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 02-NOV-2016, entry version 151. DE RecName: Full=Tyrosine-protein kinase SYK; DE EC=2.7.10.2; DE AltName: Full=Spleen tyrosine kinase; DE AltName: Full=p72Syk; 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], AND ALTERNATIVE SPLICING (ISOFORMS SYKA RP AND SYKB). RX 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 FUNCTION IN PHOSPHORYLATION OF HCLS1. RX PubMed=8611520; DOI=10.1021/bi9528614; RA Ruzzene M., Brunati A.M., Marin O., Donella-Deana A., Pinna L.A.; RT "SH2 domains mediate the sequential phosphorylation of HS1 protein by RT p72syk and Src-related protein tyrosine kinases."; RL Biochemistry 35:5327-5332(1996). RN [3] RP PHOSPHORYLATION AT TYR-317 BY LYN, AND PHOSPHORYLATION AT TYR-342 AND RP TYR-346. RX 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: Non-receptor tyrosine kinase which mediates signal CC transduction downstream of a variety of transmembrane receptors CC including classical immunoreceptors like the B-cell receptor CC (BCR). Regulates several biological processes including innate and CC adaptive immunity, cell adhesion, osteoclast maturation, platelet CC activation and vascular development. Assembles into signaling CC complexes with activated receptors at the plasma membrane via CC interaction between its SH2 domains and the receptor tyrosine- CC phosphorylated ITAM domains. The association with the receptor can CC also be indirect and mediated by adapter proteins containing ITAM CC or partial hemITAM domains. The phosphorylation of the ITAM CC domains is generally mediated by SRC subfamily kinases upon CC engagement of the receptor. More rarely signal transduction via CC SYK could be ITAM-independent. Direct downstream effectors CC phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and CC BLNK. Initially identified as essential in B-cell receptor (BCR) CC signaling, it is necessary for the maturation of B-cells most CC probably at the pro-B to pre-B transition. Activated upon BCR CC engagement, it phosphorylates and activates BLNK an adapter CC linking the activated BCR to downstream signaling adapters and CC effectors. It also phosphorylates and activates PLCG1 and the PKC CC signaling pathway. It also phosphorylates BTK and regulates its CC activity in B-cell antigen receptor (BCR)-coupled signaling. In CC addition to its function downstream of BCR plays also a role in T- CC cell receptor signaling. Plays also a crucial role in the innate CC immune response to fungal, bacterial and viral pathogens. It is CC for instance activated by the membrane lectin CLEC7A. Upon CC stimulation by fungal proteins, CLEC7A together with SYK activates CC immune cells inducing the production of ROS. Also activates the CC inflammasome and NF-kappa-B-mediated transcription of chemokines CC and cytokines in presence of pathogens. Regulates neutrophil CC degranulation and phagocytosis through activation of the MAPK CC signaling cascade. Also mediates the activation of dendritic cells CC by cell necrosis stimuli. Also involved in mast cells activation. CC Also functions downstream of receptors mediating cell adhesion. CC Relays for instance, integrin-mediated neutrophils and macrophages CC activation and P-selectin receptor/SELPG-mediated recruitment of CC leukocytes to inflammatory loci. Plays also a role in non-immune CC processes. It is for instance involved in vascular development CC where it may regulate blood and lymphatic vascular separation. It CC is also required for osteoclast development and function. CC Functions in the activation of platelets by collagen, mediating CC PLCG2 phosphorylation and activation. May be coupled to the CC collagen receptor by the ITAM domain-containing FCER1G. Also CC activated by the membrane lectin CLEC1B that is required for CC activation of platelets by PDPN/podoplanin. Involved in platelet CC adhesion being activated by ITGB3 engaged by fibrinogen. CC {ECO:0000269|PubMed:8611520}. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE- CC ProRule:PRU10028}. CC -!- ENZYME REGULATION: Autoinhibited. Intramolecular binding of the CC interdomains A and B (also called linker region) to parts of the CC catalytic domain keep the catalytic center in an inactive CC conformation. The phosphorylation of the interdomains or the CC binding of the SH2 domains with dually phosphorylated ITAM domains CC on transmembrane proteins disrupt those intramolecular CC interactions allowing the kinase domain to adopt an active CC conformation. The phosphorylation of SYK and of the ITAM domains CC which is responsible for SYK activation is essentially mediated by CC SRC subfamily kinases, like LYN, upon transmembrane receptors CC engagement. May also be negatively regulated by PTPN6 through CC dephosphorylation. Downstream signaling adapters and intermediates CC like BLNK or RHOH may mediate positive and/or negative feedback CC regulation. Negatively regulated by CBL and CBLB through CC ubiquitination and probable degradation (By similarity). CC Phosphorylates SH3BP2 which in turn may regulate SYK through LYN CC (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Interacts with LYN; phosphorylates SYK. Interacts with CC RHOH (phosphorylated); regulates mast cells activation. Interacts CC with NFAM1 (phosphorylated); probably involved in BCR signaling. CC Interacts with VAV1 (via SH2 domain); phosphorylates VAV1 upon BCR CC activation. Interacts with GAB2 (phosphorylated); probably CC involved in IgE Fc receptor signaling. Interacts (via its SH2 CC domains) with CD79A (via its phosphorylated ITAM domain); the CC interaction stimulates SYK autophosphorylation and activation. CC Interacts with FCRL3. Interacts (via SH2 domains) with FCER1G (via CC ITAM domain); activates SYK and mediates neutrophils and CC macrophages integrin-mediated activation. Interacts with ITGB2 and CC FGR; involved in ITGB2 downstream signaling. Interacts with ITGB3; CC upon activation by ITGB3 promotes platelet adhesion. Interacts CC (via SH2 domains) with TYROBP (via ITAM domain); involved in CC neutrophils and macrophages integrin-mediated activation. CC Interacts with MSN and SELPLG; mediates the selectin-dependent CC activation of SYK by SELPLG. Interacts with BLNK (via SH2 domain). CC Interacts (via the second SH2 domain) with USP25 (via C-terminus); CC phosphorylates USP25 and regulates USP25 intracellular levels. CC Interacts (via SH2 domains) with CLEC1B (dimer). Interacts with CC CLEC7A; participates in leukocyte activation in presence of fungal CC pathogens. Interacts (phosphorylated) with SLA; may regulate SYK CC through CBL recruitment. Interacts with YWHAG; attenuates BCR- CC induced membrane translocation and activation of SYK (By CC similarity). Interacts (via SH2 domains) with GCSAM; the CC interaction increases after B-cell receptor stimulation, resulting CC in enhanced SYK autophosphorylation and activity (By similarity). CC Interacts with TNS2; leading to the phosphorylation of SYK (By CC similarity). Interacts with FLNA (via filamin repeat 5); docks SYK CC to the plasma membrane (By similarity). Interacts with CEACAM1; CC lipopolysaccharide activated neutrophils induce phosphorylation of CC SYK resulting in the formation of a complex including TLR4, CC phosphorylated form of SYK and CEACAM1, which in turn, recruits CC PTPN6 that dephosphorylates SYK, reducing the production of CC reactive oxygen species (ROS) and lysosome disruption, leading to CC a reduction of the inflammasome activity (By similarity). CC {ECO:0000250|UniProtKB:P43405, ECO:0000250|UniProtKB:P48025}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}. Cytoplasm, CC cytosol {ECO:0000305}. 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 -!- DOMAIN: The SH2 domains mediate the interaction of SYK with the CC phosphorylated ITAM domains of transmembrane proteins. Some CC proteins like CLEC1B have a partial ITAM domain (also called CC hemITAM) containing a single YxxL motif. The interaction with SYK CC requires CLEC1B homodimerization (By similarity). {ECO:0000250}. CC -!- PTM: Autophosphorylated. Phosphorylated on tyrosine residues by CC LYN following receptors engagement. Phosphorylation on Tyr-317 CC creates a binding site for CBL, an adapter protein that serves as CC a negative regulator of BCR-stimulated calcium ion signaling (By CC similarity). Phosphorylation at Tyr-342 creates a binding site for CC VAV1 (By similarity). Phosphorylation on Tyr-342 and Tyr-346 CC enhances the phosphorylation and activation of phospholipase C- CC gamma and the early phase of calcium ion mobilization via a CC phosphoinositide 3-kinase-independent pathway (By similarity). CC Phosphorylation on Ser-291 is very common, it peaks 5 minutes CC after BCR stimulation, and creates a binding site for YWHAG (By CC similarity). Phosphorylation at Tyr-624 creates a binding site for CC BLNK (By similarity). Dephosphorylated by PTPN6 (By similarity). CC {ECO:0000250}. CC -!- PTM: Ubiquitinated by CBLB after BCR activation; which promotes CC proteasomal degradation. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. SYK/ZAP-70 subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- SIMILARITY: Contains 2 SH2 domains. {ECO:0000255|PROSITE- CC ProRule:PRU00191}. 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 RefSeq; NP_036890.1; NM_012758.1. [Q64725-1] DR UniGene; Rn.87407; -. DR ProteinModelPortal; Q64725; -. DR BioGrid; 247220; 2. DR IntAct; Q64725; 1. DR STRING; 10116.ENSRNOP00000016942; -. DR BindingDB; Q64725; -. DR ChEMBL; CHEMBL4364; -. DR iPTMnet; Q64725; -. DR PhosphoSitePlus; Q64725; -. DR PaxDb; Q64725; -. DR PRIDE; Q64725; -. DR GeneID; 25155; -. DR KEGG; rno:25155; -. DR CTD; 6850; -. DR RGD; 3796; Syk. DR eggNOG; ENOG410IH0T; Eukaryota. DR eggNOG; COG0515; LUCA. DR HOGENOM; HOG000113264; -. DR HOVERGEN; HBG001540; -. DR InParanoid; Q64725; -. DR KO; K05855; -. DR PhylomeDB; Q64725; -. DR BRENDA; 2.7.10.2; 5301. DR Reactome; R-RNO-2029481; FCGR activation. DR Reactome; R-RNO-2454202; Fc epsilon receptor (FCERI) signaling. DR PRO; PR:Q64725; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB. DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISS:UniProtKB. DR GO; GO:0019904; F:protein domain specific binding; IMP:RGD. DR GO; GO:0004672; F:protein kinase activity; IDA:RGD. DR GO; GO:0004713; F:protein tyrosine kinase activity; EXP:Reactome. DR GO; GO:0005102; F:receptor binding; IBA:GO_Central. DR GO; GO:0002250; P:adaptive immune response; ISS:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW. DR GO; GO:0050853; P:B cell receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0048514; P:blood vessel morphogenesis; ISS:UniProtKB. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISS:UniProtKB. DR GO; GO:0071226; P:cellular response to molecule of fungal origin; ISS:UniProtKB. DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome. DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central. DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB. DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro. DR GO; GO:0002366; P:leukocyte activation involved in immune response; ISS:UniProtKB. DR GO; GO:0007159; P:leukocyte cell-cell adhesion; ISS:UniProtKB. DR GO; GO:0001945; P:lymph vessel development; ISS:UniProtKB. DR GO; GO:0002281; P:macrophage activation involved in immune response; ISS:UniProtKB. DR GO; GO:0002283; P:neutrophil activation involved in immune response; ISS:UniProtKB. DR GO; GO:0030593; P:neutrophil chemotaxis; ISS:UniProtKB. DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IBA:GO_Central. DR GO; GO:0046641; P:positive regulation of alpha-beta T cell proliferation; IBA:GO_Central. DR GO; GO:0045579; P:positive regulation of B cell differentiation; IBA:GO_Central. DR GO; GO:0045780; P:positive regulation of bone resorption; ISS:UniProtKB. DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; ISS:UniProtKB. DR GO; GO:0043306; P:positive regulation of mast cell degranulation; IMP:RGD. DR GO; GO:0046777; P:protein autophosphorylation; IDA:RGD. DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB. DR GO; GO:0031623; P:receptor internalization; ISS:UniProtKB. DR GO; GO:0090237; P:regulation of arachidonic acid secretion; ISS:UniProtKB. DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:0050776; P:regulation of immune response; IDA:RGD. DR GO; GO:0043313; P:regulation of neutrophil degranulation; ISS:UniProtKB. DR GO; GO:0050764; P:regulation of phagocytosis; ISS:UniProtKB. DR GO; GO:0010543; P:regulation of platelet activation; ISS:UniProtKB. DR GO; GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB. DR GO; GO:0032928; P:regulation of superoxide anion generation; ISS:UniProtKB. DR GO; GO:0002554; P:serotonin secretion by platelet; ISS:UniProtKB. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR Gene3D; 1.10.930.10; -; 1. DR Gene3D; 3.30.505.10; -; 2. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR023420; Kinase_SYK/ZAP-70_inter-SH2. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR000980; SH2. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR012234; Tyr_kinase_non-rcpt_SYK/ZAP70. 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; SSF55550; SSF55550; 2. DR SUPFAM; SSF56112; SSF56112; 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 Adaptive immunity; Alternative splicing; Angiogenesis; ATP-binding; KW Cell membrane; Complete proteome; Cytoplasm; Immunity; KW Innate immunity; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; KW Reference proteome; 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. {ECO:0000255|PROSITE- FT ProRule:PRU00191}. FT DOMAIN 167 258 SH2 2. {ECO:0000255|PROSITE- FT ProRule:PRU00191}. FT DOMAIN 365 625 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 371 379 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT REGION 107 166 Interdomain A. {ECO:0000250}. FT REGION 259 364 Interdomain B. {ECO:0000250}. FT ACT_SITE 488 488 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10028}. FT BINDING 396 396 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOD_RES 27 27 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 43 43 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 46 46 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 130 130 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 201 201 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 255 255 Phosphothreonine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 270 270 Phosphoserine. FT {ECO:0000250|UniProtKB:P48025}. FT MOD_RES 289 289 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 290 290 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 291 291 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 310 310 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 311 311 Phosphothreonine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 313 313 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 317 317 Phosphotyrosine; by LYN. FT {ECO:0000269|PubMed:12077122}. FT MOD_RES 339 339 Phosphothreonine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 342 342 Phosphotyrosine. FT {ECO:0000269|PubMed:12077122}. FT MOD_RES 344 344 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 346 346 Phosphotyrosine. FT {ECO:0000269|PubMed:12077122}. FT MOD_RES 358 358 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 373 373 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 378 378 Phosphothreonine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 478 478 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 501 501 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 519 519 Phosphotyrosine; by autocatalysis. FT {ECO:0000250}. FT MOD_RES 520 520 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 524 524 Phosphothreonine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 540 540 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P48025}. FT MOD_RES 573 573 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 576 576 Phosphothreonine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 623 623 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 624 624 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 625 625 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT VAR_SEQ 277 299 Missing (in isoform SykA). {ECO:0000305}. 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 //