ID SRC8_MOUSE Reviewed; 546 AA. AC Q60598; Q3UGC2; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 27-MAR-2024, entry version 211. DE RecName: Full=Src substrate cortactin; GN Name=Cttn; Synonyms=Ems1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=BALB/cJ; RX PubMed=7516062; RA Miglarese M.R., Mannion-Henderson J., Wu H., Parsons J.T., Bender T.P.; RT "The protein tyrosine kinase substrate cortactin is differentially RT expressed in murine B lymphoid tumors."; RL Oncogene 9:1989-1997(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 125-138; 273-289 AND RP 534-543, AND PHOSPHORYLATION. RX PubMed=7693700; DOI=10.1016/s0021-9258(20)80543-2; RA Zhan X., Hu X., Hampton B., Burgess W.H., Friesel R., Maciag T.; RT "Murine cortactin is phosphorylated in response to fibroblast growth RT factor-1 on tyrosine residues late in the G1 phase of the BALB/c 3T3 cell RT cycle."; RL J. Biol. Chem. 268:24427-24431(1993). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Amnion, and Heart; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP IDENTIFICATION IN A COMPLEX WITH NCAM1; CDH2; PLCG1; FRS2; SRC; SHC1; FGFR4 RP AND GAP43. RX PubMed=11433297; DOI=10.1038/35083041; RA Cavallaro U., Niedermeyer J., Fuxa M., Christofori G.; RT "N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor RT signalling."; RL Nat. Cell Biol. 3:650-657(2001). RN [6] RP SUBCELLULAR LOCATION, AND INTERACTION WITH FGD1. RX PubMed=12913069; DOI=10.1093/hmg/ddg209; RA Hou P., Estrada L., Kinley A.W., Parsons J.T., Vojtek A.B., Gorski J.L.; RT "Fgd1, the Cdc42 GEF responsible for faciogenital dysplasia, directly RT interacts with cortactin and mAbp1 to modulate cell shape."; RL Hum. Mol. Genet. 12:1981-1993(2003). RN [7] RP FUNCTION IN ACTIN BUNDLE FORMATION, AND PHOSPHORYLATION. RX PubMed=17403031; DOI=10.1111/j.1471-4159.2007.04485.x; RA Bourguignon L.Y., Gilad E., Peyrollier K., Brightman A., Swanson R.A.; RT "Hyaluronan-CD44 interaction stimulates Rac1 signaling and PKN gamma kinase RT activation leading to cytoskeleton function and cell migration in RT astrocytes."; RL J. Neurochem. 101:1002-1017(2007). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401; SER-405 AND SER-407, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [9] RP FUNCTION, INTERACTION WITH KCNA2, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP TRP-22; TYR-421; TYR-466 AND TYR-482. RX PubMed=17959782; DOI=10.1073/pnas.0703865104; RA Williams M.R., Markey J.C., Doczi M.A., Morielli A.D.; RT "An essential role for cortactin in the modulation of the potassium channel RT Kv1.2."; RL Proc. Natl. Acad. Sci. U.S.A. 104:17412-17417(2007). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113; THR-401; SER-405; RP SER-407 AND SER-418, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [11] RP PHOSPHORYLATION AT TYR-482 AND TYR-485. RX PubMed=22252131; DOI=10.1038/emboj.2011.496; RA Mukherjee M., Chow S.Y., Yusoff P., Seetharaman J., Ng C., Sinniah S., RA Koh X.W., Asgar N.F., Li D., Yim D., Jackson R.A., Yew J., Qian J., Iyu A., RA Lim Y.P., Zhou X., Sze S.K., Guy G.R., Sivaraman J.; RT "Structure of a novel phosphotyrosine-binding domain in Hakai that targets RT E-cadherin."; RL EMBO J. 31:1308-1319(2012). RN [12] RP FUNCTION, INTERACTION WITH CTTNBP2, AND SUBCELLULAR LOCATION. RX PubMed=22262902; DOI=10.1523/jneurosci.4405-11.2012; RA Chen Y.K., Hsueh Y.P.; RT "Cortactin-binding protein 2 modulates the mobility of cortactin and RT regulates dendritic spine formation and maintenance."; RL J. Neurosci. 32:1043-1055(2012). RN [13] RP INTERACTION WITH CTTNBP2NL, AND SUBCELLULAR LOCATION. RX PubMed=23015759; DOI=10.1091/mbc.e12-05-0365; RA Chen Y.K., Chen C.Y., Hu H.T., Hsueh Y.P.; RT "CTTNBP2, but not CTTNBP2NL, regulates dendritic spinogenesis and synaptic RT distribution of the striatin-PP2A complex."; RL Mol. Biol. Cell 23:4383-4392(2012). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-87; LYS-124; LYS-144; LYS-161; RP LYS-181; LYS-198; LYS-235; LYS-272; LYS-295; LYS-309 AND LYS-346, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001; RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.; RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic RT pathways."; RL Mol. Cell 50:919-930(2013). RN [15] RP INTERACTION WITH NEDD9. RX PubMed=24574519; DOI=10.1158/1541-7786.mcr-13-0654; RA Kozyreva V.K., McLaughlin S.L., Livengood R.H., Calkins R.A., Kelley L.C., RA Rajulapati A., Ice R.J., Smolkin M.B., Weed S.A., Pugacheva E.N.; RT "NEDD9 regulates actin dynamics through cortactin deacetylation in an RT AURKA/HDAC6-dependent manner."; RL Mol. Cancer Res. 12:681-693(2014). RN [16] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-119, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [17] RP INTERACTION WITH DIP2A, ACETYLATION AT LYS-107; LYS-152; LYS-171; LYS-181; RP LYS-193; LYS-235; LYS-309 AND LYS-314, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=31600191; DOI=10.1371/journal.pbio.3000461; RA Ma J., Zhang L.Q., He Z.X., He X.X., Wang Y.J., Jian Y.L., Wang X., RA Zhang B.B., Su C., Lu J., Huang B.Q., Zhang Y., Wang G.Y., Guo W.X., RA Qiu D.L., Mei L., Xiong W.C., Zheng Y.W., Zhu X.J.; RT "Autism candidate gene DIP2A regulates spine morphogenesis via acetylation RT of cortactin."; RL PLoS Biol. 17:e3000461-e3000461(2019). RN [18] RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 487-546 IN COMPLEX WITH ABL2, AND RP INTERACTION WITH ABL2. RX PubMed=22297987; DOI=10.1107/s1744309111056132; RA Liu W., MacGrath S.M., Koleske A.J., Boggon T.J.; RT "Lysozyme contamination facilitates crystallization of a heterotrimeric RT cortactin-Arg-lysozyme complex."; RL Acta Crystallogr. F 68:154-158(2012). CC -!- FUNCTION: Contributes to the organization of the actin cytoskeleton and CC cell shape (PubMed:17403031). Plays a role in the formation of CC lamellipodia and in cell migration (By similarity). Plays a role in the CC regulation of neuron morphology, axon growth and formation of neuronal CC growth cones (By similarity). Through its interaction with CTTNBP2, CC involved in the regulation of neuronal spine density (PubMed:22262902). CC Plays a role in focal adhesion assembly and turnover (By similarity). CC In complex with ABL1 and MYLK regulates cortical actin-based CC cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)- CC mediated endothelial cell (EC) barrier enhancement (By similarity). CC Plays a role in intracellular protein transport and endocytosis, and in CC modulating the levels of potassium channels present at the cell CC membrane (PubMed:17959782). Plays a role in receptor-mediated CC endocytosis via clathrin-coated pits (By similarity). Required for CC stabilization of KCNH1 channels at the cell membrane (By similarity). CC {ECO:0000250|UniProtKB:Q14247, ECO:0000250|UniProtKB:Q66HL2, CC ECO:0000269|PubMed:17403031, ECO:0000269|PubMed:17959782, CC ECO:0000269|PubMed:22262902}. CC -!- SUBUNIT: Part of a complex composed of NEDD9, AURKA and CTTN; within CC the complex NEDD9 acts as a scaffold protein and is required for CC complex formation (By similarity). Interacts (via N-terminus) with CC NEDD9 (PubMed:24574519). Identified in a complex containing FGFR4, CC NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Forms a complex CC with ABL1 and MYLK (By similarity). Interacts with SHANK2 and SHANK3 CC (via its SH3 domain). Interacts with PLXDC2 and SRCIN1. Interacts with CC SAMSN1 (via SH3 domain). Interacts (via SH3 domain) with ASAP1 (via CC Pro-rich region). Interacts (via SH3 domain) with DNM2. Interacts with CC ACTN1 (By similarity). Interacts with FER. Interacts