Reviewed, UniProtKB/Swiss-Prot P07948 (LYN_HUMAN)

Names and origin

Protein names

Recommended name:
    Tyrosine-protein kinase Lyn
    EC=2.7.10.2

Gene names

Name:

LYN

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	512 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with phosphorylated LIME1 and with CD79A upon BCR activation. Interacts with Epstein-Barr virus LMP2A. Interacts with TGFB1I1. 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 PPP1R15A via the SH3 domain. Ref.6 Ref.7 Ref.8 Ref.11
Tissue specificity	Expressed in primary neuroblastoma tumors.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. Contains 1 protein kinase domain. Contains 1 SH2 domain. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Host-virus interaction
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Proto-oncogene
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Lipoprotein Myristate Palmitate Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	erythrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of tyrosine phosphorylation of STAT protein Inferred from sequence or structural similarity. Source: UniProtKB protein amino acid phosphorylation Ref.1 Traceable author statement. Source: ProtInc response to hormone stimulus Inferred from sequence or structural similarity. Source: UniProtKB signal transduction Traceable author statement. Source: ProtInc
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA membrane raft Inferred from direct assay. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction. Source: UniProtKB receptor signaling protein tyrosine kinase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	O92972	2	EBI-79452,EBI-710506	From a different organism.
	P26660	1	EBI-79452,EBI-706322	From a different organism.
	P27958	5	EBI-79452,EBI-706378	From a different organism.
	Q9WMX2	2	EBI-79452,EBI-710918	From a different organism.
Arap3	Q8R5G7	2	EBI-79452,EBI-621463	From a different organism.
Asap1	Q9QWY8-1	1	EBI-79452,EBI-698517	From a different organism.
Asap1	Q9QWY8-2	1	EBI-79452,EBI-698524	From a different organism.
CD22	P20273	1	EBI-79452,EBI-78277
CDK4	P11802	1	EBI-79452,EBI-295644
CDKN1B	P46527	2	EBI-79452,EBI-519280
CSNK2B	P67870	1	EBI-79452,EBI-348169
GP6	Q9HCN6	2	EBI-79452,EBI-515278
KHDRBS1	Q07666	1	EBI-79452,EBI-1364
Sphk1	Q8CI15	1	EBI-79452,EBI-985291	From a different organism.
SPHK2	Q9NRA0	1	EBI-79452,EBI-985324
Sphk2	Q9JIA7	1	EBI-79452,EBI-985434	From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform LYN A (identifier: P07948-1)

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 LYN B (identifier: P07948-2)

The sequence of this isoform differs from the canonical sequence as follows:
     23-43: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 512

511

Tyrosine-protein kinase Lyn

PRO_0000088129

Regions

Domain

63 – 123

61

SH3

Domain

129 – 226

98

SH2

Domain

247 – 501

255

Protein kinase

Nucleotide binding

253 – 261

9

ATP By similarity

Sites

Active site

367

1

Proton acceptor By similarity

Binding site

275

1

ATP By similarity

Amino acid modifications

Modified residue

11

1

Phosphoserine Ref.10 Ref.15 Ref.16

Modified residue

13

1

Phosphoserine Ref.15 Ref.16 Ref.13 Ref.14

Modified residue

32

1

Phosphotyrosine Ref.15

Modified residue

193

1

Phosphotyrosine Ref.12

Modified residue

194

1

Phosphotyrosine Ref.15 Ref.12

Modified residue

228

1

Phosphoserine Ref.15

Modified residue

306

1

Phosphotyrosine Ref.12

Modified residue

397

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

473

1

Phosphotyrosine Ref.15 Ref.12

Modified residue

508

1

Phosphotyrosine Ref.10 Ref.15 Ref.12 Ref.9

Lipidation

2

1

N-myristoyl glycine By similarity

Lipidation

3

1

S-palmitoyl cysteine By similarity

Natural variations

Alternative sequence

23 – 43

21

Missing in isoform LYN B.

VSP_005002

Natural variant

385

1

D → Y in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.17

VAR_041737

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

512

Helix Strand Turn

Details...

