Full text data of CTTN
CTTN
(EMS1)
[Confidence: low (only semi-automatic identification from reviews)]
Src substrate cortactin (Amplaxin; Oncogene EMS1)
Src substrate cortactin (Amplaxin; Oncogene EMS1)
UniProt
Q14247
ID SRC8_HUMAN Reviewed; 550 AA.
AC Q14247; Q8N707; Q96H99;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 25-NOV-2008, sequence version 2.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Src substrate cortactin;
DE AltName: Full=Amplaxin;
DE AltName: Full=Oncogene EMS1;
GN Name=CTTN; Synonyms=EMS1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Mammary gland;
RX PubMed=1532244;
RA Schuuring E.M.D., Verhoeven E., Mooi W.J., Michalides R.J.A.;
RT "Identification and cloning of two overexpressed genes, U21B31/PRAD1
RT and EMS1, within the amplified chromosome 11q13 region in human
RT carcinomas.";
RL Oncogene 7:355-361(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RC TISSUE=Mammary gland;
RX PubMed=8474448;
RA Schuuring E.M.D., Verhoeven E., Litvinov S., Michalides R.J.A.;
RT "The product of the EMS1 gene, amplified and overexpressed in human
RT carcinomas, is homologous to a v-src substrate and is located in cell-
RT substratum contact sites.";
RL Mol. Cell. Biol. 13:2891-2898(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4]
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.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Placenta, and Testis;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH FER, PHOSPHORYLATION OF CTTN, AND SUBCELLULAR
RP LOCATION.
RX PubMed=9722593; DOI=10.1074/jbc.273.36.23542;
RA Kim L., Wong T.W.;
RT "Growth factor-dependent phosphorylation of the actin-binding protein
RT cortactin is mediated by the cytoplasmic tyrosine kinase FER.";
RL J. Biol. Chem. 273:23542-23548(1998).
RN [8]
RP INTERACTION WITH MYLK, AND PHOSPHORYLATION BY SRC.
RX PubMed=12408982; DOI=10.1016/S0006-291X(02)02492-0;
RA Dudek S.M., Birukov K.G., Zhan X., Garcia J.G.N.;
RT "Novel interaction of cortactin with endothelial cell myosin light
RT chain kinase.";
RL Biochem. Biophys. Res. Commun. 298:511-519(2002).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites
RT from human T cells using immobilized metal affinity chromatography and
RT tandem mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [10]
RP INTERACTION WITH PLXDC2.
RX PubMed=15574754; DOI=10.1158/0008-5472.CAN-04-2716;
RA Nanda A., Buckhaults P., Seaman S., Agrawal N., Boutin P.,
RA Shankara S., Nacht M., Teicher B., Stampfl J., Singh S.,
RA Vogelstein B., Kinzler K.W., St Croix B.;
RT "Identification of a binding partner for the endothelial cell surface
RT proteins TEM7 and TEM7R.";
RL Cancer Res. 64:8507-8511(2004).
RN [11]
RP PHOSPHORYLATION.
RX PubMed=15561106; DOI=10.1016/j.yexcr.2004.09.005;
RA Continolo S., Baruzzi A., Majeed M., Caveggion E., Fumagalli L.,
RA Lowell C.A., Berton G.;
RT "The proto-oncogene Fgr regulates cell migration and this requires its
RT plasma membrane localization.";
RL Exp. Cell Res. 302:253-269(2005).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-453, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405 AND SER-418, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Prostate cancer;
RX PubMed=17487921; DOI=10.1002/elps.200600782;
RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.;
RT "Toward a global characterization of the phosphoproteome in prostate
RT cancer cells: identification of phosphoproteins in the LNCaP cell
RT line.";
RL Electrophoresis 28:2027-2034(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405 AND TYR-421, AND
RP MASS SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405; THR-411; SER-417
RP AND SER-418, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [21]
RP INTERACTION WITH SRCIN1.
RX PubMed=19146815; DOI=10.1016/j.neuron.2008.11.013;
RA Jaworski J., Kapitein L.C., Gouveia S.M., Dortland B.R., Wulf P.S.,
RA Grigoriev I., Camera P., Spangler S.A., Di Stefano P., Demmers J.,
RA Krugers H., Defilippi P., Akhmanova A., Hoogenraad C.C.;
RT "Dynamic microtubules regulate dendritic spine morphology and synaptic
RT plasticity.";
RL Neuron 61:85-100(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405; SER-418; TYR-421
RP AND TYR-446, AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-87; LYS-198; LYS-235;
RP LYS-272; LYS-304 AND LYS-309, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [24]
RP INTERACTION WITH MYLK AND ABL1.
RX PubMed=20861316; DOI=10.1091/mbc.E09-10-0876;
RA Dudek S.M., Chiang E.T., Camp S.M., Guo Y., Zhao J., Brown M.E.,
RA Singleton P.A., Wang L., Desai A., Arce F.T., Lal R., Van Eyk J.E.,
RA Imam S.Z., Garcia J.G.N.;
RT "Abl tyrosine kinase phosphorylates nonmuscle Myosin light chain
RT kinase to regulate endothelial barrier function.";
RL Mol. Biol. Cell 21:4042-4056(2010).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-399; THR-401; SER-405
RP AND SER-418, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [27]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SAMSN1.
RX PubMed=21296879; DOI=10.1074/jbc.M110.155184;
RA von Holleben M., Gohla A., Janssen K.P., Iritani B.M., Beer-Hammer S.;
RT "The immunoinhibitory adapter protein SRC homology domain 3 lymphocyte
RT protein 2 (SLy2) regulates actin dynamics and B cell spreading.";
RL J. Biol. Chem. 286:13489-13501(2011).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-418, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [30]
RP STRUCTURE BY NMR OF 485-550.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structures of the SH3 domain of human Src substrate
RT cortactin.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [31]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 490-550 IN COMPLEX WITH
RP ASAP1, FUNCTION, INTERACTION WITH ASAP1 AND DNM2, AND SUBCELLULAR
RP LOCATION.
