Reviewed, UniProtKB/Swiss-Prot P48025 (KSYK_MOUSE)

Names and origin

Protein names

Recommended name:
    Tyrosine-protein kinase SYK
    EC=2.7.10.2
Alternative name(s):
    Spleen tyrosine kinase

Gene names

Name:

Syk

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	629 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Positive effector of BCR-stimulated responses. Couples the B-cell antigen receptor (BCR) to the mobilization of calcium ion either through a phosphoinositide 3-kinase-dependent pathway, when not phosphorylated on tyrosines of the linker region, or through a phospholipase C-gamma-dependent pathway, when phosphorylated on Tyr-342 and Tyr-346. Thus the differential phosphorylation of Syk can determine the pathway by which BCR is coupled to the regulation of intracellular calcium ion By similarity.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with SLA when it is phosphorylated. The interaction with SLA may link it to CBL, leading to its destruction. Interacts with FCRL3 By similarity. Interacts with phosphorylated NFAM1. Interacts through its SH2 domains with the phosphorylated ITAM domain of CD79A which stimulates SYK autophosphorylation and activation.
Post-translational modification	Autophosphorylated By similarity. Phosphorylation on Tyr-317 creates a binding site for c-Cbl, an adapter protein that serves as a negative regulator of BCR-stimulated calcium ion signaling By similarity. Phosphorylation on Tyr-342 and Tyr-346 enhances the phosphorylation and activation of phospholipase C-gamma and the early phase of calcium ion mobilization via a phosphoinositide 3-kinase-independent pathway By similarity. Ubiquitinated by CBLB after BCR activation; which promotes proteasomal degradation. Ref.5
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
Domain	Repeat SH2 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	B cell receptor signaling pathway Inferred from direct assay. Source: MGI G-protein coupled receptor protein signaling pathway Traceable author statement. Source: MGI activation of JUN kinase activity Inferred from mutant phenotype. Source: MGI beta selection Inferred from genetic interaction. Source: MGI enzyme linked receptor protein signaling pathway Inferred from direct assay. Source: MGI leukotriene biosynthetic process Inferred from mutant phenotype. Source: MGI peptidyl-tyrosine phosphorylation Inferred from direct assay. Source: MGI positive regulation of B cell differentiation Ref.1 Inferred from mutant phenotype. Source: MGI positive regulation of alpha-beta T cell differentiation Inferred from genetic interaction. Source: MGI positive regulation of alpha-beta T cell proliferation Inferred from genetic interaction. Source: MGI positive regulation of calcium-mediated signaling Inferred from mutant phenotype. Source: MGI positive regulation of gamma-delta T cell differentiation Ref.1 Inferred from mutant phenotype. Source: MGI positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process Inferred from mutant phenotype. Source: MGI positive regulation of interleukin-3 biosynthetic process Inferred from mutant phenotype. Source: MGI positive regulation of mast cell degranulation Inferred from mutant phenotype. Source: MGI positive regulation of peptidyl-tyrosine phosphorylation Inferred from mutant phenotype. Source: MGI protein amino acid autophosphorylation Inferred from direct assay. Source: MGI serotonin secretion Inferred from mutant phenotype. Source: MGI
Cellular component	B cell receptor complex Inferred from direct assay. Source: MGI cytoplasm Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from direct assay. Source: MGI non-membrane spanning protein tyrosine kinase activity Inferred from direct assay. Source: MGI protein binding Inferred from physical interaction. Source: IntAct receptor signaling protein tyrosine kinase activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Cd22	P35329	1	EBI-300116,EBI-300059
POU2AF1	Q16633	1	EBI-300116,EBI-943588	From a different organism.
Pou2af1	Q64693	2	EBI-300116,EBI-943530

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 629	629	Tyrosine-protein kinase SYK		PRO_0000088166
Regions
	Domain	14 – 106	93	SH2 1
	Domain	167 – 258	92	SH2 2
	Domain	365 – 625	261	Protein kinase
	Nucleotide binding	371 – 379	9	ATP By similarity
	Region	259 – 364	106	Linker
Sites
	Active site	488	1	Proton acceptor By similarity
	Binding site	396	1	ATP By similarity
Amino acid modifications
	Modified residue	290	1	Phosphotyrosine By similarity
	Modified residue	291	1	Phosphoserine By similarity
	Modified residue	310	1	Phosphoserine Ref.7
	Modified residue	313	1	Phosphoserine Ref.7
	Modified residue	317	1	Phosphotyrosine Ref.7
	Modified residue	342	1	Phosphotyrosine Ref.7
	Modified residue	346	1	Phosphotyrosine Ref.7
	Modified residue	519	1	Phosphotyrosine; by autocatalysis Ref.7
	Modified residue	520	1	Phosphotyrosine Ref.7
	Modified residue	540	1	Phosphotyrosine Ref.7
	Modified residue	623	1	Phosphotyrosine Ref.7
	Modified residue	624	1	Phosphotyrosine Ref.7
Experimental info
	Sequence conflict	326	1	Missing in CAA90034. Ref.2
	Sequence conflict	446 – 447	2	EL → DV in CAA90034. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P48025-1 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: 2F98D21601F8224E	FASTA	629	71,376
	10 20 30 40 50 60 MAGSAVDSAN HLTYFFGNIT REEAEDYLVQ GGMTDGLYLL RQSRNYLGGF ALSVAHNRKA 70 80 90 100 110 120 HHYTIERELN GTYAISGGRA HASPADLCHY HSQEPDGLIC LLKKPFNRPP GVQPKTGPFE 130 140 150 160 170 180 DLKENLIREY VKQTWNLQGQ ALEQAIISQK PQLEKLIATT AHEKMPWFHG NISRDESEQT 190 200 210 220 230 240 VLIGSKTNGK FLIRARDNSG SYALCLLHEG KVLHYRIDRD KTGKLSIPEG KKFDTLWQLV 250 260 270 280 290 300 EHYSYKPDGL LRVLTVPCQK IGAQMGHPGS PNAHPVTWSP GGIISRIKSY SFPKPGHKKP 310 320 330 340 350 360 APPQGSRPES TVSFNPYEPT GGPWGPDRGL QREALPMDTE VYESPYADPE EIRPKEVYLD 370 380 390 400 410 420 RSLLTLEDNE LGSGNFGTVK KGYYQMKKVV KTVAVKILKN EANDPALKDE LLAEANVMQQ 430 440 450 460 470 480 LDNPYIVRMI GICEAESWML VMEMAELGPL NKYLQQNRHI KDKNIIELVH QVSMGMKYLE 490 500 510 520 530 540 ESNFVHRDLA ARNVLLVTQH YAKISDFGLS KALRADENYY KAQTHGKWPV KWYAPECINY 550 560 570 580 590 600 YKFSSKSDVW SFGVLMWEAF SYGQKPYRGM KGSEVTAMLE KGERMGCPAG CPREMYDLMN 610 620 LCWTYDVENR PGFTAVELRL RNYYYDVVN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk." Turner M., Mee P.J., Costello P.S., Williams O., Price A.A., Duddy L.P., Furlong M.T., Geahlen R.L., Tybulewicz V.L. Nature 378:298-302(1995) [PubMed: 7477352] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Molecular characterization of the murine syk protein tyrosine kinase cDNA, transcripts and protein." Flueck M., Zuercher G., Andres A., Ziemiecki A. Biochem. Biophys. Res. Commun. 213:273-281(1995) [PubMed: 7639745] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Spleen.
[3]	Richards J.D., Gold M.R., Hourihane S.L., Defranco A.L., Matsuuchi L. Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Ig alpha/Ig beta immunoreceptor tyrosine activation motif binding and autophosphorylation." Rowley R.B., Burkhardt A.L., Chao H.-G., Matsueda G.R., Bolen J.B. J. Biol. Chem. 270:11590-11594(1995) [PubMed: 7538118] [Abstract] Cited for: INTERACTION WITH CD79A.
[5]	"Cbl-b negatively regulates B cell antigen receptor signaling in mature B cells through ubiquitination of the tyrosine kinase Syk." Sohn H.W., Gu H., Pierce S.K. J. Exp. Med. 197:1511-1524(2003) [PubMed: 12771181] [Abstract] Cited for: UBIQUITINATION.
[6]	"NFAM1, an immunoreceptor tyrosine-based activation motif-bearing molecule that regulates B cell development and signaling." Ohtsuka M., Arase H., Takeuchi A., Yamasaki S., Shiina R., Suenaga T., Sakurai D., Yokosuka T., Arase N., Iwashima M., Kitamura T., Moriya H., Saito T. Proc. Natl. Acad. Sci. U.S.A. 101:8126-8131(2004) [PubMed: 15143214] [Abstract] Cited for: INTERACTION WITH NFAM1.
[7]	"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling." Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R. J. Immunol. 179:5864-5876(2007) [PubMed: 17947660] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310; SER-313; TYR-317; TYR-342; TYR-346; TYR-519; TYR-520; TYR-540; TYR-623 AND TYR-624, MASS SPECTROMETRY. Tissue: Mast cell.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U25685 mRNA. Translation: AAA87462.1. Z49877 mRNA. Translation: CAA90034.1. U36776 mRNA. Translation: AAA79996.1.
IPI	IPI00137932.
PIR	I48781.
RefSeq	NP_035648.2.
UniGene	Mm.375031
3D structure databases
HSSP	HSSP built from PDB template 1A81 based on UniProtKB P43405.
SMR	P48025. Positions 8-261, 357-629.
ModBase	Search...
Protein-protein interaction databases
IntAct	P48025. 4 interactions.
PTM databases
PhosphoSite	P48025.
Proteomic databases
PRIDE	P48025.
Genome annotation databases
Ensembl	ENSMUSG00000021457. Mus musculus. [Contig view]
GeneID	20963.
KEGG	mmu:20963.
Organism-specific databases
MGI	MGI:99515. Syk.
Phylogenomic databases
HOGENOM	P48025.
HOVERGEN	P48025.
OMA	P48025. HYSYKAD.
Enzyme and pathway databases
BRENDA	2.7.10.2. 244.
Gene expression databases
ArrayExpress	P48025.
Bgee	P48025.
CleanEx	MM_SYK.
GermOnline	ENSMUSG00000021457. Mus musculus.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR000980. SH2. IPR012234. Tyr_kinase_SYK. IPR001245. Tyr_pkinase. IPR008266. Tyr_pkinase_AS. [Graphical view]
Gene3D	G3DSA:3.30.505.10. SH2. 2 hits.
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 2 hits. [Graphical view]
PIRSF	PIRSF000604. TyrPK_SYK. 1 hit.
PRINTS	PR00401. SH2DOMAIN. PR00109. TYRKINASE.
ProDom	PD000001. Prot_kinase. 1 hit. PD000093. SH2. 2 hits. [Graphical view] [Entries sharing at least one domain]
SMART	SM00252. SH2. 2 hits. SM00219. TyrKc. 1 hit. [Graphical view]
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 Resources
NextBio	299918.
SOURCE	Search...

Entry information

Entry name

KSYK_MOUSE

Accession

Primary (citable) accession number: P48025

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	October 1, 1996
Last modified:	June 16, 2009
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)