CTTN cortactin [Homo sapiens (human)] - Gene

Summary

Official Symbol: CTTNprovided by HGNC
Official Full Name: cortactinprovided by HGNC
Primary source: HGNC:HGNC:3338
See related: Ensembl:ENSG00000085733 MIM:164765; Vega:OTTHUMG00000134307
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: EMS1
Summary: This gene is overexpressed in breast cancer and squamous cell carcinomas of the head and neck. The encoded protein is localized in the cytoplasm and in areas of the cell-substratum contacts. This gene has two roles: (1) regulating the interactions between components of adherens-type junctions and (2) organizing the cytoskeleton and cell adhesion structures of epithelia and carcinoma cells. During apoptosis, the encoded protein is degraded in a caspase-dependent manner. The aberrant regulation of this gene contributes to tumor cell invasion and metastasis. Three splice variants that encode different isoforms have been identified for this gene. [provided by RefSeq, May 2010]
Expression: Ubiquitous expression in gall bladder (RPKM 41.5), adrenal (RPKM 38.4) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 11q13.3

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	11	NC_000011.10 (70398506..70436584)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (70244612..70282690)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Cortactin depletion in HMEC-1 cells results in increased stress fibre contractility and endothelial barrier destabilisation. Secretion of the barrier-stabilising hormone adrenomedullin, which activates Rap1 and counteracts actomyosin contractility, was reduced in supernatants of cortactin-depleted endothelium. Cortactin acts in controlling actomyosin contractility with consequences for endothelial barrier integrity.
Title: Loss of cortactin causes endothelial barrier dysfunction via disturbed adrenomedullin secretion and actomyosin contractility.
Data show that cortactin-mediated p21Cip1 nuclear export and degradation facilitating MCP1-induced human aortic smooth muscle cell (HASMC) proliferation.
Title: Novel role of cortactin in G protein-coupled receptor agonist-induced nuclear export and degradation of p21Cip1.
Mena(INV) promotes invadopodium maturation by inhibiting normal dephosphorylation of cortactin at tyrosine 421 by the phosphatase PTP1B.
Title: Mena<sup>INV</sup> dysregulates cortactin phosphorylation to promote invadopodium maturation.
CTTN expression increases EGFR protein levels and enhances the activation of the MAPK signaling pathway. CTTN expression also inhibits the ubiquitin-mediated degradation of EGFR by suppressing the coupling of c-Cbl with EGFR.
Title: Cortactin promotes colorectal cancer cell proliferation by activating the EGFR-MAPK pathway.
the study revealed that PTBP1 facilitates colorectal cancer migration and invasion activities by inclusion of cortactin exon 11
Title: High expression of PTBP1 promote invasion of colorectal cancer by alternative splicing of cortactin.
Overall, the authors find that p27 directly promotes cell invasion by facilitating invadopodia turnover via the Rac1/PAK1/Cortactin pathway.
Title: p27<sup>Kip1</sup> promotes invadopodia turnover and invasion through the regulation of the PAK1/Cortactin pathway.
Tyrosine dephosphorylation of the cytoskeletal scaffold, cortactin, recruits the RhoA antagonist SRGAP1 to relax adherens junctions in response to HGF.
Title: Tyrosine dephosphorylated cortactin downregulates contractility at the epithelial zonula adherens through SRGAP1.
cortactin binds to E-cadherin, and that a posttranslational modification of cortactin, RhoA-induced phosphorylation by protein kinase D1 (PKD1; also known as PRKD1) at S298, impairs adherens junction assembly and supports their dissolution.
Title: Cortactin is a scaffolding platform for the E-cadherin adhesion complex and is regulated by protein kinase D1 phosphorylation.
Unique role for PBF in regulating CTTN function to promote endocrine cell invasion and migration.
Title: Pro-invasive Effect of Proto-oncogene PBF Is Modulated by an Interaction with Cortactin.
AMPK phosphorylation of cortactin followed by SIRT1 deacetylation modulates the interaction of cortactin and cortical-actin in response to shear stress. Functionally, this AMPK/SIRT1 coregulated cortactin-F-actin dynamics is required for endothelial nitric oxide synthase subcellular translocation/activation and is atheroprotective.
Title: AMP-Activated Protein Kinase and Sirtuin 1 Coregulation of Cortactin Contributes to Endothelial Function.