Beta strand

66 – 72

7

Beta strand

78 – 80

3

Beta strand

89 – 95

7

Beta strand

97 – 104

8

Turn

105 – 107

3

Beta strand

110 – 114

5

Turn

115 – 117

3

Beta strand

118 – 120

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform LYN A [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 408D3D461204E378	FASTA	512	58,574
	10 20 30 40 50 60 MGCIKSKGKD SLSDDGVDLK TQPVRNTERT IYVRDPTSNK QQRPVPESQL LPGQRFQTKD 70 80 90 100 110 120 PEEQGDIVVA LYPYDGIHPD DLSFKKGEKM KVLEEHGEWW KAKSLLTKKE GFIPSNYVAK 130 140 150 160 170 180 LNTLETEEWF FKDITRKDAE RQLLAPGNSA GAFLIRESET LKGSFSLSVR DFDPVHGDVI 190 200 210 220 230 240 KHYKIRSLDN GGYYISPRIT FPCISDMIKH YQKQADGLCR RLEKACISPK PQKPWDKDAW 250 260 270 280 290 300 EIPRESIKLV KRLGAGQFGE VWMGYYNNST KVAVKTLKPG TMSVQAFLEE ANLMKTLQHD 310 320 330 340 350 360 KLVRLYAVVT REEPIYIITE YMAKGSLLDF LKSDEGGKVL LPKLIDFSAQ IAEGMAYIER 370 380 390 400 410 420 KNYIHRDLRA ANVLVSESLM CKIADFGLAR VIEDNEYTAR EGAKFPIKWT APEAINFGCF 430 440 450 460 470 480 TIKSDVWSFG ILLYEIVTYG KIPYPGRTNA DVMTALSQGY RMPRVENCPD ELYDIMKMCW 490 500 510 KEKAEERPTF DYLQSVLDDF YTATEGQYQQ QP
	Isoform LYN B. Checksum: D74E4074D4B0C92A	FASTA	491	56,033
	10 20 30 40 50 60 MGCIKSKGKD SLSDDGVDLK TQPVPESQLL PGQRFQTKDP EEQGDIVVAL YPYDGIHPDD 70 80 90 100 110 120 LSFKKGEKMK VLEEHGEWWK AKSLLTKKEG FIPSNYVAKL NTLETEEWFF KDITRKDAER 130 140 150 160 170 180 QLLAPGNSAG AFLIRESETL KGSFSLSVRD FDPVHGDVIK HYKIRSLDNG GYYISPRITF 190 200 210 220 230 240 PCISDMIKHY QKQADGLCRR LEKACISPKP QKPWDKDAWE IPRESIKLVK RLGAGQFGEV 250 260 270 280 290 300 WMGYYNNSTK VAVKTLKPGT MSVQAFLEEA NLMKTLQHDK LVRLYAVVTR EEPIYIITEY 310 320 330 340 350 360 MAKGSLLDFL KSDEGGKVLL PKLIDFSAQI AEGMAYIERK NYIHRDLRAA NVLVSESLMC 370 380 390 400 410 420 KIADFGLARV IEDNEYTARE GAKFPIKWTA PEAINFGCFT IKSDVWSFGI LLYEIVTYGK 430 440 450 460 470 480 IPYPGRTNAD VMTALSQGYR MPRVENCPDE LYDIMKMCWK EKAEERPTFD YLQSVLDDFY 490 TATEGQYQQQ P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The yes-related cellular gene lyn encodes a possible tyrosine kinase similar to p56lck." Yamanashi Y., Fukushige S., Semba K., Sukegawa J., Miyajima N., Matsubara K., Yamamoto T., Toyoshima K. Mol. Cell. Biol. 7:237-243(1987) [PubMed: 3561390] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The cDNAs encoding two forms of the LYN protein tyrosine kinase are expressed in rat mast cells and human myeloid cells." Rider L.G., Raben N., Miller L., Jelsema C. Gene 138:219-222(1994) [PubMed: 8125304] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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] (ISOFORM LYN A).
[4]	"Putative tyrosine kinases expressed in K-562 human leukemia cells." Partanen J., Maekelae T.P., Alitalo R., Lehvaeslaiho H., Alitalo K. Proc. Natl. Acad. Sci. U.S.A. 87:8913-8917(1990) [PubMed: 2247464] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 369-424.
[5]	"Expression of the B cell-associated tyrosine kinase gene Lyn in primary neuroblastoma tumours and its modulation during the differentiation of neuroblastoma cell lines." Bielke W., Ziemiecki A., Kappos L., Miescher G.C. Biochem. Biophys. Res. Commun. 186:1403-1409(1992) [PubMed: 1510669] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 369-424.
[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]	"Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis." Grishin A.V., Azhipa O., Semenov I., Corey S.J. Proc. Natl. Acad. Sci. U.S.A. 98:10172-10177(2001) [PubMed: 11517336] [Abstract] Cited for: INTERACTION WITH PPP1R15A.
[8]	"DF3/MUC1 signaling in multiple myeloma cells is regulated by interleukin-7." Li Y., Chen W., Ren J., Yu W.H., Li Q., Yoshida K., Kufe D. Cancer Biol. Ther. 2:187-193(2003) [PubMed: 12750561] [Abstract] Cited for: INTERACTION WITH MUC1.
[9]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-508, MASS SPECTROMETRY.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11 AND TYR-508, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Paxillin family members function as Csk-binding proteins that regulate Lyn activity in human and murine platelets." Rathore V.B., Okada M., Newman P.J., Newman D.K. Biochem. J. 403:275-281(2007) [PubMed: 17233630] [Abstract] Cited for: INTERACTION WITH TGFB1I1.
[12]	"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-193; TYR-194; TYR-306; TYR-397; TYR-473 AND TYR-508, MASS SPECTROMETRY.
[13]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, MASS SPECTROMETRY.
[14]	"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-13 AND TYR-397, MASS SPECTROMETRY. Tissue: Platelet.
[15]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11; SER-13; TYR-32; TYR-194; SER-228; TYR-397; TYR-473 AND TYR-508, MASS SPECTROMETRY.
[16]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11 AND SER-13, MASS SPECTROMETRY.
[17]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] TYR-385.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M16038 mRNA. Translation: AAA59540.1.
M79321 mRNA. Translation: AAB50019.1.
BC075001 mRNA. Translation: AAH75001.1.
BC075002 mRNA. Translation: AAH75002.1.
BC126456 mRNA. Translation: AAI26457.1.
BC126458 mRNA. Translation: AAI26459.1.

