ID   SORF2_CAEEL             Reviewed;        1382 AA.
AC   Q10122; D7SFK0; Q45EK8; Q45EK9;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   02-DEC-2020, sequence version 4.
DT   03-AUG-2022, entry version 127.
DE   RecName: Full=Suppressor of organelle fusion 2 {ECO:0000303|PubMed:26783301};
DE   AltName: Full=WD repeat-containing protein 81 homolog sorf-2 {ECO:0000305};
GN   Name=sorf-2 {ECO:0000303|PubMed:26783301, ECO:0000312|WormBase:F52C9.1};
GN   ORFNames=F52C9.1 {ECO:0000312|WormBase:F52C9.1};
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 [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   [2]
RP   FUNCTION, INTERACTION WITH SORF-1 AND BEC-1, SUBCELLULAR LOCATION, AND
RP   DISRUPTION PHENOTYPE.
RX   PubMed=26783301; DOI=10.1083/jcb.201506081;
RA   Liu K., Jian Y., Sun X., Yang C., Gao Z., Zhang Z., Liu X., Li Y., Xu J.,
RA   Jing Y., Mitani S., He S., Yang C.;
RT   "Negative regulation of phosphatidylinositol 3-phosphate levels in early-
RT   to-late endosome conversion.";
RL   J. Cell Biol. 212:181-198(2016).
RN   [3]
RP   ERRATUM OF PUBMED:26783301.
RX   PubMed=26975852; DOI=10.1083/jcb.20150608103012016c;
RA   Liu K., Jian Y., Sun X., Yang C., Gao Z., Zhang Z., Liu X., Li Y., Xu J.,
RA   Jing Y., Mitani S., He S., Yang C.;
RT   "Correction: Negative regulation of phosphatidylinositol 3-phosphate levels
RT   in early-to-late endosome conversion.";
RL   J. Cell Biol. 212:739-739(2016).
CC   -!- FUNCTION: Together with sorf-1 negatively regulates the levels of
CC       phosphatidylinositol 3-phosphate (PtdIns3P) to enable the conversion of
CC       early endosomes to late endosomes. Binds to sorf-1 and the sorf-1-sorf-
CC       2 complex likely acts through bec-1, a non-catalytic subunit of
CC       phosphatidylinositol 3-kinase (PI3K), to suppress PI3K activity,
CC       thereby negatively regulating endosomal PtdIns3P levels.
CC       {ECO:0000269|PubMed:26783301}.
CC   -!- SUBUNIT: Interacts with sorf-1; the interaction is direct. Interacts
CC       with bec-1. {ECO:0000269|PubMed:26783301}.
CC   -!- INTERACTION:
CC       Q10122; Q22592: bec-1; NbExp=3; IntAct=EBI-13941960, EBI-2413500;
CC       Q10122; Q23533: sorf-1; NbExp=2; IntAct=EBI-13941960, EBI-13941886;
CC   -!- SUBCELLULAR LOCATION: Early endosome {ECO:0000305|PubMed:26783301}.
CC       Late endosome {ECO:0000305|PubMed:26783301}. Cytoplasm
CC       {ECO:0000269|PubMed:26783301}.
CC   -!- DISRUPTION PHENOTYPE: Coelomocytes contain larger early and late
CC       endosomes enriched with PtdIns3P. Delayed conversion of early endosomes
CC       to late endosomes with early endosomes retaining PtdInsP3 for a longer
CC       duration of time which may possibly be due to a delay in either the
CC       turnover or transport of PtdIns3P out of the endosome. This leads to
CC       continuous fusion of early endosomes which continues until rab-5 is
CC       displaced and rab-7 is recruited. Double knockout with sorf-1 results
CC       in a similar phenotype as the individual single sorf-2 knockout. Double
CC       knockout with bec-1 results in smaller endosomes and an irregular
CC       distribution pattern of PtdIns3P in the cytoplasm. Double knockout with
CC       vps-18, a subunit of the CORVET/HOPS complex, results in larger
CC       endosomes and larger lysosomes and thus suppresses the
CC       endosome/lysosome fusion defect in the vps-18 single mutant. Likewise,
CC       RNAi-mediated knockdown in a vps-11, vps-39 or vps-41 mutant background
CC       (subunits of the CORVET/HOPS complex) also suppresses the
CC       endosome/lysosome fusion defects in the vps-11, vps-39 and vps-41
CC       single mutants. However, RNAi-mediated knockout in a mutant background
CC       of the CORVET/HOPS complex subunits vps-16 or vps-33.1, does not
CC       suppress the endosome/lysosome fusion defects in the individual vps-16
CC       and vps-33.1 single mutants. Double knockout with proteins involved in
CC       rab-5 to rab-7 switching in early to late endosome conversion such as
CC       rab-7, sand-1 and tbc-2 results in enlarged vacuoles, delayed endosomal
CC       cargo transport and persistent PtdIns3P in early endosomes in
CC       coelomocytes. {ECO:0000269|PubMed:26783301}.
CC   -!- SIMILARITY: Belongs to the WD repeat WDR81 family. {ECO:0000305}.
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DR   EMBL; BX284603; CCD71617.2; -; Genomic_DNA.
DR   PIR; T16423; T16423.
DR   RefSeq; NP_001254925.1; NM_001267996.1.
DR   AlphaFoldDB; Q10122; -.
DR   SMR; Q10122; -.
DR   BioGRID; 532355; 5.
DR   ComplexPortal; CPX-1059; Sorf-1-Sorf-2 complex.
DR   IntAct; Q10122; 2.
DR   STRING; 6239.F52C9.1.2; -.
DR   EPD; Q10122; -.
DR   PaxDb; Q10122; -.
DR   PeptideAtlas; Q10122; -.
DR   PRIDE; Q10122; -.
DR   EnsemblMetazoa; F52C9.1.1; F52C9.1.1; WBGene00018672.
DR   UCSC; F52C9.1b; c. elegans.
DR   WormBase; F52C9.1; CE54107; WBGene00018672; sorf-2.
DR   eggNOG; KOG1786; Eukaryota.
DR   eggNOG; KOG4190; Eukaryota.
DR   eggNOG; KOG4435; Eukaryota.
DR   InParanoid; Q10122; -.
DR   OrthoDB; 101142at2759; -.
DR   PRO; PR:Q10122; -.
DR   Proteomes; UP000001940; Chromosome III.
DR   Bgee; WBGene00018672; Expressed in embryo and 3 other tissues.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR   GO; GO:0031905; C:early endosome lumen; IDA:ComplexPortal.
DR   GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR   GO; GO:0031313; C:extrinsic component of endosome membrane; ISS:UniProtKB.
DR   GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR   GO; GO:0031906; C:late endosome lumen; IDA:ComplexPortal.
DR   GO; GO:0031902; C:late endosome membrane; ISS:UniProtKB.
DR   GO; GO:0035014; F:phosphatidylinositol 3-kinase regulator activity; ISS:UniProtKB.
DR   GO; GO:0045022; P:early endosome to late endosome transport; ISS:UniProtKB.
DR   GO; GO:0016197; P:endosomal transport; IDA:ComplexPortal.
DR   GO; GO:0043553; P:negative regulation of phosphatidylinositol 3-kinase activity; IDA:ComplexPortal.
DR   GO; GO:0048284; P:organelle fusion; IGI:UniProtKB.
DR   GO; GO:2000643; P:positive regulation of early endosome to late endosome transport; IMP:UniProtKB.
DR   GO; GO:0051036; P:regulation of endosome size; IGI:UniProtKB.
DR   GO; GO:0043551; P:regulation of phosphatidylinositol 3-kinase activity; ISS:UniProtKB.
DR   CDD; cd06071; Beach; 1.
DR   Gene3D; 1.10.1540.10; -; 1.
DR   Gene3D; 2.130.10.10; -; 1.
DR   InterPro; IPR000409; BEACH_dom.
DR   InterPro; IPR036372; BEACH_dom_sf.
DR   InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR   InterPro; IPR001680; WD40_repeat.
DR   InterPro; IPR036322; WD40_repeat_dom_sf.
DR   Pfam; PF02138; Beach; 1.
DR   SMART; SM01026; Beach; 1.
DR   SMART; SM00320; WD40; 2.
DR   SUPFAM; SSF50978; SSF50978; 1.
DR   SUPFAM; SSF81837; SSF81837; 1.
DR   PROSITE; PS50082; WD_REPEATS_2; 1.
DR   PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Endosome; Reference proteome; Repeat; WD repeat.
FT   CHAIN           1..1382
FT                   /note="Suppressor of organelle fusion 2"
FT                   /id="PRO_0000065355"
FT   DOMAIN          229..463
FT                   /note="BEACH"
FT                   /evidence="ECO:0000255"
FT   REPEAT          1094..1133
FT                   /note="WD 1"
FT                   /evidence="ECO:0000255"
FT   REPEAT          1140..1176
FT                   /note="WD 2"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   1382 AA;  158308 MW;  16286AD2F0D9D62F CRC64;
     MPEEEFEWNE SKLNALSEIL TQWAPHDELK LENVILEAKM AWIHESTDAV ALEKEFEKLL
     NTSFDPLMDY EEHQRVKNGV CSPAKSTKLD WITKWANIAE KLSISHINCS KAPHKTINFQ
     RLQILPNMTS ILAIAHTEAD NVILIYGHTK EGIDFQTVLR HSYSNIPDGS LQTIHFLTKN
     LLDLYSQLFS RKITAEFKTR HFRCLPSFWL QYDVLAPIFE QFRAPRAPRI PLDEATSNWA
     NRKWENYQYL TYLNDITGRV RGEVHNHPIF PWVCDFSEEN GGFRQLNRTK YRLCKGDDQL
     REMYSREPSH HVPELLSDIG YMVYRARVEP KDNLCRHVRR KWVPEEYPST MSRMYQWTPD
     ECIPEFYDDP SIFNSCHPDM ADLRFPEFVS SPQEFIEWHR KMLEHEEVSM NLHRWIDLVF
     GFNLAIDNSK NALNLHLCFV EKNRRGLRTT GMVQLFNRPH PIRMPLNYDP KLDNYHLKME
     SFGFGMTSEH RKEPEVEPDE DSHYQIYQKI KKVRRLRHNT YFSSMVSAME VMAQIVLAPH
     LAGRFDDPDH IRRCIQLYSY RIPANYRRLF DFLFNTEQDF PDCDEFSFFV SVRLNIPTKI
     LNFSEEFGKC VSLHILRKLD VIPPFSKRSQ LIILKEVESL KKSIRLCDHM EQCVVAAFQQ
     LLEDEEACIQ SVHRLMPVIT RSLSQSALED LINPMIELIQ CETSVKLLDR RFLMHVSICY
     GTHTFLDLFL PPIVEACASM NCDRSVVAKE SIMWLAKRYG PVICAKFISS NVLRIMASCY
     EAFEMVGLEQ QPKAVFNVVL QGDETCSRIE SLLSEIVLTY SVTFITVQFL PFCVDLIEQF
     HKRSSVQLEP GLVSVFRIVE LSIRSMSDHQ LMNYLEEFII QKVIYRVLTI LLDASFQFSS
     MRVRIIIICK VCQLLHSITQ KIGTENTRIY ANQPFKLMFS TFSEIYETDE ELRINLRKRP
     SENTLFEVPL WMVEDVVDKF AKEWGVPFLS SFCDDPAFLI PFVSNSSSSS SPPASIAHSP
     PSAFTAYSLG GMSSGNRLFS LSASSPVNSV NSLGGLSFCD SGSLSAVWCA RVSAAVCGVD
     NYRFDHLSLC NYTGHQEKIR KLAAISNENS FVSASSDKTV KLWSIKPELD EIGCQWTYQK
     HTRPVHDITI LADNSIASTD GVLHVWDPFR TTLLAQMEWD SKEGSGGNIM RVENVDRHIL
     SAICSLHSTV KLFDSRVGGW TCELKVSPGP GLTRAITVRD KGNKMAVALS NGTLAILDAR
     NGKINALAQT NSTHTVSVNW LSDTRLLVCD ADECGIFLET NPRAHIVRKL QDPVSAACLT
     DNSLVTLQNG TILRVYRNSG ELQIETKIRP DELPGTPTAV LPLPLNCSYL IGSSHGAIRL
     MC