Q00944

EV
Gene name
PTK2 (FAK, FAK1)
Protein name
Focal adhesion kinase 1
Names
FADK 1, Focal adhesion kinase-related nonkinase, FRNK, p41/p43FRNK, Protein-tyrosine kinase 2, p125FAK, pp125FAK
Species
Gallus gallus (Chicken)
KEGG Pathway
gga:396416
EC number
2.7.10.2: Protein-tyrosine kinases
Protein Class
FERM AND PDZ DOMAIN-CONTAINING PROTEIN FAMILY MEMBER (PTHR46221)

Descriptions

Focal adhesion kinase (FAK) integrates signals from integrin and growth factor receptors to regulate cellular responses including cell adhesion, migration and survival.
The inactive structure reveals a mechanism of inhibition in which the N-terminal FERM domain directly binds the kinase domain, blocking access to the catalytic cleft and protecting the FAK activation loop from Src phosphorylation. Additionally, the FERM domain sequesters the Tyr397 autophosphorylation and Src recruitment site, which lies in the linker connecting the FERM and kinase domains. FAK is activated by autophosphorylation at Tyr-397, which promotes interaction with Src and phosphorylation at Tyr-576 and Tyr-577 in the kinase activation loop.

Autoinhibitory domains (AIDs)

35-355 (FERM domain) EV

Target domain

422-680 (Protein kinase domain)

Relief mechanism

Ligand binding, Partner binding

Assay

Deletion assay, Mutagenesis experiment, Structural analysis

Accessory elements

563-587 (Activation loop from InterPro)

Target domain

422-680 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

35 structures for Q00944

Entry ID Method Resolution Chain Position Source
1KTM NMR - A 916-1053 PDB
1PV3 NMR - A 920-1053 PDB
1QVX NMR - A 920-1053 PDB
2AEH X-ray 253 A A/B 31-399 PDB
2AL6 X-ray 235 A A/B 31-405 PDB
2J0J X-ray 280 A A 31-686 PDB
2J0K X-ray 300 A A/B 31-686 PDB
2J0L X-ray 230 A A 411-686 PDB
2J0M X-ray 280 A PDB
2JKK X-ray 200 A A 411-686 PDB
2JKM X-ray 231 A A 411-686 PDB
2JKO X-ray 165 A A 411-686 PDB
2JKQ X-ray 260 A A 411-686 PDB
2L6F NMR - A 916-1053 PDB
2L6G NMR - A 916-1053 PDB
2L6H NMR - A 916-1053 PDB
3ZDT X-ray 315 A A/B 31-405 PDB
4BRX X-ray 205 A A 411-686 PDB
4C7T X-ray 205 A A 411-686 PDB
4CYE X-ray 320 A A/B 31-405 PDB
4D4R X-ray 155 A A/B 411-686 PDB
4D4S X-ray 200 A A/B 411-686 PDB
4D4V X-ray 210 A A/B 411-686 PDB
4D4Y X-ray 180 A A/B 411-686 PDB
4D55 X-ray 230 A A 411-686 PDB
4D58 X-ray 195 A A/B 411-686 PDB
4D5H X-ray 175 A A/B 411-686 PDB
4D5K X-ray 175 A A/B 411-686 PDB
6CB0 X-ray 197 A A/B 31-405 PDB
6GCR X-ray 230 A A 411-686 PDB
6GCW X-ray 200 A A/B 411-686 PDB
6GCX X-ray 155 A A 411-686 PDB
6TY3 EM 632 A A/B 30-686 PDB
6TY4 EM 596 A A/B 30-686 PDB
AF-Q00944-F1 Predicted AlphaFoldDB

10 variants for Q00944

Variant ID(s) Position Change Description Diseaes Association Provenance
rs731758621 106 N>H No Ensembl
rs733675923 564 D>G No Ensembl
rs738409887 643 M>I No Ensembl
rs739787424 647 C>R No Ensembl
rs740816587 888 S>R No Ensembl
rs734685984 889 L>P No Ensembl
rs740517256 905 I>N No Ensembl
rs737460072 962 L>R No Ensembl
rs739207746 1030 V>G No Ensembl
rs738557295 1037 D>G No Ensembl