IPI

IPI00298625.
IPI00432416.

PIR

TVHULY. A26719.

RefSeq

NP_002341.1.

UniGene

Hs.699154

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1W1F	NMR	-	A	61-122	[»]
1WA7	NMR	-	A	61-123	[»]

SMR

P07948. Positions 67-512.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:1056N.

IntAct

P07948. 26 interactions.

PTM databases

PhosphoSite

P07948.

2-D gel databases

REPRODUCTION-2DPAGE

P07948.

Proteomic databases

PRIDE

P07948.

Genome annotation databases

Ensembl

ENSG00000147507. Homo sapiens. [Contig view]

GeneID

4067.

Organism-specific databases

GeneCards

GC08P056954.

H-InvDB

HIX0025560.

HGNC

HGNC:6735. LYN.

HPA

CAB004492.
HPA001231.

MIM

165120. gene.

PharmGKB

PA30498.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P07948.

Enzyme and pathway databases

BRENDA

2.7.10.2. 247.

Pathway_Interaction_DB

alphasynuclein_pathway. Alpha-synuclein signaling.
amb2_neutrophils_pathway. amb2 Integrin signaling.
bcr_5pathway. BCR signaling pathway.
pi3kcipathway. Class I PI3K signaling events.
epha_fwdpathway. EPHA forward signaling.
ephrinbrevpathway. Ephrin B reverse signaling.
epopathway. EPO signaling pathway.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
glypican_1pathway. Glypican 1 network.
lysophospholipid_pathway. LPA receptor mediated events.
pdgfrbpathway. PDGFR-beta signaling pathway.
p38alphabetapathway. Regulation of p38-alpha and p38-beta.
ptp1bpathway. Signaling events mediated by PTP1B.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
txa2pathway. Thromboxane A2 receptor signaling.

Reactome

REACT_604. Hemostasis.
REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpress

P07948.

Bgee

P07948.

CleanEx

HS_LYN.

Family and domain databases

InterPro

IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
[Graphical view]

Gene3D

G3DSA:3.30.505.10. SH2. 1 hit.

Pfam

PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.
PR00109. TYRKINASE.

ProDom

PD000001. Prot_kinase. 1 hit.
PD000093. SH2. 1 hit.
PD000066. SH3. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

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.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

15944.

PMAP-CutDB

P07948.

SOURCE

Search...

Entry information

Entry name

LYN_HUMAN

Accession

Primary (citable) accession number: P07948
Secondary accession number(s): A0AVQ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 125 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)