ID KSYK_RAT Reviewed; 629 AA. AC Q64725; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 08-MAR-2011, entry version 99. DE RecName: Full=Tyrosine-protein kinase SYK; DE EC=2.7.10.2; DE AltName: Full=Spleen tyrosine kinase; GN Name=Syk; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=95279402; PubMed=7759516; DOI=10.1074/jbc.270.21.12659; RA Rowley R.B., Bolen J.B., Fargnoli J.; RT "Molecular cloning of rodent p72Syk. Evidence of alternative mRNA RT splicing."; RL J. Biol. Chem. 270:12659-12664(1995). RN [2] RP PHOSPHORYLATION AT TYR-317; TYR-342 AND TYR-346. RX MEDLINE=22191330; PubMed=12077122; DOI=10.1074/jbc.M201362200; RA Hong J.J., Yankee T.M., Harrison M.L., Geahlen R.L.; RT "Regulation of signaling in B cells through the phosphorylation of Syk RT on linker region tyrosines. A mechanism for negative signaling by the RT Lyn tyrosine kinase."; RL J. Biol. Chem. 277:31703-31714(2002). CC -!- FUNCTION: Positive effector of BCR-stimulated responses. Couples CC the B-cell antigen receptor (BCR) to the mobilization of calcium CC ion either through a phosphoinositide 3-kinase-dependent pathway, CC when not phosphorylated on tyrosines of the linker region, or CC through a phospholipase C-gamma-dependent pathway, when CC phosphorylated on Tyr-342 and Tyr-346. Thus the differential CC phosphorylation of Syk can determine the pathway by which BCR is CC coupled to the regulation of intracellular calcium ion. CC Phosphorylates USP25 and regulates its intracellular levels (By CC similarity). CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. CC -!- SUBUNIT: Interacts with CBL and SLA when it is phosphorylated. The CC interaction with SLA may link it to CBL, leading to its CC destruction. Interacts with phosphorylated NFAM1. Interacts CC through its SH2 domains with the phosphorylated ITAM domain of CC CD79A which stimulates SYK autophosphorylation and activation. CC Interacts with FCRL3 and RHOH.Interacts (via the second SH2 CC domain) with USP25 (via C-terminus) (By similarity). Interacts CC with GAB2 (By similarity). CC -!- INTERACTION: CC O00241:SIRPB1 (xeno); NbExp=1; IntAct=EBI-2615512, EBI-2615458; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=SykB; CC IsoId=Q64725-1; Sequence=Displayed; CC Name=SykA; CC IsoId=Q64725-2; Sequence=VSP_005011; CC -!- PTM: Autophosphorylated (By similarity). CC -!- PTM: Phosphorylation on Tyr-317 creates a binding site for CBL, an CC adapter protein that serves as a negative regulator of BCR- CC stimulated calcium ion signaling. CC -!- PTM: Phosphorylation on Tyr-342 and Tyr-346 enhances the CC phosphorylation and activation of phospholipase C-gamma and the CC early phase of calcium ion mobilization via a phosphoinositide 3- CC kinase-independent pathway. CC -!- PTM: Ubiquitinated by CBLB after BCR activation; which promotes CC proteasomal degradation (By similarity). CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. SYK/ZAP-70 subfamily. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SIMILARITY: Contains 2 SH2 domains. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U21684; AAA75167.1; -; mRNA. DR EMBL; U21683; AAA75166.1; -; mRNA. DR IPI; IPI00215301; -. DR IPI; IPI00231540; -. DR RefSeq; NP_036890.1; NM_012758.1. DR UniGene; Rn.87407; -. DR ProteinModelPortal; Q64725; -. DR SMR; Q64725; 8-629. DR IntAct; Q64725; 1. DR STRING; Q64725; -. DR PhosphoSite; Q64725; -. DR Ensembl; ENSRNOT00000016942; ENSRNOP00000016942; ENSRNOG00000012160. DR GeneID; 25155; -. DR KEGG; rno:25155; -. DR UCSC; NM_012758; rat. DR UCSC; U21683; rat. DR CTD; 25155; -. DR RGD; 3796; Syk. DR GeneTree; ENSGT00600000084269; -. DR HOVERGEN; HBG001540; -. DR InParanoid; Q64725; -. DR OrthoDB; EOG4WSW93; -. DR BRENDA; 2.7.10.2; 248. DR NextBio; 605611; -. DR ArrayExpress; Q64725; -. DR Genevestigator; Q64725; -. DR GermOnline; ENSRNOG00000012160; Rattus norvegicus. DR GO; GO:0005737; C:cytoplasm; IEA:InterPro. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:EC. DR GO; GO:0019904; F:protein domain specific binding; IMP:RGD. DR GO; GO:0043306; P:positive regulation of mast cell degranulation; IMP:RGD. DR GO; GO:0046777; P:protein autophosphorylation; IDA:RGD. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR023420; Kinase_SYK/ZAP-70_inter-SH2. DR InterPro; IPR000719; Prot_kinase_cat_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr-Pkinase. DR InterPro; IPR000980; SH2. DR InterPro; IPR012234; Tyr_kinase_non-rcpt_SYK/ZAP70. DR InterPro; IPR020635; Tyr_Pkinase_cat_dom. DR InterPro; IPR008266; Tyr_prot_kinase_AS. DR Gene3D; G3DSA:1.10.930.10; G3DSA:1.10.930.10; 1. DR Gene3D; G3DSA:3.30.505.10; SH2; 2. DR Pfam; PF07714; Pkinase_Tyr; 1. DR Pfam; PF00017; SH2; 2. DR PIRSF; PIRSF000604; TyrPK_SYK; 1. DR PRINTS; PR00401; SH2DOMAIN. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00252; SH2; 2. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF56112; Kinase_like; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50001; SH2; 2. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Kinase; Nucleotide-binding; KW Phosphoprotein; Repeat; SH2 domain; Transferase; KW Tyrosine-protein kinase; Ubl conjugation. FT CHAIN 1 629 Tyrosine-protein kinase SYK. FT /FTId=PRO_0000088167. FT DOMAIN 14 106 SH2 1. FT DOMAIN 167 258 SH2 2. FT DOMAIN 365 625 Protein kinase. FT NP_BIND 371 379 ATP (By similarity). FT REGION 259 364 Linker. FT ACT_SITE 488 488 Proton acceptor (By similarity). FT BINDING 396 396 ATP (By similarity). FT MOD_RES 27 27 Phosphotyrosine (By similarity). FT MOD_RES 289 289 Phosphoserine (By similarity). FT MOD_RES 290 290 Phosphotyrosine (By similarity). FT MOD_RES 291 291 Phosphoserine (By similarity). FT MOD_RES 310 310 Phosphoserine (By similarity). FT MOD_RES 313 313 Phosphoserine (By similarity). FT MOD_RES 317 317 Phosphotyrosine; by LYN. FT MOD_RES 342 342 Phosphotyrosine. FT MOD_RES 346 346 Phosphotyrosine. FT MOD_RES 519 519 Phosphotyrosine; by autocatalysis (By FT similarity). FT MOD_RES 520 520 Phosphotyrosine (By similarity). FT MOD_RES 540 540 Phosphotyrosine (By similarity). FT MOD_RES 623 623 Phosphotyrosine (By similarity). FT MOD_RES 624 624 Phosphotyrosine (By similarity). FT VAR_SEQ 277 299 Missing (in isoform SykA). FT /FTId=VSP_005011. SQ SEQUENCE 629 AA; 71529 MW; 81169A643EC6A6FE CRC64; MAGNAVDNAN HLTYFFGNIT REEAEDYLVQ GGMTDGLYLL RQSRNYLGGF ALSVAHNRKA HHYTIERELN GTYAISGGRA HASPADLCHY HSQEPEGLVC LLKKPFNRPP GVQPKTGPFE DLKENLIREY VKQTWNLQGQ ALEQAIISQK PQLEKLIATT AHEKMPWFHG NISRDESEQT VLIGSKTNGK FLIRARDNNG SFALCLLHEG KVLHYRIDRD KTGKLSIPEG KKFDTLWQLV EHYSYKPDGL LRVLTVPCQK IGVQMGHPGS SNAHPVTWSP GGIISRIKSY SFPKPGHKKP PPPQGSRPES TVSFNPYEPT GGAWGPDRGL QREALPMDTE VYESPYADPE EIRPKEVYLD RKLLTLEDNE LGSGNFGTVK KGYYQMKKVV KTVAVKILKN EANDPALKDE LLAEANVMQQ LDNPYIVRMI GICEAESWML VMEMAAWGPL NKYLQQNRHI KDKNIIELVH QVSMGMKYLE ESNFVHRDLA ARNVLLVTQH YAKISDFGLS KALRADENYY KAQTHGKWPV KWYAPECINY FKFSSKSDVW SFGVLMWEAF SYGQKPYRGM KGSEVTAMLE KGERMGCPPG CPREMYDLMF LCWTYDVENR PGFAAVELRL RNYYYDVVN //