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Q14289 (FAK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 169. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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'. 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. Ref.1 Ref.9 Ref.10 Ref.12 Ref.15 Ref.16 Ref.17 Ref.19 Ref.20 Ref.22 Ref.23 Ref.24 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.33 Ref.34 Ref.36 Ref.38 Ref.39 Ref.41 Ref.46 Ref.47

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.19 Ref.20 Ref.23 Ref.30 Ref.44 Ref.46

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. Inhibited by PF-562,271, BIRB796, PF-4618433 and by PF-431396, PF-2318841 and their derivatives. Inhibited by sulfoximine-substituted trifluoromethylpyrimidines. Inhibited by 4-amino and 5-aryl substituted pyridinone compounds. Ref.23 Ref.30 Ref.44 Ref.46

Subunit structure

Homodimer, or homooligomer. Interacts with SIRPA and SH2D3C. Interacts with ARHGAP10. Interacts with DLG4 By similarity. 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 PDPK1. Interacts (hypophosphorylated) with PXN. Interacts with RB1CC1. Interacts with RHOU. Interacts with VAV1. Interacts with LPXN and PTPN12. Ref.1 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.21 Ref.22 Ref.24 Ref.27 Ref.28 Ref.29 Ref.31 Ref.33 Ref.38 Ref.45

Subcellular location

Cytoplasm. Cytoplasmperinuclear region. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell junctionfocal adhesion. Cell projectionlamellipodium. Cytoplasmcell cortex. Nucleus. Note: Interaction with NPHP1 induces the membrane-association of the kinase. Colocalizes with integrins at the cell periphery. Ref.16 Ref.17 Ref.24 Ref.29 Ref.34

Tissue specificity

Most abundant in the brain, with highest levels in amygdala and hippocampus. Low levels in kidney (at protein level). Also expressed in spleen and lymphocytes. Ref.1 Ref.5

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. Ref.5 Ref.9 Ref.14 Ref.20 Ref.21 Ref.28 Ref.29 Ref.31 Ref.33 Ref.35 Ref.36

Involvement in disease

Aberrant PTK2B/PYK2 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. Elevated PTK2B/PYK2 expression is seen in gliomas, hepatocellular carcinoma, lung cancer and breast cancer. Ref.23 Ref.24 Ref.30 Ref.39 Ref.41 Ref.46 Ref.47

Miscellaneous

Promotes bone resorption, and thus PTK2B/PYK2 inhibitors might be used to treat osteoporosis.

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
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMAPK cascade

Inferred from electronic annotation. Source: Ensembl

activation of Janus kinase activity

Inferred from mutant phenotype Ref.10. Source: UniProtKB

activation of Rac GTPase activity

Inferred from electronic annotation. Source: Ensembl

apoptotic process

Traceable author statement PubMed 10880513. Source: ProtInc

blood vessel endothelial cell migration

Inferred from electronic annotation. Source: Ensembl

bone resorption

Inferred from sequence or structural similarity. Source: UniProtKB

cell surface receptor signaling pathway

Inferred from mutant phenotype Ref.9. Source: UniProtKB

cellular defense response

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

cellular response to retinoic acid

Inferred from mutant phenotype PubMed 17910947. Source: BHF-UCL

chemokine-mediated signaling pathway

Inferred from sequence or structural similarity. 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 mutant phenotype Ref.19. Source: UniProtKB

ionotropic glutamate receptor signaling pathway

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

long-term synaptic potentiation

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

marginal zone B cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptotic process

Inferred from mutant phenotype Ref.34. Source: UniProtKB

negative regulation of bone mineralization

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell proliferation

Inferred from mutant phenotype Ref.19. Source: UniProtKB

negative regulation of muscle cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of myeloid cell differentiation

Inferred from mutant phenotype Ref.19. Source: UniProtKB

negative regulation of neuron apoptotic process

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

negative regulation of potassium ion transport

Inferred from direct assay Ref.1. Source: UniProtKB

neuron projection development

Inferred from electronic annotation. Source: Ensembl

oocyte maturation

Inferred from electronic annotation. Source: Ensembl

peptidyl-tyrosine autophosphorylation

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.1. Source: UniProtKB

positive regulation of B cell chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from mutant phenotype Ref.1. Source: UniProtKB

positive regulation of JNK cascade

Inferred from mutant phenotype Ref.10. Source: UniProtKB

positive regulation of JUN kinase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of actin filament polymerization

