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Protein

Tyrosine-protein kinase Lyn

Gene

Lyn

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. 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, PTK2B/PYK2, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. 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 (By similarity). Phosphorylates LPXN on 'Tyr-72' (By similarity). Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation.By similarity

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation1 Publication

Enzyme regulationi

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/CD45.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei275ATPPROSITE-ProRule annotation1
Active sitei367Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi253 – 261ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • enzyme binding Source: RGD
  • ephrin receptor binding Source: RGD
  • gamma-tubulin binding Source: RGD
  • glycosphingolipid binding Source: RGD
  • integrin binding Source: RGD
  • ion channel binding Source: RGD
  • kinase activity Source: RGD
  • non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  • phosphoprotein binding Source: RGD
  • phosphorylation-dependent protein binding Source: RGD
  • platelet-derived growth factor receptor binding Source: RGD
  • protein kinase activity Source: RGD
  • protein tyrosine kinase activity Source: RGD
  • receptor binding Source: RGD
  • SH3 domain binding Source: RGD
  • ubiquitin protein ligase binding Source: RGD

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
Biological processAdaptive immunity, Immunity, Inflammatory response, Innate immunity
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 5301
ReactomeiR-RNO-114604 GPVI-mediated activation cascade
R-RNO-1433557 Signaling by SCF-KIT
R-RNO-1433559 Regulation of KIT signaling
R-RNO-202733 Cell surface interactions at the vascular wall
R-RNO-2029481 FCGR activation
R-RNO-2454202 Fc epsilon receptor (FCERI) signaling
R-RNO-2730905 Role of LAT2/NTAL/LAB on calcium mobilization
R-RNO-2871796 FCERI mediated MAPK activation
R-RNO-2871809 FCERI mediated Ca+2 mobilization
R-RNO-2871837 FCERI mediated NF-kB activation
R-RNO-389356 CD28 co-stimulation
R-RNO-389513 CTLA4 inhibitory signaling
R-RNO-3928662 EPHB-mediated forward signaling
R-RNO-3928663 EPHA-mediated growth cone collapse
R-RNO-3928665 EPH-ephrin mediated repulsion of cells
R-RNO-5621575 CD209 (DC-SIGN) signaling
R-RNO-5690714 CD22 mediated BCR regulation
R-RNO-69231 Cyclin D associated events in G1
R-RNO-75892 Platelet Adhesion to exposed collagen
R-RNO-912631 Regulation of signaling by CBL
R-RNO-982772 Growth hormone receptor signaling

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase Lyn (EC:2.7.10.2)
Alternative name(s):
V-yes-1 Yamaguchi sarcoma viral related oncogene homolog
p53Lyn
p56Lyn
Gene namesi
Name:Lyn
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 5

Organism-specific databases

RGDi621017 Lyn

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Golgi apparatus, Membrane, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

Chemistry databases

ChEMBLiCHEMBL4363

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000881312 – 512Tyrosine-protein kinase LynAdd BLAST511

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Lipidationi3S-palmitoyl cysteineBy similarity1
Modified residuei193PhosphotyrosineBy similarity1
Modified residuei228PhosphoserineBy similarity1
Modified residuei306PhosphotyrosineBy similarity1
Modified residuei316PhosphotyrosineCombined sources1
Modified residuei397Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei460PhosphotyrosineBy similarity1
Modified residuei473PhosphotyrosineBy similarity1
Modified residuei508Phosphotyrosine; by autocatalysis, CSK and MATKCombined sources1 Publication1

Post-translational modificationi

Ubiquitinated. Ubiquitination is SH3-dependent (By similarity).By similarity
Phosphorylated on tyrosine residues in response to KIT signaling (By similarity). Autophosphorylated. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylation at Tyr-508 inhibits kinase activity. Phosphorylated at Tyr-508 by CSK. Dephosphorylated by PTPRC/CD45. Becomes rapidly phosphorylated upon activation of the B-cell receptor and the immunoglobulin receptor FCGR1A (By similarity).By similarity

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ07014
PRIDEiQ07014

PTM databases

iPTMnetiQ07014
PhosphoSitePlusiQ07014

Expressioni

Tissue specificityi

Detected in spleen (at protein level). Expressed predominantly in B-lymphoid and myeloid cells.1 Publication

Gene expression databases

BgeeiENSRNOG00000008180
GenevisibleiQ07014 RN

Interactioni

Subunit structurei

Interacts with TEC. Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with LIME1 and with CD79A upon activation of the B-cell antigen receptor. Interacts with the B-cell receptor complex. Interacts with phosphorylated THEMIS2. Interacts with EPOR. Interacts with MS4A2/FCER1B. Interaction (via the SH2 and SH3 domains) with MUC1 is stimulated by IL7 and the subsequent phosphorylation increases the binding between MUC1 and CTNNB1/beta-catenin. Interacts with ADAM15. Interacts with NDFIP2 and more weakly with NDFIP1. Interacts with FASLG. Interacts with KIT. Interacts with HCLS1. Interacts with FCGR2B. Interacts with FCGR1A; the interaction may be indirect. Interacts with CD19, CD22, CD79A and CD79B. Interacts (via SH3 domain) with CBLC, PPP1R15A and PDE4A. Interacts with TGFB1I1. Interacts (via SH3 domain) with PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase; this interaction enhances phosphatidylinositol 3-kinase activity. Interacts with CSF2RB, the common subunit of the IL3, IL5 and CSF2 receptors. Interacts with PAG1; identified in a complex with PAG1 and STAT3. Interacts with ABL1. Interacts with PTPN6/SHP-1. Interacts (via SH3 domain) with SCIMP (via proline-rich region). Interacts with LPXN (via LD motif 3) and the interaction is induced upon B-cell antigen receptor (BCR) activation. Interacts (via SH3-domain) with ANKRD54 (via ankyrin repeat region) in an activation-independent status of LYN. Forms a multiprotein complex with ANKRD54 and HCLS1 (By similarity). Interacts (via SH2 and SH3 domains) with UNC119; leading to LYN activation (By similarity). Interacts with CD36. Interacts with LYN (By similarity).By similarity

GO - Molecular functioni

  • enzyme binding Source: RGD
  • ephrin receptor binding Source: RGD
  • gamma-tubulin binding Source: RGD
  • integrin binding Source: RGD
  • ion channel binding Source: RGD
  • phosphoprotein binding Source: RGD
  • phosphorylation-dependent protein binding Source: RGD
  • platelet-derived growth factor receptor binding Source: RGD
  • receptor binding Source: RGD
  • SH3 domain binding Source: RGD
  • ubiquitin protein ligase binding Source: RGD

Protein-protein interaction databases

BioGridi2495127 interactors.
ELMiQ07014
IntActiQ07014 3 interactors.
MINTiQ07014
STRINGi10116.ENSRNOP00000011130

Chemistry databases

BindingDBiQ07014

Structurei

3D structure databases

ProteinModelPortaliQ07014
SMRiQ07014
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini63 – 123SH3PROSITE-ProRule annotationAdd BLAST61
Domaini129 – 226SH2PROSITE-ProRule annotationAdd BLAST98
Domaini247 – 501Protein kinasePROSITE-ProRule annotationAdd BLAST255

Domaini

The protein kinase domain plays an important role in its localization in the cell membrane.By similarity

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118938
HOGENOMiHOG000233858
HOVERGENiHBG008761
InParanoidiQ07014
KOiK05854
OMAiWMAYYNN
OrthoDBiEOG091G0D46
PhylomeDBiQ07014
TreeFamiTF351634

Family and domain databases

CDDicd10364 SH2_Src_Lyn, 1 hit
cd12004 SH3_Lyn, 1 hit
Gene3Di3.30.505.101 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR035852 Lyn_SH2
IPR035748 Lyn_SH3
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit
PS50001 SH2, 1 hit
PS50002 SH3, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform LYN A (identifier: Q07014-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGCIKSKRKD NLNDDGVDMK TQPVRNTDRT IYVRDPTSNK QQRPVPESQL
60 70 80 90 100
LPGQRFQAKD PEEQGDIVVA LYPYDGIHPD DLSFKKGEKM KVLEEHGEWW
110 120 130 140 150
KAKSLSSKRE GFIPSNYVAK VNTLETEEWF FKDITRKDAE RQLLAPGNSA
160 170 180 190 200
GAFLIRESET LKGSFSLSVR DYDPMHGDVI KHYKIRSLDN GGYYISPRIT
210 220 230 240 250
FPCISDMIKH YQKQSDGLCR RLEKACISPK PQKPWDKDAW EIPRESIKLV
260 270 280 290 300
KKLGAGQFGE VWMGYYNNST KVAVKTLKPG TMSAQAFLEE ANLMKTLQHD
310 320 330 340 350
KLVRLYAVVT KEEPIYIITE FMAKGSLLDF LKSDEGSKVL LPKLIDFSAQ
360 370 380 390 400
IAEGMAYIER KNYIHRDLRA ANVLVSESLM CKIADFGLAR VIEDNEYTAR
410 420 430 440 450
EGAKFPIKWT APEAINFGCF TIKSDVWSFG ILLYEIVTYG KIPYPGRTNA
460 470 480 490 500
DVMTALSQGY RMPRMENCPD ELYDIMKMCW KESAEERPTF DYLQSVLDDF
510
YTATEGQYQQ QP
Length:512
Mass (Da):58,660
Last modified:January 23, 2007 - v3
Checksum:iE03615E229CD43F1
GO
Isoform LYN B (identifier: Q07014-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     25-45: Missing.

Show »
Length:491
Mass (Da):56,133
Checksum:i6FFFB1609E015180
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti231P → L in AAA20944 (PubMed:8125304).Curated1
Sequence conflicti231P → L in AAA20945 (PubMed:8125304).Curated1
Sequence conflicti308V → A in AAA20944 (PubMed:8125304).Curated1
Sequence conflicti308V → A in AAA20945 (PubMed:8125304).Curated1
Sequence conflicti419C → Y in AAA20944 (PubMed:8125304).Curated1
Sequence conflicti419C → Y in AAA20945 (PubMed:8125304).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00500425 – 45Missing in isoform LYN B. CuratedAdd BLAST21

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L14951 mRNA Translation: AAA41549.1
L14782 mRNA Translation: AAA20944.1
L14823 mRNA Translation: AAA20945.1
AF000300 mRNA Translation: AAB71344.1
AF000301 mRNA Translation: AAB71345.1
AF000302 mRNA Translation: AAB71346.1
PIRiI56160
PT0198
RefSeqiNP_001104568.1, NM_001111098.1 [Q07014-2]
NP_110484.1, NM_030857.2 [Q07014-1]
XP_006237896.1, XM_006237834.3 [Q07014-1]
UniGeneiRn.4338

Genome annotation databases

EnsembliENSRNOT00000011130; ENSRNOP00000011130; ENSRNOG00000008180 [Q07014-1]
GeneIDi81515
KEGGirno:81515
UCSCiRGD:621017 rat [Q07014-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiLYN_RAT
AccessioniPrimary (citable) accession number: Q07014
Secondary accession number(s): Q63320
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: January 23, 2007
Last modified: April 25, 2018
This is version 178 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome