SH3G2_RAT
ID SH3G2_RAT Reviewed; 352 AA.
AC O35179;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Endophilin-A1;
DE AltName: Full=Endophilin-1;
DE AltName: Full=SH3 domain protein 2A;
DE AltName: Full=SH3 domain-containing GRB2-like protein 2;
DE AltName: Full=SH3p4;
GN Name=Sh3gl2; Synonyms=Sh3d2a, Sh3p4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-79.
RX PubMed=8889548; DOI=10.1101/gr.6.9.791;
RA Bonaldo M.F., Lennon G., Soares M.B.;
RT "Normalization and subtraction: two approaches to facilitate gene
RT discovery.";
RL Genome Res. 6:791-806(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 15-352.
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 105-352, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND INTERACTION WITH DNM1 AND SYNJ1.
RC TISSUE=Brain;
RX PubMed=9238017; DOI=10.1073/pnas.94.16.8569;
RA Ringstad N., Nemoto Y., De Camilli P.;
RT "The SH3p4/Sh3p8/SH3p13 protein family: binding partners for synaptojanin
RT and dynamin via a Grb2-like Src homology 3 domain.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:8569-8574(1997).
RN [4]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH SYNJ1.
RX PubMed=9341169; DOI=10.1074/jbc.272.43.27239;
RA Micheva K.D., Kay B.K., McPherson P.S.;
RT "Synaptojanin forms two separate complexes in the nerve terminal.
RT Interactions with endophilin and amphiphysin.";
RL J. Biol. Chem. 272:27239-27245(1997).
RN [5]
RP INTERACTION WITH MAP4K3; SYNJ1 AND DNM1.
RX PubMed=11384986; DOI=10.1074/jbc.m103198200;
RA Ramjaun A.R., Angers A., Legendre-Guillemin V., Tong X.-K., McPherson P.S.;
RT "Endophilin regulates JNK activation through its interaction with the
RT germinal center kinase-like kinase.";
RL J. Biol. Chem. 276:28913-28919(2001).
RN [6]
RP FUNCTION, AND DOMAIN.
RX PubMed=11604418; DOI=10.1083/jcb.200107075;
RA Farsad K., Ringstad N., Takei K., Floyd S.R., Rose K., De Camilli P.;
RT "Generation of high curvature membranes mediated by direct endophilin
RT bilayer interactions.";
RL J. Cell Biol. 155:193-200(2001).
RN [7]
RP MUTAGENESIS OF LEU-263.
RX PubMed=15066995; DOI=10.1074/jbc.m312607200;
RA Sugiura H., Iwata K., Matsuoka M., Hayashi H., Takemiya T., Yasuda S.,
RA Ichikawa M., Yamauchi T., Mehlen P., Haga T., Yamagata K.;
RT "Inhibitory role of endophilin 3 in receptor-mediated endocytosis.";
RL J. Biol. Chem. 279:23343-23348(2004).
RN [8]
RP SHOWS THAT SH3GL2 HAS NO LYSOPHOSPHATIDIC ACID ACYLTRANSFERASE ACTIVITY.
RX PubMed=16319893; DOI=10.1038/nature04136;
RA Gallop J.L., Butler P.J., McMahon H.T.;
RT "Endophilin and CtBP/BARS are not acyl transferases in endocytosis or Golgi
RT fission.";
RL Nature 438:675-678(2005).
RN [9]
RP STRUCTURE BY NMR OF 291-352, AND DOMAIN.
RX PubMed=16763557; DOI=10.1038/sj.emboj.7601176;
RA Masuda M., Takeda S., Sone M., Ohki T., Mori H., Kamioka Y., Mochizuki N.;
RT "Endophilin BAR domain drives membrane curvature by two newly identified
RT structure-based mechanisms.";
RL EMBO J. 25:2889-2897(2006).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 25-247, FUNCTION, SUBUNIT, AND
RP DOMAIN.
RX PubMed=16763559; DOI=10.1038/sj.emboj.7601174;
RA Gallop J.L., Jao C.C., Kent H.M., Butler P.J., Evans P.R., Langen R.,
RA McMahon H.T.;
RT "Mechanism of endophilin N-BAR domain-mediated membrane curvature.";
RL EMBO J. 25:2898-2910(2006).
CC -!- FUNCTION: Implicated in synaptic vesicle endocytosis. May recruit other
CC proteins to membranes with high curvature. Required for BDNF-dependent
CC dendrite outgrowth. Cooperates with SH3GL2 to mediate BDNF-NTRK2 early
CC endocytic trafficking and signaling from early endosomes (By
CC similarity). {ECO:0000250|UniProtKB:Q62420,
CC ECO:0000269|PubMed:11604418, ECO:0000269|PubMed:16763559}.