with KCNA2 (via CC non-phosphorylated C-terminus). Interacts with FGD1. Interacts with CC ABL2 (PubMed:22297987). Interacts with CTTNBP2NL; this interaction may CC target CTTN to stress fibers. Interacts with CTTNBP2; this interaction CC may target CTTN at the cell cortex or dendritic spines. Interacts with CC KCNH1 (By similarity). Interacts (via SH3 domain) with DIP2A (via N- CC terminus); the interaction enhances CTTN acetylation and is required CC for proper synaptic transmission (PubMed:31600191). CC {ECO:0000250|UniProtKB:Q14247, ECO:0000250|UniProtKB:Q66HL2, CC ECO:0000269|PubMed:11433297, ECO:0000269|PubMed:12913069, CC ECO:0000269|PubMed:17959782, ECO:0000269|PubMed:22262902, CC ECO:0000269|PubMed:22297987, ECO:0000269|PubMed:23015759, CC ECO:0000269|PubMed:24574519, ECO:0000269|PubMed:31600191}. CC -!- INTERACTION: CC Q60598; Q99JY9: Actr3; NbExp=5; IntAct=EBI-397955, EBI-773994; CC Q60598; Q9JIY2: Cbll1; NbExp=4; IntAct=EBI-397955, EBI-7644904; CC Q60598; P30999: Ctnnd1; NbExp=4; IntAct=EBI-397955, EBI-529924; CC Q60598; P39054: Dnm2; NbExp=2; IntAct=EBI-397955, EBI-642337; CC Q60598; Q9JKY5: Hip1r; NbExp=4; IntAct=EBI-397955, EBI-642457; CC Q60598; P63141: Kcna2; NbExp=3; IntAct=EBI-397955, EBI-644033; CC Q60598; Q08460: Kcnma1; NbExp=2; IntAct=EBI-397955, EBI-1633915; CC Q60598; Q91YD9: Wasl; NbExp=4; IntAct=EBI-397955, EBI-642417; CC Q60598; P61157: ACTR3; Xeno; NbExp=4; IntAct=EBI-397955, EBI-351419; CC Q60598; Q8X482: espF(U); Xeno; NbExp=6; IntAct=EBI-397955, EBI-22229752; CC Q60598; Q9UBN7: HDAC6; Xeno; NbExp=3; IntAct=EBI-397955, EBI-301697; CC Q60598; O43312: MTSS1; Xeno; NbExp=2; IntAct=EBI-397955, EBI-473954; CC Q60598; Q7DB77: tir; Xeno; NbExp=4; IntAct=EBI-397955, EBI-6480811; CC Q60598; O08816: Wasl; Xeno; NbExp=2; IntAct=EBI-397955, EBI-6142604; CC Q60598; Q95107: WASL; Xeno; NbExp=2; IntAct=EBI-397955, EBI-6162776; CC Q60598; O43516: WIPF1; Xeno; NbExp=4; IntAct=EBI-397955, EBI-346356; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton CC {ECO:0000250|UniProtKB:Q14247}. Cell projection, lamellipodium CC {ECO:0000250|UniProtKB:Q14247}. Cell projection, ruffle. Cell CC projection, dendrite. Cell projection {ECO:0000250|UniProtKB:Q66HL2}. CC Cell membrane {ECO:0000250|UniProtKB:Q66HL2}; Peripheral membrane CC protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cell projection, CC podosome {ECO:0000250|UniProtKB:Q01406}. Cell junction CC {ECO:0000250|UniProtKB:Q66HL2}. Cell junction, focal adhesion CC {ECO:0000250|UniProtKB:Q66HL2}. Membrane, clathrin-coated pit CC {ECO:0000250|UniProtKB:Q66HL2}. Cell projection, dendritic spine. CC Cytoplasm, cell cortex {ECO:0000250|UniProtKB:Q14247}. Endoplasmic CC reticulum {ECO:0000250|UniProtKB:Q01406}. Note=Colocalizes transiently CC with PTK2/FAK1 at focal adhesions (By similarity). Associated with CC membrane ruffles and lamellipodia. In the presence of CTTNBP2NL, CC colocalizes with stress fibers. In the presence of CTTNBP2, localizes CC at the cell cortex. In response to neuronal activation by glutamate, CC redistributes from dendritic spines to the dendritic shaft. Colocalizes CC with DNM2 at the basis of filopodia in hippocampus neuron growth zones CC (By similarity). {ECO:0000250|UniProtKB:Q14247, CC ECO:0000250|UniProtKB:Q66HL2}. CC -!- TISSUE SPECIFICITY: Expressed in most tissues, except in B-lymphocytes CC or plasma cells. CC -!- DOMAIN: The SH3 motif may mediate binding to the cytoskeleton. CC {ECO:0000305}. CC -!- PTM: Acetylated. {ECO:0000250|UniProtKB:Q14247}. CC -!