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Q5PXS1

- LCK_AOTNA

UniProt

Q5PXS1 - LCK_AOTNA

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Protein
Tyrosine-protein kinase Lck
Gene
LCK
Organism
Aotus nancymaae (Ma's night monkey)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

Functioni

Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP By similarity.

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Enzyme regulationi

The relative activities of the inhibitory tyrosine-protein kinase CSK and the activating tyrosine-protein phosphatase PTPRC/CD45 determine the level of LCK activity. These interactions allow rapid and efficient activation of LCK in response to TCR stimulation By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei273 – 2731ATP By similarity
Active sitei364 – 3641Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi251 – 2599ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. SH2 domain binding Source: UniProtKB
  3. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
  4. protein serine/threonine phosphatase activity Source: UniProtKB
  5. protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

  1. T cell differentiation Source: UniProtKB
  2. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  3. cellular zinc ion homeostasis Source: UniProtKB
  4. dephosphorylation Source: GOC
  5. peptidyl-tyrosine phosphorylation Source: GOC
  6. positive regulation of T cell activation Source: UniProtKB
  7. positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  8. response to drug Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase Lck (EC:2.7.10.2)
Alternative name(s):
Lymphocyte cell-specific protein-tyrosine kinase
Proto-oncogene Lck
p56-LCK
Gene namesi
Name:LCK
OrganismiAotus nancymaae (Ma's night monkey)
Taxonomic identifieri37293 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniPlatyrrhiniAotidaeAotus

Subcellular locationi

Cytoplasm By similarity. Cell membrane; Lipid-anchor; Cytoplasmic side By similarity
Note: Present in lipid rafts in an inactive form By similarity.

GO - Cellular componenti

  1. membrane raft Source: UniProtKB
  2. pericentriolar material Source: UniProtKB
  3. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 509508Tyrosine-protein kinase Lck
PRO_0000088123Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine By similarity
Lipidationi3 – 31S-palmitoyl cysteine By similarity
Lipidationi5 – 51S-palmitoyl cysteine By similarity
Modified residuei102 – 1021Phosphoserine By similarity
Modified residuei159 – 1591Phosphothreonine By similarity
Modified residuei162 – 1621Phosphoserine By similarity
Modified residuei194 – 1941Phosphoserine By similarity
Modified residuei394 – 3941Phosphotyrosine; by autocatalysis By similarity
Modified residuei505 – 5051Phosphotyrosine; by CSK By similarity

Post-translational modificationi

Autophosphorylated on Tyr-394, increasing enzymatic activity, this site is dephosphorylated by PTN22. Phosphorylated on Tyr-505 by CSK, decreasing activity. Dephosphorylated by PTPRC/CD45. Dephosphorylation at Tyr-394 by PTPN2 negatively regulates T-cells differentiation By similarity.
Myristoylation is required prior to palmitoylation By similarity.
Palmitoylation regulates subcellular location By similarity.

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein

Interactioni

Subunit structurei

Binds to the cytoplasmic domain of cell surface receptors, such as AXL, CD2, CD4, CD5, CD8, CD44, CD45 and CD122. Also binds to effector molecules, such as PI4K, VAV1, RASA1, FYB and to other protein kinases including CDK1, RAF1, ZAP70 and SYK. Binds to phosphatidylinositol 3'-kinase (PI3K) from T-lymphocytes through its SH3 domain and to the tyrosine phosphorylated form of KHDRBS1/p70 through its SH2 domain. Interacts with SQSTM1. Interacts with phosphorylated LIME1. LIME1. Interacts with CBLB and PTPRH. Interacts with RUNX3. Forms a signaling complex with EPHA1, PTK2B AND PI3-KINASE; upon activation by EFNA1 which may regulate T-lymphocytes migration. Associates with ZAP70 and RHOH; these interactions allow LCK-mediated RHOH and CD3 subunit phosphorylation in the presence of functional ZAP70 By similarity.

Structurei

3D structure databases

ProteinModelPortaliQ5PXS1.
SMRiQ5PXS1. Positions 7-35, 65-509.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini61 – 12161SH3
Add
BLAST
Domaini127 – 22498SH2
Add
BLAST
Domaini245 – 498254Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 7271Interactions with CD4 and CD8 By similarity
Add
BLAST
Regioni154 – 24289Interaction with PTPRH By similarity
Add
BLAST

Domaini

The SH2 domain mediates interaction with SQSTM1. Interaction is regulated by Ser-59 phosphorylation By similarity.

Sequence similaritiesi

Contains 1 SH2 domain.
Contains 1 SH3 domain.

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

HOVERGENiHBG008761.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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]

Sequencei

Sequence statusi: Complete.

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

Q5PXS1-1 [UniParc]FASTAAdd to Basket

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MGCGCSSHPE DDWMENIDVC ENCHYPIVPL DGKATLLFRN GSEVRDPLVR    50
YEGSNPPASP LQDNLVIALH SYKPSHDGDL GFEKGEQLRI LEQNGEWWKA 100
QSLTTGQEGF IPFNFVAKAN SLEPEPWFFK NLSRKDAERQ LLAPGNTHGS 150
FLIRESESTA GSFSLSVRDF DQNQGEVVKH YKIRNLDNGG FYISPRITFP 200
GLHELVRHYT NASDGLCTRL SRPCQTQKPQ KPWWEDEWEV PRETLKLVER 250
LGAGQFGEVW MGYYNDHTKV AVKSLKQGSM SPDAFLAEAN LMKQLQHQRL 300
VRLYAVVTQE PIYIITEYME NGSLVDFLKT PSGIKLTINK LLDMAAQIAE 350
GMAFIEERNY IHRDLRAANI LVSDTLSCKI ADFGLARLIE DNEYTAREGA 400
KFPIKWTAPE AINYGTFTIK SDVWSFGILL TEIVTHGRIP YPGMTNPEVI 450
QNLERGYRMV RPDNCPEELY HLMMLCWKER PEDRPTFDYL RSVLEDFFTA 500
TEGQYQPQP 509
Length:509
Mass (Da):58,172
Last modified:January 23, 2007 - v4
Checksum:i8B61951BDD070EA4
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY821852 mRNA. Translation: AAV70114.2.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY821852 mRNA. Translation: AAV70114.2 .

3D structure databases

ProteinModelPortali Q5PXS1.
SMRi Q5PXS1. Positions 7-35, 65-509.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Phylogenomic databases

HOVERGENi HBG008761.

Family and domain databases

Gene3Di 3.30.505.10. 1 hit.
InterProi IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view ]
Pfami PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view ]
PRINTSi PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTi SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi 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 ]
ProtoNeti Search...

Publicationsi

  1. Perez-Quintero L.A., Vernot J.P.
    Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiLCK_AOTNA
AccessioniPrimary (citable) accession number: Q5PXS1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 8, 2005
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 75 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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