CTTN

Summary

CTTN (cortactin, HGNC:3338) is a protein-coding gene on chromosome 11q13.3, encoding Src substrate cortactin (Q14247). Contributes to the organization of the actin cytoskeleton and cell shape.

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.

Source: NCBI Gene 2017 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 132 total
• Druggable target: yes
• MANE Select transcript: NM_005231

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3338
Approved symbol	CTTN
Name	cortactin
Location	11q13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000085733
Ensembl biotype	protein_coding
OMIM	164765
Entrez	2017

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 24 protein_coding, 8 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000301843, ENST00000346329, ENST00000376561, ENST00000393747, ENST00000415461, ENST00000482755, ENST00000483662, ENST00000498223, ENST00000525276, ENST00000525852, ENST00000527622, ENST00000527962, ENST00000529736, ENST00000532334, ENST00000533931, ENST00000882295, ENST00000882296, ENST00000882297, ENST00000882298, ENST00000882299, ENST00000882300, ENST00000938470, ENST00000938471, ENST00000938472, ENST00000938473, ENST00000938474, ENST00000938475, ENST00000938476, ENST00000938477, ENST00000938478, ENST00000938479, ENST00000938480, ENST00000947761, ENST00000947762, ENST00000947763

RefSeq mRNA: 3 — MANE Select: NM_005231 NM_001184740, NM_005231, NM_138565

CCDS: CCDS41680, CCDS53676, CCDS8197

Canonical transcript exons

ENST00000301843 — 18 exons

Exon	Start	End
ENSE00001064326	70419746	70419856
ENSE00001064327	70417013	70417123
ENSE00001064328	70415663	70415717
ENSE00001064329	70420400	70420510
ENSE00001064330	70414542	70414652
ENSE00001119698	70405265	70405361
ENSE00001230269	70421470	70421580
ENSE00001330492	70398529	70398614
ENSE00001893938	70435026	70436575
ENSE00003524160	70433101	70433278
ENSE00003538982	70433647	70433718
ENSE00003588443	70431191	70431280
ENSE00003646170	70407518	70407591
ENSE00003660953	70425332	70425401
ENSE00003674546	70409831	70409960
ENSE00003681810	70422940	70422995
ENSE00003684603	70407298	70407384
ENSE00003693785	70429051	70429199

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 99.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 82.9574 / max 1063.6702, expressed in 1694 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115666	82.4503	1693
115670	0.3567	164
115669	0.1504	53

Top tissues by expression

141 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.25	gold quality
left ovary	UBERON:0002119	99.21	gold quality
body of uterus	UBERON:0009853	99.21	gold quality
right ovary	UBERON:0002118	99.19	gold quality
ovary	UBERON:0000992	99.12	gold quality
right adrenal gland cortex	UBERON:0035827	99.09	gold quality
mucosa of stomach	UBERON:0001199	99.05	gold quality
myometrium	UBERON:0001296	99.05	gold quality
right adrenal gland	UBERON:0001233	99.04	gold quality
endocervix	UBERON:0000458	99.00	gold quality
right uterine tube	UBERON:0001302	99.00	gold quality
metanephros cortex	UBERON:0010533	99.00	gold quality
left adrenal gland cortex	UBERON:0035825	98.98	gold quality
left adrenal gland	UBERON:0001234	98.96	gold quality
vagina	UBERON:0000996	98.95	gold quality
ascending aorta	UBERON:0001496	98.94	gold quality
thoracic aorta	UBERON:0001515	98.93	gold quality
descending thoracic aorta	UBERON:0002345	98.93	gold quality
pituitary gland	UBERON:0000007	98.88	gold quality
adrenal gland	UBERON:0002369	98.87	gold quality
ectocervix	UBERON:0012249	98.86	gold quality
tibial nerve	UBERON:0001323	98.84	gold quality
uterine cervix	UBERON:0000002	98.82	gold quality
right lobe of thyroid gland	UBERON:0001119	98.81	gold quality
left lobe of thyroid gland	UBERON:0001120	98.81	gold quality
skin of leg	UBERON:0001511	98.80	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.78	gold quality
left uterine tube	UBERON:0001303	98.77	gold quality
thyroid gland	UBERON:0002046	98.77	gold quality
lower esophagus	UBERON:0013473	98.77	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-75688	yes	4885.70
E-MTAB-6678	yes	204.09
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT3, TXK

miRNA regulators (miRDB)

