FCSD2_HUMAN
ID FCSD2_HUMAN Reviewed; 740 AA.
AC O94868; B4DNI3; Q7L8J9; Q8WVM2; Q96FV7; Q9UF77;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 3.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=F-BAR and double SH3 domains protein 2;
DE AltName: Full=Carom {ECO:0000303|PubMed:14627983};
DE AltName: Full=Protein nervous wreck 1 {ECO:0000250|UniProtKB:Q3USJ8};
DE Short=NWK1 {ECO:0000250|UniProtKB:Q3USJ8};
DE AltName: Full=SH3 multiple domains protein 3;
GN Name=FCHSD2; Synonyms=KIAA0769, SH3MD3;
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 2), TISSUE SPECIFICITY, AND INTERACTION
RP WITH CASK AND MAGI1.
RC TISSUE=Lung;
RX PubMed=14627983; DOI=10.1038/sj.onc.1206996;
RA Ohno H., Hirabayashi S., Kansaku A., Yao I., Tajima M., Nishimura W.,
RA Ohnishi H., Mashima H., Fujita T., Omata M., Hata Y.;
RT "Carom: a novel membrane-associated guanylate kinase-interacting protein
RT with two SH3 domains.";
RL Oncogene 22:8422-8431(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XI. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:277-286(1998).
RN [3]
RP SEQUENCE REVISION.
RA Okazaki N., Kikuno R.F., Nagase T., Ohara O., Koga H.;
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Bone marrow, and Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 138-740.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP IDENTIFICATION.
RX PubMed=15067381;
RA Katoh M., Katoh M.;
RT "Identification and characterization of human FCHSD1 and FCHSD2 genes in
RT silico.";
RL Int. J. Mol. Med. 13:749-754(2004).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-675 AND SER-681, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-681, IDENTIFICATION
RP BY MASS SPECTROMETRY, AND MUTAGENESIS OF SER-681.
RX PubMed=30249660; DOI=10.1073/pnas.1810209115;
RA Xiao G.Y., Mohanakrishnan A., Schmid S.L.;
RT "Role for ERK1/2-dependent activation of FCHSD2 in cancer cell-selective
RT regulation of clathrin-mediated endocytosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E9570-E9579(2018).
RN [12]
RP STRUCTURE BY NMR OF 464-530 AND 569-628.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the second SH3 domain of human KIAA0769 protein.";
RL Submitted (OCT-2006) to the PDB data bank.
RN [13] {ECO:0007744|PDB:6GBU}
RP X-RAY CRYSTALLOGRAPHY (3.44 ANGSTROMS) OF 567-629 IN COMPLEX WITH ITSN1,
RP SUBUNIT, INTERACTION WITH WASL AND ITSN1, FUNCTION, SUBCELLULAR LOCATION,
RP LIPID-BINDING, DOMAIN, AND MUTAGENESIS OF TYR-478; TYR-480; PRO-521;
RP TYR-524; TYR-576; PHE-607 AND 622-VAL-LEU-623.
RX PubMed=29887380; DOI=10.1016/j.cell.2018.05.020;
RA Almeida-Souza L., Frank R.A.W., Garcia-Nafria J., Colussi A.,
RA Gunawardana N., Johnson C.M., Yu M., Howard G., Andrews B., Vallis Y.,
RA McMahon H.T.;
RT "A Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin-
RT Coated Pits.";
RL Cell 174:325-337(2018).
CC -!- FUNCTION: Adapter protein that plays a role in endocytosis via
CC clathrin-coated pits. Contributes to the internalization of cell
CC surface receptors, such as integrin ITGB1 and transferrin receptor
CC (PubMed:29887380). Promotes endocytosis of EGFR in cancer cells, and
CC thereby contributes to the down-regulation of EGFR signaling
CC (PubMed:30249660). Recruited to clathrin-coated pits during a mid-to-
CC late stage of assembly, where it is required for normal progress from
CC U-shaped intermediate stage pits to terminal, omega-shaped pits
CC (PubMed:29887380). Binds to membranes enriched in phosphatidylinositol
CC 3,4-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate
CC (PubMed:29887380). When bound to membranes, promotes actin
CC polymerization via its interaction with WAS and/or WASL which leads to
CC the activation of the Arp2/3 complex. Does not promote actin
CC polymerisation in the absence of membranes (PubMed:29887380).
