Q14289 (FAK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	PTK2B
Synonyms:	FAK2, PYK2, RAFTK

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1009 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca2+ levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2. Ref.1 Ref.9 Ref.10 Ref.12 Ref.15 Ref.16 Ref.17 Ref.19 Ref.20 Ref.22 Ref.23 Ref.24 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.33 Ref.34 Ref.36 Ref.38 Ref.39 Ref.41 Ref.46 Ref.47
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.19 Ref.20 Ref.23 Ref.30 Ref.44 Ref.46
Enzyme regulation	Activated in response to stimuli that lead to increased intracellular Ca2+ levels; this activation is indirect and may be mediated by calcium-mediated production of reactive oxygen species (ROS). Activated by autophosphorylation at Tyr-402; this creates a binding site for SRC family kinases and leads to phosphorylation at additional tyrosine residues. Phosphorylation at Tyr-402, Tyr-579 and Tyr-580 is required for optimal kinase activity. Inhibited by PF-562,271, BIRB796, PF-4618433 and by PF-431396, PF-2318841 and their derivatives. Inhibited by sulfoximine-substituted trifluoromethylpyrimidines. Inhibited by 4-amino and 5-aryl substituted pyridinone compounds. Ref.23 Ref.30 Ref.44 Ref.46
Subunit structure	Homodimer, or homooligomer. Interacts with SIRPA and SH2D3C. Interacts with ARHGAP10. Interacts with DLG4 By similarity. Interacts with NPHP1, ASAP1, ASAP2, ARHGAP26, SKAP2 and TGFB1I1. The Tyr-402 phosphorylated form interacts with SRC (via SH2 domain) and SRC family members. Forms a signaling complex with EPHA1, LCK and phosphatidylinositol 3-kinase; upon activation by EFNA1. Interacts with GRB2 (via SH2 domain). Interacts with P53/TP53 and MDM2. Interacts with MYLK. Interacts with BCAR1. Interacts with PDPK1. Interacts (hypophosphorylated) with PXN. Interacts with RB1CC1. Interacts with RHOU. Interacts with VAV1. Interacts with LPXN and PTPN12. Ref.1 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.21 Ref.22 Ref.24 Ref.27 Ref.28 Ref.29 Ref.31 Ref.33 Ref.38 Ref.45
Subcellular location	Cytoplasm. Cytoplasm › perinuclear region. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell junction › focal adhesion. Cell projection › lamellipodium. Cytoplasm › cell cortex. Nucleus. Note: Interaction with NPHP1 induces the membrane-association of the kinase. Colocalizes with integrins at the cell periphery. Ref.16 Ref.17 Ref.24 Ref.29 Ref.34
Tissue specificity	Most abundant in the brain, with highest levels in amygdala and hippocampus. Low levels in kidney (at protein level). Also expressed in spleen and lymphocytes. Ref.1 Ref.5
Post-translational modification	Phosphorylated on tyrosine residues in response to various stimuli that elevate the intracellular calcium concentration; this activation is indirect and may be mediated by production of reactive oxygen species (ROS). Tyr-402 is the major autophosphorylation site, but other kinases can also phosphorylate Tyr-402. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-402 promotes interaction with SRC and SRC family members, leading to phosphorylation at Tyr-579; Tyr-580 and Tyr-881. Phosphorylation at Tyr-881 is important for interaction with GRB2. Phosphorylated on tyrosine residues upon activation of FGR and PKC. Recruitment by NPHP1 to cell matrix adhesions initiates Tyr-402 phosphorylation. In monocytes, adherence to substrata is required for tyrosine phosphorylation and kinase activation. Angiotensin II, thapsigargin and L-alpha-lysophosphatidic acid (LPA) also induce autophosphorylation and increase kinase activity. Phosphorylation by MYLK promotes ITGB2 activation and is thus essential to trigger neutrophil transmigration during lung injury. Dephosphorylated by PTPN12. Ref.5 Ref.9 Ref.14 Ref.20 Ref.21 Ref.28 Ref.29 Ref.31 Ref.33 Ref.35 Ref.36
Involvement in disease	Aberrant PTK2B/PYK2 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. Elevated PTK2B/PYK2 expression is seen in gliomas, hepatocellular carcinoma, lung cancer and breast cancer. Ref.23 Ref.24 Ref.30 Ref.39 Ref.41 Ref.46 Ref.47
Miscellaneous	Promotes bone resorption, and thus PTK2B/PYK2 inhibitors might be used to treat osteoporosis.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. FAK subfamily. Contains 1 FERM domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Adaptive immunity Angiogenesis Immunity
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Inferred from electronic annotation. Source: Compara activation of Janus kinase activity Inferred from mutant phenotype Ref.10. Source: UniProtKB activation of Rac GTPase activity Inferred from electronic annotation. Source: Compara apoptotic process Traceable author statement PubMed 10880513. Source: ProtInc blood vessel endothelial cell migration Inferred from electronic annotation. Source: Compara bone resorption Inferred from sequence or structural similarity. Source: UniProtKB cellular response to retinoic acid Inferred from mutant phenotype PubMed 17910947. Source: BHF-UCL chemokine-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB elevation of cytosolic calcium ion concentration Inferred from electronic annotation. Source: Compara epidermal growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara focal adhesion assembly Inferred from electronic annotation. Source: Compara glial cell proliferation Inferred from electronic annotation. Source: Compara integrin-mediated