LST4_CAEEL
ID LST4_CAEEL Reviewed; 566 AA.
AC Q8I4E2; D3NQ98; J7SA60; Q8I4E1; Q9XXG2; Q9XXG3;
DT 26-JUN-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Sorting nexin lst-4 {ECO:0000250|UniProtKB:Q8WV41};
DE AltName: Full=Lateral signaling target protein 4 {ECO:0000303|PubMed:21148288, ECO:0000303|PubMed:21494661};
GN Name=lst-4 {ECO:0000312|EMBL:CAA19487.2, ECO:0000312|WormBase:Y37A1B.2a};
GN ORFNames=Y37A1B.2;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:CAA19487.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:CAA19487.2};
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 FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=14752159; DOI=10.1126/science.1091639;
RA Yoo A.S., Bais C., Greenwald I.;
RT "Crosstalk between the EGFR and LIN-12/Notch pathways in C. elegans vulval
RT development.";
RL Science 303:663-666(2004).
RN [3] {ECO:0000305}
RP FUNCTION.
RX PubMed=18425118; DOI=10.1038/ncb1718;
RA Kinchen J.M., Doukoumetzidis K., Almendinger J., Stergiou L.,
RA Tosello-Trampont A., Sifri C.D., Hengartner M.O., Ravichandran K.S.;
RT "A pathway for phagosome maturation during engulfment of apoptotic cells.";
RL Nat. Cell Biol. 10:556-566(2008).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH DYN-1, DOMAIN, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF ARG-265; LYS-494 AND ARG-501.
RX PubMed=21148288; DOI=10.1091/mbc.e10-09-0756;
RA Lu N., Shen Q., Mahoney T.R., Liu X., Zhou Z.;
RT "Three sorting nexins drive the degradation of apoptotic cells in response
RT to PtdIns(3)P signaling.";
RL Mol. Biol. Cell 22:354-374(2011).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF 265-ARG--LYS-267.
RX PubMed=21494661; DOI=10.1371/journal.pone.0018325;
RA Almendinger J., Doukoumetzidis K., Kinchen J.M., Kaech A.,
RA Ravichandran K.S., Hengartner M.O.;
RT "A conserved role for SNX9-family members in the regulation of phagosome
RT maturation during engulfment of apoptotic cells.";
RL PLoS ONE 6:E18325-E18325(2011).
RN [6] {ECO:0000305}
RP SUBCELLULAR LOCATION.
RX PubMed=22272187; DOI=10.1371/journal.pbio.1001245;
RA Lu N., Shen Q., Mahoney T.R., Neukomm L.J., Wang Y., Zhou Z.;
RT "Two PI 3-kinases and one PI 3-phosphatase together establish the cyclic
RT waves of phagosomal PtdIns(3)P critical for the degradation of apoptotic
RT cells.";
RL PLoS Biol. 10:E1001245-E1001245(2012).
CC -!- FUNCTION: Involved in the signaling of vulval development by acting as
CC a negative regulator of epidermal growth factor receptor (EGFR)
CC signaling. Aids in phagosomal membrane tubule formation which is
CC required for phagosomal fusion with endosomes and lysosomes. Also
CC recruits rab-7 to phagosomes by an interaction with dyn-1. These are
CC events leading to phagosome maturation which is a step in apoptotic
CC cell corpse clearance. Binds phosphatidylinositol-3,4,5-trisphosphate.
CC {ECO:0000269|PubMed:14752159, ECO:0000269|PubMed:18425118,
CC ECO:0000269|PubMed:21148288, ECO:0000269|PubMed:21494661}.
CC -!- SUBUNIT: Homodimer. Isoform d interacts (via SH3 domain) with dyn-1.
CC {ECO:0000269|PubMed:21148288}.
CC -!- INTERACTION:
CC Q8I4E2; P39055: dyn-1; NbExp=4; IntAct=EBI-4325777, EBI-317945;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21148288,
CC ECO:0000269|PubMed:21494661, ECO:0000269|PubMed:22272187}. Cytoplasmic
CC vesicle, phagosome membrane {ECO:0000269|PubMed:21148288,
CC ECO:0000269|PubMed:21494661, ECO:0000269|PubMed:22272187}.
