Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0013379
UniProt IDP43405
Primary gene name(s)SYK
Synonym gene name(s)unknown
Protein nameTyrosine-protein kinase SYK
Protein functionNon-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. 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. 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. {ECO:0000250|UniProtKB:P48025, ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:12456653, ECO:0000269|PubMed:15388330, ECO:0000269|PubMed:19909739, ECO:0000269|PubMed:8657103, ECO:0000269|PubMed:9535867}.
Subcellular locationCell membrane {ECO:0000305}. Cytoplasm, cytosol {ECO:0000305}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P43405
Gene Ontology
(Biological Process)
Complete annatation
activation of JUN kinase activity [GO:0007257];
adaptive immune response [GO:0002250];
angiogenesis [GO:0001525];
animal organ morphogenesis [GO:0009887];
B cell receptor signaling pathway [GO:0050853];
beta selection [GO:0043366];
blood vessel morphogenesis [GO:0048514];
cell proliferation [GO:0008283];
cellular response to low-density lipoprotein particle stimulus [GO:0071404];
cellular response to molecule of fungal origin [GO:0071226];
defense response to bacterium [GO:0042742];
Fc-epsilon receptor signaling pathway [GO:0038095];
Fc-gamma receptor signaling pathway involved in phagocytosis [GO:0038096];
inflammatory response [GO:0006954];
innate immune response [GO:0045087];
integrin-mediated signaling pathway [GO:0007229];
leukocyte activation involved in immune response [GO:0002366];
leukocyte cell-cell adhesion [GO:0007159];
leukotriene biosynthetic process [GO:0019370];
lymph vessel development [GO:0001945];
macrophage activation involved in immune response [GO:0002281];
neutrophil activation involved in immune response [GO:0002283];
neutrophil chemotaxis [GO:0030593];
peptidyl-serine phosphorylation [GO:0018105];
peptidyl-tyrosine autophosphorylation [GO:0038083];
platelet activation [GO:0030168];
positive regulation of alpha-beta T cell differentiation [GO:0046638];
positive regulation of alpha-beta T cell proliferation [GO:0046641];
positive regulation of B cell differentiation [GO:0045579];
positive regulation of bone resorption [GO:0045780];
positive regulation of calcium-mediated signaling [GO:0050850];
positive regulation of cell adhesion mediated by integrin [GO:0033630];
positive regulation of cytokine secretion [GO:0050715];
positive regulation of gamma-delta T cell differentiation [GO:0045588];
positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process [GO:0045425];
positive regulation of interleukin-3 biosynthetic process [GO:0045401];
positive regulation of mast cell degranulation [GO:0043306];
positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731];
positive regulation of receptor internalization [GO:0002092];
positive regulation of type I interferon production [GO:0032481];
protein phosphorylation [GO:0006468];
receptor internalization [GO:0031623];
regulation of arachidonic acid secretion [GO:0090237];
regulation of ERK1 and ERK2 cascade [GO:0070372];
regulation of neutrophil degranulation [GO:0043313];
regulation of phagocytosis [GO:0050764];
regulation of platelet activation [GO:0010543];
regulation of platelet aggregation [GO:0090330];
regulation of sequence-specific DNA binding transcription factor activity [GO:0051090];
regulation of superoxide anion generation [GO:0032928];
regulation of tumor necrosis factor-mediated signaling pathway [GO:0010803];
serotonin secretion by platelet [GO:0002554];
stimulatory C-type lectin receptor signaling pathway [GO:0002223];
transcription factor import into nucleus [GO:0042991];
transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
integrin binding [GO:0005178];
non-membrane spanning protein tyrosine kinase activity [GO:0004715];
protein kinase activity [GO:0004672];
protein serine/threonine kinase activity [GO:0004674];
protein tyrosine kinase activity [GO:0004713];
receptor signaling protein tyrosine kinase activity [GO:0004716]
Gene Ontology
(Cellular Component)
Complete annatation
B cell receptor complex [GO:0019815];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
early phagosome [GO:0032009];
extrinsic component of cytoplasmic side of plasma membrane [GO:0031234];
nucleus [GO:0005634];
plasma membrane [GO:0005886];
protein complex [GO:0043234];
T cell receptor complex [GO:0042101]
Protein-protein interaction112717
Phylogenetic treeP43405
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3unknownunknownunknown
AZA vs. DISUunknownunknownunknown
AZA vs. IL7unknownunknownunknown
AZA vs. SAHAunknownunknownunknown
DISU vs. CD3unknownunknownunknown
DISU vs. IL7unknownunknownunknown
DISU vs. SAHAunknownunknownunknown
DMSO vs. AZAunknownunknownunknown
DMSO vs. CD3unknownunknownunknown
DMSO vs. DISUunknownunknownunknown
DMSO vs. IL7unknownunknownunknown
DMSO vs. SAHAunknownunknownunknown
HIV vs. Mock in Activation2.279131604655250.2109894986870950.999983755607037
HIV vs. Mock in Latencyunknownunknownunknown
IL7 vs. CD3unknownunknownunknown
SAHA vs. CD3unknownunknownunknown
SAHA vs. IL7unknownunknownunknown
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 1.2343 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB02010 Staurosporine experimental unknown unknown
DB06834 N-(2-hydroxy-1,1-dimethylethyl)-1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxamide experimental unknown unknown
DB07159 6-({5-fluoro-2-[(3,4,5-trimethoxyphenyl)amino]pyrimidin-4-yl}amino)-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one experimental unknown unknown
DB07194 2-{2-[(3,5-dimethylphenyl)amino]pyrimidin-4-yl}-N-[(1S)-2-hydroxy-1-methylethyl]-4-methyl-1,3-thiazole-5-carboxamide experimental unknown unknown
DB08361 2-{[(1R,2S)-2-aminocyclohexyl]amino}-4-[(3-methylphenyl)amino]pyrimidine-5-carboxamide experimental unknown unknown
DB08846 Ellagic Acid investigational unknown inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1A81 X-ray 3.0Å A/C/E/G/I/K=9-262.
