Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9QVP9 (FAK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein-tyrosine kinase 2-beta

EC=2.7.10.2
Alternative name(s):
Calcium-dependent tyrosine kinase
Short name=CADTK
Calcium-regulated non-receptor proline-rich tyrosine kinase
Cell adhesion kinase beta
Short name=CAK-beta
Short name=CAKB
Focal adhesion kinase 2
Short name=FADK 2
Proline-rich tyrosine kinase 2
Related adhesion focal tyrosine kinase
Short name=RAFTK
Gene names
Name:Ptk2b
Synonyms:Fak2, Pyk2, Raftk
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1009 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376' By similarity. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca2+ levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2 By similarity. Ref.9 Ref.10 Ref.15 Ref.16 Ref.18 Ref.19 Ref.21 Ref.22 Ref.24 Ref.25 Ref.26 Ref.28

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.21

Enzyme regulation

Activated in response to stimuli that lead to increased intracellular Ca2+ levels; this activation is indirect and may be mediated by calcium-mediated production of reactive oxygen species (ROS). Activated by autophosphorylation at Tyr-402; this creates a binding site for SRC family kinases and leads to phosphorylation at additional tyrosine residues. Phosphorylation at Tyr-402, Tyr-579 and Tyr-580 is required for optimal kinase activity. Ref.21 Ref.26

Subunit structure

Homodimer, or homooligomer. Interacts with NPHP1, ASAP1, ASAP2, ARHGAP26, SKAP2 and TGFB1I1. The Tyr-402 phosphorylated form interacts with SRC (via SH2 domain) and SRC family members. Forms a signaling complex with EPHA1, LCK and phosphatidylinositol 3-kinase; upon activation by EFNA1. Interacts with GRB2 (via SH2 domain). Interacts with P53/TP53 and MDM2. Interacts with MYLK. Interacts with BCAR1. Interacts with RB1CC1. Interacts with RHOU. Interacts with VAV1. Interacts with PDPK1. Interacts with DLG4. Interacts with LPXN and PTPN12. Interacts with SIRPA and SH2D3C. Interacts (hypophosphorylated) with PXN. Interacts with ARHGAP10. Ref.6 Ref.7 Ref.8 Ref.10 Ref.12 Ref.13 Ref.14 Ref.16 Ref.18 Ref.22 Ref.27

Subcellular location

Cytoplasm. Cytoplasmperinuclear region By similarity. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell junctionfocal adhesion. Cell projectionlamellipodium By similarity. Cytoplasmcell cortex By similarity. Nucleus By similarity. Note: Colocalizes with integrins at the cell periphery By similarity. Interaction with NPHP1 induces the membrane-association of the kinase. Colocalizes with PXN at the microtubule-organizing center. The tyrosine phosphorylated form is detected at cell-cell contacts. Ref.25 Ref.27

Post-translational modification

Phosphorylated on tyrosine residues in response to various stimuli that elevate the intracellular calcium concentration; this activation is indirect and may be mediated by production of reactive oxygen species (ROS). Tyr-402 is the major autophosphorylation site, but other kinases can also phosphorylate Tyr-402. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-402 promotes interaction with SRC and SRC family members, leading to phosphorylation at Tyr-579; Tyr-580 and Tyr-881. Phosphorylation at Tyr-881 is important for interaction with GRB2. Phosphorylated on tyrosine residues upon activation of FGR and PKC. Recruitment by NPHP1 to cell matrix adhesions initiates Tyr-402 phosphorylation. In monocytes, adherence to substrata is required for tyrosine phosphorylation and kinase activation. Angiotensin II, thapsigargin and L-alpha-lysophosphatidic acid (LPA) also induce autophosphorylation and increase kinase activity. Phosphorylation by MYLK promotes ITGB2 activation and is thus essential to trigger neutrophil transmigration during lung injury. Dephosphorylated by PTPN12 By similarity. Ref.11 Ref.12 Ref.16 Ref.17 Ref.22 Ref.26 Ref.27

Disruption phenotype

Mice are born at the expected Mendelian rate, appear normal and are fertile. Mice display increased bone formation and high bone mass, due to defects in osteoclastic bone resorption. Osteoclasts display defects in actin cytoskeleton reorganization, plus altered Rho activity, microtubule stabilization and podosome organization. Mice also display increased differentiation and activity of osteoprogenitor cells. Macrophages from mutant mice display defects in their responses to chemokines, including defects in cell polarization, actin cytoskeleton reorganization, directed migration towards sites of inflammation, but also defects in the regulation of intracellular Ca2+ levels, phosphatidylinositol 3-kinase activity and inositol 1,4,5-trisphosphate production. Mutant mice have normal B cell polulations in bone marrow, lymph nodes and blood, but lack marginal zone B-cells in the spleen. Ref.9 Ref.15 Ref.19 Ref.21

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. FAK subfamily.

