Protein:HCK |
Protein Summary |
 Gene summary |
| Gene name: HCK | ASpdb.0 ID: 3055 | Gene | Gene symbol | HCK | Gene ID | 3055 |
| Gene name | HCK proto-oncogene, Src family tyrosine kinase |
| Synonyms | AIPCV|JTK9|p59Hck|p61Hck |
| Cytomap | 20q11.21 |
| Type of gene | protein-coding |
| Description | tyrosine-protein kinase HCKhematopoietic cell kinasehemopoietic cell kinasep59-HCK/p60-HCK |
| Modification date | 20240411 |
| UniProtAcc | P08631 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | HCK | GO:0005764 | lysosome | 15998323 |
| Gene | HCK | GO:0005829 | cytosol | - |
| Gene | HCK | GO:0005884 | actin filament | 15998323 |
| Gene | HCK | GO:0005886 | plasma membrane | - |
| Gene | HCK | GO:0005901 | caveola | 7791757 |
| Gene | HCK | GO:0043231 | intracellular membrane-bounded organelle | - |
| Gene | HCK | GO:0071801 | regulation of podosome assembly | 15998323 |
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 |
| P08631-1 | P08631-1_1ad5_A.pdb | 1AD5 | X-ray | 2.6 | A | 79 | 526 |
| 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 |
| P08631 | HCK | P08631-1 | P08631-2 | 526 | 505 | 1 | 21 | Deletion | none | none | 0 | 0 |
| P08631 | HCK | P08631-1 | P08631-3 | 526 | 504 | 1 | 21 | Deletion | none | none | 0 | 0 |
| P08631 | HCK | P08631-1 | P08631-3 | 526 | 504 | 76 | 76 | Deletion | none | none | 54 | 54 |
| P08631 | HCK | P08631-1 | P08631-4 | 526 | 525 | 76 | 76 | Deletion | none | none | 75 | 75 |
| Multiple sequence alignment of our canonical and alternatively spliced HCK |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of HCK |
| UniProt-id | ENSG | ENST | ENSP |
| P08631-1 | ENSG00000101336.18 | ENST00000375852.5 | ENSP00000365012.3 |
| P08631-2 | ENSG00000101336.18 | ENST00000520553.5 | ENSP00000429848.1 |
| P08631-2 | ENSG00000101336.18 | ENST00000629881.2 | ENSP00000486627.1 |
| P08631-3 | ENSG00000101336.18 | ENST00000518730.5 | ENSP00000427757.1 |
| P08631-4 | ENSG00000101336.18 | ENST00000375862.7 | ENSP00000365022.3 |
| UniProt-id | NM ID | NP ID |
| P08631-1 | NM_002110.3 | NP_002101.2 |
| P08631-2 | NM_001172129.1 | NP_001165600.1 |
| P08631-2 | NM_001172133.1 | NP_001165604.1 |
| P08631-3 | NM_001172131.1 | NP_001165602.1 |
| P08631-4 | NM_001172130.1 | NP_001165601.1 |
| Amino acid sequences of our canonical and alternatively spliced HCK |
| accession_id | Protein sequence |
| P08631-1 | MGGRSSCEDPGCPRDEERAPRMGCMKSKFLQVGGNTFSKTETSASPHCPVYVPDPTSTIKPGPNSHNSNTPGIREAGSEDIIVVALYDYE AIHHEDLSFQKGDQMVVLEESGEWWKARSLATRKEGYIPSNYVARVDSLETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSY SLSVRDYDPRQGDTVKHYKIRTLDNGGFYISPRSTFSTLQELVDHYKKGNDGLCQKLSVPCMSSKPQKPWEKDAWEIPRESLKLEKKLGA GQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLID FSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEI |
| P08631-2 | MGCMKSKFLQVGGNTFSKTETSASPHCPVYVPDPTSTIKPGPNSHNSNTPGIREAGSEDIIVVALYDYEAIHHEDLSFQKGDQMVVLEES GEWWKARSLATRKEGYIPSNYVARVDSLETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSYSLSVRDYDPRQGDTVKHYKIR TLDNGGFYISPRSTFSTLQELVDHYKKGNDGLCQKLSVPCMSSKPQKPWEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKT MKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLIDFSAQIAEGMAFIEQRNYIHRD LRAANILVSASLVCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALE |
| P08631-3 | MGCMKSKFLQVGGNTFSKTETSASPHCPVYVPDPTSTIKPGPNSHNSNTPGIREGSEDIIVVALYDYEAIHHEDLSFQKGDQMVVLEESG EWWKARSLATRKEGYIPSNYVARVDSLETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSYSLSVRDYDPRQGDTVKHYKIRT LDNGGFYISPRSTFSTLQELVDHYKKGNDGLCQKLSVPCMSSKPQKPWEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTM KPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDL RAANILVSASLVCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALER |
| P08631-4 | MGGRSSCEDPGCPRDEERAPRMGCMKSKFLQVGGNTFSKTETSASPHCPVYVPDPTSTIKPGPNSHNSNTPGIREGSEDIIVVALYDYEA IHHEDLSFQKGDQMVVLEESGEWWKARSLATRKEGYIPSNYVARVDSLETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSYS LSVRDYDPRQGDTVKHYKIRTLDNGGFYISPRSTFSTLQELVDHYKKGNDGLCQKLSVPCMSSKPQKPWEKDAWEIPRESLKLEKKLGAG QFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLIDF SAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIV |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| HCK (go to UniProt):P08631 |
| 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 |
| P08631 | Region | 1 | 20 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=21 |
