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IID00714
UniprotP43405
ProteinTyrosine-protein kinase SYK
GeneSYK
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
635
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 1-635 Monomer :
 Evidence X-RAY 4fl3 A Reference
       Region 4fl3 A 1-8 disorder
       Region 4fl3 A 9-261 order
       Region 4fl3 A 262-337 disorder
       Region 4fl3 A 338-521 order
       Region 4fl3 A 522-534 disorder
       Region 4fl3 A 535-635 order
 Evidence X-RAY 4fl2 A Reference
       Region 4fl2 A 1-8 disorder
       Region 4fl2 A 9-264 order
       Region 4fl2 A 265-336 disorder
       Region 4fl2 A 337-635 order
Seq 9-262 Hetero hexamer : P07766
 Evidence X-RAY 1a81 E Reference
       Region 1a81 E 9-117 order
       Region 1a81 E 118-151 disorder
       Region 1a81 E 152-262 order
 Evidence X-RAY 1a81 C Reference
       Region 1a81 C 9-262 order
 Evidence X-RAY 1a81 A Reference
       Region 1a81 A 9-262 order
 Evidence X-RAY 1a81 K Reference
       Region 1a81 K 9-117 order
       Region 1a81 K 118-151 disorder
       Region 1a81 K 152-262 order
 Evidence X-RAY 1a81 I Reference
       Region 1a81 I 9-262 order
 Evidence X-RAY 1a81 G Reference
       Region 1a81 G 9-117 order
       Region 1a81 G 118-151 disorder
       Region 1a81 G 152-262 order
Seq 163-265 Monomer :
 Evidence NMR 1csz A Reference
       Region 1csz A 163-265 order
 Evidence NMR 1csy A Reference
       Region 1csy A 163-265 order
       Region 1csy A 198-200 high_rmsd
       Region 1csy A 264-265 high_rmsd
Seq 317-329 Hetero tetramer : IID00300Complex
 Evidence X-RAY 3buw C Reference
       Region 3buw C 317-318 disorder
       Region 3buw C 319-327 order
       Region 3buw C 328-329 disorder
 Evidence X-RAY 3buw A Reference
       Region 3buw A 317-318 disorder
       Region 3buw A 319-327 order
       Region 3buw A 328-329 disorder
Seq 343-635 Monomer :
 Evidence X-RAY 4yjv A Reference
       Region 4yjv A 355-363 disorder
       Region 4yjv A 364-377 order
       Region 4yjv A 378-382 disorder
       Region 4yjv A 383-633 order
       Region 4yjv A 634-635 disorder
 Evidence X-RAY 4yju A Reference
       Region 4yju A 355-363 disorder
       Region 4yju A 364-528 order
       Region 4yju A 529-531 disorder
       Region 4yju A 532-633 order
       Region 4yju A 634-635 disorder
 Evidence X-RAY 4yjt A Reference
       Region 4yjt A 355-363 disorder
       Region 4yjt A 364-633 order
       Region 4yjt A 634-635 disorder
 Evidence X-RAY 4yjs A Reference
       Region 4yjs A 355-363 disorder
       Region 4yjs A 364-377 order
       Region 4yjs A 378-382 disorder
       Region 4yjs A 383-404 order
       Region 4yjs A 405-411 disorder
       Region 4yjs A 412-632 order
       Region 4yjs A 633-635 disorder
 Evidence X-RAY 4yjr A Reference
       Region 4yjr A 355-363 disorder
       Region 4yjr A 364-377 order
       Region 4yjr A 378-382 disorder
       Region 4yjr A 383-633 order
       Region 4yjr A 634-635 disorder
 Evidence X-RAY 4yjq A Reference
       Region 4yjq A 355-363 disorder
       Region 4yjq A 364-378 order
       Region 4yjq A 379-382 disorder
       Region 4yjq A 383-633 order
       Region 4yjq A 634-635 disorder
 Evidence X-RAY 4yjp A Reference
       Region 4yjp A 355-363 disorder
       Region 4yjp A 364-406 order
       Region 4yjp A 407-409 disorder
       Region 4yjp A 410-528 order
       Region 4yjp A 529-531 disorder
       Region 4yjp A 532-632 order
       Region 4yjp A 633-635 disorder
 Evidence X-RAY 4yjo A Reference
       Region 4yjo A 355-362 disorder
       Region 4yjo A 363-528 order
       Region 4yjo A 529-531 disorder
       Region 4yjo A 532-632 order
       Region 4yjo A 633-635 disorder
 Evidence X-RAY 1xbc A Reference
       Region 1xbc A 356-362 disorder
       Region 1xbc A 363-404 order
       Region 1xbc A 405-410 disorder