Contains 1 FERM domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processAdaptive immunity
Angiogenesis
Immunity
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Membrane
Nucleus
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processMAPK cascade

Inferred from electronic annotation. Source: Ensembl

activation of Janus kinase activity

Inferred from electronic annotation. Source: Ensembl

activation of Rac GTPase activity

Inferred from electronic annotation. Source: Ensembl

blood vessel endothelial cell migration

Inferred from electronic annotation. Source: Ensembl

bone resorption

Inferred from mutant phenotype Ref.16. Source: UniProtKB

cellular response to retinoic acid

Inferred from electronic annotation. Source: Ensembl

chemokine-mediated signaling pathway

Inferred from mutant phenotype Ref.15. Source: UniProtKB

epidermal growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

focal adhesion assembly

Inferred from electronic annotation. Source: Ensembl

glial cell proliferation

Inferred from electronic annotation. Source: Ensembl

integrin-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

marginal zone B cell differentiation

Inferred from mutant phenotype Ref.9. Source: UniProtKB

negative regulation of apoptotic process

Inferred from mutant phenotype Ref.25. Source: UniProtKB

negative regulation of bone mineralization

Inferred from mutant phenotype Ref.21. Source: UniProtKB

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of muscle cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of myeloid cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of potassium ion transport

Inferred from electronic annotation. Source: Ensembl

neuron projection development

Inferred from electronic annotation. Source: Ensembl

oocyte maturation

Inferred from electronic annotation. Source: Ensembl

positive regulation of B cell chemotaxis

Inferred from mutant phenotype Ref.9. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of JNK cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of JUN kinase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of actin filament polymerization

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of angiogenesis

Inferred from mutant phenotype Ref.18. Source: UniProtKB

positive regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from mutant phenotype Ref.25. Source: UniProtKB

positive regulation of cell-matrix adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of endothelial cell migration

Inferred from mutant phenotype Ref.18. Source: UniProtKB

positive regulation of neuron projection development

Inferred from electronic annotation. Source: Ensembl

positive regulation of nitric-oxide synthase activity

Inferred from mutant phenotype Ref.18. Source: UniProtKB

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of phosphatidylinositol 3-kinase activity

Inferred from mutant phenotype Ref.15. Source: UniProtKB

positive regulation of protein kinase activity

Inferred from mutant phenotype Ref.18. Source: UniProtKB

positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype Ref.25. Source: UniProtKB

positive regulation of reactive oxygen species metabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of translation