signaling pathway Inferred from mutant phenotype Ref.19. Source: UniProtKB marginal zone B cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of apoptotic process Inferred from mutant phenotype Ref.34. Source: UniProtKB negative regulation of bone mineralization Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell proliferation Inferred from mutant phenotype Ref.19. Source: UniProtKB negative regulation of myeloid cell differentiation Inferred from mutant phenotype Ref.19. Source: UniProtKB negative regulation of potassium ion transport Inferred from direct assay Ref.1. Source: UniProtKB neuron projection development Inferred from electronic annotation. Source: Compara oocyte maturation Inferred from electronic annotation. Source: Compara positive regulation of B cell chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of ERK1 and ERK2 cascade Inferred from mutant phenotype Ref.1. Source: UniProtKB positive regulation of JNK cascade Inferred from mutant phenotype Ref.10. Source: UniProtKB positive regulation of JUN kinase activity Inferred from electronic annotation. Source: Compara positive regulation of actin filament polymerization Inferred from mutant phenotype Ref.24. Source: UniProtKB positive regulation of angiogenesis Inferred from electronic annotation. Source: Compara positive regulation of cell growth Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from mutant phenotype Ref.24. Source: UniProtKB positive regulation of cell-matrix adhesion Inferred from mutant phenotype Ref.24. Source: UniProtKB positive regulation of endothelial cell migration Inferred from direct assay PubMed 21245381. Source: BHF-UCL positive regulation of neuron projection development Inferred from mutant phenotype PubMed 17910947. Source: BHF-UCL positive regulation of nitric-oxide synthase activity Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 21245381. Source: BHF-UCL positive regulation of phosphatidylinositol 3-kinase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: Compara positive regulation of reactive oxygen species metabolic process Inferred from electronic annotation. Source: Compara positive regulation of translation Inferred from electronic annotation. Source: Compara protein autophosphorylation Traceable author statement Ref.9. Source: UniProtKB regulation of actin cytoskeleton reorganization Inferred from sequence or structural similarity. Source: UniProtKB regulation of cGMP biosynthetic process Inferred from electronic annotation. Source: Compara regulation of cGMP-mediated signaling Inferred from electronic annotation. Source: Compara regulation of calcium-mediated signaling Inferred from electronic annotation. Source: Compara regulation of cell shape Inferred from mutant phenotype Ref.31. Source: UniProtKB regulation of establishment of cell polarity Inferred from sequence or structural similarity. Source: UniProtKB regulation of inositol trisphosphate biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB regulation of macrophage chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB regulation of nitric oxide biosynthetic process Inferred from electronic annotation. Source: Compara regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from direct assay Ref.34. Source: UniProtKB regulation of release of sequestered calcium ion into cytosol Inferred from sequence or structural similarity. Source: UniProtKB response to cAMP Inferred from electronic annotation. Source: Compara response to calcium ion Inferred from electronic annotation. Source: Compara response to cocaine Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to glucose stimulus Inferred from electronic annotation. Source: Compara response to hormone stimulus Inferred from electronic annotation. Source: Compara response to hydrogen peroxide Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to lithium ion Inferred from electronic annotation. Source: Compara response to mechanical stimulus Inferred from electronic annotation. Source: Compara response to osmotic stress Inferred from electronic annotation. Source: Compara response to stress Traceable author statement PubMed 8939945. Source: ProtInc signal complex assembly Traceable author statement PubMed 7529876. Source: ProtInc sprouting angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB stress fiber assembly Inferred from electronic annotation. Source: Compara tumor necrosis factor-mediated signaling pathway Inferred from mutant phenotype Ref.10. Source: UniProtKB vascular endothelial growth factor receptor signaling pathway Inferred from mutant phenotype PubMed 21245381. Source: BHF-UCL
Cellular_component	axon Inferred from electronic annotation. Source: Compara cell cortex Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome focal adhesion Inferred from direct assay Ref.24. Source: UniProtKB growth cone Inferred from electronic annotation. Source: Compara lamellipodium Inferred from direct assay Ref.24. Source: UniProtKB membrane raft Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay Ref.34. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay Ref.24. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic density Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from direct assay Ref.1. Source: UniProtKB signal transducer activity Non-traceable author statement PubMed 10867021. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RHOU	Q7L0Q8	4	EBI-298640,EBI-1638043

