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Q14289

- FAK2_HUMAN

UniProt

Q14289 - FAK2_HUMAN

Protein

Protein-tyrosine kinase 2-beta

Gene

PTK2B

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 171 (01 Oct 2014)
      Sequence version 2 (15 Jul 1998)
      Previous versions | rss
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    Functioni

    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/PYK2.25 Publications

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.6 PublicationsPROSITE-ProRule annotation

    Enzyme regulationi

    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.4 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei457 – 4571ATP
    Active sitei549 – 5491Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi431 – 4399ATP
    Nucleotide bindingi503 – 5097ATP

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. calmodulin-dependent protein kinase activity Source: Alzheimers_University_of_Toronto
    3. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
    4. protein binding Source: UniProtKB
    5. protein tyrosine kinase activity Source: ProtInc
    6. signal transducer activity Source: ProtInc

    GO - Biological processi

    1. activation of Janus kinase activity Source: UniProtKB
    2. activation of Rac GTPase activity Source: Ensembl
    3. apoptotic process Source: ProtInc
    4. blood vessel endothelial cell migration Source: Ensembl
    5. bone resorption Source: UniProtKB
    6. cell surface receptor signaling pathway Source: UniProtKB
    7. cellular defense response Source: Alzheimers_University_of_Toronto
    8. cellular response to retinoic acid Source: BHF-UCL
    9. chemokine-mediated signaling pathway Source: UniProtKB
    10. epidermal growth factor receptor signaling pathway Source: Ensembl
    11. focal adhesion assembly Source: Ensembl
    12. glial cell proliferation Source: Ensembl
    13. integrin-mediated signaling pathway Source: UniProtKB
    14. ionotropic glutamate receptor signaling pathway Source: Alzheimers_University_of_Toronto
    15. long-term synaptic potentiation Source: Alzheimers_University_of_Toronto
    16. MAPK cascade Source: Ensembl
    17. marginal zone B cell differentiation Source: UniProtKB
    18. negative regulation of apoptotic process Source: UniProtKB
    19. negative regulation of bone mineralization Source: UniProtKB
    20. negative regulation of cell proliferation Source: UniProtKB
    21. negative regulation of muscle cell apoptotic process Source: Ensembl
    22. negative regulation of myeloid cell differentiation Source: UniProtKB
    23. negative regulation of neuron apoptotic process Source: Alzheimers_University_of_Toronto
    24. negative regulation of potassium ion transport Source: UniProtKB
    25. neuron projection development Source: Ensembl
    26. oocyte maturation Source: Ensembl
    27. peptidyl-tyrosine autophosphorylation Source: Alzheimers_University_of_Toronto
    28. peptidyl-tyrosine phosphorylation Source: UniProtKB
    29. positive regulation of actin filament polymerization Source: UniProtKB
    30. positive regulation of angiogenesis Source: Ensembl
    31. positive regulation of B cell chemotaxis Source: UniProtKB
    32. positive regulation of cell growth Source: Ensembl
    33. positive regulation of cell-matrix adhesion Source: UniProtKB
    34. positive regulation of cell migration Source: UniProtKB
    35. positive regulation of cell proliferation Source: UniProtKB
    36. positive regulation of cytosolic calcium ion concentration Source: Ensembl
    37. positive regulation of endothelial cell migration Source: BHF-UCL
    38. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    39. positive regulation of excitatory postsynaptic membrane potential Source: Alzheimers_University_of_Toronto
    40. positive regulation of JNK cascade Source: UniProtKB
    41. positive regulation of JUN kinase activity Source: Ensembl
    42. positive regulation of neuron projection development Source: BHF-UCL
    43. positive regulation of nitric-oxide synthase activity Source: Ensembl
    44. positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
    45. positive regulation of phosphatidylinositol 3-kinase activity Source: UniProtKB
    46. positive regulation of protein kinase activity Source: UniProtKB
    47. positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: Ensembl
    48. positive regulation of reactive oxygen species metabolic process Source: Ensembl
    49. positive regulation of synaptic transmission, glutamatergic Source: Alzheimers_University_of_Toronto
    50. positive regulation of translation Source: Ensembl
    51. protein autophosphorylation Source: UniProtKB
    52. protein complex assembly Source: ProtInc
    53. protein phosphorylation Source: ProtInc
    54. regulation of actin cytoskeleton reorganization Source: UniProtKB
    55. regulation of calcium-mediated signaling Source: Ensembl
    56. regulation of cell adhesion Source: UniProtKB
    57. regulation of cell shape Source: UniProtKB
    58. regulation of cGMP biosynthetic process Source: Ensembl
    59. regulation of cGMP-mediated signaling Source: Ensembl
    60. regulation of establishment of cell polarity Source: UniProtKB
    61. regulation of inositol trisphosphate biosynthetic process Source: UniProtKB
    62. regulation of macrophage chemotaxis Source: UniProtKB
    63. regulation of nitric oxide biosynthetic process Source: Ensembl
    64. regulation of N-methyl-D-aspartate selective glutamate receptor activity Source: Alzheimers_University_of_Toronto
    65. regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: UniProtKB
    66. regulation of release of sequestered calcium ion into cytosol Source: UniProtKB
    67. response to calcium ion Source: Ensembl
    68. response to cAMP Source: Ensembl
    69. response to cocaine Source: Ensembl
    70. response to drug Source: Ensembl
    71. response to ethanol Source: Ensembl
    72. response to glucose Source: Ensembl
    73. response to hormone Source: Ensembl
    74. response to hydrogen peroxide Source: Ensembl
    75. response to hypoxia Source: Ensembl
    76. response to lithium ion Source: Ensembl
    77. response to mechanical stimulus Source: Ensembl
    78. response to osmotic stress Source: Ensembl
    79. response to stress Source: ProtInc
    80. signal complex assembly Source: ProtInc
    81. signal transduction Source: ProtInc
    82. sprouting angiogenesis Source: UniProtKB
    83. stress fiber assembly Source: Ensembl
    84. tumor necrosis factor-mediated signaling pathway Source: UniProtKB
    85. vascular endothelial growth factor receptor signaling pathway Source: BHF-UCL

