Nuclear protein localization protein 4 homolog (NPLOC4)

The protein contains 608 amino acids for an estimated molecular weight of 68120 Da.

 

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). (updated: Dec. 20, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 13%
Model score: 0
No model available.

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The reference OMIM entry for this protein is 606590

Nuclear protein localization 4, s. cerevisiae, homolog of; nploc4
Npl4, s. cerevisiae, homolog of
Kiaa1499

CLONING

By screening for cDNAs with the potential to encode large proteins expressed in brain, Nagase et al. (2000) identified a cDNA encoding the human homolog of yeast Npl4, which they designated KIAA1499. The deduced 660-amino acid human protein was predicted to be 34% identical to the yeast protein. RT-PCR analysis detected ubiquitous expression that was highest in brain, followed by spleen. Within brain, expression was strongest in amygdala and substantia nigra, followed by caudate nucleus. UFD1L (601754), which maps to chromosome 22q11.2, a region deleted in patients with DiGeorge syndrome (DGS; 188400) or velocardiofacial syndrome (VCFS; 192420), is similar to a yeast protein essential for the ubiquitin-mediated protein degradation pathway. Rat Ufd1l binds to Npl4, a component of the nuclear pore complex. By RT-PCR with degenerate primers based on rat Npl4, followed by database searching, Botta et al. (2001) obtained a cDNA encoding human NPL4. Sequence analysis predicted that the 608-amino acid transmembrane protein, which is 96% homologous to the rat protein, contains 5 potential N-glycosylation sites, 8 potential N-myristoylation sites, several phosphorylation sites, and a C-terminal zinc finger motif. Northern blot analysis detected a major transcript of 4.5 kb and minor transcripts of 9.5 and 2.5 kb. Expression was most abundant in brain, heart, skeletal muscle, kidney, and fetal liver. Yeast 2-hybrid analysis confirmed the interaction of UFD1L and NPL4 in human. Sequence analysis identified no pathologic variants in the NPL4 gene in 7 DGS/VCFS patients with no 22q11 deletions or mutations in the UFD1L gene.

GENE STRUCTURE

By Southern blot analysis, Botta et al. (2001) determined that the NPL4 gene spans 40 kb.

MAPPING

By analysis of a human-rodent hybrid panel, Nagase et al. (2000) mapped the NPLOC4 gene, which they identified as KIAA1499, to chromosome 17. Using FISH, Botta et al. (2001) refined the localization to 17qter. ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 606590 was added.