SRC8_MOUSE
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 03-AUG-2022, entry version 202.
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, Pancreas,
RC 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 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 [16]
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 [17]
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 the invasiveness of cancer cells, and the formation of
CC metastases (By similarity). Plays a role in focal adhesion assembly and
CC turnover (By similarity). In complex with ABL1 and MYLK regulates
CC cortical actin-based cytoskeletal rearrangement critical to sphingosine
CC 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement
CC (By similarity). Plays a role in intracellular protein transport and
CC endocytosis, and in modulating the levels of potassium channels present
CC at the cell membrane (PubMed:17959782). Plays a role in receptor-
CC mediated endocytosis via clathrin-coated pits (By similarity). Required
CC for stabilization of KCNH1 channels at the cell membrane (By
CC similarity). {ECO:0000250|UniProtKB:Q14247,
CC ECO:0000250|UniProtKB:Q66HL2, ECO:0000269|PubMed:17403031,
CC ECO:0000269|PubMed:17959782, ECO:0000269|PubMed:22262902}.
CC -!- SUBUNIT: Interacts with SHANK2 and SHANK3 (via its SH3 domain).
CC Interacts with PLXDC2 and SRCIN1. Interacts with SAMSN1 (via SH3
CC domain). Interacts (via SH3 domain) with ASAP1 (via Pro-rich region).
CC Interacts (via SH3 domain) with DNM2. Interacts with ACTN1 (By
CC similarity). Interacts with FER. Forms a complex with ABL1 and MYLK (By
CC similarity). Interacts with KCNA2 (via non-phosphorylated C-terminus).
CC Interacts with FGD1. Identified in a complex containing FGFR4, NCAM1,
CC CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts with ABL2
CC (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: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. Cell projection,
CC lamellipodium. Cell projection, ruffle. Cytoplasm, cell cortex. Cell
CC projection {ECO:0000250|UniProtKB:Q66HL2}. Cell projection, podosome
CC {ECO:0000250|UniProtKB:Q01406}. Cell projection, dendritic spine
CC {ECO:0000250}. Cell projection, dendrite {ECO:0000250}. Cell membrane
CC {ECO:0000250|UniProtKB:Q66HL2}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cell junction
CC {ECO:0000250|UniProtKB:Q66HL2}. Membrane, clathrin-coated pit
CC {ECO:0000250|UniProtKB:Q66HL2}. Cell junction, focal adhesion
CC {ECO:0000250|UniProtKB:Q66HL2}. Note=Colocalizes transiently with
CC PTK2/FAK1 at focal adhesions (By similarity). Associated with membrane
CC ruffles and lamellipodia. In the presence of CTTNBP2NL, colocalizes
CC with stress fibers. In the presence of CTTNBP2, localizes at the cell
CC cortex. In response to neuronal activation by glutamate, redistributes
CC from dendritic spines to the dendritic shaft. Colocalizes with DNM2 at
CC the basis of filopodia in hippocampus neuron growth zones (By
CC 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: 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}.
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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 PDBsum; 3ULR; -.
DR PDBsum; 5NV1; -.
DR PDBsum; 5NVJ; -.
DR PDBsum; 5NXJ; -.
DR AlphaFoldDB; Q60598; -.
DR SMR; Q60598; -.
DR BioGRID; 198978; 38.
DR CORUM; Q60598; -.
DR DIP; DIP-31562N; -.
DR ELM; Q60598; -.
DR IntAct; Q60598; 44.
DR MINT; Q60598; -.
DR STRING; 10090.ENSMUSP00000099368; -.
DR iPTMnet; Q60598; -.
DR PhosphoSitePlus; Q60598; -.
DR jPOST; Q60598; -.
DR MaxQB; Q60598; -.
DR PaxDb; Q60598; -.
DR PeptideAtlas; Q60598; -.
DR PRIDE; Q60598; -.
DR ProteomicsDB; 257360; -.
DR Antibodypedia; 4416; 975 antibodies from 45 providers.
DR DNASU; 13043; -.
DR Ensembl; ENSMUST00000103079; ENSMUSP00000099368; ENSMUSG00000031078.
DR GeneID; 13043; -.
DR KEGG; mmu:13043; -.
DR UCSC; uc009kqh.2; mouse.
DR CTD; 2017; -.
DR MGI; MGI:99695; Cttn.
DR VEuPathDB; HostDB:ENSMUSG00000031078; -.
DR eggNOG; ENOG502QS6C; Eukaryota.
DR GeneTree; ENSGT00940000158565; -.
DR InParanoid; Q60598; -.
DR OMA; PQKHASQ; -.
DR OrthoDB; 1243441at2759; -.
DR PhylomeDB; Q60598; -.
DR TreeFam; TF318935; -.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR BioGRID-ORCS; 13043; 6 hits in 75 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 266 other tissues.
DR ExpressionAtlas; Q60598; baseline and differential.
DR Genevisible; Q60598; MM.
DR GO; GO:0005884; C:actin filament; ISO:MGI.
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:0005925; C:focal adhesion; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0030426; C:growth cone; 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: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:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0030041; P:actin filament polymerization; IEA:InterPro.
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: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:1903146; P:regulation of autophagy of mitochondrion; IMP:ParkinsonsUK-UCL.
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:0006930; P:substrate-dependent cell migration, cell extension; IGI:MGI.
DR CDD; cd11959; SH3_Cortactin; 1.
DR DisProt; DP01752; -.
DR InterPro; IPR015503; Cortactin.
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:SF15; PTHR10829:SF15; 3.
DR Pfam; PF02218; HS1_rep; 7.
DR Pfam; PF14604; SH3_9; 1.
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; Cell junction; Cell membrane; Cell projection;
KW Coated pit; Coiled coil; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Endocytosis; Isopeptide bond; Membrane;
KW Methylation; Phosphoprotein; Reference proteome; Repeat; SH3 domain;
KW 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