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q14289-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q14289-2)

Also known as: PYK2H;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1009

1009

Protein-tyrosine kinase 2-beta

PRO_0000088081

Regions

Domain

39 – 359

321

FERM

Domain

425 – 683

259

Protein kinase

Nucleotide binding

431 – 439

9

ATP

Nucleotide binding

503 – 509

7

ATP

Region

801 – 1009

209

Interaction with TGFB1I1 By similarity

Region

868 – 1009

142

Focal adhesion targeting (FAT)

Compositional bias

702 – 767

66

Pro-rich

Compositional bias

831 – 869

39

Pro-rich

Sites

Active site

549

1

Proton acceptor By similarity

Binding site

457

1

ATP

Amino acid modifications

Modified residue

361

1

Phosphoserine Ref.32

Modified residue

375

1

Phosphoserine Ref.25 Ref.26 Ref.32

Modified residue

399

1

Phosphoserine Ref.32

Modified residue

402

1

Phosphotyrosine; by autocatalysis Ref.14 Ref.20 Ref.21 Ref.29 Ref.33 Ref.35 Ref.36

Modified residue

440

1

Phosphotyrosine By similarity

Modified residue

579

1

Phosphotyrosine; by SRC, LYN and LCK

Modified residue

580

1

Phosphotyrosine; by SRC, LYN and LCK Ref.35 Ref.36

Modified residue

722

1

Phosphotyrosine Ref.32

Modified residue

762

1

Phosphoserine Ref.32

Modified residue

765

1

Phosphothreonine Ref.26

Modified residue

819

1

Phosphotyrosine Ref.32

Modified residue

834

1

Phosphotyrosine Ref.32

Modified residue

839

1

Phosphoserine Ref.26 Ref.32

Modified residue

842

1

Phosphothreonine Ref.26 Ref.32

Modified residue

849

1

Phosphotyrosine Ref.32

Modified residue

866

1

Phosphoserine Ref.32

Modified residue

881

1

Phosphotyrosine; by SRC Ref.33

Natural variations

Alternative sequence

739 – 780

42

Missing in isoform 2.

VSP_004981

Natural variant

359

1

Q → E. Ref.49
Corresponds to variant rs56175011 [ dbSNP | Ensembl ].

VAR_041687

Natural variant

698

1

R → H. Ref.49
Corresponds to variant rs35174236 [ dbSNP | Ensembl ].

VAR_041688

Natural variant

808

1

L → P. Ref.49
Corresponds to variant rs55747955 [ dbSNP | Ensembl ].

VAR_041689

Natural variant

838

1

K → T. Ref.32 Ref.49
Corresponds to variant rs751019 [ dbSNP | Ensembl ].

VAR_020284

Natural variant

970

1

E → K. Ref.49
Corresponds to variant rs56263944 [ dbSNP | Ensembl ].

VAR_041690

Experimental info

Mutagenesis

402

1

Y → F: Abolishes autophosphorylation. Abolishes interaction with SRC. Ref.9

Mutagenesis

457

1

K → A: Abolishes kinase activity. Ref.20

Mutagenesis

859

1

P → A: Loss of interaction with NPHP1. Ref.14

Mutagenesis

881

1

Y → F: Loss of phosphorylation site. Strongly reduced interaction with GRB2. Ref.33

Sequence conflict

23

1

A → G in BAA08289. Ref.3

Sequence conflict

23

1

A → G in AAC05330. Ref.3

Sequence conflict

256

1

G → P in AAB47217. Ref.2

Sequence conflict

435

1

F → L in AAC05330. Ref.3

Sequence conflict

780

1

R → G in AAB47217. Ref.2

Sequence conflict

985

1

V → M in AAH36651. Ref.8

Secondary structure

1

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1009

Helix Strand Turn

Details...