Inferred from electronic annotation. Source: Ensembl

regulation of actin cytoskeleton reorganization

Inferred from mutant phenotype Ref.15Ref.18. Source: UniProtKB

regulation of cGMP biosynthetic process

Inferred from mutant phenotype Ref.18. Source: UniProtKB

regulation of cGMP-mediated signaling

Inferred from mutant phenotype Ref.18. Source: UniProtKB

regulation of calcium-mediated signaling

Inferred from mutant phenotype Ref.18. Source: UniProtKB

regulation of cell shape

Inferred from mutant phenotype Ref.15. Source: UniProtKB

regulation of establishment of cell polarity

Inferred from mutant phenotype Ref.15. Source: UniProtKB

regulation of inositol trisphosphate biosynthetic process

Inferred from mutant phenotype Ref.15. Source: UniProtKB

regulation of macrophage chemotaxis

Inferred from mutant phenotype Ref.15. Source: UniProtKB

regulation of nitric oxide biosynthetic process

Inferred from mutant phenotype Ref.18. Source: UniProtKB

regulation of release of sequestered calcium ion into cytosol

Inferred from mutant phenotype Ref.15. Source: UniProtKB

response to cAMP

Inferred from electronic annotation. Source: Ensembl

response to calcium ion

Inferred from electronic annotation. Source: Ensembl

response to cocaine

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to glucose

Inferred from electronic annotation. Source: Ensembl

response to hormone

Inferred from electronic annotation. Source: Ensembl

response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to lithium ion

Inferred from electronic annotation. Source: Ensembl

response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

response to osmotic stress

Inferred from electronic annotation. Source: Ensembl

signal complex assembly

Inferred from electronic annotation. Source: InterPro

sprouting angiogenesis

Inferred from mutant phenotype Ref.28. Source: UniProtKB

stress fiber assembly

Inferred from electronic annotation. Source: Ensembl

tumor necrosis factor-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

vascular endothelial growth factor receptor signaling pathway

Inferred from mutant phenotype Ref.18. Source: UniProtKB

   Cellular_componentaxon

Inferred from electronic annotation. Source: Ensembl

cell cortex

Inferred from electronic annotation. Source: UniProtKB-SubCell

focal adhesion

Inferred from electronic annotation. Source: UniProtKB-SubCell

growth cone

Inferred from electronic annotation. Source: Ensembl

lamellipodium

Inferred from sequence or structural similarity. Source: UniProtKB

membrane raft

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay Ref.25. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

postsynaptic density

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

non-membrane spanning protein tyrosine kinase activity

Inferred from direct assay Ref.21. Source: UniProtKB

signal transducer activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10091009Protein-tyrosine kinase 2-beta
PRO_0000088082

Regions

Domain39 – 359321FERM
Domain425 – 683259Protein kinase
Nucleotide binding431 – 4399ATP By similarity
Nucleotide binding503 – 5097ATP By similarity
Region801 – 1009209Interaction with TGFB1I1 By similarity
Region868 – 1009142Focal adhesion targeting (FAT)
Compositional bias701 – 76767Pro-rich
Compositional bias831 – 86939Pro-rich

Sites

Active site5491Proton acceptor By similarity
Binding site4571ATP By similarity

Amino acid modifications

Modified residue3611Phosphoserine By similarity
Modified residue3751Phosphoserine Ref.23
Modified residue3991Phosphoserine By similarity
Modified residue4021Phosphotyrosine; by autocatalysis Ref.11 Ref.12 Ref.16 Ref.20 Ref.27
Modified residue4401Phosphotyrosine
Modified residue5791Phosphotyrosine; by SRC, LYN and LCK Ref.20
Modified residue5801Phosphotyrosine; by SRC, LYN and LCK Ref.11 Ref.20 Ref.27
Modified residue7221Phosphotyrosine By similarity
Modified residue7621Phosphoserine By similarity
Modified residue7651Phosphothreonine By similarity
Modified residue8341Phosphotyrosine By similarity
Modified residue8391Phosphoserine By similarity
Modified residue8421Phosphothreonine By similarity
Modified residue8491Phosphotyrosine By similarity
Modified residue8661Phosphoserine By similarity
Modified residue8811Phosphotyrosine Ref.11 Ref.27

Experimental info

Mutagenesis4021Y → A: Loss of phosphorylation and interaction with SRC, and inhibition of bone resorption. Ref.16
Sequence conflict3061K → R in AAI37705. Ref.4
Sequence conflict3061K → R in AAI44850. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q9QVP9 [UniParc].

Last modified October 3, 2012. Version 2.
Checksum: A17C858ECC9990E9

FASTA1,009115,794
        10         20         30         40         50         60 
MSGVSEPLSR VKVGTLRRPE GPPEPMVVVP VDVEKEDVRI LKVCFYSNSF NPGKNFKLVK 

        70         80         90        100        110        120 
CTVQTEIQEI ITSILLSGRI GPNIQLAECY GLRLKHMKSD EIHWLHPQMT VGEVQDKYEC 

       130        140        150        160        170        180 
LHVEAEWRYD LQIRYLPEDF MESLKEDRTT LLYFYQQLRN DYMQRYASKV SEGMALQLGC 

       190        200        210        220        230        240 
LELRRFFKDM PHNALDKKSN FELLEKEVGL DLFFPKQMQE NLKPKQFRKM IQQTFQQYAS 

       250        260        270        280        290        300 
LREEECVMKF FNTLAGFANI DQETYRCELI QGWNITVDLV IGPKGIRQLT SQDTKPTCLA 

       310        320        330        340        350        360 
EFKQIKSIRC LPLEETQAVL QLGIEGAPQS LSIKTSSLAE AENMADLIDG YCRLQGEHKG 