RX PubMed=16636290; DOI=10.1073/pnas.0509166103;
RA Hashimoto S., Hirose M., Hashimoto A., Morishige M., Yamada A.,
RA Hosaka H., Akagi K., Ogawa E., Oneyama C., Agatsuma T., Okada M.,
RA Kobayashi H., Wada H., Nakano H., Ikegami T., Nakagawa A., Sabe H.;
RT "Targeting AMAP1 and cortactin binding bearing an atypical src
RT homology 3/proline interface for prevention of breast cancer invasion
RT and metastasis.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7036-7041(2006).
CC -!- FUNCTION: Contributes to the organization of the actin
CC cytoskeleton and cell structure. In complex with ABL1 and MYLK
CC regulates cortical actin-based cytoskeletal rearrangement critical
CC to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC)
CC barrier enhancement. Plays a role in the regulation of cell
CC migration. Plays a role in the invasiveness of cancer cells, and
CC the formation of metastases.
CC -!- SUBUNIT: Interacts with SHANK2 and SHANK3 (via its SH3 domain).
CC Also interacts with FGD1. Identified in a complex containing
CC FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN.
CC Interacts with ABL2 (By similarity). Interacts with PLXDC2 and
CC SRCIN1. Interacts with SAMSN1 (via SH3 domain). Interacts (via SH3
CC domain) with ASAP1 (via Pro-rich region). Interacts with DNM2 and
CC FER. Forms a complex made of ABL1 and MYLK. Interacts with
CC CTTNBP2NL; this interaction may target CTTN to stress fibers.
CC Interacts with CTTNBP2; this interaction may target CTTN at the
CC cell cortex or dendritic spines.
CC -!- INTERACTION:
CC Q9ULH1:ASAP1; NbExp=7; IntAct=EBI-351886, EBI-346622;
CC Q9JIY2:Cbll1 (xeno); NbExp=8; IntAct=EBI-351886, EBI-7644904;
CC P50570:DNM2; NbExp=5; IntAct=EBI-351886, EBI-346547;
CC Q9UBN7:HDAC6; NbExp=3; IntAct=EBI-351886, EBI-301697;
CC Q08460:Kcnma1 (xeno); NbExp=3; IntAct=EBI-351886, EBI-1633915;
CC P18031:PTPN1; NbExp=2; IntAct=EBI-351886, EBI-968788;
CC Q9QWI6-2:Srcin1 (xeno); NbExp=2; IntAct=EBI-351886, EBI-775607;
CC B7UM99:tir (xeno); NbExp=3; IntAct=EBI-351886, EBI-2504426;
CC P42768:WAS; NbExp=3; IntAct=EBI-351886, EBI-346375;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cell projection,
CC lamellipodium. Cell projection, ruffle. Cell projection, dendrite
CC (By similarity). Cell projection, dendritic spine (By similarity).
CC Note=Associated with membrane ruffles and lamellipodia. In the
CC presence of CTTNBP2NL, colocalizes with stress fibers (By
CC similarity). In the presence of CTTNBP2, localizes at the cell
CC cortex (By similarity). In response to neuronal activation by
CC glutamate, redistributes from dendritic spines to the dendritic
CC shaft (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q14247-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14247-2; Sequence=VSP_043120, VSP_043121;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q14247-3; Sequence=VSP_043120;
CC -!- DOMAIN: The SH3 motif may mediate binding to the cytoskeleton.
CC -!- PTM: Phosphorylated by PKN2 at both serine and threonine residues
CC in a GTP-bound Rac1-dependent manner in hyaluronan-induced
CC astrocytes and hence down-regulated CTTN ability to associates
CC with filamentous actin (By similarity). Phosphorylated by FER.
CC Tyrosine phosphorylation in transformed cells may contribute to
CC cellular growth regulation and transformation. Phosphorylated in
CC response to FGR activation. Phosphorylation by SRC promotes MYLK
CC binding.
CC -!- SIMILARITY: Contains 7 cortactin repeats.
CC -!- SIMILARITY: Contains 1 SH3 domain.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Cortactin entry;
CC URL="http://en.wikipedia.org/wiki/Cortactin";
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DR EMBL; M98343; AAA58455.1; -; mRNA.
DR EMBL; AK291097; BAF83786.1; -; mRNA.
DR EMBL; AP000487; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW74766.1; -; Genomic_DNA.
DR EMBL; CH471076; EAW74768.1; -; Genomic_DNA.
DR EMBL; BC008799; AAH08799.1; -; mRNA.
DR EMBL; BC033889; AAH33889.1; -; mRNA.
DR PIR; A48063; A48063.
DR RefSeq; NP_001171669.1; NM_001184740.1.
DR RefSeq; NP_005222.2; NM_005231.3.
DR RefSeq; NP_612632.1; NM_138565.2.
DR UniGene; Hs.596164; -.
DR PDB; 1X69; NMR; -; A=485-550.
DR PDB; 2D1X; X-ray; 1.90 A; A/B/C/D=490-550.
DR PDBsum; 1X69; -.
DR PDBsum; 2D1X; -.
DR ProteinModelPortal; Q14247; -.
DR SMR; Q14247; 490-550.
DR IntAct; Q14247; 32.
DR MINT; MINT-361929; -.
DR STRING; 9606.ENSP00000301843; -.
DR PhosphoSite; Q14247; -.
DR DMDM; 215273892; -.
DR OGP; Q14247; -.
DR PaxDb; Q14247; -.
DR PRIDE; Q14247; -.
DR DNASU; 2017; -.
DR Ensembl; ENST00000301843; ENSP00000301843; ENSG00000085733.
DR Ensembl; ENST00000346329; ENSP00000317189; ENSG00000085733.
DR Ensembl; ENST00000376561; ENSP00000365745; ENSG00000085733.
DR GeneID; 2017; -.
DR KEGG; hsa:2017; -.
DR UCSC; uc001opv.4; human.
DR CTD; 2017; -.
DR GeneCards; GC11P070244; -.
DR HGNC; HGNC:3338; CTTN.
DR HPA; CAB011235; -.
DR MIM; 164765; gene.
DR neXtProt; NX_Q14247; -.
DR PharmGKB; PA27775; -.
DR eggNOG; NOG123488; -.
