P43405 (KSYK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase SYK
EC=2.7.10.2

Alternative name(s):
Spleen tyrosine kinase
p72-Syk

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.
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. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. Beside its function downstream of BCR plays also a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade. Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Plays also a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen.
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. May also be negatively regulated by PTPN6 through dephosphorylation. Downstream signaling adapters and intermediates like BLNK or RHOH may mediate positive and/or negative feedback regulation. Negatively regulated by CBL and CBLB through ubiquitination and probable degradation. Phosphorylates SH3BP2 which in turn may regulate SYK through LYN By similarity.
Subunit structure	Interacts with LYN; phosphorylates SYK By similarity. Interacts with RHOH (phosphorylated); regulates mast cells activation By similarity. Interacts with NFAM1 (phosphorylated); probably involved in BCR signaling By similarity. Interacts with VAV1 (via SH2 domain); phosphorylates VAV1 upon BCR activation. Interacts with GAB2 (phosphorylated); probably involved in IgE Fc receptor signaling By similarity. Interacts (via its SH2 domains) with CD79A (via its phosphorylated ITAM domain); the interaction stimulates SYK autophosphorylation and activation By similarity. Interacts with FCRL3. Interacts (via SH2 domains) with FCER1G (via ITAM domain); activates SYK and mediates neutrophils and macrophages integrin-mediated activation By similarity. Interacts with ITGB2 and FGR; involved in ITGB2 downstream signaling By similarity. Interacts with ITGB3; upon activation by ITGB3 promotes platelet adhesion. Interacts (via SH2 domains) with TYROBP (via ITAM domain); involved in neutrophils and macrophages integrin-mediated activation By similarity. Interacts with MSN and SELPLG; mediates the selectin-dependent activation of SYK by SELPLG. Interacts with BLNK (via SH2 domain). Interacts (via the second SH2 domain) with USP25 (via C-terminus); phosphorylates USP25 and regulates USP25 intracellular levels. Interacts (via SH2 domains) with CLEC1B (dimer). Interacts with CLEC7A; participatex in leukocyte activation in presence of fungal pathogens. Interacts (phosphorylated) with SLA; may regulate SYK through CBL recruitment. Interacts with YWHAG; attenuates BCR-induced membrane translocation and activation of SYK. Interacts with Epstein-Barr virus LMP2A.
Subcellular location	Cell membrane Probable. Cytoplasm › cytosol Probable.
Tissue specificity	Widely expressed in hematopoietic cells (at protein level). Within the B-cells compartment it is for instance expressed for pro-B-cells to plasma cells.
Domain	The SH2 domains mediate the interaction of SYK with the phosphorylated ITAM domains of transmembrane proteins. Some proteins like CLEC1B have a partial ITAM domain (also called hemITAM) containing a single YxxL motif. The interaction with SYK requires CLEC1B homodimerization.
Post-translational modification	Ubiquitinated by CBLB after BCR activation; which promotes proteasomal degradation By similarity. Autophosphorylated. Phosphorylated on tyrosine residues by LYN following receptors engagement. Phosphorylation on Tyr-323 creates a binding site for CBL, an adapter protein that serves as a negative regulator of BCR-stimulated calcium ion signaling. Phosphorylation at Tyr-348 creates a binding site for VAV1. 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. Phosphorylation on Ser-297 is very common, it peaks 5 minutes after BCR stimulation, and creates a binding site for YWHAG. Phosphorylation at Tyr-630 creates a binding site for BLNK. Dephosphorylated by PTPN6.
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	Adaptive immunity Angiogenesis Host-virus interaction Immunity Innate immunity
Cellular component	Cell membrane Cytoplasm Membrane
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 Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell proliferation Traceable author statement. Source: ProtInc integrin-mediated signaling pathway Non-traceable author statement. Source: UniProtKB interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW leukocyte cell-cell adhesion Inferred from direct assay. Source: UniProtKB neutrophil chemotaxis Inferred from direct assay. Source: UniProtKB organ morphogenesis Traceable author statement. Source: ProtInc platelet activation Traceable author statement. Source: Reactome protein complex assembly Traceable author statement. Source: ProtInc
Cellular component	T cell receptor complex Inferred from direct assay. Source: MGI cytosol Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW integrin binding Inferred from physical interaction. Source: UniProtKB non-membrane spanning protein tyrosine kinase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CD22	P20273	4	EBI-78302,EBI-78277

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

108 – 167

60

Interdomain A

Region

260 – 370

111

Interdomain B

Sites

Active site

494

1

Proton acceptor By similarity

Binding site

402

1

ATP By similarity

Amino acid modifications

Modified residue

28

1

Phosphotyrosine Ref.25 Ref.29

Modified residue

44

1

Phosphoserine Ref.29

Modified residue

47

1

Phosphotyrosine Ref.29

Modified residue

131

1

Phosphotyrosine Ref.29

Modified residue

202

1

Phosphoserine Ref.29

Modified residue

256

1

Phosphothreonine Ref.29

Modified residue

295

1

Phosphoserine Ref.24 Ref.29

Modified residue

296

1

Phosphotyrosine Ref.19 Ref.24 Ref.29

Modified residue

297

1

Phosphoserine Ref.23 Ref.29

Modified residue

316

1

Phosphoserine Ref.29

Modified residue

317

1

Phosphothreonine Ref.29

Modified residue

319

1

Phosphoserine Ref.24 Ref.29

Modified residue

323

1

Phosphotyrosine; by LYN Ref.19 Ref.20 Ref.24 Ref.29

Modified residue

345

1

Phosphothreonine Ref.29

Modified residue

348

1

Phosphotyrosine Ref.17 Ref.19 Ref.29

Modified residue

350

1

Phosphoserine Ref.29

Modified residue

352

1

Phosphotyrosine Ref.17 Ref.19 Ref.24 Ref.29

Modified residue

364

1

Phosphotyrosine Ref.29

Modified residue

379

1

Phosphoserine Ref.29

Modified residue

384

1

Phosphothreonine Ref.29

Modified residue

484

1

Phosphotyrosine Ref.29

Modified residue

507

1

Phosphotyrosine Ref.29

Modified residue

525

1

Phosphotyrosine; by autocatalysis Ref.29

Modified residue

526

1

Phosphotyrosine Ref.19 Ref.29

Modified residue

530

1

Phosphothreonine Ref.29

Modified residue

546

1

Phosphotyrosine By similarity

Modified residue

579

1

Phosphoserine Ref.29

Modified residue

582

1

Phosphothreonine Ref.29

Modified residue

629

1

Phosphotyrosine Ref.29

Modified residue

630

1

Phosphotyrosine Ref.29

Modified residue

631

1

Phosphotyrosine Ref.29

Natural variations

Alternative sequence

283 – 305

23

Missing in isoform Short.

VSP_005010

Natural variant

45

1

R → H.
Corresponds to variant rs16906862 [ dbSNP | Ensembl ].

VAR_033838

Experimental info

Mutagenesis

297

1

S → A: Abolishes YWHAG binding.

Mutagenesis

630

1

Y → F: Loss of interaction with BLNK.

Sequence conflict

119

1

P → A in CAA51970. Ref.5

Sequence conflict

250

1

G → P in CAA51970. Ref.5

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	FASTA	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], TISSUE SPECIFICITY, AUTOPHOSPHORYLATION.
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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.
[5]	"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.
[6]	"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.
[7]	"Functional and physical interactions of Syk family kinases with the Vav proto-oncogene product." Deckert M., Tartare-Deckert S., Couture C., Mustelin T., Altman A. Immunity 5:591-604(1996) [PubMed: 8986718] [Abstract] Cited for: INTERACTION WITH VAV1.
[8]	"Phospholipase C-gamma1 interacts with conserved phosphotyrosyl residues in the linker region of Syk and is a substrate for Syk." Law C.L., Chandran K.A., Sidorenko S.P., Clark E.A. Mol. Cell. Biol. 16:1305-1315(1996) [PubMed: 8657103] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF PLCG1, INTERACTION WITH PLCG1.
[9]	"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: FUNCTION IN PHOSPHORYLATION OF CBL, INTERACTION WITH CBL.
[10]	"Cbl-mediated negative regulation of the Syk tyrosine kinase. A critical role for Cbl phosphotyrosine-binding domain binding to Syk phosphotyrosine 323." Lupher M.L. Jr., Rao N., Lill N.L., Andoniou C.E., Miyake S., Clark E.A., Druker B., Band H. J. Biol. Chem. 273:35273-35281(1998) [PubMed: 9857068] [Abstract] Cited for: ENZYME REGULATION, INTERACTION WITH CBL.
[11]	"Dephosphorylation of ZAP-70 and inhibition of T cell activation by activated SHP1." Brockdorff J., Williams S., Couture C., Mustelin T. Eur. J. Immunol. 29:2539-2550(1999) [PubMed: 10458769] [Abstract] Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN6, ENZYME REGULATION.
[12]	"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.
[13]	"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.
[14]	"BLNK: molecular scaffolding through 'cis'-mediated organization of signaling proteins." Chiu C.W., Dalton M., Ishiai M., Kurosaki T., Chan A.C. EMBO J. 21:6461-6472(2002) [PubMed: 12456653] [Abstract] Cited for: FUNCTION IN B-CELL RECEPTOR SIGNALING PATHWAY, FUNCTION IN PHOSPHORYLATION OF BLNK.
[15]	"ITAM-based interaction of ERM proteins with Syk mediates signaling by the leukocyte adhesion receptor PSGL-1." Urzainqui A., Serrador J.M., Viedma F., Yanez-Mo M., Rodriguez A., Corbi A.L., Alonso-Lebrero J.L., Luque A., Deckert M., Vazquez J., Sanchez-Madrid F. Immunity 17:401-412(2002) [PubMed: 12387735] [Abstract] Cited for: FUNCTION IN CELL ADHESION, INTERACTION WITH SELPLG AND MSN.
[16]	"Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton." Obergfell A., Eto K., Mocsai A., Buensuceso C., Moores S.L., Brugge J.S., Lowell C.A., Shattil S.J. J. Cell Biol. 157:265-275(2002) [PubMed: 11940607] [Abstract] Cited for: INTERACTION WITH ITGB3.
[17]	"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.
[18]	"Association of the Src homology 2 domain-containing leukocyte phosphoprotein of 76 kD (SLP-76) with the p85 subunit of phosphoinositide 3-kinase." Shim E.K., Moon C.S., Lee G.Y., Ha Y.J., Chae S.K., Lee J.R. FEBS Lett. 575:35-40(2004) [PubMed: 15388330] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF LCP2.
[19]	"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. Tissue: Lung carcinoma.
[20]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-323, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[21]	"The kinase Syk as an adaptor controlling sustained calcium signalling and B-cell development." Kulathu Y., Hobeika E., Turchinovich G., Reth M. EMBO J. 27:1333-1344(2008) [PubMed: 18369315] [Abstract] Cited for: INTERACTION WITH BLNK, ENZYME REGULATION, MUTAGENESIS OF TYR-630, PHOSPHORYLATION AT TYR-630.
[22]	"Molecular mechanism of the Syk activation switch." Tsang E., Giannetti A.M., Shaw D., Dinh M., Tse J.K., Gandhi S., Ho H., Wang S., Papp E., Bradshaw J.M. J. Biol. Chem. 283:32650-32659(2008) [PubMed: 18818202] [Abstract] Cited for: ENZYME REGULATION.
[23]	"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.
[24]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-295; TYR-296; SER-319; TYR-323 AND TYR-352, MASS SPECTROMETRY.
[25]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-28, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[26]	"CLEC-2 activates Syk through dimerization." Hughes C.E., Pollitt A.Y., Mori J., Eble J.A., Tomlinson M.G., Hartwig J.H., O'Callaghan C.A., Fuetterer K., Watson S.P. Blood 115:2947-2955(2010) [PubMed: 20154219] [Abstract] Cited for: INTERACTION WITH CLEC1B.
[27]	"Functional interaction between the ubiquitin-specific protease 25 and the SYK tyrosine kinase." Cholay M., Reverdy C., Benarous R., Colland F., Daviet L. Exp. Cell Res. 316:667-675(2010) [PubMed: 19909739] [Abstract] Cited for: INTERACTION WITH USP25, FUNCTION.
[28]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]	"Complex phosphorylation dynamics control the composition of the Syk interactome in B cells." Bohnenberger H., Oellerich T., Engelke M., Hsiao H.H., Urlaub H., Wienands J. Eur. J. Immunol. 41:1550-1562(2011) [PubMed: 21469132] [Abstract] Cited for: PHOSPHORYLATION AT TYR-28; SER-44; TYR-47; TYR-131; SER-202; THR-256; SER-295; TYR-296; SER-297; SER-316; THR-317; SER-319; TYR-323; THR-345; TYR-348; SER-350; TYR-352; TYR-364; SER-379; THR-384; TYR-484; TYR-507; TYR-525; TYR-526; THR-530; SER-579; THR-582; TYR-629; TYR-630 AND TYR-631, INTERACTION WITH YWHAG, MUTAGENESIS OF SER-297. Tissue: B-cell.
[30]	"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.
[31]	"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 SH2 DOMAINS IN COMPLEX WITH CD3E PHOSPHORYLATED ITAM DOMAIN.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z29630 mRNA. Translation: CAA82737.1.
L28824 mRNA. Translation: AAA36526.1.
AL354862 Genomic DNA. No translation available.
BC001645 mRNA. Translation: AAH01645.1.
BC011399 mRNA. Translation: AAH11399.1.
BC002962 mRNA. Translation: AAH02962.1.
X73568 mRNA. Translation: CAA51970.1.

IPI

IPI00018597.
IPI00218278.

PIR

A53596.

RefSeq

NP_001128524.1. NM_001135052.2.
NP_001167638.1. NM_001174167.1.
NP_001167639.1. NM_001174168.1.
NP_003168.2. NM_003177.5.

UniGene

Hs.371720.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A81	X-ray	3.00	A/C/E/G/I/K	9-262	[»]
1CSY	NMR	-	A	163-265	[»]
1CSZ	NMR	-	A	163-265	[»]
1XBA	X-ray	2.00	A	356-635	[»]
1XBB	X-ray	1.57	A	356-635	[»]
1XBC	X-ray	2.00	A	356-635	[»]
3BUW	X-ray	1.45	A/C	317-329	[»]
3EMG	X-ray	2.60	A	349-635	[»]
3FQE	X-ray	2.50	A	356-635	[»]
3FQH	X-ray	2.26	A/B	356-635	[»]
3FQS	X-ray	2.10	A	356-635	[»]
3SRV	X-ray	1.95	A/B	360-635	[»]

ProteinModelPortal

P43405.

SMR

P43405. Positions 7-635.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-253N.

IntAct

P43405. 6 interactions.

MINT

MINT-148486.

STRING

P43405.

PTM databases

PhosphoSite

P43405.

Polymorphism databases

DMDM

1174527.

Proteomic databases

PeptideAtlas

P43405.

PRIDE

P43405.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000375746; ENSP00000364898; ENSG00000165025.
ENST00000375754; ENSP00000364907; ENSG00000165025.

GeneID

6850.

KEGG

hsa:6850.

UCSC

uc004aqz.1. human.

Organism-specific databases

CTD

6850.

GeneCards

GC09P093564.

H-InvDB

HIX0008158.

HGNC

HGNC:11491. SYK.

HPA

CAB007773.
HPA001384.

MIM

600085. gene.

neXtProt

NX_P43405.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG06189.

HOGENOM

HBG714705.

HOVERGEN

HBG001540.

InParanoid

P43405.

OMA

HYSYKAD.

OrthoDB

EOG4WSW93.

PhylomeDB

P43405.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Pathway_Interaction_DB

alphasynuclein_pathway. Alpha-synuclein signaling.
nfkappabatypicalpathway. Atypical NF-kappaB pathway.
bcr_5pathway. BCR signaling pathway.
pi3kcipathway. Class I PI3K signaling events.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
il2_1pathway. IL2-mediated signaling events.
avb3_opn_pathway. Osteopontin-mediated events.
txa2pathway. Thromboxane A2 receptor signaling.

Reactome

REACT_111102. Signal Transduction.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P43405.

Bgee

P43405.

CleanEx

HS_SYK.

Genevestigator

P43405.

GermOnline

ENSG00000165025. Homo sapiens.

Family and domain databases

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.
IPR000980. SH2.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR020757. Tyr_kinase_non-rcpt_SYK.
IPR012234. Tyr_kinase_non-rcpt_SYK/ZAP70.
[Graphical view]

Gene3D

G3DSA:1.10.930.10. G3DSA:1.10.930.10. 1 hit.
G3DSA:3.30.505.10. SH2. 2 hits.

KO

K05855.

PANTHER

PTHR24418:SF99. PTHR24418:SF99. 1 hit.

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

BindingDB

P43405.

NextBio

26739.

SOURCE

Search...

Entry information

Entry name

KSYK_HUMAN

Accession

Primary (citable) accession number: P43405

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	January 25, 2012
This is version 143 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.