No associated diseases with Q00944

11 regional properties for Q00944

Type Name Position InterPro Accession
domain FERM domain 35 - 355 IPR000299
domain Protein kinase domain 422 - 680 IPR000719
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 422 - 676 IPR001245
domain Focal adhesion kinase, targeting (FAT) domain 915 - 1046 IPR005189
active_site Tyrosine-protein kinase, active site 542 - 554 IPR008266
binding_site Protein kinase, ATP binding site 428 - 454 IPR017441
domain FERM central domain 135 - 250 IPR019748
domain Band 4.1 domain 31 - 258 IPR019749
domain Tyrosine-protein kinase, catalytic domain 422 - 676 IPR020635
domain Focal adhesion kinase, N-terminal 35 - 130 IPR041390
domain FAK1/PYK2, FERM domain C-lobe 254 - 364 IPR041784

Functions

Description
EC Number 2.7.10.2 Protein-tyrosine kinases
Subcellular Localization
  • Cell junction, focal adhesion
  • Cell membrane ; Peripheral membrane protein ; Cytoplasmic side
  • Cytoplasm, perinuclear region
  • Cytoplasm, cell cortex
  • Cytoplasm, cytoskeleton
  • Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
  • Nucleus
  • Cytoplasm, cytoskeleton, cilium basal body
  • Cytoplasm
  • Constituent of focal adhesions
  • Detected at microtubules
PANTHER Family PTHR46221 FERM AND PDZ DOMAIN-CONTAINING PROTEIN FAMILY MEMBER
PANTHER Subfamily PTHR46221:SF8 NON-SPECIFIC PROTEIN-TYROSINE KINASE
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

8 GO annotations of cellular component

Name Definition
ciliary basal body A membrane-tethered, short cylindrical array of microtubules and associated proteins found at the base of a eukaryotic cilium (also called flagellum) that is similar in structure to a centriole and derives from it. The cilium basal body is the site of assembly and remodelling of the cilium and serves as a nucleation site for axoneme growth. As well as anchoring the cilium, it is thought to provide a selective gateway regulating the entry of ciliary proteins and vesicles by intraflagellar transport.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
dendritic spine A small, membranous protrusion from a dendrite that forms a postsynaptic compartment, typically receiving input from a single presynapse. They function as partially isolated biochemical and an electrical compartments. Spine morphology is variable:they can be thin, stubby, mushroom, or branched, with a continuum of intermediate morphologies. They typically terminate in a bulb shape, linked to the dendritic shaft by a restriction. Spine remodeling is though to be involved in synaptic plasticity.
extrinsic component of cytoplasmic side of plasma membrane The component of a plasma membrane consisting of gene products and protein complexes that are loosely bound to its cytoplasmic surface, but not integrated into the hydrophobic region.
focal adhesion A cell-substrate junction that anchors the cell to the extracellular matrix and that forms a point of termination of actin filaments. In insects focal adhesion has also been referred to as hemi-adherens junction (HAJ).
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
perinuclear region of cytoplasm Cytoplasm situated near, or occurring around, the nucleus.
sarcolemma The outer membrane of a muscle cell, consisting of the plasma membrane, a covering basement membrane (about 100 nm thick and sometimes common to more than one fiber), and the associated loose network of collagen fibers.

9 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
calcium-dependent cysteine-type endopeptidase activity Catalysis of the hydrolysis of nonterminal peptide bonds in a polypeptide chain by a mechanism using a cysteine residue at the enzyme active center, and requiring the presence of calcium.
identical protein binding Binding to an identical protein or proteins.
integrin binding Binding to an integrin.
non-membrane spanning protein tyrosine kinase activity Catalysis of the reaction: ATP + protein L-tyrosine = ADP + protein L-tyrosine phosphate by a non-membrane spanning protein.
protease binding Binding to a protease or a peptidase.
protein serine/threonine/tyrosine kinase activity Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.
protein tyrosine kinase activity Catalysis of the reaction: ATP + a protein tyrosine = ADP + protein tyrosine phosphate.
signaling receptor binding Binding to one or more specific sites on a receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.

