ID   UBC2_CAEEL              Reviewed;         147 AA.
AC   P35129;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1994, sequence version 1.
DT   27-MAR-2024, entry version 186.
DE   RecName: Full=Ubiquitin-conjugating enzyme E2 2;
DE            EC=2.3.2.23;
DE   AltName: Full=E2 ubiquitin-conjugating enzyme 2;
DE   AltName: Full=Lethal protein 70;
DE   AltName: Full=Ubiquitin carrier protein 2;
DE   AltName: Full=Ubiquitin-protein ligase 2;
GN   Name=let-70 {ECO:0000303|PubMed:8670823, ECO:0000312|WormBase:M7.1};
GN   Synonyms=ubc-2 {ECO:0000303|PubMed:8441382,
GN   ECO:0000312|WormBase:M7.1}; ORFNames=M7.1 {ECO:0000312|WormBase:M7.1};
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DEVELOPMENTAL STAGE.
RX   PubMed=8441382; DOI=10.1128/mcb.13.3.1371-1377.1993;
RA   Zhen M., Heinlein R., Jones D., Jentsch S., Candido E.P.M.;
RT   "The ubc-2 gene of Caenorhabditis elegans encodes a ubiquitin-conjugating
RT   enzyme involved in selective protein degradation.";
RL   Mol. Cell. Biol. 13:1371-1377(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP   AND MUTAGENESIS OF HIS-75.
RX   PubMed=8670823; DOI=10.1002/j.1460-2075.1996.tb00687.x;
RA   Zhen M., Scheni J.E., Baillie D.L., Candido E.P.M.;
RT   "An essential ubiquitin-conjugating enzyme with tissue and developmental
RT   specificity in the nematode Caenorhabditis elegans.";
RL   EMBO J. 15:3229-3237(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Bristol N2;
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   [4]
RP   FUNCTION, INTERACTION WITH BRC-1-BRD-1 HETERODIMER, SUBCELLULAR LOCATION,
RP   AND DISRUPTION PHENOTYPE.
RX   PubMed=16628214; DOI=10.1038/sj.emboj.7601102;
RA   Polanowska J., Martin J.S., Garcia-Muse T., Petalcorin M.I.R.,
RA   Boulton S.J.;
RT   "A conserved pathway to activate BRCA1-dependent ubiquitylation at DNA
RT   damage sites.";
RL   EMBO J. 25:2178-2188(2006).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP   AND MUTAGENESIS OF PRO-61.
RX   PubMed=26952214; DOI=10.7554/elife.12821;
RA   Kinet M.J., Malin J.A., Abraham M.C., Blum E.S., Silverman M.R., Lu Y.,
RA   Shaham S.;
RT   "HSF-1 activates the ubiquitin proteasome system to promote non-apoptotic
RT   developmental cell death in C. elegans.";
RL   Elife 5:0-0(2016).
CC   -!- FUNCTION: Catalyzes the covalent attachment of ubiquitin to other
CC       proteins (By similarity). Mediates the selective degradation of short-
CC       lived and abnormal proteins (PubMed:16628214). Plays a role in the DNA
CC       damage response (PubMed:16628214). In particular, in response to
CC       ionizing radiation, associates with the E3 ubiquitin-protein ligase
CC       brc-1-brd-1 heterodimer on chromatin to activate E3-ubiquitin ligase
CC       activity of the heterodimer, and thus its DNA damage repair mechanisms
CC       (PubMed:16628214). Required, cell autonomously, for death of the linker
CC       cell, a male-specific cell which guides the elongation of the gonad;
CC       perhaps acting as part of the ubiquitin proteasome system (UPS) and
CC       modulated by heat shock transcription factor hsf-1 (PubMed:26952214).
CC       {ECO:0000250|UniProtKB:P06104, ECO:0000269|PubMed:16628214,
CC       ECO:0000269|PubMed:26952214}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine +
CC         [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-
CC         activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-
CC         conjugating enzyme]-L-cysteine.; EC=2.3.2.23;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU00388, ECO:0000255|PROSITE-
CC         ProRule:PRU10133};
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC       {ECO:0000255|PROSITE-ProRule:PRU00388}.