| P08631 | Region | 1 | 20 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=21 |
Gene Isoform Structures and Expression Levels for HCK |
| Gene structures of our canonical and alternative spliced genes of HCK * 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 P08631-1 |
| 3D view using mol* of P08631-2 |
| 3D view using mol* of P08631-3 |
| 3D view using mol* of P08631-4 |
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 P08631-1 |
 |
| pLDDT distribution across the protein length of P08631-2 |
 |
| pLDDT distribution across the protein length of P08631-3 |
 |
| pLDDT distribution across the protein length of P08631-4 |
 |
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 P08631-1 |
 |
| Ramachandran plot of P08631-2 |
 |
| Ramachandran plot of P08631-3 |
 |
| Ramachandran plot of P08631-4 |
 |
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 |
| P08631-1 | 1.081 | 175 | 1.088 | 507.64 | 0.451 | 0.819 | 1.068 | 0.823 | 1.055 | 0.781 | 1.208 | 268,269,271,272,273,274,276,288,290,292,302,309,31 8,320,331,333,335,336,339,340,343,379,381,383,385, 386,388,398,399,400,401,402,403,406,411,418,420 |
| P08631-2 | 1.079 | 180 | 1.075 | 517.93 | 0.504 | 0.816 | 1.041 | 0.927 | 1.088 | 0.852 | 0.99 | 247,248,250,251,252,253,255,267,269,271,288,297,29 9,310,312,314,315,318,319,322,358,359,360,362,364, 365,367,377,378,379,380,381,382,385,390,396,397,39 8,399 |
| P08631-3 | 1.084 | 180 | 1.082 | 495.978 | 0.419 | 0.823 | 1.083 | 0.842 | 1.08 | 0.779 | 1.151 | 246,247,249,250,251,252,254,266,268,270,287,296,29 8,309,311,313,314,317,318,321,357,359,361,363,364, 366,376,377,378,379,380,381,384,389,396 |
| P08631-4 | 1.088 | 219 | 1.113 | 683.942 | 0.463 | 0.803 | 1.027 | 0.923 | 0.948 | 0.974 | 1.206 | 22,265,267,268,270,271,272,273,275,277,287,289,291 ,296,301,305,308,317,319,330,332,334,335,336,337,3 38,339,342,343,346,347,348,378,380,382,384,385,387 ,397,398,399,400,401,402,405,410,417,418,419 |
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 P08631-1_P08631-1_1ad5_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 P08631-1_1ad5_A_P08631-2.pdb |
| 3D view using mol* of P08631-1_1ad5_A_P08631-3.pdb |
| 3D view using mol* of P08631-1_1ad5_A_P08631-4.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P08631-1_P08631-2.pdb |
| 3D view using mol* of P08631-1_P08631-3.pdb |
| 3D view using mol* of P08631-1_P08631-4.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P08631-1_vs_P08631-2.png |
 < |
| ./stats/secondary_structure/figure/P08631-1_vs_P08631-3.png |
 < |
| ./stats/secondary_structure/figure/P08631-1_vs_P08631-4.png |
 < |
| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P08631-1_vs_P08631-2.png |
 < |
| ./stats/relative_asa/P08631-1_vs_P08631-3.png |
 < |
| ./stats/relative_asa/P08631-1_vs_P08631-4.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 HCK |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P08631 | HCK | DB06616 | Bosutinib | approved | inhibitor |
| P08631 | HCK | DB12010 | Fostamatinib | approved, investigational | inhibitor |
| P08631 | HCK | DB04216 | Quercetin | experimental, investigational | |
| P08631 | HCK | DB01809 | 1-Ter-Butyl-3-P-Tolyl-1h-Pyrazolo[3,4-D]Pyrimidin-4-Ylamine | experimental | |
| P08631 | HCK | DB01962 | Phosphonotyrosine | experimental |
Related Diseases to HCK |
| Previous studies relating to the alternative splicing of HCK and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| HCK | 19211505 | Identification of tyrosine kinase, HCK, and tumor suppressor, BIN1, as potential mediators of AHI-1 oncogene in primary and transformed CTCL cells. | AHI-1 is an oncogene often targeted by provirus insertional mutagenesis in murine leukemias and lymphomas. Aberrant expression of human AHI-1 occurs in cutaneous T-cell lymphoma (CTCL) cells and in CD4(+)CD7(-) Sezary cells from patients with Sezary syndrome. Stable knockdown of AHI-1 using retroviral-mediated RNA interference in CTCL cells inhibits their transforming activity in vitro and in vivo. To identify genes involved in AHI-1-mediated transformation, microarray analysis was performed to identify differentially expressed genes in AHI-1-suppressed CTCL cells. Fifteen up-regulated and 6 down-regulated genes were identified and confirmed by quantitative reverse transcription-polymerase chain reaction. Seven were further confirmed