CC Note=Recruited to phagosomal surface by phosphatidylinositol
CC trisphosphate. BAR and PX domains are required for the phagosomal
CC localization. {ECO:0000269|PubMed:21148288,
CC ECO:0000269|PubMed:21494661, ECO:0000269|PubMed:22272187}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=c {ECO:0000269|PubMed:9851916};
CC IsoId=Q8I4E2-1; Sequence=Displayed;
CC Name=a {ECO:0000269|PubMed:9851916};
CC IsoId=Q8I4E2-2; Sequence=VSP_046632, VSP_046633;
CC Name=b {ECO:0000269|PubMed:9851916};
CC IsoId=Q8I4E2-3; Sequence=VSP_046629;
CC Name=d {ECO:0000269|PubMed:9851916};
CC IsoId=Q8I4E2-4; Sequence=VSP_046634;
CC Name=e {ECO:0000269|PubMed:9851916};
CC IsoId=Q8I4E2-5; Sequence=VSP_046628;
CC Name=f {ECO:0000269|PubMed:9851916};
CC IsoId=Q8I4E2-6; Sequence=VSP_046630, VSP_046631;
CC -!- TISSUE SPECIFICITY: Expressed in vulval precursor cells (VPCs) and
CC apoptotic germ cells. Colocalizes with actin, dyn-1 and rab-5 in early
CC phagosomes. {ECO:0000269|PubMed:14752159, ECO:0000269|PubMed:21494661}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in all 6 vulval precursor cells
CC (VPCs). At the time of inductive signaling, expression forms a gradient
CC in response to inductive signal: expression is low in P6.p,
CC intermediate in P5.p and P7.p and undiminished in P3.p, P4.p, and P8.p.
CC Later, expression becomes strong again in P5.p and P7.p.
CC {ECO:0000269|PubMed:14752159}.
CC -!- DOMAIN: The BAR and PX domains are required for recruitment to the
CC phagosome. {ECO:0000269|PubMed:21148288}.
CC -!- DOMAIN: The SH3 domain is involved in phagosome maturation.
CC {ECO:0000269|PubMed:21494661}.
CC -!- DISRUPTION PHENOTYPE: Aberrant vulval development, ectopic vulval
CC induction, retained cell corpses and defective recruitment of dyn-1 and
CC rab-7 to phagosomal surfaces. {ECO:0000269|PubMed:14752159,
CC ECO:0000269|PubMed:21148288, ECO:0000269|PubMed:21494661}.
CC -!- SIMILARITY: Belongs to the sorting nexin family. {ECO:0000255}.
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DR EMBL; AL023835; CAA19486.1; -; Genomic_DNA.
DR EMBL; AL023835; CAA19487.2; -; Genomic_DNA.
DR EMBL; AL023835; CAD56253.1; -; Genomic_DNA.
DR EMBL; AL023835; CAD56254.1; -; Genomic_DNA.
DR EMBL; AL023835; CBK19491.1; -; Genomic_DNA.
DR EMBL; AL023835; CCM09420.1; -; Genomic_DNA.
DR RefSeq; NP_001255779.1; NM_001268850.1. [Q8I4E2-5]
DR RefSeq; NP_001263811.1; NM_001276882.1. [Q8I4E2-6]
DR RefSeq; NP_502693.2; NM_070292.4.
DR RefSeq; NP_502694.1; NM_070293.5. [Q8I4E2-2]
DR RefSeq; NP_502695.2; NM_070294.4.
DR RefSeq; NP_872090.1; NM_182290.3. [Q8I4E2-4]
DR AlphaFoldDB; Q8I4E2; -.
DR SMR; Q8I4E2; -.
DR BioGRID; 43445; 12.
DR IntAct; Q8I4E2; 6.
DR STRING; 6239.Y37A1B.2b; -.