Inferred from mutant phenotype Ref.24. Source: UniProtKB

positive regulation of angiogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell migration

Inferred from mutant phenotype Ref.24. Source: UniProtKB

positive regulation of cell proliferation

Inferred from mutant phenotype Ref.24. Source: UniProtKB

positive regulation of cell-matrix adhesion

Inferred from mutant phenotype Ref.24. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of endothelial cell migration

Inferred from direct assay PubMed 21245381. Source: BHF-UCL

positive regulation of excitatory postsynaptic membrane potential

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

positive regulation of neuron projection development

Inferred from mutant phenotype PubMed 17910947. Source: BHF-UCL

positive regulation of nitric-oxide synthase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 21245381. Source: BHF-UCL

positive regulation of phosphatidylinositol 3-kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein kinase activity

Inferred from mutant phenotype Ref.1. Source: UniProtKB

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

Inferred from electronic annotation. Source: Ensembl

positive regulation of reactive oxygen species metabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of synaptic transmission, glutamatergic

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

positive regulation of translation

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Traceable author statement Ref.9. Source: UniProtKB

protein complex assembly

Traceable author statement PubMed 10867021. Source: ProtInc

protein phosphorylation

Traceable author statement PubMed 7529876. Source: ProtInc

regulation of N-methyl-D-aspartate selective glutamate receptor activity

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

regulation of actin cytoskeleton reorganization

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cGMP biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of cGMP-mediated signaling

Inferred from electronic annotation. Source: Ensembl

regulation of calcium-mediated signaling

Inferred from electronic annotation. Source: Ensembl

regulation of cell adhesion

Inferred from mutant phenotype Ref.31. Source: UniProtKB

regulation of cell shape

Inferred from mutant phenotype Ref.31. Source: UniProtKB

regulation of establishment of cell polarity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of inositol trisphosphate biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of macrophage chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of nitric oxide biosynthetic process

Inferred from electronic annotation. Source: Ensembl

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

Inferred from direct assay Ref.34. Source: UniProtKB

regulation of release of sequestered calcium ion into cytosol

Inferred from sequence or structural similarity. 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

response to stress

Traceable author statement PubMed 8939945. Source: ProtInc

signal complex assembly

Traceable author statement PubMed 7529876. Source: ProtInc

signal transduction

Traceable author statement PubMed 10867021Ref.4. Source: ProtInc

sprouting angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

stress fiber assembly

Inferred from electronic annotation. Source: Ensembl

tumor necrosis factor-mediated signaling pathway

Inferred from mutant phenotype Ref.10. Source: UniProtKB

vascular endothelial growth factor receptor signaling pathway

Inferred from mutant phenotype PubMed 21245381. Source: BHF-UCL

   Cellular_componentN-methyl-D-aspartate selective glutamate receptor complex

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

apical dendrite

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

axon

Inferred from electronic annotation. Source: Ensembl

cell body

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

cell cortex

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

dendrite

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

focal adhesion

Inferred from direct assay Ref.24. Source: UniProtKB

growth cone

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

lamellipodium

Inferred from direct assay Ref.24. Source: UniProtKB

membrane raft

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

nucleus

Inferred from direct assay Ref.34. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay Ref.24. Source: UniProtKB

postsynaptic density

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

calmodulin-dependent protein kinase activity

Inferred from sequence or structural similarity. Source: Alzheimers_University_of_Toronto

non-membrane spanning protein tyrosine kinase activity

Inferred from direct assay Ref.1. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 9020138. Source: UniProtKB

protein tyrosine kinase activity

Traceable author statement PubMed 8939945. Source: ProtInc

signal transducer activity

Non-traceable author statement PubMed 10867021. Source: ProtInc

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q14289-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q14289-2)

Also known as: PYK2H;

The sequence of this isoform differs from the canonical sequence as follows:
     739-780: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10091009Protein-tyrosine kinase 2-beta
PRO_0000088081