1CSY NMR - A=163-265.
1CSZ NMR - A=163-265.
1XBA X-ray 2.0Å A=356-635.
1XBB X-ray 1.5Å A=356-635.
1XBC X-ray 2.0Å A=356-635.
3BUW X-ray 1.4Å A/C=317-329.
3EMG X-ray 2.6Å A=349-635.
3FQE X-ray 2.5Å A=356-635.
3FQH X-ray 2.2Å A/B=356-635.
3FQS X-ray 2.1Å A=356-635.
3SRV X-ray 1.9Å A/B=360-635.
3TUB X-ray 2.2Å A=343-635.
3TUC X-ray 2.1Å A=343-635.
3TUD X-ray 2.3Å A=343-635.
3VF8 X-ray 2.0Å A=343-635.
3VF9 X-ray 2.3Å A=343-635.
4DFL X-ray 1.9Å A=363-635.
4DFN X-ray 2.4Å A=363-635.
4F4P X-ray 2.3Å A=365-635.
4FL1 X-ray 1.7Å A=356-635.
4FL2 X-ray 2.1Å A=1-635.
4FL3 X-ray 1.9Å A=1-635.
4FYN X-ray 2.3Å A=356-635.
4FYO X-ray 1.4Å A=356-635.
4FZ6 X-ray 1.8Å A=356-635.
4FZ7 X-ray 1.7Å A=356-635.
4GFG X-ray 2.3Å A=356-635.
4I0R X-ray 2.1Å A=356-635.
4I0S X-ray 1.9Å A=356-635.
4I0T X-ray 1.7Å A=356-635.
4PUZ X-ray 2.0Å A/B=356-635.
4PV0 X-ray 2.0Å A=363-635.
4PX6 X-ray 1.6Å A=356-635.
4RSS X-ray 1.8Å A=356-635.
4RX7 X-ray 1.8Å A=356-635.
4RX8 X-ray 1.5Å A=356-635.
4RX9 X-ray 1.7Å A=356-635.
4WNM X-ray 2.5Å A=343-635.
4XG2 X-ray 2.2Å A=356-635.
4XG3 X-ray 2.3Å A/B=356-635.
4XG4 X-ray 2.3Å A=356-635.
4XG6 X-ray 2.4Å A=356-635.
4XG7 X-ray 1.7Å A=356-635.
4XG8 X-ray 2.4Å A/C=356-635.
4XG9 X-ray 2.9Å A/B=356-635.
4YJO X-ray 1.6Å A=355-635.
4YJP X-ray 1.8Å A=355-635.
4YJQ X-ray 1.3Å A=355-635.
4YJR X-ray 1.3Å A=355-635.
4YJS X-ray 2.2Å A=355-635.
4YJT X-ray 1.5Å A=355-635.
4YJU X-ray 1.6Å A=355-635.
4YJV X-ray 1.6Å A=355-635.
5C26 X-ray 1.9Å A=343-635.
5C27 X-ray 2.1Å A=343-635.
5CXH X-ray 1.9Å A=356-635.
5CXZ X-ray 1.7Å A=356-635.
5CY3 X-ray 1.7Å A=356-635.
5GHV X-ray 2.8Å A/B=356-635.
5LMA X-ray 1.4Å A=360-635.
5LMB X-ray 1.9Å A/B=360-635.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Nef recruits 18005690
Pr55(Gag) interacts with 24447338

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04072 Phospholipase D signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04611 Platelet activation - Homo sapiens (human)
hsa04650 Natural killer cell mediated cytotoxicity - Homo sapiens (human)
hsa04662 B cell receptor signaling pathway - Homo sapiens (human)
hsa04664 Fc epsilon RI signaling pathway - Homo sapiens (human)
hsa04666 Fc gamma R-mediated phagocytosis - Homo sapiens (human)
hsa05152 Tuberculosis - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)