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
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
109.20200228	current	GRCh38.p13 (GCF_000001405.39)	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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Mechanistically, RNF128 interference activated the Wnt pathway via simultaneously ubiquitinating CD44/cortactin (CTTN), resulting in CD44 and c-Myc transcription, thus revealed that RNF128 participated in a positive feedback of the Wnt pathway-CD44 loop.
Title: Downregulation of RNF128 activates Wnt/β-catenin signaling to induce cellular EMT and stemness via CD44 and CTTN ubiquitination in melanoma.
We confirmed the link between CTTN overexpression and progression in a large cohort of patients with oral squamous cell carcinoma.
Title: Cortactin expression: Association with disease progression and survival in oral squamous cell carcinoma.
cortactin is mainly expressed in subsets of chronic lymphocytic leukemia and diffuse large b-cell lymphoma and in hairy cell leukemia. Cortactin may represent a novel marker for the differential diagnosis between chronic lymphocytic leukemia and mantle cell lymphoma.
Title: Cortactin expression in non-Hodgkin B-cell lymphomas: a new marker for the differential diagnosis between chronic lymphocytic leukemia and mantle cell lymphoma.
This study reports that both cortactin and fascin-1 play key roles in extracellular vesicle release by regulating endosomal trafficking or invadopodia formation and function.
Title: Cortactin and fascin-1 regulate extracellular vesicle release by controlling endosomal trafficking or invadopodia formation and function.
high expression of miR-545 inhibits EMT in GC and the oncogenic actions of EMS1.
Title: MiRNA-545 negatively regulates the oncogenic activity of EMS1 in gastric cancer.
The results suggest that ATP13A2 recruits HDAC6 to lysosomes to deacetylate CTTN and promotes autophagosome-lysosome fusion and autophagy which are impaired in Parkinson disease patients.
Title: ATP13A2 facilitates HDAC6 recruitment to lysosome to promote autophagosome-lysosome fusion.
High cortactin expression in B-cell acute lymphoblastic leukemia is associated with increased transendothelial migration and bone marrow relapse.
Title: High cortactin expression in B-cell acute lymphoblastic leukemia is associated with increased transendothelial migration and bone marrow relapse.
Patients with myasthenia gravis (MG) without antibodies to the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) have been classified as having double-seronegative myasthenia gravis (dSNMG). The sera from dSNMG patients was screened with 9000 proteins. We identified cortactin, an intracellular protein that interacts with agrin/MuSK favoring AChR aggregation, as a new antigen. Review.
Title: Diagnostic utility of cortactin antibodies in myasthenia gravis.
CTTN phosphorylation is strongly associated with cutaneous squamous cell carcinoma (CSCC) pathogenesis and may serve as a molecular biomarker of CSCC.
Title: The Pathogenic Effect of Cortactin Tyrosine Phosphorylation in Cutaneous Squamous Cell Carcinoma.
Cortactin plays an important role in ROR1-dependent Wnt5a-enhanced CLL-cell migration.
Title: Wnt5a causes ROR1 to complex and activate cortactin to enhance migration of chronic lymphocytic leukemia cells.

Submit: New GeneRIF Correction See all GeneRIFs (182)

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

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: 239 organisms have orthologs with human gene CTTN
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
actin filament binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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 axon extension	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of dendritic spine morphogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of smooth muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
postsynaptic actin cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info	PubMed
receptor-mediated endocytosis	ISS Inferred from Sequence or Structural Similarity more info
regulation of actin filament polymerization	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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 actin cytoskeleton	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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
dendrite	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info
podosome	IEA Inferred from Electronic Annotation more info
postsynaptic density	IBA Inferred from Biological aspect of Ancestor more info	PubMed
postsynaptic membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
ruffle	ISS Inferred from Sequence or Structural Similarity more info
site of polarized growth	IBA Inferred from Biological aspect of Ancestor more info	PubMed
colocalizes_with voltage-gated potassium channel complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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); epididymis secretory sperm binding protein; 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

5024..43070

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001184740.2 → 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, BC033889, DA716772

Consensus CDS

CCDS53676.1

UniProtKB/Swiss-Prot

Q14247

Related

ENSP00000365745.3, ENST00000376561.7

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_005231.4 → 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, ENST00000301843.13

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, ENST00000346329.7

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 Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p13 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