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Protein

Src substrate cortactin

Gene

Cttn

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Contributes to the organization of the actin cytoskeleton and cell shape (PubMed:18768925). Plays a role in the formation of lamellipodia and in cell migration (PubMed:18768925). Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (PubMed:21210813). Through its interaction with CTTNBP2, involved in the regulation of neuronal spine density (By similarity). Plays a role in the invasiveness of cancer cells, and the formation of metastases (By similarity). Plays a role in focal adhesion assembly and turnover (PubMed:18768925, PubMed:22952866). In complex with ABL1 and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement (By similarity). Plays a role in intracellular protein transport and endocytosis, and in modulating the levels of potassium channels present at the cell membrane (By similarity). Plays a role in receptor-mediated endocytosis via clathrin-coated pits (PubMed:12612086, PubMed:19995918). Required for stabilization of KCNH1 channels at the cell membrane (By similarity).By similarity5 Publications

GO - Molecular functioni

  • Arp2/3 complex binding Source: RGD
  • proline-rich region binding Source: RGD

GO - Biological processi

Keywordsi

Biological processEndocytosis

Enzyme and pathway databases

ReactomeiR-RNO-8856828 Clathrin-mediated endocytosis

Names & Taxonomyi

Protein namesi
Recommended name:
Src substrate cortactin
Gene namesi
Name:CttnImported
OrganismiRattus norvegicus (Rat)Imported
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi619839 Cttn

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Coated pit, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi368S → A: Inhibits actin polymerization; when associated with A-381. 1 Publication1
Mutagenesisi381S → A: Inhibits actin polymerization; when associated with A-368. 1 Publication1
Mutagenesisi384Y → E: Promotes reorganization of the actin cytoskeleton and cell motility; when associated with E-429 and E-445. 1 Publication1
Mutagenesisi384Y → F: Impairs receptor-mediated endocytosis. Increases the stability of focal adhesion and decreases their turnover; when associated with F-429 and F-445. 2 Publications1
Mutagenesisi429Y → E: Promotes reorganization of the actin cytoskeleton and cell motility; when associated with E-384 and E-445. 1 Publication1
Mutagenesisi429Y → F: Impairs receptor-mediated endocytosis. Increases the stability of focal adhesion and decreases their turnover; when associated with F-384 and F-445. 2 Publications1
Mutagenesisi445Y → E: Promotes reorganization of the actin cytoskeleton and cell motility; when associated with E-384 and E-429. 1 Publication1
Mutagenesisi445Y → F: Impairs receptor-mediated endocytosis. Increases the stability of focal adhesion and decreases their turnover; when associated with F-384 and F-429. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004317001 – 509Src substrate cortactinAdd BLAST509

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei87N6-acetyllysineBy similarity1
Modified residuei113PhosphoserineBy similarity1
Modified residuei119Omega-N-methylarginineBy similarity1
Modified residuei124N6-acetyllysineBy similarity1
Modified residuei144N6-acetyllysine; alternateBy similarity1
Cross-linki144Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity
Cross-linki144Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei150PhosphoserineBy similarity1
Modified residuei161N6-acetyllysineBy similarity1
Modified residuei181N6-acetyllysine; alternateBy similarity1
Cross-linki181Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity
Cross-linki181Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei198N6-acetyllysineBy similarity1
Cross-linki218Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Modified residuei235N6-acetyllysineBy similarity1
Modified residuei261PhosphoserineBy similarity1
Modified residuei267N6-acetyllysineBy similarity1
Modified residuei272N6-acetyllysineBy similarity1
Modified residuei309N6-acetyllysineBy similarity1
Modified residuei364PhosphothreonineCombined sources1
Modified residuei368PhosphoserineCombined sources1
Modified residuei370PhosphoserineCombined sources1
Modified residuei380PhosphoserineBy similarity1
Modified residuei381PhosphoserineBy similarity1
Modified residuei384Phosphotyrosine; by FAK11 Publication1
Modified residuei405PhosphotyrosineBy similarity1
Modified residuei406PhosphoserineBy similarity1
Modified residuei429Phosphotyrosine; by FAK11 Publication1
Modified residuei445Phosphotyrosine; by FAK11 Publication1
Modified residuei445Phosphotyrosine; by SRCBy similarity1
Modified residuei448Phosphotyrosine; by SRCBy similarity1

