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Protein

Protein-tyrosine kinase 2-beta

Gene

Ptk2b

Organism
Mus musculus (Mouse)
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' (By similarity). Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca2+ levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2 (By similarity).By similarity12 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation1 Publication

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.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei457ATPPROSITE-ProRule annotation1
Active sitei549Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi431 – 439ATPPROSITE-ProRule annotation9
Nucleotide bindingi503 – 509ATPPROSITE-ProRule annotation7

GO - Molecular functioni

GO - Biological processi

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. 3474.
ReactomeiR-MMU-391160. Signal regulatory protein (SIRP) family interactions.
R-MMU-4420097. VEGFA-VEGFR2 Pathway.
R-MMU-451927. Interleukin-2 signaling.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:104908. Ptk2b.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Disruption phenotypei

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi402Y → A: Loss of phosphorylation and interaction with SRC, and inhibition of bone resorption. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1075289.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000880821 – 1009Protein-tyrosine kinase 2-betaAdd BLAST1009

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei361PhosphoserineBy similarity1
Modified residuei375PhosphoserineCombined sources1
Modified residuei399PhosphoserineBy similarity1
Modified residuei402Phosphotyrosine; by autocatalysisCombined sources5 Publications1
Modified residuei579Phosphotyrosine; by SRC, LYN and LCKCombined sources1 Publication1
Modified residuei580Phosphotyrosine; by SRC, LYN and LCKCombined sources2 Publications1
Modified residuei722PhosphotyrosineBy similarity1
Modified residuei762PhosphoserineBy similarity1
Modified residuei765PhosphothreonineBy similarity1
Modified residuei834PhosphotyrosineBy similarity1
Modified residuei839PhosphoserineBy similarity1
Modified residuei842PhosphothreonineBy similarity1
Modified residuei849PhosphotyrosineBy similarity1
Modified residuei866PhosphoserineBy similarity1
Modified residuei881Phosphotyrosine2 Publications1

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 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9QVP9.
MaxQBiQ9QVP9.
PaxDbiQ9QVP9.
PRIDEiQ9QVP9.

PTM databases

iPTMnetiQ9QVP9.
PhosphoSitePlusiQ9QVP9.

Expressioni

Gene expression databases

BgeeiENSMUSG00000059456.
CleanExiMM_PTK2B.
ExpressionAtlasiQ9QVP9. baseline and differential.
GenevisibleiQ9QVP9. MM.

Interactioni

Subunit structurei

Homodimer, or homooligomer. 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 RB1CC1. Interacts with RHOU. Interacts with VAV1. Interacts with PDPK1. Interacts with DLG4. Interacts with LPXN and PTPN12. Interacts with SIRPA and SH2D3C. Interacts (hypophosphorylated) with PXN. Interacts with ARHGAP10.By similarity11 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202467. 10 interactors.
IntActiQ9QVP9. 5 interactors.
MINTiMINT-266339.
STRINGi10090.ENSMUSP00000022622.

Chemistry databases

BindingDBiQ9QVP9.

Structurei

3D structure databases

ProteinModelPortaliQ9QVP9.
SMRiQ9QVP9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini39 – 359FERMPROSITE-ProRule annotationAdd BLAST321
Domaini425 – 683Protein kinasePROSITE-ProRule annotationAdd BLAST259

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni801 – 1009Interaction with TGFB1I1By similarityAdd BLAST209
Regioni868 – 1009Focal adhesion targeting (FAT)Add BLAST142

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi701 – 767Pro-richAdd BLAST67
Compositional biasi831 – 869Pro-richAdd BLAST39

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

eggNOGiKOG4257. Eukaryota.
ENOG410ZH9Y. LUCA.
GeneTreeiENSGT00760000118799.
HOGENOMiHOG000069938.
HOVERGENiHBG004018.
InParanoidiQ9QVP9.
KOiK05871.
OMAiVKTCKKD.
OrthoDBiEOG091G03BN.

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.
IPR011993. PH_dom-like.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR030610. PTK2B.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR24418:SF94. PTHR24418:SF94. 1 hit.
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.
SSF50729. SSF50729. 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]

Sequencei

Sequence statusi: Complete.

Q9QVP9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGVSEPLSR VKVGTLRRPE GPPEPMVVVP VDVEKEDVRI LKVCFYSNSF
60 70 80 90 100
NPGKNFKLVK CTVQTEIQEI ITSILLSGRI GPNIQLAECY 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 SQDTKPTCLA
310 320 330 340 350
EFKQIKSIRC LPLEETQAVL QLGIEGAPQS LSIKTSSLAE AENMADLIDG
360 370 380 390 400
YCRLQGEHKG SLIMHAKKDG EKRNSLPQIP TLNLEARRSH LSESCSIESD
410 420 430 440 450
IYAEIPDETL RRPGGPQYGV AREEVVLNRI LGEGFFGEVY EGVYTNHKGE
460 470 480 490 500
KINVAVKTCK KDCTQDNKEK FMSEAVIMKN LDHPHIVKLI GIIEEEPTWI
510 520 530 540 550
IMELYPYGEL GHYLERNKNS LKVPTLVLYT LQICKAMAYL ESINCVHRDI
560 570 580 590 600
AVRNILVASP ECVKLGDFGL SRYIEDEDYY KASVTRLPIK WMSPESINFR
610 620 630 640 650
RFTTASDVWM FAVCMWEILS FGKQPFFWLE NKDVIGVLEK GDRLPKPELC
660 670 680 690 700
PPVLYTLMTR CWDYDPSDRP RFTELVCSLS DIYQMEKDIA IEQERNARYR
710 720 730 740 750
PPKILEPTTF QEPPPKPSRP KYRPPPQTNL LAPKLQFQVP EGLCASSPTL
760 770 780 790 800
TSPMEYPSPV NSLHTPPLHR HNVFKRHSMR EEDFIRPSSR EEAQQLWEAE
810 820 830 840 850
KIKMKQVLER QQKQMVEDSQ WLRREERCLD PMVYMNDKSP LTPEKEAGYT
860 870 880 890 900
EFTGPPQKPP RLGAQSIQPT ANLDRTDDLV YHNVMTLVEA VLELKNKLGQ
910 920 930 940 950
LPPEDYVVVV KNVGLNLRKL IGSVDDLLPS LPASSRTEIE GTQKLLNKDL
960 970 980 990 1000
AELINKMKLA QQNAVTSLSE DCKRQMLTAS HTLAVDAKNL LDAVDQAKVV

ANLAHPPAE
Length:1,009
Mass (Da):115,794
Last modified:October 3, 2012 - v2
Checksum:iA17C858ECC9990E9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti306K → R in AAI37705 (PubMed:15489334).Curated1
Sequence conflicti306K → R in AAI44850 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC126272 Genomic DNA. No translation available.
AC140329 Genomic DNA. No translation available.
CH466535 Genomic DNA. Translation: EDL36001.1.
BC137704 mRNA. Translation: AAI37705.1.
BC144849 mRNA. Translation: AAI44850.1.
CCDSiCCDS49526.1.
RefSeqiNP_001155838.1. NM_001162366.1.
XP_006518789.1. XM_006518726.3.
XP_011243296.1. XM_011244994.2.
UniGeneiMm.21613.

Genome annotation databases

EnsembliENSMUST00000022622; ENSMUSP00000022622; ENSMUSG00000059456.
ENSMUST00000178730; ENSMUSP00000137008; ENSMUSG00000059456.
GeneIDi19229.
KEGGimmu:19229.
UCSCiuc011znr.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC126272 Genomic DNA. No translation available.
AC140329 Genomic DNA. No translation available.
CH466535 Genomic DNA. Translation: EDL36001.1.
BC137704 mRNA. Translation: AAI37705.1.
BC144849 mRNA. Translation: AAI44850.1.
CCDSiCCDS49526.1.
RefSeqiNP_001155838.1. NM_001162366.1.
XP_006518789.1. XM_006518726.3.
XP_011243296.1. XM_011244994.2.
UniGeneiMm.21613.

3D structure databases

ProteinModelPortaliQ9QVP9.
SMRiQ9QVP9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202467. 10 interactors.
IntActiQ9QVP9. 5 interactors.
MINTiMINT-266339.
STRINGi10090.ENSMUSP00000022622.

Chemistry databases

BindingDBiQ9QVP9.
ChEMBLiCHEMBL1075289.

PTM databases

iPTMnetiQ9QVP9.
PhosphoSitePlusiQ9QVP9.

Proteomic databases

EPDiQ9QVP9.
MaxQBiQ9QVP9.
PaxDbiQ9QVP9.
PRIDEiQ9QVP9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000022622; ENSMUSP00000022622; ENSMUSG00000059456.
ENSMUST00000178730; ENSMUSP00000137008; ENSMUSG00000059456.
GeneIDi19229.
KEGGimmu:19229.
UCSCiuc011znr.1. mouse.

Organism-specific databases

CTDi2185.
MGIiMGI:104908. Ptk2b.

Phylogenomic databases

eggNOGiKOG4257. Eukaryota.
ENOG410ZH9Y. LUCA.
GeneTreeiENSGT00760000118799.
HOGENOMiHOG000069938.
HOVERGENiHBG004018.
InParanoidiQ9QVP9.
KOiK05871.
OMAiVKTCKKD.
OrthoDBiEOG091G03BN.

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiR-MMU-391160. Signal regulatory protein (SIRP) family interactions.
R-MMU-4420097. VEGFA-VEGFR2 Pathway.
R-MMU-451927. Interleukin-2 signaling.

Miscellaneous databases

PROiQ9QVP9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000059456.
CleanExiMM_PTK2B.
ExpressionAtlasiQ9QVP9. baseline and differential.
GenevisibleiQ9QVP9. MM.

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.
IPR011993. PH_dom-like.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR030610. PTK2B.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR24418:SF94. PTHR24418:SF94. 1 hit.
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.
SSF50729. SSF50729. 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...

Entry informationi

Entry nameiFAK2_MOUSE
AccessioniPrimary (citable) accession number: Q9QVP9
Secondary accession number(s): B2RQ16, G3X8V1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: October 3, 2012
Last modified: November 30, 2016
This is version 168 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

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 one 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.