CC {ECO:0000269|PubMed:29887380, ECO:0000269|PubMed:30249660}.
CC -!- SUBUNIT: Homodimer (PubMed:29887380). Interacts (via SH3 domain 2) with
CC ITSN1 (via SH3 domain 4). Recruited to clathrin-coated pits during a
CC mid-to-late stage of assembly via interaction with ITSN1. Interacts
CC (via SH3 domain 1) with WASL (PubMed:29887380). Interacts with WAS (By
CC similarity). Interacts with CASK and MAGI1. CASK inhibits interaction
CC with MAGI1 (PubMed:14627983). {ECO:0000250|UniProtKB:Q3USJ8,
CC ECO:0000269|PubMed:14627983, ECO:0000269|PubMed:29887380}.
CC -!- INTERACTION:
CC O94868; Q9NUQ8: ABCF3; NbExp=4; IntAct=EBI-1215612, EBI-717672;
CC O94868; Q8IZU0: FAM9B; NbExp=4; IntAct=EBI-1215612, EBI-10175124;
CC O94868; Q9BVG8: KIFC3; NbExp=3; IntAct=EBI-1215612, EBI-2125614;
CC O94868; Q96QZ7: MAGI1; NbExp=5; IntAct=EBI-1215612, EBI-924464;
CC O94868; Q5JR59: MTUS2; NbExp=4; IntAct=EBI-1215612, EBI-742948;
CC O94868; P55072: VCP; NbExp=2; IntAct=EBI-1215612, EBI-355164;
CC O94868; Q62915: Cask; Xeno; NbExp=2; IntAct=EBI-1215612, EBI-704635;
CC O94868-3; Q15027: ACAP1; NbExp=3; IntAct=EBI-11958845, EBI-751746;
CC O94868-3; Q49AR9: ANKS1A; NbExp=3; IntAct=EBI-11958845, EBI-11954519;
CC O94868-3; Q8N5M1: ATPAF2; NbExp=3; IntAct=EBI-11958845, EBI-1166928;
CC O94868-3; Q96GS4: BORCS6; NbExp=4; IntAct=EBI-11958845, EBI-10193358;
CC O94868-3; Q96HB5: CCDC120; NbExp=3; IntAct=EBI-11958845, EBI-744556;
CC O94868-3; G5E9W6: CCDC183; NbExp=3; IntAct=EBI-11958845, EBI-17212717;
CC O94868-3; Q8TD31-3: CCHCR1; NbExp=5; IntAct=EBI-11958845, EBI-10175300;
CC O94868-3; Q07002: CDK18; NbExp=3; IntAct=EBI-11958845, EBI-746238;
CC O94868-3; P78358: CTAG1B; NbExp=3; IntAct=EBI-11958845, EBI-1188472;
CC O94868-3; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-11958845, EBI-744099;
CC O94868-3; P22607: FGFR3; NbExp=3; IntAct=EBI-11958845, EBI-348399;
CC O94868-3; Q96D09: GPRASP2; NbExp=3; IntAct=EBI-11958845, EBI-473189;
CC O94868-3; P06396: GSN; NbExp=3; IntAct=EBI-11958845, EBI-351506;
CC O94868-3; P56524-2: HDAC4; NbExp=3; IntAct=EBI-11958845, EBI-11953488;
CC O94868-3; O14964: HGS; NbExp=3; IntAct=EBI-11958845, EBI-740220;
CC O94868-3; Q86YM7: HOMER1; NbExp=3; IntAct=EBI-11958845, EBI-746815;
CC O94868-3; P01112: HRAS; NbExp=3; IntAct=EBI-11958845, EBI-350145;
CC O94868-3; O95447: LCA5L; NbExp=3; IntAct=EBI-11958845, EBI-8473670;
CC O94868-3; O95751: LDOC1; NbExp=3; IntAct=EBI-11958845, EBI-740738;
CC O94868-3; P55081: MFAP1; NbExp=3; IntAct=EBI-11958845, EBI-1048159;
CC O94868-3; Q8NEH6: MNS1; NbExp=3; IntAct=EBI-11958845, EBI-743811;
CC O94868-3; Q9Y605: MRFAP1; NbExp=3; IntAct=EBI-11958845, EBI-995714;