Post-translational modificationi

Phosphorylated by FER. Phosphorylated in response to FGR activation. Phosphorylation by SRC promotes MYLK binding (By similarity). Tyrosine phosphorylation in transformed cells may contribute to cellular growth regulation and transformation. Phosphorylated by PKN2 at both serine and threonine residues in a GTP-bound Rac1-dependent manner in hyaluronan-induced astrocytes and hence down-regulated CTTN ability to associate with filamentous actin (By similarity). Phosphorylated on tyrosine residues in response to CHRM1 activation (PubMed:12151401). Phosphorylated by PTK2/FAK1 in response to cell adhesion (PubMed:22952866).By similarity3 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ66HL2
PRIDEiQ66HL2

PTM databases

iPTMnetiQ66HL2

Expressioni

Tissue specificityi

Detected in liver (at protein level).1 Publication

Gene expression databases

BgeeiENSRNOG00000047280 Expressed in 9 organ(s), highest expression level in brain
GenevisibleiQ66HL2 RN

Interactioni

Subunit structurei

Interacts with SHANK2 and SHANK3 (via its SH3 domain). Interacts with PLXDC2 and SRCIN1. Interacts with SAMSN1 (via SH3 domain). Interacts (via SH3 domain) with ASAP1 (via Pro-rich region). Interacts with FER. Forms a complex with ABL1 and MYLK (By similarity). Interacts with FGD1. Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts with ABL2. Interacts with CTTNBP2NL; this interaction may target CTTN to stress fibers. Interacts with CTTNBP2; this interaction may target CTTN at the cell cortex or dendritic spines (By similarity). Interacts (via SH3 domain) with DNM2 (PubMed:21210813). Interacts with ACTN1 (PubMed:21210813). Interacts with KCNA2 (via non-phosphorylated C-terminus) (PubMed:12151401, PubMed:17959782). Interacts with PTK2/FAK1 (PubMed:22952866). Interacts with KCNH1 (PubMed:23144454).By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Cfl1P455924EBI-6273816,EBI-917556

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ66HL2, 4 interactors
STRINGi10116.ENSRNOP00000051742

Structurei

3D structure databases

ProteinModelPortaliQ66HL2
SMRiQ66HL2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati80 – 116Cortactin 1PROSITE-ProRule annotationAdd BLAST37
Repeati117 – 153Cortactin 2PROSITE-ProRule annotationAdd BLAST37
Repeati154 – 190Cortactin 3PROSITE-ProRule annotationAdd BLAST37
Repeati191 – 227Cortactin 4PROSITE-ProRule annotationAdd BLAST37
Repeati228 – 264Cortactin 5PROSITE-ProRule annotationAdd BLAST37
Repeati265 – 287Cortactin 6; truncatedPROSITE-ProRule annotationAdd BLAST23
Domaini451 – 509SH3PROSITE-ProRule annotationAdd BLAST59

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili311 – 364Sequence analysisAdd BLAST54

Domaini

The SH3 motif may mediate binding to the cytoskeleton.Curated

Keywords - Domaini

Coiled coil, Repeat, SH3 domain

Phylogenomic databases

eggNOGiENOG410IFV2 Eukaryota
ENOG410XTAK LUCA
GeneTreeiENSGT00530000062953
HOGENOMiHOG000006523
HOVERGENiHBG005994
KOiK06106
OrthoDBiEOG091G0CPX
PhylomeDBiQ66HL2
TreeFamiTF318935

Family and domain databases

CDDicd11959 SH3_Cortactin, 1 hit
InterProiView protein in InterPro
IPR015503 Cortactin
IPR035716 Cortactin_SH3
IPR003134 Hs1_Cortactin
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR10829:SF15 PTHR10829:SF15, 3 hits
PfamiView protein in Pfam
PF02218 HS1_rep, 6 hits
PF14604 SH3_9, 1 hit
PRINTSiPR00452 SH3DOMAIN
SMARTiView protein in SMART
SM00326 SH3, 1 hit
SUPFAMiSSF50044 SSF50044, 2 hits
PROSITEiView protein in PROSITE
PS51090 CORTACTIN, 6 hits
PS50002 SH3, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.iShow all

Q66HL2-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MWKASAGHAV SITQDDGGAD DWETDPDFVN DVSEKEQRWG AKTVQGSGHQ
60 70 80 90 100
EHINIHKLRE NVFQEHQTLK EKELETGPKA SHGYGGKFGV EQDRMDKSAV
110 120 130 140 150
GHEYQSKLSK HCSQVDSVRG FGGKFGVQMD RVDQSAVGFE YQGKTEKHAS
160 170 180 190 200
QKDYSSGFGG KYGVQADRVD KSAVGFDYQG KTEKHESQKD YSKGFGGKYG
210 220 230 240 250
IDKDKVDKSA VGFEYQGKTE KHESQKDYVK GFGGKFGVQT DRQDKCALGW
260 270 280 290 300
DHQEKLQLHE SQKDYAKGFG GKYGVQKDRM DKNASTFEEV VQVPSAYQKT
310 320 330 340 350
VPIEAVTSKT SNIRANFENL AKEREQEDRR KAEAERAQRM AQERQEQEEA
360 370 380 390 400
RRKLEEQARA KKQTPPASPS PQPAEDRPPS SPIYEDAAPL KAEPSYGSSE
410 420 430 440 450
PEPEYSTEAA GLPEASNQQG LAYTSEPVYE TTEVPGHYQA EDDTYDGYES
460 470 480 490 500
DLGITAIALY DYQAAGDDEI SFDPDDVITN IEMIDDGWWR GVCKGRYGLF

