LYN
entrez
4067
canonical
uniprot
P07948
canonical
ensembl
ENSG00000254087
resolver
ensp
ENSP00000428424
resolver
ensp
ENSP00000428924
resolver
genesymbol
LYN
resolver
genesymbol_syn
JTK8
resolver
hgnc
HGNC:6735
resolver
uniprot
A0AVQ5
resolver
uniprot
A8K379
resolver
uniprot
B4DQ79
resolver
uniprot
Q6NUK7
resolver
uniprot_entry
A8K379_HUMAN
resolver
uniprot_entry
B4DQ79_HUMAN
resolver
uniprot_entry
LYN_HUMAN
resolver
uniprot_entry
Q6NUK7_HUMAN
resolver
uniprot_sec
A0AVQ5
resolver
activity_regulation
ACTIVITY REGULATION: Subject to autoinhibition, mediated by intramolecular interactions between the SH2 domain and the C-terminal phosphotyrosine. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylated by CSK at Tyr-508; phosphorylation at Tyr-508 inhibits kinase activity. Kinase activity is modulated by dephosphorylation by PTPRC/CD45. Inhibited by Dasatinib, PP2, and SU6656. {ECO:0000269|PubMed:16920712, ECO:0000269|PubMed:7935444}.
uniprot
proteins
amino_acid_sequence
MGCIKSKGKDSLSDDGVDLKTQPVRNTERTIYVRDPTSNKQQRPVPESQLLPGQRFQTKDPEEQGDIVVALYPYDGIHPDDLSFKKGEKMKVLEEHGEWWKAKSLLTKKEGFIPSNYVAKLNTLETEEWFFKDITRKDAERQLLAPGNSAGAFLIRESETLKGSFSLSVRDFDPVHGDVIKHYKIRSLDNGGYYISPRITFPCISDMIKHYQKQADGLCRRLEKACISPKPQKPWDKDAWEIPRESIKLVKRLGAGQFGEVWMGYYNNSTKVAVKTLKPGTMSVQAFLEEANLMKTLQHDKLVRLYAVVTREEPIYIITEYMAKGSLLDFLKSDEGGKVLLPKLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGCFTIKSDVWSFGILLYEIVTYGKIPYPGRTNADVMTALSQGYRMPRVENCPDELYDIMKMCWKEKAEERPTFDYLQSVLDDFYTATEGQYQQQP
uniprot
proteins
disease_involvement
DISEASE: Autoinflammatory disease, systemic, with vasculitis (SAIDV) [MIM:620376]: An autosomal dominant disorder characterized by systemic autoinflammation manifesting in the first hours of life with diffuse purpuric skin lesions, fever, hepatosplenomegaly, and increased C-reactive protein. Additional clinical features include periorbital edema, conjunctivitis, urticaria, atopic dermatitis, abdominal pain, and arthralgia. Laboratory studies may show leukocytosis, thrombocytopenia, and autoantibodies. {ECO:0000269|PubMed:16920712, ECO:0000269|PubMed:36122175, ECO:0000269|PubMed:36932076, ECO:0000269|Ref.67}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=Constitutively phosphorylated and activated in cells from a number of chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) patients. Mediates phosphorylation of the BCR-ABL fusion protein. Abnormally elevated expression levels or activation of LYN signaling may play a role in survival and proliferation of some types of cancer cells.
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
function
FUNCTION: Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Involved in the regulation of endothelial activation, neutrophil adhesion and transendothelial migration (PubMed:36932076). Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL fusion protein. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. Phosphorylates SCIMP on 'Tyr-107'; this enhances binding of SCIMP to TLR4, promoting the phosphorylation of TLR4, and a selective cytokine response to lipopolysaccharide in macrophages (By similarity). Phosphorylates CLNK (By similarity). Phosphorylates BCAR1/CAS and NEDD9/HEF1 (PubMed:9020138). {ECO:0000250|UniProtKB:P25911, ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:10748115, ECO:0000269|PubMed:10891478, ECO:0000269|PubMed:11435302, ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:11825908, ECO:0000269|PubMed:14726379, ECO:0000269|PubMed:15795233, ECO:0000269|PubMed:16467205, ECO:0000269|PubMed:17640867, ECO:0000269|PubMed:17977829, ECO:0000269|PubMed:18056483, ECO:0000269|PubMed:18070987, ECO:0000269|PubMed:18235045, ECO:0000269|PubMed:18577747, ECO:0000269|PubMed:18802065, ECO:0000269|PubMed:19290919, ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:36122175, ECO:0000269|PubMed:36932076, ECO:0000269|PubMed:7687428, ECO:0000269|PubMed:9020138}.
uniprot
proteins
mass_dalton
58574
uniprot
proteins
mutagenesis
MUTAGEN 2; /note="G->A: Loss of localization to the cell membrane; when associated with A-3."; /evidence="ECO:0000269|PubMed:18817770"; MUTAGEN 3; /note="C->A: Loss of localization to the cell membrane; when associated with A-2."; /evidence="ECO:0000269|PubMed:18817770"; MUTAGEN 275; /note="K->A: Loss of activity and no effect on localization to the cell membrane. Abundant localization in the nucleus; when associated with A-2 and A-3."; /evidence="ECO:0000269|PubMed:11435302, ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:15173188, ECO:0000269|PubMed:18817770"; MUTAGEN 275; /note="K->L,R: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:11435302, ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:15173188, ECO:0000269|PubMed:18817770"; MUTAGEN 346; /note="D->A: Impedes the trafficking from the Golgi apparatus toward the cell membrane; when associated with A-353; A-498 and A-499."; /evidence="ECO:0000269|PubMed:15173188"; MUTAGEN 353; /note="E->A: Impedes the trafficking from the Golgi apparatus toward the cell membrane; when associated with A-346; A-498 and A-499."; /evidence="ECO:0000269|PubMed:15173188"; MUTAGEN 397; /note="Y->F: Strongly reduced kinase activity."; /evidence="ECO:0000269|PubMed:16920712"; MUTAGEN 498; /note="D->A: Impedes the trafficking from the Golgi apparatus toward the cell membrane; when associated with A-346; A-353 and A-499."; /evidence="ECO:0000269|PubMed:15173188"; MUTAGEN 499; /note="D->A: Impedes the trafficking from the Golgi apparatus toward the cell membrane; when associated with A-346; A-353 and A-498."; /evidence="ECO:0000269|PubMed:15173188
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by CBL, leading to its degradation. Ubiquitination is SH3-dependent. {ECO:0000269|PubMed:16920712, ECO:0000269|PubMed:20534535}.; PTM: Autophosphorylated (PubMed:18056483, PubMed:18070987, PubMed:7935444, PubMed:9171348, PubMed:9341198). Phosphorylated on tyrosine residues in response to KIT signaling (PubMed:9341198). Phosphorylation at Tyr-397 is required for optimal activity (PubMed:16920712). Phosphorylation at Tyr-508 inhibits kinase activity (PubMed:9171348). Phosphorylated at Tyr-508 by CSK (PubMed:7935444). Dephosphorylated by PTPRC/CD45 (By similarity). Becomes rapidly phosphorylated upon activation of the B-cell receptor and the immunoglobulin receptor FCGR1A (PubMed:8064233). Phosphorylated in response to ITGB1 in B-cells (PubMed:9020138). {ECO:0000250|UniProtKB:P25911, ECO:0000269|PubMed:16920712, ECO:0000269|PubMed:18056483, ECO:0000269|PubMed:18070987, ECO:0000269|PubMed:7935444, ECO:0000269|PubMed:8064233, ECO:0000269|PubMed:9020138, ECO:0000269|PubMed:9171348, ECO:0000269|PubMed:9341198}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
SRC subfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10362357
uniprot
proteins
pubmed
10574931
uniprot
proteins
pubmed
10748115
uniprot
proteins
pubmed
10891478
uniprot
proteins
pubmed
11306681
uniprot
proteins
pubmed
11435302
uniprot
proteins
pubmed
11517336
uniprot
proteins
pubmed
11825908
uniprot
proteins
pubmed
11955060
uniprot
proteins
pubmed
12496276
uniprot
proteins
pubmed
12750561
uniprot
proteins
pubmed
14726379
uniprot
proteins
pubmed
1510669
uniprot
proteins
pubmed
15173188
uniprot
proteins
pubmed
15220000
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15489917
uniprot
proteins
pubmed
15592455
uniprot
proteins
pubmed
15664155
uniprot
proteins
pubmed
15795233
uniprot
proteins
pubmed
16129412
uniprot
proteins
pubmed
16155203
uniprot
proteins
pubmed
16467205
uniprot
proteins
pubmed
16801133
uniprot
proteins
pubmed
16912036
uniprot
proteins
pubmed
16920712
uniprot
proteins
pubmed
17233630
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17640867
uniprot
proteins
pubmed
17977829
uniprot
proteins
pubmed
18056483
uniprot
proteins
pubmed
18070987
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
18235045
uniprot
proteins
pubmed
18577747
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18772004
uniprot
proteins
pubmed
18802065
uniprot
proteins
pubmed
18817770
uniprot
proteins
pubmed
19290919
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19718658
uniprot
proteins
pubmed
19807924
uniprot
proteins
pubmed
19857964
uniprot
proteins
pubmed
20037584
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20534535
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21930792
uniprot
proteins
pubmed
2247464
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25255805
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
3561390
uniprot
proteins
pubmed
36122175
uniprot
proteins
pubmed
36932076
uniprot
proteins
pubmed
7682714
uniprot
proteins
pubmed
7687428
uniprot
proteins
pubmed
7895172
uniprot
proteins
pubmed
7935444
uniprot
proteins
pubmed
8064233
uniprot
proteins
pubmed
8125304
uniprot
proteins
pubmed
9020138
uniprot
proteins
pubmed
9171348
uniprot
proteins
pubmed
9232445
uniprot
proteins
pubmed
9341198
uniprot
proteins
sequence_length
512
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane. Nucleus. Cytoplasm. Cytoplasm, perinuclear region. Golgi apparatus. Membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}. Note=Accumulates in the nucleus by inhibition of CRM1-mediated nuclear export. Nuclear accumulation is increased by inhibition of its kinase activity. The trafficking from the Golgi apparatus to the plasma membrane occurs in a kinase domain-dependent but kinase activity independent manner and is mediated by exocytic vesicular transport. Detected on plasma membrane lipid rafts.
uniprot
proteins