       370        380        390        400        410        420 
SLIMHAKKDG EKRNSLPQIP TLNLEARRSH LSESCSIESD IYAEIPDETL RRPGGPQYGV 

       430        440        450        460        470        480 
AREEVVLNRI LGEGFFGEVY EGVYTNHKGE KINVAVKTCK KDCTQDNKEK FMSEAVIMKN 

       490        500        510        520        530        540 
LDHPHIVKLI GIIEEEPTWI IMELYPYGEL GHYLERNKNS LKVPTLVLYT LQICKAMAYL 

       550        560        570        580        590        600 
ESINCVHRDI AVRNILVASP ECVKLGDFGL SRYIEDEDYY KASVTRLPIK WMSPESINFR 

       610        620        630        640        650        660 
RFTTASDVWM FAVCMWEILS FGKQPFFWLE NKDVIGVLEK GDRLPKPELC PPVLYTLMTR 

       670        680        690        700        710        720 
CWDYDPSDRP RFTELVCSLS DIYQMEKDIA IEQERNARYR PPKILEPTTF QEPPPKPSRP 

       730        740        750        760        770        780 
KYRPPPQTNL LAPKLQFQVP EGLCASSPTL TSPMEYPSPV NSLHTPPLHR HNVFKRHSMR 

       790        800        810        820        830        840 
EEDFIRPSSR EEAQQLWEAE KIKMKQVLER QQKQMVEDSQ WLRREERCLD PMVYMNDKSP 

       850        860        870        880        890        900 
LTPEKEAGYT EFTGPPQKPP RLGAQSIQPT ANLDRTDDLV YHNVMTLVEA VLELKNKLGQ 

       910        920        930        940        950        960 
LPPEDYVVVV KNVGLNLRKL IGSVDDLLPS LPASSRTEIE GTQKLLNKDL AELINKMKLA 