Submit: New GeneRIF Correction See all GeneRIFs (166)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Pr55(Gag)	gag	Cellular biotinylated cortactin (CTTN) protein is incorporated into HIV-1 Gag virus-like particles	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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Bacterial invasion of epithelial cells, organism-specific biosystem (from KEGG)
Bacterial invasion of epithelial cells, organism-specific biosystemMany pathogenic bacteria can invade phagocytic and non-phagocytic cells and colonize them intracellularly, then become disseminated to other cells. Invasive bacteria induce their own uptake by non-ph...
Bacterial invasion of epithelial cells, conserved biosystem (from KEGG)
Bacterial invasion of epithelial cells, conserved biosystemMany pathogenic bacteria can invade phagocytic and non-phagocytic cells and colonize them intracellularly, then become disseminated to other cells. Invasive bacteria induce their own uptake by non-ph...
Clathrin-mediated endocytosis, organism-specific biosystem (from REACTOME)
Clathrin-mediated endocytosis, organism-specific biosystemClathrin-mediated endocytosis (CME) is one of a number of process that control the uptake of material from the plasma membrane, and leads to the formation of clathrin-coated vesicles (Pearse et al, 1...
E-cadherin signaling in the nascent adherens junction, organism-specific biosystem (from Pathway Interaction Database)
E-cadherin signaling in the nascent adherens junction, organism-specific biosystem
E-cadherin signaling in the nascent adherens junction
FGF signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
FGF signaling pathway, organism-specific biosystem
FGF signaling pathway
Hepatitis C and Hepatocellular Carcinoma, organism-specific biosystem (from WikiPathways)
Hepatitis C and Hepatocellular Carcinoma, organism-specific biosystemPathway model based on hub miRNAs and their putative targets from network analysis. - From a set of differentially expressed genes in both chronic HCV (hepatitis C virus) and HCC (hepatocellular carc...
Membrane Trafficking, organism-specific biosystem (from REACTOME)
Membrane Trafficking, organism-specific biosystemThe secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is ma...
N-cadherin signaling events, organism-specific biosystem (from Pathway Interaction Database)
N-cadherin signaling events, organism-specific biosystem
N-cadherin signaling events
Pathogenic Escherichia coli infection, organism-specific biosystem (from KEGG)
Pathogenic Escherichia coli infection, organism-specific biosystemEnteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) are closely related pathogenic strains of Escherichia coli. The hallmark of EPEC/EHEC infections [DS:H00278 H00277] is induction o...
Pathogenic Escherichia coli infection, conserved biosystem (from KEGG)
Pathogenic Escherichia coli infection, conserved biosystemEnteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) are closely related pathogenic strains of Escherichia coli. The hallmark of EPEC/EHEC infections [DS:H00278 H00277] is induction o...
Pathogenic Escherichia coli infection, organism-specific biosystem (from WikiPathways)
Pathogenic Escherichia coli infection, organism-specific biosystemSources: [http://www.genome.jp/kegg/pathway/hsa/hsa05130.html KEGG]
Proteoglycans in cancer, organism-specific biosystem (from KEGG)
Proteoglycans in cancer, organism-specific biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
Proteoglycans in cancer, conserved biosystem (from KEGG)
Proteoglycans in cancer, conserved biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
RHO GTPase Effectors, organism-specific biosystem (from REACTOME)
RHO GTPase Effectors, organism-specific biosystemRHO GTPases regulate cell behaviour by activating a number of downstream effectors that regulate cytoskeletal organization, intracellular trafficking and transcription (reviewed by Sahai and Marshall...
RHO GTPases activate PAKs, organism-specific biosystem (from REACTOME)
RHO GTPases activate PAKs, organism-specific biosystemThe PAKs (p21-activated kinases) are a family of serine/threonine kinases mainly implicated in cytoskeletal rearrangements. All PAKs share a conserved catalytic domain located at the carboxyl terminu...
Shigellosis, organism-specific biosystem (from KEGG)
Shigellosis, organism-specific biosystemShigellosis, or bacillary dysentery, is an intestinal infection caused by Shigella, a genus of enterobacteria. Shigella are potential food-borne pathogens that are capable of colonizing the intestina...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by Rho GTPases, organism-specific biosystem (from REACTOME)
Signaling by Rho GTPases, organism-specific biosystemThe Rho family of small guanine nucleotide binding proteins is one of five generally recognized branches of the Ras superfamily. Like most Ras superfamily members, typical Rho proteins function as bi...
Syndecan-3-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
Syndecan-3-mediated signaling events, organism-specific biosystem
Syndecan-3-mediated signaling events
Tight junction, organism-specific biosystem (from KEGG)
Tight junction, organism-specific biosystemTight junctions (TJs) are essential for establishing a selectively permeable barrier to diffusion through the paracellular space between neighboring cells. TJs are composed of at least three types of...
Tight junction, conserved biosystem (from KEGG)
Tight junction, conserved biosystemTight junctions (TJs) are essential for establishing a selectively permeable barrier to diffusion through the paracellular space between neighboring cells. TJs are composed of at least three types of...
Vesicle-mediated transport, organism-specific biosystem (from REACTOME)
Vesicle-mediated transport, organism-specific biosystemThe transit of proteins and other cargo through the cell requires a cellular transport process in which transported substances are moved in membrane-bounded vesicles. Transported substances are enclo...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

