Protein:LCK |
Protein Summary |
 Gene summary |
| Gene name: LCK | ASpdb.0 ID: 3932 | Gene | Gene symbol | LCK | Gene ID | 3932 |
| Gene name | LCK proto-oncogene, Src family tyrosine kinase |
| Synonyms | IMD22|LSK|YT16|p56lck|pp58lck |
| Cytomap | 1p35.2 |
| Type of gene | protein-coding |
| Description | tyrosine-protein kinase LckT-lymphocyte specific protein tyrosine kinase p56lckleukocyte C-terminal Src kinaselymphocyte cell-specific protein-tyrosine kinasep56(LSTRA) protein-tyrosine kinaseproto-oncogene tyrosine-protein kinase LCKt cell-specific |
| Modification date | 20240411 |
| UniProtAcc | P06239 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | LCK | GO:0000242 | pericentriolar material | 7513706 |
| Gene | LCK | GO:0001772 | immunological synapse | 20007709 |
| Gene | LCK | GO:0004713 | protein tyrosine kinase activity | 214242|8478617 |
| Gene | LCK | GO:0004715 | non-membrane spanning protein tyrosine kinase activity | 8681956|11606584 |
| Gene | LCK | GO:0004722 | protein serine/threonine phosphatase activity | 8506364 |
| Gene | LCK | GO:0005886 | plasma membrane | 12150984 |
| Gene | LCK | GO:0006468 | protein phosphorylation | 214242 |
| Gene | LCK | GO:0006919 | activation of cysteine-type endopeptidase activity involved in apoptotic process | 16116473 |
| Gene | LCK | GO:0009410 | response to xenobiotic stimulus | 16116473 |
| Gene | LCK | GO:0016004 | phospholipase activator activity | 11606584 |
| Gene | LCK | GO:0035556 | intracellular signal transduction | 8681956 |
| Gene | LCK | GO:0038083 | peptidyl-tyrosine autophosphorylation | 8478617 |
| Gene | LCK | GO:0038094 | Fc-gamma receptor signaling pathway | 8478617 |
| Gene | LCK | GO:0045121 | membrane raft | 12150984|12732664 |
| Gene | LCK | GO:0050870 | positive regulation of T cell activation | 8943371 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P06239-1 | P06239-1_6pdj_A.pdb | 6PDJ | X-ray | 1.81 | A | 225 | 500 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P06239 | LCK | P06239-1 | P06239-2 | 509 | 363 | 348 | 363 | Substitution | IAEGMAFIEERNYIHR | VRRLGRGAGQGNRPVT | 348 | 363 |
| P06239 | LCK | P06239-1 | P06239-2 | 509 | 363 | 364 | 509 | Deletion | none | none | 363 | 363 |
| P06239 | LCK | P06239-1 | P06239-3 | 509 | 539 | 321 | 321 | Substitution | N | NDTLLDSQLEEKGLGASPWGNLGQQLLLLPT | 321 | 351 |
| Multiple sequence alignment of our canonical and alternatively spliced LCK |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of LCK |
| UniProt-id | ENSG | ENST | ENSP |
| P06239-1 | ENSG00000182866.18 | ENST00000336890.10 | ENSP00000337825.5 |
| P06239-3 | ENSG00000182866.18 | ENST00000333070.4 | ENSP00000328213.4 |
| UniProt-id | NM ID | NP ID |
| P06239-1 | NM_001042771.2 | NP_001036236.1 |
| P06239-1 | NM_005356.4 | NP_005347.3 |
| Amino acid sequences of our canonical and alternatively spliced LCK |
| accession_id | Protein sequence |
| P06239-1 | MGCGCSSHPEDDWMENIDVCENCHYPIVPLDGKGTLLIRNGSEVRDPLVTYEGSNPPASPLQDNLVIALHSYEPSHDGDLGFEKGEQLRI LEQSGEWWKAQSLTTGQEGFIPFNFVAKANSLEPEPWFFKNLSRKDAERQLLAPGNTHGSFLIRESESTAGSFSLSVRDFDQNQGEVVKH YKIRNLDNGGFYISPRITFPGLHELVRHYTNASDGLCTRLSRPCQTQKPQKPWWEDEWEVPRETLKLVERLGAGQFGEVWMGYYNGHTKV AVKSLKQGSMSPDAFLAEANLMKQLQHQRLVRLYAVVTQEPIYIITEYMENGSLVDFLKTPSGIKLTINKLLDMAAQIAEGMAFIEERNY IHRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVI |
| P06239-2 | MGCGCSSHPEDDWMENIDVCENCHYPIVPLDGKGTLLIRNGSEVRDPLVTYEGSNPPASPLQDNLVIALHSYEPSHDGDLGFEKGEQLRI LEQSGEWWKAQSLTTGQEGFIPFNFVAKANSLEPEPWFFKNLSRKDAERQLLAPGNTHGSFLIRESESTAGSFSLSVRDFDQNQGEVVKH YKIRNLDNGGFYISPRITFPGLHELVRHYTNASDGLCTRLSRPCQTQKPQKPWWEDEWEVPRETLKLVERLGAGQFGEVWMGYYNGHTKV AVKSLKQGSMSPDAFLAEANLMKQLQHQRLVRLYAVVTQEPIYIITEYMENGSLVDFLKTPSGIKLTINKLLDMAAQVRRLGRGAGQGNR |