       970        980        990       1000 
QQNAVTSLSE DCKRQMLTAS HTLAVDAKNL LDAVDQAKVV ANLAHPPAE 

« Hide

References

« Hide 'large scale' references
[1]"Identification and characterization of a novel related adhesion focal tyrosine kinase (RAFTK) from megakaryocytes and brain."
Avraham S., London R., Fu Y., Ota S., Hiregowdara D., Li J., Jiang S., Pasztor L.M., White R.A., Groopman J.E., Avraham H.
J. Biol. Chem. 270:27742-27751(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]Lubec G., Sunyer B., Chen W.-Q.
Submitted (JAN-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 469-479, MASS SPECTROMETRY.
Strain: OF1.
Tissue: Hippocampus.
[6]"The related adhesion focal tyrosine kinase forms a complex with paxillin in hematopoietic cells."
Salgia R., Avraham S., Pisick E., Li J.L., Raja S., Greenfield E.A., Sattler M., Avraham H., Griffin J.D.
J. Biol. Chem. 271:31222-31226(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PXN.
[7]"Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions."
Matsuya M., Sasaki H., Aoto H., Mitaka T., Nagura K., Ohba T., Ishino M., Takahashi S., Suzuki R., Sasaki T.
J. Biol. Chem. 273:1003-1014(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TGFB1I1.
[8]"SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-protein complexes in macrophages."
Timms J.F., Swanson K.D., Marie-Cardine A., Raab M., Rudd C.E., Schraven B., Neel B.G.
Curr. Biol. 9:927-930(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SIRPA.
[9]"Absence of marginal zone B cells in Pyk-2-deficient mice defines their role in the humoral response."
Guinamard R., Okigaki M., Schlessinger J., Ravetch J.V.
Nat. Immunol. 1:31-36(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION IN B-CELL DIFFERENTIATION; B-CELL CHEMOTAXIS AND IMMUNE RESPONSE.
[10]"Regulation of CDC42 GTPase by proline-rich tyrosine kinase 2 interacting with PSGAP, a novel pleckstrin homology and Src homology 3 domain containing rhoGAP protein."
Ren X.-R., Du Q.-S., Huang Y.-Z., Ao S.-Z., Mei L., Xiong W.-C.
J. Cell Biol. 152:971-984(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARHGAP10, FUNCTION IN REGULATION OF ARHGAP10 ACTIVITY AND ACTIVATION OF CDC42 AND RHOA.
[11]"Different modes and qualities of tyrosine phosphorylation of Fak and Pyk2 during epithelial-mesenchymal transdifferentiation and cell migration: analysis of specific phosphorylation events using site-directed antibodies."
Nakamura K., Yano H., Schaefer E., Sabe H.
Oncogene 20:2626-2635(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-402; TYR-580 AND TYR-881.
[12]"Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers phosphorylation of Pyk2."
Benzing T., Gerke P., Hoepker K., Hildebrandt F., Kim E., Walz G.
Proc. Natl. Acad. Sci. U.S.A. 98:9784-9789(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-402, INTERACTION WITH NPHP1.
[13]"A novel hematopoietic adaptor protein, Chat-H, positively regulates T cell receptor-mediated interleukin-2 production by Jurkat cells."
Sakakibara A., Hattori S., Nakamura S., Katagiri T.
J. Biol. Chem. 278:6012-6017(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SH2D3C.
[14]"Leupaxin is a critical adaptor protein in the adhesion zone of the osteoclast."
Gupta A., Lee B.S., Khadeer M.A., Tang Z., Chellaiah M., Abu-Amer Y., Goldknopf J., Hruska K.A.
J. Bone Miner. Res. 18:669-685(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LPXN AMD PTPN12.
[15]"Pyk2 regulates multiple signaling events crucial for macrophage morphology and migration."
Okigaki M., Davis C., Falasca M., Harroch S., Felsenfeld D.P., Sheetz M.P., Schlessinger J.
Proc. Natl. Acad. Sci. U.S.A. 100:10740-10745(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[16]"Src kinase activity is essential for osteoclast function."
Miyazaki T., Sanjay A., Neff L., Tanaka S., Horne W.C., Baron R.
J. Biol. Chem. 279:17660-17666(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN BONE RESORPTION, INTERACTION WITH SRC, PHOSPHORYLATION AT TYR-402, MUTAGENESIS OF TYR-402.
[17]"The proto-oncogene Fgr regulates cell migration and this requires its plasma membrane localization."
Continolo S., Baruzzi A., Majeed M., Caveggion E., Fumagalli L., Lowell C.A., Berton G.
Exp. Cell Res. 302:253-269(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION IN RESPONSE TO FGR.
[18]"Central role of calcium-dependent tyrosine kinase PYK2 in endothelial nitric oxide synthase-mediated angiogenic response and vascular function."
Matsui A., Okigaki M., Amano K., Adachi Y., Jin D., Takai S., Yamashita T., Kawashima S., Kurihara T., Miyazaki M., Tateishi K., Matsunaga S., Katsume A., Honshou S., Takahashi T., Matoba S., Kusaba T., Tatsumi T., Matsubara H.
Circulation 116:1041-1051(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN VEGFA SIGNALING; REGULATION OF INTRACELLULAR CALCIUM LEVELS; ACTIVATION OF AKT1 AND RAC1; PHOSPHORYLATION OF SRC; REORGANIZATION OF ACTIN CYTOSKELETON; CELL MIGRATION AND ANGIOGENESIS, INTERACTION WITH SRC.
[19]"Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(-/-) mice."
Gil-Henn H., Destaing O., Sims N.A., Aoki K., Alles N., Neff L., Sanjay A., Bruzzaniti A., De Camilli P., Baron R., Schlessinger J.
J. Cell Biol. 178:1053-1064(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[20]"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402; TYR-579 AND TYR-580, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Mast cell.
[21]"Proline-rich tyrosine kinase 2 regulates osteoprogenitor cells and bone formation, and offers an anabolic treatment approach for osteoporosis."
Buckbinder L., Crawford D.T., Qi H., Ke H.Z., Olson L.M., Long K.R., Bonnette P.C., Baumann A.P., Hambor J.E., Grasser W.A. III, Pan L.C., Owen T.A., Luzzio M.J., Hulford C.A., Gebhard D.F., Paralkar V.M., Simmons H.A., Kath J.C. expand/collapse author list , Roberts W.G., Smock S.L., Guzman-Perez A., Brown T.A., Li M.
Proc. Natl. Acad. Sci. U.S.A. 104:10619-10624(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION.
[22]"Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating beta2 integrins."
Xu J., Gao X.-P., Ramchandran R., Zhao Y.-Y., Vogel S.M., Malik A.B.
Nat. Immunol. 9:880-886(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION DURING LUNG INJURY, PHOSPHORYLATION BY MYLK, INTERACTION WITH MYLK.
[23]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]"B cell receptor-induced phosphorylation of Pyk2 and focal adhesion kinase involves integrins and the Rap GTPases and is required for B cell spreading."
Tse K.W., Dang-Lawson M., Lee R.L., Vong D., Bulic A., Buckbinder L., Gold M.R.
J. Biol. Chem. 284:22865-22877(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[25]"Pyk2 inhibition of p53 as an adaptive and intrinsic mechanism facilitating cell proliferation and survival."
Lim S.T., Miller N.L., Nam J.O., Chen X.L., Lim Y., Schlaepfer D.D.
J. Biol. Chem. 285:1743-1753(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL PROLIFERATION AND REGULATION OT P53/TP53 UBIQUITINATION, SUBCELLULAR LOCATION.
[26]"Regulation of the tyrosine kinase Pyk2 by calcium is through production of reactive oxygen species in cytotoxic T lymphocytes."
Lysechko T.L., Cheung S.M., Ostergaard H.L.
J. Biol. Chem. 285:31174-31184(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION, ENZYME REGULATION.
[27]"Hypophosphorylated and inactive Pyk2 associates with paxillin at the microtubule organizing center in hematopoietic cells."
St-Pierre J., Lysechko T.L., Ostergaard H.L.
Cell. Signal. 23:718-730(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PXN, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-402; TYR-580 AND TYR-881.
[28]"Decreased cell adhesion promotes angiogenesis in a Pyk2-dependent manner."
Shen C.J., Raghavan S., Xu Z., Baranski J.D., Yu X., Wozniak M.A., Miller J.S., Gupta M., Buckbinder L., Chen C.S.
Exp. Cell Res. 317:1860-1871(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN SPROUTING ANGIOGENESIS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AC126272 Genomic DNA. No translation available.
AC140329 Genomic DNA. No translation available.
CH466535 Genomic DNA. Translation: EDL36001.1.
BC137704 mRNA. Translation: AAI37705.1.
BC144849 mRNA. Translation: AAI44850.1.
RefSeqNP_001155838.1. NM_001162366.1.
XP_006518789.1. XM_006518726.1.
UniGeneMm.21613.

