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