| P06239-3 | MGCGCSSHPEDDWMENIDVCENCHYPIVPLDGKGTLLIRNGSEVRDPLVTYEGSNPPASPLQDNLVIALHSYEPSHDGDLGFEKGEQLRI LEQSGEWWKAQSLTTGQEGFIPFNFVAKANSLEPEPWFFKNLSRKDAERQLLAPGNTHGSFLIRESESTAGSFSLSVRDFDQNQGEVVKH YKIRNLDNGGFYISPRITFPGLHELVRHYTNASDGLCTRLSRPCQTQKPQKPWWEDEWEVPRETLKLVERLGAGQFGEVWMGYYNGHTKV AVKSLKQGSMSPDAFLAEANLMKQLQHQRLVRLYAVVTQEPIYIITEYMENDTLLDSQLEEKGLGASPWGNLGQQLLLLPTGSLVDFLKT PSGIKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKFPIKWTAPEAINYGTFTIK |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| LCK (go to UniProt):P06239 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P06239 | Domain | 245 | 498 | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Substitution;Start=348;End=363 |
| P06239 | Domain | 245 | 498 | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Deletion;Start=364;End=509 |
| P06239 | Domain | 245 | 498 | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Substitution;Start=321;End=321 |
Gene Isoform Structures and Expression Levels for LCK |
| Gene structures of our canonical and alternative spliced genes of LCK * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
 |
| Expression levels of gene isoforms across TCGA. |
 |
Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P06239-1 |
| 3D view using mol* of P06239-2 |
| 3D view using mol* of P06239-3 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P06239-1 |
 |
| pLDDT distribution across the protein length of P06239-2 |
 |
| pLDDT distribution across the protein length of P06239-3 |
 |
Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P06239-1 |
 |
Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P06239-1 | 1.065 | 159 | 0.969 | 466.48 | 0.428 | 0.796 | 1.031 | 0.166 | 1.376 | 0.12 | 0.606 | 134,135,138,139,142,169,171,174,175,176,177,178,17 9,180,339,340,342,343,346,376,494,495,497,498,499, 502,503,504,505,506 |
| P06239-2 | 1.01 | 148 | 1.051 | 391.363 | 0.627 | 0.671 | 0.882 | 0.556 | 0.896 | 0.621 | 1.329 | 95,96,97,233,234,235,238,251,256,259,271,273,275,2 79,285,288,289,292,293,294,295,296,297,300,301,302 ,303,304,306,314,316,317,318,319,322,323,326 |
| P06239-3 | 1.031 | 275 | 1.052 | 771.407 | 0.548 | 0.735 | 0.965 | 0.868 | 1.008 | 0.861 | 1.35 | 251,252,254,255,256,257,259,271,273,292,301,303,31 4,316,317,318,319,321,348,349,350,351,352,353,356, 357,360,362,393,394,396,398,399,401,404,411,412,41 3,415,416,417,424,425,426,427,430,431,432,433,434, 435,436,437,441,442,443,445,447,469,476,480 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
 |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P06239-1_P06239-1_6pdj_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P06239-1_6pdj_A_P06239-2.pdb |
| 3D view using mol* of P06239-1_6pdj_A_P06239-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P06239-1_P06239-2.pdb |
| 3D view using mol* of P06239-1_P06239-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P06239-1_vs_P06239-2.png |
 < |
| ./stats/secondary_structure/figure/P06239-1_vs_P06239-3.png |
 < |
| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P06239-1_vs_P06239-2.png |
 < |
| ./stats/relative_asa/P06239-1_vs_P06239-3.png |
 < |
Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to LCK |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P06239 | LCK | DB01830 | AP-22408 | experimental | |
| P06239 | LCK | DB01254 | Dasatinib | approved, investigational | inhibitor, multitarget |