DR HOGENOM; HOG000006523; -.
DR HOVERGEN; HBG005994; -.
DR KO; K06106; -.
DR OMA; HESQQDY; -.
DR OrthoDB; EOG7V49ZC; -.
DR ChiTaRS; CTTN; human.
DR EvolutionaryTrace; Q14247; -.
DR GeneWiki; Cortactin; -.
DR GenomeRNAi; 2017; -.
DR NextBio; 8171; -.
DR PRO; PR:Q14247; -.
DR ArrayExpress; Q14247; -.
DR Bgee; Q14247; -.
DR CleanEx; HS_CTTN; -.
DR Genevestigator; Q14247; -.
DR GO; GO:0005938; C:cell cortex; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; TAS:ProtInc.
DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR InterPro; IPR015503; Cortactin.
DR InterPro; IPR003134; Hs1_Cortactin.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR10829:SF4; PTHR10829:SF4; 1.
DR Pfam; PF02218; HS1_rep; 7.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS51090; CORTACTIN; 7.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell projection;
KW Complete proteome; Cytoplasm; Cytoskeleton; Phosphoprotein;
KW Reference proteome; Repeat; SH3 domain.
FT CHAIN 1 550 Src substrate cortactin.
FT /FTId=PRO_0000072189.
FT REPEAT 80 116 Cortactin 1.
FT REPEAT 117 153 Cortactin 2.
FT REPEAT 154 190 Cortactin 3.
FT REPEAT 191 227 Cortactin 4.
FT REPEAT 228 264 Cortactin 5.
FT REPEAT 265 301 Cortactin 6.
FT REPEAT 302 324 Cortactin 7; truncated.
FT DOMAIN 492 550 SH3.
FT MOD_RES 87 87 N6-acetyllysine.
FT MOD_RES 198 198 N6-acetyllysine.
FT MOD_RES 235 235 N6-acetyllysine.
FT MOD_RES 272 272 N6-acetyllysine.
FT MOD_RES 304 304 N6-acetyllysine.
FT MOD_RES 309 309 N6-acetyllysine.
FT MOD_RES 399 399 Phosphothreonine.
FT MOD_RES 401 401 Phosphothreonine.
FT MOD_RES 405 405 Phosphoserine.
FT MOD_RES 411 411 Phosphothreonine.
FT MOD_RES 417 417 Phosphoserine.
FT MOD_RES 418 418 Phosphoserine.
FT MOD_RES 421 421 Phosphotyrosine; by SRC.
FT MOD_RES 446 446 Phosphotyrosine.
FT MOD_RES 453 453 Phosphotyrosine.
FT MOD_RES 486 486 Phosphotyrosine; by SRC.
FT MOD_RES 489 489 Phosphotyrosine; by SRC.
FT VAR_SEQ 264 300 Missing (in isoform 2 and isoform 3).
FT /FTId=VSP_043120.
FT VAR_SEQ 538 550 YGLFPANYVELRQ -> FRELAFSCVRVALVPIKCSRDLPG
FT QARGLRSALWRVGRKDCPRRGASSRVSLLGRRGLGLMEVNP
FT ELSHPEHRSCHVRWEICLCHTVTARRIRKLISFLRSREAGP
FT VPSCSQVGGVSFQKVTWKCLGTWVPECP (in isoform
FT 2).
FT /FTId=VSP_043121.
FT CONFLICT 495 495 I -> Y (in Ref. 1; AAA58455).
FT STRAND 497 499
FT STRAND 506 510
FT STRAND 518 523
FT STRAND 526 534
FT STRAND 537 542
FT HELIX 543 545
FT STRAND 546 548
SQ SEQUENCE 550 AA; 61586 MW; 7799326C2B4383BB CRC64;
MWKASAGHAV SIAQDDAGAD DWETDPDFVN DVSEKEQRWG AKTVQGSGHQ EHINIHKLRE
NVFQEHQTLK EKELETGPKA SHGYGGKFGV EQDRMDKSAV GHEYQSKLSK HCSQVDSVRG
FGGKFGVQMD RVDQSAVGFE YQGKTEKHAS QKDYSSGFGG KYGVQADRVD KSAVGFDYQG
KTEKHESQRD YSKGFGGKYG IDKDKVDKSA VGFEYQGKTE KHESQKDYVK GFGGKFGVQT
DRQDKCALGW DHQEKLQLHE SQKDYKTGFG GKFGVQSERQ DSAAVGFDYK EKLAKHESQQ
DYSKGFGGKY GVQKDRMDKN ASTFEDVTQV SSAYQKTVPV EAVTSKTSNI RANFENLAKE
KEQEDRRKAE AERAQRMAKE RQEQEEARRK LEEQARAKTQ TPPVSPAPQP TEERLPSSPV
YEDAASFKAE LSYRGPVSGT EPEPVYSMEA ADYREASSQQ GLAYATEAVY ESAEAPGHYP
AEDSTYDEYE NDLGITAVAL YDYQAAGDDE ISFDPDDIIT NIEMIDDGWW RGVCKGRYGL
FPANYVELRQ
//
ID SRC8_HUMAN Reviewed; 550 AA.
AC Q14247; Q8N707; Q96H99;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 25-NOV-2008, sequence version 2.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Src substrate cortactin;
DE AltName: Full=Amplaxin;
DE AltName: Full=Oncogene EMS1;
GN Name=CTTN; Synonyms=EMS1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Mammary gland;
RX PubMed=1532244;
RA Schuuring E.M.D., Verhoeven E., Mooi W.J., Michalides R.J.A.;
RT "Identification and cloning of two overexpressed genes, U21B31/PRAD1
RT and EMS1, within the amplified chromosome 11q13 region in human
RT carcinomas.";
RL Oncogene 7:355-361(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RC TISSUE=Mammary gland;
RX PubMed=8474448;
RA Schuuring E.M.D., Verhoeven E., Litvinov S., Michalides R.J.A.;
RT "The product of the EMS1 gene, amplified and overexpressed in human
RT carcinomas, is homologous to a v-src substrate and is located in cell-
RT substratum contact sites.";
RL Mol. Cell. Biol. 13:2891-2898(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4]
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.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Placenta, and Testis;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH FER, PHOSPHORYLATION OF CTTN, AND SUBCELLULAR
RP LOCATION.
RX PubMed=9722593; DOI=10.1074/jbc.273.36.23542;
RA Kim L., Wong T.W.;
RT "Growth factor-dependent phosphorylation of the actin-binding protein
RT cortactin is mediated by the cytoplasmic tyrosine kinase FER.";
RL J. Biol. Chem. 273:23542-23548(1998).
RN [8]
RP INTERACTION WITH MYLK, AND PHOSPHORYLATION BY SRC.
RX PubMed=12408982; DOI=10.1016/S0006-291X(02)02492-0;
RA Dudek S.M., Birukov K.G., Zhan X., Garcia J.G.N.;
RT "Novel interaction of cortactin with endothelial cell myosin light
RT chain kinase.";
RL Biochem. Biophys. Res. Commun. 298:511-519(2002).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites
RT from human T cells using immobilized metal affinity chromatography and
RT tandem mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [10]
RP INTERACTION WITH PLXDC2.
RX PubMed=15574754; DOI=10.1158/0008-5472.CAN-04-2716;
RA Nanda A., Buckhaults P., Seaman S., Agrawal N., Boutin P.,
RA Shankara S., Nacht M., Teicher B., Stampfl J., Singh S.,
RA Vogelstein B., Kinzler K.W., St Croix B.;
RT "Identification of a binding partner for the endothelial cell surface
RT proteins TEM7 and TEM7R.";
RL Cancer Res. 64:8507-8511(2004).
RN [11]
RP PHOSPHORYLATION.
RX PubMed=15561106; DOI=10.1016/j.yexcr.2004.09.005;
RA Continolo S., Baruzzi A., Majeed M., Caveggion E., Fumagalli L.,
RA Lowell C.A., Berton G.;
RT "The proto-oncogene Fgr regulates cell migration and this requires its
RT plasma membrane localization.";
RL Exp. Cell Res. 302:253-269(2005).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-453, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405 AND SER-418, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Prostate cancer;
RX PubMed=17487921; DOI=10.1002/elps.200600782;
RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.;
RT "Toward a global characterization of the phosphoproteome in prostate
RT cancer cells: identification of phosphoproteins in the LNCaP cell
RT line.";
RL Electrophoresis 28:2027-2034(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405 AND TYR-421, AND
RP MASS SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405; THR-411; SER-417
RP AND SER-418, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [21]
RP INTERACTION WITH SRCIN1.
RX PubMed=19146815; DOI=10.1016/j.neuron.2008.11.013;
RA Jaworski J., Kapitein L.C., Gouveia S.M., Dortland B.R., Wulf P.S.,
RA Grigoriev I., Camera P., Spangler S.A., Di Stefano P., Demmers J.,
RA Krugers H., Defilippi P., Akhmanova A., Hoogenraad C.C.;
RT "Dynamic microtubules regulate dendritic spine morphology and synaptic
RT plasticity.";
RL Neuron 61:85-100(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405; SER-418; TYR-421
RP AND TYR-446, AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-87; LYS-198; LYS-235;
RP LYS-272; LYS-304 AND LYS-309, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [24]
RP INTERACTION WITH MYLK AND ABL1.
RX PubMed=20861316; DOI=10.1091/mbc.E09-10-0876;
RA Dudek S.M., Chiang E.T., Camp S.M., Guo Y., Zhao J., Brown M.E.,
RA Singleton P.A., Wang L., Desai A., Arce F.T., Lal R., Van Eyk J.E.,
RA Imam S.Z., Garcia J.G.N.;
RT "Abl tyrosine kinase phosphorylates nonmuscle Myosin light chain
RT kinase to regulate endothelial barrier function.";
RL Mol. Biol. Cell 21:4042-4056(2010).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-399; THR-401; SER-405
RP AND SER-418, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [27]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SAMSN1.
RX PubMed=21296879; DOI=10.1074/jbc.M110.155184;
RA von Holleben M., Gohla A., Janssen K.P., Iritani B.M., Beer-Hammer S.;
RT "The immunoinhibitory adapter protein SRC homology domain 3 lymphocyte
RT protein 2 (SLy2) regulates actin dynamics and B cell spreading.";
RL J. Biol. Chem. 286:13489-13501(2011).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-418, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [30]
RP STRUCTURE BY NMR OF 485-550.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structures of the SH3 domain of human Src substrate
RT cortactin.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [31]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 490-550 IN COMPLEX WITH
RP ASAP1, FUNCTION, INTERACTION WITH ASAP1 AND DNM2, AND SUBCELLULAR
RP LOCATION.
RX PubMed=16636290; DOI=10.1073/pnas.0509166103;
RA Hashimoto S., Hirose M., Hashimoto A., Morishige M., Yamada A.,
RA Hosaka H., Akagi K., Ogawa E., Oneyama C., Agatsuma T., Okada M.,
RA Kobayashi H., Wada H., Nakano H., Ikegami T., Nakagawa A., Sabe H.;
RT "Targeting AMAP1 and cortactin binding bearing an atypical src
RT homology 3/proline interface for prevention of breast cancer invasion
RT and metastasis.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7036-7041(2006).
CC -!- FUNCTION: Contributes to the organization of the actin
CC cytoskeleton and cell structure. In complex with ABL1 and MYLK
CC regulates cortical actin-based cytoskeletal rearrangement critical
CC to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC)
CC barrier enhancement. Plays a role in the regulation of cell
CC migration. Plays a role in the invasiveness of cancer cells, and
CC the formation of metastases.
CC -!- SUBUNIT: Interacts with SHANK2 and SHANK3 (via its SH3 domain).
CC Also interacts with FGD1. Identified in a complex containing
CC FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN.
CC Interacts with ABL2 (By similarity). Interacts with PLXDC2 and
CC SRCIN1. Interacts with SAMSN1 (via SH3 domain). Interacts (via SH3
CC domain) with ASAP1 (via Pro-rich region). Interacts with DNM2 and
CC FER. Forms a complex made of ABL1 and MYLK. Interacts with
CC CTTNBP2NL; this interaction may target CTTN to stress fibers.