- PTM: Phosphorylated by FER. Phosphorylated in response to FGR CC activation (PubMed:7693700). Phosphorylation by SRC promotes MYLK CC binding (By similarity). Phosphorylated on tyrosine residues in CC response to CHRM1 activation (By similarity). Phosphorylated by CC PTK2/FAK1 in response to cell adhesion (By similarity). Tyrosine CC phosphorylation in transformed cells may contribute to cellular growth CC regulation and transformation. Phosphorylated by PKN2 at both serine CC and threonine residues in a GTP-bound Rac1-dependent manner in CC hyaluronan-induced astrocytes and hence down-regulated CTTN ability to CC associate with filamentous actin. {ECO:0000250|UniProtKB:Q14247, CC ECO:0000250|UniProtKB:Q66HL2, ECO:0000269|PubMed:17403031, CC ECO:0000269|PubMed:22252131, ECO:0000269|PubMed:7693700}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U03184; AAA19689.1; -; mRNA. DR EMBL; AK146856; BAE27485.1; -; mRNA. DR EMBL; AK148010; BAE28287.1; -; mRNA. DR EMBL; AK168699; BAE40543.1; -; mRNA. DR EMBL; CH466531; EDL18251.1; -; Genomic_DNA. DR CCDS; CCDS22049.1; -. DR PIR; I48899; I48899. DR RefSeq; NP_031829.2; NM_007803.5. DR PDB; 3ULR; X-ray; 1.65 A; B=487-546. DR PDB; 5NV1; X-ray; 1.51 A; A=490-546. DR PDB; 5NVJ; X-ray; 1.18 A; A/B=490-546. DR PDB; 5NXJ; X-ray; 2.28 A; A/B/C/D/E/F=490-546. DR PDB; 7PLL; NMR; -; A=490-546. DR PDB; 8TAH; EM; 2.89 A; H=1-76. DR PDBsum; 3ULR; -. DR PDBsum; 5NV1; -. DR PDBsum; 5NVJ; -. DR PDBsum; 5NXJ; -. DR PDBsum; 7PLL; -. DR PDBsum; 8TAH; -. DR AlphaFoldDB; Q60598; -. DR EMDB; EMD-41135; -. DR SMR; Q60598; -. DR BioGRID; 198978; 46. DR CORUM; Q60598; -. DR DIP; DIP-31562N; -. DR ELM; Q60598; -. DR IntAct; Q60598; 44. DR MINT; Q60598; -. DR STRING; 10090.ENSMUSP00000099368; -. DR GlyGen; Q60598; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q60598; -. DR PhosphoSitePlus; Q60598; -. DR SwissPalm; Q60598; -. DR jPOST; Q60598; -. DR MaxQB; Q60598; -. DR PaxDb; 10090-ENSMUSP00000099368; -. DR PeptideAtlas; Q60598; -. DR ProteomicsDB; 257360; -. DR Pumba; Q60598; -. DR Antibodypedia; 4416; 1087 antibodies from 45 providers. DR DNASU; 13043; -. DR Ensembl; ENSMUST00000103079.4; ENSMUSP00000099368.4; ENSMUSG00000031078.16. DR GeneID; 13043; -. DR KEGG; mmu:13043; -. DR UCSC; uc009kqh.2; mouse. DR AGR; MGI:99695; -. DR CTD; 2017; -. DR MGI; MGI:99695; Cttn. DR VEuPathDB; HostDB:ENSMUSG00000031078; -. DR eggNOG; ENOG502QS6C; Eukaryota. DR GeneTree; ENSGT00940000158565; -. DR InParanoid; Q60598; -. DR OMA; KFDESWW; -. DR OrthoDB; 101008at2759; -. DR PhylomeDB; Q60598; -. DR TreeFam; TF318935; -. DR BioGRID-ORCS; 13043; 7 hits in 80 CRISPR screens. DR ChiTaRS; Cttn; mouse. DR PRO; PR:Q60598; -. DR Proteomes; UP000000589; Chromosome 7. DR RNAct; Q60598; Protein. DR Bgee; ENSMUSG00000031078; Expressed in renal medulla collecting duct and 270 other cell types or tissues. DR ExpressionAtlas; Q60598; baseline and differential. DR GO; GO:0005884; C:actin filament; IEA:Ensembl. DR GO; GO:0005938; C:cell cortex; IDA:MGI. DR GO; GO:0030054; C:cell junction; ISS:UniProtKB. DR GO; GO:0005905; C:clathrin-coated pit; ISS:UniProtKB. DR GO; GO:0030864; C:cortical actin cytoskeleton; IBA:GO_Central. DR GO; GO:0030863; C:cortical cytoskeleton; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell. DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI. DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI. DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB. DR GO; GO:1990023; C:mitotic spindle midzone; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0002102; C:podosome; IDA:MGI. DR GO; GO:0098794; C:postsynapse; ISO:MGI. DR GO; GO:0098871; C:postsynaptic actin cytoskeleton; ISO:MGI. DR GO; GO:0001726; C:ruffle; IDA:UniProtKB. DR GO; GO:0030427; C:site of polarized growth; IBA:GO_Central. DR GO; GO:0008076; C:voltage-gated potassium channel complex; ISO:MGI. DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central. DR GO; GO:0071933; F:Arp2/3 complex binding; ISO:MGI. DR GO; GO:0005522; F:profilin binding; ISO:MGI. DR GO; GO:0070064; F:proline-rich region binding; ISO:MGI. DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:UniProtKB. DR GO; GO:0048870; P:cell motility; ISS:UniProtKB. DR GO; GO:0097062; P:dendritic spine maintenance; IGI:MGI. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IGI:MGI. DR GO; GO:0048041; P:focal adhesion assembly; ISS:UniProtKB. DR GO; GO:0006886; P:intracellular protein transport; IMP:UniProtKB. DR GO; GO:0097581; P:lamellipodium organization; ISS:UniProtKB. DR GO; GO:0098885; P:modification of postsynaptic actin cytoskeleton; ISO:MGI. DR GO; GO:0099010; P:modification of postsynaptic structure; ISO:MGI. DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IGI:MGI. DR GO; GO:0048812; P:neuron projection morphogenesis; ISS:UniProtKB. DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISS:UniProtKB. DR GO; GO:0050921; P:positive regulation of chemotaxis; ISO:MGI. DR GO; GO:0045987; P:positive regulation of smooth muscle contraction; ISO:MGI. DR GO; GO:0006898; P:receptor-mediated endocytosis; ISS:UniProtKB. DR GO; GO:0030833; P:regulation of actin filament polymerization; IBA:GO_Central. DR GO; GO:0030516; P:regulation of axon extension; ISS:UniProtKB. DR GO; GO:0060491; P:regulation of cell projection assembly; ISO:MGI. DR GO; GO:1901524; P:regulation of mitophagy; IMP:ParkinsonsUK-UCL. DR GO; GO:0006930; P:substrate-dependent cell migration, cell extension; IGI:MGI. DR CDD; cd11959; SH3_Cortactin; 1. DR DisProt; DP01752; -. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR InterPro; IPR035716; Cortactin_SH3. DR InterPro; IPR003134; Hs1_Cortactin. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR PANTHER; PTHR10829; CORTACTIN AND DREBRIN; 1. DR PANTHER; PTHR10829:SF15; SRC SUBSTRATE CORTACTIN; 1. DR Pfam; PF02218; HS1_rep; 7. DR Pfam; PF14604; SH3_9; 1. DR PRINTS; PR00499; P67PHOX. DR PRINTS; PR00452; SH3DOMAIN. DR SMART; SM00326; SH3; 1. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS51090; CORTACTIN; 7. DR PROSITE; PS50002; SH3; 1. DR Genevisible; Q60598; MM. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cell junction; Cell membrane; Cell projection; KW Coated pit; Coiled coil; Cytoplasm; Cytoskeleton; KW Direct protein sequencing; Endocytosis; Endoplasmic reticulum; KW Isopeptide bond; Membrane; Methylation; Phosphoprotein; Reference proteome; KW Repeat; SH3 domain; Synapse; Ubl conjugation. FT CHAIN 1..546 FT /note="Src substrate cortactin" FT /id="PRO_0000072190" FT REPEAT 80..116 FT /note="Cortactin 1" FT REPEAT 117..153 FT /note="Cortactin 2" FT REPEAT 154..190 FT /note="Cortactin 3" FT REPEAT 191..227 FT /note="Cortactin 4" FT REPEAT 228..264 FT /note="Cortactin 5" FT REPEAT 265..301 FT /note="Cortactin 6" FT REPEAT 302..324 FT /note="Cortactin 7; truncated" FT DOMAIN 488..546 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT REGION 1..28 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 355..424 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 348..401 FT /evidence="ECO:0000255" FT COMPBIAS 355..397 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 87 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 107 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:31600191" FT MOD_RES 113 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 119 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 124 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 144 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 150 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q14247" FT MOD_RES 152 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:31600191" FT MOD_RES 161 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 171 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:31600191" FT MOD_RES 181 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:31600191, FT ECO:0007744|PubMed:23806337" FT MOD_RES 193 