       Region 1xbc A 411-635 order
 Evidence X-RAY 1xbb A Reference
       Region 1xbb A 356-362 disorder
       Region 1xbb A 363-405 order
       Region 1xbb A 406-410 disorder
       Region 1xbb A 411-528 order
       Region 1xbb A 529-532 disorder
       Region 1xbb A 533-635 order
 Evidence X-RAY 1xba A Reference
       Region 1xba A 356-362 disorder
       Region 1xba A 363-392 order
       Region 1xba A 393-394 disorder
       Region 1xba A 395-404 order
       Region 1xba A 405-410 disorder
       Region 1xba A 411-635 order
 Evidence X-RAY 3vf9 A Reference
       Region 3vf9 A 343-363 disorder
       Region 3vf9 A 364-393 order
       Region 3vf9 A 394-394 disorder
       Region 3vf9 A 395-404 order
       Region 3vf9 A 405-410 disorder
       Region 3vf9 A 411-635 order
 Evidence X-RAY 3vf8 A Reference
       Region 3vf8 A 343-362 disorder
       Region 3vf8 A 363-392 order
       Region 3vf8 A 393-394 disorder
       Region 3vf8 A 395-404 order
       Region 3vf8 A 405-410 disorder
       Region 3vf8 A 411-635 order
 Evidence X-RAY 3tud A Reference
       Region 3tud A 343-362 disorder
       Region 3tud A 363-513 order
       Region 3tud A 514-531 disorder
       Region 3tud A 532-635 order
 Evidence X-RAY 3tuc A Reference
       Region 3tuc A 343-357 disorder
       Region 3tuc A 358-515 order
       Region 3tuc A 516-534 disorder
       Region 3tuc A 535-633 order
       Region 3tuc A 634-635 disorder
 Evidence X-RAY 3tub A Reference
       Region 3tub A 343-361 disorder
       Region 3tub A 362-515 order
       Region 3tub A 516-534 disorder
       Region 3tub A 535-633 order
       Region 3tub A 634-635 disorder
 Evidence X-RAY 3srv B Reference
       Region 3srv B 360-363 disorder
       Region 3srv B 364-404 order
       Region 3srv B 405-410 disorder
       Region 3srv B 411-632 order
       Region 3srv B 633-635 disorder
 Evidence X-RAY 3srv A Reference
       Region 3srv A 360-363 disorder
       Region 3srv A 364-378 order
       Region 3srv A 379-380 disorder
       Region 3srv A 381-405 order
       Region 3srv A 406-411 disorder
       Region 3srv A 412-634 order
       Region 3srv A 635-635 disorder
 Evidence X-RAY 4rx9 A Reference
       Region 4rx9 A 356-362 disorder
       Region 4rx9 A 363-378 order
       Region 4rx9 A 379-381 disorder
       Region 4rx9 A 382-405 order
       Region 4rx9 A 406-410 disorder
       Region 4rx9 A 411-530 order
       Region 4rx9 A 531-531 disorder
       Region 4rx9 A 532-635 order
 Evidence X-RAY 4rx8 A Reference
       Region 4rx8 A 356-363 disorder
       Region 4rx8 A 364-405 order
       Region 4rx8 A 406-410 disorder
       Region 4rx8 A 411-530 order
       Region 4rx8 A 531-531 disorder
       Region 4rx8 A 532-635 order
 Evidence X-RAY 4rx7 A Reference
       Region 4rx7 A 356-362 disorder
       Region 4rx7 A 363-407 order
       Region 4rx7 A 408-410 disorder
       Region 4rx7 A 411-635 order
 Evidence X-RAY 4rss A Reference
       Region 4rss A 356-363 disorder
       Region 4rss A 364-408 order
       Region 4rss A 409-410 disorder
       Region 4rss A 411-634 order
       Region 4rss A 635-635 disorder
 Evidence X-RAY 4px6 A Reference
       Region 4px6 A 356-363 disorder
       Region 4px6 A 364-392 order
       Region 4px6 A 393-394 disorder
       Region 4px6 A 395-405 order
       Region 4px6 A 406-410 disorder
       Region 4px6 A 411-528 order
       Region 4px6 A 529-532 disorder
       Region 4px6 A 533-635 order
 Evidence X-RAY 4pv0 A Reference
       Region 4pv0 A 363-379 order
       Region 4pv0 A 380-381 disorder
       Region 4pv0 A 382-405 order
       Region 4pv0 A 406-410 disorder
       Region 4pv0 A 411-635 order
 Evidence X-RAY 4puz B Reference
       Region 4puz B 356-362 disorder
       Region 4puz B 363-405 order
       Region 4puz B 406-410 disorder
       Region 4puz B 411-529 order
       Region 4puz B 530-532 disorder
       Region 4puz B 533-635 order
 Evidence X-RAY 4puz A Reference
       Region 4puz A 356-362 disorder
       Region 4puz A 363-405 order
       Region 4puz A 406-410 disorder
       Region 4puz A 411-529 order
       Region 4puz A 530-532 disorder
       Region 4puz A 533-633 order
       Region 4puz A 634-635 disorder
 Evidence X-RAY 4i0t A Reference
       Region 4i0t A 356-362 disorder
       Region 4i0t A 363-404 order
       Region 4i0t A 405-410 disorder
       Region 4i0t A 411-528 order
       Region 4i0t A 529-533 disorder
       Region 4i0t A 534-635 order
 Evidence X-RAY 4i0s A Reference
       Region 4i0s A 356-362 disorder
       Region 4i0s A 363-404 order
       Region 4i0s A 405-410 disorder
       Region 4i0s A 411-528 order
       Region 4i0s A 529-532 disorder
       Region 4i0s A 533-635 order
 Evidence X-RAY 4i0r A Reference
       Region 4i0r A 356-362 disorder
       Region 4i0r A 363-374 order
       Region 4i0r A 375-375 disorder
       Region 4i0r A 376-379 order
       Region 4i0r A 380-382 disorder
       Region 4i0r A 383-405 order
       Region 4i0r A 406-410 disorder
       Region 4i0r A 411-528 order
       Region 4i0r A 529-532 disorder
       Region 4i0r A 533-635 order
 Evidence X-RAY 4gfg A Reference
       Region 4gfg A 356-362 disorder
       Region 4gfg A 363-635 order
 Evidence X-RAY 4fz7 A Reference
       Region 4fz7 A 356-362 disorder
       Region 4fz7 A 363-379 order
       Region 4fz7 A 380-381 disorder
       Region 4fz7 A 382-404 order
       Region 4fz7 A 405-410 disorder
       Region 4fz7 A 411-528 order
       Region 4fz7 A 529-532 disorder
       Region 4fz7 A 533-635 order
 Evidence X-RAY 4fz6 A Reference
       Region 4fz6 A 356-362 disorder
       Region 4fz6 A 363-379 order
       Region 4fz6 A 380-381 disorder
       Region 4fz6 A 382-405 order
       Region 4fz6 A 406-410 disorder
       Region 4fz6 A 411-528 order
       Region 4fz6 A 529-532 disorder
       Region 4fz6 A 533-635 order
 Evidence X-RAY 4fyo A Reference
       Region 4fyo A 356-362 disorder
       Region 4fyo A 363-404 order
       Region 4fyo A 405-410 disorder
       Region 4fyo A 411-528 order
       Region 4fyo A 529-532 disorder
       Region 4fyo A 533-635 order
 Evidence X-RAY 4fyn A Reference
       Region 4fyn A 356-362 disorder
       Region 4fyn A 363-379 order
       Region 4fyn A 380-380 disorder
       Region 4fyn A 381-405 order
       Region 4fyn A 406-410 disorder
       Region 4fyn A 411-528 order
       Region 4fyn A 529-532 disorder
       Region 4fyn A 533-635 order
 Evidence X-RAY 3fqs A Reference
       Region 3fqs A 356-362 disorder
       Region 3fqs A 363-405 order
       Region 3fqs A 406-410 disorder
       Region 3fqs A 411-528 order
       Region 3fqs A 529-532 disorder
       Region 3fqs A 533-635 order
 Evidence X-RAY 3fqh B Reference
       Region 3fqh B 356-362 disorder
       Region 3fqh B 363-379 order
       Region 3fqh B 380-383 disorder
       Region 3fqh B 384-405 order
       Region 3fqh B 406-410 disorder
       Region 3fqh B 411-528 order
       Region 3fqh B 529-532 disorder
       Region 3fqh B 533-633 order
       Region 3fqh B 634-635 disorder
 Evidence X-RAY 3fqh A Reference
       Region 3fqh A 356-362 disorder
       Region 3fqh A 363-378 order
       Region 3fqh A 379-383 disorder
       Region 3fqh A 384-405 order
       Region 3fqh A 406-410 disorder
       Region 3fqh A 411-634 order
       Region 3fqh A 635-635 disorder
 Evidence X-RAY 3fqe A Reference
       Region 3fqe A 356-362 disorder
       Region 3fqe A 363-405 order
       Region 3fqe A 406-410 disorder
       Region 3fqe A 411-529 order
       Region 3fqe A 530-532 disorder
       Region 3fqe A 533-635 order
 Evidence X-RAY 4fl1 A Reference
       Region 4fl1 A 356-362 disorder
       Region 4fl1 A 363-405 order
       Region 4fl1 A 406-410 disorder
       Region 4fl1 A 411-635 order
 Evidence X-RAY 4f4p A Reference
       Region 4f4p A 365-389 order
       Region 4f4p A 390-395 disorder
       Region 4f4p A 396-405 order
       Region 4f4p A 406-410 disorder
       Region 4f4p A 411-635 order
 Evidence X-RAY 3emg A Reference
       Region 3emg A 349-364 disorder
       Region 3emg A 365-392 order
       Region 3emg A 393-393 disorder
       Region 3emg A 394-405 order
       Region 3emg A 406-412 disorder
       Region 3emg A 413-528 order
       Region 3emg A 529-532 disorder
       Region 3emg A 533-631 order
       Region 3emg A 632-635 disorder
 Evidence X-RAY 4dfn A Reference
       Region 4dfn A 363-405 order
       Region 4dfn A 406-410 disorder
       Region 4dfn A 411-635 order
 Evidence X-RAY 4dfl A Reference
       Region 4dfl A 363-379 order
       Region 4dfl A 380-382 disorder
       Region 4dfl A 383-392 order
       Region 4dfl A 393-394 disorder
       Region 4dfl A 395-404 order
       Region 4dfl A 405-410 disorder
       Region 4dfl A 411-635 order
 Evidence X-RAY 5cy3 A Reference
       Region 5cy3 A 356-359 disorder
       Region 5cy3 A 360-407 order
       Region 5cy3 A 408-409 disorder
       Region 5cy3 A 410-635 order
 Evidence X-RAY 5cxz A Reference
       Region 5cxz A 356-362 disorder
       Region 5cxz A 363-406 order
       Region 5cxz A 407-411 disorder
       Region 5cxz A 412-531 order
       Region 5cxz A 532-532 disorder
       Region 5cxz A 533-635 order
 Evidence X-RAY 5cxh A Reference
       Region 5cxh A 356-362 disorder
       Region 5cxh A 363-635 order
Seq 343-635 Hetero dimer :
 Evidence X-RAY 5c27 A Reference
       Region 5c27 A 343-362 disorder
       Region 5c27 A 363-635 order
Seq 343-635 Hetero dimer :
 Evidence X-RAY 5c26 A Reference
       Region 5c26 A 343-362 disorder
       Region 5c26 A 363-635 order
SeqProS verified 319-327 Hetero tetramer : IID00300Complex
       Region 3buw A 319-327 order
       Region 3buw C 319-327 order
       Region 4fl2 A 265-336 disorder
Seqphosphorylation
    631-631 Phosphotyrosine
    630-630 Phosphotyrosine
    629-629 Phosphotyrosine
    582-582 Phosphothreonine
    546-546 Phosphotyrosine
    579-579 Phosphoserine
    530-530 Phosphothreonine
    526-526 Phosphotyrosine
    525-525 Phosphotyrosine; by autocatalysis
    507-507 Phosphotyrosine
    484-484 Phosphotyrosine
    379-379 Phosphoserine
    384-384 Phosphothreonine
    364-364 Phosphotyrosine
    352-352 Phosphotyrosine
    350-350 Phosphoserine
    348-348 Phosphotyrosine
    345-345 Phosphothreonine
    319-319 Phosphoserine
    323-323 Phosphotyrosine; by LYN
    317-317 Phosphothreonine
    316-316 Phosphoserine
    297-297 Phosphoserine
    295-295 Phosphoserine
    296-296 Phosphotyrosine
    256-256 Phosphothreonine
    202-202 Phosphoserine
    131-131 Phosphotyrosine
    47-47 Phosphotyrosine
    44-44 Phosphoserine
    28-28 Phosphotyrosine
 
Prediction
NeProc
Disorder 1-7,279-288,293-346
Order 8-278,289-292,347-635
ProS 279-288,293-308,318-346
AlphaFold
Disorder 1-9,263-337,408-408,518-518,521-534
Order 10-262,338-407,409-517,519-520,535-635
Pfam Hmmer
PF00017 15-92 4.6e-30
PF00017 168-244 5.5e-32
PF07714 370-626 2.7e-127
Function
Function in SwissProt
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. In addition to 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 (By similarity). Required for the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770). Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (By similarity). 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. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (By similarity).
Biological Process
Diagram with PDB data
SYK/CBLCrystal structure of c-Cbl-TKB domain complexed with its binding motif in Syk