Tyrosine-protein kinase ZAP-70 (EC 2.7.10.2) (70 kDa zeta-chain associated protein) (Syk-related tyrosine kinase)
1_MPDPA 6_ AHLPF 11_ FYGSI 16_ SRAEA 21_ EEHLK 26_ LAGMA 31_ DGLFL 36_ LRQCL 41_ RSLGG 46_ YVLSL 51_ VHDVR 56_ FHHFP 61_ IERQL 66_ NGTYA 71_ IAGGK 76_ AHCGP 81_ AELCE 86_ FYSRD 91_ PDGLP 96_ CNLRK 101_ PCNRP 106_ SGLEP 111_ QPGVF 116_ DCLRD 121_ AMVRD 126_ YVRQT 131_ WKLEG 136_ EALEQ 141_ AIISQ 146_ APQVE 151_ KLIAT 156_ TAHER 161_ MPWYH 166_ SSLTR 171_ EEAER 176_ KLYSG 181_ AQTDG 186_ KFLLR 191_ PRKEQ 196_ GTYAL 201_ SLIYG 206_ KTVYH 211_ YLISQ 216_ DKAGK 221_ YCIPE 226_ GTKFD 231_ TLWQL 236_ VEYLK 241_ LKADG 246_ LIYCL 251_ KEACP 256_ NSSAS 261_ NASGA 266_ AAPTL 271_ PAHPS 276_ TLTHP 281_ QRRID 286_ TLNSD 291_ GYTPE 296_ PARIT 301_ SPDKP 306_ RPMPM 311_ DTSVY 316_ ESPYS 321_ DPEEL 326_ KDKKL 331_ FLKRD 336_ NLLIA 341_ DIELG 346_ CGNFG 351_ SVRQG 356_ VYRMR 361_ KKQID 366_ VAIKV 371_ LKQGT 376_ EKADT 381_ EEMMR 386_ EAQIM 391_ HQLDN 396_ PYIVR 401_ LIGVC 406_ QAEAL 411_ MLVME 416_ MAGGG 421_ PLHKF 426_ LVGKR 431_ EEIPV 436_ SNVAE 441_ LLHQV 446_ SMGMK 451_ YLEEK 456_ NFVHR 461_ DLAAR 466_ NVLLV 471_ NRHYA 476_ KISDF 481_ GLSKA 486_ LGADD 491_ SYYTA 496_ RSAGK 501_ WPLKW 506_ YAPEC 511_ INFRK 516_ FSSRS 521_ DVWSY 526_ GVTMW 531_ EALSY 536_ GQKPY 541_ KKMKG 546_ PEVMA 551_ FIEQG 556_ KRMEC 561_ PPECP 566_ PELYA 571_ LMSDC 576_ WIYKW 581_ EDRPD 586_ FLTVE 591_ QRMRA 596_ CYYSL 601_ ASKVE 606_ GPPGS 611_TQKAE
1: Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Also contributes to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR)