F1N9Y5 (KSYK_CHICK) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase SYK
EC=2.7.10.2

Gene names

Name:	SYK
ORF Names:	RCJMB04_19o18

Organism

Gallus gallus (Chicken) [Reference proteome]

Taxonomic identifier

9031 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Sauropsida › Sauria › Archosauria › Dinosauria › Saurischia › Theropoda › Coelurosauria › Aves › Neognathae › Galliformes › Phasianidae › Phasianinae › Gallus

Protein attributes

Sequence length	613 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. 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 VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. 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. Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. Ref.3
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	Autoinhibited. Intramolecular binding of the interdomains A and B (also called linker region) to parts of the catalytic domain keep the catalytic center in an inactive conformation. The phosphorylation of the interdomains or the binding of the SH2 domains with dually phosphorylated ITAM domains on transmembrane proteins disrupt those intramolecular interactions allowing the kinase domain to adopt an active conformation. The phosphorylation of SYK and of the ITAM domains which is responsible for SYK activation is essentially mediated by SRC subfamily kinases, like LYN, upon transmembrane receptors engagement. Downstream signaling adapters and intermediates may mediate positive and/or negative feedback regulation By similarity.
Subcellular location	Cell membrane Probable. Cytoplasm › cytosol Probable.
Domain	The SH2 domains mediate the interaction of SYK with the phosphorylated ITAM domains of transmembrane proteins By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily. Contains 1 protein kinase domain. Contains 2 SH2 domains.

