Reviewed, UniProtKB/Swiss-Prot P43405 (KSYK_HUMAN)

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

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	635 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-348 and Tyr-352. 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 CBL and SLA when it is phosphorylated. The interaction with SLA may link it to CBL, leading to its destruction. Interacts with phosphorylated NFAM1 By similarity. Interacts with Epstein-Barr virus LMP2A. Interacts through its SH2 domains with the phosphorylated ITAM domain of CD79A which stimulates SYK autophosphorylation and activation. Interacts with FCRL3.
Post-translational modification	Autophosphorylated. Phosphorylation on Tyr-323 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-348 and Tyr-352 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 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	Host-virus interaction
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat SH2 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	integrin-mediated signaling pathway Non-traceable author statement. Source: UniProtKB interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW leukocyte adhesion Inferred from direct assay. Source: UniProtKB neutrophil chemotaxis Inferred from direct assay. Source: UniProtKB organ morphogenesis Traceable author statement. Source: ProtInc protein complex assembly Ref.2 Traceable author statement. Source: ProtInc
Cellular component	T cell receptor complex Inferred from direct assay. Source: MGI cytoplasm Inferred from electronic annotation. Source: InterPro nucleus Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro integrin binding Inferred from physical interaction. Source: UniProtKB non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CD22	P20273	1	EBI-78302,EBI-78277
FCER1G	P30273	1	EBI-78302,EBI-515289
ITGB2	P05107	1	EBI-78302,EBI-300173

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P43405-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: P43405-2)

The sequence of this isoform differs from the canonical sequence as follows:
     283-305: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 635

635

Tyrosine-protein kinase SYK

PRO_0000088165

Regions

Domain

15 – 107

93

SH2 1

Domain

168 – 259

92

SH2 2

Domain

371 – 631

261

Protein kinase

Nucleotide binding

377 – 385

9

ATP By similarity

Region

260 – 370

111

Linker

Sites

Active site

494

1

Proton acceptor By similarity

Binding site

402

1

ATP By similarity

Amino acid modifications

Modified residue

296

1

Phosphotyrosine

Modified residue

297

1

Phosphoserine

Modified residue

316

1

Phosphoserine By similarity

Modified residue

319

1

Phosphoserine By similarity

Modified residue

323

1

Phosphotyrosine; by LYN

Modified residue

348

1

Phosphotyrosine

Modified residue

352

1

Phosphotyrosine

Modified residue

525

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

526

1

Phosphotyrosine

Modified residue

546

1

Phosphotyrosine By similarity

Modified residue

629

1

Phosphotyrosine By similarity

Modified residue

630

1

Phosphotyrosine By similarity

Natural variations

Alternative sequence

283 – 305

23

Missing in isoform Short.

VSP_005010

Natural variant

45

1

R → H: dbSNP rs16906862.

VAR_033838

Experimental info

Sequence conflict

119

1

P → A in CAA51970. Ref.4

Sequence conflict

250

1

G → P in CAA51970. Ref.4

Secondary structure

1

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635

Helix Strand Turn

Details...

Beta strand

166 – 169

4

Helix

176 – 184

9

Beta strand

191 – 195

5

Beta strand

198 – 201

4

Beta strand

203 – 211

9

Beta strand

213 – 219

7

Beta strand

222 – 224

3

Beta strand

229 – 231

3

Helix

237 – 244

8

Beta strand

251 – 253

3

Helix

367 – 369

3

Beta strand

370 – 379

10

Beta strand

384 – 391

8

Beta strand

396 – 403

8

Helix

412 – 424

13

Beta strand

435 – 449

15

Helix

456 – 462

7

Helix

468 – 487

20

Helix

497 – 499

3

Beta strand

500 – 504

5

Beta strand

507 – 510

4

Beta strand

524 – 527

4

Helix

536 – 538

3

Helix

541 – 546

6

Beta strand

548 – 550

3

Helix

551 – 566

16

Turn

567 – 569

3

Helix

578 – 586

9

Helix

599 – 608

10

Helix

613 – 615

3

Helix

619 – 635

17

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified November 1, 1995. Version 1. Checksum: EAA6BDE65881FC68	FASTA	635	72,066
	10 20 30 40 50 60 MASSGMADSA NHLPFFFGNI TREEAEDYLV QGGMSDGLYL LRQSRNYLGG FALSVAHGRK 70 80 90 100 110 120 AHHYTIEREL NGTYAIAGGR THASPADLCH YHSQESDGLV CLLKKPFNRP QGVQPKTGPF 130 140 150 160 170 180 EDLKENLIRE YVKQTWNLQG QALEQAIISQ KPQLEKLIAT TAHEKMPWFH GKISREESEQ 190 200 210 220 230 240 IVLIGSKTNG KFLIRARDNN GSYALCLLHE GKVLHYRIDK DKTGKLSIPE GKKFDTLWQL 250 260 270 280 290 300 VEHYSYKADG LLRVLTVPCQ KIGTQGNVNF GGRPQLPGSH PATWSAGGII SRIKSYSFPK 310 320 330 340 350 360 PGHRKSSPAQ GNRQESTVSF NPYEPELAPW AADKGPQREA LPMDTEVYES PYADPEEIRP 370 380 390 400 410 420 KEVYLDRKLL TLEDKELGSG NFGTVKKGYY QMKKVVKTVA VKILKNEAND PALKDELLAE 430 440 450 460 470 480 ANVMQQLDNP YIVRMIGICE AESWMLVMEM AELGPLNKYL QQNRHVKDKN IIELVHQVSM 490 500 510 520 530 540 GMKYLEESNF VHRDLAARNV LLVTQHYAKI SDFGLSKALR ADENYYKAQT HGKWPVKWYA 550 560 570 580 590 600 PECINYYKFS SKSDVWSFGV LMWEAFSYGQ KPYRGMKGSE VTAMLEKGER MGCPAGCPRE 610 620 630 MYDLMNLCWT YDVENRPGFA AVELRLRNYY YDVVN
	Isoform Short [UniParc]. Checksum: 1D4FD24C6C9F5C53		612	69,510
	10 20 30 40 50 60 MASSGMADSA NHLPFFFGNI TREEAEDYLV QGGMSDGLYL LRQSRNYLGG FALSVAHGRK 70 80 90 100 110 120 AHHYTIEREL NGTYAIAGGR THASPADLCH YHSQESDGLV CLLKKPFNRP QGVQPKTGPF 130 140 150 160 170 180 EDLKENLIRE YVKQTWNLQG QALEQAIISQ KPQLEKLIAT TAHEKMPWFH GKISREESEQ 190 200 210 220 230 240 IVLIGSKTNG KFLIRARDNN GSYALCLLHE GKVLHYRIDK DKTGKLSIPE GKKFDTLWQL 250 260 270 280 290 300 VEHYSYKADG LLRVLTVPCQ KIGTQGNVNF GGRPQLPGSH PASSPAQGNR QESTVSFNPY 310 320 330 340 350 360 EPELAPWAAD KGPQREALPM DTEVYESPYA DPEEIRPKEV YLDRKLLTLE DKELGSGNFG 370 380 390 400 410 420 TVKKGYYQMK KVVKTVAVKI LKNEANDPAL KDELLAEANV MQQLDNPYIV RMIGICEAES 430 440 450 460 470 480 WMLVMEMAEL GPLNKYLQQN RHVKDKNIIE LVHQVSMGMK YLEESNFVHR DLAARNVLLV 490 500 510 520 530 540 TQHYAKISDF GLSKALRADE NYYKAQTHGK WPVKWYAPEC INYYKFSSKS DVWSFGVLMW 550 560 570 580 590 600 EAFSYGQKPY RGMKGSEVTA MLEKGERMGC PAGCPREMYD LMNLCWTYDV ENRPGFAAVE 610 LRLRNYYYDV VN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the cDNA for the deleted syk kinase homologous to ZAP-70 from human basophilic leukemia cell line (KU812)." Yagi S., Suzuki K., Hasegawa A., Okumura K., Ra C. Biochem. Biophys. Res. Commun. 200:28-34(1994) [PubMed: 7513161] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Molecular cloning of human Syk. A B cell protein-tyrosine kinase associated with the surface immunoglobulin M-B cell receptor complex." Law C.-L., Sidorenko S.P., Chandran K.A., Draves K.E., Chan A.C., Weiss A., Edelhoff S., Disteche C.M., Clark E.A. J. Biol. Chem. 269:12310-12319(1994) [PubMed: 8163536] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND SHORT). Tissue: Eye and Lymph.
[4]	"Molecular cloning of the human homologue to the pig protein-tyrosine kinase syk." Mueller B., Cooper L., Terhorst C. Immunogenetics 39:359-362(1994) [PubMed: 8168854] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-635. Tissue: Tonsil.
[5]	"Integral membrane protein 2 of Epstein-Barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases." Miller C.L., Burkhardt A.L., Lee J.H., Stealey B., Longnecker R., Bolen J.B., Kieff E. Immunity 2:155-166(1995) [PubMed: 7895172] [Abstract] Cited for: INTERACTION WITH EPSTEIN-BARR VIRUS LMP2A.
[6]	"Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and Syk tyrosine kinases." Deckert M., Elly C., Altman A., Liu Y.C. J. Biol. Chem. 273:8867-8874(1998) [PubMed: 9535867] [Abstract] Cited for: INTERACTION WITH CBL.
[7]	"SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling." Tang J., Sawasdikosol S., Chang J.-H., Burakoff S.J. Proc. Natl. Acad. Sci. U.S.A. 96:9775-9780(1999) [PubMed: 10449770] [Abstract] Cited for: INTERACTION WITH SLA.
[8]	"Molecular cloning and characterization of SPAP1, an inhibitory receptor." Xu M.-J., Zhao R., Zhao Z.J. Biochem. Biophys. Res. Commun. 280:768-775(2001) [PubMed: 11162587] [Abstract] Cited for: INTERACTION WITH FCRL3.
[9]	"Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry." Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C. Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003) [PubMed: 12522270] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-348 AND TYR-352, MASS SPECTROMETRY.
[10]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-296; TYR-323; TYR-348; TYR-352 AND TYR-526, MASS SPECTROMETRY.
[11]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-297, MASS SPECTROMETRY. Tissue: Platelet.
[12]	"Solution structure of the C-terminal SH2 domain of the human tyrosine kinase Syk complexed with a phosphotyrosine pentapeptide." Narula S.S., Yuan R.W., Adams S.E., Green O.M., Green J., Philips T.B., Zydowsky L.D., Botfield M.C., Hatada M., Laird E.R., Zoller M.J., Karas J.L., Dalgarno D.C. Structure 3:1061-1073(1995) [PubMed: 8590001] [Abstract] Cited for: STRUCTURE BY NMR OF 163-265.
[13]	"Structural basis for Syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptide." Fuetterer K., Wong J., Grucza R.A., Chan A.C., Waksman G. J. Mol. Biol. 281:523-537(1998) [PubMed: 9698567] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 9-262 IN COMPLEX WITH CD3E.
+	Additional computationally mapped references.

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