NPL4_MOUSE
ID NPL4_MOUSE Reviewed; 608 AA.
AC P60670; B1ATY4; B1ATY5;
DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Nuclear protein localization protein 4 homolog;
DE Short=Protein NPL4;
GN Name=Nploc4; Synonyms=Kiaa1499, Npl4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-179, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [6]
RP INTERACTION WITH ZFAND2B.
RX PubMed=24160817; DOI=10.1042/bj20130710;
RA Glinka T., Alter J., Braunstein I., Tzach L., Wei Sheng C., Geifman S.,
RA Edelmann M.J., Kessler B.M., Stanhill A.;
RT "Signal-peptide-mediated translocation is regulated by a p97-AIRAPL
RT complex.";
RL Biochem. J. 457:253-261(2014).
CC -!- FUNCTION: The ternary complex containing UFD1, VCP and NPLOC4 binds
CC ubiquitinated proteins and is necessary for the export of misfolded
CC proteins from the ER to the cytoplasm, where they are degraded by the
CC proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly
CC at the end of mitosis and is necessary for the formation of a closed
CC nuclear envelope (By similarity). Acts as a negative regulator of type
CC I interferon production via the complex formed with VCP and UFD1, which
CC binds to DDX58/RIG-I and recruits RNF125 to promote ubiquitination and
CC degradation of DDX58/RIG-I (By similarity).
CC {ECO:0000250|UniProtKB:Q8TAT6, ECO:0000250|UniProtKB:Q9ES54}.
CC -!- PATHWAY: Protein degradation; proteasomal ubiquitin-dependent pathway.
CC -!- SUBUNIT: Heterodimer with UFD1. The heterodimer binds ubiquitinated
CC proteins. The heterodimer binds to VCP and inhibits Golgi membrane
CC fusion (By similarity). Interacts with ZFAND2B; probably through VCP
CC (PubMed:24160817). {ECO:0000250|UniProtKB:Q9ES54,
CC ECO:0000269|PubMed:24160817}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9ES54}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q9ES54}. Nucleus {ECO:0000250|UniProtKB:Q9ES54}.
CC Note=Associated with the endoplasmic reticulum and nuclear.
CC {ECO:0000250|UniProtKB:Q9ES54}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P60670-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P60670-2; Sequence=VSP_009790;
CC -!- DOMAIN: Binds ubiquitinated proteins via its RanBP2-type zinc finger.
CC {ECO:0000250|UniProtKB:Q9ES54}.
CC -!- SIMILARITY: Belongs to the NPL4 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC98185.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK129375; BAC98185.1; ALT_INIT; mRNA.
DR EMBL; AL669855; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC065156; AAH65156.1; -; mRNA.
DR CCDS; CCDS25732.1; -. [P60670-2]
DR CCDS; CCDS56827.1; -. [P60670-1]
DR RefSeq; NP_001181952.1; NM_001195023.1. [P60670-1]
DR RefSeq; NP_955763.1; NM_199469.2. [P60670-2]
DR PDB; 2PJH; NMR; -; A=1-80.
DR PDBsum; 2PJH; -.
DR AlphaFoldDB; P60670; -.
DR SMR; P60670; -.
DR BioGRID; 229901; 36.
DR ComplexPortal; CPX-136; Vcp-Npl4-Ufd1 AAA ATPase complex.
DR CORUM; P60670; -.
DR IntAct; P60670; 3.
DR STRING; 10090.ENSMUSP00000099306; -.
DR iPTMnet; P60670; -.
DR PhosphoSitePlus; P60670; -.
DR EPD; P60670; -.
DR jPOST; P60670; -.
DR MaxQB; P60670; -.
DR PaxDb; P60670; -.
DR PeptideAtlas; P60670; -.
DR PRIDE; P60670; -.
DR ProteomicsDB; 295511; -. [P60670-1]
DR ProteomicsDB; 295512; -. [P60670-2]
DR Antibodypedia; 10070; 144 antibodies from 28 providers.
DR DNASU; 217365; -.
DR Ensembl; ENSMUST00000044271; ENSMUSP00000035851; ENSMUSG00000039703. [P60670-1]
DR Ensembl; ENSMUST00000103017; ENSMUSP00000099306; ENSMUSG00000039703. [P60670-2]
DR GeneID; 217365; -.
DR KEGG; mmu:217365; -.
DR UCSC; uc007msp.2; mouse. [P60670-2]
DR UCSC; uc007msq.2; mouse. [P60670-1]
DR CTD; 55666; -.
DR MGI; MGI:2679787; Nploc4.
DR VEuPathDB; HostDB:ENSMUSG00000039703; -.
DR eggNOG; KOG2834; Eukaryota.
DR GeneTree; ENSGT00390000018731; -.
DR HOGENOM; CLU_017172_2_0_1; -.
DR InParanoid; P60670; -.
DR OMA; KWSRTGR; -.
DR PhylomeDB; P60670; -.
DR TreeFam; TF314173; -.
DR Reactome; R-MMU-110320; Translesion Synthesis by POLH.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-9755511; KEAP1-NFE2L2 pathway.