50 targeting CTTN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-3685	99.62	68.83	1621

Literature-anchored findings (GeneRIF, showing 40)

• The structure and membrane orientation of this large enigmatic protein was characterized by raising and employing antibodies directed against discrete Odz polypeptide regions. (PMID:11964164)
• the odz gene is required for multiple cell types in the compound retina (PMID:17685476)
• Data indicate that during embryonic development, the expression of Filamin and Ten-m partially overlap in ectodermal cells. (PMID:21857973)
• identification of two evolutionarily conserved, epidermal growth factor (EGF)-repeat containing transmembrane Teneurin proteins, Ten-m and Ten-a, as synaptic-partner-matching molecules between projection neuron dendrites and olfactory receptor neuron axons (PMID:22425994)
• study identifies the Teneurins as a key bi-directional trans-synaptic signal involved in general synapse organization, and demonstrates that proteins such as these can also regulate target selection (PMID:22426000)
• Ten-m acts in projection neurons autonomously to regulate acetylcholine receptor cluster number and transsynaptically to regulate olfactory receptor neurons active zone number. (PMID:25310239)
• Ten-m/Odz may have had an ancient role in cell-cell communication, parallel to the Notch and wnt pathways. The Ten-m protein binds to the membrane with properties which resemble other membrane-based biochemical oscillators. The oscillatory properties of Ten-m may play a seminal role in arthropod segmentation. (PMID:28461810)
• substrate for caspase cleavage during apoptosis (PMID:11689006)
• Primary arrest of circulating platelets on collagen involves phosphorylation of Syk, cortactin and focal adhesion kinase (PMID:11988077)
• The Src-cortactin pathway is required for clustering of E-selectin and ICAM-1 in endothelial cells (PMID:12060669)
• Cdc42/Rac1-dependent activation of PAK may trigger early platelet shape change, at least in part through the regulation of cortactin binding to PAK. (PMID:12453877)
• cortactin links receptor endocytosis to actin polymerization by binding both CD2AP and the Arp2/3 complex, which may facilitate the trafficking of internalized growth factor receptors (PMID:12672817)
• alternative splicing of the F-actin binding domain of cortactin is a new mechanism by which cortactin influences cell migration (PMID:12952985)
• cortactin and EC myosin light chain kinase have roles in mediating lung vascular barrier augmentation evoked by S1P (PMID:15056655)
• RhoGAP functionally interacts with cortactin and represents a novel determinant in the regulation of cell dynamics. (PMID:15064355)
• Data suggest that hyaluronan-CD44 interaction with Rac1-protein kinase N gamma plays a pivotal role in phospholipase C gamma1-regulated calcium signaling and cortactin-cytoskeleton function required for keratinocyte cell-cell adhesion and differentiation. (PMID:15123640)
• HAX-1 binds bile salt export protein (BSEP), cortactin, MDR1, and MDR2. HAX-1 and cortactin regulate BSEP abundance in the apical membrane of cells. (PMID:15159385)
• Erk phosphorylation liberates the SH3 domain of cortactin from intramolecular interactions with proline-rich regions, causing it to synergize with WASP and N-WASP in activating the Arp2/3 complex (PMID:15169891)
• Suppression of cortactin expression with a cortactin antisense oligo significantly impaired S1P-induced capillary formation, migration of endothelial cells, and actin assembly at the cell periphery. (PMID:15242766)
• a major role for a Crk-cortactin complex in actin polymerization downstream of tyrosine kinase signaling (PMID:15263018)
• Overexpression of cortactin may play a role in the metastasis of HCC by influencing cell motility, and cortactin could be a sensitive marker for HCC with intrahepatic metastasis. (PMID:15464244)
• cortactin can restrict N-WASP localization around EGF-bead-induced protrusions (PMID:15579908)
• The p47phox:actin interaction, through cortactin, plays an important role in Ang II-mediated site-directed assembly of functionally active NAD(P)H oxidase, ROS generation, and activation of redox-sensitive p38MAP kinase and Akt, but not ERK1/2. (PMID:15618548)
• EMS1 amplification parallels with the progress of oral carcinogenesis. (PMID:15842855)
• Cortactin promotes cell motility by enhancing lamellipodial persistence, at least in part through regulation of Arp2/3 complex. (PMID:16051170)
• Cortactin recruitment is dependent on the activation of a phosphoinositide-3-kinase/Rac1-GTPase signalling pathway, which is required for actin polymerization and internalization of N. meningitidis. (PMID:16076899)
• Our results demonstrated the dominant expression of p85 form of cortactin in colorectal cancer for the first time. (PMID:16261345)
• cortactin is the crucial gene within the 11q13 amplicon that mediates the invasive potential of human carcinomas (PMID:16280034)
• Tyrosine phosphorylation of cortactin by Src family kinases regulates neutrophil transmigration. (PMID:16385081)
• We describe that S1P-stimulated cortactin translocation to the cell periphery to form lamellipodia is specifically mediated by the endothelial S1P1 G-protein coupled receptor, and is regulated by G(i)-mediated Akt-dependent S1P1 receptor phosphorylation. (PMID:16416022)
• Co-localization of cortactin and phosphotyrosine identifies invadopodial complexes closely associated with the plasma membrane at active sites of focal degradation of the extracellular matrix in breast cancer cells. (PMID:16442522)
• Our findings suggest that cortactin plays a role in Listeria internalization, but not in the formation of actin clouds and tails, or in bacteria intracellular motility. (PMID:16489553)
• Increased levels of cortactin, as found in human carcinomas, promote cell migration and invasion by reducing cell spreading and intercellular adhesive strength. (PMID:16527272)
• Cortactin is a requirement for pedestal formation and suggest a novel function for the predicted alpha-helical region of cortactin in actin assembly induced by EPEC and EHEC. (PMID:16611226)
• Results suggest that the AMAP1/cortactin complex, which is not detected in normal mammary epithelial cells, is an excellent drug target for cancer therapeutics. (PMID:16636290)
• functional importance of cortactin to CD44s-promoted metastasis was demonstrated by selective suppression of cortactin in CD44-expressing MCF7F-B5 and MDA-MB-231 breast cancer cells using RNAi (PMID:16652145)
• EMS1 amplification is uncommon and appears to be late event in the development of ethmoid sinus adenocarcinoma. (PMID:16815198)
• The identification of 17 new sites of phosphorylation in cortactin is reported. (PMID:16825425)
• Results suggest that ATP-mediated barrier protection is associated with cytoskeletal activation and is dependent on both Rac activation and cortactin. (PMID:16825658)
• Plays important role in CXCR4 signaling and trafficking as well as in receptor-mediated cell migration. (PMID:16905744)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cttn	ENSDARG00000011777
mus_musculus	Cttn	ENSMUSG00000031078
rattus_norvegicus	Cttn	ENSRNOG00000050994

