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Protein

Nuclear protein localization protein 4 homolog

Gene

NPLOC4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

The ternary complex containing UFD1L, 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-UFD1L-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope (By similarity).By similarity

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

  • ER-associated ubiquitin-dependent protein catabolic process Source: HGNC
  • error-free translesion synthesis Source: Reactome
  • Golgi organization Source: HGNC
  • retrograde protein transport, ER to cytosol Source: ParkinsonsUK-UCL
  • ubiquitin-dependent protein catabolic process Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Chaperone

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:G66-32454-MONOMER.
ReactomeiR-HSA-110320. Translesion Synthesis by POLH.
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

HGNCiHGNC:18261. NPLOC4.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB-SubCell
  • endoplasmic reticulum Source: HGNC
  • nuclear outer membrane-endoplasmic reticulum membrane network Source: HGNC
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • UFD1-NPL4 complex Source: ParkinsonsUK-UCL
  • VCP-NPL4-UFD1 AAA ATPase complex Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Nucleus

Pathology & Biotechi

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 UFD1L. The heterodimer binds ubiquitinated proteins. The heterodimer binds to VCP and inhibits Golgi membrane fusion.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
UFD1LQ928904EBI-1994109,EBI-1994090

GO - Molecular functioni

Protein-protein interaction databases

BioGridi120798. 107 interactors.
DIPiDIP-44059N.
IntActiQ8TAT6. 21 interactors.
MINTiMINT-3043958.
STRINGi9606.ENSP00000331487.

Structurei

3D structure databases

ProteinModelPortaliQ8TAT6.
SMRiQ8TAT6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

Binds ubiquitinated proteins via its RanBP2-type zinc finger.

Sequence similaritiesi

Belongs to the NPL4 family.Curated
Contains 1 RanBP2-type zinc finger.PROSITE-ProRule annotation

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.
OMAiCRDHPPW.
OrthoDBiEOG091G0Q00.
PhylomeDBiQ8TAT6.
TreeFamiTF314173.

Family and domain databases

CDDicd08061. MPN_NPL4. 1 hit.
InterProiIPR016563. Npl4.
IPR007717. NPL4_C.
IPR024682. Npl4_Ub-like_dom.
IPR007716. NPL4_Zn-bd_put.
IPR029071. Ubiquitin-rel_dom.
IPR001876. Znf_RanBP2.
[Graphical view]
PfamiPF05021. NPL4. 1 hit.
PF11543. UN_NPL4. 1 hit.
PF05020. zf-NPL4. 1 hit.
[Graphical view]
PIRSFiPIRSF010052. Polyub_prc_Npl4. 1 hit.
SMARTiSM00547. ZnF_RBZ. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF90209. SSF90209. 1 hit.
PROSITEiPS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
[Graphical view]

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ8TAT6.
SMRiQ8TAT6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120798. 107 interactors.
DIPiDIP-44059N.
IntActiQ8TAT6. 21 interactors.
MINTiMINT-3043958.
STRINGi9606.ENSP00000331487.

Protein family/group databases

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

PTM databases

iPTMnetiQ8TAT6.
PhosphoSitePlusiQ8TAT6.

Polymorphism and mutation databases

BioMutaiNPLOC4.
DMDMi50428974.

Proteomic databases

EPDiQ8TAT6.
MaxQBiQ8TAT6.
PaxDbiQ8TAT6.
PeptideAtlasiQ8TAT6.
PRIDEiQ8TAT6.

Protocols and materials databases

DNASUi55666.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi55666.
DisGeNETi55666.
GeneCardsiNPLOC4.
HGNCiHGNC:18261. NPLOC4.
HPAiHPA021560.
HPA023295.
MIMi606590. gene.
neXtProtiNX_Q8TAT6.
OpenTargetsiENSG00000182446.
PharmGKBiPA143485558.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00144.
BioCyciZFISH:G66-32454-MONOMER.
ReactomeiR-HSA-110320. Translesion Synthesis by POLH.

Miscellaneous databases

ChiTaRSiNPLOC4. human.
GeneWikiiNPLOC4.
GenomeRNAii55666.
PROiQ8TAT6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182446.
CleanExiHS_NPLOC4.
ExpressionAtlasiQ8TAT6. baseline and differential.
GenevisibleiQ8TAT6. HS.

Family and domain databases

CDDicd08061. MPN_NPL4. 1 hit.
InterProiIPR016563. Npl4.
IPR007717. NPL4_C.
IPR024682. Npl4_Ub-like_dom.
IPR007716. NPL4_Zn-bd_put.
IPR029071. Ubiquitin-rel_dom.
IPR001876. Znf_RanBP2.
[Graphical view]
PfamiPF05021. NPL4. 1 hit.
PF11543. UN_NPL4. 1 hit.
PF05020. zf-NPL4. 1 hit.
[Graphical view]
PIRSFiPIRSF010052. Polyub_prc_Npl4. 1 hit.
SMARTiSM00547. ZnF_RBZ. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF90209. SSF90209. 1 hit.
PROSITEiPS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNPL4_HUMAN
AccessioniPrimary (citable) accession number: Q8TAT6
Secondary accession number(s): Q8N3J1
, Q9H8V2, Q9H964, Q9NWR5, Q9P229
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 29, 2004
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 133 of the entry and version 3 of the sequence. [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

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.