CC Interacts with CTTNBP2; this interaction may target CTTN at the
CC cell cortex or dendritic spines.
CC -!- INTERACTION:
CC Q9ULH1:ASAP1; NbExp=7; IntAct=EBI-351886, EBI-346622;
CC Q9JIY2:Cbll1 (xeno); NbExp=8; IntAct=EBI-351886, EBI-7644904;
CC P50570:DNM2; NbExp=5; IntAct=EBI-351886, EBI-346547;
CC Q9UBN7:HDAC6; NbExp=3; IntAct=EBI-351886, EBI-301697;
CC Q08460:Kcnma1 (xeno); NbExp=3; IntAct=EBI-351886, EBI-1633915;
CC P18031:PTPN1; NbExp=2; IntAct=EBI-351886, EBI-968788;
CC Q9QWI6-2:Srcin1 (xeno); NbExp=2; IntAct=EBI-351886, EBI-775607;
CC B7UM99:tir (xeno); NbExp=3; IntAct=EBI-351886, EBI-2504426;
CC P42768:WAS; NbExp=3; IntAct=EBI-351886, EBI-346375;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cell projection,
CC lamellipodium. Cell projection, ruffle. Cell projection, dendrite
CC (By similarity). Cell projection, dendritic spine (By similarity).
CC Note=Associated with membrane ruffles and lamellipodia. In the
CC presence of CTTNBP2NL, colocalizes with stress fibers (By
CC similarity). In the presence of CTTNBP2, localizes at the cell
CC cortex (By similarity). In response to neuronal activation by
CC glutamate, redistributes from dendritic spines to the dendritic
CC shaft (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q14247-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14247-2; Sequence=VSP_043120, VSP_043121;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q14247-3; Sequence=VSP_043120;
CC -!- DOMAIN: The SH3 motif may mediate binding to the cytoskeleton.
CC -!- PTM: Phosphorylated by PKN2 at both serine and threonine residues
CC in a GTP-bound Rac1-dependent manner in hyaluronan-induced
CC astrocytes and hence down-regulated CTTN ability to associates
CC with filamentous actin (By similarity). Phosphorylated by FER.
CC Tyrosine phosphorylation in transformed cells may contribute to
CC cellular growth regulation and transformation. Phosphorylated in
CC response to FGR activation. Phosphorylation by SRC promotes MYLK
CC binding.
CC -!- SIMILARITY: Contains 7 cortactin repeats.
CC -!- SIMILARITY: Contains 1 SH3 domain.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Cortactin entry;
CC URL="http://en.wikipedia.org/wiki/Cortactin";
CC -----------------------------------------------------------------------
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DR EMBL; M98343; AAA58455.1; -; mRNA.
DR EMBL; AK291097; BAF83786.1; -; mRNA.
DR EMBL; AP000487; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW74766.1; -; Genomic_DNA.
DR EMBL; CH471076; EAW74768.1; -; Genomic_DNA.
DR EMBL; BC008799; AAH08799.1; -; mRNA.
DR EMBL; BC033889; AAH33889.1; -; mRNA.
DR PIR; A48063; A48063.
DR RefSeq; NP_001171669.1; NM_001184740.1.
DR RefSeq; NP_005222.2; NM_005231.3.
DR RefSeq; NP_612632.1; NM_138565.2.
DR UniGene; Hs.596164; -.
DR PDB; 1X69; NMR; -; A=485-550.
DR PDB; 2D1X; X-ray; 1.90 A; A/B/C/D=490-550.
DR PDBsum; 1X69; -.
DR PDBsum; 2D1X; -.
DR ProteinModelPortal; Q14247; -.
DR SMR; Q14247; 490-550.
DR IntAct; Q14247; 32.
DR MINT; MINT-361929; -.
DR STRING; 9606.ENSP00000301843; -.
DR PhosphoSite; Q14247; -.
DR DMDM; 215273892; -.
DR OGP; Q14247; -.
DR PaxDb; Q14247; -.
DR PRIDE; Q14247; -.
DR DNASU; 2017; -.
DR Ensembl; ENST00000301843; ENSP00000301843; ENSG00000085733.
DR Ensembl; ENST00000346329; ENSP00000317189; ENSG00000085733.
DR Ensembl; ENST00000376561; ENSP00000365745; ENSG00000085733.
DR GeneID; 2017; -.
DR KEGG; hsa:2017; -.
DR UCSC; uc001opv.4; human.
DR CTD; 2017; -.
DR GeneCards; GC11P070244; -.
DR HGNC; HGNC:3338; CTTN.
DR HPA; CAB011235; -.
DR MIM; 164765; gene.
DR neXtProt; NX_Q14247; -.
DR PharmGKB; PA27775; -.
DR eggNOG; NOG123488; -.
DR HOGENOM; HOG000006523; -.
DR HOVERGEN; HBG005994; -.
DR KO; K06106; -.
DR OMA; HESQQDY; -.
DR OrthoDB; EOG7V49ZC; -.
DR ChiTaRS; CTTN; human.
DR EvolutionaryTrace; Q14247; -.
DR GeneWiki; Cortactin; -.
DR GenomeRNAi; 2017; -.
DR NextBio; 8171; -.
DR PRO; PR:Q14247; -.
DR ArrayExpress; Q14247; -.
DR Bgee; Q14247; -.
DR CleanEx; HS_CTTN; -.
DR Genevestigator; Q14247; -.
DR GO; GO:0005938; C:cell cortex; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; TAS:ProtInc.
DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR InterPro; IPR015503; Cortactin.
DR InterPro; IPR003134; Hs1_Cortactin.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR10829:SF4; PTHR10829:SF4; 1.
DR Pfam; PF02218; HS1_rep; 7.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS51090; CORTACTIN; 7.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell projection;
KW Complete proteome; Cytoplasm; Cytoskeleton; Phosphoprotein;
KW Reference proteome; Repeat; SH3 domain.
FT CHAIN 1 550 Src substrate cortactin.
FT /FTId=PRO_0000072189.
FT REPEAT 80 116 Cortactin 1.