Paralogs (4): COTL1 (ENSG00000103187), DBN1 (ENSG00000113758), DBNL (ENSG00000136279), HCLS1 (ENSG00000180353)

Protein

Protein identifiers

Src substrate cortactin — Q14247 (reviewed: Q14247)

Alternative names: Amplaxin, Oncogene EMS1

All UniProt accessions (3): Q14247, H0YCD9, H0YEV2

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Part of a complex composed of NEDD9, AURKA and CTTN; within the complex NEDD9 acts as a scaffold protein and is required for complex formation. Interacts (via N-terminus) with NEDD9. Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Forms a complex made of ABL1 and MYLK. Interacts with SHANK2 and SHANK3 (via its SH3 domain). Interacts with FGD1. Interacts with ABL2. Interacts with KCNA2 (via non-phosphorylated C-terminus). Interacts with PLXDC2 and SRCIN1. Interacts with SAMSN1 (via SH3 domain). Interacts (via SH3 domain) with ASAP1 (via Pro-rich region). Interacts (via SH3 domain) with DNM2. Interacts with ACTN1. Interacts with FER. 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. Interacts with KCNH1. Interacts (via SH3 domain) with DIP2A (via N-terminus); the interaction enhances CTTN acetylation and is required for proper synaptic transmission. Interacts with XIRP1 (via N-terminus); the interaction promotes CTTN localization to intercalated disks in cardiomyocytes.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Lamellipodium. Ruffle. Dendrite. Cell membrane. Podosome. Cell junction. Focal adhesion. Membrane. Clathrin-coated pit. Dendritic spine. Cell cortex. Endoplasmic reticulum.

Post-translational modifications. 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 associates with filamentous actin. Phosphorylated on tyrosine residues in response to CHRM1 activation. Phosphorylated by PTK2/FAK1 in response to cell adhesion. Phosphorylated by FER. Tyrosine phosphorylation in transformed cells may contribute to cellular growth regulation and transformation. Phosphorylated in response to FGR activation. Phosphorylation by SRC promotes MYLK binding. Acetylated.

Domain organisation. The SH3 motif may mediate binding to the cytoskeleton.

Isoforms (3)

UniProt ID	Names	Canonical?
Q14247-1	1	yes
Q14247-2	2
Q14247-3	3

RefSeq proteins (3): NP_001171669, NP_005222, NP_612632 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR003134	Hs1_Cortactin	Repeat
IPR035716	Cortactin_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily

Pfam: PF02218, PF14604

UniProt features (66 total): modified residue 36, repeat 7, cross-link 6, strand 6, region of interest 2, compositionally biased region 2, splice variant 2, chain 1, coiled-coil region 1, sequence conflict 1, helix 1, domain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2D1X	X-RAY DIFFRACTION	1.9
1X69	SOLUTION NMR
9EZN	SOLUTION NMR
9EZO	SOLUTION NMR
9EZP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14247-F1	63.11	0.18

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (42): 87, 107, 113, 119, 124, 144, 150, 152, 161, 171, 181, 193, 198, 235, 261, 272, 295, 304, 309, 314 …

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5627123	RHO GTPases activate PAKs
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 394 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, JI_RESPONSE_TO_FSH_UP, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_FOCAL_ADHESION_ASSEMBLY, MENSE_HYPOXIA_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY

GO Biological Process (21): intracellular protein transport (GO:0006886), receptor-mediated endocytosis (GO:0006898), substrate-dependent cell migration, cell extension (GO:0006930), signal transduction (GO:0007165), actin cytoskeleton organization (GO:0030036), regulation of axon extension (GO:0030516), positive regulation of actin filament polymerization (GO:0030838), positive regulation of smooth muscle contraction (GO:0045987), focal adhesion assembly (GO:0048041), neuron projection morphogenesis (GO:0048812), cell motility (GO:0048870), positive regulation of chemotaxis (GO:0050921), regulation of cell projection assembly (GO:0060491), dendritic spine maintenance (GO:0097062), extrinsic apoptotic signaling pathway (GO:0097191), lamellipodium organization (GO:0097581), modification of postsynaptic actin cytoskeleton (GO:0098885), regulation of mitophagy (GO:1901524), negative regulation of extrinsic apoptotic signaling pathway (GO:2001237), endocytosis (GO:0006897), modification of postsynaptic structure (GO:0099010)

GO Molecular Function (5): profilin binding (GO:0005522), cadherin binding (GO:0045296), proline-rich region binding (GO:0070064), Arp2/3 complex binding (GO:0071933), protein binding (GO:0005515)