    Keywords - Molecular functioni

    Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Adaptive immunity, Angiogenesis, Immunity

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.2. 2681.
    ReactomeiREACT_23916. Signal regulatory protein (SIRP) family interactions.
    REACT_27283. Interleukin-2 signaling.
    SignaLinkiQ14289.

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:PTK2B
    Synonyms:FAK2, PYK2, RAFTK
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:9612. PTK2B.

    Subcellular locationi

    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.

    GO - Cellular componenti

    1. apical dendrite Source: Alzheimers_University_of_Toronto
    2. axon Source: Ensembl
    3. cell body Source: Alzheimers_University_of_Toronto
    4. cell cortex Source: UniProtKB-SubCell
    5. cytoplasm Source: HPA
    6. cytosol Source: Reactome
    7. dendrite Source: Alzheimers_University_of_Toronto
    8. focal adhesion Source: UniProtKB
    9. growth cone Source: Alzheimers_University_of_Toronto
    10. lamellipodium Source: UniProtKB
    11. membrane raft Source: Ensembl
    12. neuronal cell body Source: Alzheimers_University_of_Toronto
    13. N-methyl-D-aspartate selective glutamate receptor complex Source: Alzheimers_University_of_Toronto
    14. nucleus Source: UniProtKB
    15. perinuclear region of cytoplasm Source: UniProtKB
    16. postsynaptic density Source: Alzheimers_University_of_Toronto

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    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.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi402 – 4021Y → F: Abolishes autophosphorylation. Abolishes interaction with SRC. 1 Publication
    Mutagenesisi457 – 4571K → A: Abolishes kinase activity. 1 Publication
    Mutagenesisi859 – 8591P → A: Loss of interaction with NPHP1. 1 Publication
    Mutagenesisi881 – 8811Y → F: Loss of phosphorylation site. Strongly reduced interaction with GRB2. 1 Publication

    Organism-specific databases

    PharmGKBiPA33956.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10091009Protein-tyrosine kinase 2-betaPRO_0000088081Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei361 – 3611Phosphoserine1 Publication
    Modified residuei375 – 3751Phosphoserine3 Publications
    Modified residuei399 – 3991Phosphoserine1 Publication
    Modified residuei402 – 4021Phosphotyrosine; by autocatalysis7 Publications
    Modified residuei440 – 4401PhosphotyrosineBy similarity
    Modified residuei579 – 5791Phosphotyrosine; by SRC, LYN and LCKBy similarity
    Modified residuei580 – 5801Phosphotyrosine; by SRC, LYN and LCK2 Publications
    Modified residuei722 – 7221Phosphotyrosine1 Publication
    Modified residuei762 – 7621Phosphoserine1 Publication
    Modified residuei765 – 7651Phosphothreonine1 Publication
    Modified residuei819 – 8191Phosphotyrosine1 Publication
    Modified residuei834 – 8341Phosphotyrosine1 Publication
    Modified residuei839 – 8391Phosphoserine2 Publications
    Modified residuei842 – 8421Phosphothreonine2 Publications
    Modified residuei849 – 8491Phosphotyrosine1 Publication
    Modified residuei866 – 8661Phosphoserine1 Publication
    Modified residuei881 – 8811Phosphotyrosine; by SRC1 Publication

    Post-translational modificationi

    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 PTPN12.12 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ14289.
    PaxDbiQ14289.
    PRIDEiQ14289.

    PTM databases

    PhosphoSiteiQ14289.

    Expressioni

    Tissue specificityi

    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.2 Publications

    Gene expression databases

    ArrayExpressiQ14289.
    BgeeiQ14289.
    CleanExiHS_PTK2B.
    GenevestigatoriQ14289.

    Organism-specific databases

    HPAiCAB003850.
    HPA026091.
    HPA026276.

    Interactioni

    Subunit structurei

    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.By similarity21 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    RHOUQ7L0Q84EBI-298640,EBI-1638043
    SRCP129313EBI-298640,EBI-621482

    Protein-protein interaction databases

    BioGridi108480. 63 interactions.
    IntActiQ14289. 14 interactions.
    MINTiMINT-1211326.
    STRINGi9606.ENSP00000332816.

    Structurei

    Secondary structure

    1
    1009
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi35 – 373
    Beta strandi38 – 458
    Beta strandi48 – 503
    Helixi52 – 543
    Beta strandi55 – 628
    Helixi67 – 7610
    Turni77 – 804
    Helixi87 – 893
    Beta strandi90 – 9910
    Beta strandi102 – 1054
    Helixi111 – 1177
    Turni119 – 1213
    Helixi124 – 1263
    Beta strandi127 – 1337
    Turni138 – 1403
    Helixi141 – 1444
    Helixi148 – 16518
    Turni166 – 1694
    Helixi172 – 18615
    Turni187 – 1893
    Helixi194 – 1963
    Helixi198 – 20710
    Helixi210 – 2123
    Helixi216 – 2216
    Helixi224 – 23815
    Helixi243 – 25412
    Beta strandi263 – 27311
    Beta strandi277 – 2826
    Beta strandi285 – 2895
    Beta strandi297 – 3004
    Helixi302 – 3043
    Beta strandi310 – 3134
    Turni314 – 3163
    Beta strandi317 – 3226
    Beta strandi331 – 3366
    Helixi338 – 35518
    Beta strandi356 – 3605
    Helixi422 – 4243
    Beta strandi425 – 4339
    Beta strandi435 – 44511
    Beta strandi447 – 4493
    Beta strandi451 – 4588
    Beta strandi461 – 4633
    Helixi465 – 48117
    Beta strandi489 – 4935
    Beta strandi495 – 4973
    Beta strandi499 – 5035
    Helixi510 – 5178
    Turni518 – 5203
    Helixi523 – 54220
    Beta strandi546 – 5483
    Helixi552 – 5543
    Beta strandi555 – 5595
    Beta strandi562 – 5654
    Helixi570 – 5723
    Helixi589 – 5913
    Helixi594 – 5996
    Helixi604 – 61916
    Turni620 – 6223
    Turni625 – 6284
    Helixi631 – 6333
    Helixi634 – 6407
    Helixi652 – 66110
    Helixi666 – 6683
    Helixi672 – 69120
    Helixi879 – 89719
    Helixi898 – 9003
    Helixi903 – 92725
    Helixi928 – 9303
    Helixi933 – 96230
    Turni963 – 9653
    Helixi969 – 100335

