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Target has curated data in GtoImmuPdb
Target id: 2085
Nomenclature: mitogen-activated protein kinase kinase kinase kinase 1
Abbreviated Name: HPK1
Family: KHS subfamily
Annotation status:
Annotated and awaiting review. Please contact us if you can help with reviewing.
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Gene and Protein Information ![]() |
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Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 821 | 19q13.1-q13.4 | MAP4K1 | mitogen-activated protein kinase kinase kinase kinase 1 | |
Mouse | - | 827 | 7 B1 | Map4k1 | mitogen-activated protein kinase kinase kinase kinase 1 | |
Rat | - | 827 | 1 q21 | Map4k1 | mitogen activated protein kinase kinase kinase kinase 1 |
Previous and Unofficial Names ![]() |
hematopoietic progenitor kinase 1 | MAPK/ERK kinase kinase kinase 1 |
Database Links ![]() |
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BRENDA | 2.7.11.1 |
Ensembl Gene | ENSG00000104814 (Hs), ENSMUSG00000037337 (Mm), ENSRNOG00000020505 (Rn) |
Entrez Gene | 11184 (Hs), 26411 (Mm), 292763 (Rn) |
Human Protein Atlas | ENSG00000104814 (Hs) |
KEGG Enzyme | 2.7.11.1 |
KEGG Gene | hsa:11184 (Hs), mmu:26411 (Mm), rno:292763 (Rn) |
OMIM | 601983 (Hs) |
RefSeq Nucleotide | NM_001042600 (Hs), NM_008279 (Mm), NM_001106243 (Rn) |
RefSeq Protein | NP_001036065 (Hs), NP_032305 (Mm), NP_001099713 (Rn) |
UniProtKB | Q92918 (Hs), P70218 (Mm) |
Wikipedia | MAP4K1 (Hs) |
Enzyme Reaction ![]() |
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DiscoveRx KINOMEscan® screen ![]() |
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A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform. http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan Reference: 3,10 |
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Target used in screen: HPK1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
Immunopharmacology Comments |
HPK1 inhibits T-cell receptor (TCR) signaling via a mechanism that induces phosphorylation and ubiquitination of SLP-76, it inhibits B-cell receptor signaling by inducing phosphorylation and ubiquitination of BLNK [9]. |
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Physiological Consequences of Altering Gene Expression ![]() |
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General Comments |
Hematopoietic progenitor kinase 1 (HPK1) regulates stress responses, proliferation, and apoptosis in hematopoietic cells. HPK1 has been identified as a novel target for cancer immunotherapy, whose inhibition may activate anti-tumour activity of both dendritic cells and T cells [6]. In contrast, a specific role of HPK1 as a novel tumor suppressor has been suggested by studies in pancreatic cancer [8]. |
1. Alzabin S, Bhardwaj N, Kiefer F, Sawasdikosol S, Burakoff S. (2009) Hematopoietic progenitor kinase 1 is a negative regulator of dendritic cell activation. J. Immunol., 182 (10): 6187-94. [PMID:19414772]
2. Chuang HC, Wang X, Tan TH. (2016) MAP4K Family Kinases in Immunity and Inflammation. Adv. Immunol., 129: 277-314. [PMID:26791862]
3. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1046-51. [PMID:22037378]
4. Hu MC, Qiu WR, Wang X, Meyer CF, Tan TH. (1996) Human HPK1, a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade. Genes Dev., 10 (18): 2251-64. [PMID:8824585]
5. Kiefer F, Tibbles LA, Anafi M, Janssen A, Zanke BW, Lassam N, Pawson T, Woodgett JR, Iscove NN. (1996) HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway. EMBO J., 15 (24): 7013-25. [PMID:9003777]
6. Sawasdikosol S, Zha R, Yang B, Burakoff S. (2012) HPK1 as a novel target for cancer immunotherapy. Immunol. Res., 54 (1-3): 262-5. [PMID:22477524]
7. Shui JW, Boomer JS, Han J, Xu J, Dement GA, Zhou G, Tan TH. (2007) Hematopoietic progenitor kinase 1 negatively regulates T cell receptor signaling and T cell-mediated immune responses. Nat. Immunol., 8 (1): 84-91. [PMID:17115060]
8. Wang H, Song X, Logsdon C, Zhou G, Evans DB, Abbruzzese JL, Hamilton SR, Tan TH, Wang H. (2009) Proteasome-mediated degradation and functions of hematopoietic progenitor kinase 1 in pancreatic cancer. Cancer Res., 69 (3): 1063-70. [PMID:19141650]
9. Wang X, Li JP, Kuo HK, Chiu LL, Dement GA, Lan JL, Chen DY, Yang CY, Hu H, Tan TH. (2012) Down-regulation of B cell receptor signaling by hematopoietic progenitor kinase 1 (HPK1)-mediated phosphorylation and ubiquitination of activated B cell linker protein (BLNK). J. Biol. Chem., 287 (14): 11037-48. [PMID:22334673]
10. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem. Biol., 17 (11): 1241-9. [PMID:21095574]
KHS subfamily: mitogen-activated protein kinase kinase kinase kinase 1. Last modified on 05/06/2018. Accessed on 21/02/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2085.