focal adhesion kinase 2 (protein tyrosine kinase 2 beta, FADK 2, proline-rich tyrosine kinase 2, cell adhesion kinase beta, CAK beta, Ca+2-dependent tyrosine kinase, CADTK, related adhesion focal tyrosine kinase, RAFTK, PTK2B, FAK2, PYK2, RAFTK)

Function: - role in Ca⁺² induced regulation of ion channel(s) & activation of the MAP kinase signalling pathway - may represent signaling intermediate between neuropeptide activated receptors or neurotransmitters that increase Ca⁺² flux & the downstream signals that regulate neuronal activity - interacts with the SH2 domain of Grb2 - may phosphorylate the voltage-gated K⁺ channel protein Kv1.2 - its activation is highly correlated with the stimulation of c-Jun N-terminal kinase activity - role in osmotic stress-dependent SNCA Tyr-125 phosphorylation - interacts with Crk-associated substrate (Cas), PTPNS1 & SH2D3C (putative) - interacts with nephrocystin, DDEF2, OPHN1L, SKAP2 & TGFB1I1 - phosphorylated on Tyr in response to various stimuli that elevate intracellular Ca⁺² concentration, as well as by PKC activation - recruitment by nephrocystin to cell matrix adhesions initiates Tyr-402 phosphorylation - in monocytes, adherence to substrata is required for tyrosine phosphorylation & kinase activation - angiotensin 2, thapsigargin & L-alpha-lysophosphatidic acid also induce autophosphorylation & increase kinase activity (putative) ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate Structure: - belongs to the protein kinase superfamily, Tyr protein kinase family, FAK subfamily - contains 1 FERM domain contains 1 protein kinase domain Compartment: - cytoplasm, cell membrane - interaction with nephrocystin induces membrane-association Alternative splicing: named isoforms=2 Expression: - most abundant in the brain, with highest levels in amygdala & hippocampus - low levels in kidney - also expressed in spleen & lymphocytes

Properties

SIZE: entity length = 1009 aa MW = 116 kD COMPARTMENT: cytoplasm STATE: active state MOTIF: FERM domain NAME: FERM domain SITE: 39-359 Ser phosphorylation site {S375} Tyr phosphorylation site {Y402} kinase domain SITE: 425-683 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 431-439 ATP-binding site NAME: ATP-binding site SITE: 457-457 aspartate residue {D549} Tyr phosphorylation site {Y579} Tyr phosphorylation site {Y580} proline-rich region SITE: 702-767 MOTIF: proline residue (SEVERAL) TGFB1I1 interaction {801-1009} MOTIF: proline-rich region SITE: 831-869 MOTIF: proline residue (SEVERAL) Focal adhesion targeting (FAT) NAME: Focal adhesion targeting (FAT) SITE: 868-1009 MOTIF: Tyr phosphorylation site binding site FOR-BINDING-OF: Paxillin Tyr phosphorylation site {Y881}

Database Correlations

OMIM 601212 UniProt Q14289 PFAM correlations KEGG correlations ENZYME 2.7.10.2

References

UniProt :accession Q14289