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliQ14289.
    SMRiQ14289. Positions 21-692, 867-1007.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ14289.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini39 – 359321FERMPROSITE-ProRule annotationAdd
    BLAST
    Domaini425 – 683259Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni801 – 1009209Interaction with TGFB1I1By similarityAdd
    BLAST
    Regioni868 – 1009142Focal adhesion targeting (FAT)Add
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi702 – 76766Pro-richAdd
    BLAST
    Compositional biasi831 – 86939Pro-richAdd
    BLAST

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. FAK subfamily.PROSITE-ProRule annotation
    Contains 1 FERM domain.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000069938.
    HOVERGENiHBG004018.
    InParanoidiQ14289.
    KOiK05871.
    OMAiQMLTASH.
    OrthoDBiEOG7ZSHSB.
    PhylomeDBiQ14289.
    TreeFamiTF316643.

    Family and domain databases

    Gene3Di1.20.80.10. 1 hit.
    InterProiIPR019749. 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]
    PfamiPF00373. FERM_M. 1 hit.
    PF03623. Focal_AT. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view]
    PRINTSiPR00109. TYRKINASE.
    ProDomiPD006413. Focal_adhesion_target_reg. 1 hit.
    [Graphical view] [Entries sharing at least one domain]
    SMARTiSM00295. B41. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF47031. SSF47031. 1 hit.
    SSF54236. SSF54236. 1 hit.
    SSF56112. SSF56112. 1 hit.
    SSF68993. SSF68993. 1 hit.
    PROSITEiPS50057. FERM_3. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q14289-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MSGVSEPLSR VKLGTLRRPE GPAEPMVVVP VDVEKEDVRI LKVCFYSNSF     50
    NPGKNFKLVK CTVQTEIREI ITSILLSGRI GPNIRLAECY GLRLKHMKSD 100
    EIHWLHPQMT VGEVQDKYEC LHVEAEWRYD LQIRYLPEDF MESLKEDRTT 150
    LLYFYQQLRN DYMQRYASKV SEGMALQLGC LELRRFFKDM PHNALDKKSN 200
    FELLEKEVGL DLFFPKQMQE NLKPKQFRKM IQQTFQQYAS LREEECVMKF 250
    FNTLAGFANI DQETYRCELI QGWNITVDLV IGPKGIRQLT SQDAKPTCLA 300
    EFKQIRSIRC LPLEEGQAVL QLGIEGAPQA LSIKTSSLAE AENMADLIDG 350
    YCRLQGEHQG SLIIHPRKDG EKRNSLPQIP MLNLEARRSH LSESCSIESD 400
    IYAEIPDETL RRPGGPQYGI AREDVVLNRI LGEGFFGEVY EGVYTNHKGE 450
    KINVAVKTCK KDCTLDNKEK FMSEAVIMKN LDHPHIVKLI GIIEEEPTWI 500
    IMELYPYGEL GHYLERNKNS LKVLTLVLYS LQICKAMAYL ESINCVHRDI 550
    AVRNILVASP ECVKLGDFGL SRYIEDEDYY KASVTRLPIK WMSPESINFR 600
    RFTTASDVWM FAVCMWEILS FGKQPFFWLE NKDVIGVLEK GDRLPKPDLC 650
    PPVLYTLMTR CWDYDPSDRP RFTELVCSLS DVYQMEKDIA MEQERNARYR 700
    TPKILEPTAF QEPPPKPSRP KYRPPPQTNL LAPKLQFQVP EGLCASSPTL 750
    TSPMEYPSPV NSLHTPPLHR HNVFKRHSMR EEDFIQPSSR EEAQQLWEAE 800
    KVKMRQILDK QQKQMVEDYQ WLRQEEKSLD PMVYMNDKSP LTPEKEVGYL 850
    EFTGPPQKPP RLGAQSIQPT ANLDRTDDLV YLNVMELVRA VLELKNELCQ 900
    LPPEGYVVVV KNVGLTLRKL IGSVDDLLPS LPSSSRTEIE GTQKLLNKDL 950
    AELINKMRLA QQNAVTSLSE ECKRQMLTAS HTLAVDAKNL LDAVDQAKVL 1000
    ANLAHPPAE 1009
    Length:1,009
    Mass (Da):115,875
    Last modified:July 15, 1998 - v2
    Checksum:i420B21046274E7C2
    GO
    Isoform 2 (identifier: Q14289-2) [UniParc]FASTAAdd to Basket