Helix

35 – 37

3

Beta strand

38 – 45

8

Beta strand

48 – 50

3

Helix

52 – 54

3

Beta strand

55 – 62

8

Helix

67 – 76

10

Turn

77 – 80

4

Helix

87 – 89

3

Beta strand

90 – 99

10

Beta strand

102 – 105

4

Helix

111 – 117

7

Turn

119 – 121

3

Helix

124 – 126

3

Beta strand

127 – 133

7

Turn

138 – 140

3

Helix

141 – 144

4

Helix

148 – 165

18

Turn

166 – 169

4

Helix

172 – 186

15

Turn

187 – 189

3

Helix

194 – 196

3

Helix

198 – 207

10

Helix

210 – 212

3

Helix

216 – 221

6

Helix

224 – 238

15

Helix

243 – 254

12

Beta strand

263 – 273

11

Beta strand

277 – 282

6

Beta strand

285 – 289

5

Beta strand

297 – 300

4

Helix

302 – 304

3

Beta strand

310 – 313

4

Turn

314 – 316

3

Beta strand

317 – 322

6

Beta strand

331 – 336

6

Helix

338 – 355

18

Beta strand

356 – 360

5

Helix

422 – 424

3

Beta strand

425 – 433

9

Beta strand

435 – 445

11

Beta strand

447 – 449

3

Beta strand

451 – 458

8

Beta strand

461 – 463

3

Helix

465 – 481

17

Beta strand

489 – 493

5

Beta strand

495 – 497

3

Beta strand

499 – 503

5

Helix

510 – 517

8

Turn

518 – 520

3

Helix

523 – 542

20

Beta strand

546 – 548

3

Helix

552 – 554

3

Beta strand

555 – 559

5

Beta strand

562 – 565

4

Helix

570 – 572

3

Helix

589 – 591

3

Helix

594 – 599

6

Helix

604 – 619

16

Turn

620 – 622

3

Turn

625 – 628

4

Helix

631 – 633

3

Helix

634 – 640

7

Helix

652 – 661

10

Helix

666 – 668

3

Helix

672 – 691

20

Helix

879 – 897

19

Helix

898 – 900

3

Helix

903 – 927

25

Helix

928 – 930

3

Helix

933 – 962

30

Turn

963 – 965

3

Helix

969 – 1003

35

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 15, 1998. Version 2. Checksum: 420B21046274E7C2	FASTA	1,009	115,875
	10 20 30 40 50 60 MSGVSEPLSR VKLGTLRRPE GPAEPMVVVP VDVEKEDVRI LKVCFYSNSF NPGKNFKLVK 70 80 90 100 110 120 CTVQTEIREI ITSILLSGRI GPNIRLAECY GLRLKHMKSD EIHWLHPQMT VGEVQDKYEC 130 140 150 160 170 180 LHVEAEWRYD LQIRYLPEDF MESLKEDRTT LLYFYQQLRN DYMQRYASKV SEGMALQLGC 190 200 210 220 230 240 LELRRFFKDM PHNALDKKSN FELLEKEVGL DLFFPKQMQE NLKPKQFRKM IQQTFQQYAS 250 260 270 280 290 300 LREEECVMKF FNTLAGFANI DQETYRCELI QGWNITVDLV IGPKGIRQLT SQDAKPTCLA 310 320 330 340 350 360 EFKQIRSIRC LPLEEGQAVL QLGIEGAPQA LSIKTSSLAE AENMADLIDG YCRLQGEHQG 370 380 390 400 410 420 SLIIHPRKDG EKRNSLPQIP MLNLEARRSH LSESCSIESD IYAEIPDETL RRPGGPQYGI 430 440 450 460 470 480 AREDVVLNRI LGEGFFGEVY EGVYTNHKGE KINVAVKTCK KDCTLDNKEK FMSEAVIMKN 490 500 510 520 530 540 LDHPHIVKLI GIIEEEPTWI IMELYPYGEL GHYLERNKNS LKVLTLVLYS LQICKAMAYL 550 560 570 580 590 600 ESINCVHRDI AVRNILVASP ECVKLGDFGL SRYIEDEDYY KASVTRLPIK WMSPESINFR 610 620 630 640 650 660 RFTTASDVWM FAVCMWEILS FGKQPFFWLE NKDVIGVLEK GDRLPKPDLC PPVLYTLMTR 670 680 690 700 710 720 CWDYDPSDRP RFTELVCSLS DVYQMEKDIA MEQERNARYR TPKILEPTAF QEPPPKPSRP 730 740 750 760 770 780 KYRPPPQTNL LAPKLQFQVP EGLCASSPTL TSPMEYPSPV NSLHTPPLHR HNVFKRHSMR 790 800 810 820 830 840 EEDFIQPSSR EEAQQLWEAE KVKMRQILDK QQKQMVEDYQ WLRQEEKSLD PMVYMNDKSP 850 860 870 880 890 900 LTPEKEVGYL EFTGPPQKPP RLGAQSIQPT ANLDRTDDLV YLNVMELVRA VLELKNELCQ 910 920 930 940 950 960 LPPEGYVVVV KNVGLTLRKL IGSVDDLLPS LPSSSRTEIE GTQKLLNKDL AELINKMRLA 970 980 990 1000 QQNAVTSLSE ECKRQMLTAS HTLAVDAKNL LDAVDQAKVL ANLAHPPAE
	Isoform 2 (PYK2H) [UniParc]. Checksum: 4AFDAA83908F2902	FASTA	967	111,183
	10 20 30 40 50 60 MSGVSEPLSR VKLGTLRRPE GPAEPMVVVP VDVEKEDVRI LKVCFYSNSF NPGKNFKLVK 70 80 90 100 110 120 CTVQTEIREI ITSILLSGRI GPNIRLAECY GLRLKHMKSD EIHWLHPQMT VGEVQDKYEC 130 140 150 160 170 180 LHVEAEWRYD LQIRYLPEDF MESLKEDRTT LLYFYQQLRN DYMQRYASKV SEGMALQLGC 190 200 210 220 230 240 LELRRFFKDM PHNALDKKSN FELLEKEVGL DLFFPKQMQE NLKPKQFRKM IQQTFQQYAS 250 260 270 280 290 300 LREEECVMKF FNTLAGFANI DQETYRCELI QGWNITVDLV IGPKGIRQLT SQDAKPTCLA 310 320 330 340 350 360 EFKQIRSIRC LPLEEGQAVL QLGIEGAPQA LSIKTSSLAE AENMADLIDG YCRLQGEHQG 370 380 390 400 410 420 SLIIHPRKDG EKRNSLPQIP MLNLEARRSH LSESCSIESD IYAEIPDETL RRPGGPQYGI 430 440 450 460 470 480 AREDVVLNRI LGEGFFGEVY EGVYTNHKGE KINVAVKTCK KDCTLDNKEK FMSEAVIMKN 490 500 510 520 530 540 LDHPHIVKLI GIIEEEPTWI IMELYPYGEL GHYLERNKNS LKVLTLVLYS LQICKAMAYL 550 560 570 580 590 600 ESINCVHRDI AVRNILVASP ECVKLGDFGL SRYIEDEDYY KASVTRLPIK WMSPESINFR 610 620 630 640 650 660 RFTTASDVWM FAVCMWEILS FGKQPFFWLE NKDVIGVLEK GDRLPKPDLC PPVLYTLMTR 670 680 690 700 710 720 CWDYDPSDRP RFTELVCSLS DVYQMEKDIA MEQERNARYR TPKILEPTAF QEPPPKPSRP 730 740 750 760 770 780 KYRPPPQTNL LAPKLQFQEE DFIQPSSREE AQQLWEAEKV KMRQILDKQQ KQMVEDYQWL 790 800 810 820 830 840 RQEEKSLDPM VYMNDKSPLT PEKEVGYLEF TGPPQKPPRL GAQSIQPTAN LDRTDDLVYL 850 860 870 880 890 900 NVMELVRAVL ELKNELCQLP PEGYVVVVKN VGLTLRKLIG SVDDLLPSLP SSSRTEIEGT 910 920 930 940 950 960 QKLLNKDLAE LINKMRLAQQ NAVTSLSEEC KRQMLTASHT LAVDAKNLLD AVDQAKVLAN LAHPPAE

References

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[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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lymph and Testis.
[9]	"A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation." Dikic I., Tokiwa G., Lev S., Courtneidge S.A., Schlessinger J. Nature 383:547-550(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF SRC AND ACTIVATION OF THE MAP KINASE SIGNALING CASCADE, INTERACTION WITH SRC, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-402.
[10]	"Activation of Pyk2 by stress signals and coupling with JNK signaling pathway." Tokiwa G., Dikic I., Lev S., Schlessinger J. Science 273:792-794(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN TNF SIGNALING AND ACTIVATION OF MAPK8/JNK1.
[11]	"Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions." Matsuya M., Sasaki H., Aoto H., Mitaka T., Nagura K., Ohba T., Ishino M., Takahashi S., Suzuki R., Sasaki T. J. Biol. Chem. 273:1003-1014(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TGFB1I1.
[12]	"Identification of a new Pyk2 target protein with Arf-GAP activity." Andreev J., Simon J.-P., Sabatini D.D., Kam J., Plowman G., Randazzo P.A., Schlessinger J. Mol. Cell. Biol. 19:2338-2350(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ASAP2, FUNCTION.
[13]	"Suppression of Pyk2 kinase and cellular activities by FIP200." Ueda H., Abbi S., Zheng C., Guan J.-L. J. Cell Biol. 149:423-430(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RB1CC1.
[14]	"Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers phosphorylation of Pyk2." Benzing T., Gerke P., Hoepker K., Hildebrandt F., Kim E., Walz G. Proc. Natl. Acad. Sci. U.S.A. 98:9784-9789(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-402, MUTAGENESIS OF PRO-859, INTERACTION WITH NPHP1.
[15]	"The tyrosine kinase Pyk2 regulates Arf1 activity by phosphorylation and inhibition of the Arf-GTPase-activating protein ASAP1." Kruljac-Letunic A., Moelleken J., Kallin A., Wieland F., Blaukat A. J. Biol. Chem. 278:29560-29570(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ASAP1 PHOSPHORYLATION AND REGULATION OF ASAP1 ACTIVITY, INTERACTION WITH ASAP1.
[16]	"Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein phosphorylation." Takahashi T., Yamashita H., Nagano Y., Nakamura T., Ohmori H., Avraham H., Avraham S., Yasuda M., Matsumoto M. J. Biol. Chem. 278:42225-42233(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SKAP2, SUBCELLULAR LOCATION, FUNCTION.
[17]	"Pyk2- and Src-dependent tyrosine phosphorylation of PDK1 regulates focal adhesions." Taniyama Y., Weber D.S., Rocic P., Hilenski L., Akers M.L., Park J., Hemmings B.A., Alexander R.W., Griendling K.K. Mol. Cell. Biol. 23:8019-8029(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PDPK1, SUBCELLULAR LOCATION.
[18]	"Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry." Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C. Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]	"Integrin engagement-induced inhibition of human myelopoiesis is mediated by proline-rich tyrosine kinase 2 gene products." Dylla S.J., Deyle D.R., Theunissen K., Padurean A.M., Verfaillie C.M. Exp. Hematol. 32:365-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN INTEGRIN SIGNALING AND IN REGULATION OF CELL PROLIFERATION, CATALYTIC ACTIVITY, CHARACTERIZATION OF ISOFORM 2.
[20]	"RAFTK/Pyk2 activation is mediated by trans-acting autophosphorylation in a Src-independent manner." Park S.Y., Avraham H.K., Avraham S. J. Biol. Chem. 279:33315-33322(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-402, CATALYTIC ACTIVITY, FUNCTION IN SRC-MEDIATED PHOSPHORYLATION OF PXN, MUTAGENESIS OF LYS-457.
[21]	"Interaction of Pyk2 and PTP-PEST with leupaxin in prostate cancer cells." Sahu S.N., Nunez S., Bai G., Gupta A. Am. J. Physiol. 292:C2288-C2296(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LPXN AND PTPN12, PHOSPHORYLATION AT TYR-402, DEPHOSPHORYLATION BY PTPN12.
[22]	"Ephrin-A1 stimulates migration of CD8+CCR7+ T lymphocytes." Hjorthaug H.S., Aasheim H.C. Eur. J. Immunol. 37:2326-2336(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN MIGRATION OF T-LYMPHOCYTES, INTERACTION WITH EPHA1; LCK AND PI3-KINASE.
[23]	"Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271." Roberts W.G., Ung E., Whalen P., Cooper B., Hulford C., Autry C., Richter D., Emerson E., Lin J., Kath J., Coleman K., Yao L., Martinez-Alsina L., Lorenzen M., Berliner M., Luzzio M., Patel N., Schmitt E. , LaGreca S., Jani J., Wessel M., Marr E., Griffor M., Vajdos F. Cancer Res. 68:1935-1944(2008) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, ROLE IN DISEASE.
[24]	"Proline-rich tyrosine kinase 2 (Pyk2) promotes proliferation and invasiveness of hepatocellular carcinoma cells through c-Src/ERK activation." Sun C.K., Man K., Ng K.T., Ho J.W., Lim Z.X., Cheng Q., Lo C.M., Poon R.T., Fan S.T. Carcinogenesis 29:2096-2105(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL ADHESION; MIGRATION; PROLIFERATION; REGULATION OF ACTIN FIBER POLYMERIZATION AND IN ACTIVATION OF SRC; MAPK1/ERK2 AND MAPK3/ERK1, INTERACTION WITH SRC, SUBCELLULAR LOCATION, ROLE IN DISEASE.
[25]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[27]	"The atypical Rho GTPase Wrch1 collaborates with the nonreceptor tyrosine kinases Pyk2 and Src in regulating cytoskeletal dynamics." Ruusala A., Aspenstrom P. Mol. Cell. Biol. 28:1802-1814(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RHOU, FUNCTION IN REORGANIZATION OF ACTIN CYTOSKELETON AND SRC-MEDIATED RHOU PHOSPHORYLATION.