PANYVELRQ
Length:509
Mass (Da):56,942
Last modified:October 11, 2004 - v1
Checksum:i059CDB52681E2592
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D3ZGE6D3ZGE6_RAT
Cortactin, isoform CRA_c
Cttn rCG_48092
546Annotation score:
A0A0G2JZ13A0A0G2JZ13_RAT
Src substrate cortactin
Cttn
472Annotation score:
A0A1B0GWS4A0A1B0GWS4_RAT
Src substrate cortactin
Cttn
213Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06009380 Genomic DNA No translation available.
AABR06009448 Genomic DNA No translation available.
CH473953 Genomic DNA Translation: EDM12238.1
BC081802 mRNA Translation: AAH81802.1
RefSeqiNP_068640.2, NM_021868.2
XP_017445759.1, XM_017590270.1
UniGeneiRn.107869

Genome annotation databases

EnsembliENSRNOT00000028283; ENSRNOP00000028283; ENSRNOG00000050994
ENSRNOT00000079805; ENSRNOP00000072540; ENSRNOG00000047280
ENSRNOT00000092916; ENSRNOP00000075952; ENSRNOG00000047280
GeneIDi60465
KEGGirno:60465
UCSCiRGD:619839 rat

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06009380 Genomic DNA No translation available.
AABR06009448 Genomic DNA No translation available.
CH473953 Genomic DNA Translation: EDM12238.1
BC081802 mRNA Translation: AAH81802.1
RefSeqiNP_068640.2, NM_021868.2
XP_017445759.1, XM_017590270.1
UniGeneiRn.107869

3D structure databases

ProteinModelPortaliQ66HL2
SMRiQ66HL2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ66HL2, 4 interactors
STRINGi10116.ENSRNOP00000051742

PTM databases

iPTMnetiQ66HL2

Proteomic databases

PaxDbiQ66HL2
PRIDEiQ66HL2

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000028283; ENSRNOP00000028283; ENSRNOG00000050994
ENSRNOT00000079805; ENSRNOP00000072540; ENSRNOG00000047280
ENSRNOT00000092916; ENSRNOP00000075952; ENSRNOG00000047280
GeneIDi60465
KEGGirno:60465
UCSCiRGD:619839 rat

Organism-specific databases

CTDi2017
RGDi619839 Cttn

Phylogenomic databases

eggNOGiENOG410IFV2 Eukaryota
ENOG410XTAK LUCA
GeneTreeiENSGT00530000062953
HOGENOMiHOG000006523
HOVERGENiHBG005994
KOiK06106
OrthoDBiEOG091G0CPX
PhylomeDBiQ66HL2
TreeFamiTF318935

Enzyme and pathway databases

ReactomeiR-RNO-8856828 Clathrin-mediated endocytosis

Miscellaneous databases

PROiPR:Q66HL2

Gene expression databases

BgeeiENSRNOG00000047280 Expressed in 9 organ(s), highest expression level in brain
GenevisibleiQ66HL2 RN

Family and domain databases

CDDicd11959 SH3_Cortactin, 1 hit
InterProiView protein in InterPro
IPR015503 Cortactin
IPR035716 Cortactin_SH3
IPR003134 Hs1_Cortactin
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR10829:SF15 PTHR10829:SF15, 3 hits
PfamiView protein in Pfam
PF02218 HS1_rep, 6 hits
PF14604 SH3_9, 1 hit
PRINTSiPR00452 SH3DOMAIN
SMARTiView protein in SMART
SM00326 SH3, 1 hit
SUPFAMiSSF50044 SSF50044, 2 hits
PROSITEiView protein in PROSITE
PS51090 CORTACTIN, 6 hits
PS50002 SH3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSRC8_RAT
AccessioniPrimary (citable) accession number: Q66HL2
Secondary accession number(s): D3ZRB0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 4, 2015
Last sequence update: October 11, 2004
Last modified: September 12, 2018
This is version 120 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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