CC -!- SUBUNIT: Monomer; in cytoplasm. Homodimer; when associated with
CC membranes (By similarity). Interacts with OPHN1 (By similarity).
CC Interacts with SYNJ1 (PubMed:9341169, PubMed:9238017, PubMed:11384986).
CC Interacts with DNM1 (PubMed:9238017, PubMed:11384986). Interacts with
CC MAP4K3; the interaction appears to regulate MAP4K3-mediated JNK
CC activation (PubMed:11384986). Interacts with PDCD6IP (By similarity).
CC Interacts with ATXN2 (By similarity). Interacts with ADAM9 and ADAM15
CC cytoplasmic tails (By similarity). Interacts with BIN2 (By similarity).
CC Interacts with TMEM108 (By similarity). Interacts with ADGRB2 (By
CC similarity). {ECO:0000250|UniProtKB:Q62420,
CC ECO:0000250|UniProtKB:Q99962, ECO:0000269|PubMed:11384986,
CC ECO:0000269|PubMed:9238017, ECO:0000269|PubMed:9341169}.
CC -!- INTERACTION:
CC O35179; P21575: Dnm1; NbExp=6; IntAct=EBI-1149197, EBI-80070;
CC O35179; Q62910: Synj1; NbExp=2; IntAct=EBI-1149197, EBI-1149123;
CC O35179; O43295: SRGAP3; Xeno; NbExp=3; IntAct=EBI-1149197, EBI-368166;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9238017,
CC ECO:0000269|PubMed:9341169}. Membrane {ECO:0000269|PubMed:9238017};
CC Peripheral membrane protein {ECO:0000269|PubMed:9238017}. Early
CC endosome {ECO:0000250|UniProtKB:Q62420}. Presynapse
CC {ECO:0000269|PubMed:9341169}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain (PubMed:9341169). Expressed
CC at low level in the kidney. {ECO:0000269|PubMed:9238017,
CC ECO:0000269|PubMed:9341169}.
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. {ECO:0000269|PubMed:11604418,
CC ECO:0000269|PubMed:16763557, ECO:0000269|PubMed:16763559}.
CC -!- MISCELLANEOUS: The N-BAR domain binds liposomes and mediates
CC dimerization of BAR domains upon liposome binding. It induces formation
CC of tubules from liposomes as well as fusion of liposome tubules. Cells
CC overexpressing Sh3gl2 show no effect on transferrin uptake.
CC -!- SIMILARITY: Belongs to the endophilin family. {ECO:0000305}.
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DR EMBL; AI044966; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC112121; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF009603; AAC14883.1; -; mRNA.
DR RefSeq; NP_446387.1; NM_053935.1.
DR PDB; 2C08; X-ray; 2.90 A; A=25-247.
DR PDB; 2KNB; NMR; -; B=291-352.
DR PDB; 3IQL; X-ray; 1.40 A; A/B=291-352.
DR PDBsum; 2C08; -.
DR PDBsum; 2KNB; -.
DR PDBsum; 3IQL; -.
DR AlphaFoldDB; O35179; -.
DR BMRB; O35179; -.
DR SMR; O35179; -.
DR BioGRID; 250599; 4.
DR CORUM; O35179; -.
DR ELM; O35179; -.
DR IntAct; O35179; 11.
DR MINT; O35179; -.
DR STRING; 10116.ENSRNOP00000008999; -.
DR iPTMnet; O35179; -.
DR PhosphoSitePlus; O35179; -.
DR SwissPalm; O35179; -.
DR jPOST; O35179; -.
DR PaxDb; O35179; -.
DR PRIDE; O35179; -.
DR GeneID; 116743; -.
DR KEGG; rno:116743; -.
DR UCSC; RGD:620276; rat.
DR CTD; 6456; -.
DR RGD; 620276; Sh3gl2.
DR VEuPathDB; HostDB:ENSRNOG00000006761; -.
DR eggNOG; KOG1118; Eukaryota.
DR HOGENOM; CLU_047887_0_0_1; -.
DR InParanoid; O35179; -.
DR OMA; XIRQASS; -.
DR OrthoDB; 788657at2759; -.
DR PhylomeDB; O35179; -.
DR Reactome; R-RNO-177504; Retrograde neurotrophin signalling.
DR Reactome; R-RNO-182971; EGFR downregulation.
DR Reactome; R-RNO-2132295; MHC class II antigen presentation.
DR Reactome; R-RNO-432720; Lysosome Vesicle Biogenesis.
DR Reactome; R-RNO-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-RNO-437239; Recycling pathway of L1.
DR Reactome; R-RNO-6807004; Negative regulation of MET activity.
DR Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR EvolutionaryTrace; O35179; -.
DR PRO; PR:O35179; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000006761; Expressed in cerebellum and 19 other tissues.
DR Genevisible; O35179; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0097441; C:basal dendrite; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IDA:SynGO.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0098684; C:photoreceptor ribbon synapse; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098793; C:presynapse; IDA:RGD.
DR GO; GO:0099523; C:presynaptic cytosol; ISO:RGD.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0030672; C:synaptic vesicle membrane; IDA:SynGO.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0008289; F:lipid binding; IDA:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:RGD.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:1990416; P:cellular response to brain-derived neurotrophic factor stimulus; ISS:UniProtKB.
DR GO; GO:0097484; P:dendrite extension; ISS:UniProtKB.
DR GO; GO:0060988; P:lipid tube assembly; IDA:RGD.
DR GO; GO:0097753; P:membrane bending; IMP:RGD.
DR GO; GO:0097749; P:membrane tubulation; IDA:RGD.
DR GO; GO:1905604; P:negative regulation of blood-brain barrier permeability; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:1903527; P:positive regulation of membrane tubulation; IMP:RGD.
DR GO; GO:2000369; P:regulation of clathrin-dependent endocytosis; IMP:RGD.
DR GO; GO:0002090; P:regulation of receptor internalization; ISO:RGD.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; IDA:SynGO.
DR GO; GO:0016191; P:synaptic vesicle uncoating; ISO:RGD.
DR GO; GO:0099050; P:vesicle scission; IDA:RGD.
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; IPR035824; Endophilin_A_SH3.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
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; Cell projection; Coiled coil; Cytoplasm; Endocytosis;
KW Endosome; Lipid-binding; Membrane; Phosphoprotein; Reference proteome;
KW SH3 domain; Synapse.
FT CHAIN 1..352
FT /note="Endophilin-A1"
FT /id="PRO_0000146749"
FT DOMAIN 18..249
FT /note="BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00361"
FT DOMAIN 290..349
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 1..125
FT /note="Binds and tubulates liposomes"
FT REGION 1..21
FT /note="Membrane-binding amphipathic helix"
FT REGION 60..87
FT /note="Required for dimerization upon membrane association"
FT REGION 246..289
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 181..250
FT /evidence="ECO:0000255"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62420"
FT MOD_RES 299
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q62419"
FT MUTAGEN 263
FT /note="L->P: Confers inhibition of transferrin uptake
FT comparable to Sh3gl3 upon overexpression."
FT /evidence="ECO:0000269|PubMed:15066995"
FT CONFLICT 78
FT /note="R -> H (in Ref. 1; AI044966)"
FT /evidence="ECO:0000305"
FT HELIX 31..58
FT /evidence="ECO:0007829|PDB:2C08"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:2C08"
FT HELIX 89..104
FT /evidence="ECO:0007829|PDB:2C08"
FT STRAND 106..109
FT /evidence="ECO:0007829|PDB:2C08"
FT HELIX 110..138
FT /evidence="ECO:0007829|PDB:2C08"
FT HELIX 140..173
FT /evidence="ECO:0007829|PDB:2C08"
FT TURN 174..177
FT /evidence="ECO:0007829|PDB:2C08"
FT HELIX 180..205
FT /evidence="ECO:0007829|PDB:2C08"
FT HELIX 208..245
FT /evidence="ECO:0007829|PDB:2C08"
FT STRAND 294..299
FT /evidence="ECO:0007829|PDB:3IQL"
FT STRAND 316..322
FT /evidence="ECO:0007829|PDB:3IQL"
FT STRAND 324..332
FT /evidence="ECO:0007829|PDB:3IQL"
FT STRAND 335..340
FT /evidence="ECO:0007829|PDB:3IQL"
FT HELIX 341..343
FT /evidence="ECO:0007829|PDB:3IQL"
FT STRAND 344..348
FT /evidence="ECO:0007829|PDB:3IQL"
SQ SEQUENCE 352 AA; 39899 MW; 382B6F651885B679 CRC64;
MSVAGLKKQF HKATQKVSEK VGGAEGTKLD DDFKEMERKV DVTSRAVMEI MTKTIEYLQP
NPASRAKLSM INTMSKIRGQ EKGPGYPQAE ALLAEAMLKF GRELGDDCNF GPALGEVGEA
MRELSEVKDS LDMEVKQNFI DPLQNLHDKD LREIQHHLKK LEGRRLDFDY KKKRQGKIPD
EELRQALEKF DESKEIAESS MFNLLEMDIE QVSQLSALVQ AQLEYHKQAV QILQQVTVRL
EERIRQASSQ PRREYQPKPR MSLEFATGDG TQPNGGLSHT GTPKPAGVQM DQPCCRALYD
FEPENEGELG FKEGDIITLT NQIDENWYEG MLHGQSGFFP INYVEILVAL PH