Regions

Domain39 – 359321FERM
Domain425 – 683259Protein kinase
Nucleotide binding431 – 4399ATP
Nucleotide binding503 – 5097ATP
Region801 – 1009209Interaction with TGFB1I1 By similarity
Region868 – 1009142Focal adhesion targeting (FAT)
Compositional bias702 – 76766Pro-rich
Compositional bias831 – 86939Pro-rich

Sites

Active site5491Proton acceptor By similarity
Binding site4571ATP

Amino acid modifications

Modified residue3611Phosphoserine Ref.32
Modified residue3751Phosphoserine Ref.25 Ref.26 Ref.32
Modified residue3991Phosphoserine Ref.32
Modified residue4021Phosphotyrosine; by autocatalysis Ref.14 Ref.20 Ref.21 Ref.29 Ref.33 Ref.35 Ref.36
Modified residue4401Phosphotyrosine By similarity
Modified residue5791Phosphotyrosine; by SRC, LYN and LCK By similarity
Modified residue5801Phosphotyrosine; by SRC, LYN and LCK Ref.35 Ref.36
Modified residue7221Phosphotyrosine Ref.32
Modified residue7621Phosphoserine Ref.32
Modified residue7651Phosphothreonine Ref.26
Modified residue8191Phosphotyrosine Ref.32
Modified residue8341Phosphotyrosine Ref.32
Modified residue8391Phosphoserine Ref.26 Ref.32
Modified residue8421Phosphothreonine Ref.26 Ref.32
Modified residue8491Phosphotyrosine Ref.32
Modified residue8661Phosphoserine Ref.32
Modified residue8811Phosphotyrosine; by SRC Ref.33

Natural variations

Alternative sequence739 – 78042Missing in isoform 2.
VSP_004981
Natural variant3591Q → E. Ref.49
Corresponds to variant rs56175011 [ dbSNP | Ensembl ].
VAR_041687
Natural variant6981R → H. Ref.49
Corresponds to variant rs35174236 [ dbSNP | Ensembl ].
VAR_041688
Natural variant8081L → P. Ref.49
Corresponds to variant rs55747955 [ dbSNP | Ensembl ].
VAR_041689
Natural variant8381K → T. Ref.32 Ref.49
Corresponds to variant rs751019 [ dbSNP | Ensembl ].
VAR_020284
Natural variant9701E → K. Ref.49
Corresponds to variant rs56263944 [ dbSNP | Ensembl ].
VAR_041690

Experimental info

Mutagenesis4021Y → F: Abolishes autophosphorylation. Abolishes interaction with SRC. Ref.9
Mutagenesis4571K → A: Abolishes kinase activity. Ref.20
Mutagenesis8591P → A: Loss of interaction with NPHP1. Ref.14
Mutagenesis8811Y → F: Loss of phosphorylation site. Strongly reduced interaction with GRB2. Ref.33
Sequence conflict231A → G in BAA08289. Ref.3
Sequence conflict231A → G in AAC05330. Ref.3
Sequence conflict2561G → P in AAB47217. Ref.2
Sequence conflict4351F → L in AAC05330. Ref.3
Sequence conflict7801R → G in AAB47217. Ref.2
Sequence conflict9851V → M in AAH36651. Ref.8

Secondary structure

.............................................................................................................................. 1009
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 15, 1998. Version 2.
Checksum: 420B21046274E7C2

FASTA1,009115,875
        10         20         30         40         50         60 
MSGVSEPLSR VKLGTLRRPE GPAEPMVVVP VDVEKEDVRI LKVCFYSNSF NPGKNFKLVK 

        70         80         90        100        110        120 
CTVQTEIREI ITSILLSGRI GPNIRLAECY 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 SQDAKPTCLA 

       310        320        330        340        350        360 
EFKQIRSIRC LPLEEGQAVL QLGIEGAPQA LSIKTSSLAE AENMADLIDG YCRLQGEHQG 

       370        380        390        400        410        420 
SLIIHPRKDG EKRNSLPQIP MLNLEARRSH LSESCSIESD IYAEIPDETL RRPGGPQYGI 

