ID SH3GH_CAEEL Reviewed; 381 AA.
AC B1V8A0; A5A8Q9; A5A8R0; O61843; Q6TM46;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 1.
DT 27-MAR-2024, entry version 114.
DE RecName: Full=Endophilin-A homolog {ECO:0000305|PubMed:14622579};
DE AltName: Full=Endophilin-1 homolog {ECO:0000305|PubMed:14622579};
DE AltName: Full=Uncoordinated protein 57 {ECO:0000312|WormBase:T04D1.3d};
GN Name=unc-57 {ECO:0000312|WormBase:T04D1.3d};
GN ORFNames=T04D1.3 {ECO:0000312|WormBase:T04D1.3d};
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|EMBL:AAQ96373.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=14622579; DOI=10.1016/s0896-6273(03)00667-6;
RA Schuske K.R., Richmond J.E., Matthies D.S., Davis W.S., Runz S., Rube D.A.,
RA van der Bliek A.M., Jorgensen E.M.;
RT "Endophilin is required for synaptic vesicle endocytosis by localizing
RT synaptojanin.";
RL Neuron 40:749-762(2003).
RN [2] {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 [3] {ECO:0000305}
RP FUNCTION.
RX PubMed=17928447; DOI=10.1523/jneurosci.1941-07.2007;
RA Parker J.A., Metzler M., Georgiou J., Mage M., Roder J.C., Rose A.M.,
RA Hayden M.R., Neri C.;
RT "Huntingtin-interacting protein 1 influences worm and mouse presynaptic
RT function and protects Caenorhabditis elegans neurons against mutant
RT polyglutamine toxicity.";
RL J. Neurosci. 27:11056-11064(2007).
RN [4] {ECO:0000305}
RP SUBCELLULAR LOCATION.
RX PubMed=18094048; DOI=10.1091/mbc.e07-07-0719;
RA Marza E., Long T., Saiardi A., Sumakovic M., Eimer S., Hall D.H.,
RA Lesa G.M.;
RT "Polyunsaturated fatty acids influence synaptojanin localization to
RT regulate synaptic vesicle recycling.";
RL Mol. Biol. Cell 19:833-842(2008).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF 1-MET--PRO-26
RP AND ALA-66.
RX PubMed=21029864; DOI=10.1016/j.cell.2010.09.024;
RA Bai J., Hu Z., Dittman J.S., Pym E.C., Kaplan J.M.;
RT "Endophilin functions as a membrane-bending molecule and is delivered to
RT endocytic zones by exocytosis.";
RL Cell 143:430-441(2010).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=22157748; DOI=10.1038/emboj.2011.447;
RA Troulinaki K., Tavernarakis N.;
RT "Endocytosis and intracellular trafficking contribute to necrotic
RT neurodegeneration in C. elegans.";
RL EMBO J. 31:654-666(2012).
CC -!- FUNCTION: Involved in synaptic vesicle (SV) recycling in neurons
CC probably by regulating clathrin-mediated endocytosis (PubMed:14622579,
CC PubMed:21029864). By controlling SV endocytosis, regulates the rate of
CC excitatory postsynaptic currents (EPSCs) at neuromuscular junctions and
CC thus locomotion (PubMed:21029864). In a similar manner, involved in
CC necrotic neuronal cell death induced by abnormal hyperactivation of ion
CC channels (PubMed:22157748). Plays a minor role in responses to
CC mechanical stimuli (PubMed:17928447). Plays a minor role in unc-
CC 26/synaptojanin localization to synapses (PubMed:14622579).
CC {ECO:0000269|PubMed:14622579, ECO:0000269|PubMed:17928447,
CC ECO:0000269|PubMed:21029864, ECO:0000269|PubMed:22157748}.
CC -!- SUBUNIT: May form a homodimer (via the BAR domain).
CC {ECO:0000303|PubMed:21029864}.
CC -!- SUBCELLULAR LOCATION: Synapse {ECO:0000269|PubMed:14622579,
CC ECO:0000269|PubMed:18094048, ECO:0000269|PubMed:21029864}. Cytoplasmic
CC vesicle, secretory vesicle, synaptic vesicle
CC {ECO:0000269|PubMed:14622579, ECO:0000269|PubMed:21029864}. Membrane
CC {ECO:0000305|PubMed:21029864}; Peripheral membrane protein
CC {ECO:0000305|PubMed:21029864}. Note=Localizes to neuromuscular
CC junctions. Co-localizes with snb-1/synaptobrevin and rab-3 but not dyn-
CC 1 and apt-4 (PubMed:14622579, PubMed:21029864). Exocytosis promotes
CC dissociation from synaptic vesicles (PubMed:21029864).
CC {ECO:0000269|PubMed:14622579, ECO:0000269|PubMed:21029864}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=d {ECO:0000312|WormBase:T04D1.3d};
CC IsoId=B1V8A0-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:T04D1.3a};
CC IsoId=B1V8A0-2; Sequence=VSP_058674, VSP_058675;
CC Name=b {ECO:0000312|WormBase:T04D1.3b};
CC IsoId=B1V8A0-3; Sequence=VSP_058673, VSP_058675;
CC Name=c {ECO:0000312|WormBase:T04D1.3c};
CC IsoId=B1V8A0-4; Sequence=VSP_058675;
CC -!- TISSUE SPECIFICITY: Expressed in neurons and posterior intestine.
CC {ECO:0000269|PubMed:14622579}.
CC -!- DOMAIN: An N-terminal amphipathic helix, the BAR domain and a second
CC amphipathic helix inserted into helix 1 of the BAR domain (N-BAR
CC domain) induce membrane curvature and bind curved membranes. The BAR
CC domain dimer forms a rigid crescent shaped bundle of helices with the
CC pair of second amphipathic helices protruding towards the membrane-
CC binding surface (By similarity). Essential for synaptic vesicle
CC endocytosis (PubMed:21029864). Plays a role in unc-57 localization to
CC synaptic vesicles (PubMed:21029864). Dimerization and membrane-bending
CC activity are required neither for binding to synaptic vesicles nor for
CC unbinding following synaptic vesicle exocytosis (PubMed:21029864).
CC {ECO:0000250|UniProtKB:Q99962, ECO:0000269|PubMed:21029864}.
CC -!- DOMAIN: The SH3 domain is required for unc-26/synaptojanin localization
CC to synapses but is dispensable for endocytosis and unc-57 targeting to
CC synaptic vesicles. {ECO:0000269|PubMed:21029864}.
CC -!- SIMILARITY: Belongs to the endophilin family. {ECO:0000305}.
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DR EMBL; AY394006; AAQ96373.1; -; mRNA.
DR EMBL; BX284601; CCD61260.1; -; Genomic_DNA.
DR EMBL; BX284601; CCD61261.1; -; Genomic_DNA.
DR EMBL; BX284601; CCD61262.1; -; Genomic_DNA.
DR EMBL; BX284601; CCD61263.1; -; Genomic_DNA.
DR PIR; T33150; T33150.
DR RefSeq; NP_001040680.1; NM_001047215.3. [B1V8A0-2]
DR RefSeq; NP_001040681.1; NM_001047216.1. [B1V8A0-3]
DR RefSeq; NP_001122512.1; NM_001129040.2. [B1V8A0-4]
DR RefSeq; NP_001122513.1; NM_001129041.2. [B1V8A0-1]
DR AlphaFoldDB; B1V8A0; -.
DR SMR; B1V8A0; -.
DR DIP; DIP-25104N; -.
DR IntAct; B1V8A0; 45.
DR STRING; 6239.T04D1.3d.1; -.
DR EPD; B1V8A0; -.
DR PaxDb; 6239-T04D1-3d; -.
DR EnsemblMetazoa; T04D1.3a.1; T04D1.3a.1; WBGene00006791. [B1V8A0-2]
DR EnsemblMetazoa; T04D1.3b.1; T04D1.3b.1; WBGene00006791. [B1V8A0-3]
DR EnsemblMetazoa; T04D1.3c.1; T04D1.3c.1; WBGene00006791. [B1V8A0-4]
DR EnsemblMetazoa; T04D1.3d.1; T04D1.3d.1; WBGene00006791. [B1V8A0-1]
DR GeneID; 172078; -.
DR KEGG; cel:CELE_T04D1.3; -.
DR UCSC; T04D1.3d; c. elegans.
DR AGR; WB:WBGene00006791; -.
DR WormBase; T04D1.3a; CE37042; WBGene00006791; unc-57. [B1V8A0-2]
DR WormBase; T04D1.3b; CE39765; WBGene00006791; unc-57. [B1V8A0-3]
DR WormBase; T04D1.3c; CE41009; WBGene00006791; unc-57. [B1V8A0-4]
DR WormBase; T04D1.3d; CE42509; WBGene00006791; unc-57. [B1V8A0-1]
DR eggNOG; KOG1118; Eukaryota.
DR GeneTree; ENSGT00940000157398; -.
DR InParanoid; B1V8A0; -.
DR OMA; DCKKRQQ; -.
DR OrthoDB; 25371at2759; -.
DR PhylomeDB; B1V8A0; -.
DR Reactome; R-CEL-182971; EGFR downregulation.
DR Reactome; R-CEL-432720; Lysosome Vesicle Biogenesis.
DR Reactome; R-CEL-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-CEL-437239; Recycling pathway of L1.
DR Reactome; R-CEL-6807004; Negative regulation of MET activity.
DR Reactome; R-CEL-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-CEL-8856828; Clathrin-mediated endocytosis.
DR SignaLink; B1V8A0; -.
DR PRO; PR:B1V8A0; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00006791; Expressed in larva and 4 other cell types or tissues.
DR GO; GO:0098978; C:glutamatergic synapse; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031594; C:neuromuscular junction; IDA:WormBase.
DR GO; GO:0098793; C:presynapse; IBA:GO_Central.
DR GO; GO:0008021; C:synaptic vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0072583; P:clathrin-dependent endocytosis; IMP:WormBase.
DR GO; GO:0070266; P:necroptotic process; IGI:WormBase.
DR GO; GO:0016191; P:synaptic vesicle uncoating; IBA:GO_Central.
DR CDD; cd07592; BAR_Endophilin_A; 1.
DR CDD; cd11803; SH3_Endophilin_A; 1.
DR Gene3D; 1.20.1270.60; Arfaptin homology (AH) domain/BAR domain; 1.
DR Gene3D; 2.30.30.40; SH3 Domains; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR004148; BAR_dom.
DR InterPro; IPR035824; Endophilin_A_SH3.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR14167:SF30; ENDOPHILIN-A; 1.
DR PANTHER; PTHR14167; SH3 DOMAIN-CONTAINING; 1.
DR Pfam; PF03114; BAR; 1.
DR Pfam; PF07653; SH3_2; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00721; BAR; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF103657; BAR/IMD domain-like; 1.
DR SUPFAM; SSF50044; SH3-domain; 1.
DR PROSITE; PS51021; BAR; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasmic vesicle; Endocytosis;
KW Membrane; Necrosis; Reference proteome; SH3 domain; Synapse.
FT CHAIN 1..381
FT /note="Endophilin-A homolog"
FT /evidence="ECO:0000305"
FT /id="PRO_0000438523"
FT DOMAIN 18..247
FT /note="BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00361"
FT DOMAIN 320..379
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 1..21
FT /note="Membrane-binding amphipathic helix"
FT /evidence="ECO:0000250|UniProtKB:Q99962"
FT REGION 246..323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 170..238
FT /evidence="ECO:0000255"
FT COMPBIAS 261..288
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 303..317
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..277
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_058673"
FT VAR_SEQ 269..270
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_058674"
FT VAR_SEQ 288..289
FT /note="Missing (in isoform a, isoform b and isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_058675"
FT MUTAGEN 1..26
FT /note="Missing: Locomotion is almost completely impaired.
FT Severe reduction in synaptic vesicle endocytosis and in the
FT rate of excitatory postsynaptic currents (EPSCs) at
FT neuromuscular junctions."
FT /evidence="ECO:0000269|PubMed:21029864"
FT MUTAGEN 66
FT /note="A->W: May increase membrane-binding activity in
FT vitro. Does not affect its localization to synaptic
FT vesicles."
FT /evidence="ECO:0000269|PubMed:21029864"
FT CONFLICT 217
FT /note="I -> T (in Ref. 1; AAQ96373)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 381 AA; 42856 MW; 3F6A96595F837422 CRC64;
MSLSGLRKQF NKANQYLSET MGAAEPTKLD DVFNEMEKNV DTTYNLITDL VAGTNEYLQP
NPATRAKMAT QVALSKVRGT TKTSPYPQTE GMLADVMQKY GQQLGDNSDL GKSLNDAAET
YRQMADIKYQ MEDNVKQNFL DPLTHLQNNE LKDVNHHRTK LKGRRLDYDC KKRQQRRDDE
MIQAEEKLEE SKRLAEMSMF NVLSNDVEQI SQLRALIEAQ LDFHRQTAQC LENLQQQLGH
RIKDAAARPR EEHVPLSVLA NESRTPRSSF RSPAPSDMSH NSTAAAAFKM PPQNGGGITQ
APPSYQGPPP GGLPPPLSQQ QKPQCRALFD FDAQSEGELD FKEGTLIELV SQIDENWYEG
RVNGKTGLFP VTYVQVLVPL K
//
