubiquitin recognition factorprovided by HGNC
Primary source: HGNC:HGNC:18261
See related: Ensembl:ENSG00000182446 MIM:606590; AllianceGenome:HGNC:18261
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NPL4
Summary: Predicted to enable ubiquitin binding activity and ubiquitin protein ligase binding activity. Predicted to contribute to K48-linked polyubiquitin modification-dependent protein binding activity and K63-linked polyubiquitin modification-dependent protein binding activity. Involved in negative regulation of RIG-I signaling pathway; negative regulation of type I interferon production; and proteolysis involved in protein catabolic process. Located in nucleus. Part of UFD1-NPL4 complex and VCP-NPL4-UFD1 AAA ATPase complex. [provided by Alliance of Genome Resources, Dec 2024]
Expression: Ubiquitous expression in testis (RPKM 14.2), esophagus (RPKM 10.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q25.3

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (81556885..81637112, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (82474164..82554047, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (79523911..79604138, complement)

Chromosome 17 - NC_000017.11 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

NPLOC4 is a potential target and a poor prognostic signature in lung squamous cell carcinoma.
Title: NPLOC4 is a potential target and a poor prognostic signature in lung squamous cell carcinoma.
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.
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.
Targeting NPL4 via drug repositioning using disulfiram for the treatment of clear cell renal cell carcinoma.
Title: Targeting NPL4 via drug repositioning using disulfiram for the treatment of clear cell renal cell carcinoma.
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.
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.
p97-Ufd1-Npl4 is an integral part of G2/M checkpoint signaling and thereby suppresses chromosome instability.
Title: The p97-Ufd1-Npl4 ATPase complex ensures robustness of the G2/M checkpoint by facilitating CDC25A degradation.
Data indicate that the p97-UFD1L-NPL4 protein complex specifically associates with ubiquitinated IkappaBalpha via the interactions between p97 and the SCF(beta-TRCP) ubiquitin ligase.
Title: The p97-UFD1L-NPL4 protein complex mediates cytokine-induced IκBα proteolysis.

Submit: New GeneRIF Correction See all GeneRIFs (16)

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

EBI GWAS Catalog

Description
Digital quantification of human eye color highlights genetic association of three new loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

SHGC-148718 (e-PCR)
- UniSTS:183047

RH46882 (e-PCR)
- UniSTS:16399

RH79771 (e-PCR)
- UniSTS:86817

STS-N27028 (e-PCR)
- UniSTS:58927

SHGC-156246 (e-PCR)
- UniSTS:183096

D10S16 (e-PCR)
- UniSTS:155756

SHGC-58033 (e-PCR)
- UniSTS:641

D17S1511E (e-PCR)
- UniSTS:151717

GDB:631802 (e-PCR)
- UniSTS:158429

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATPase binding	IEA Inferred from Electronic Annotation more info
enables K48-linked polyubiquitin modification-dependent protein binding	IEA Inferred from Electronic Annotation more info
enables K63-linked polyubiquitin modification-dependent protein binding	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info
enables ubiquitin binding	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in ERAD pathway	ISO Inferred from Sequence Orthology more info
involved_in Golgi organization	ISS Inferred from Sequence or Structural Similarity 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 ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
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	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 endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in nuclear outer membrane-endoplasmic reticulum membrane network	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	HDA more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: nuclear protein localization protein 4 homolog

Names: NPLOC4 ubiquitin recognition factor; nuclear protein localization 4 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_001369698.1 → NP_001356627.1 nuclear protein localization protein 4 homolog isoform 2

Status: VALIDATED

Source sequence(s)

AC137896, AC139530

UniProtKB/TrEMBL

A0A994J7H4

Conserved Domains (5) summary

smart00547
Location:589 → 611

ZnF_RBZ; Zinc finger domain

sd00029
Location:589 → 608

zf-RanBP2; RanBP2-type Zn finger [structural motif]

pfam05021
Location:249 → 561

NPL4; NPL4 family

pfam05020
Location:105 → 245

zf-NPL4; NPL4 family, putative zinc binding region

pfam11543
Location:1 → 80

UN_NPL4; Nuclear pore localization protein NPL4
NM_017921.4 → NP_060391.2 nuclear protein localization protein 4 homolog isoform 1

See identical proteins and their annotated locations for NP_060391.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes isoform 1.