FT REPEAT 117 153 Cortactin 2.
FT REPEAT 154 190 Cortactin 3.
FT REPEAT 191 227 Cortactin 4.
FT REPEAT 228 264 Cortactin 5.
FT REPEAT 265 301 Cortactin 6.
FT REPEAT 302 324 Cortactin 7; truncated.
FT DOMAIN 492 550 SH3.
FT MOD_RES 87 87 N6-acetyllysine.
FT MOD_RES 198 198 N6-acetyllysine.
FT MOD_RES 235 235 N6-acetyllysine.
FT MOD_RES 272 272 N6-acetyllysine.
FT MOD_RES 304 304 N6-acetyllysine.
FT MOD_RES 309 309 N6-acetyllysine.
FT MOD_RES 399 399 Phosphothreonine.
FT MOD_RES 401 401 Phosphothreonine.
FT MOD_RES 405 405 Phosphoserine.
FT MOD_RES 411 411 Phosphothreonine.
FT MOD_RES 417 417 Phosphoserine.
FT MOD_RES 418 418 Phosphoserine.
FT MOD_RES 421 421 Phosphotyrosine; by SRC.
FT MOD_RES 446 446 Phosphotyrosine.
FT MOD_RES 453 453 Phosphotyrosine.
FT MOD_RES 486 486 Phosphotyrosine; by SRC.
FT MOD_RES 489 489 Phosphotyrosine; by SRC.
FT VAR_SEQ 264 300 Missing (in isoform 2 and isoform 3).
FT /FTId=VSP_043120.
FT VAR_SEQ 538 550 YGLFPANYVELRQ -> FRELAFSCVRVALVPIKCSRDLPG
FT QARGLRSALWRVGRKDCPRRGASSRVSLLGRRGLGLMEVNP
FT ELSHPEHRSCHVRWEICLCHTVTARRIRKLISFLRSREAGP
FT VPSCSQVGGVSFQKVTWKCLGTWVPECP (in isoform
FT 2).
FT /FTId=VSP_043121.
FT CONFLICT 495 495 I -> Y (in Ref. 1; AAA58455).
FT STRAND 497 499
FT STRAND 506 510
FT STRAND 518 523
FT STRAND 526 534
FT STRAND 537 542
FT HELIX 543 545
FT STRAND 546 548
SQ SEQUENCE 550 AA; 61586 MW; 7799326C2B4383BB CRC64;
MWKASAGHAV SIAQDDAGAD DWETDPDFVN DVSEKEQRWG AKTVQGSGHQ EHINIHKLRE
NVFQEHQTLK EKELETGPKA SHGYGGKFGV EQDRMDKSAV GHEYQSKLSK HCSQVDSVRG
FGGKFGVQMD RVDQSAVGFE YQGKTEKHAS QKDYSSGFGG KYGVQADRVD KSAVGFDYQG
KTEKHESQRD YSKGFGGKYG IDKDKVDKSA VGFEYQGKTE KHESQKDYVK GFGGKFGVQT
DRQDKCALGW DHQEKLQLHE SQKDYKTGFG GKFGVQSERQ DSAAVGFDYK EKLAKHESQQ
DYSKGFGGKY GVQKDRMDKN ASTFEDVTQV SSAYQKTVPV EAVTSKTSNI RANFENLAKE
KEQEDRRKAE AERAQRMAKE RQEQEEARRK LEEQARAKTQ TPPVSPAPQP TEERLPSSPV
YEDAASFKAE LSYRGPVSGT EPEPVYSMEA ADYREASSQQ GLAYATEAVY ESAEAPGHYP
AEDSTYDEYE NDLGITAVAL YDYQAAGDDE ISFDPDDIIT NIEMIDDGWW RGVCKGRYGL
FPANYVELRQ
//
MIM
164765
*RECORD*
*FIELD* NO
164765
*FIELD* TI
*164765 CORTACTIN; CTTN
;;ONCOGENE EMS1; EMS1
*FIELD* TX
DESCRIPTION
Cortactin is a multidomain protein that functions as a key regulator of
read morethe actin cytoskeleton. It has roles in many actin-based cellular
processes, including cell migration and invasion, tumor cell metastasis,
and endocytosis (summary by Tegtmeyer et al., 2011).
CLONING
Amplification of the 11q13 region is frequently found in breast cancer
and in squamous cell carcinomas of the head and neck. The known
oncogenes within the amplified 11q13 region, INT2 (164950) and FGF4
(164980), are rarely expressed in these tumors, indicating that another,
hitherto unidentified gene or genes are involved in the unfavorable
clinical course of disease associated with such amplification. To
identify the gene or genes, Schuuring et al. (1992) constructed a cDNA
library from a cell line with an 11q13 amplification and performed a
differential cDNA cloning using labeled cDNAs from human squamous cell
carcinoma cell lines with and without an 11q13 amplification. They
isolated 2 cDNA clones, U21B31 and U21C8, which recognized genes
amplified and overexpressed in cell lines harboring an 11q13
amplification. Sequence analysis of the U21C8 cDNA clone revealed no
homology to known genes; they called this gene EMS1. The U21B31 cDNA
clone corresponded to the 3-prime end of the PRAD1 protooncogene
(168461).
Van Damme et al. (1997) stated that EMS1 is the human homolog of chicken
cortactin, an actin-binding protein involved in the restructuring of the
cortical actin cytoskeleton. Chicken cortactin is a substrate for the
pp60v-src tyrosine kinase (see 190090).
GENE FUNCTION
Human cortactin is overexpressed in carcinoma cells with an
amplification of 11q13 and is found in 2 forms, designated p80 and p85.
Van Damme et al. (1997) found that in carcinoma cells with the 11q13
amplification, p85 was produced from p80 by posttranslational
modification. Also, treatment of these cells with epidermal growth
factor (131530) or vanadate caused conversion of p80 to p85 and enhanced
phosphorylation of the p85 form. Both overexpression and
posttranslational modification of cortactin coincided with its
redistribution from the cytoplasm to cell-matrix contact sites, implying
a role for cortactin in the modulation of cellular adhesive properties.
