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UBXN3_CAEEL
ID   UBXN3_CAEEL             Reviewed;         613 AA.
AC   H2L056; A0A0K3ARL0; A0A0K3ATZ0; A0A0K3AWX1; Q6A589;
DT   23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT   21-MAR-2012, sequence version 1.
DT   03-AUG-2022, entry version 68.
DE   RecName: Full=UBX domain-containing protein 3 {ECO:0000305};
GN   Name=ubxn-3 {ECO:0000312|WormBase:F48A11.5a};
GN   ORFNames=F48A11.5 {ECO:0000312|WormBase:F48A11.5a};
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN   [1] {ECO:0000312|Proteomes:UP000001940}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX   PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG   The C. elegans sequencing consortium;
RT   "Genome sequence of the nematode C. elegans: a platform for investigating
RT   biology.";
RL   Science 282:2012-2018(1998).
RN   [2] {ECO:0000305}
RP   TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=17498661; DOI=10.1016/j.bbrc.2007.04.163;
RA   Yamauchi S., Sasagawa Y., Ogura T., Yamanaka K.;
RT   "Differential expression pattern of UBX family genes in Caenorhabditis
RT   elegans.";
RL   Biochem. Biophys. Res. Commun. 358:545-552(2007).
RN   [3] {ECO:0000305}
RP   FUNCTION, IDENTIFICATION IN A COMPLEX WITH CDC-48.1; UFD-1 AND NPL-4.1,
RP   INTERACTION WITH CDC-48.1 AND CDC-48.2, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=20977550; DOI=10.1111/j.1365-2443.2010.01454.x;
RA   Sasagawa Y., Yamanaka K., Saito-Sasagawa Y., Ogura T.;
RT   "Caenorhabditis elegans UBX cofactors for CDC-48/p97 control
RT   spermatogenesis.";
RL   Genes Cells 15:1201-1215(2010).
RN   [4] {ECO:0000305}
RP   FUNCTION, IDENTIFICATION IN A COMPLEX WITH CDC-48 AND CDT-1, INTERACTION
RP   WITH CDC-48 AND CDT-1, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE,
RP   DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 582-PHE--LYS-584.
RX   PubMed=26842564; DOI=10.1038/ncomms10612;
RA   Franz A., Pirson P.A., Pilger D., Halder S., Achuthankutty D., Kashkar H.,
RA   Ramadan K., Hoppe T.;
RT   "Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard
RT   DNA replication fork progression.";
RL   Nat. Commun. 7:10612-10612(2016).
RN   [5] {ECO:0000305}
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=28368371; DOI=10.1038/ncb3500;
RA   Sonneville R., Moreno S.P., Knebel A., Johnson C., Hastie C.J., Gartner A.,
RA   Gambus A., Labib K.;
RT   "CUL-2LRR-1 and UBXN-3 drive replisome disassembly during DNA replication
RT   termination and mitosis.";
RL   Nat. Cell Biol. 19:468-479(2017).
CC   -!- FUNCTION: Ubiquitin-binding protein which acts as an adapter for ATPase
CC       cdc-48.1 and/or cdc-48.2, conferring substrate specificity
CC       (PubMed:20977550, PubMed:26842564, PubMed:28368371). Together with
CC       ubxn-1 and ubxn-2, plays a role in hermaphrodite spermatogenesis
CC       probably by promoting the degradation of sex determination terminal
CC       factor tra-1 (PubMed:20977550). During mitosis, ensures the degradation
CC       of DNA licensing factor cdt-1 and the disassembly of the DNA
CC       replication CMG helicase complex by promoting the dissociation from
CC       chromatin of several of its components including cdc-45 and sld-5
CC       (PubMed:26842564, PubMed:28368371). {ECO:0000269|PubMed:20977550,
CC       ECO:0000269|PubMed:26842564, ECO:0000269|PubMed:28368371}.
CC   -!- SUBUNIT: Forms a complex composed of ubxn-3, cdc-48.1, ufd-1 and npl-
CC       4.1 (PubMed:20977550). Forms a complex composed of ubxn-3, cdc-48.1
CC       and/or cdc-48.2 and substrate cdt-1 (PubMed:26842564). Interacts (via
CC       FPK motif) with cdc-48.1 (via N-terminus) and cdc-48.2 (via N-terminus)
CC       (PubMed:20977550, PubMed:26842564). Interacts (via N-terminus) with
CC       cdt-1 and ubiquitinated protein substrates; the interaction is cdc-48-
CC       independent (PubMed:26842564). May interact with npl-4.1
CC       (PubMed:20977550). {ECO:0000269|PubMed:20977550,
CC       ECO:0000269|PubMed:26842564}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26842564}. Cytoplasm,
CC       perinuclear region {ECO:0000269|PubMed:20977550}. Chromosome
CC       {ECO:0000269|PubMed:26842564}. Cytoplasm {ECO:0000269|PubMed:26842564}.
CC       Note=Colocalizes with cdc-48.1 to the perinuclear region in
CC       spermatocytes (PubMed:20977550). Localizes to the nucleus during S
CC       phase in a cdc-48 and npl-4-dependent manner (PubMed:26842564).