CC O94868-3; P31321: PRKAR1B; NbExp=3; IntAct=EBI-11958845, EBI-2805516;
CC O94868-3; Q6NUQ1: RINT1; NbExp=3; IntAct=EBI-11958845, EBI-726876;
CC O94868-3; Q6UVJ0: SASS6; NbExp=3; IntAct=EBI-11958845, EBI-1570153;
CC O94868-3; Q9UJW9: SERTAD3; NbExp=3; IntAct=EBI-11958845, EBI-748621;
CC O94868-3; Q9H788: SH2D4A; NbExp=5; IntAct=EBI-11958845, EBI-747035;
CC O94868-3; Q08117-2: TLE5; NbExp=3; IntAct=EBI-11958845, EBI-11741437;
CC O94868-3; Q3SY00: TSGA10IP; NbExp=3; IntAct=EBI-11958845, EBI-10241197;
CC O94868-3; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-11958845, EBI-739895;
CC O94868-3; A5D8V6: VPS37C; NbExp=3; IntAct=EBI-11958845, EBI-2559305;
CC O94868-3; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-11958845, EBI-6427977;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q3USJ8}. Cell
CC junction {ECO:0000269|PubMed:14627983}. Membrane, clathrin-coated pit
CC {ECO:0000269|PubMed:29887380, ECO:0000269|PubMed:30249660}. Cell
CC membrane {ECO:0000269|PubMed:14627983, ECO:0000269|PubMed:29887380,
CC ECO:0000269|PubMed:30249660}; Peripheral membrane protein
CC {ECO:0000269|PubMed:14627983, ECO:0000269|PubMed:30249660}; Cytoplasmic
CC side {ECO:0000269|PubMed:14627983, ECO:0000269|PubMed:30249660}. Cell
CC projection, stereocilium {ECO:0000250|UniProtKB:Q3USJ8}. Note=Partially
CC localized at clathrin-coated pits at the cell membrane
CC (PubMed:30249660). Detected at the cell membrane at sites around
CC clathrin-coated pits, very close to the clathrin-coated pits but not an
CC intrinsic part of the clathrin-coated pits (PubMed:29887380).
CC Colocalizes at cell-cell contacts with CDH1, but is not detected at
CC tight junctions (PubMed:14627983). {ECO:0000269|PubMed:14627983,
CC ECO:0000269|PubMed:29887380, ECO:0000269|PubMed:30249660}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O94868-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O94868-2; Sequence=VSP_023167;
CC Name=3;
CC IsoId=O94868-3; Sequence=VSP_023167, VSP_023168, VSP_023169;
CC -!- TISSUE SPECIFICITY: Liver, brain, heart, placenta, skeletal muscle,
CC pancreas, lung and kidney. {ECO:0000269|PubMed:14627983}.
CC -!- DOMAIN: The F-BAR domain has an atypical, flat shape and binds
CC preferentially to flat membranes. Upon heterologous expression, the
CC isolated F-BAR domain is localized at the cell membrane, and causes the
CC formation of cellular protrusions. {ECO:0000269|PubMed:29887380}.
CC -!- DOMAIN: Recruited to clathrin-coated pits via SH3 domain 2.
CC {ECO:0000269|PubMed:29887380}.
CC -!- DOMAIN: The two SH3 domains cooperate to maintain the protein in an
CC autoinhibited conformation that prevents promiscuous membrane binding.