       430        440        450        460        470        480 
AREDVVLNRI LGEGFFGEVY EGVYTNHKGE KINVAVKTCK KDCTLDNKEK FMSEAVIMKN 

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

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

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

       670        680        690        700        710        720 
CWDYDPSDRP RFTELVCSLS DVYQMEKDIA MEQERNARYR TPKILEPTAF QEPPPKPSRP 

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

       790        800        810        820        830        840 
EEDFIQPSSR EEAQQLWEAE KVKMRQILDK QQKQMVEDYQ WLRQEEKSLD PMVYMNDKSP 

       850        860        870        880        890        900 
LTPEKEVGYL EFTGPPQKPP RLGAQSIQPT ANLDRTDDLV YLNVMELVRA VLELKNELCQ 

       910        920        930        940        950        960 
LPPEGYVVVV KNVGLTLRKL IGSVDDLLPS LPSSSRTEIE GTQKLLNKDL AELINKMRLA 

       970        980        990       1000 
QQNAVTSLSE ECKRQMLTAS HTLAVDAKNL LDAVDQAKVL ANLAHPPAE 

« Hide

Isoform 2 (PYK2H) [UniParc].

Checksum: 4AFDAA83908F2902
Show »

FASTA967111,183

References

« Hide 'large scale' references
[1]"Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions."
Lev S., Moreno H., Martinez R., Canoll P., Peles E., Musacchio J.M., Plowman G.D., Rudy B., Schlessinger J.
Nature 376:737-745(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN REGULATION OF POTASSIUM CHANNELS; PHOSPHORYLATION OF KCNA2 AND SHC1 AND ACTIVATION OF MAPK1/ERK2, INTERACTION WITH GRB2, TISSUE SPECIFICITY.
Tissue: Brain.
[2]"Molecular cloning and assignment of FAK2, a novel human focal adhesion kinase, to 8p11.2-p22 by nonisotopic in situ hybridization."
Herzog H., Nicholl J., Hort Y.J., Sutherland G.R., Shine J.
Genomics 32:484-486(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Hippocampus.
[3]"Cloning and characterization of cell adhesion kinase beta, a novel protein-tyrosine kinase of the focal adhesion kinase subfamily."
Sasaki H., Nagura K., Ishino M., Tobioka H., Kotani K., Sasaki T.
J. Biol. Chem. 270:21206-21219(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Hippocampus.
[4]"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] (ISOFORM 1).
[5]"A calcium-dependent tyrosine kinase splice variant in human monocytes. Activation by a two-stage process involving adherence and a subsequent intracellular signal."
Li X., Hunter D., Morris J., Haskill J.S., Earp H.S.
J. Biol. Chem. 273:9361-9364(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PHOSPHORYLATION, TISSUE SPECIFICITY.
Tissue: Monocyte.
[6]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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] (ISOFORM 1).
Tissue: Lymph and Testis.
[9]"A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation."
Dikic I., Tokiwa G., Lev S., Courtneidge S.A., Schlessinger J.
Nature 383:547-550(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF SRC AND ACTIVATION OF THE MAP KINASE SIGNALING CASCADE, INTERACTION WITH SRC, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-402.
[10]"Activation of Pyk2 by stress signals and coupling with JNK signaling pathway."
Tokiwa G., Dikic I., Lev S., Schlessinger J.
Science 273:792-794(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN TNF SIGNALING AND ACTIVATION OF MAPK8/JNK1.
[11]"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.
[12]"Identification of a new Pyk2 target protein with Arf-GAP activity."
Andreev J., Simon J.-P., Sabatini D.D., Kam J., Plowman G., Randazzo P.A., Schlessinger J.
Mol. Cell. Biol. 19:2338-2350(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ASAP2, FUNCTION.
[13]"Suppression of Pyk2 kinase and cellular activities by FIP200."
Ueda H., Abbi S., Zheng C., Guan J.-L.
J. Cell Biol. 149:423-430(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RB1CC1.
[14]"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, MUTAGENESIS OF PRO-859, INTERACTION WITH NPHP1.
[15]"The tyrosine kinase Pyk2 regulates Arf1 activity by phosphorylation and inhibition of the Arf-GTPase-activating protein ASAP1."
