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FLASH GENE

Symbol

PTK2

contributors: shn/npt/pgu - updated : 14-02-2017

HGNC name	PTK2 protein tyrosine kinase 2
HGNC id	9611

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	8q24.3      Physical location : 141.668.501 - 142.011.332
Synonym name	focal adhesion kinase 1
Synonym symbol(s)	FAK1, FADK, pp125FAK, FAK
EC.number	2.7.10.1, 2.7.10.2

DNA

TYPE	functioning gene
STRUCTURE	342.83 kb     32 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	cytosine-phosphate-guanine/HTF
	Binding site   transcription factor
text structure	5'-flanking region is GC-rich and contains several potential transcription factor binding sites, including two NF-kappa B and p53 binding sites
	promoter contains four potential NANOG- binding sites with conserved TAA(T/A)TTA sequence, and mutation of the NANOG-binding sites in the PTK2 promoter inhibits up-regulation of PTK2 promoter activity, confirming that NANOG binds the four sites in the PTK2 promoter sequence
	ETV4-binding site between nucleotides -170 and +43 in the PTK2 promoter that was critical for the responsiveness to ETV4

MAPPING

cloned

Y

linked

N

status

confirmed

Map	pter - D8S1743 - D8S1717 - PTK2 - D8S1727 - D8S1713 - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005607 (transcript variant 2) 32 splicing 4442 NP_005598 - 1074 - 2004 15157737 NM_153831 (transcript variant 1) 32 splicing 4453 NP_722560 - 1052 - 2004 15157737

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth       highly Endocrine thyroid       moderately Nervous brain       moderately Reproductive male system testis     moderately Homo sapiens Respiratory respiratory tract larynx     highly   respiratory tract trachea     highly Urinary bladder       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune lymphocyte Reproductive Sertoli cell Homo sapiens

cell lineage
cell lines	lymphoid cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal FERM domain arranges into three lobes and regulates its kinase activity, and including a nuclear export signal NES1, and implicated in events at the cell cortex and in the nucleus that are crucial to cell behaviour and life-or-death decisions
	a protein kinase domain including a nuclear export signal NES2
	a NT2 domain, overexpressed and co-localized with IGF1R in pancreatic cells
	focal adhesion targeting (FAT) domain binds specifically to the CD4 endocytosis motif
	C-terminal domain can bind to a number of proteins, such as paxillin, talin, phosphoinositide 3-kinases (PI3 K) and the GTPase-activating protein ARHGAP26, leading to the localization of FAK to focal adhesions and reorganization of the actin cytoskeleton

conjugated

Other

HOMOLOGY

interspecies	ortholog to Ptk2, Rattus norvegicus
	ortholog to Ptk2, Mus musculus
	ortholog to PTK2, Pan troglodytes
	homolog to zgc:66114, Danio rerio

Homologene

FAMILY

FAK subfamily of protein tyrosine kinases

CATEGORY

adhesion , enzyme , immunity/defense , regulatory

SUBCELLULAR LOCALIZATION	plasma membrane,junction
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule
	intracellular,nucleus,nucleoplasm,nuclear bodies
	intracellular,nucleus,nucleolus
text	localized to focal adhesions
	lamellipodium
	apical plasma membrane
	nuclear translocation of PTK2 reduces contact between PTK2 and SRC

basic FUNCTION	non receptor, protein tyrosine kinase, focal adhesion kinase, playing an important role in the response of migrating cells to mechanical input
	mediating a direct interaction with the C terminal SH2 domain of phospholipase C (PCLG1)
	primary mediator of integrin signaling after integrin mediated cell adhesion and PTK2 phosphorylation
	involved in cell mobility
	playing a potential role in oncogenic transformations resulting in increased kinase activity
	plays crucial role in a variety of intracellular signaling, such as migration, proliferation, differentiation, and adhesion
	promotes cell migration by regulating focal adhesion formation and turnover through multiple signaling connections
	playing a necessary role for cell migration and tube formation
	may be a critical signaling component involved in the regulation of angiogenesis
	is functioning in cell migration, but fibril-forming collagen-induced PTK2 degradation is necessary for endothelial tube formation
	SRC and PTK2 cooperate to phosphorylate GIT2, stimulate its focal adhesion localization, and regulate cell spreading and protrusiveness
	plays a critical role in transformation and tumorigenesis and is aberrantly upregulated in many types of cancer
	central component in integrin signalling, and in T lymphocytes, with CD4 localise to the same signalling complexes after stimulation by either the human immunodeficiency virus (HIV) gp120 glycoprotein or an antigen
	mediates activation-loop independent phosphorylation, as well as Akt and ERK activation
	playing a role in phosphorylation, signaling and stability of the IGF1R
	critical tyrosine kinase that modulates cell adhesion, migration, proliferation and survival in response to extracellular signals
	EMP2-FAK association is a significant functional cellular responses in the context of in vitro models of proliferative vitreoretinopathy
	acts as a pivotal signal 'integrator', controlling and coordinating cellular responses that include cell migration, survival, proliferation and, epithelial tissue repair after DNA damage
	PTK2 and IQGAP1 regulate melusin-dependent cardiomyocyte hypertrophy and survival through MAPK1/MAPK3 activation
	controls filopodia formation and actin nucleation during axonal development
	regulates intestinal epithelial barrier function via redistribution of tight junction
	involved in cell adhesion and, in neurons, and plays a role in axonal guidance, and neurite growth and attraction
	distinct kinase-dependent and -independent activities of PTK2 differentially regulate luminal progenitors and basal mammary stem cells

CELLULAR PROCESS	cell life, proliferation/growth
	cell life, cell death/apoptosis
	cell organization/biogenesis
	cell migration & motility

PHYSIOLOGICAL PROCESS

coagulation/hemostasis , development , immunity/defense , inflammation

text	angiogenesis
	central nervous system neuron axonogenesis
	endothelial cell migration
	microtubule cytoskeleton organization and biogenesis
	neuron migration

PATHWAY

metabolism

signaling

signal transduction

a component	PTK2/ELK1 complex is found, mainly, in the cytoplasm, near the nuclear membrane periphery, raising the possibility that ELK1 may have alternative extranuclear function
	PTK2-CD4 complex represents an alternative route for eliciting T-cell-specific signals and it links gp120 engagement to distinctive T-cell signalling during HIV infection
	part of PTK2-RASA1-GRLF1 complex that regulates polarity in migrating cells
	within FAC (focal adhesion complex), the focal adhesion kinase (PTK2) and PTK2B are believed to act as important scaffolding proteins
	ABCB1 and an integrated component of the occludin/zonula occludens 1 (TJP1) adhesion complex at the BTB, structurally interacted with PTK2, creating the OCLN/TJP1/PTK2/ABCB1 regulatory complex
	PTK2 formed a complex with its E2 enzyme, UBE2H, and E3 enzyme, TRIM72