3D structure databases

ProteinModelPortalQ9QVP9.
SMRQ9QVP9. Positions 21-732, 867-1007.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9QVP9. 4 interactions.
MINTMINT-266339.

Chemistry

ChEMBLCHEMBL1075289.

PTM databases

PhosphoSiteQ9QVP9.

Proteomic databases

PaxDbQ9QVP9.
PRIDEQ9QVP9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000022622; ENSMUSP00000022622; ENSMUSG00000059456.
ENSMUST00000178730; ENSMUSP00000137008; ENSMUSG00000059456.
GeneID19229.
KEGGmmu:19229.
UCSCuc011znr.1. mouse.

Organism-specific databases

CTD2185.
MGIMGI:104908. Ptk2b.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000115459.
HOGENOMHOG000069938.
HOVERGENHBG004018.
InParanoidB2RQ16.
KOK05871.
OMAQFRKMIQ.
OrthoDBEOG7ZSHSB.

Enzyme and pathway databases

BRENDA2.7.10.2. 3474.

Gene expression databases

ArrayExpressQ9QVP9.
CleanExMM_PTK2B.
GenevestigatorQ9QVP9.

Family and domain databases

Gene3D1.20.80.10. 1 hit.
InterProIPR019749. Band_41_domain.
IPR014352. FERM/acyl-CoA-bd_prot_3-hlx.
IPR019748. FERM_central.
IPR000299. FERM_domain.
IPR005189. Focal_adhesion_kin_target_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamPF00373. FERM_M. 1 hit.
PF03623. Focal_AT. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
ProDomPD006413. Focal_adhesion_target_reg. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00295. B41. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF47031. SSF47031. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF68993. SSF68993. 1 hit.
PROSITEPS50057. FERM_3. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio296032.
PROQ9QVP9.
SOURCESearch...

Entry information

Entry nameFAK2_MOUSE
AccessionPrimary (citable) accession number: Q9QVP9
Secondary accession number(s): B2RQ16, G3X8V1
Entry history
Integrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: October 3, 2012
Last modified: March 19, 2014
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot