Aliases for NPLOC4 Gene

Aliases for NPLOC4 Gene

  • NPL4 Homolog, Ubiquitin Recognition Factor 2 3 5
  • NPL4 2 3 4
  • Nuclear Protein Localization Protein 4 Homolog 3 4
  • NPLOC4 Ubiquitin Recognition Factor 2 3
  • KIAA1499 2 4
  • Nuclear Protein Localization 4 Homolog (S. Cerevisiae) 2
  • Nuclear Protein Localization 4 Homolog 3
  • Protein NPL4 4
  • FLJ20657 2
  • NPLOC4 5

External Ids for NPLOC4 Gene

Previous GeneCards Identifiers for NPLOC4 Gene

  • GC17M077135
  • GC17M079523
  • GC17M074971

Summaries for NPLOC4 Gene

GeneCards Summary for NPLOC4 Gene

NPLOC4 (NPL4 Homolog, Ubiquitin Recognition Factor) is a Protein Coding gene. Diseases associated with NPLOC4 include Multisystem Proteinopathy and Inclusion Body Myopathy With Paget Disease Of Bone And Frontotemporal Dementia. Among its related pathways are DNA Double-Strand Break Repair and Protein processing in endoplasmic reticulum. Gene Ontology (GO) annotations related to this gene include ubiquitin protein ligase binding and ubiquitin binding.

UniProtKB/Swiss-Prot Summary for NPLOC4 Gene

  • The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope (By similarity). Acts as a negative regulator of type I interferon production via the complex formed with VCP and UFD1, which binds to DDX58/RIG-I and recruits RNF125 to promote ubiquitination and degradation of DDX58/RIG-I (PubMed:26471729).

Gene Wiki entry for NPLOC4 Gene

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NPLOC4 Gene

Genomics for NPLOC4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NPLOC4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NPLOC4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NPLOC4

Top Transcription factor binding sites by QIAGEN in the NPLOC4 gene promoter:
  • GCNF
  • GCNF-1
  • GCNF-2
  • STAT5A

Genomic Locations for NPLOC4 Gene

Latest Assembly
chr17:81,556,885-81,648,465
(GRCh38/hg38)
Size:
91,581 bases
Orientation:
Minus strand

Previous Assembly
chr17:79,523,911-79,604,138
(GRCh37/hg19 by Entrez Gene)
Size:
80,228 bases
Orientation:
Minus strand

chr17:79,523,913-79,615,495
(GRCh37/hg19 by Ensembl)
Size:
91,583 bases
Orientation:
Minus strand

Genomic View for NPLOC4 Gene

Genes around NPLOC4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NPLOC4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NPLOC4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NPLOC4 Gene

Proteins for NPLOC4 Gene

  • Protein details for NPLOC4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8TAT6-NPL4_HUMAN
    Recommended name:
    Nuclear protein localization protein 4 homolog
    Protein Accession:
    Q8TAT6
    Secondary Accessions:
    • Q8N3J1
    • Q9H8V2
    • Q9H964
    • Q9NWR5
    • Q9P229

    Protein attributes for NPLOC4 Gene

    Size:
    608 amino acids
    Molecular mass:
    68120 Da
    Quaternary structure:
    • Heterodimer with UFD1 (PubMed:11574150, PubMed:26471729). The heterodimer binds ubiquitinated proteins (By similarity). The heterodimer binds to VCP and inhibits Golgi membrane fusion (PubMed:11574150, PubMed:26471729). Interacts with ZFAND2B; probably through VCP (PubMed:24160817).
    SequenceCaution:
    • Sequence=BAA91314.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAA96023.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB14372.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB14499.1; Type=Erroneous initiation; Evidence={ECO:0000305};
    Miscellaneous:
    • [Isoform 2]: May be due to an intron retention.

    Alternative splice isoforms for NPLOC4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NPLOC4 Gene

Post-translational modifications for NPLOC4 Gene

  • Ubiquitination at Lys62, Lys68, Lys116, Lys189, Lys207, Lys243, Lys260, Lys302, Lys307, Lys404, Lys431, and Lys544
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for NPLOC4 Gene

Domains & Families for NPLOC4 Gene

Gene Families for NPLOC4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transporters

Protein Domains for NPLOC4 Gene

Suggested Antigen Peptide Sequences for NPLOC4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ57969, highly similar to Nuclear protein localization protein 4 homolog (B4DG89_HUMAN)
  • Nuclear protein localization protein 4 homolog (NPL4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8TAT6

UniProtKB/Swiss-Prot:

NPL4_HUMAN :
  • Binds ubiquitinated proteins via its RanBP2-type zinc finger.
  • Belongs to the NPL4 family.
Domain:
  • Binds ubiquitinated proteins via its RanBP2-type zinc finger.
Family:
  • Belongs to the NPL4 family.
genes like me logo Genes that share domains with NPLOC4: view

Function for NPLOC4 Gene

Molecular function for NPLOC4 Gene

UniProtKB/Swiss-Prot Function:
The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope (By similarity). Acts as a negative regulator of type I interferon production via the complex formed with VCP and UFD1, which binds to DDX58/RIG-I and recruits RNF125 to promote ubiquitination and degradation of DDX58/RIG-I (PubMed:26471729).

Phenotypes From GWAS Catalog for NPLOC4 Gene

Gene Ontology (GO) - Molecular Function for NPLOC4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 11574150
GO:0031625 ubiquitin protein ligase binding IBA 21873635
GO:0043130 ubiquitin binding IBA 21873635
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with NPLOC4: view
genes like me logo Genes that share phenotypes with NPLOC4: view

Animal Models for NPLOC4 Gene

MGI Knock Outs for NPLOC4:
  • Nploc4 Nploc4<tm1a(EUCOMM)Wtsi>

miRNA for NPLOC4 Gene

miRTarBase miRNAs that target NPLOC4

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NPLOC4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NPLOC4 Gene

Localization for NPLOC4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NPLOC4 Gene

Cytoplasm, cytosol. Endoplasmic reticulum. Nucleus. Note=Associated with the endoplasmic reticulum and nuclear. {ECO:0000250 UniProtKB:Q9ES54}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NPLOC4 gene
Compartment Confidence
nucleus 5
endoplasmic reticulum 5
cytosol 5
mitochondrion 2
endosome 2
lysosome 2
golgi apparatus 2
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
  • Cytosol (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NPLOC4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA 21873635
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA --
GO:0005783 endoplasmic reticulum ISS 11574150
GO:0005829 cytosol IEA --
genes like me logo Genes that share ontologies with NPLOC4: view

Pathways & Interactions for NPLOC4 Gene

genes like me logo Genes that share pathways with NPLOC4: view

Pathways by source for NPLOC4 Gene

2 GeneGo (Thomson Reuters) pathways for NPLOC4 Gene
  • Regulation of degradation of deltaF508 CFTR in CF
  • Regulation of degradation of wt-CFTR

UniProtKB/Swiss-Prot Q8TAT6-NPL4_HUMAN

  • Pathway: Protein degradation; proteasomal ubiquitin-dependent pathway.

SIGNOR curated interactions for NPLOC4 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for NPLOC4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006511 ubiquitin-dependent protein catabolic process IBA,IMP 26471729
GO:0007030 Golgi organization ISS 11574150
GO:0030433 ubiquitin-dependent ERAD pathway ISS 11574150
GO:0030970 retrograde protein transport, ER to cytosol IMP 25660456
GO:0032480 negative regulation of type I interferon production IMP 26471729
genes like me logo Genes that share ontologies with NPLOC4: view

Drugs & Compounds for NPLOC4 Gene

No Compound Related Data Available

Transcripts for NPLOC4 Gene

mRNA/cDNA for NPLOC4 Gene

2 REFSEQ mRNAs :
20 NCBI additional mRNA sequence :
21 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NPLOC4

Alternative Splicing Database (ASD) splice patterns (SP) for NPLOC4 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14a · 14b ^ 15a · 15b ^ 16 ^ 17 ^ 18a · 18b ^ 19a · 19b ^ 20a · 20b ^ 21 ^
SP1: - - - - - - - -
SP2: - - - - - -
SP3: - - - - - -
SP4: - - - -
SP5: - - - - -
SP6: - - - - -
SP7: - - - -
SP8: - - -
SP9: -
SP10:

ExUns: 22 ^ 23a · 23b · 23c · 23d · 23e · 23f · 23g · 23h · 23i
SP1: -
SP2: -
SP3:
SP4:
SP5: -
SP6: -
SP7: -
SP8: -
SP9: -
SP10: -

Relevant External Links for NPLOC4 Gene

GeneLoc Exon Structure for
NPLOC4

Expression for NPLOC4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NPLOC4 Gene

mRNA differential expression in normal tissues according to GTEx for NPLOC4 Gene

This gene is overexpressed in Muscle - Skeletal (x4.6).

Protein differential expression in normal tissues from HIPED for NPLOC4 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (12.9) and Lymph node (6.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NPLOC4 Gene



Protein tissue co-expression partners for NPLOC4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NPLOC4

SOURCE GeneReport for Unigene cluster for NPLOC4 Gene:

Hs.464333

mRNA Expression by UniProt/SwissProt for NPLOC4 Gene:

Q8TAT6-NPL4_HUMAN
Tissue specificity: Expressed at highest levels in brain, heart, skeletal muscle, kidney and fetal liver.

Evidence on tissue expression from TISSUES for NPLOC4 Gene

  • Nervous system(4.9)
  • Liver(4.5)
  • Pancreas(4.5)
  • Blood(4.4)
  • Skin(3.1)
  • Lung(2.7)
  • Intestine(2.4)
  • Kidney(2.3)
  • Muscle(2.2)
  • Eye(2.1)
genes like me logo Genes that share expression patterns with NPLOC4: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for NPLOC4 Gene

Orthologs for NPLOC4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for NPLOC4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NPLOC4 29 30
  • 99.4 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia -- 30
  • 96 (a)
OneToMany
-- 30
  • 78 (a)
OneToMany
Cow
(Bos Taurus)
Mammalia NPLOC4 29 30
  • 90.57 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NPLOC4 29 30
  • 90.44 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Nploc4 29
  • 89.36 (n)
Mouse
(Mus musculus)
Mammalia Nploc4 29 16 30
  • 89.04 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia NPLOC4 30
  • 82 (a)
OneToOne
Chicken
(Gallus gallus)
Aves NPLOC4 29 30
  • 82.13 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia NPLOC4 30
  • 91 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia nploc4 29
  • 76.43 (n)
African clawed frog
(Xenopus laevis)
Amphibia npl4-prov 29
Zebrafish
(Danio rerio)
Actinopterygii nploc4 29 30
  • 75.32 (n)
OneToOne
wufi11f09 29
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP001986 29
  • 55.44 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta Npl4 29 30
  • 55.41 (n)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea npl-4.2 29 30
  • 51.08 (n)
OneToMany
npl-4.1 30
  • 44 (a)
OneToMany
A. gosspyii yeast
(Eremothecium gossypii)
Saccharomycetes AGOS_AGR211W 29
  • 48.9 (n)
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0E24575g 29
  • 45.63 (n)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes NPL4 29 30 32
  • 45.42 (n)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.4296 30
  • 47 (a)
OneToOne
Bread mold
(Neurospora crassa)
Ascomycetes NCU02680 29
  • 46.85 (n)
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes npl4 29
  • 45.07 (n)
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.14013 29
Species where no ortholog for NPLOC4 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for NPLOC4 Gene

ENSEMBL:
Gene Tree for NPLOC4 (if available)
TreeFam:
Gene Tree for NPLOC4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NPLOC4: view image
Alliance of Genome Resources:
Additional Orthologs for NPLOC4