[28]	"Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating beta2 integrins." Xu J., Gao X.-P., Ramchandran R., Zhao Y.-Y., Vogel S.M., Malik A.B. Nat. Immunol. 9:880-886(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION DURING LUNG INJURY, PHOSPHORYLATION BY MYLK, INTERACTION WITH MYLK.
[29]	"A Pyk2-Vav1 complex is recruited to beta3-adhesion sites to initiate Rho activation." Gao C., Blystone S.D. Biochem. J. 420:49-56(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN REGULATION OF ACTIN CYTOSKELETON REORGANIZATION AND ACTIVATION OF RHO FAMILY GTPASES, PHOSPHORYLATION AT TYR-402, SUBCELLULAR LOCATION, INTERACTION WITH VAV1.
[30]	"Identification of small molecule inhibitors of proline-rich tyrosine kinase 2 (Pyk2) with osteogenic activity in osteoblast cells." Allen J.G., Lee M.R., Han C.Y., Scherrer J., Flynn S., Boucher C., Zhao H., O'Connor A.B., Roveto P., Bauer D., Graceffa R., Richards W.G., Babij P. Bioorg. Med. Chem. Lett. 19:4924-4928(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ROLE IN DISEASE, CATALYTIC ACTIVITY, ENZYME REGULATION.
[31]	"Pyk2 mediates endothelin-1 signaling via p130Cas/BCAR3 cascade and regulates human glomerular mesangial cell adhesion and spreading." Rufanova V.A., Alexanian A., Wakatsuki T., Lerner A., Sorokin A. J. Cell. Physiol. 219:45-56(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL ADHESION AND SPREADING, AUTOPHOSPHORYLATION, INTERACTION WITH BCAR1.
[32]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361; SER-375; SER-399; TYR-722; SER-762; TYR-819; TYR-834; SER-839; THR-842; TYR-849 AND SER-866, VARIANT [LARGE SCALE ANALYSIS] THR-838, MASS SPECTROMETRY.
[33]	"Recruitment of Pyk2 to SHPS-1 signaling complex is required for IGF-I-dependent mitogenic signaling in vascular smooth muscle cells." Shen X., Xi G., Radhakrishnan Y., Clemmons D.R. Cell. Mol. Life Sci. 67:3893-3903(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN IGF1 SIGNALING AND ACTIVATION OF MAPK1/ERK2 AND MAPK3/ERK1, INTERACTION WITH SRC AND GRB2, PHOSPHORYLATION AT TYR-402 AND TYR-881, MUTAGENESIS OF TYR-881.
[34]	"Pyk2 inhibition of p53 as an adaptive and intrinsic mechanism facilitating cell proliferation and survival." Lim S.T., Miller N.L., Nam J.O., Chen X.L., Lim Y., Schlaepfer D.D. J. Biol. Chem. 285:1743-1753(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL PROLIFERATION AND REGULATION OF P53/TP53 UBIQUITINATION, SUBCELLULAR LOCATION.
[35]	"The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 and 580 occurs via a distinct mechanism than other receptor systems." Collins M., Tremblay M., Chapman N., Curtiss M., Rothman P.B., Houtman J.C. J. Leukoc. Biol. 87:691-701(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-402 AND TYR-580 BY FYN AND LCK.
[36]	"T cell receptor activation leads to two distinct phases of Pyk2 activation and actin cytoskeletal rearrangement in human T cells." Collins M., Bartelt R.R., Houtman J.C. Mol. Immunol. 47:1665-1674(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN T-CELL RECEPTOR-MEDIATED SIGNALING, PHOSPHORYLATION AT TYR-402 AND TYR-580.
[37]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[38]	"Nephrocystin-4 regulates Pyk2-induced tyrosine phosphorylation of nephrocystin-1 to control targeting to monocilia." Liebau M.C., Hopker K., Muller R.U., Schmedding I., Zank S., Schairer B., Fabretti F., Hohne M., Bartram M.P., Dafinger C., Hackl M., Burst V., Habbig S., Zentgraf H., Blaukat A., Walz G., Benzing T., Schermer B. J. Biol. Chem. 286:14237-14245(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NPHP1, FUNCTION IN PHOSPHORYLATION OF NPHP1.
[39]	"Proline-rich tyrosine kinase 2 (Pyk2) promotes cell motility of hepatocellular carcinoma through induction of epithelial to mesenchymal transition." Sun C.K., Ng K.T., Lim Z.X., Cheng Q., Lo C.M., Poon R.T., Man K., Wong N., Fan S.T. PLoS ONE 6:E18878-E18878(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN REORGANIZATION OF CYTOSKELETON; FORMATION OF MEMBRANE RUFFLES AND CELL MIGRATION, ROLE IN DISEASE.
[40]	"Focal adhesion kinase-related protein tyrosine kinase Pyk2 in T-cell activation and function." Ostergaard H.L., Lysechko T.L. Immunol. Res. 31:267-282(2005) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON ROLE IN IMMUNITY.
[41]	"Targeting Pyk2 for therapeutic intervention." Lipinski C.A., Loftus J.C. Expert Opin. Ther. Targets 14:95-108(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION; SIGNALING; INTERACTION PARTNERS; ENZYME REGULATION; PHOSPHORYLATION, ROLE IN DISEASE.
[42]	"Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions." Schaller M.D. J. Cell Sci. 123:1007-1013(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[43]	"Redox sensitive Pyk2 as a target for therapeutics in breast cancer." Felty Q. Front. Biosci. 16:568-577(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON ROLE IN DISEASE.
[44]	"Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase 2 (PYK2): structure-activity relationships and strategies for the elimination of reactive metabolite formation." Walker D.P., Bi F.C., Kalgutkar A.S., Bauman J.N., Zhao S.X., Soglia J.R., Aspnes G.E., Kung D.W., Klug-McLeod J., Zawistoski M.P., McGlynn M.A., Oliver R., Dunn M., Li J.C., Richter D.T., Cooper B.A., Kath J.C., Hulford C.A. , 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U33284 mRNA. Translation: AAC50203.1.
L49207 mRNA. Translation: AAB47217.1.
D45853 mRNA. Translation: BAA08289.1.
U43522 mRNA. Translation: AAC05330.1.
S80542 mRNA. Translation: AAB35701.1.
AF311103 Genomic DNA. No translation available.
CH471080 Genomic DNA. Translation: EAW63553.1.
CH471080 Genomic DNA. Translation: EAW63555.1.
CH471080 Genomic DNA. Translation: EAW63556.1.
BC036651 mRNA. Translation: AAH36651.1.
BC042599 mRNA. Translation: AAH42599.1.

IPI

IPI00029702.
IPI00216435.

PIR

S60248.

RefSeq

NP_004094.3. NM_004103.4.
NP_775266.1. NM_173174.2.
NP_775267.1. NM_173175.2.
NP_775268.1. NM_173176.2.

UniGene

Hs.491322.
Hs.735450.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

Q14289.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q14289. 7 interactions.

MINT

MINT-1211326.

STRING

9606.ENSP00000332816.

PTM databases

PhosphoSite

Q14289.

Polymorphism databases

DMDM

3183003.

Proteomic databases

PaxDb

Q14289.

PRIDE

Q14289.

Protocols and materials databases

DNASU

2185.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000338238; ENSP00000342242; ENSG00000120899.
ENST00000346049; ENSP00000332816; ENSG00000120899.
ENST00000397501; ENSP00000380638; ENSG00000120899.
ENST00000420218; ENSP00000391995; ENSG00000120899.
ENST00000517339; ENSP00000427931; ENSG00000120899.
ENST00000544172; ENSP00000440926; ENSG00000120899.

GeneID

2185.

KEGG

hsa:2185.

UCSC

uc003xfn.2. human.
uc003xfq.2. human.

Organism-specific databases

CTD

2185.

GeneCards

GC08P027224.

H-InvDB

HIX0168898.

HGNC

HGNC:9612. PTK2B.

HPA

CAB003850.
HPA026091.
HPA026276.

MIM

601212. gene.

neXtProt

NX_Q14289.

PharmGKB

PA33956.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000069938.

HOVERGEN

HBG004018.

InParanoid

Q14289.

KO

K05871.

OMA

CKRQMLT.

OrthoDB

EOG4SF956.

PhylomeDB

Q14289.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Pathway_Interaction_DB

alphasynuclein_pathway. Alpha-synuclein signaling.
ar_pathway. Coregulation of Androgen receptor activity.
endothelinpathway. Endothelins.
fgf_pathway. FGF signaling pathway.
il2_1pathway. IL2-mediated signaling events.
avb3_integrin_pathway. Integrins in angiogenesis.
lysophospholipid_pathway. LPA receptor mediated events.
avb3_opn_pathway. Osteopontin-mediated events.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.

Reactome

REACT_111155. Cell-Cell communication.
REACT_6900. Immune System.

SignaLink

Q14289.

Gene expression databases

ArrayExpress

Q14289.

Bgee

Q14289.

CleanEx

HS_PTK2B.

Genevestigator

Q14289.

GermOnline

ENSG00000120899. Homo sapiens.

Family and domain databases

Gene3D

1.20.80.10. 1 hit.

InterPro

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_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]

Pfam

PF00373. FERM_M. 1 hit.
PF03623. Focal_AT. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]

PRINTS

PR00109. TYRKINASE.

ProDom

PD006413. Focal_adhesion_target_reg. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00295. B41. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF47031. FERM_3-hlx. 1 hit.
SSF68993. Focal_AT. 1 hit.
SSF56112. Kinase_like. 1 hit.

PROSITE

PS00660. FERM_1. False negative.
PS00661. FERM_2. False negative.
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]

ProtoNet

Search...

Other

BindingDB

Q14289.

ChEMBL

CHEMBL5469.

ChiTaRS

PTK2B. human.

EvolutionaryTrace

Q14289.

GenomeRNAi

2185.

NextBio

8821.

SOURCE

Search...

Entry information

Entry name

FAK2_HUMAN

Accession

Primary (citable) accession number: Q14289
Secondary accession number(s): D3DST0 , Q13475, Q14290, Q16709, Q6PID4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 15, 1998
Last modified:	May 29, 2013
This is version 157 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.