CC       {ECO:0000269|PubMed:20977550, ECO:0000269|PubMed:26842564}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=a {ECO:0000312|WormBase:F48A11.5a};
CC         IsoId=H2L056-1; Sequence=Displayed;
CC       Name=b {ECO:0000312|WormBase:F48A11.5b};
CC         IsoId=H2L056-2; Sequence=VSP_059594;
CC       Name=c {ECO:0000312|WormBase:F48A11.5c};
CC         IsoId=H2L056-3; Sequence=VSP_059593, VSP_059594;
CC       Name=d {ECO:0000312|WormBase:F48A11.5d};
CC         IsoId=H2L056-4; Sequence=VSP_059592;
CC       Name=e {ECO:0000312|WormBase:F48A11.5e};
CC         IsoId=H2L056-5; Sequence=VSP_059593;
CC   -!- TISSUE SPECIFICITY: Expressed in the germline (at protein level)
CC       (PubMed:17498661, PubMed:20977550). Expressed in spermatocytes but not
CC       in mature sperm (at protein level) (PubMed:20977550). Expressed in the
CC       spermatheca and nerve cells (PubMed:17498661).
CC       {ECO:0000269|PubMed:17498661, ECO:0000269|PubMed:20977550}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in embryos (at protein level)
CC       (PubMed:17498661, PubMed:26842564). Also expressed in L4 larvae and
CC       adults (PubMed:17498661). Expressed to a lesser extent between L1 and
CC       L3 larval stages (PubMed:17498661). {ECO:0000269|PubMed:17498661,
CC       ECO:0000269|PubMed:26842564}.
CC   -!- DISRUPTION PHENOTYPE: Causes approximately 30 percent embryonic
CC       lethality (PubMed:26842564). RNAi-mediated knockdown does not cause any
CC       visible phenotype (PubMed:20977550). Cell division at the 3-cell stage
CC       is delayed. In a cdc-48.1 (tm544) mutant background, the delay in cell
CC       cycle progression is further enhanced and DNA replication is impaired
CC       resulting in the formation of DNA repair rad-51 foci (PubMed:26842564).
CC       In addition, cdt-1 degradation and disassembly of cdc-45 and sld-5 from
CC       the chromatin during mitosis is impaired (PubMed:26842564).
CC       Simultaneous RNAi-mediated knockdown of lrr-1, causes a failure to
CC       disassemble components of the CGM helicase complex psf-1, cdc-45 and
CC       spd-5 from the chromatin resulting in their abnormal association with
CC       chromatin during mitosis (PubMed:28368371). Simultaneous RNAi-mediated
CC       knockdown of ubxn-1 and ubxn-2, causes 50 percent embryonic lethality
CC       (PubMed:20977550). The surviving hermaphrodite progeny are sterile due
CC       to a lack of sperm (PubMed:20977550). Abnormal accumulation of sex
CC       determination terminal factor tra-1 (PubMed:20977550). Germline
CC       development is normal (PubMed:20977550). In males, sperm production is
CC       normal (PubMed:20977550). {ECO:0000269|PubMed:20977550,
CC       ECO:0000269|PubMed:26842564, ECO:0000269|PubMed:28368371}.
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DR   EMBL; BX284602; CCD71486.1; -; Genomic_DNA.
DR   EMBL; BX284602; CCD71487.1; -; Genomic_DNA.
DR   EMBL; BX284602; CTQ86486.1; -; Genomic_DNA.
DR   EMBL; BX284602; CTQ86487.1; -; Genomic_DNA.
DR   EMBL; BX284602; CTQ86488.1; -; Genomic_DNA.
DR   RefSeq; NP_001022180.2; NM_001027009.2.
DR   RefSeq; NP_001022181.2; NM_001027010.3. [H2L056-2]
DR   RefSeq; NP_001300547.1; NM_001313618.1. [H2L056-3]
DR   RefSeq; NP_001300548.1; NM_001313619.1. [H2L056-4]
DR   RefSeq; NP_001300549.1; NM_001313620.1. [H2L056-5]
DR   AlphaFoldDB; H2L056; -.
DR   SMR; H2L056; -.
DR   STRING; 6239.F48A11.5a; -.
DR   EPD; H2L056; -.
DR   PaxDb; H2L056; -.
DR   PeptideAtlas; H2L056; -.
DR   EnsemblMetazoa; F48A11.5a.1; F48A11.5a.1; WBGene00018586. [H2L056-1]
DR   EnsemblMetazoa; F48A11.5b.1; F48A11.5b.1; WBGene00018586. [H2L056-2]
DR   EnsemblMetazoa; F48A11.5c.1; F48A11.5c.1; WBGene00018586. [H2L056-3]
DR   EnsemblMetazoa; F48A11.5d.1; F48A11.5d.1; WBGene00018586. [H2L056-4]
DR   EnsemblMetazoa; F48A11.5e.1; F48A11.5e.1; WBGene00018586. [H2L056-5]
DR   GeneID; 173407; -.
DR   KEGG; cel:CELE_F48A11.5; -.
DR   UCSC; F48A11.5b; c. elegans.