Paralogs for NPLOC4 Gene

(54) SIMAP similar genes for NPLOC4 Gene using alignment to 9 proteins:

  • NPL4_HUMAN
  • B4DG89_HUMAN
  • I3L0W3_HUMAN
  • I3L281_HUMAN
  • I3L283_HUMAN
  • I3L3I1_HUMAN
  • I3L4S2_HUMAN
  • I3L4U9_HUMAN
  • K7EJN1_HUMAN
genes like me logo Genes that share paralogs with NPLOC4: view

No data available for Paralogs for NPLOC4 Gene

Variants for NPLOC4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NPLOC4 Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
rs113318717 Benign: not provided 81,559,353(-) G/A
NM_017921.4(NPLOC4):c.1733C>T (p.Thr578Met)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
rs17852307 Benign: not provided 81,572,047(-) C/A
NM_017921.4(NPLOC4):c.1323G>T (p.Arg441=)
NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS
rs201095089 Benign: not provided 81,559,406(-) G/A
NM_017921.4(NPLOC4):c.1680C>T (p.Gly560=)
NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS
rs201622340 Likely Benign: not provided 81,559,396(-) G/C
NM_017921.4(NPLOC4):c.1690C>G (p.Pro564Ala)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for NPLOC4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for NPLOC4 Gene

Variant ID Type Subtype PubMed ID
dgv1522n106 CNV deletion 24896259
esv1009816 CNV insertion 20482838
esv1319911 CNV deletion 17803354
esv26223 CNV gain+loss 19812545
esv2666942 CNV deletion 23128226
esv2667665 CNV deletion 23128226
esv2716454 CNV deletion 23290073
esv3363550 CNV insertion 20981092
esv3554885 CNV deletion 23714750
esv9166 CNV loss 19470904
nsv1071812 CNV deletion 25765185
nsv1150393 CNV insertion 26484159
nsv2164 CNV insertion 18451855
nsv428351 CNV gain 18775914
nsv470620 CNV loss 18288195
nsv471902 CNV novel sequence insertion 20440878
nsv828128 CNV loss 20364138
nsv833567 CNV loss 17160897
nsv833568 CNV loss 17160897
nsv952389 CNV deletion 24416366
nsv954534 CNV deletion 24416366

Variation tolerance for NPLOC4 Gene

Residual Variation Intolerance Score: 50.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.34; 7.61% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NPLOC4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NPLOC4
Leiden Open Variation Database (LOVD)
NPLOC4

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NPLOC4 Gene

Disorders for NPLOC4 Gene

MalaCards: The human disease database

(3) MalaCards diseases for NPLOC4 Gene - From: COP and GCD

- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for NPLOC4

genes like me logo Genes that share disorders with NPLOC4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NPLOC4 Gene

Publications for NPLOC4 Gene

  1. Cloning and characterization of the gene encoding human NPL4, a protein interacting with the ubiquitin fusion-degradation protein (UFD1L). (PMID: 11574150) Botta A … Novelli G (Gene 2001) 2 3 4 22
  2. A non-canonical role of the p97 complex in RIG-I antiviral signaling. (PMID: 26471729) Hao Q … Zhou Z (The EMBO journal 2015) 3 4
  3. The p97-Ufd1-Npl4 ATPase complex ensures robustness of the G2/M checkpoint by facilitating CDC25A degradation. (PMID: 24429874) Riemer A … Meyer H (Cell cycle (Georgetown, Tex.) 2014) 2 3
  4. Signal-peptide-mediated translocation is regulated by a p97-AIRAPL complex. (PMID: 24160817) Glinka T … Stanhill A (The Biochemical journal 2014) 3 4
  5. Digital quantification of human eye color highlights genetic association of three new loci. (PMID: 20463881) Liu F … Kayser M (PLoS genetics 2010) 3 40

Products for NPLOC4 Gene

Sources for NPLOC4 Gene