GO Cellular Component (28): ruffle (GO:0001726), podosome (GO:0002102), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cytoskeleton (GO:0005856), actin filament (GO:0005884), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), focal adhesion (GO:0005925), cell cortex (GO:0005938), voltage-gated potassium channel complex (GO:0008076), lamellipodium (GO:0030027), endocytic vesicle (GO:0030139), growth cone (GO:0030426), cortical cytoskeleton (GO:0030863), dendritic spine (GO:0043197), postsynaptic actin cytoskeleton (GO:0098871), glutamatergic synapse (GO:0098978), mitotic spindle midzone (GO:1990023), membrane (GO:0016020), cell junction (GO:0030054), dendrite (GO:0030425), cell projection (GO:0042995), synapse (GO:0045202), anchoring junction (GO:0070161), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
RHO GTPase Effectors	1
Membrane Trafficking	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Vesicle-mediated transport	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
endomembrane system	3
cellular process	2
protein binding	2
cell leading edge	2
plasma membrane bounded cell projection	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
actin cytoskeleton	2
membrane	2
cell periphery	2
postsynapse	2
intracellular protein localization	1
protein transport	1
intracellular transport	1
endocytosis	1
substrate-dependent cell migration	1
plasma membrane bounded cell projection assembly	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytoskeleton organization	1
actin filament-based process	1
regulation of developmental growth	1
axon extension	1
regulation of extent of cell growth	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
smooth muscle contraction	1
regulation of smooth muscle contraction	1
positive regulation of muscle contraction	1
cell-substrate junction assembly	1
cell-matrix adhesion	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
chemotaxis	1

Protein interactions and networks

STRING

4494 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTTN	WASL	O00401	997
CTTN	SRC	P12931	997
CTTN	CFL2	Q9Y281	995
CTTN	CFL1	P23528	995
CTTN	PXN	P49023	994
CTTN	WAS	P42768	994
CTTN	TJP1	Q07157	989
CTTN	HDAC6	Q9UBN7	989
CTTN	SCIN	Q9Y6U3	985
CTTN	GSN	P06396	985
CTTN	DNM2	P50570	983
CTTN	CTTNBP2	Q8WZ74	973
CTTN	SH3PXD2A	Q5TCZ1	971
CTTN	WIPF1	O43516	970
CTTN	VCL	P18206	966

IntAct

234 interactions, top by confidence:

A	B	Type	Score
ASAP1	CTTN	psi-mi:“MI:0915”(physical association)	0.770
CTTN	HDAC6	psi-mi:“MI:0407”(direct interaction)	0.720
CTTN	HDAC6	psi-mi:“MI:0915”(physical association)	0.720
HDAC6	CTTN	psi-mi:“MI:0915”(physical association)	0.720
CTTN	HDAC6	psi-mi:“MI:0403”(colocalization)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
EGFR	CTTN	psi-mi:“MI:0915”(physical association)	0.630
Kcnma1	CTTN	psi-mi:“MI:0915”(physical association)	0.590
CTTN	tir	psi-mi:“MI:0407”(direct interaction)	0.540
tir	CTTN	psi-mi:“MI:0915”(physical association)	0.540
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
SH2D4A	TF	psi-mi:“MI:0914”(association)	0.530
Srcin1	CTTN	psi-mi:“MI:0915”(physical association)	0.500
CTTN	Cbll1	psi-mi:“MI:0915”(physical association)	0.500
Cbll1	CTTN	psi-mi:“MI:0915”(physical association)	0.500
CTTN	ACTR3	psi-mi:“MI:0403”(colocalization)	0.490
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (598): SPRR2A (Reconstituted Complex), CTTN (Affinity Capture-MS), CTTN (Affinity Capture-MS), CTTN (Two-hybrid), CTTN (Two-hybrid), WIPF1 (Two-hybrid), COPS7A (Co-fractionation), HEXIM1 (Co-fractionation), MYO1E (Co-fractionation), USO1 (Co-fractionation), CTTN (Affinity Capture-MS), CTTN (Affinity Capture-MS), CTTN (Proximity Label-MS), CTTN (Affinity Capture-MS), CTTN (Affinity Capture-MS)

ESM2 similar proteins: A0MZ66, A0MZ67, A2APB8, A4IH24, A4UGR9, A6H6Z7, A9JRM0, D4A702, E7F7X0, O35867, O60566, P13505, P14317, P49710, Q14247, Q1LVV0, Q28IH8, Q2MJV9, Q3B820, Q3MHH7, Q4KM62, Q4R6Q9, Q4U4S6, Q5E9V3, Q5NVK0, Q5PZ43, Q5R6I2, Q5RAF2, Q60598, Q66HL2, Q66KE9, Q6AYN9, Q6DDV8, Q6DFB7, Q6NUF4, Q6P0R8, Q6ZUJ8, Q71LX6, Q7T0S7, Q80ZU5