Kruljac-Letunic A., Moelleken J., Kallin A., Wieland F., Blaukat A.
J. Biol. Chem. 278:29560-29570(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ASAP1 PHOSPHORYLATION AND REGULATION OF ASAP1 ACTIVITY, INTERACTION WITH ASAP1.
[16]"Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein phosphorylation."
Takahashi T., Yamashita H., Nagano Y., Nakamura T., Ohmori H., Avraham H., Avraham S., Yasuda M., Matsumoto M.
J. Biol. Chem. 278:42225-42233(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SKAP2, SUBCELLULAR LOCATION, FUNCTION.
[17]"Pyk2- and Src-dependent tyrosine phosphorylation of PDK1 regulates focal adhesions."
Taniyama Y., Weber D.S., Rocic P., Hilenski L., Akers M.L., Park J., Hemmings B.A., Alexander R.W., Griendling K.K.
Mol. Cell. Biol. 23:8019-8029(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PDPK1, SUBCELLULAR LOCATION.
[18]"Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry."
Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.
Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"Integrin engagement-induced inhibition of human myelopoiesis is mediated by proline-rich tyrosine kinase 2 gene products."
Dylla S.J., Deyle D.R., Theunissen K., Padurean A.M., Verfaillie C.M.
Exp. Hematol. 32:365-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INTEGRIN SIGNALING AND IN REGULATION OF CELL PROLIFERATION, CATALYTIC ACTIVITY, CHARACTERIZATION OF ISOFORM 2.
[20]"RAFTK/Pyk2 activation is mediated by trans-acting autophosphorylation in a Src-independent manner."
Park S.Y., Avraham H.K., Avraham S.
J. Biol. Chem. 279:33315-33322(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-402, CATALYTIC ACTIVITY, FUNCTION IN SRC-MEDIATED PHOSPHORYLATION OF PXN, MUTAGENESIS OF LYS-457.
[21]"Interaction of Pyk2 and PTP-PEST with leupaxin in prostate cancer cells."
Sahu S.N., Nunez S., Bai G., Gupta A.
Am. J. Physiol. 292:C2288-C2296(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LPXN AND PTPN12, PHOSPHORYLATION AT TYR-402, DEPHOSPHORYLATION BY PTPN12.
[22]"Ephrin-A1 stimulates migration of CD8+CCR7+ T lymphocytes."
Hjorthaug H.S., Aasheim H.C.
Eur. J. Immunol. 37:2326-2336(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MIGRATION OF T-LYMPHOCYTES, INTERACTION WITH EPHA1; LCK AND PI3-KINASE.
[23]"Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271."
Roberts W.G., Ung E., Whalen P., Cooper B., Hulford C., Autry C., Richter D., Emerson E., Lin J., Kath J., Coleman K., Yao L., Martinez-Alsina L., Lorenzen M., Berliner M., Luzzio M., Patel N., Schmitt E. expand/collapse author list , LaGreca S., Jani J., Wessel M., Marr E., Griffor M., Vajdos F.
Cancer Res. 68:1935-1944(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, ROLE IN DISEASE.
[24]"Proline-rich tyrosine kinase 2 (Pyk2) promotes proliferation and invasiveness of hepatocellular carcinoma cells through c-Src/ERK activation."
Sun C.K., Man K., Ng K.T., Ho J.W., Lim Z.X., Cheng Q., Lo C.M., Poon R.T., Fan S.T.
Carcinogenesis 29:2096-2105(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL ADHESION; MIGRATION; PROLIFERATION; REGULATION OF ACTIN FIBER POLYMERIZATION AND IN ACTIVATION OF SRC; MAPK1/ERK2 AND MAPK3/ERK1, INTERACTION WITH SRC, SUBCELLULAR LOCATION, ROLE IN DISEASE.
[25]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[26]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375; THR-765; SER-839 AND THR-842, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[27]"The atypical Rho GTPase Wrch1 collaborates with the nonreceptor tyrosine kinases Pyk2 and Src in regulating cytoskeletal dynamics."
Ruusala A., Aspenstrom P.
Mol. Cell. Biol. 28:1802-1814(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RHOU, FUNCTION IN REORGANIZATION OF ACTIN CYTOSKELETON AND SRC-MEDIATED RHOU PHOSPHORYLATION.
[28]"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.
[29]"A Pyk2-Vav1 complex is recruited to beta3-adhesion sites to initiate Rho activation."
Gao C., Blystone S.D.
