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   24-JAN-2024, entry version 156.
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,
RC   Pancreas, 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 RIGI and recruits RNF125 to promote ubiquitination and
CC       degradation of RIGI (By similarity). {ECO:0000250|UniProtKB:Q8TAT6,
CC       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; 37.
DR   ComplexPortal; CPX-136; Vcp-Npl4-Ufd1 AAA ATPase complex.
DR   CORUM; P60670; -.
DR   IntAct; P60670; 3.
DR   STRING; 10090.ENSMUSP00000035851; -.
DR   iPTMnet; P60670; -.
DR   PhosphoSitePlus; P60670; -.
DR   SwissPalm; P60670; -.
DR   EPD; P60670; -.
DR   jPOST; P60670; -.
DR   MaxQB; P60670; -.
DR   PaxDb; 10090-ENSMUSP00000099306; -.
DR   PeptideAtlas; P60670; -.
DR   ProteomicsDB; 295511; -. [P60670-1]
DR   ProteomicsDB; 295512; -. [P60670-2]
DR   Pumba; P60670; -.
DR   Antibodypedia; 10070; 165 antibodies from 28 providers.
DR   DNASU; 217365; -.
DR   Ensembl; ENSMUST00000044271.15; ENSMUSP00000035851.9; ENSMUSG00000039703.17. [P60670-1]
DR   Ensembl; ENSMUST00000103017.4; ENSMUSP00000099306.4; ENSMUSG00000039703.17. [P60670-2]
DR   GeneID; 217365; -.
DR   KEGG; mmu:217365; -.
DR   UCSC; uc007msp.2; mouse. [P60670-2]
DR   UCSC; uc007msq.2; mouse. [P60670-1]
DR   AGR; MGI:2679787; -.
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   OrthoDB; 5400828at2759; -.
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 78 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 249 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
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; IBA:GO_Central.
DR   GO; GO:0036501; C:UFD1-NPL4 complex; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0034098; C:VCP-NPL4-UFD1 AAA ATPase complex; EXP:ComplexPortal.
DR   GO; GO:0051117; F:ATPase 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; EXP:ComplexPortal.
DR   GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; EXP:ComplexPortal.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR   CDD; cd08061; MPN_NPL4; 1.
DR   Gene3D; 3.40.140.10; Cytidine Deaminase, domain 2; 1.
DR   Gene3D; 2.30.30.380; Zn-finger domain of Sec23/24; 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; NUCLEAR PROTEIN LOCALIZATION 4; 1.
DR   PANTHER; PTHR12710:SF0; NUCLEAR PROTEIN LOCALIZATION PROTEIN 4 HOMOLOG; 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; SSF90209; Ran binding protein zinc finger-like; 1.
DR   SUPFAM; SSF54236; Ubiquitin-like; 1.
DR   PROSITE; PS50249; MPN; 1.
DR   PROSITE; PS01358; ZF_RANBP2_1; 1.
DR   PROSITE; PS50199; ZF_RANBP2_2; 1.
DR   Genevisible; P60670; MM.
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
//