CC   -!- SUBUNIT: Interacts with the brc-1-brd-1 heterodimer following ionizing
CC       irradiation. {ECO:0000269|PubMed:16628214}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16628214,
CC       ECO:0000269|PubMed:26952214}. Chromosome {ECO:0000269|PubMed:16628214}.
CC       Cytoplasm {ECO:0000269|PubMed:26952214}.
CC   -!- TISSUE SPECIFICITY: Expressed in the nervous system.
CC       {ECO:0000269|PubMed:8670823}.
CC   -!- DEVELOPMENTAL STAGE: Expressed at all stages of development
CC       (PubMed:8441382, PubMed:8670823). Expressed in most embryonic tissues
CC       and larval tissues at the early stages (PubMed:8670823). Highly
CC       expressed in neurons, pharynx, the hyperdermis and body muscles in L1,
CC       L2, L3 and dauer larvae (PubMed:8670823). From the L4 stage of larval
CC       development and in adults, expression is mainly restricted to the
CC       nervous system, but is also expressed in the pharynx and hyperdermis
CC       (PubMed:8670823). Expressed in the linker cell, a male-specific cell
CC       which guides the elongation of the gonad, about 1-2 hours before
CC       induction of linker cell death (PubMed:26952214).
CC       {ECO:0000269|PubMed:26952214, ECO:0000269|PubMed:8441382,
CC       ECO:0000269|PubMed:8670823}.
CC   -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in reduced
CC       ubiquitination at DNA damage sites (PubMed:16628214). Inappropriate
CC       survival of male gonadal linker cell (PubMed:26952214).
CC       {ECO:0000269|PubMed:16628214, ECO:0000269|PubMed:26952214}.
CC   -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00388}.
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DR   EMBL; S56051; AAB25489.2; -; Genomic_DNA.
DR   EMBL; Z68337; CAA92745.1; -; Genomic_DNA.
DR   PIR; A48145; A48145.
DR   PIR; T23820; T23820.
DR   RefSeq; NP_502065.1; NM_069664.4.
DR   PDB; 1Z2U; X-ray; 1.10 A; A=1-147.
DR   PDBsum; 1Z2U; -.
DR   AlphaFoldDB; P35129; -.
DR   SMR; P35129; -.
DR   BioGRID; 43106; 25.
DR   DIP; DIP-24306N; -.
DR   IntAct; P35129; 2.
DR   STRING; 6239.M7.1.1; -.
DR   EPD; P35129; -.
DR   PaxDb; 6239-M7-1; -.
DR   PeptideAtlas; P35129; -.
DR   EnsemblMetazoa; M7.1.1; M7.1.1; WBGene00002344.
DR   GeneID; 178006; -.
DR   KEGG; cel:CELE_M7.1; -.
DR   UCSC; M7.1; c. elegans.
DR   AGR; WB:WBGene00002344; -.
DR   WormBase; M7.1; CE03482; WBGene00002344; let-70.
DR   eggNOG; KOG0417; Eukaryota.
DR   GeneTree; ENSGT00940000155109; -.
DR   HOGENOM; CLU_030988_13_3_1; -.
DR   InParanoid; P35129; -.
DR   OMA; PNIASMY; -.
DR   OrthoDB; 5478564at2759; -.
DR   PhylomeDB; P35129; -.
DR   Reactome; R-CEL-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR   Reactome; R-CEL-201451; Signaling by BMP.
DR   Reactome; R-CEL-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR   Reactome; R-CEL-5357905; Regulation of TNFR1 signaling.
DR   Reactome; R-CEL-5689896; Ovarian tumor domain proteases.
DR   Reactome; R-CEL-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR   Reactome; R-CEL-8951664; Neddylation.
DR   Reactome; R-CEL-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   UniPathway; UPA00143; -.
DR   EvolutionaryTrace; P35129; -.
DR   PRO; PR:P35129; -.
DR   Proteomes; UP000001940; Chromosome IV.
