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Protein

Nuclear protein localization protein 4 homolog

Gene

NPLOC4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity1 Publication

Pathwayi: proteasomal ubiquitin-dependent pathway

This protein is involved in the pathway proteasomal ubiquitin-dependent pathway, which is part of Protein degradation.
View all proteins of this organism that are known to be involved in the pathway proteasomal ubiquitin-dependent pathway and in Protein degradation.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri580 – 608RanBP2-typePROSITE-ProRule annotationAdd BLAST29

GO - Molecular functioni

GO - Biological processi

  • error-free translesion synthesis Source: Reactome
  • Golgi organization Source: HGNC
  • negative regulation of RIG-I signaling pathway Source: UniProtKB
  • negative regulation of type I interferon production Source: UniProtKB
  • retrograde protein transport, ER to cytosol Source: ParkinsonsUK-UCL
  • ubiquitin-dependent ERAD pathway Source: HGNC
  • ubiquitin-dependent protein catabolic process Source: UniProtKB

Keywordsi

Molecular functionChaperone
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-110320 Translesion Synthesis by POLH
SIGNORiQ8TAT6
UniPathwayiUPA00144

Protein family/group databases

TCDBi3.A.16.1.1 the endoplasmic reticular retrotranslocon (er-rt) family

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear protein localization protein 4 homolog
Short name:
Protein NPL4
Gene namesi
Name:NPLOC4
Synonyms:KIAA1499, NPL4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000182446.13
HGNCiHGNC:18261 NPLOC4
MIMi606590 gene
neXtProtiNX_Q8TAT6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi6 – 8IIR → AIA: Abolished interaction with VCP; when associated with A-17 and A-50. 1 Publication3
Mutagenesisi17R → A: Abolished interaction with VCP; when associated with 6-A--A-8 and A-50. 1 Publication1
Mutagenesisi50R → A: Abolished interaction with VCP; when associated with 6-A--A-8 and A-17. 1 Publication1

Organism-specific databases

DisGeNETi55666
OpenTargetsiENSG00000182446
PharmGKBiPA143485558

Polymorphism and mutation databases

BioMutaiNPLOC4
DMDMi50428974

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00000579412 – 608Nuclear protein localization protein 4 homologAdd BLAST607

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei179N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ8TAT6
MaxQBiQ8TAT6
PaxDbiQ8TAT6
PeptideAtlasiQ8TAT6
PRIDEiQ8TAT6

PTM databases

iPTMnetiQ8TAT6
PhosphoSitePlusiQ8TAT6

Expressioni

Tissue specificityi

Expressed at highest levels in brain, heart, skeletal muscle, kidney and fetal liver.1 Publication

Gene expression databases

BgeeiENSG00000182446
CleanExiHS_NPLOC4
ExpressionAtlasiQ8TAT6 baseline and differential
GenevisibleiQ8TAT6 HS

Organism-specific databases

HPAiHPA021560
HPA023295

Interactioni

Subunit structurei

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).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
UFD1Q928905EBI-1994109,EBI-1994090

GO - Molecular functioni

Protein-protein interaction databases

BioGridi120798, 122 interactors
CORUMiQ8TAT6
DIPiDIP-44059N
IntActiQ8TAT6, 21 interactors
MINTiQ8TAT6
STRINGi9606.ENSP00000331487

Structurei

3D structure databases

ProteinModelPortaliQ8TAT6
SMRiQ8TAT6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini226 – 363MPNPROSITE-ProRule annotationAdd BLAST138

Domaini

Binds ubiquitinated proteins via its RanBP2-type zinc finger.By similarity

Sequence similaritiesi

Belongs to the NPL4 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri580 – 608RanBP2-typePROSITE-ProRule annotationAdd BLAST29

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG2834 Eukaryota
COG5100 LUCA
GeneTreeiENSGT00390000018731
HOGENOMiHOG000008139
HOVERGENiHBG052659
InParanoidiQ8TAT6
KOiK14015
OMAiKIKHGDM
OrthoDBiEOG091G0Q00
PhylomeDBiQ8TAT6
TreeFamiTF314173