A008X45 (e-PCR)
- UniSTS:23338

D8S2279 (e-PCR)
- UniSTS:473907

EMS1 (e-PCR)
- UniSTS:34626

D11S2382 (e-PCR)
- UniSTS:27473

RH65644 (e-PCR)
- UniSTS:87922

D1S1425 (e-PCR)
- UniSTS:149621

RH46594 (e-PCR)
- UniSTS:65669

RH17764 (e-PCR)
- UniSTS:52918

RH121473 (e-PCR)
- UniSTS:134601

Homology

Homologs of the CTTN gene: The CTTN gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 223 organisms have orthologs with human gene CTTN
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
cadherin binding	HDA more info	PubMed
profilin binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
actin cytoskeleton reorganization	ISS Inferred from Sequence or Structural Similarity more info
actin filament polymerization	IEA Inferred from Electronic Annotation more info
cell motility	ISS Inferred from Sequence or Structural Similarity more info
dendritic spine maintenance	IEA Inferred from Electronic Annotation more info
focal adhesion assembly	ISS Inferred from Sequence or Structural Similarity more info
intracellular protein transport	IMP Inferred from Mutant Phenotype more info	PubMed
lamellipodium organization	ISS Inferred from Sequence or Structural Similarity more info
membrane organization	TAS Traceable Author Statement more info
negative regulation of extrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
neuron projection morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of actin filament polymerization	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of actin filament polymerization	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of smooth muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
receptor-mediated endocytosis	ISS Inferred from Sequence or Structural Similarity more info
regulation of autophagy of mitochondrion	IEA Inferred from Electronic Annotation more info
regulation of axon extension	ISS Inferred from Sequence or Structural Similarity more info
substrate-dependent cell migration, cell extension	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
Golgi apparatus	IDA Inferred from Direct Assay more info
colocalizes_with actin filament	IDA Inferred from Direct Assay more info	PubMed
cell cortex	IDA Inferred from Direct Assay more info	PubMed
cell cortex	ISS Inferred from Sequence or Structural Similarity more info
clathrin-coated pit	ISS Inferred from Sequence or Structural Similarity more info
cortical cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
cytoskeleton	TAS Traceable Author Statement more info	PubMed
cytosol	IDA Inferred from Direct Assay more info
cytosol	TAS Traceable Author Statement more info
dendritic spine	IEA Inferred from Electronic Annotation more info
focal adhesion	HDA more info	PubMed
colocalizes_with growth cone	ISS Inferred from Sequence or Structural Similarity more info
intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
lamellipodium	IDA Inferred from Direct Assay more info	PubMed
lamellipodium	ISS Inferred from Sequence or Structural Similarity more info
mitotic spindle midzone	IEA Inferred from Electronic Annotation more info
plasma membrane	IDA Inferred from Direct Assay more info
podosome	IEA Inferred from Electronic Annotation more info
ruffle	ISS Inferred from Sequence or Structural Similarity more info
colocalizes_with voltage-gated potassium channel complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: src substrate cortactin

Names: 1110020L01Rik; amplaxin; ems1 sequence (mammary tumor and squamous cell carcinoma-associated (p80/85 src substrate); oncogene EMS1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029881.1 RefSeqGene

Range

5001..43079

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001184740.1 → NP_001171669.1 src substrate cortactin isoform c

See identical proteins and their annotated locations for NP_001171669.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses different splice sites in the 3' coding region, which changes reading frame and the termination stop codon, compared to variant 1. The resulting protein (isoform c) has a longer and distinct C-terminus when it is compared to isoform a.

Source sequence(s)

AA325227, BC008799, BC033889, DA716772

Consensus CDS

CCDS53676.1

UniProtKB/Swiss-Prot

Q14247

Related

ENSP00000365745.3, OTTHUMP00000235667, ENST00000376561.7, OTTHUMT00000394097

Conserved Domains (3) summary

pfam02218
Location:231 → 266

HS1_rep; Repeat in HS1/Cortactin

cl05005
Location:288 → 363

TAF4; TATA Binding Protein (TBP) Associated Factor 4 (TAF4) is one of several TAFs that bind TBP and is involved in forming Transcription Factor IID (TFIID) complex

cl17036
Location:459 → 501

SH3; Src Homology 3 domain superfamily
NM_005231.3 → NP_005222.2 src substrate cortactin isoform a

See identical proteins and their annotated locations for NP_005222.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) is the longest transcript.

Source sequence(s)

AK222613, AK291097, BC008799, DA716772

Consensus CDS

CCDS41680.1

UniProtKB/Swiss-Prot

Q14247

UniProtKB/TrEMBL

Q53HG7

Related

ENSP00000301843.8, OTTHUMP00000165962, ENST00000301843.12, OTTHUMT00000259233

Conserved Domains (3) summary

cd11959
Location:496 → 548

SH3_Cortactin; Src homology 3 domain of Cortactin

pfam02218
Location:231 → 266

HS1_rep; Repeat in HS1/Cortactin

cl05005
Location:325 → 400

TAF4; TATA Binding Protein (TBP) Associated Factor 4 (TAF4) is one of several TAFs that bind TBP and is involved in forming Transcription Factor IID (TFIID) complex
NM_138565.2 → NP_612632.1 src substrate cortactin isoform b

See identical proteins and their annotated locations for NP_612632.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an internal segment of sequence, compared to variant 1. The resulting protein (isoform b) has the same N- and C- termini but is shorter when it is compared to isoform a.

Source sequence(s)

AK222613, BC008799, DA716772

Consensus CDS

CCDS8197.1

UniProtKB/Swiss-Prot

Q14247

UniProtKB/TrEMBL

A0A024R5M3, Q53HG7

Related

ENSP00000317189.4, OTTHUMP00000165961, ENST00000346329.7, OTTHUMT00000259232

Conserved Domains (4) summary

cd11959
Location:459 → 511

SH3_Cortactin; Src homology 3 domain of Cortactin

pfam02218
Location:231 → 266

HS1_rep; Repeat in HS1/Cortactin

pfam15927
Location:322 → 359

Casc1_N; Cancer susceptibility candidate 1 N-terminus

cl26557
Location:310 → 445

RNase_E_G; Ribonuclease E/G family

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p12 Primary Assembly

Range

70398506..70436584

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006718447.3 → XP_006718510.1 src substrate cortactin isoform X1

Conserved Domains (3) summary

cd11959
Location:422 → 474

SH3_Cortactin; Src homology 3 domain of Cortactin

pfam02218
Location:157 → 192

HS1_rep; Repeat in HS1/Cortactin

cl05005
Location:251 → 326

TAF4; TATA Binding Protein (TBP) Associated Factor 4 (TAF4) is one of several TAFs that bind TBP and is involved in forming Transcription Factor IID (TFIID) complex
XM_006718448.4 → XP_006718511.1 src substrate cortactin isoform X2

Conserved Domains (1) summary

pfam02218
Location:231 → 266

HS1_rep; Repeat in HS1/Cortactin
XM_017017312.2 → XP_016872801.1 src substrate cortactin isoform X3