INTERACTION

DNA

RNA

small molecule

nucleotide,

ATP

protein	growth factor receptor-bound protein 2, GBR2
	Crk-associated tyrosine kinase substrate p130Cas
	talin 1, TLN1
	Rho GTPase activating protein 26, ARHGAP26
	neural precursor cell expressed, developmentally down-regulated 9, NEDD9
	Syk protein-tyrosine kinase, Syk
	protein tyrosine kinase 2 beta, PTK2B
	transforming growth factor beta 1 induced transcript 1, TGFB1I1
	c-Cbl-associated protein, CAP
	Janus kinase 2, JAK2
	insulin receptor substrate 1, IRS1
	embryonal Fyn-associated substrate, Efs
	growth factor receptor-bound protein 7, GBR7
	phosphatase and tensin homolog, PTEN
	PDGF- and EGF-receptor (PDGFR and EGFR) signalling complexes
	EPH receptor A2, EPHA2
	polycystic kidney disease 1, PKD1
	transforming growth factor beta 1 induced transcript 1, TGFB1I1
	interaction between the PH domain of Etk and the FERM domain of FAK
	Ezrin, EZR
	ArfGAP with SH3 domain, ankyrin repeat and PH domain 1, ASAP1
	c-Jun N-terminal kinase (JNK)/stress activated protein kinase-associated protein 1, JSAP1
	NCK adaptor protein 2, NCK2
	activates Src family kinases via c-Src SH2/SH3 interactions
	triple functional domain (PTPRF interacting), TRIO
	protein inhibitor of activated STAT 1, PIAS1
	calcium- and integrin-binding protein, CIB
	potassium large conductance calcium-activated channel subfamily M alpha member 1, KCNMA1
	death domain kinase receptor-interacting protein, RIP
	netrin 1, NTN1
	N-terminal transactivation domain of p53
	dynamin
	SAP90/PSD-95-Associated Protein-3, SAPAP3
	EPH receptor B2, EPHB2
	vascular endothelial growth factor receptor-3, VEGFR3
	tuberous sclerosis complex 2, TSC2
	CAS family members and with GIT1, SORBS1 and BCAR3
	MAPK7
	ARHGAP21 interacts with the C-terminal region of Focal Adhesion Kinase (PTK2)
	IGF1R (role in phosphorylation, signaling and stability of the IGF1R)
	binding-protein partner for ELK1, a finding that significantly broadens the potential functioning of PTK2 and ELK1
	with ARHGEF11 and ROCK2, cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts
	DLGAP3 and ASAP1
	PTK2 binds the pleckstrin homology domain of AGAP2, and the binding is independent of PTK2 activation following epidermal growth factor receptor stimulation
	IGF1R and plays an important role in cancer cell survival
	epithelial membrane protein 2, EMP2
	GNB1-mediated FYN activation integrates PTK2 with adherens junctions, preventing persistent endothelial barrier leakiness
	interactio with CADM1 (PTK2 is its binding partner and effector in shaping growth cones)
	interacting with XIAP (XIAP modulates PTK2 activity through the control of PTK2 phosphorylation)
	scaffold and tyrosine kinase protein that binds to itself and cellular partners through its four-point-one, ezrin, radixin, moesin (FERM) domain
	ZG16B-mediated PTK2 activation plays an important role in pancreatic cancer progression
	PTK2 modulates radial glia-dependent neuronal migration through GJB2
	suppression of vimentin intermediate filaments by PTK2 facilitates the assembly of podosome rosettes
	DLC1 binds to the FAT domain of PTK2 through at least some of the FAT sequences that bind paxillin, although it remains possible that other regions of PTK2 may also interact with DLC1
	PTK2 is a novel regulator of SNAIL1-dependent epithelial-mesenchymal transition in embryonic cells
	ABCB1 is involved in regulating BTB dynamics, likely via its interaction with PTK2, which modulates the phosphorylation status of the OCLN/TJP1 protein complex
	alternative linkage for PTK2-talin interactions within nascent adhesions essential for the control of cell migrationv
	modulates CDC42 activity downstream of positive and negative axon guidance cues
	XIAP plays a key role in vascular functions of PTK2B or PTK2B domain-mediated vascular functions of PTK2
	cell spreading promotes the association of cortactin and PTK2 and tyrosine phosphorylation of CTTN disrupts this interaction, which may explain how it inhibits cell spreading
	NANOG binds the PTK2 promoter, up-regulates PTK2, and directly binds and is phosphorylated by PTK2 that regulates cell morphology, growth, and invasion
	binds and phosphorylates wild type NANOG protein but not the mutant NANOG with Y35F and Y174F mutations
	is a critical intracellular adaptor for ADAM15-dependent enhancement of PTK2/SRC activation
	PTK2 inhibition resulted in the loss of the GATA4 transcription factor required for TNF-induced VCAM1 production
	contributes to cytokine signaling and bone resorption in osteoclasts and partially compensates for the absence of PTK2B to maintain proper adhesion structures in these cells
	stabilizes focal adhesion signaling in the absence of adhesion, as assessed by reduced caspase-dependent cleavage of PTK2 following cell detachment and sustained activity of the AKT1 signaling pathway
	important roles for a PTK6-PTK2-AKT1 signaling axis in promoting anchorage-independent cell survival
	TM4SF5 directly binds to and activates PTK2 in an adhesion-dependent manner, to regulate cell migration and invasion
	is a critical downstream regulator of GRPR, which mediates tumorigenesis and metastasis in neuroblastoma
	STK11 serves as a PTK2 repressor to stabilize focal adhesion sites
	link between PTK2 and BMP4 induction of mesenchymal stem cells (MSCs) adipogenesis, and may indicate a potential therapeutic approach targeting PTK2 for dealing with obesity
	THOC2 can play specific roles in neuronal cells and, possibly in combination with PTK2 reduction, may affect normal neural network formation, leading to cognitive impairment and cerebellar congenital hypoplasia
	GNB2L1 scaffolds AGAP2 to PTK2 to regulate PTK2 activity and cell adhesion during the differentiation process
	GRB2 is a new PTK2 activator awith an essential role in coordinating PTPRA tyrosine phosphorylation to enable downstream integrin signaling and migration
	ETV4 is able to transactivate PTK2 expression through binding to the promoter region of PTK2
	PTK2 negatively regulates LCK function downstream of the T cell antigen receptor
	TRIM72 induces PTK2 ubiquitination with the aid of UBE2H during skeletal myogenesis
	is a novel positive regulator of cellular protrusion formation and neurite outgrowth through the PTK2 signaling pathway
	interaction between ARHGEF28 and PTK2, a non-receptor tyrosine kinase that controls migration properties of normal and tumor cells
	LAMA2-mediated PTK2 activation in podocytes is an important early event in Alport glomerular pathogenesis
	RACGAP1 promoted the activations of RHOA, PTK2, PXN and triggered focal adhesion formation and cytoskeletal rearrangement
	CA8 might facilitate cancer cell invasion via the activation of PTK2-MMP9 signaling
	MUC5AC interacts with integrin beta4 that mediates phosphorylation of PTK2 at Y397 leading to lung cancer cell migration
	TGFB1I1 appears to enhance complex formation between MMP14 and PTK2 in activated endothelial cells, which likely coordinates matrix proteolysis and cell motility
	PTK2B, but not PTK2, could directly phosphorylate PYCARD at Tyr146, and only the phosphorylated PYCARD could participate in speck formation and trigger IL1B secretion
	MARVELD1 regulated neuronal migration by mediating the formation of glial fibres and ITGB1/PTK2 signalling pathway
	PTK2 UPS impairment via SQSTM1 phosphorylation in TARDBP proteinopathies

cell & other

REGULATION

activated by	tyrosine-phosphorylation in response to either integrin clustering or via G-protein coupled receptor (GPCR) occupancy by ligands such as bombesin or lysophosphatidic acid, or via LDL receptor occupancy
	integrin LFA-1

Other	acetylation
	phosphorylated via integrins or growth factor receptors
	phosphorylated by tyrosine aminotransferase, Tat
	phosphorylated bythrombin
	phosphorylated by EMP2 overexpression
	phosphorylated by ret proto-oncogene

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in hepatocellular carcinoma constitutional fusion       PTK2-THOC2 gene fusion in a patient with psychomotor retardation and congenital cerebellar hypoplasia

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer digestive pancreas targeting interaction PTK2/IGF1R with small molecules is a novel strategy for treatment of pancreatic cancer or other cancers miscelleaneous urinary   FAK inhibitors, might be employed as a novel therapeutic approach for treating Alport renal disease in its early stages

ANIMAL & CELL MODELS

	FAK-deficient mice display a general defect of mesoderm development, and cells from these embryos have reduced mobility in vitro
	Null mutation of FAK results in embryonic lethality, and FAK-/- fibroblasts exhibit cell migration defects in culture
	keratinocyte cell death was observed after fak deletion in vitro and in vivo in mice
	mice in which FAK is selectively inactivated in cardiomyocytes develop eccentric cardiac hypertrophy ncreased heart/body weight ratios, elevated markers of cardiac hypertrophy, multifocal interstitial fibrosis, and increased collagen I and VI expression
	focal adhesion kinase (FAK) conditional knockout mice display Cardiac developmental defects and eccentric right ventricular hypertrophy