DR EPD; Q8I4E2; -.
DR PaxDb; Q8I4E2; -.
DR PeptideAtlas; Q8I4E2; -.
DR EnsemblMetazoa; Y37A1B.2a.1; Y37A1B.2a.1; WBGene00003086. [Q8I4E2-2]
DR EnsemblMetazoa; Y37A1B.2b.1; Y37A1B.2b.1; WBGene00003086. [Q8I4E2-3]
DR EnsemblMetazoa; Y37A1B.2c.1; Y37A1B.2c.1; WBGene00003086. [Q8I4E2-1]
DR EnsemblMetazoa; Y37A1B.2d.1; Y37A1B.2d.1; WBGene00003086. [Q8I4E2-4]
DR EnsemblMetazoa; Y37A1B.2e.1; Y37A1B.2e.1; WBGene00003086. [Q8I4E2-5]
DR EnsemblMetazoa; Y37A1B.2f.1; Y37A1B.2f.1; WBGene00003086. [Q8I4E2-6]
DR GeneID; 178361; -.
DR KEGG; cel:CELE_Y37A1B.2; -.
DR UCSC; Y37A1B.2b; c. elegans.
DR CTD; 178361; -.
DR WormBase; Y37A1B.2a; CE19071; WBGene00003086; lst-4. [Q8I4E2-2]
DR WormBase; Y37A1B.2b; CE32245; WBGene00003086; lst-4. [Q8I4E2-3]
DR WormBase; Y37A1B.2c; CE32246; WBGene00003086; lst-4. [Q8I4E2-1]
DR WormBase; Y37A1B.2d; CE32247; WBGene00003086; lst-4. [Q8I4E2-4]
DR WormBase; Y37A1B.2e; CE44602; WBGene00003086; lst-4. [Q8I4E2-5]
DR WormBase; Y37A1B.2f; CE47745; WBGene00003086; lst-4. [Q8I4E2-6]
DR eggNOG; KOG2528; Eukaryota.
DR GeneTree; ENSGT00940000166896; -.
DR OMA; DGINDRC; -.
DR OrthoDB; 811995at2759; -.
DR Reactome; R-CEL-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-CEL-8856828; Clathrin-mediated endocytosis.
DR SignaLink; Q8I4E2; -.
DR PRO; PR:Q8I4E2; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00003086; Expressed in germ line (C elegans) and 4 other tissues.
DR ExpressionAtlas; Q8I4E2; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0032009; C:early phagosome; IDA:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:WormBase.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0051020; F:GTPase binding; IPI:WormBase.
DR GO; GO:0019902; F:phosphatase binding; IPI:WormBase.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:WormBase.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:WormBase.
DR GO; GO:0043621; F:protein self-association; IPI:WormBase.
DR GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR GO; GO:0016197; P:endosomal transport; IBA:GO_Central.
DR GO; GO:0097194; P:execution phase of apoptosis; IMP:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; IEA:InterPro.
DR GO; GO:0090387; P:phagolysosome assembly involved in apoptotic cell clearance; IMP:UniProtKB.
DR GO; GO:0090386; P:phagosome maturation involved in apoptotic cell clearance; IMP:UniProtKB.
DR GO; GO:0090389; P:phagosome-lysosome fusion involved in apoptotic cell clearance; IMP:WormBase.
DR GO; GO:0097320; P:plasma membrane tubulation; IBA:GO_Central.
DR GO; GO:0015031; P:protein transport; IEA:InterPro.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR014536; Snx9_fam.
DR InterPro; IPR019497; Sorting_nexin_WASP-bd-dom.
DR Pfam; PF10456; BAR_3_WASP_bdg; 1.
DR Pfam; PF00787; PX; 1.
DR Pfam; PF14604; SH3_9; 1.
DR PIRSF; PIRSF027744; Snx9; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00312; PX; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50195; PX; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Cytoplasmic vesicle; Lipid-binding;
KW Membrane; Reference proteome; SH3 domain.
