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receptor interacting serine/threonine kinase 4

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Target not currently curated in GtoImmuPdb

Target id: 2192

Nomenclature: receptor interacting serine/threonine kinase 4

Abbreviated Name: ANKRD3

Family: Receptor interacting protein kinase (RIPK) family

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 832 21q22.3 RIPK4 receptor interacting serine/threonine kinase 4
Mouse - 786 16 C4 Ripk4 receptor-interacting serine-threonine kinase 4
Rat - 786 11q12 Ripk4 receptor-interacting serine-threonine kinase 4
Previous and Unofficial Names Click here for help
RIP4 | ANKK2 | ankyrin repeat domain 3 | DIK | PKC-delta-interacting protein kinase | PKK | protein kinase C-associated kinase
Database Links Click here for help
Alphafold
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of murine receptor-interacting protein 4 (Ripk4) D143N bound to staurosporine.
PDB Id:  5WNL
Ligand:  staurosporine
Resolution:  2.5Å
Species:  Mouse
References:  3
Enzyme Reaction Click here for help
EC Number: 2.7.11.1
DiscoveRx KINOMEscan® screen Click here for help
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: 2,5

Key to terms and symbols Click column headers to sort
Target used in screen: RIPK4
Ligand Sp. Type Action Value Parameter
lestaurtinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 7.9 pKd
TG-100-115 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.9 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.7 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.7 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Popliteal pterygium syndrome 2, lethal type
Synonyms: Bartsocas-Papas syndrome [Orphanet: ORPHA1234]
Popliteal pterygium syndrome [Disease Ontology: DOID:0060055]
Disease Ontology: DOID:0060055
OMIM: 263650
Orphanet: ORPHA1234
General Comments
In humans RIPK4 acts as a protein kinase C (PKC)-δ-interacting protein kinase that is expressed in the epithelium and most non-nervous tissues. It is required for activation of both the NF-κB and JNK-AP-1 pathways in HEK-293T cells [1], and may play a role in Wnt signalling [4]. Huang et al. (2018) have demonstrated in crystallographic studies that a dimeric structure of mouse Ripk4 is required for catalytic activity [3].

References

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1. Chen L, Haider K, Ponda M, Cariappa A, Rowitch D, Pillai S. (2001) Protein kinase C-associated kinase (PKK), a novel membrane-associated, ankyrin repeat-containing protein kinase. J Biol Chem, 276 (24): 21737-44. [PMID:11278382]

2. 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]

3. Huang CS, Oberbeck N, Hsiao YC, Liu P, Johnson AR, Dixit VM, Hymowitz SG. (2018) Crystal Structure of Ripk4 Reveals Dimerization-Dependent Kinase Activity. Structure, 26 (5): 767-777.e5. [PMID:29706531]

4. Huang X, McGann JC, Liu BY, Hannoush RN, Lill JR, Pham V, Newton K, Kakunda M, Liu J, Yu C et al.. (2013) Phosphorylation of Dishevelled by protein kinase RIPK4 regulates Wnt signaling. Science, 339 (6126): 1441-5. [PMID:23371553]

5. 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]

How to cite this page

Receptor interacting protein kinase (RIPK) family: receptor interacting serine/threonine kinase 4. Last modified on 26/09/2018. Accessed on 23/09/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2192.