ID SH3G3_HUMAN Reviewed; 347 AA. AC Q99963; O43553; O43554; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 24-JAN-2024, entry version 208. DE RecName: Full=Endophilin-A3; DE AltName: Full=EEN-B2; DE AltName: Full=Endophilin-3; DE AltName: Full=SH3 domain protein 2C; DE AltName: Full=SH3 domain-containing GRB2-like protein 3; GN Name=SH3GL3; Synonyms=CNSA3, SH3D2C; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fetal brain; RX PubMed=9169142; DOI=10.1006/geno.1997.4645; RA Giachino C., Lantelme E., Lanzetti L., Saccone S., Della Valle G., RA Migone N.; RT "A novel SH3-containing human gene family preferentially expressed in the RT central nervous system."; RL Genomics 41:427-434(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4). RC TISSUE=Brain; RA So C.W., So C.K.C., Sham M.H., Chan L.C.; RT "A family of EEN-like genes coding for SH3-domain containing proteins are RT preferentially expressed in human brain."; RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP INTERACTION WITH HUNTINGTIN EXON 1 PROTEIN. RX PubMed=9809064; DOI=10.1016/s1097-2765(00)80142-2; RA Sittler A., Walter S., Wedemeyer N., Hasenbank R., Scherzinger E., RA Eickhoff H., Bates G.P., Lehrach H., Wanker E.E.; RT "SH3GL3 associates with the Huntingtin exon 1 protein and promotes the RT formation of polygln-containing protein aggregates."; RL Mol. Cell 2:427-436(1998). RN [4] RP INTERACTION WITH SYNJ1. RX PubMed=10542231; DOI=10.1074/jbc.274.45.32001; RA Cestra G., Castagnoli L., Dente L., Minenkova O., Petrelli A., Migone N., RA Hoffmueller U., Schneider-Mergener J., Cesareni G.; RT "The SH3 domains of endophilin and amphiphysin bind to the proline-rich RT region of synaptojanin 1 at distinct sites that display an unconventional RT binding specificity."; RL J. Biol. Chem. 274:32001-32007(1999). RN [5] RP INTERACTION WITH SGIP1. RX PubMed=15919751; DOI=10.1210/en.2005-0282; RA Trevaskis J., Walder K., Foletta V., Kerr-Bayles L., McMillan J., RA Cooper A., Lee S., Bolton K., Prior M., Fahey R., Whitecross K., RA Morton G.J., Schwartz M.W., Collier G.R.; RT "Src homology 3-domain growth factor receptor-bound 2-like (endophilin) RT interacting protein 1, a novel neuronal protein that regulates energy RT balance."; RL Endocrinology 146:3757-3764(2005). RN [6] RP INTERACTION WITH ATXN2. RX PubMed=18602463; DOI=10.1016/j.cellsig.2008.05.018; RA Nonis D., Schmidt M.H., van de Loo S., Eich F., Dikic I., Nowock J., RA Auburger G.; RT "Ataxin-2 associates with the endocytosis complex and affects EGF receptor RT trafficking."; RL Cell. Signal. 20:1725-1739(2008). RN [7] RP INTERACTION WITH FASLG. RX PubMed=19807924; DOI=10.1186/1471-2172-10-53; RA Voss M., Lettau M., Janssen O.; RT "Identification of SH3 domain interaction partners of human FasL (CD178) by RT phage display screening."; RL BMC Immunol. 10:53-53(2009). RN [8] RP INTERACTION WITH DYDC1. RX PubMed=19545932; DOI=10.1016/j.ejcb.2009.05.001; RA Li S., Qiao Y., Di Q., Le X., Zhang L., Zhang X., Zhang C., Cheng J., RA Zong S., Koide S.S., Miao S., Wang L.; RT "Interaction of SH3P13 and DYDC1 protein: a germ cell component that RT regulates acrosome biogenesis during spermiogenesis."; RL Eur. J. Cell Biol. 88:509-520(2009). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [10] RP INTERACTION WITH BIN2. RX PubMed=23285027; DOI=10.1371/journal.pone.0052401; RA Sanchez-Barrena M.J., Vallis Y., Clatworthy M.R., Doherty G.J., RA Veprintsev D.B., Evans P.R., McMahon H.T.; RT "Bin2 is a membrane sculpting N-BAR protein that influences leucocyte RT podosomes, motility and phagocytosis."; RL PLoS ONE 7:E52401-E52401(2012). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-265, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) OF 22-256. RG RIKEN structural genomics initiative (RSGI); RT "Crystal structure of BAR domain of endophilin-III."; RL Submitted (FEB-2009) to the PDB data bank. CC -!- FUNCTION: Implicated in endocytosis. May recruit other proteins to CC membranes with high curvature (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Interacts with ARC (By similarity). Interacts with DNM1, SGIP1 CC and SYNJ1. Interacts with the huntingtin exon 1 protein (HDEX1P) CC containing a glutamine repeat in the pathological range and promotes CC formation of insoluble polyglutamine-containing aggregates in vivo. CC Interacts with DYDC1. Interacts with FASLG. Interacts with ATXN2. CC Interacts with BIN2. {ECO:0000250, ECO:0000269|PubMed:10542231, CC ECO:0000269|PubMed:15919751, ECO:0000269|PubMed:18602463, CC ECO:0000269|PubMed:19545932, ECO:0000269|PubMed:19807924, CC ECO:0000269|PubMed:23285027, ECO:0000269|PubMed:9809064}. CC -!- INTERACTION: CC Q99963; Q99700: ATXN2; NbExp=11; IntAct=EBI-473910, EBI-697691; CC Q99963; P42858: HTT; NbExp=9; IntAct=EBI-473910, EBI-466029; CC Q99963; Q70E73: RAPH1; NbExp=4; IntAct=EBI-473910, EBI-3940924; CC Q99963; Q99961: SH3GL1; NbExp=4; IntAct=EBI-473910, EBI-697911; CC Q99963; Q99962: SH3GL2; NbExp=5; IntAct=EBI-473910, EBI-77938; CC Q99963; Q99963: SH3GL3; NbExp=3; IntAct=EBI-473910, EBI-473910; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O35180}. Early CC endosome membrane {ECO:0000250|UniProtKB:O35180}; Peripheral membrane CC protein {ECO:0000250|UniProtKB:O35180}. Note=Associated with CC postsynaptic endosomes in hippocampal neurons. Associated with CC presynaptic endosomes in olfactory neurons. CC {ECO:0000250|UniProtKB:O35180}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=EEN-B2-L1; CC IsoId=Q99963-1; Sequence=Displayed; CC Name=2; Synonyms=EEN-B2-L2; CC IsoId=Q99963-2; Sequence=VSP_001441; CC Name=3; Synonyms=EEN-B2-L3; CC IsoId=Q99963-3; Sequence=VSP_001440; CC Name=4; Synonyms=EEN-B2-L4; CC IsoId=Q99963-4; Sequence=VSP_001442; CC -!- TISSUE SPECIFICITY: Brain and testis. 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. CC {ECO:0000250}. CC -!- SIMILARITY: Belongs to the endophilin family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X99664; CAA67978.1; -; mRNA. DR EMBL; AF036269; AAC04765.1; -; mRNA. DR EMBL; AF036270; AAC04766.1; -; mRNA. DR EMBL; AF036271; AAC04767.1; -; mRNA. DR EMBL; AF036272; AAC04768.1; -; mRNA. DR CCDS; CCDS10325.2; -. [Q99963-1] DR CCDS; CCDS73772.1; -. [Q99963-3] DR RefSeq; NP_001288037.1; NM_001301108.1. [Q99963-2] DR RefSeq; NP_001288038.1; NM_001301109.1. [Q99963-3] DR RefSeq; NP_001311112.1; NM_001324183.1. [Q99963-3] DR RefSeq; NP_001311114.1; NM_001324185.1. [Q99963-2] DR