Biochem. J. 420:49-56(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REGULATION OF ACTIN CYTOSKELETON REORGANIZATION AND ACTIVATION OF RHO FAMILY GTPASES, PHOSPHORYLATION AT TYR-402, SUBCELLULAR LOCATION, INTERACTION WITH VAV1.
[30]"Identification of small molecule inhibitors of proline-rich tyrosine kinase 2 (Pyk2) with osteogenic activity in osteoblast cells."
Allen J.G., Lee M.R., Han C.Y., Scherrer J., Flynn S., Boucher C., Zhao H., O'Connor A.B., Roveto P., Bauer D., Graceffa R., Richards W.G., Babij P.
Bioorg. Med. Chem. Lett. 19:4924-4928(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ROLE IN DISEASE, CATALYTIC ACTIVITY, ENZYME REGULATION.
[31]"Pyk2 mediates endothelin-1 signaling via p130Cas/BCAR3 cascade and regulates human glomerular mesangial cell adhesion and spreading."
Rufanova V.A., Alexanian A., Wakatsuki T., Lerner A., Sorokin A.
J. Cell. Physiol. 219:45-56(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL ADHESION AND SPREADING, AUTOPHOSPHORYLATION, INTERACTION WITH BCAR1.
[32]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361; SER-375; SER-399; TYR-722; SER-762; TYR-819; TYR-834; SER-839; THR-842; TYR-849 AND SER-866, VARIANT [LARGE SCALE ANALYSIS] THR-838, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[33]"Recruitment of Pyk2 to SHPS-1 signaling complex is required for IGF-I-dependent mitogenic signaling in vascular smooth muscle cells."
Shen X., Xi G., Radhakrishnan Y., Clemmons D.R.
Cell. Mol. Life Sci. 67:3893-3903(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN IGF1 SIGNALING AND ACTIVATION OF MAPK1/ERK2 AND MAPK3/ERK1, INTERACTION WITH SRC AND GRB2, PHOSPHORYLATION AT TYR-402 AND TYR-881, MUTAGENESIS OF TYR-881.
[34]"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 OF P53/TP53 UBIQUITINATION, SUBCELLULAR LOCATION.
[35]"The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 and 580 occurs via a distinct mechanism than other receptor systems."
Collins M., Tremblay M., Chapman N., Curtiss M., Rothman P.B., Houtman J.C.
J. Leukoc. Biol. 87:691-701(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-402 AND TYR-580 BY FYN AND LCK.
[36]"T cell receptor activation leads to two distinct phases of Pyk2 activation and actin cytoskeletal rearrangement in human T cells."
Collins M., Bartelt R.R., Houtman J.C.
Mol. Immunol. 47:1665-1674(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN T-CELL RECEPTOR-MEDIATED SIGNALING, PHOSPHORYLATION AT TYR-402 AND TYR-580.
[37]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[38]"Nephrocystin-4 regulates Pyk2-induced tyrosine phosphorylation of nephrocystin-1 to control targeting to monocilia."
Liebau M.C., Hopker K., Muller R.U., Schmedding I., Zank S., Schairer B., Fabretti F., Hohne M., Bartram M.P., Dafinger C., Hackl M., Burst V., Habbig S., Zentgraf H., Blaukat A., Walz G., Benzing T., Schermer B.
J. Biol. Chem. 286:14237-14245(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NPHP1, FUNCTION IN PHOSPHORYLATION OF NPHP1.
[39]"Proline-rich tyrosine kinase 2 (Pyk2) promotes cell motility of hepatocellular carcinoma through induction of epithelial to mesenchymal transition."
Sun C.K., Ng K.T., Lim Z.X., Cheng Q., Lo C.M., Poon R.T., Man K., Wong N., Fan S.T.
PLoS ONE 6:E18878-E18878(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REORGANIZATION OF CYTOSKELETON; FORMATION OF MEMBRANE RUFFLES AND CELL MIGRATION, ROLE IN DISEASE.
[40]"Focal adhesion kinase-related protein tyrosine kinase Pyk2 in T-cell activation and function."
Ostergaard H.L., Lysechko T.L.
Immunol. Res. 31:267-282(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON ROLE IN IMMUNITY.
[41]"Targeting Pyk2 for therapeutic intervention."
Lipinski C.A., Loftus J.C.
Expert Opin. Ther. Targets 14:95-108(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION; SIGNALING; INTERACTION PARTNERS; ENZYME REGULATION; PHOSPHORYLATION, ROLE IN DISEASE.
[42]"Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions."
Schaller M.D.