FT CHAIN 1..566
FT /note="Sorting nexin lst-4"
FT /id="PRO_0000422772"
FT DOMAIN 1..61
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 227..339
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT DOMAIN 362..566
FT /note="BAR"
FT /evidence="ECO:0000255"
FT REGION 59..179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 62..80
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 106..124
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 158..172
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..509
FT /note="Missing (in isoform e)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_046628"
FT VAR_SEQ 1..66
FT /note="MAQVKAEYDFQSQPNTGELSISAGEVLTVIRENIDGGWIEGRNVRGSVGLFP
FT ESYVTPYQASRPPP -> MLFTSSLRKAVENYPTPPGGSSEDAHRQLLERRRKQMLRRH
FT TCSTLIKQDTSASPHKMKPPILMEEEDEQHSTGKHSSRKSSFKKSGAISKS (in
FT isoform b)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_046629"
FT VAR_SEQ 2..79
FT /note="AQVKAEYDFQSQPNTGELSISAGEVLTVIRENIDGGWIEGRNVRGSVGLFPE
FT SYVTPYQASRPPPVLPPPLPPTSSGP -> STDDETRSSQQDGAYPSSKRNGSVGSSTR
FT STSTKKRLSRQDSTARRRRLSEERDSRRRVEKSVSSCLSSNRSHHDQNK (in
FT isoform f)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_046630"
FT VAR_SEQ 80..140
FT /note="Missing (in isoform f)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_046631"
FT VAR_SEQ 141..163
FT /note="EPTRPNVQSSIGSNSRRDLSRSH -> VFLKFYFNFLIVQFLSVLFIPSN
FT (in isoform a)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_046632"
FT VAR_SEQ 165..566
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_046633"
FT VAR_SEQ 260..261
FT /note="Missing (in isoform d)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_046634"
FT MUTAGEN 265..267
FT /note="RYK->QAA: Defective recruitment to the phagosome."
FT /evidence="ECO:0000269|PubMed:21494661"
FT MUTAGEN 265
FT /note="R->Q: Defect recruitment by phosphoinositide to
FT phagosomal surface."
FT /evidence="ECO:0000269|PubMed:21148288"
FT MUTAGEN 494
FT /note="K->E: Defective recruitment to the phagosome."
FT /evidence="ECO:0000269|PubMed:21148288"
FT MUTAGEN 501
FT /note="R->E: Defective recruitment to the phagosome."
FT /evidence="ECO:0000269|PubMed:21148288"
SQ SEQUENCE 566 AA; 64329 MW; 77CFBE901A3E3B24 CRC64;
MAQVKAEYDF QSQPNTGELS ISAGEVLTVI RENIDGGWIE GRNVRGSVGL FPESYVTPYQ
ASRPPPVLPP PLPPTSSGPP AASSRPFDDW GGASEVAAPP SYGAQHHHQP TPSVPEVTRS
SYPSQNDDFD DEWTDEDDEQ EPTRPNVQSS IGSNSRRDLS RSHSEHGGPD RGSNKVNKNI
NRFSNFVKSG VEAYVIGESK TTSQISERHE VVMNNGIIQW KPIQQYYTCI VDKPKKESKL
KGLKSFIAYS ITSSLTNIQR QVSRRYKHFD WLHEQLSAKY VLIPIPPLPE KQVAGRYEED
LIDHRKHILQ LWVNKICRHP VLSQSEVWLH FISCTDEKDW KNGKRRAEKD EYIGGAFLNC
ITVPHQPLDP NNVDMQVERF QRSVKTSEEA MRVMQERMNM FQKVFAGPVK QNWQKMGSAF
KTLQQSFEID ETVASRRLTE ALAYTASEYH EIGQVFDAHT KNDMEPVLEN LYSYKGTVQN
VPDIIQVHKQ AVQKFRDSEG RLSSAEAEKM KQRIDAMSYT VIAEVQHQTA EKVEDMKSTM
GTYLKKQAMF YQEVATKLTS LAARYD
