Tyrosine-protein kinase SYK (EC 2.7.10.2) (Spleen tyrosine kinase) (p72-Syk)
1_MASSG 6_ MADSA 11_ NHLPF 16_ FFGNI 21_ TREEA 26_ EDYLV 31_ QGGMS 36_ DGLYL 41_ LRQSR 46_ NYLGG 51_ FALSV 56_ AHGRK 61_ AHHYT 66_ IEREL 71_ NGTYA 76_ IAGGR 81_ THASP 86_ ADLCH 91_ YHSQE 96_ SDGLV 101_ CLLKK 106_ PFNRP 111_ QGVQP 116_ KTGPF 121_ EDLKE 126_ NLIRE 131_ YVKQT 136_ WNLQG 141_ QALEQ 146_ AIISQ 151_ KPQLE 156_ KLIAT 161_ TAHEK 166_ MPWFH 171_ GKISR 176_ EESEQ 181_ IVLIG 186_ SKTNG 191_ KFLIR 196_ ARDNN 201_ GSYAL 206_ CLLHE 211_ GKVLH 216_ YRIDK 221_ DKTGK 226_ LSIPE 231_ GKKFD 236_ TLWQL 241_ VEHYS 246_ YKADG 251_ LLRVL 256_ TVPCQ 261_ KIGTQ 266_ GNVNF 271_ GGRPQ 276_ LPGSH 281_ PATWS 286_ AGGII 291_ SRIKS 296_ YSFPK 301_ PGHRK 306_ SSPAQ 311_ GNRQE 316_ STVSF 321_ NPYEP 326_ ELAPW 331_ AADKG 336_ PQREA 341_ LPMDT 346_ EVYES 351_ PYADP 356_ EEIRP 361_ KEVYL 366_ DRKLL 371_ TLEDK 376_ ELGSG 381_ NFGTV 386_ KKGYY 391_ QMKKV 396_ VKTVA 401_ VKILK 406_ NEAND 411_ PALKD 416_ ELLAE 421_ ANVMQ 426_ QLDNP 431_ YIVRM 436_ IGICE 441_ AESWM 446_ LVMEM 451_ AELGP 456_ LNKYL 461_ QQNRH 466_ VKDKN 471_ IIELV 476_ HQVSM 481_ GMKYL 486_ EESNF 491_ VHRDL 496_ AARNV 501_ LLVTQ 506_ HYAKI 511_ SDFGL 516_ SKALR 521_ ADENY 526_ YKAQT 531_ HGKWP 536_ VKWYA 541_ PECIN 546_ YYKFS 551_ SKSDV 556_ WSFGV 561_ LMWEA 566_ FSYGQ 571_ KPYRG 576_ MKGSE 581_ VTAML 586_ EKGER 591_ MGCPA 596_ GCPRE 601_ MYDLM 606_ NLCWT 611_ YDVEN 616_ RPGFA 621_ AVELR 626_LRNYY
1: Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development (PubMed:12387735, PubMed:33782605). Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include DEPTOR, VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK (PubMed:12456653, PubMed:15388330, PubMed:34634301, PubMed:8657103). Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition (PubMed:12456653). Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR also plays a role in T-cell receptor signaling. Also plays a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade (By similarity). Required for the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770). Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (By similarity). Also functions downstream of receptors mediating cell adhesion (PubMed:12387735). Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Also plays a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (By similarity)