DR   Bgee; WBGene00002344; Expressed in embryo and 4 other cell types or tissues.
DR   GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0061631; F:ubiquitin conjugating enzyme activity; IMP:UniProtKB.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:WormBase.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:WormBase.
DR   GO; GO:0010623; P:programmed cell death involved in cell development; IMP:UniProtKB.
DR   GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR   GO; GO:0016567; P:protein ubiquitination; IDA:WormBase.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:WormBase.
DR   CDD; cd00195; UBCc; 1.
DR   Gene3D; 3.10.110.10; Ubiquitin Conjugating Enzyme; 1.
DR   InterPro; IPR000608; UBQ-conjugat_E2.
DR   InterPro; IPR023313; UBQ-conjugating_AS.
DR   InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR   PANTHER; PTHR24068; UBIQUITIN-CONJUGATING ENZYME E2; 1.
DR   PANTHER; PTHR24068:SF74; UBIQUITIN-CONJUGATING ENZYME E2-17 KDA; 1.
DR   Pfam; PF00179; UQ_con; 1.
DR   SMART; SM00212; UBCc; 1.
DR   SUPFAM; SSF54495; UBC-like; 1.
DR   PROSITE; PS00183; UBC_1; 1.
DR   PROSITE; PS50127; UBC_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Chromosome; Cytoplasm; Nucleotide-binding;
KW   Nucleus; Reference proteome; Transferase; Ubl conjugation pathway.
FT   CHAIN           1..147
FT                   /note="Ubiquitin-conjugating enzyme E2 2"
FT                   /id="PRO_0000082515"
FT   DOMAIN          1..147
FT                   /note="UBC core"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT   ACT_SITE        85
FT                   /note="Glycyl thioester intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00388,
FT                   ECO:0000255|PROSITE-ProRule:PRU10133"
FT   MUTAGEN         61
FT                   /note="P->S: In ns770; Viable. Inappropriate survival of
FT                   male gonadal linker cell; exacerbated on a heat shock
FT                   transcription factor hsf-1 mutant background. Simultaneous
FT                   RNAi-mediated knockdown of cul-3 causes a synergistic
FT                   increase in linker cell survival."
FT                   /evidence="ECO:0000269|PubMed:26952214"
FT   MUTAGEN         75
FT                   /note="H->Y: In s1132; hermaphrodites arrest during the
FT                   early stages of larval stages."
FT                   /evidence="ECO:0000269|PubMed:8670823"
FT   HELIX           1..15
FT                   /evidence="ECO:0007829|PDB:1Z2U"
FT   STRAND          19..26
FT                   /evidence="ECO:0007829|PDB:1Z2U"
FT   STRAND          29..38
FT                   /evidence="ECO:0007829|PDB:1Z2U"
FT   TURN            44..47
FT                   /evidence="ECO:0007829|PDB:1Z2U"
FT   STRAND          49..55
FT                   /evidence="ECO:0007829|PDB:1Z2U"
FT   TURN            58..61
FT                   /evidence="ECO:0007829|PDB:1Z2U"
FT   STRAND          66..71
FT                   /evidence="ECO:0007829|PDB:1Z2U"
FT   HELIX           87..89
FT                   /evidence="ECO:0007829|PDB:1Z2U"
FT   TURN            90..92
FT                   /evidence="ECO:0007829|PDB:1Z2U"
FT   HELIX           99..111
FT                   /evidence="ECO:0007829|PDB:1Z2U"
FT   HELIX           121..129
FT                   /evidence="ECO:0007829|PDB:1Z2U"
FT   HELIX           131..145
FT                   /evidence="ECO:0007829|PDB:1Z2U"
SQ   SEQUENCE   147 AA;  16705 MW;  9E91884D307F2120 CRC64;
     MALKRIQKEL QDLGRDPPAQ CSAGPVGDDL FHWQATIMGP PESPYQGGVF FLTIHFPTDY
     PFKPPKVAFT TRIYHPNINS NGSICLDILR SQWSPALTIS KVLLSICSLL CDPNPDDPLV
     PEIARIYKTD RERYNQLARE WTQKYAM
//