CC {ECO:0000269|PubMed:29887380}.
CC -!- PTM: Phosphorylated. Phosphorylation on a Ser residue is important for
CC recruitment to the cell membrane and for its role in promoting
CC endocytosis. {ECO:0000269|PubMed:30249660}.
CC -!- CAUTION: The function in endocytosis may depend on the cell type. Plays
CC a role in EGFR endocytosis via clathrin-coated pits in cancer cells,
CC but apparently not in normal cells (PubMed:30249660). A later study
CC used both HeLa cells and BSC1 cells (a C.aethiops kidney cell line),
CC and did not mention any cell-type specific effects (PubMed:29887380).
CC {ECO:0000269|PubMed:29887380, ECO:0000269|PubMed:30249660,
CC ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA34489.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB018312; BAA34489.2; ALT_INIT; mRNA.
DR EMBL; AP002381; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP002455; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK297928; BAG60245.1; -; mRNA.
DR EMBL; AP004241; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC010394; AAH10394.1; -; mRNA.
DR EMBL; BC017751; AAH17751.1; -; mRNA.
DR EMBL; AL133567; CAB63720.1; -; mRNA.
DR CCDS; CCDS8218.2; -. [O94868-1]
DR PIR; T43489; T43489.
DR RefSeq; NP_055639.2; NM_014824.2. [O94868-1]
DR PDB; 2DL5; NMR; -; A=466-530.
DR PDB; 2DL7; NMR; -; A=569-628.
DR PDB; 6GBU; X-ray; 3.44 A; A/C/E/G=567-629.
DR PDBsum; 2DL5; -.
DR PDBsum; 2DL7; -.
DR PDBsum; 6GBU; -.
DR AlphaFoldDB; O94868; -.
DR SMR; O94868; -.
DR BioGRID; 115205; 64.
DR IntAct; O94868; 61.
DR MINT; O94868; -.
DR STRING; 9606.ENSP00000386722; -.
DR iPTMnet; O94868; -.
DR PhosphoSitePlus; O94868; -.
DR BioMuta; FCHSD2; -.
DR EPD; O94868; -.
DR jPOST; O94868; -.
DR MassIVE; O94868; -.
DR MaxQB; O94868; -.
DR PaxDb; O94868; -.
DR PeptideAtlas; O94868; -.
DR PRIDE; O94868; -.
DR ProteomicsDB; 50505; -. [O94868-1]
DR ProteomicsDB; 50506; -. [O94868-2]
DR ProteomicsDB; 50507; -. [O94868-3]
DR Antibodypedia; 49955; 105 antibodies from 20 providers.
DR DNASU; 9873; -.
DR Ensembl; ENST00000311172.11; ENSP00000308978.7; ENSG00000137478.15. [O94868-2]
DR Ensembl; ENST00000409418.9; ENSP00000386722.4; ENSG00000137478.15. [O94868-1]
DR Ensembl; ENST00000409853.5; ENSP00000386314.1; ENSG00000137478.15. [O94868-3]
DR GeneID; 9873; -.
DR KEGG; hsa:9873; -.
DR MANE-Select; ENST00000409418.9; ENSP00000386722.4; NM_014824.3; NP_055639.2.
DR UCSC; uc001oth.5; human. [O94868-1]
DR CTD; 9873; -.
DR DisGeNET; 9873; -.
DR GeneCards; FCHSD2; -.
DR HGNC; HGNC:29114; FCHSD2.
DR HPA; ENSG00000137478; Low tissue specificity.
DR MIM; 617556; gene.
DR neXtProt; NX_O94868; -.
DR OpenTargets; ENSG00000137478; -.
DR PharmGKB; PA128394562; -.
DR VEuPathDB; HostDB:ENSG00000137478; -.
DR eggNOG; KOG3565; Eukaryota.
DR GeneTree; ENSGT00510000046732; -.
DR HOGENOM; CLU_013546_2_0_1; -.
DR InParanoid; O94868; -.
DR OrthoDB; 348563at2759; -.
DR PhylomeDB; O94868; -.
DR TreeFam; TF324557; -.
DR PathwayCommons; O94868; -.
DR SignaLink; O94868; -.
DR BioGRID-ORCS; 9873; 14 hits in 1081 CRISPR screens.
DR ChiTaRS; FCHSD2; human.
DR EvolutionaryTrace; O94868; -.
DR GeneWiki; FCHSD2; -.
DR GenomeRNAi; 9873; -.
DR Pharos; O94868; Tbio.
DR PRO; PR:O94868; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O94868; protein.
DR Bgee; ENSG00000137478; Expressed in cortical plate and 192 other tissues.
DR ExpressionAtlas; O94868; baseline and differential.
DR Genevisible; O94868; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0031594; C:neuromuscular junction; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IBA:GO_Central.
DR GO; GO:0120043; C:stereocilium shaft; ISS:UniProtKB.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0072583; P:clathrin-dependent endocytosis; IMP:UniProtKB.
DR GO; GO:0061024; P:membrane organization; IEA:Ensembl.
DR GO; GO:0007274; P:neuromuscular synaptic transmission; IBA:GO_Central.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISS:UniProtKB.
DR GO; GO:2000601; P:positive regulation of Arp2/3 complex-mediated actin nucleation; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IBA:GO_Central.
DR CDD; cd11894; SH3_FCHSD2_2; 1.
DR CDD; cd11761; SH3_FCHSD_1; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR031160; F_BAR.
DR InterPro; IPR001060; FCH_dom.
DR InterPro; IPR034934; FCHSD2.
DR InterPro; IPR035556; FCHSD2_SH3_2.
DR InterPro; IPR035460; FCHSD_SH3_1.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR15735:SF11; PTHR15735:SF11; 1.
DR Pfam; PF00611; FCH; 1.
DR Pfam; PF00018; SH3_1; 1.
DR Pfam; PF14604; SH3_9; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00055; FCH; 1.
DR SMART; SM00326; SH3; 2.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF50044; SSF50044; 2.
DR PROSITE; PS51741; F_BAR; 1.
DR PROSITE; PS50002; SH3; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Cell membrane;
KW Cell projection; Coated pit; Coiled coil; Cytoplasm; Endocytosis;
KW Lipid-binding; Membrane; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; SH3 domain; Transport.
FT CHAIN 1..740
FT /note="F-BAR and double SH3 domains protein 2"
FT /id="PRO_0000278214"
FT DOMAIN 8..282
FT /note="F-BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT DOMAIN 469..530
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 567..629
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 303..323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 567..629
FT /note="Required and sufficient for location at clathrin-
FT coated pits"
FT /evidence="ECO:0000269|PubMed:29887380"
FT REGION 633..740
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 356..397
FT /evidence="ECO:0000255"
FT COMPBIAS 648..669
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 676..705
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 675
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 681
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:30249660,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..56
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14627983,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9872452"
FT /id="VSP_023167"
FT VAR_SEQ 569..571
FT /note="VCF -> GKD (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023168"
FT VAR_SEQ 572..740
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023169"
FT MUTAGEN 478
FT /note="Y->A: Loss of ability to promote actin
FT polymerization; when associated with A-480."
FT /evidence="ECO:0000269|PubMed:29887380"
FT MUTAGEN 480
FT /note="Y->A: Loss of ability to promote actin
FT polymerization; when associated with A-478."
FT /evidence="ECO:0000269|PubMed:29887380"
FT MUTAGEN 521
FT /note="P->A: Loss of ability to promote actin
FT polymerization; when associated with A-524."
FT /evidence="ECO:0000269|PubMed:29887380"
FT MUTAGEN 524
FT /note="Y->A: Loss of ability to promote actin
FT polymerization; when associated with A-521."