DR   CTD; 173407; -.
DR   WormBase; F48A11.5a; CE46198; WBGene00018586; ubxn-3. [H2L056-1]
DR   WormBase; F48A11.5b; CE46277; WBGene00018586; ubxn-3. [H2L056-2]
DR   WormBase; F48A11.5c; CE50808; WBGene00018586; ubxn-3. [H2L056-3]
DR   WormBase; F48A11.5d; CE50868; WBGene00018586; ubxn-3. [H2L056-4]
DR   WormBase; F48A11.5e; CE50740; WBGene00018586; ubxn-3. [H2L056-5]
DR   eggNOG; KOG1363; Eukaryota.
DR   GeneTree; ENSGT00940000154831; -.
DR   HOGENOM; CLU_034590_0_0_1; -.
DR   InParanoid; H2L056; -.
DR   OMA; THRIWTS; -.
DR   OrthoDB; 845154at2759; -.
DR   PhylomeDB; H2L056; -.
DR   PRO; PR:H2L056; -.
DR   Proteomes; UP000001940; Chromosome II.
DR   Bgee; WBGene00018586; Expressed in adult organism and 3 other tissues.
DR   GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:WormBase.
DR   GO; GO:0036435; F:K48-linked polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR   GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB.
DR   GO; GO:0043130; F:ubiquitin binding; IBA:GO_Central.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0042006; P:masculinization of hermaphroditic germ-line; IGI:UniProtKB.
DR   GO; GO:0045977; P:positive regulation of mitotic cell cycle, embryonic; IGI:UniProtKB.
DR   GO; GO:0045732; P:positive regulation of protein catabolic process; IGI:UniProtKB.
DR   GO; GO:1905634; P:regulation of protein localization to chromatin; IGI:UniProtKB.
DR   GO; GO:0007283; P:spermatogenesis; IGI:UniProtKB.
DR   GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IBA:GO_Central.
DR   CDD; cd01771; UBX_UBXN3A; 1.
DR   InterPro; IPR033043; FAF1-like_UBX.
DR   InterPro; IPR006577; UAS.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   InterPro; IPR001012; UBX_dom.
DR   SMART; SM00594; UAS; 1.
DR   SUPFAM; SSF54236; SSF54236; 1.
DR   PROSITE; PS50033; UBX; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Chromosome; Coiled coil; Cytoplasm; Differentiation;
KW   Nucleus; Reference proteome; Spermatogenesis.
FT   CHAIN           1..613
FT                   /note="UBX domain-containing protein 3"
FT                   /id="PRO_0000444375"
FT   DOMAIN          531..610
FT                   /note="UBX"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00215"
FT   REGION          67..223
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          453..472
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          452..517
FT                   /evidence="ECO:0000255"
FT   MOTIF           582..584
FT                   /note="Interaction with cdc-48"
FT                   /evidence="ECO:0000269|PubMed:26842564"
FT   COMPBIAS        86..109
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        151..176
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1..379
FT                   /note="Missing (in isoform d)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_059592"
FT   VAR_SEQ         1..94
FT                   /note="Missing (in isoform c and isoform e)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_059593"
FT   VAR_SEQ         119..123
FT                   /note="Missing (in isoform b and isoform c)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_059594"
FT   MUTAGEN         582..584
FT                   /note="FPK->NAA,SGG: Prevents interaction with cdc-48
FT                   without affecting the interaction with cdt-1 and
FT                   ubiquitinated protein substrates."
FT                   /evidence="ECO:0000269|PubMed:26842564"
SQ   SEQUENCE   613 AA;  69673 MW;  120DE35C1516E510 CRC64;
     MDLTASLEDD QREKLRQYTE FTHQQDYEVA IGTLASLNWN LEQAIEAHLM QEDKNDDEDP
     EILETIPAAA SGRNAGASSS SRFEPEVINI EDDEMPATRG RRRGRAVTPD ETTTVDNQVK
     RLRIDDGSSS SSNGAATHHR GAAIPRQKRG QATEPTPSSS GSSSASFSSR RGTRANPVPP
     PNQEPAHPES ARQNGGILAS RHNNHNNQQN NHHHHHQRIP INPRRVDVFN VDSDEDDDSM
     AIAYEDDDDG VHEVHHSEVV ARGSGPPNGR IPMIPDGFSS VSDALRNFVA IFSDRFCSTP
     QTQAFMPPFY TEPLPAAVKE AFDHPNSEHR RPLLFYINHD RSIAANIFAS QVLCSETVST
     LIRHQYVLFP WDITSDSNLM LFLEYLQAAN MGDVRTIIQR LAMSKIESFP LMAIVVKERN
     SYRLVDYCRG TDTSDQVMEK LLSGVSEYSD IRMNEQSERR EREEREAIRN QQEAEYKASL
     AADKARMEAK QQEIEEQRLE EERKLREEEE ECVRRQTVAS TVPEEPPASA PLAEIINVKF
     RLPEGGQDMR RFRRLESIQT LINYLSSKGY SPDKFKYFNS DFPKKEITRH FDLSHNFADT
     KWPAREQIFV EEI
 
 
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