Williams et al. (2007) stated that suppression of Kv1.2 (KCNA2;
176262)-mediated potassium channel currents occurs by endocytosis of the
channel protein following its tyrosine phosphorylation. Using pull-down
assays with purified recombinant proteins, they had previously
demonstrated direct interaction between Kv1.2 and cortactin that was
reduced by tyrosine phosphorylation of Kv1.2 (Hattan et al., 2002).
Using cells and cDNAs from several species, including human, Williams et
al. (2007) showed that cortactin interacted with Kv1.2 in vivo and was
required for Kv1.2 membrane localization and channel function. Depletion
of endogenous cortactin in HEK293 cells via RNA interference reduced
surface Kv1.2 levels, which could be restored by introduction of mouse
cortactin. Kv1.2 trafficking required the cortactin actin regulatory
domains and was modulated by phosphorylation of cortactin C-terminal
tyrosines. Williams et al. (2007) concluded that cortactin-mediated
actin remodeling in excitable cells has a direct impact on membrane
excitability.
Tegtmeyer et al. (2011) found that knockdown of CTTN via small
interfering RNA in a human gastric adenocarcinoma cell line inhibited
cell scattering and elongation induced by infection with Helicobacter
pylori (Hp). Hp-induced scattering and elongation correlated with
activation of PAK1 (602590) and ERK1 (MAPK3; 601795)/ERK2 (MAPK1;
176948) and inactivation of SRC (190090). Phospho-specific antibodies to
CTTN serine residues showed phosphorylation and membrane expression
after Hp infection, while tyrosine residues of CTTN were
dephosphorylated. Ser418 and ser405 residues were specifically
phosphorylated in p80 and p85, respectively. Hp-induced serine
phosphorylation in CTTN was independent of the Hp cytotoxin-associated
gene A (CagA) effector protein, whereas tyrosine dephosphorylation in
CTTN was dependent on CagA. Immunoprecipitation analysis detected
interaction of CTTN with N-WASP (WASL; 605056) and actin only in
uninfected cells. Immunofluorescence analysis of uninfected cells
demonstrated localization of CTTN in cytoplasm and membrane, which
shifted after Hp infection to colocalization with FAK (PTK2; 600758) at
the tip and base of cellular elongations. Interaction of CTTN with FAK
required phosphorylation of either ser405 or ser418, but not both
simultaneously, and involved binding of the CTTN SH3 domain with a PxxP
motif, designated PR3, of FAK. Binding of CTTN phosphorylated at ser405,
but not CTTN phosphorylated at ser418, to FAK increased FAK kinase
activity. Tegtmeyer et al. (2011) proposed that Hp targets cortactin to
protect the gastric epithelium from excessive cell lifting and to ensure
sustained infection in the stomach.
MAPPING
Gross (2012) mapped the CTTN gene to chromosome 11q13.3 based on an
alignment of the CTTN sequence (GenBank GENBANK BC008799) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Gross, M. B.: Personal Communication. Baltimore, Md. 3/21/2012.
2. Hattan, D.; Nesti, E.; Cachero, T. G.; Morielli, A. D.: Tyrosine
phosphorylation of Kv1.2 modulates its interaction with the actin-binding
protein cortactin. J. Biol. Chem. 277: 38596-38606, 2002.
3. Schuuring, E.; Verhoeven, E.; Mooi, W. J.; Michalides, R. J. A.
M.: Identification and cloning of two overexpressed genes, U21B31/PRAD1
and EMS1, within the amplified chromosome 11q13 region in human carcinomas. Oncogene 7:
355-361, 1992.
4. Tegtmeyer, N.; Wittelsberger, R.; Hartig, R.; Wessler, S.; Martinez-Quiles,
N.; Backert, S.: Serine phosphorylation of cortactin controls focal
adhesion kinase activity and cell scattering induced by Helicobacter
pylori. Cell Host Microbe 9: 520-531, 2011.
5. van Damme, H.; Brok, H.; Schuuring-Scholtes, E.; Schuuring, E.
: The redistribution of cortactin into cell-matrix contact sites in
human carcinoma cells with 11q13 amplification is associated with
both overexpression and post-translational modification. J. Biol.
Chem. 272: 7374-7380, 1997.
6. Williams, M. R.; Markey, J. C.; Doczi, M. A.; Morielli, A. D.:
An essential role for cortactin in the modulation of the potassium
channel Kv1.2. Proc. Nat. Acad. Sci. 104: 17412-17417, 2007.
*FIELD* CN
Matthew B. Gross - updated: 03/21/2012
Paul J. Converse - updated: 3/15/2012
Patricia A. Hartz - updated: 8/20/2008
Jennifer P. Macke - updated: 11/16/1998
*FIELD* CD
Victor A. McKusick: 5/27/1993
*FIELD* ED
mgross: 03/21/2012
terry: 3/15/2012
mgross: 8/21/2008
terry: 8/20/2008
alopez: 11/16/1998
terry: 8/11/1998
carol: 5/28/1993
carol: 5/27/1993
*RECORD*
*FIELD* NO
164765
*FIELD* TI
*164765 CORTACTIN; CTTN
;;ONCOGENE EMS1; EMS1
*FIELD* TX
DESCRIPTION
Cortactin is a multidomain protein that functions as a key regulator of
read morethe actin cytoskeleton. It has roles in many actin-based cellular
processes, including cell migration and invasion, tumor cell metastasis,
and endocytosis (summary by Tegtmeyer et al., 2011).
CLONING
Amplification of the 11q13 region is frequently found in breast cancer
and in squamous cell carcinomas of the head and neck. The known
oncogenes within the amplified 11q13 region, INT2 (164950) and FGF4
(164980), are rarely expressed in these tumors, indicating that another,
hitherto unidentified gene or genes are involved in the unfavorable
clinical course of disease associated with such amplification. To
identify the gene or genes, Schuuring et al. (1992) constructed a cDNA
library from a cell line with an 11q13 amplification and performed a
differential cDNA cloning using labeled cDNAs from human squamous cell
carcinoma cell lines with and without an 11q13 amplification. They
isolated 2 cDNA clones, U21B31 and U21C8, which recognized genes
amplified and overexpressed in cell lines harboring an 11q13
amplification. Sequence analysis of the U21C8 cDNA clone revealed no
homology to known genes; they called this gene EMS1. The U21B31 cDNA
clone corresponded to the 3-prime end of the PRAD1 protooncogene
(168461).
Van Damme et al. (1997) stated that EMS1 is the human homolog of chicken
cortactin, an actin-binding protein involved in the restructuring of the
cortical actin cytoskeleton. Chicken cortactin is a substrate for the
pp60v-src tyrosine kinase (see 190090).
GENE FUNCTION
Human cortactin is overexpressed in carcinoma cells with an
amplification of 11q13 and is found in 2 forms, designated p80 and p85.
Van Damme et al. (1997) found that in carcinoma cells with the 11q13
amplification, p85 was produced from p80 by posttranslational
modification. Also, treatment of these cells with epidermal growth
factor (131530) or vanadate caused conversion of p80 to p85 and enhanced
phosphorylation of the p85 form. Both overexpression and
posttranslational modification of cortactin coincided with its
redistribution from the cytoplasm to cell-matrix contact sites, implying
a role for cortactin in the modulation of cellular adhesive properties.
Williams et al. (2007) stated that suppression of Kv1.2 (KCNA2;
176262)-mediated potassium channel currents occurs by endocytosis of the
channel protein following its tyrosine phosphorylation. Using pull-down
assays with purified recombinant proteins, they had previously
demonstrated direct interaction between Kv1.2 and cortactin that was
reduced by tyrosine phosphorylation of Kv1.2 (Hattan et al., 2002).
Using cells and cDNAs from several species, including human, Williams et
al. (2007) showed that cortactin interacted with Kv1.2 in vivo and was
required for Kv1.2 membrane localization and channel function. Depletion
of endogenous cortactin in HEK293 cells via RNA interference reduced
surface Kv1.2 levels, which could be restored by introduction of mouse
cortactin. Kv1.2 trafficking required the cortactin actin regulatory
domains and was modulated by phosphorylation of cortactin C-terminal
tyrosines. Williams et al. (2007) concluded that cortactin-mediated
actin remodeling in excitable cells has a direct impact on membrane
excitability.
Tegtmeyer et al. (2011) found that knockdown of CTTN via small
interfering RNA in a human gastric adenocarcinoma cell line inhibited
cell scattering and elongation induced by infection with Helicobacter
pylori (Hp). Hp-induced scattering and elongation correlated with
activation of PAK1 (602590) and ERK1 (MAPK3; 601795)/ERK2 (MAPK1;
176948) and inactivation of SRC (190090). Phospho-specific antibodies to
CTTN serine residues showed phosphorylation and membrane expression
after Hp infection, while tyrosine residues of CTTN were
dephosphorylated. Ser418 and ser405 residues were specifically
phosphorylated in p80 and p85, respectively. Hp-induced serine
phosphorylation in CTTN was independent of the Hp cytotoxin-associated
gene A (CagA) effector protein, whereas tyrosine dephosphorylation in
CTTN was dependent on CagA. Immunoprecipitation analysis detected
interaction of CTTN with N-WASP (WASL; 605056) and actin only in
uninfected cells. Immunofluorescence analysis of uninfected cells
demonstrated localization of CTTN in cytoplasm and membrane, which
shifted after Hp infection to colocalization with FAK (PTK2; 600758) at
the tip and base of cellular elongations. Interaction of CTTN with FAK
required phosphorylation of either ser405 or ser418, but not both
simultaneously, and involved binding of the CTTN SH3 domain with a PxxP
motif, designated PR3, of FAK. Binding of CTTN phosphorylated at ser405,
but not CTTN phosphorylated at ser418, to FAK increased FAK kinase
activity. Tegtmeyer et al. (2011) proposed that Hp targets cortactin to
protect the gastric epithelium from excessive cell lifting and to ensure
sustained infection in the stomach.
MAPPING
Gross (2012) mapped the CTTN gene to chromosome 11q13.3 based on an
alignment of the CTTN sequence (GenBank GENBANK BC008799) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Gross, M. B.: Personal Communication. Baltimore, Md. 3/21/2012.
2. Hattan, D.; Nesti, E.; Cachero, T. G.; Morielli, A. D.: Tyrosine
phosphorylation of Kv1.2 modulates its interaction with the actin-binding
protein cortactin. J. Biol. Chem. 277: 38596-38606, 2002.
3. Schuuring, E.; Verhoeven, E.; Mooi, W. J.; Michalides, R. J. A.
M.: Identification and cloning of two overexpressed genes, U21B31/PRAD1
and EMS1, within the amplified chromosome 11q13 region in human carcinomas. Oncogene 7:
355-361, 1992.
4. Tegtmeyer, N.; Wittelsberger, R.; Hartig, R.; Wessler, S.; Martinez-Quiles,
N.; Backert, S.: Serine phosphorylation of cortactin controls focal
adhesion kinase activity and cell scattering induced by Helicobacter
pylori. Cell Host Microbe 9: 520-531, 2011.
5. van Damme, H.; Brok, H.; Schuuring-Scholtes, E.; Schuuring, E.
: The redistribution of cortactin into cell-matrix contact sites in
human carcinoma cells with 11q13 amplification is associated with
both overexpression and post-translational modification. J. Biol.
Chem. 272: 7374-7380, 1997.
6. Williams, M. R.; Markey, J. C.; Doczi, M. A.; Morielli, A. D.:
An essential role for cortactin in the modulation of the potassium
channel Kv1.2. Proc. Nat. Acad. Sci. 104: 17412-17417, 2007.
*FIELD* CN
Matthew B. Gross - updated: 03/21/2012
Paul J. Converse - updated: 3/15/2012
Patricia A. Hartz - updated: 8/20/2008
Jennifer P. Macke - updated: 11/16/1998
*FIELD* CD
Victor A. McKusick: 5/27/1993
*FIELD* ED
mgross: 03/21/2012
terry: 3/15/2012
mgross: 8/21/2008
terry: 8/20/2008
alopez: 11/16/1998
terry: 8/11/1998
carol: 5/28/1993
carol: 5/27/1993