Ontologies

Keywords
Biological process	Immunity Innate immunity
Cellular component	Cell membrane Cytoplasm Membrane
Domain	Repeat SH2 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell receptor signaling pathway Inferred from mutant phenotype Ref.3. Source: UniProtKB adaptive immune response Inferred from mutant phenotype Ref.3. Source: UniProtKB blood vessel morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB cellular response to molecule of fungal origin Inferred from sequence or structural similarity. Source: UniProtKB defense response to bacterium Inferred from sequence or structural similarity. Source: UniProtKB innate immune response Inferred from sequence or structural similarity. Source: UniProtKB integrin-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB intracellular signal transduction Inferred from electronic annotation. Source: InterPro leukocyte cell-cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB lymph vessel development Inferred from sequence or structural similarity. Source: UniProtKB macrophage activation involved in immune response Inferred from sequence or structural similarity. Source: UniProtKB neutrophil activation involved in immune response Inferred from sequence or structural similarity. Source: UniProtKB neutrophil chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of bone resorption Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell adhesion mediated by integrin Inferred from sequence or structural similarity. Source: UniProtKB regulation of ERK1 and ERK2 cascade Inferred from sequence or structural similarity. Source: UniProtKB regulation of arachidonic acid secretion Inferred from sequence or structural similarity. Source: UniProtKB regulation of neutrophil degranulation Inferred from sequence or structural similarity. Source: UniProtKB regulation of phagocytosis Inferred from sequence or structural similarity. Source: UniProtKB regulation of platelet aggregation Inferred from sequence or structural similarity. Source: UniProtKB regulation of superoxide anion generation Inferred from sequence or structural similarity. Source: UniProtKB serotonin secretion by platelet Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell early phagosome Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from mutant phenotype Ref.3. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 613	613	Tyrosine-protein kinase SYK		PRO_0000415332
Regions
	Domain	14 – 106	93	SH2 1
	Domain	167 – 258	92	SH2 2
	Domain	349 – 613	265	Protein kinase
	Nucleotide binding	355 – 363	9	ATP By similarity
	Region	107 – 166	60	Interdomain A
	Region	259 – 348	90	Interdomain B
Sites
	Active site	472	1	Proton acceptor By similarity
	Binding site	380	1	ATP By similarity
Experimental info
	Sequence conflict	188	1	N → D in CAG32202. Ref.1
	Sequence conflict	398	1	E → G in CAG32202. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	F1N9Y5 [UniParc]. Last modified January 25, 2012. Version 2. Checksum: 32783B7D0C8EBC82	FASTA	613	69,901
	10 20 30 40 50 60 MASNMANPAN HLPYFFGNIT REEAEEYLMQ GGMSDGLYLL RQSRNYLGGF ALSLAYGRKV 70 80 90 100 110 120 HHYTIERELS GTYAIAGGKS HASPAELINY HSEEADGLIC LLRKSFNRPP GVEPKTGPFE 130 140 150 160 170 180 DLKENLIREY VKQTWNLQGH ALEQAIISQK PQLEKLIATT AHEKMPWFHG RISREESEHR 190 200 210 220 230 240 ILIGSRNNGK FLIRERDSNG SYALCLLNDG KVLHYRIDRD KTGKLSIPDG KRFDTLWQLV 250 260 270 280 290 300 EHYSYKPDGL LRVLSIPCPR HGSESDNVVF DTRPLPGTPS KLQTPIGAPS DDQTPFNPYV 310 320 330 340 350 360 LQRARGLIGA EKGDQREALP MDTEVYESPY ADPDEIKPKN VTLDRKLLTL EEGELGSGNF 370 380 390 400 410 420 GTVKKGFYKM KKGAKPVAVK ILKNESNDPA IKDELLREAN VMQQLDNPYI VRMIGICEAE 430 440 450 460 470 480 AWMLVMEMAE LGPLNKFLQK NRHVTEKNIT ELVHQVSMGM KYLEENNFVH RDLAARNVLL 490 500 510 520 530 540 VTQHYAKISD FGLSKALSAD ENYYKAQSHG KWPVKWYAPE CMNFYKFSSK SDVWSFGVLM 550 560 570 580 590 600 WEAFSYGQKP YKGMKGGEVA QMIERGERME CPEACPVEVY DLMKLCWTYN VDDRPGFVAV 610 ELRLRNYYYD ISH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Full-length cDNAs from chicken bursal lymphocytes to facilitate gene function analysis." Caldwell R.B., Kierzek A.M., Arakawa H., Bezzubov Y., Zaim J., Fiedler P., Kutter S., Blagodatski A., Kostovska D., Koter M., Plachy J., Carninci P., Hayashizaki Y., Buerstedde J.-M. Genome Biol. 6:R6.1-R6.9(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: CB. Tissue: Bursa of Fabricius.
[2]	"Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution." Hillier L.W., Miller W., Birney E., Warren W., Hardison R.C., Ponting C.P., Bork P., Burt D.W., Groenen M.A.M., Delany M.E., Dodgson J.B., Chinwalla A.T., Cliften P.F., Clifton S.W., Delehaunty K.D., Fronick C., Fulton R.S., Graves T.A. , Kremitzki C., Layman D., Magrini V., McPherson J.D., Miner T.L., Minx P., Nash W.E., Nhan M.N., Nelson J.O., Oddy L.G., Pohl C.S., Randall-Maher J., Smith S.M., Wallis J.W., Yang S.-P., Romanov M.N., Rondelli C.M., Paton B., Smith J., Morrice D., Daniels L., Tempest H.G., Robertson L., Masabanda J.S., Griffin D.K., Vignal A., Fillon V., Jacobbson L., Kerje S., Andersson L., Crooijmans R.P., Aerts J., van der Poel J.J., Ellegren H., Caldwell R.B., Hubbard S.J., Grafham D.V., Kierzek A.M., McLaren S.R., Overton I.M., Arakawa H., Beattie K.J., Bezzubov Y., Boardman P.E., Bonfield J.K., Croning M.D.R., Davies R.M., Francis M.D., Humphray S.J., Scott C.E., Taylor R.G., Tickle C., Brown W.R.A., Rogers J., Buerstedde J.-M., Wilson S.A., Stubbs L., Ovcharenko I., Gordon L., Lucas S., Miller M.M., Inoko H., Shiina T., Kaufman J., Salomonsen J., Skjoedt K., Wong G.K.-S., Wang J., Liu B., Wang J., Yu J., Yang H., Nefedov M., Koriabine M., Dejong P.J., Goodstadt L., Webber C., Dickens N.J., Letunic I., Suyama M., Torrents D., von Mering C., Zdobnov E.M., Makova K., Nekrutenko A., Elnitski L., Eswara P., King D.C., Yang S.-P., Tyekucheva S., Radakrishnan A., Harris R.S., Chiaromonte F., Taylor J., He J., Rijnkels M., Griffiths-Jones S., Ureta-Vidal A., Hoffman M.M., Severin J., Searle S.M.J., Law A.S., Speed D., Waddington D., Cheng Z., Tuzun E., Eichler E., Bao Z., Flicek P., Shteynberg D.D., Brent M.R., Bye J.M., Huckle E.J., Chatterji S., Dewey C., Pachter L., Kouranov A., Mourelatos Z., Hatzigeorgiou A.G., Paterson A.H., Ivarie R., Brandstrom M., Axelsson E., Backstrom N., Berlin S., Webster M.T., Pourquie O., Reymond A., Ucla C., Antonarakis S.E., Long M., Emerson J.J., Betran E., Dupanloup I., Kaessmann H., Hinrichs A.S., Bejerano G., Furey T.S., Harte R.A., Raney B., Siepel A., Kent W.J., Haussler D., Eyras E., Castelo R., Abril J.F., Castellano S., Camara F., Parra G., Guigo R., Bourque G., Tesler G., Pevzner P.A., Smit A., Fulton L.A., Mardis E.R., Wilson R.K. Nature 432:695-716(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Red jungle fowl.
[3]	"BLNK: a central linker protein in B cell activation." Fu C., Turck C.W., Kurosaki T., Chan A.C. Immunity 9:93-103(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN B-CELL RECEPTOR SIGNALING PATHWAY, FUNCTION IN PHOSPHORYLATION OF BLNK.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ720543 mRNA. Translation: CAG32202.1. AADN02069860 Genomic DNA. No translation available. AADN02069861 Genomic DNA. No translation available. AADN02069862 Genomic DNA. No translation available. AADN02069863 Genomic DNA. No translation available. AADN02069864 Genomic DNA. No translation available. AADN02069865 Genomic DNA. No translation available. AADN02069866 Genomic DNA. No translation available. AADN02069867 Genomic DNA. No translation available. AADN02069868 Genomic DNA. No translation available. AADN02069869 Genomic DNA. No translation available.
IPI	IPI00603504. IPI00679956.
RefSeq	NP_001026601.1. NM_001031430.1.
UniGene	Gga.22529.
3D structure databases
ProteinModelPortal	F1N9Y5.
ModBase	Search...
Protein-protein interaction databases
STRING	9031.ENSGALP00000032170.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSGALT00000024555; ENSGALP00000024509; ENSGALG00000015216.
GeneID	427272.
KEGG	gga:427272.
Organism-specific databases
CTD	6850.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00620000087791.
HOGENOM	HOG000113264.
HOVERGEN	HBG001540.
InParanoid	Q5ZJ91.
KO	K05855.
OMA	PKEVYLD.
OrthoDB	EOG4WSW93.
Family and domain databases
Gene3D	1.10.930.10. 1 hit. 3.30.505.10. 2 hits.
InterPro	IPR011009. Kinase-like_dom. IPR023420. Kinase_SYK/ZAP-70_inter-SH2. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR000980. SH2. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. IPR012234. Tyr_kinase_non-rcpt_SYK/ZAP70. [Graphical view]
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 2 hits. [Graphical view]
PIRSF	PIRSF000604. TyrPK_SYK. 1 hit.
PRINTS	PR00401. SH2DOMAIN. PR00109. TYRKINASE.
SMART	SM00252. SH2. 2 hits. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS50001. SH2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	20828556.

Entry information

Entry name

KSYK_CHICK

Accession

Primary (citable) accession number: F1N9Y5
Secondary accession number(s): Q5ZJ91

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 25, 2012
Last sequence update:	January 25, 2012
Last modified:	April 3, 2013
This is version 17 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program