J. Cell Sci. 123:1007-1013(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[43]"Redox sensitive Pyk2 as a target for therapeutics in breast cancer."
Felty Q.
Front. Biosci. 16:568-577(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON ROLE IN DISEASE.
[44]"Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase 2 (PYK2): structure-activity relationships and strategies for the elimination of reactive metabolite formation."
Walker D.P., Bi F.C., Kalgutkar A.S., Bauman J.N., Zhao S.X., Soglia J.R., Aspnes G.E., Kung D.W., Klug-McLeod J., Zawistoski M.P., McGlynn M.A., Oliver R., Dunn M., Li J.C., Richter D.T., Cooper B.A., Kath J.C., Hulford C.A. expand/collapse author list , Autry C.L., Luzzio M.J., Ung E.J., Roberts W.G., Bonnette P.C., Buckbinder L., Mistry A., Griffor M.C., Han S., Guzman-Perez A.
Bioorg. Med. Chem. Lett. 18:6071-6077(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 416-692 IN COMPLEX WITH PF-2318841, CATALYTIC ACTIVITY, ENZYME REGULATION.
[45]"Crystal structures of free and ligand-bound focal adhesion targeting domain of Pyk2."
Lulo J., Yuzawa S., Schlessinger J.
Biochem. Biophys. Res. Commun. 383:347-352(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 861-1009 IN COMPLEX WITH PXN, INTERACTION WITH PXN.
[46]"Sulfoximine-substituted trifluoromethylpyrimidine analogs as inhibitors of proline-rich tyrosine kinase 2 (PYK2) show reduced hERG activity."
Walker D.P., Zawistoski M.P., McGlynn M.A., Li J.C., Kung D.W., Bonnette P.C., Baumann A., Buckbinder L., Houser J.A., Boer J., Mistry A., Han S., Xing L., Guzman-Perez A.
Bioorg. Med. Chem. Lett. 19:3253-3258(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 416-692 IN COMPLEX WITH INHIBITOR P1E, ROLE IN DISEASE, CATALYTIC ACTIVITY, ENZYME REGULATION.
[47]"Structural characterization of proline-rich tyrosine kinase 2 (PYK2) reveals a unique (DFG-out) conformation and enables inhibitor design."
Han S., Mistry A., Chang J.S., Cunningham D., Griffor M., Bonnette P.C., Wang H., Chrunyk B.A., Aspnes G.E., Walker D.P., Brosius A.D., Buckbinder L.
J. Biol. Chem. 284:13193-13201(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 416-692 IN COMPLEXES WITH ATP ANALOG; PF-431396; BIRB796 AND PF-4618433, ROLE IN DISEASE.
[48]"Structure of protein tyrosine kinase 2 beta (PTK2B) kinase domain."
Structural genomics consortium (SGC)
Submitted (JUL-2011) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 414-692.
[49]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLU-359; HIS-698; PRO-808; THR-838 AND LYS-970.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U33284 mRNA. Translation: AAC50203.1.
L49207 mRNA. Translation: AAB47217.1.
D45853 mRNA. Translation: BAA08289.1.
U43522 mRNA. Translation: AAC05330.1.
S80542 mRNA. Translation: AAB35701.1.
AF311103 Genomic DNA. No translation available.
CH471080 Genomic DNA. Translation: EAW63553.1.
CH471080 Genomic DNA. Translation: EAW63555.1.
CH471080 Genomic DNA. Translation: EAW63556.1.
BC036651 mRNA. Translation: AAH36651.1.
BC042599 mRNA. Translation: AAH42599.1.
CCDSCCDS6057.1. [Q14289-1]
CCDS6058.1. [Q14289-2]
PIRS60248.
RefSeqNP_004094.3. NM_004103.4. [Q14289-1]
NP_775266.1. NM_173174.2. [Q14289-1]
NP_775267.1. NM_173175.2. [Q14289-2]
NP_775268.1. NM_173176.2. [Q14289-1]
XP_005273504.1. XM_005273447.2. [Q14289-1]
UniGeneHs.491322.
Hs.735450.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2FO6model-X45-350[»]
2LK4NMR-A871-1005[»]
3CC6X-ray1.60A414-692[»]
3ET7X-ray2.70A416-692[»]
3FZOX-ray2.20A416-692[»]
3FZPX-ray2.10A416-692[»]
3FZRX-ray2.70A416-692[»]
3FZSX-ray1.75A416-692[»]
3FZTX-ray1.95A416-692[»]
3GM1X-ray2.95A/B861-1009[»]
3GM2X-ray2.71A861-1009[»]
3GM3X-ray2.60A861-1009[»]
3H3CX-ray2.00A416-692[»]
3U3CX-ray3.70A871-1005[»]
3U3FX-ray3.10A/B/C/D871-1005[»]
4EKUX-ray3.25A21-409[»]
4H1JX-ray2.00A416-692[»]
4H1MX-ray1.99A416-692[»]
ProteinModelPortalQ14289.
SMRQ14289. Positions 21-692, 867-1007.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108480. 63 interactions.
IntActQ14289. 13 interactions.
MINTMINT-1211326.
STRING9606.ENSP00000332816.

Chemistry

BindingDBQ14289.
ChEMBLCHEMBL5469.
GuidetoPHARMACOLOGY2181.

PTM databases

PhosphoSiteQ14289.

Polymorphism databases

DMDM3183003.

Proteomic databases

MaxQBQ14289.
PaxDbQ14289.
PRIDEQ14289.

Protocols and materials databases

DNASU2185.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000338238; ENSP00000342242; ENSG00000120899. [Q14289-2]
ENST00000346049; ENSP00000332816; ENSG00000120899. [Q14289-1]
ENST00000397501; ENSP00000380638; ENSG00000120899. [Q14289-1]
ENST00000420218; ENSP00000391995; ENSG00000120899. [Q14289-2]
ENST00000517339; ENSP00000427931; ENSG00000120899. [Q14289-2]
ENST00000544172; ENSP00000440926; ENSG00000120899. [Q14289-1]
GeneID2185.
KEGGhsa:2185.
UCSCuc003xfn.2. human. [Q14289-1]
uc003xfq.2. human. [Q14289-2]

Organism-specific databases

CTD2185.
GeneCardsGC08P027224.
H-InvDBHIX0168898.
HGNCHGNC:9612. PTK2B.
HPACAB003850.
HPA026091.
HPA026276.
MIM601212. gene.
neXtProtNX_Q14289.
PharmGKBPA33956.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000069938.
HOVERGENHBG004018.
InParanoidQ14289.
KOK05871.
OMAQMLTASH.
OrthoDBEOG7ZSHSB.
PhylomeDBQ14289.
TreeFamTF316643.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
ReactomeREACT_111155. Cell-Cell communication.
REACT_6900. Immune System.
SignaLinkQ14289.

Gene expression databases

ArrayExpressQ14289.
BgeeQ14289.
CleanExHS_PTK2B.
GenevestigatorQ14289.

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.
IPR029071. Ubiquitin-rel_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.
SSF54236. SSF54236. 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

ChiTaRSPTK2B. human.
EvolutionaryTraceQ14289.
GeneWikiPTK2B.
GenomeRNAi2185.
NextBio8821.
PROQ14289.
SOURCESearch...

Entry information

Entry nameFAK2_HUMAN
AccessionPrimary (citable) accession number: Q14289
Secondary accession number(s): D3DST0 expand/collapse secondary AC list , Q13475, Q14290, Q16709, Q6PID4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1998
Last modified: July 9, 2014
This is version 169 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM