NPL4_RAT
ID NPL4_RAT Reviewed; 608 AA.
AC Q9ES54; Q3T1J3;
DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Nuclear protein localization protein 4 homolog;
DE Short=Protein NPL4;
GN Name=Nploc4; Synonyms=Npl4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 9-17; 24-31; 36-50; 71-116;
RP 161-169; 222-236; 244-252; 357-316; 405-444; 459-477 AND 536-544, FUNCTION,
RP HETERODIMERIZATION WITH UFD1, INTERACTION WITH VCP, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Liver;
RX PubMed=10811609; DOI=10.1093/emboj/19.10.2181;
RA Meyer H.H., Shorter J.G., Seemann J., Pappin D., Warren G.;
RT "A complex of mammalian ufd1 and npl4 links the AAA-ATPase, p97, to
RT ubiquitin and nuclear transport pathways.";
RL EMBO J. 19:2181-2192(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [3]
RP FUNCTION.
RX PubMed=11781570; DOI=10.1038/ncb1201-1086;
RA Hetzer M., Meyer H.H., Walther T.C., Bilbao-Cortes D., Warren G.,
RA Mattaj I.W.;
RT "Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear
RT assembly.";
RL Nat. Cell Biol. 3:1086-1091(2001).
RN [4]
RP FUNCTION.
RX PubMed=11740563; DOI=10.1038/414652a;
RA Ye Y., Meyer H.H., Rapoport T.A.;
RT "The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER
RT into the cytosol.";
RL Nature 414:652-656(2001).
RN [5]
RP FUNCTION.
RX PubMed=14636562; DOI=10.1016/s0092-8674(03)00815-8;
RA Cao K., Nakajima R., Meyer H.H., Zheng Y.;
RT "The AAA-ATPase Cdc48/p97 regulates spindle disassembly at the end of
RT mitosis.";
RL Cell 115:355-367(2003).
RN [6]
RP STRUCTURE BY NMR OF 580-608, AND FUNCTION.
RX PubMed=12411482; DOI=10.1093/emboj/cdf579;
RA Meyer H.H., Wang Y., Warren G.;
RT "Direct binding of ubiquitin conjugates by the mammalian p97 adaptor
RT complexes, p47 and Ufd1-Npl4.";
RL EMBO J. 21:5645-5652(2002).
RN [7]
RP FUNCTION, STRUCTURE BY NMR OF 580-608 IN COMPLEX WITH ZINC, AND INTERACTION
RP WITH UBIQUITIN.
RX PubMed=12644454; DOI=10.1074/jbc.m300459200;
RA Wang B., Alam S.L., Meyer H.H., Payne M., Stemmler T.L., Davis D.R.,
RA Sundquist W.I.;
RT "Structure and ubiquitin interactions of the conserved zinc finger domain
RT of Npl4.";
RL J. Biol. Chem. 278:20225-20234(2003).
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 (PubMed:10811609, PubMed:11740563, PubMed:11781570,
CC PubMed:12411482, PubMed:12644454, PubMed:14636562). Acts as a negative
CC regulator of type I interferon production via the complex formed with
CC VCP and UFD1, which binds to DDX58/RIG-I and recruits RNF125 to promote
CC ubiquitination and degradation of DDX58/RIG-I (By similarity).
CC {ECO:0000250|UniProtKB:Q8TAT6, ECO:0000269|PubMed:10811609,
CC ECO:0000269|PubMed:11740563, ECO:0000269|PubMed:11781570,
CC ECO:0000269|PubMed:12411482, ECO:0000269|PubMed:12644454,
CC ECO:0000269|PubMed:14636562}.
CC -!- PATHWAY: Protein degradation; proteasomal ubiquitin-dependent pathway.
CC -!- SUBUNIT: Heterodimer with UFD1 (PubMed:10811609, PubMed:12644454). The
CC heterodimer binds ubiquitinated proteins (PubMed:12644454). The
CC heterodimer binds to VCP and inhibits Golgi membrane fusion
CC (PubMed:10811609, PubMed:12644454). Interacts with ZFAND2B; probably
CC through VCP (By similarity). {ECO:0000250|UniProtKB:Q8TAT6,
CC ECO:0000269|PubMed:10811609, ECO:0000269|PubMed:12644454}.