RefSeq; NP_001311116.1; NM_001324187.1. [Q99963-2] DR RefSeq; NP_003018.3; NM_003027.4. [Q99963-1] DR RefSeq; XP_011520191.1; XM_011521889.1. [Q99963-3] DR RefSeq; XP_016877975.1; XM_017022486.1. [Q99963-2] DR PDB; 2EW3; NMR; -; A=285-345. DR PDB; 2Z0V; X-ray; 2.49 A; A/B=24-256. DR PDBsum; 2EW3; -. DR PDBsum; 2Z0V; -. DR AlphaFoldDB; Q99963; -. DR SMR; Q99963; -. DR BioGRID; 112354; 135. DR CORUM; Q99963; -. DR DIP; DIP-34766N; -. DR IntAct; Q99963; 135. DR MINT; Q99963; -. DR STRING; 9606.ENSP00000320092; -. DR GlyCosmos; Q99963; 1 site, 1 glycan. DR GlyGen; Q99963; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q99963; -. DR PhosphoSitePlus; Q99963; -. DR BioMuta; SH3GL3; -. DR DMDM; 12643798; -. DR EPD; Q99963; -. DR jPOST; Q99963; -. DR MassIVE; Q99963; -. DR MaxQB; Q99963; -. DR PaxDb; 9606-ENSP00000320092; -. DR PeptideAtlas; Q99963; -. DR ProteomicsDB; 78547; -. [Q99963-1] DR ProteomicsDB; 78548; -. [Q99963-2] DR ProteomicsDB; 78549; -. [Q99963-3] DR ProteomicsDB; 78550; -. [Q99963-4] DR Pumba; Q99963; -. DR Antibodypedia; 28199; 195 antibodies from 27 providers. DR DNASU; 6457; -. DR Ensembl; ENST00000324537.5; ENSP00000320092.5; ENSG00000140600.17. [Q99963-3] DR Ensembl; ENST00000427482.7; ENSP00000391372.2; ENSG00000140600.17. [Q99963-1] DR Ensembl; ENST00000708174.1; ENSP00000517113.1; ENSG00000291608.1. [Q99963-1] DR Ensembl; ENST00000708176.1; ENSP00000517115.1; ENSG00000291608.1. [Q99963-3] DR GeneID; 6457; -. DR KEGG; hsa:6457; -. DR MANE-Select; ENST00000427482.7; ENSP00000391372.2; NM_003027.5; NP_003018.3. DR UCSC; uc002bju.4; human. [Q99963-1] DR AGR; HGNC:10832; -. DR CTD; 6457; -. DR DisGeNET; 6457; -. DR GeneCards; SH3GL3; -. DR HGNC; HGNC:10832; SH3GL3. DR HPA; ENSG00000140600; Tissue enhanced (brain, testis). DR MIM; 603362; gene. DR neXtProt; NX_Q99963; -. DR OpenTargets; ENSG00000140600; -. DR PharmGKB; PA35738; -. DR VEuPathDB; HostDB:ENSG00000140600; -. DR eggNOG; KOG1118; Eukaryota. DR GeneTree; ENSGT00940000157398; -. DR HOGENOM; CLU_047887_0_0_1; -. DR InParanoid; Q99963; -. DR OMA; NFLENDX; -. DR OrthoDB; 25371at2759; -. DR PhylomeDB; Q99963; -. DR TreeFam; TF313281; -. DR PathwayCommons; Q99963; -. DR Reactome; R-HSA-182971; EGFR downregulation. DR Reactome; R-HSA-6807004; Negative regulation of MET activity. DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis. DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. DR Reactome; R-HSA-8875360; InlB-mediated entry of Listeria monocytogenes into host cell. DR Reactome; R-HSA-9031628; NGF-stimulated transcription. DR SignaLink; Q99963; -. DR SIGNOR; Q99963; -. DR BioGRID-ORCS; 6457; 11 hits in 1150 CRISPR screens. DR ChiTaRS; SH3GL3; human. DR EvolutionaryTrace; Q99963; -. DR GeneWiki; SH3GL3; -. DR GenomeRNAi; 6457; -. DR Pharos; Q99963; Tbio. DR PRO; PR:Q99963; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; Q99963; Protein. DR Bgee; ENSG00000140600; Expressed in sperm and 140 other cell types or tissues. DR ExpressionAtlas; Q99963; baseline and differential. DR GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0098978; C:glutamatergic synapse; IBA:GO_Central. DR GO; GO:0099092; C:postsynaptic density, intracellular component; IEA:Ensembl. DR GO; GO:0098845; C:postsynaptic