SH3G3_HUMAN
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 03-AUG-2022, entry version 200.
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}.
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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; 133.
DR CORUM; Q99963; -.
DR DIP; DIP-34766N; -.
DR IntAct; Q99963; 135.
DR MINT; Q99963; -.
DR STRING; 9606.ENSP00000320092; -.
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; Q99963; -.
DR PeptideAtlas; Q99963; -.
DR PRIDE; Q99963; -.
DR ProteomicsDB; 78547; -. [Q99963-1]
DR ProteomicsDB; 78548; -. [Q99963-2]
DR ProteomicsDB; 78549; -. [Q99963-3]
DR ProteomicsDB; 78550; -. [Q99963-4]
DR Antibodypedia; 28199; 160 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 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 CTD; 6457; -.
DR DisGeNET; 6457; -.
DR GeneCards; SH3GL3; -.
DR HGNC; HGNC:10832; SH3GL3.
DR HPA; ENSG00000140600; Group enriched (brain, choroid plexus, 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; 788657at2759; -.
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 1072 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 138 other tissues.
DR ExpressionAtlas; Q99963; baseline and differential.
DR Genevisible; Q99963; HS.
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:0008022; F:protein C-terminus binding; IEA:Ensembl.
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; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR004148; BAR_dom.
DR InterPro; IPR028501; Endophilin-A.
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; PTHR14167:SF45; 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; SSF103657; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS51021; BAR; 1.
DR PROSITE; PS50002; SH3; 1.
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
