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Protein

Protein-tyrosine kinase 2-beta

Gene

PTK2B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.PROSITE-ProRule annotation6 Publications

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

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_264464. VEGFA-VEGFR2 Pathway.
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 Componenti: 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. cytoskeleton Source: InterPro
  7. cytosol Source: Reactome
  8. dendrite Source: Alzheimers_University_of_Toronto
  9. extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  10. focal adhesion Source: UniProtKB
  11. growth cone Source: Alzheimers_University_of_Toronto
  12. lamellipodium Source: UniProtKB
  13. membrane raft Source: Ensembl
  14. neuronal cell body Source: Alzheimers_University_of_Toronto
  15. N-methyl-D-aspartate selective glutamate receptor complex Source: Alzheimers_University_of_Toronto
  16. nucleoplasm Source: HPA
  17. nucleus Source: UniProtKB
  18. perinuclear region of cytoplasm Source: UniProtKB
  19. postsynaptic density Source: Alzheimers_University_of_Toronto
Complete GO annotation...

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 PTPN12.9 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

BgeeiQ14289.
CleanExiHS_PTK2B.
ExpressionAtlasiQ14289. baseline and differential.
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 KCNA2 (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. 64 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 – 373Combined sources
Beta strandi38 – 458Combined sources
Beta strandi48 – 503Combined sources
Helixi52 – 543Combined sources
Beta strandi55 – 628Combined sources
Helixi67 – 7610Combined sources
Turni77 – 804Combined sources
Helixi87 – 893Combined sources
Beta strandi90 – 9910Combined sources
Beta strandi102 – 1054Combined sources
Helixi111 – 1177Combined sources
Turni119 – 1213Combined sources
Helixi124 – 1263Combined sources
Beta strandi127 – 1337Combined sources
Turni138 – 1403Combined sources
Helixi141 – 1444Combined sources
Helixi148 – 16518Combined sources
Turni166 – 1694Combined sources
Helixi172 – 18615Combined sources
Turni187 – 1893Combined sources
Helixi194 – 1963Combined sources
Helixi198 – 20710Combined sources
Helixi210 – 2123Combined sources
Helixi216 – 2216Combined sources
Helixi224 – 23815Combined sources
Helixi243 – 25412Combined sources
Beta strandi263 – 27311Combined sources
Beta strandi277 – 2826Combined sources
Beta strandi285 – 2895Combined sources
Beta strandi297 – 3004Combined sources
Helixi302 – 3043Combined sources
Beta strandi310 – 3134Combined sources
Turni314 – 3163Combined sources
Beta strandi317 – 3226Combined sources
Beta strandi331 – 3366Combined sources
Helixi338 – 35518Combined sources
Beta strandi356 – 3605Combined sources
Helixi422 – 4243Combined sources
Beta strandi425 – 4339Combined sources
Beta strandi435 – 44511Combined sources
Beta strandi447 – 4493Combined sources
Beta strandi451 – 4588Combined sources
Beta strandi461 – 4633Combined sources
Helixi465 – 48117Combined sources
Beta strandi489 – 4935Combined sources
Beta strandi495 – 4973Combined sources
Beta strandi499 – 5035Combined sources
Helixi510 – 5178Combined sources
Turni518 – 5203Combined sources
Helixi523 – 54220Combined sources
Beta strandi546 – 5483Combined sources
Helixi552 – 5543Combined sources
Beta strandi555 – 5595Combined sources
Beta strandi562 – 5654Combined sources
Helixi570 – 5723Combined sources
Helixi589 – 5913Combined sources
Helixi594 – 5996Combined sources
Helixi604 – 61916Combined sources
Turni620 – 6223Combined sources
Turni625 – 6284Combined sources
Helixi631 – 6333Combined sources
Helixi634 – 6407Combined sources
Helixi652 – 66110Combined sources
Helixi666 – 6683Combined sources
Helixi672 – 69120Combined sources
Helixi879 – 89719Combined sources
Helixi898 – 9003Combined sources
Helixi903 – 92725Combined sources
Helixi928 – 9303Combined sources
Helixi933 – 96230Combined sources
Turni963 – 9653Combined sources
Helixi969 – 100335Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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[»]
3U3FX-ray3.10A/B/C/D871-1005[»]
4EKUX-ray3.25A21-409[»]
4H1JX-ray2.00A416-692[»]
4H1MX-ray1.99A416-692[»]
4R32X-ray3.50A871-1005[»]
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.
GeneTreeiENSGT00760000118799.
HOGENOMiHOG000069938.
HOVERGENiHBG004018.
InParanoidiQ14289.
KOiK05871.
OMAiVKTCKKD.
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. AlignAdd to basket

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

        10         20         30         40         50
MSGVSEPLSR VKLGTLRRPE GPAEPMVVVP VDVEKEDVRI LKVCFYSNSF
60 70 80 90 100
NPGKNFKLVK CTVQTEIREI ITSILLSGRI GPNIRLAECY GLRLKHMKSD
110 120 130 140 150
EIHWLHPQMT VGEVQDKYEC LHVEAEWRYD LQIRYLPEDF MESLKEDRTT
160 170 180 190 200
LLYFYQQLRN DYMQRYASKV SEGMALQLGC LELRRFFKDM PHNALDKKSN
210 220 230 240 250
FELLEKEVGL DLFFPKQMQE NLKPKQFRKM IQQTFQQYAS LREEECVMKF
260 270 280 290 300
FNTLAGFANI DQETYRCELI QGWNITVDLV IGPKGIRQLT SQDAKPTCLA
310 320 330 340 350
EFKQIRSIRC LPLEEGQAVL QLGIEGAPQA LSIKTSSLAE AENMADLIDG
360 370 380 390 400
YCRLQGEHQG SLIIHPRKDG EKRNSLPQIP MLNLEARRSH LSESCSIESD
410 420 430 440 450
IYAEIPDETL RRPGGPQYGI AREDVVLNRI LGEGFFGEVY EGVYTNHKGE
460 470 480 490 500
KINVAVKTCK KDCTLDNKEK FMSEAVIMKN LDHPHIVKLI GIIEEEPTWI
510 520 530 540 550
IMELYPYGEL GHYLERNKNS LKVLTLVLYS LQICKAMAYL ESINCVHRDI
560 570 580 590 600
AVRNILVASP ECVKLGDFGL SRYIEDEDYY KASVTRLPIK WMSPESINFR
610 620 630 640 650
RFTTASDVWM FAVCMWEILS FGKQPFFWLE NKDVIGVLEK GDRLPKPDLC
660 670 680 690 700
PPVLYTLMTR CWDYDPSDRP RFTELVCSLS DVYQMEKDIA MEQERNARYR
710 720 730 740 750
TPKILEPTAF QEPPPKPSRP KYRPPPQTNL LAPKLQFQVP EGLCASSPTL
760 770 780 790 800
TSPMEYPSPV NSLHTPPLHR HNVFKRHSMR EEDFIQPSSR EEAQQLWEAE
810 820 830 840 850
KVKMRQILDK QQKQMVEDYQ WLRQEEKSLD PMVYMNDKSP LTPEKEVGYL
860 870 880 890 900
EFTGPPQKPP RLGAQSIQPT ANLDRTDDLV YLNVMELVRA VLELKNELCQ
910 920 930 940 950
LPPEGYVVVV KNVGLTLRKL IGSVDDLLPS LPSSSRTEIE GTQKLLNKDL
960 970 980 990 1000
AELINKMRLA QQNAVTSLSE ECKRQMLTAS HTLAVDAKNL LDAVDQAKVL

ANLAHPPAE
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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[»]
3U3FX-ray3.10A/B/C/D871-1005[»]
4EKUX-ray3.25A21-409[»]
4H1JX-ray2.00A416-692[»]
4H1MX-ray1.99A416-692[»]
4R32X-ray3.50A871-1005[»]
ProteinModelPortaliQ14289.
SMRiQ14289. Positions 21-692, 867-1007.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108480. 64 interactions.
IntActiQ14289. 14 interactions.
MINTiMINT-1211326.
STRINGi9606.ENSP00000332816.

Chemistry

BindingDBiQ14289.
ChEMBLiCHEMBL5469.
DrugBankiDB01097. Leflunomide.
GuidetoPHARMACOLOGYi2181.

PTM databases

PhosphoSiteiQ14289.

Polymorphism databases

DMDMi3183003.

Proteomic databases

MaxQBiQ14289.
PaxDbiQ14289.
PRIDEiQ14289.

Protocols and materials databases

DNASUi2185.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi2185.
GeneCardsiGC08P027224.
H-InvDBHIX0168898.
HGNCiHGNC:9612. PTK2B.
HPAiCAB003850.
HPA026091.
HPA026276.
MIMi601212. gene.
neXtProtiNX_Q14289.
PharmGKBiPA33956.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118799.
HOGENOMiHOG000069938.
HOVERGENiHBG004018.
InParanoidiQ14289.
KOiK05871.
OMAiVKTCKKD.
OrthoDBiEOG7ZSHSB.
PhylomeDBiQ14289.
TreeFamiTF316643.

Enzyme and pathway databases

BRENDAi2.7.10.2. 2681.
ReactomeiREACT_23916. Signal regulatory protein (SIRP) family interactions.
REACT_264464. VEGFA-VEGFR2 Pathway.
REACT_27283. Interleukin-2 signaling.
SignaLinkiQ14289.

Miscellaneous databases

ChiTaRSiPTK2B. human.
EvolutionaryTraceiQ14289.
GeneWikiiPTK2B.
GenomeRNAii2185.
NextBioi8821.
PROiQ14289.
SOURCEiSearch...

Gene expression databases

BgeeiQ14289.
CleanExiHS_PTK2B.
ExpressionAtlasiQ14289. baseline and differential.
GenevestigatoriQ14289.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1994) [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(1995) [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(1994) [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(1994) [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(1997) [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(2005) [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(2003) [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(1995) [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(1995) [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(1997) [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(1998) [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(1999) [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(2000) [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(2002) [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(2002) [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(2002) [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(2003) [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(2003) [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(2006) [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(2006) [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(2007) [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(2007) [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(2007) [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(2007) [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(2008) [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(2008) [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(2008) [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(2009) [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(2009) [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(2009) [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(2009) [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(2010) [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(2010) [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(2004) [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(2009) [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(2010) [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(2007) [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(2008) [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(2008) [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(2008) [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 (JUN-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(2006) [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: April 1, 2015
This is version 177 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.