endosome; IEA:Ensembl. DR GO; GO:0098793; C:presynapse; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW. DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc. DR GO; GO:1900186; P:negative regulation of clathrin-dependent endocytosis; IEA:Ensembl. DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0016191; P:synaptic vesicle uncoating; IBA:GO_Central. DR CDD; cd07615; BAR_Endophilin_A3; 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; IPR032469; Endophilin-A3_BAR. DR InterPro; IPR035824; Endophilin_A_SH3. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR PANTHER; PTHR14167:SF45; ENDOPHILIN-A3; 1. DR PANTHER; PTHR14167; SH3 DOMAIN-CONTAINING; 1. DR Pfam; PF03114; BAR; 1. DR Pfam; PF00018; SH3_1; 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. DR Genevisible; Q99963; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm; Endocytosis; KW Endosome; Lipid-binding; Membrane; Phosphoprotein; Reference proteome; KW SH3 domain. FT CHAIN 1..347 FT /note="Endophilin-A3" FT /id="PRO_0000146750" FT DOMAIN 18..249 FT /note="BAR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00361" FT DOMAIN 285..344 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT REGION 1..21 FT /note="Membrane-binding amphipathic helix" FT /evidence="ECO:0000250" FT REGION 60..87 FT /note="Required for dimerization upon membrane association" FT /evidence="ECO:0000250" FT REGION 218..254 FT /note="Interaction with ARC" FT /evidence="ECO:0000250" FT REGION 248..271 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 181..201 FT /evidence="ECO:0000255" FT MOD_RES 265 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..69 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_001441" FT VAR_SEQ 1..14 FT /note="MSVAGLKKQFHKAS -> MDGIFAGIICNQANRCLTWTSQ (in isoform FT 3)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_001440" FT VAR_SEQ 311..347 FT /note="IITLTNQIDENWYEGMIHGESGFFPINYVEVIVPLPQ -> GTFRKIKRETK FT IKMCRKKIVNIYKLKDQQH (in isoform 4)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_001442" FT HELIX 31..58 FT /evidence="ECO:0007829|PDB:2Z0V" FT HELIX 62..69 FT /evidence="ECO:0007829|PDB:2Z0V" FT HELIX 89..104 FT /evidence="ECO:0007829|PDB:2Z0V" FT HELIX 109..138 FT /evidence="ECO:0007829|PDB:2Z0V" FT HELIX 140..148 FT /evidence="ECO:0007829|PDB:2Z0V" FT HELIX 150..172 FT /evidence="ECO:0007829|PDB:2Z0V" FT TURN 173..176 FT /evidence="ECO:0007829|PDB:2Z0V" FT HELIX 180..206 FT /evidence="ECO:0007829|PDB:2Z0V" FT HELIX 209..246 FT /evidence="ECO:0007829|PDB:2Z0V" FT STRAND 289..294 FT /evidence="ECO:0007829|PDB:2EW3" FT STRAND 311..327 FT /evidence="ECO:0007829|PDB:2EW3" FT STRAND 330..335 FT /evidence="ECO:0007829|PDB:2EW3" FT HELIX 336..338 FT /evidence="ECO:0007829|PDB:2EW3" FT STRAND 339..342 FT /evidence="ECO:0007829|PDB:2EW3" SQ SEQUENCE 347 AA; 39285 MW; D68DA7B28574C4E6 CRC64; MSVAGLKKQF HKASQLFSEK ISGAEGTKLD DEFLDMERKI DVTNKVVAEI LSKTTEYLQP NPAYRAKLGM LNTVSKIRGQ VKTTGYPQTE GLLGDCMLKY GKELGEDSTF GNALIEVGES MKLMAEVKDS LDINVKQTFI DPLQLLQDKD LKEIGHHLKK LEGRRLDYDY KKKRVGKIPD EEVRQAVEKF EESKELAERS MFNFLENDVE QVSQLAVFIE AALDYHRQST EILQELQSKL QMRISAASSV PRREYKPRPV KRSSSELNGV STTSVVKTTG SNIPMDQPCC RGLYDFEPEN QGELGFKEGD IITLTNQIDE NWYEGMIHGE SGFFPINYVE VIVPLPQ //