Family and domain databases

CDDicd08061 MPN_NPL4, 1 hit
InterProiView protein in InterPro
IPR037518 MPN
IPR016563 Npl4
IPR007717 NPL4_C
IPR024682 Npl4_Ub-like_dom
IPR007716 NPL4_Zn-bd_put
IPR029071 Ubiquitin-like_domsf
IPR001876 Znf_RanBP2
IPR036443 Znf_RanBP2_sf
PfamiView protein in Pfam
PF05021 NPL4, 1 hit
PF11543 UN_NPL4, 1 hit
PF05020 zf-NPL4, 1 hit
PIRSFiPIRSF010052 Polyub_prc_Npl4, 1 hit
SMARTiView protein in SMART
SM00547 ZnF_RBZ, 1 hit
SUPFAMiSSF54236 SSF54236, 1 hit
SSF90209 SSF90209, 1 hit
PROSITEiView protein in PROSITE
PS50249 MPN, 1 hit
PS01358 ZF_RANBP2_1, 1 hit
PS50199 ZF_RANBP2_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8TAT6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAESIIIRVQ SPDGVKRITA TKRETAATFL KKVAKEFGFQ NNGFSVYINR
60 70 80 90 100
NKTGEITASS NKSLNLLKIK HGDLLFLFPS SLAGPSSEME TSVPPGFKVF
110 120 130 140 150
GAPNVVEDEI DQYLSKQDGK IYRSRDPQLC RHGPLGKCVH CVPLEPFDED
160 170 180 190 200
YLNHLEPPVK HMSFHAYIRK LTGGADKGKF VALENISCKI KSGCEGHLPW
210 220 230 240 250
PNGICTKCQP SAITLNRQKY RHVDNIMFEN HTVADRFLDF WRKTGNQHFG
260 270 280 290 300
YLYGRYTEHK DIPLGIRAEV AAIYEPPQIG TQNSLELLED PKAEVVDEIA
310 320 330 340 350
AKLGLRKVGW IFTDLVSEDT RKGTVRYSRN KDTYFLSSEE CITAGDFQNK
360 370 380 390 400
HPNMCRLSPD GHFGSKFVTA VATGGPDNQV HFEGYQVSNQ CMALVRDECL
410 420 430 440 450
LPCKDAPELG YAKESSSEQY VPDVFYKDVD KFGNEITQLA RPLPVEYLII
460 470 480 490 500
DITTTFPKDP VYTFSISQNP FPIENRDVLG ETQDFHSLAT YLSQNTSSVF
510 520 530 540 550
LDTISDFHLL LFLVTNEVMP LQDSISLLLE AVRTRNEELA QTWKRSEQWA
560 570 580 590 600
TIEQLCSTVG GQLPGLHEYG AVGGSTHTAT AAMWACQHCT FMNQPGTGHC

EMCSLPRT
Length:608
Mass (Da):68,120
Last modified:January 23, 2007 - v3
Checksum:i6ED6A0145F15C01D
GO
Isoform 2 (identifier: Q8TAT6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     558-608: TVGGQLPGLH...HCEMCSLPRT → EYPHPLPRHP...PPCQARGRLR

Note: May be due to an intron retention. No experimental confirmation available.
Show »
Length:617
Mass (Da):69,461
Checksum:iB295DB62353575A3
GO

Sequence cautioni

The sequence BAA91314 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAA96023 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAB14372 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAB14499 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti246N → S in BAB14499 (PubMed:14702039).Curated1
Sequence conflicti248H → Q in BAA91314 (PubMed:14702039).Curated1
Sequence conflicti573G → E in BAA91314 (PubMed:14702039).Curated1
Sequence conflicti592M → V in BAB14499 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_009789558 – 608TVGGQ…SLPRT → EYPHPLPRHPVAGAGEQPTL HSSPLPVVPWIPHPAASWQV PSAMQRVETRPPCQARGRLR in isoform 2. 1 PublicationAdd BLAST51

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB040932 mRNA Translation: BAA96023.1 Different initiation.
AK000664 mRNA Translation: BAA91314.1 Different initiation.
AK023046 mRNA Translation: BAB14372.1 Different initiation.
AK023272 mRNA Translation: BAB14499.1 Different initiation.
BC025930 mRNA Translation: AAH25930.1
AL834300 mRNA Translation: CAD38971.1
CCDSiCCDS45812.1 [Q8TAT6-1]
RefSeqiNP_060391.2, NM_017921.3 [Q8TAT6-1]
XP_011523281.1, XM_011524979.1 [Q8TAT6-2]
UniGeneiHs.464333

Genome annotation databases

EnsembliENST00000331134; ENSP00000331487; ENSG00000182446 [Q8TAT6-1]
ENST00000374747; ENSP00000363879; ENSG00000182446 [Q8TAT6-2]
GeneIDi55666
KEGGihsa:55666
UCSCiuc002kat.5 human [Q8TAT6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNPL4_HUMAN
AccessioniPrimary (citable) accession number: Q8TAT6
Secondary accession number(s): Q8N3J1
, Q9H8V2, Q9H964, Q9NWR5, Q9P229
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 29, 2004
Last sequence update: January 23, 2007
Last modified: March 28, 2018
This is version 146 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health