in a microarray analysis of CD4(+)CD7(-) Sezary cells from Sezary syndrome patients. HCK and BIN1 emerged as new candidate cooperative genes, with differential protein expression, which correlates with observed transcript changes. Interestingly, changes in HCK phosphorylation and biologic response to its inhibitor, dasatinib, were observed in AHI-1-suppressed or -overexpressed cells. The tumor suppressor BIN1 physically interacts with MYC in CTCL cells, which also exhibit differential MYC protein expression. In addition, aberrant expression of alternative splicing forms of BIN1 was observed in primary and transformed CTCL cells. These findings indicate that HCK and BIN1 may play critical roles in AHI-1-mediated leukemic transformation of human CTCL cells. | D002471 | Cell Transformation, Neoplastic |
| HCK | 19211505 | Identification of tyrosine kinase, HCK, and tumor suppressor, BIN1, as potential mediators of AHI-1 oncogene in primary and transformed CTCL cells. | AHI-1 is an oncogene often targeted by provirus insertional mutagenesis in murine leukemias and lymphomas. Aberrant expression of human AHI-1 occurs in cutaneous T-cell lymphoma (CTCL) cells and in CD4(+)CD7(-) Sezary cells from patients with Sezary syndrome. Stable knockdown of AHI-1 using retroviral-mediated RNA interference in CTCL cells inhibits their transforming activity in vitro and in vivo. To identify genes involved in AHI-1-mediated transformation, microarray analysis was performed to identify differentially expressed genes in AHI-1-suppressed CTCL cells. Fifteen up-regulated and 6 down-regulated genes were identified and confirmed by quantitative reverse transcription-polymerase chain reaction. Seven were further confirmed in a microarray analysis of CD4(+)CD7(-) Sezary cells from Sezary syndrome patients. HCK and BIN1 emerged as new candidate cooperative genes, with differential protein expression, which correlates with observed transcript changes. Interestingly, changes in HCK phosphorylation and biologic response to its inhibitor, dasatinib, were observed in AHI-1-suppressed or -overexpressed cells. The tumor suppressor BIN1 physically interacts with MYC in CTCL cells, which also exhibit differential MYC protein expression. In addition, aberrant expression of alternative splicing forms of BIN1 was observed in primary and transformed CTCL cells. These findings indicate that HCK and BIN1 may play critical roles in AHI-1-mediated leukemic transformation of human CTCL cells. | D016410 | Lymphoma, T-Cell, Cutaneous |
| HCK | 19211505 | Identification of tyrosine kinase, HCK, and tumor suppressor, BIN1, as potential mediators of AHI-1 oncogene in primary and transformed CTCL cells. | AHI-1 is an oncogene often targeted by provirus insertional mutagenesis in murine leukemias and lymphomas. Aberrant expression of human AHI-1 occurs in cutaneous T-cell lymphoma (CTCL) cells and in CD4(+)CD7(-) Sezary cells from patients with Sezary syndrome. Stable knockdown of AHI-1 using retroviral-mediated RNA interference in CTCL cells inhibits their transforming activity in vitro and in vivo. To identify genes involved in AHI-1-mediated transformation, microarray analysis was performed to identify differentially expressed genes in AHI-1-suppressed CTCL cells. Fifteen up-regulated and 6 down-regulated genes were identified and confirmed by quantitative reverse transcription-polymerase chain reaction. Seven were further confirmed in a microarray analysis of CD4(+)CD7(-) Sezary cells from Sezary syndrome patients. HCK and BIN1 emerged as new candidate cooperative genes, with differential protein expression, which correlates with observed transcript changes. Interestingly, changes in HCK phosphorylation and biologic response to its inhibitor, dasatinib, were observed in AHI-1-suppressed or -overexpressed cells. The tumor suppressor BIN1 physically interacts with MYC in CTCL cells, which also exhibit differential MYC protein expression. In addition, aberrant expression of alternative splicing forms of BIN1 was observed in primary and transformed CTCL cells. These findings indicate that HCK and BIN1 may play critical roles in AHI-1-mediated leukemic transformation of human CTCL cells. | D012751 | Sezary Syndrome |
Clinically important variants in HCK |
| (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 |