| P06239 | LCK | DB03023 | 1-Tert-Butyl-3-(4-Chloro-Phenyl)-1h-Pyrazolo[3,4-D]Pyrimidin-4-Ylamine | experimental | |
| P06239 | LCK | DB07146 | 2,3-DIPHENYL-N-(2-PIPERAZIN-1-YLETHYL)FURO[2,3-B]PYRIDIN-4-AMINE | experimental | |
| P06239 | LCK | DB08901 | Ponatinib | approved, investigational | inhibitor |
| P06239 | LCK | DB09079 | Nintedanib | approved | inhibitor |
| P06239 | LCK | DB04395 | Phosphoaminophosphonic Acid-Adenylate Ester | experimental | |
| P06239 | LCK | DB07297 | 5,6-DIPHENYL-N-(2-PIPERAZIN-1-YLETHYL)FURO[2,3-D]PYRIMIDIN-4-AMINE | experimental | |
| P06239 | LCK | DB08056 | N-(2,6-dimethylphenyl)-5-phenylimidazo[1,5-a]pyrazin-8-amine | experimental | |
| P06239 | LCK | DB08057 | N-(2-chloro-6-methylphenyl)-8-[(3S)-3-methylpiperazin-1-yl]imidazo[1,5-a]quinoxalin-4-amine | experimental | |
| P06239 | LCK | DB12010 | Fostamatinib | approved, investigational | inhibitor |
| P06239 | LCK | DB15035 | Zanubrutinib | approved, investigational | inhibitor |
| P06239 | LCK | DB04003 | {4-[(2S)-2-Acetamido-3-({(1S)-1-[3-carbamoyl-4-(cyclohexylmethoxy)phenyl]ethyl}amino)-3-oxopropyl]-2-phosphonophenoxy}acetic acid | experimental | |
| P06239 | LCK | DB16656 | Zotiraciclib | investigational | inhibitor |
| P06239 | LCK | DB06925 | 3-(2-AMINOQUINAZOLIN-6-YL)-4-METHYL-N-[3-(TRIFLUOROMETHYL)PHENYL]BENZAMIDE | experimental | |
| P06239 | LCK | DB02010 | Staurosporine | experimental | |
| P06239 | LCK | DB08055 | N-(2-chlorophenyl)-5-phenylimidazo[1,5-a]pyrazin-8-amine | experimental |
Related Diseases to LCK |
| Previous studies relating to the alternative splicing of LCK and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| LCK | 8086341 | Pattern of expression of five alternative transcripts of the lck gene in different hematopoietic malignancies: correlation of the level of lck messenger RNA I B with the immature phenotype of the malignancy. | The lck gene encodes a tyrosine protein kinase of the src family which is highly expressed in T-lymphocytes. Two widely separated promoters govern expression of the lck gene. We report in this study that alternative splicing between cryptic donor and acceptor sites in the 5' untranslated region of the transcripts initiated at the type I promoter give rise to three different type I lck mRNAs, I A, I B, and I C. Altogether with the types II A and II B reported previously, the lck transcription is thus characterized by five alternative transcripts. We further used the complementary DNA-polymerase chain reaction assay to describe the pattern of expression of these five lck transcripts in different hematopoietic cell lines and in blood or bone marrow samples from healthy donors and leukemic patients. We report that the transcript II A is by far the major transcript present both in human samples and in T-cell lines. The low lck expression in B-cell lines is characterized by the quite exclusive presence of the transcript I B. We show that hematopoietic diseases characterized by the presence of immature cells [acute myeloid leukemia (AML-0 and AML-1) and T- and B-cell acute lymphoid leukemia] exhibit a marked increase of the transcript I B. No significant difference from the normal pattern is observed in AML according to the differentiation stage (AML-2 to AML-5). A normal pattern of lck expression is restored in AML-0 and AML-1 patients at complete remission. | D007938 | Leukemia |
Clinically important variants in LCK |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
Copyright 2024-PresentThe University of Texas Health Science Center at Houston (UTHealth Houston) Web File Viewing | Emergency Information |