CC -!- INTERACTION:
CC Q9ES54; Q9ES53: Ufd1; NbExp=6; IntAct=EBI-1993990, EBI-399031;
CC Q9ES54; P70362: Ufd1; Xeno; NbExp=18; IntAct=EBI-1993990, EBI-7961331;
CC Q9ES54; Q01853: Vcp; Xeno; NbExp=11; IntAct=EBI-1993990, EBI-80597;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10811609}.
CC Endoplasmic reticulum {ECO:0000269|PubMed:10811609}. Nucleus
CC {ECO:0000269|PubMed:10811609}. Note=Associated with the endoplasmic
CC reticulum and nuclear.
CC -!- DOMAIN: Binds ubiquitinated proteins via its RanBP2-type zinc finger.
CC {ECO:0000269|PubMed:12644454}.
CC -!- SIMILARITY: Belongs to the NPL4 family. {ECO:0000305}.
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DR EMBL; AF234600; AAG27534.1; -; mRNA.
DR EMBL; BC101887; AAI01888.1; -; mRNA.
DR RefSeq; NP_542144.1; NM_080577.2.
DR PDB; 1NJ3; NMR; -; A=580-608.
DR PDB; 1Q5W; NMR; -; A=580-608.
DR PDBsum; 1NJ3; -.
DR PDBsum; 1Q5W; -.
DR AlphaFoldDB; Q9ES54; -.
DR SMR; Q9ES54; -.
DR BioGRID; 250817; 8.
DR ComplexPortal; CPX-138; Vcp-Npl4-Ufd1 AAA ATPase complex.
DR CORUM; Q9ES54; -.
DR DIP; DIP-41365N; -.
DR IntAct; Q9ES54; 11.
DR MINT; Q9ES54; -.
DR STRING; 10116.ENSRNOP00000051856; -.
DR iPTMnet; Q9ES54; -.
DR PhosphoSitePlus; Q9ES54; -.
DR jPOST; Q9ES54; -.
DR PaxDb; Q9ES54; -.
DR PRIDE; Q9ES54; -.
DR Ensembl; ENSRNOT00000080188; ENSRNOP00000068982; ENSRNOG00000036698.
DR GeneID; 140639; -.
DR KEGG; rno:140639; -.
DR CTD; 55666; -.
DR RGD; 620794; Nploc4.
DR eggNOG; KOG2834; Eukaryota.
DR GeneTree; ENSGT00390000018731; -.
DR InParanoid; Q9ES54; -.
DR OrthoDB; 1106766at2759; -.
DR PhylomeDB; Q9ES54; -.
DR Reactome; R-RNO-110320; Translesion Synthesis by POLH.
DR Reactome; R-RNO-8951664; Neddylation.
DR Reactome; R-RNO-9755511; KEAP1-NFE2L2 pathway.
DR UniPathway; UPA00144; -.
DR EvolutionaryTrace; Q9ES54; -.
DR PRO; PR:Q9ES54; -.
DR Proteomes; UP000002494; Chromosome 10.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0036501; C:UFD1-NPL4 complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0034098; C:VCP-NPL4-UFD1 AAA ATPase complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051117; F:ATPase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0043130; F:ubiquitin binding; IDA:BHF-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:BHF-UCL.
DR GO; GO:0007030; P:Golgi organization; IDA: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; IC:ComplexPortal.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR CDD; cd08061; MPN_NPL4; 1.
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; Chaperone; Cytoplasm; Direct protein sequencing;
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_0000057943"
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:0000250|UniProtKB:P60670"
FT STRAND 587..589
FT /evidence="ECO:0007829|PDB:1NJ3"
FT STRAND 601..603
FT /evidence="ECO:0007829|PDB:1NJ3"
SQ SEQUENCE 608 AA; 68056 MW; F6F57DDEA53594A3 CRC64;
MAESIIIRVQ SPDGVKRITA TKRETAATFL KKVAKEFGFQ NNGFSVYINR NKTGEITASS
SKSLHLLKIK HGDLLFLFPS SLAGPSSEME TSTSVGLKAF GAPHVVEDEI DQYLSKQDGK
IYRSRDPQLC RHGPLGKCVH CVPLEPFDED YLNHLEPPVK HMSFHAYIRK LTGGADKGKF
VALENISCKI KSGCEGHLPW PNGICTKCQP SAITLNRQKY RHVDNIMFEN HTVADRFLDF
WRKTGNQHFG YLYGRYTEHK DIPLGIRAEV AAIYEPPQIG TQNSLELLED PKAEVVDEIA
SKLGLRKVGW 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