Source sequence(s)

AB040932, AC137896, AK000664, BC025930, HY116973

Consensus CDS

CCDS45812.1

UniProtKB/Swiss-Prot

Q8N3J1, Q8TAT6, Q9H8V2, Q9H964, Q9NWR5, Q9P229

UniProtKB/TrEMBL

A0A994J7H4

Related

ENSP00000331487.5, ENST00000331134.11

Conserved Domains (5) summary

COG5100
Location:5 → 560

NPL4; Nuclear pore protein [Nuclear structure]

sd00029
Location:584 → 603

zf-RanBP2; RanBP2-type Zn finger [structural motif]

pfam05020
Location:105 → 245

zf-NPL4; NPL4 family, putative zinc binding region

pfam05021
Location:249 → 556

NPL4; NPL4 family

pfam11543
Location:1 → 80

UN_NPL4; Nuclear pore localization protein NPL4

RNA

NR_130139.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC137896, AK000664, BU542911, CK903591, HY179409
NR_130140.2 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (3) lacks multiple 5' exons and contains an alternate 5' terminal exon, compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon, found in variant 1.

Source sequence(s)

AC137896, AK000664, DA998574

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_000017.11 Reference GRCh38.p14 Primary Assembly

Range

81556885..81637112 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047436365.1 → XP_047292321.1 nuclear protein localization protein 4 homolog isoform X3

UniProtKB/TrEMBL

A0A994J7H4
XM_011524980.2 → XP_011523282.1 nuclear protein localization protein 4 homolog isoform X2

UniProtKB/TrEMBL

A0A994J7H4

Conserved Domains (4) summary

COG5100
Location:5 → 564

NPL4; Nuclear pore protein [Nuclear structure]

pfam05020
Location:105 → 245

zf-NPL4; NPL4 family, putative zinc binding region

pfam05021
Location:249 → 561

NPL4; NPL4 family

pfam11543
Location:1 → 80

UN_NPL4; Nuclear pore localization protein NPL4
XM_047436368.1 → XP_047292324.1 nuclear protein localization protein 4 homolog isoform X7
XM_011524982.3 → XP_011523284.1 nuclear protein localization protein 4 homolog isoform X4

UniProtKB/TrEMBL

A0A994J7H4

Conserved Domains (4) summary

COG5100
Location:5 → 564

NPL4; Nuclear pore protein [Nuclear structure]

pfam05020
Location:105 → 245

zf-NPL4; NPL4 family, putative zinc binding region

pfam05021
Location:249 → 561

NPL4; NPL4 family

pfam11543
Location:1 → 80

UN_NPL4; Nuclear pore localization protein NPL4
XM_047436366.1 → XP_047292322.1 nuclear protein localization protein 4 homolog isoform X5

UniProtKB/TrEMBL

A0A994J7H4
XM_011524979.2 → XP_011523281.1 nuclear protein localization protein 4 homolog isoform X1

See identical proteins and their annotated locations for XP_011523281.1

UniProtKB/TrEMBL

A0A994J7H4

Related

ENSP00000363879.5, ENST00000374747.9

Conserved Domains (4) summary

COG5100
Location:5 → 558

NPL4; Nuclear pore protein [Nuclear structure]

pfam05020
Location:105 → 245

zf-NPL4; NPL4 family, putative zinc binding region

pfam05021
Location:249 → 556

NPL4; NPL4 family

pfam11543
Location:1 → 80

UN_NPL4; Nuclear pore localization protein NPL4
XM_047436367.1 → XP_047292323.1 nuclear protein localization protein 4 homolog isoform X6

Alternate T2T-CHM13v2.0

Genomic

NC_060941.1 Alternate T2T-CHM13v2.0

Range

82474164..82554047 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054316630.1 → XP_054172605.1 nuclear protein localization protein 4 homolog isoform X3

UniProtKB/TrEMBL

A0A994J7H4
XM_054316629.1 → XP_054172604.1 nuclear protein localization protein 4 homolog isoform X2

UniProtKB/TrEMBL

A0A994J7H4
XM_054316635.1 → XP_054172610.1 nuclear protein localization protein 4 homolog isoform X7
XM_054316631.1 → XP_054172606.1 nuclear protein localization protein 4 homolog isoform X8

UniProtKB/TrEMBL

A0A994J7H4
XM_054316632.1 → XP_054172607.1 nuclear protein localization protein 4 homolog isoform X4

UniProtKB/TrEMBL

A0A994J7H4
XM_054316633.1 → XP_054172608.1 nuclear protein localization protein 4 homolog isoform X5

UniProtKB/TrEMBL

A0A994J7H4
XM_054316628.1 → XP_054172603.1 nuclear protein localization protein 4 homolog isoform X1

UniProtKB/TrEMBL

A0A994J7H4
XM_054316634.1 → XP_054172609.1 nuclear protein localization protein 4 homolog isoform X6