DR UniPathway; UPA00144; -.
DR BioGRID-ORCS; 217365; 27 hits in 73 CRISPR screens.
DR ChiTaRS; Nploc4; mouse.
DR EvolutionaryTrace; P60670; -.
DR PRO; PR:P60670; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P60670; protein.
DR Bgee; ENSMUSG00000039703; Expressed in spermatocyte and 246 other tissues.
DR Genevisible; P60670; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:HGNC-UCL.
DR GO; GO:0042175; C:nuclear outer membrane-endoplasmic reticulum membrane network; ISS:HGNC-UCL.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0036501; C:UFD1-NPL4 complex; ISS:ParkinsonsUK-UCL.
DR GO; GO:0034098; C:VCP-NPL4-UFD1 AAA ATPase complex; ISS:UniProtKB.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0036435; F:K48-linked polyubiquitin modification-dependent protein binding; ISO:MGI.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0043130; F:ubiquitin binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0007030; P:Golgi organization; ISS:HGNC-UCL.
DR GO; GO:0039536; P:negative regulation of RIG-I signaling pathway; ISS:UniProtKB.
DR GO; GO:0032480; P:negative regulation of type I interferon production; ISS:UniProtKB.
DR GO; GO:0030970; P:retrograde protein transport, ER to cytosol; ISS:ParkinsonsUK-UCL.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISS:HGNC-UCL.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR CDD; cd08061; MPN_NPL4; 1.
DR IDEAL; IID50029; -.
DR InterPro; IPR037518; MPN.
DR InterPro; IPR016563; Npl4.
DR InterPro; IPR007717; NPL4_C.
DR InterPro; IPR024682; Npl4_Ub-like_dom.
DR InterPro; IPR007716; NPL4_Zn-bd_put.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR001876; Znf_RanBP2.
DR InterPro; IPR036443; Znf_RanBP2_sf.
DR PANTHER; PTHR12710; PTHR12710; 1.
DR Pfam; PF05021; NPL4; 1.
DR Pfam; PF11543; UN_NPL4; 1.
DR Pfam; PF05020; zf-NPL4; 1.
DR PIRSF; PIRSF010052; Polyub_prc_Npl4; 1.
DR SMART; SM00547; ZnF_RBZ; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF90209; SSF90209; 1.
DR PROSITE; PS50249; MPN; 1.
DR PROSITE; PS01358; ZF_RANBP2_1; 1.
DR PROSITE; PS50199; ZF_RANBP2_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chaperone; Cytoplasm;
KW Endoplasmic reticulum; Metal-binding; Nucleus; Reference proteome; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q8TAT6"
FT CHAIN 2..608
FT /note="Nuclear protein localization protein 4 homolog"
FT /id="PRO_0000057942"
FT DOMAIN 226..363
FT /note="MPN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT ZN_FING 580..608
FT /note="RanBP2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q8TAT6"
FT MOD_RES 179
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT VAR_SEQ 452..483
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009790"
FT STRAND 8..10
FT /evidence="ECO:0007829|PDB:2PJH"
FT STRAND 12..17
FT /evidence="ECO:0007829|PDB:2PJH"
FT HELIX 26..36
FT /evidence="ECO:0007829|PDB:2PJH"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:2PJH"
FT HELIX 52..55
FT /evidence="ECO:0007829|PDB:2PJH"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:2PJH"
FT TURN 63..67
FT /evidence="ECO:0007829|PDB:2PJH"
SQ SEQUENCE 608 AA; 68017 MW; 378E31B35D559336 CRC64;
MAESIIIRVQ SPDGVKRITA TKRETAATFL KKVAKEFGFQ NNGFSVYINR NKTGEITASS
SKSLHLLKIK HGDLLFLFPS SLAGPSSEME TSTSVGLKAF GAPNVVEDEI DQYLSKQDGK
IYRSRDPQLC RHGPLGKCVH CVPLEPFDED YLNHLEPPVK HMSFHAYIRK LTGGADKGKF
VALENISCKI KSGCEGHLPW PNGICTKCQP SAITLNRQKY RHVDNIMFEN HTVADRFLDF
WRKTGNQHFG YLYGRYTEHK DIPLGIRAEV AAIYEPPQIG TQNSLELLED PKAEVVDEIA
AKLGLRKVGW IFTDLVSEDT RKGTVRYSRN KDTYFLSSEE CITAGDFQNK HPNICRLSPD
GHFGSKFVTA VATGGPDNQV HFEGYQVSNQ CMALVRDECL LPCKDAPELG YAKESSSEQY
VPDVFYKDID KFGNEITQLA RPLPVEYLII DITTTFPKDP VYTFSISQNP FPIENRDVLG
ETQDFHSLAT YLSQNTSSVF LDTISDFHLL LFLVTNEVMP LQDSISLLLE AVRTRNEELA
QTWKKSEQWA TIEQLCSTVG VQLPGLHEFG AVGGSARAAT SAMWACQHCT FMNQPGTGHC
EMCSLPRT