24 GO annotations of biological process

Name Definition
actin filament organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments. Includes processes that control the spatial distribution of actin filaments, such as organizing filaments into meshworks, bundles, or other structures, as by cross-linking.
angiogenesis Blood vessel formation when new vessels emerge from the proliferation of pre-existing blood vessels.
angiogenesis involved in wound healing Blood vessel formation when new vessels emerge from the proliferation of pre-existing blood vessels and contribute to the series of events that restore integrity to a damaged tissue, following an injury.
cell differentiation The process in which relatively unspecialized cells, e.g. embryonic or regenerative cells, acquire specialized structural and/or functional features that characterize the cells, tissues, or organs of the mature organism or some other relatively stable phase of the organism's life history. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state.
epidermal growth factor receptor signaling pathway The series of molecular signals initiated by binding of a ligand to the tyrosine kinase receptor EGFR (ERBB1) on the surface of a cell. The pathway ends with regulation of a downstream cellular process, e.g. transcription.
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
negative regulation of anoikis Any process that stops, prevents or reduces the frequency, rate or extent of anoikis.
negative regulation of cell-substrate adhesion Any process that decreases the frequency, rate or extent of cell-substrate adhesion. Cell-substrate adhesion is the attachment of a cell to the underlying substrate via adhesion molecules.
negative regulation of protein autophosphorylation Any process that stops, prevents or decreases the rate of the phosphorylation by a protein of one or more of its own residues.
positive regulation of cell migration Any process that activates or increases the frequency, rate or extent of cell migration.
positive regulation of cell population proliferation Any process that activates or increases the rate or extent of cell proliferation.
positive regulation of focal adhesion assembly Any process that activates or increases the frequency, rate or extent of focal adhesion assembly, the establishment and maturation of focal adhesions.
positive regulation of protein binding Any process that activates or increases the frequency, rate or extent of protein binding.
positive regulation of protein tyrosine kinase activity Any process that increases the rate, frequency, or extent of protein tyrosine kinase activity.
positive regulation of substrate-dependent cell migration, cell attachment to substrate Any process that activates or increases the frequency, rate or extent of substrate-dependent cell migration, cell attachment to substrate.
protein autophosphorylation The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation).
protein phosphorylation The process of introducing a phosphate group on to a protein.
radial glia-guided pyramidal neuron migration The radial migration of a pyramidal neuron along radial glial cells.
regulation of cell adhesion Any process that modulates the frequency, rate or extent of attachment of a cell to another cell or to the extracellular matrix.
response to muscle stretch Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a myofibril being extended beyond its slack length.
response to pH Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a pH stimulus. pH is a measure of the acidity or basicity of an aqueous solution.
signal complex assembly The aggregation, arrangement and bonding together of a set of components to form a complex capable of relaying a signal within a cell.
transmembrane receptor protein tyrosine kinase signaling pathway The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses tyrosine kinase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.
wound healing, spreading of cells The migration of a cell along or through a wound gap that contributes to the reestablishment of a continuous surface.

15 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
F1N9Y5 SYK Tyrosine-protein kinase SYK Gallus gallus (Chicken) SS
Q02977 YRK Proto-oncogene tyrosine-protein kinase Yrk Gallus gallus (Chicken) SS
P00523 SRC Proto-oncogene tyrosine-protein kinase Src Gallus gallus (Chicken) EV
P09324 YES1 Tyrosine-protein kinase Yes Gallus gallus (Chicken) SS
P41239 CSK Tyrosine-protein kinase CSK Gallus gallus (Chicken) SS
P42683 LCK Proto-oncogene tyrosine-protein kinase LCK Gallus gallus (Chicken) SS
Q05876 FYN Tyrosine-protein kinase Fyn Gallus gallus (Chicken) SS
Q8JH64 BTK Tyrosine-protein kinase BTK Gallus gallus (Chicken) SS
Q14289 PTK2B Protein-tyrosine kinase 2-beta Homo sapiens (Human) PR
Q05397 PTK2 Focal adhesion kinase 1 Homo sapiens (Human) EV
Q9QVP9 Ptk2b Protein-tyrosine kinase 2-beta Mus musculus (Mouse) PR
P34152 Ptk2 Focal adhesion kinase 1 Mus musculus (Mouse) SS
P70600 Ptk2b Protein-tyrosine kinase 2-beta Rattus norvegicus (Rat) PR
O35346 Ptk2 Focal adhesion kinase 1 Rattus norvegicus (Rat) SS
Q95YD4 kin-32 Inactive tyrosine-protein kinase kin-32 Caenorhabditis elegans PR
10 20 30 40 50 60
MAAAYLDPNL NHTPSSSAKT HLGTGMERSP GAMERVLKVF HYFENSSEPT TWASIIRHGD
70 80 90 100 110 120
ATDVRGIIQK IVDCHKVKNV ACYGLRLSHL QSEEVHWLHL DMGVSNVREK FELAHPPEEW
130 140 150 160 170 180
KYELRIRYLP KGFLNQFTED KPTLNFFYQQ VKNDYMLEIA DQVDQEIALK LGCLEIRRSY
190 200 210 220 230 240
GEMRGNALEK KSNYEVLEKD VGLRRFFPKS LLDSVKAKTL RKLIQQTFRQ FANLNREESI
250 260 270 280 290 300
LKFFEILSPV YRFDKECFKC ALGSSWIISV ELAIGPEEGI SYLTDKGANP THLADFNQVQ
310 320 330 340 350 360
TIQYSNSEDK DRKGMLQLKI AGAPEPLTVT APSLTIAENM ADLIDGYCRL VNGATQSFII
370 380 390 400 410 420
RPQKEGERAL PSIPKLANNE KQGVRSHTVS VSETDDYAEI IDEEDTYTMP STRDYEIQRE
430 440 450 460 470 480
RIELGRCIGE GQFGDVHQGI YMSPENPAMA VAIKTCKNCT SDSVREKFLQ EALTMRQFDH
490 500 510 520 530 540
PHIVKLIGVI TENPVWIIME LCTLGELRSF LQVRKFSLDL ASLILYAYQL STALAYLESK
550 560 570 580 590 600
RFVHRDIAAR NVLVSATDCV KLGDFGLSRY MEDSTYYKAS KGKLPIKWMA PESINFRRFT
610 620 630 640 650 660
SASDVWMFGV CMWEILMHGV KPFQGVKNND VIGRIENGER LPMPPNCPPT LYSLMTKCWA
670 680 690 700 710 720
YDPSRRPRFT ELKAQLSTIL EEEKLQQEER MRMESRRQVT VSWDSGGSDE APPKPSRPGY
730 740 750 760 770 780
PSPRSSEGFY PSPQHMVQPN HYQVSGYSGS HGIPAMAGSI YPGQASLLDQ TDSWNHRPQE
790 800 810 820 830 840
VSAWQPNMED SGTLDVRGMG QVLPTHLMEE RLIRQQQEME EDQRWLEKEE RFLVMKPDVR
850 860 870 880 890 900
LSRGSIERED GGLQGPAGNQ HIYQPVGKPD HAAPPKKPPR PGAPHLGSLA SLNSPVDSYN
910 920 930 940 950 960
EGVKIKPQEI SPPPTANLDR SNDKVYENVT GLVKAVIEMS SKIQPAPPEE YVPMVKEVGL
970 980 990 1000 1010 1020
ALRTLLATVD ESLPVLPAST HREIEMAQKL LNSDLAELIN KMKLAQQYVM TSLQQEYKKQ
1030 1040 1050
MLTAAHALAV DAKNLLDVID QARLKMISQS RPH