    Also known as: PYK2H

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

    Show »
    Length:967
    Mass (Da):111,183
    Checksum:i4AFDAA83908F2902
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti23 – 231A → G in BAA08289. (PubMed:7673154)Curated
    Sequence conflicti23 – 231A → G in AAC05330. (PubMed:7673154)Curated
    Sequence conflicti256 – 2561G → P in AAB47217. (PubMed:8838818)Curated
    Sequence conflicti435 – 4351F → L in AAC05330. (PubMed:7673154)Curated
    Sequence conflicti780 – 7801R → G in AAB47217. (PubMed:8838818)Curated
    Sequence conflicti985 – 9851V → M in AAH36651. (PubMed:15489334)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti359 – 3591Q → E.1 Publication
    Corresponds to variant rs56175011 [ dbSNP | Ensembl ].
    VAR_041687
    Natural varianti698 – 6981R → H.1 Publication
    Corresponds to variant rs35174236 [ dbSNP | Ensembl ].
    VAR_041688
    Natural varianti808 – 8081L → P.1 Publication
    Corresponds to variant rs55747955 [ dbSNP | Ensembl ].
    VAR_041689
    Natural varianti838 – 8381K → T.2 Publications
    Corresponds to variant rs751019 [ dbSNP | Ensembl ].
    VAR_020284
    Natural varianti970 – 9701E → K.1 Publication
    Corresponds to variant rs56263944 [ dbSNP | Ensembl ].
    VAR_041690

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei739 – 78042Missing in isoform 2. 1 PublicationVSP_004981Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS6057.1. [Q14289-1]
    CCDS6058.1. [Q14289-2]
    PIRiS60248.
    RefSeqiNP_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]
    UniGeneiHs.491322.
    Hs.735450.

    Genome annotation databases

    EnsembliENST00000346049; ENSP00000332816; ENSG00000120899. [Q14289-1]
    ENST00000397501; ENSP00000380638; ENSG00000120899. [Q14289-1]
    ENST00000420218; ENSP00000391995; ENSG00000120899. [Q14289-2]
    ENST00000517339; ENSP00000427931; ENSG00000120899. [Q14289-2]
    GeneIDi2185.
    KEGGihsa:2185.
    UCSCiuc003xfn.2. human. [Q14289-1]
    uc003xfq.2. human. [Q14289-2]

    Polymorphism databases

    DMDMi3183003.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS6057.1. [Q14289-1 ]
    CCDS6058.1. [Q14289-2 ]
    PIRi S60248.
    RefSeqi NP_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 ]
    UniGenei Hs.491322.
    Hs.735450.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2FO6 model - X 45-350 [» ]
    2LK4 NMR - A 871-1005 [» ]
    3CC6 X-ray 1.60 A 414-692 [» ]
    3ET7 X-ray 2.70 A 416-692 [» ]
    3FZO X-ray 2.20 A 416-692 [» ]
    3FZP X-ray 2.10 A 416-692 [» ]
    3FZR X-ray 2.70 A 416-692 [» ]
    3FZS X-ray 1.75 A 416-692 [» ]
    3FZT X-ray 1.95 A 416-692 [» ]
    3GM1 X-ray 2.95 A/B 861-1009 [» ]
    3GM2 X-ray 2.71 A 861-1009 [» ]
    3GM3 X-ray 2.60 A 861-1009 [» ]
    3H3C X-ray 2.00 A 416-692 [» ]
    3U3C X-ray 3.70 A 871-1005 [» ]
    3U3F X-ray 3.10 A/B/C/D 871-1005 [» ]
    4EKU X-ray 3.25 A 21-409 [» ]
    4H1J X-ray 2.00 A 416-692 [» ]
    4H1M X-ray 1.99 A 416-692 [» ]
    ProteinModelPortali Q14289.
    SMRi Q14289. Positions 21-692, 867-1007.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108480. 63 interactions.
    IntActi Q14289. 14 interactions.
    MINTi MINT-1211326.
    STRINGi 9606.ENSP00000332816.

    Chemistry

    BindingDBi Q14289.
    ChEMBLi CHEMBL5469.
    GuidetoPHARMACOLOGYi 2181.

    PTM databases

    PhosphoSitei Q14289.

    Polymorphism databases

    DMDMi 3183003.

    Proteomic databases

    MaxQBi Q14289.
    PaxDbi Q14289.
    PRIDEi Q14289.

    Protocols and materials databases

    DNASUi 2185.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000346049 ; ENSP00000332816 ; ENSG00000120899 . [Q14289-1 ]
    ENST00000397501 ; ENSP00000380638 ; ENSG00000120899 . [Q14289-1 ]
    ENST00000420218 ; ENSP00000391995 ; ENSG00000120899 . [Q14289-2 ]
    ENST00000517339 ; ENSP00000427931 ; ENSG00000120899 . [Q14289-2 ]
    GeneIDi 2185.
    KEGGi hsa:2185.
    UCSCi uc003xfn.2. human. [Q14289-1 ]
    uc003xfq.2. human. [Q14289-2 ]

    Organism-specific databases

    CTDi 2185.
    GeneCardsi GC08P027224.
    H-InvDB HIX0168898.
    HGNCi HGNC:9612. PTK2B.
    HPAi CAB003850.
    HPA026091.
    HPA026276.
    MIMi 601212. gene.
    neXtProti NX_Q14289.
    PharmGKBi PA33956.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000069938.
    HOVERGENi HBG004018.
    InParanoidi Q14289.
    KOi K05871.
    OMAi QMLTASH.
    OrthoDBi EOG7ZSHSB.
    PhylomeDBi Q14289.
    TreeFami TF316643.

    Enzyme and pathway databases

    BRENDAi 2.7.10.2. 2681.
    Reactomei REACT_23916. Signal regulatory protein (SIRP) family interactions.
    REACT_27283. Interleukin-2 signaling.
    SignaLinki Q14289.

    Miscellaneous databases

    ChiTaRSi PTK2B. human.
    EvolutionaryTracei Q14289.
    GeneWikii PTK2B.
    GenomeRNAii 2185.
    NextBioi 8821.
    PROi Q14289.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q14289.
    Bgeei Q14289.
    CleanExi HS_PTK2B.
    Genevestigatori Q14289.

    Family and domain databases

    Gene3Di 1.20.80.10. 1 hit.
    InterProi IPR019749. 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 ]
    Pfami PF00373. FERM_M. 1 hit.
    PF03623. Focal_AT. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view ]
    PRINTSi PR00109. TYRKINASE.
    ProDomi PD006413. Focal_adhesion_target_reg. 1 hit.
    [Graphical view ] [Entries sharing at least one domain ]
    SMARTi SM00295. B41. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47031. SSF47031. 1 hit.
    SSF54236. SSF54236. 1 hit.
    SSF56112. SSF56112. 1 hit.
    SSF68993. SSF68993. 1 hit.
    PROSITEi PS50057. FERM_3. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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. 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. 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. 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. 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. 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. 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.
      , 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.
      , 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.

    Entry informationi

    Entry nameiFAK2_HUMAN
    AccessioniPrimary (citable) accession number: Q14289
    Secondary accession number(s): D3DST0
    , Q13475, Q14290, Q16709, Q6PID4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: July 15, 1998
    Last modified: October 1, 2014
    This is version 171 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Miscellaneous

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

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 8
      Human chromosome 8: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3