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:31600191" FT MOD_RES 198 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 235 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:31600191, FT ECO:0007744|PubMed:23806337" FT MOD_RES 261 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q14247" FT MOD_RES 272 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 295 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 304 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q14247" FT MOD_RES 309 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:31600191, FT ECO:0007744|PubMed:23806337" FT MOD_RES 314 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:31600191" FT MOD_RES 346 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 401 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 405 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 407 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 417 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q14247" FT MOD_RES 418 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 421 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q66HL2" FT MOD_RES 442 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q14247" FT MOD_RES 443 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q14247" FT MOD_RES 466 FT /note="Phosphotyrosine; by FAK1" FT /evidence="ECO:0000250|UniProtKB:Q66HL2" FT MOD_RES 482 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:22252131" FT MOD_RES 485 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:22252131" FT CROSSLNK 144 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0000250|UniProtKB:Q14247" FT CROSSLNK 144 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:Q14247" FT CROSSLNK 181 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0000250|UniProtKB:Q14247" FT CROSSLNK 181 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:Q14247" FT CROSSLNK 218 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1)" FT /evidence="ECO:0000250|UniProtKB:Q14247" FT CROSSLNK 295 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:Q14247" FT MUTAGEN 22 FT /note="W->A: Abolishes cortactin-mediated endocytosis of FT KCNA2." FT /evidence="ECO:0000269|PubMed:17959782" FT MUTAGEN 421 FT /note="Y->F: No effect on interaction with KCNA2." FT /evidence="ECO:0000269|PubMed:17959782" FT MUTAGEN 466 FT /note="Y->F: No effect on interaction with KCNA2, but FT decreases KCNA2 levels at the cell membrane." FT /evidence="ECO:0000269|PubMed:17959782" FT MUTAGEN 482 FT /note="Y->F: No effect on interaction with KCNA2, but FT decreases KCNA2 levels at the cell membrane." FT /evidence="ECO:0000269|PubMed:17959782" FT CONFLICT 9 FT /note="A -> R (in Ref. 2; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 298 FT /note="S -> P (in Ref. 1; AAA19689)" FT /evidence="ECO:0000305" FT STRAND 493..495 FT /evidence="ECO:0007829|PDB:5NVJ" FT STRAND 514..519 FT /evidence="ECO:0007829|PDB:5NVJ" FT STRAND 522..530 FT /evidence="ECO:0007829|PDB:5NVJ" FT STRAND 533..538 FT /evidence="ECO:0007829|PDB:5NVJ" FT HELIX 539..541 FT /evidence="ECO:0007829|PDB:5NVJ" FT STRAND 542..544 FT /evidence="ECO:0007829|PDB:5NVJ" SQ SEQUENCE 546 AA; 61250 MW; 8F5CA026ACCD6D4F CRC64; MWKASAGHAV SITQDDGGAD DWETDPDFVN DVSEKEQRWG AKTVQGSGHQ EHINIHKLRE NVFQEHQTLK EKELETGPKA SHGYGGKFGV EQDRMDRSAV GHEYQSKLSK HCSQVDSVRG FGGKFGVQMD RVDQSAVGFE YQGKTEKHAS QKDYSSGFGG KYGVQADRVD KSAVGFDYQG KTEKHESQKD YSKGFGGKYG IDKDKVDKSA VGFEYQGKTE KHESQKDYVK GFGGKFGVQT DRQDKCALGW DHQEKLQLHE SQKDYKTGFG GKFGVQSERQ DSSAVGFDYK ERLAKHESQQ DYAKGFGGKY GVQKDRMDKN ASTFEEVVQV PSAYQKTVPI EAVTSKTSNI RANFENLAKE REQEDRRKAE AERAQRMAKE RQEQEEARRK LEEQARAKKQ TPPASPSPQP IEDRPPSSPI YEDAAPFKAE PSYRGSEPEP EYSIEAAGIP EAGSQQGLTY TSEPVYETTE APGHYQAEDD TYDGYESDLG ITAIALYDYQ AAGDDEISFD PDDIITNIEM IDDGWWRGVC KGRYGLFPAN YVELRQ //