FT /evidence="ECO:0000269|PubMed:29887380"
FT MUTAGEN 576
FT /note="Y->S: Abolishes interaction with ITSN1 and location
FT at clathrin-coated pits; when associated with S-607."
FT /evidence="ECO:0000269|PubMed:29887380"
FT MUTAGEN 607
FT /note="F->S: Abolishes interaction with ITSN1 and location
FT at clathrin-coated pits; when associated with S-576."
FT /evidence="ECO:0000269|PubMed:29887380"
FT MUTAGEN 622..623
FT /note="VL->KK: Abolishes interaction with ITSN1."
FT /evidence="ECO:0000269|PubMed:29887380"
FT MUTAGEN 681
FT /note="S->A: Impaired recruitment to the cell membrane."
FT /evidence="ECO:0000269|PubMed:30249660"
FT MUTAGEN 681
FT /note="S->E: Increased recruitment to the cell membrane."
FT /evidence="ECO:0000269|PubMed:30249660"
FT STRAND 470..476
FT /evidence="ECO:0007829|PDB:2DL5"
FT STRAND 492..500
FT /evidence="ECO:0007829|PDB:2DL5"
FT STRAND 503..511
FT /evidence="ECO:0007829|PDB:2DL5"
FT STRAND 517..521
FT /evidence="ECO:0007829|PDB:2DL5"
FT TURN 522..524
FT /evidence="ECO:0007829|PDB:2DL5"
FT STRAND 571..576
FT /evidence="ECO:0007829|PDB:6GBU"
FT STRAND 581..585
FT /evidence="ECO:0007829|PDB:6GBU"
FT STRAND 593..598
FT /evidence="ECO:0007829|PDB:6GBU"
FT STRAND 602..604
FT /evidence="ECO:0007829|PDB:6GBU"
FT STRAND 606..612
FT /evidence="ECO:0007829|PDB:6GBU"
FT STRAND 615..620
FT /evidence="ECO:0007829|PDB:6GBU"
FT HELIX 621..623
FT /evidence="ECO:0007829|PDB:6GBU"
FT STRAND 624..626
FT /evidence="ECO:0007829|PDB:6GBU"
SQ SEQUENCE 740 AA; 84276 MW; 3AF4DAC3CAD24C28 CRC64;
MQPPPRKVKV TQELKNIQVE QMTKLQAKHQ AECDLLEDMR TFSQKKAAIE REYAQGMQKL
ASQYLKRDWP GVKADDRNDY RSMYPVWKSF LEGTMQVAQS RMNICENYKN FISEPARTVR
SLKEQQLKRC VDQLTKIQTE LQETVKDLAK GKKKYFETEQ MAHAVREKAD IEAKSKLSLF
QSRISLQKAS VKLKARRSEC NSKATHARND YLLTLAAANA HQDRYYQTDL VNIMKALDGN
VYDHLKDYLI AFSRTELETC QAVQNTFQFL LENSSKVVRD YNLQLFLQEN AVFHKPQPFQ
FQPCDSDTSR QLESETGTTE EHSLNKEARK WATRVAREHK NIVHQQRVLN DLECHGAAVS
EQSRAELEQK IDEARENIRK AEIIKLKAEA RLDLLKQIGV SVDTWLKSAM NQVMEELENE
RWARPPAVTS NGTLHSLNAD TEREEGEEFE DNMDVFDDSS SSPSGTLRNY PLTCKVVYSY
KASQPDELTI EEHEVLEVIE DGDMEDWVKA RNKVGQVGYV PEKYLQFPTS NSLLSMLQSL
AALDSRSHTS SNSTEAELVS GSLNGDASVC FVKALYDYEG QTDDELSFPE GAIIRILNKE
NQDDDGFWEG EFNGRIGVFP SVLVEELSAS ENGDTPWMRE IQISPSPKPH ASLPPLPLYD
QPPSSPYPSP DKRSSLYFPR SPSANEKSLH AESPGFSQAS RHTPETSYGK LRPVRAAPPP
PTQNHRRPAE KIEDVEITLV