Diamond homologs: A3LXQ8, A6H7G2, A6ZR73, A7MBI0, B3LRN4, B5VHP4, B8R1V5, C4Y1G1, C7GKW5, E7KBW4, E7KMS3, E7LTJ6, E7Q311, E7QE10, G5EC32, O13154, O35179, O35180, O42287, O60861, O74749, O75886, O76041, O77506, O88811, P08487, P10569, P10686, P14317, P18302, P19174, P20929, P34121, P34416, P40073, P49710, P70297, Q01406, Q07266, Q09822

SIGNOR signaling

45 interactions.

A	Effect	B	Mechanism
PRKD1	down-regulates	CTTN	phosphorylation
MAPK1	up-regulates	CTTN	phosphorylation
MAPK3	up-regulates	CTTN	phosphorylation
PAK1	up-regulates	CTTN	phosphorylation
CTTN	“up-regulates activity”	ARP2/3	binding
CTTN	up-regulates	Dendritic_spine_morphogenesis
NMDA	“up-regulates quantity”	CTTN	relocalization
“NMDA receptor_2A”	“up-regulates quantity”	CTTN	relocalization
“NMDA receptor_2B”	“up-regulates quantity”	CTTN	relocalization
“NMDA receptor_2C”	“up-regulates quantity”	CTTN	relocalization
“NMDA receptor_2D”	“up-regulates quantity”	CTTN	relocalization
Gbeta	up-regulates	CTTN	phosphorylation
ERK1/2	up-regulates	CTTN	phosphorylation
PTPN6	“down-regulates activity”	CTTN	dephosphorylation
PTPN1	“up-regulates activity”	CTTN	dephosphorylation
PTK2	“down-regulates activity”	CTTN	phosphorylation
PTK2B	“up-regulates activity”	CTTN	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 187 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RHO GTPases activate PAKs	5	20.8×	2e-04
Parasite infection	7	18.5×	8e-06
Leishmania phagocytosis	7	18.5×	8e-06
Signaling by RAS mutants	5	16.1×	6e-04
Fcgamma receptor (FCGR) dependent phagocytosis	7	14.9×	3e-05
RHO GTPases Activate WASPs and WAVEs	6	14.5×	2e-04
FCGR3A-mediated phagocytosis	10	14.3×	7e-07
Sensory processing of sound	6	14.1×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of synaptic vesicle endocytosis	5	27.9×	6e-04
cellular response to reactive oxygen species	5	12.9×	6e-03
establishment or maintenance of cell polarity	5	12.6×	6e-03
cellular response to type II interferon	9	11.8×	1e-04
platelet aggregation	5	10.6×	8e-03
epidermal growth factor receptor signaling pathway	6	9.3×	6e-03
negative regulation of translation	7	8.6×	5e-03
actin filament organization	8	6.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

132 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	90
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3613 predictions. Top by Δscore:

Variant	Effect	Δscore
11:70407423:TGG:T	donor_gain	1.0000
11:70407425:G:GT	donor_gain	1.0000
11:70407512:TTTCA:T	acceptor_loss	1.0000
11:70407513:TTCA:T	acceptor_loss	1.0000
11:70407514:TCA:T	acceptor_loss	1.0000
11:70407515:CA:C	acceptor_loss	1.0000
11:70407516:A:AG	acceptor_gain	1.0000
11:70407516:A:C	acceptor_loss	1.0000
11:70407516:AGAAT:A	acceptor_gain	1.0000
11:70407517:G:GA	acceptor_gain	1.0000
11:70407517:GA:G	acceptor_gain	1.0000
11:70407517:GAA:G	acceptor_gain	1.0000
11:70407517:GAAT:G	acceptor_gain	1.0000
11:70407517:GAATG:G	acceptor_gain	1.0000
11:70407592:G:GG	donor_gain	1.0000
11:70407727:G:GG	donor_gain	1.0000
11:70409825:A:AG	acceptor_gain	1.0000
11:70409826:T:G	acceptor_gain	1.0000
11:70409828:A:AG	acceptor_gain	1.0000
11:70409829:A:G	acceptor_gain	1.0000
11:70409830:G:GG	acceptor_gain	1.0000
11:70414534:T:A	acceptor_gain	1.0000
11:70414540:A:AG	acceptor_gain	1.0000
11:70414541:G:GA	acceptor_gain	1.0000
11:70414541:GT:G	acceptor_gain	1.0000
11:70414541:GTC:G	acceptor_gain	1.0000
11:70414541:GTCA:G	acceptor_gain	1.0000
11:70414651:AGG:A	donor_loss	1.0000
11:70414653:G:C	donor_loss	1.0000
11:70417011:A:AG	acceptor_gain	1.0000

AlphaMissense

3649 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:70407361:T:A	W22R	1.000
11:70407361:T:C	W22R	1.000
11:70407363:G:C	W22C	1.000
11:70407363:G:T	W22C	1.000
11:70433698:C:A	A499D	1.000
11:70435094:T:A	W529R	1.000
11:70435094:T:C	W529R	1.000
11:70435096:G:C	W529C	1.000
11:70435096:G:T	W529C	1.000
11:70435103:G:T	G532W	1.000
11:70435104:G:A	G532E	1.000
11:70435131:T:C	F541S	1.000
11:70407379:T:C	F28L	0.999
11:70407381:T:A	F28L	0.999
11:70407381:T:G	F28L	0.999
11:70407544:A:C	R38S	0.999
11:70407544:A:T	R38S	0.999
11:70407545:T:A	W39R	0.999
11:70407545:T:C	W39R	0.999
11:70409842:T:C	L58P	0.999
11:70433692:C:A	A497D	0.999
11:70435047:T:C	F513S	0.999
11:70435065:T:A	I519N	0.999
11:70435065:T:G	I519S	0.999
11:70435095:G:C	W529S	0.999
11:70435097:T:A	W530R	0.999
11:70435097:T:C	W530R	0.999
11:70435103:G:A	G532R	0.999
11:70435103:G:C	G532R	0.999
11:70435125:G:A	G539E	0.999

dbSNP variants (sampled 300 via entrez): RS1000011739 (11:70428679 C>T), RS1000091501 (11:70421408 T>A,C), RS1000147458 (11:70414181 T>A), RS1000243801 (11:70424526 G>A,T), RS1000289099 (11:70409721 G>C), RS1000293673 (11:70409249 A>C,G), RS1000366715 (11:70414046 G>A,C), RS1000454306 (11:70429176 G>A,C), RS1000455043 (11:70433784 C>G), RS1000469437 (11:70415163 C>G,T), RS1000508855 (11:70428971 C>T), RS1000595780 (11:70410339 A>G), RS1000621958 (11:70400217 C>T), RS1000710415 (11:70415036 G>A), RS1000764084 (11:70405707 G>A)

Disease associations

OMIM: gene MIM:164765 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295820 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.27	Kd	53.56	nM	CHEMBL3752910
7.22	ED50	60.52	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148179: Binding affinity to human CTTN incubated for 45 mins by Kinobead based pull down assay	kd	0.0536	uM

CTD chemical–gene interactions

94 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	4
bisphenol A	increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Acetaminophen	decreases expression, increases expression, affects cotreatment	2
Cisplatin	increases expression, affects cotreatment	2
Fluorouracil	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	affects cotreatment, increases expression, decreases expression	2
Cyclosporine	increases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
chloroacetaldehyde	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, increases expression	1
titanium dioxide	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
hydroxyhydroquinone	increases expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
nickel subsulfide	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
ochratoxin A	decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
nefazodone	affects cotreatment, increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118757	Binding	Binding affinity to CTTN in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2VG	Abcam HEK293T CTTN KO	Transformed cell line	Female
CVCL_SK17	HAP1 CTTN (-) 1	Cancer cell line	Male
CVCL_SK18	HAP1 CTTN (-) 2	Cancer cell line	Male
CVCL_SK19	HAP1 CTTN (-) 3	Cancer cell line	Male
CVCL_SK20	HAP1 CTTN (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.