Ripk4 receptor-interacting serine-threonine kinase 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Ripk4provided by MGI
Official Full Name: receptor-interacting serine-threonine kinase 4provided by MGI
Primary source: MGI:MGI:1919638
See related: Ensembl:ENSMUSG00000005251 AllianceGenome:MGI:1919638
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: DIk; PKK; RIP4; ANKK2; Ankrd3; 2310069J12Rik
Summary: Enables protein serine kinase activity. Involved in skin development. Located in cytoplasm. Is expressed in several structures, including alimentary system; central nervous system; genitourinary system; integumental system; and sensory organ. Used to study popliteal pterygium syndrome. Orthologous to human RIPK4 (receptor interacting serine/threonine kinase 4). [provided by Alliance of Genome Resources, Oct 2024]
Expression: Broad expression in bladder adult (RPKM 16.9), colon adult (RPKM 10.1) and 17 other tissues See more
Orthologs: human all
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Genomic context

Location:: 16 C4; 16 57.63 cM

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	16	NC_000082.7 (97543133..97564979, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	16	NC_000082.6 (97741933..97763779, complement)

Chromosome 16 - NC_000082.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

RIPK4 downregulation impairs Wnt3A-stimulated invasiveness via Wnt/beta-catenin signaling in melanoma cells and tumor growth in vivo.
Title: RIPK4 downregulation impairs Wnt3A-stimulated invasiveness via Wnt/β-catenin signaling in melanoma cells and tumor growth in vivo.
results explain how RIPK4 and IRF6 function to ensure the integrity of the epidermis and provide mechanistic insights into why developmental syndromes that are characterized by orofacial, skin and genital abnormalities result when this axis goes awry
Title: The RIPK4-IRF6 signalling axis safeguards epidermal differentiation and barrier function.
Study of keratinocyte-specific RIPK4 knockout (KO) mice found that RIPK4 in keratinocytes is essential for the establishment of a functional inside-out skin barrier but is not required for the formation of a functional outside-in barrier during development. In addition, we show that epithelial fusions in RIPK4 full KO mice are E-cadherin dependent.
Title: Keratinocyte-Specific Ablation of RIPK4 Allows Epidermal Cornification but Impairs Skin Barrier Formation.
Study presents the first crystal structure of Ripk4 and uses a structure- and biochemistry-guided approach to demonstrate that the Ripk4 homodimer is essential for catalytic activity.
Title: Crystal Structure of Ripk4 Reveals Dimerization-Dependent Kinase Activity.
We further define the interactions of keratinocyte PKK with TP63 and NF-kappaB signaling, highlighting the importance of this protein as a tumor suppressor in skin squamous cell carcinoma development.
Title: PKK deletion in basal keratinocytes promotes tumorigenesis after chemical carcinogenesis.
this work uncovers a critical role of PKK in lupus development
Title: PKK deficiency in B cells prevents lupus development in Sle lupus mice.
these results reveal a critical role of PKK in the maintenance of recirculating mature B cells as well as the development of B1 cells in mice
Title: A critical role for the protein kinase PKK in the maintenance of recirculating mature B cells and the development of B1 cells.
This approach identified a key signaling event, phosphorylation of a desmosome component, PKP1 (plakophilin-1) by RIPK4 (receptor-interacting serine-threonine kinase 4) during epidermal differentiation.
Title: Phosphorylation of Pkp1 by RIPK4 regulates epidermal differentiation and skin tumorigenesis.
RIP4 functions in the epidermis through PKC-specific signaling pathways to regulate differentiation and inflammation
Title: RIP4 regulates epidermal differentiation and cutaneous inflammation.
Data show that RIP4 is a critical component of a novel pathway that controls keratinocyte differentiation.
Title: RIP4 is an ankyrin repeat-containing kinase essential for keratinocyte differentiation.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Targeted (5) 1 citation

General gene information

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Markers

Ankrd3 (e-PCR), detects polymorphism
- UniSTS:233998

G67859 (e-PCR)
- UniSTS:228507

AI552420 (e-PCR)
- UniSTS:180950

Ripk4 (e-PCR), detects polymorphism
- UniSTS:259037

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine kinase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in morphogenesis of an epithelium	IEA Inferred from Electronic Annotation more info
involved_in morphogenesis of an epithelium	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of NF-kappaB transcription factor activity	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of NF-kappaB transcription factor activity	ISO Inferred from Sequence Orthology more info
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in skin development	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: receptor-interacting serine/threonine-protein kinase 4

Names: PKC-associated protein kinase; PKC-regulated protein kinase; ankyrin repeat domain-containing protein 3

NP_076152.2

EC 2.7.11.1

XP_011244456.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_023663.7 → NP_076152.2 receptor-interacting serine/threonine-protein kinase 4

See identical proteins and their annotated locations for NP_076152.2

Status: VALIDATED

Source sequence(s)

AC121560

Consensus CDS

CCDS28360.1

UniProtKB/Swiss-Prot

Q3UM04, Q9ERK0

Related

ENSMUSP00000019386.9, ENSMUST00000019386.10

Conserved Domains (5) summary

smart00219
Location:26 → 279

TyrKc; Tyrosine kinase, catalytic domain

cd00204
Location:600 → 725

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

cd14025
Location:25 → 290

STKc_RIP4_like; Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar proteins

pfam12796
Location:610 → 701

Ank_2; Ankyrin repeats (3 copies)

sd00045
Location:605 → 636

ANK; ANK repeat [structural motif]

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000082.7 Reference GRCm39 C57BL/6J

Range

97543133..97564979 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011246154.2 → XP_011244456.1 receptor-interacting serine/threonine-protein kinase 4 isoform X1

UniProtKB/TrEMBL

D3YXY4

Conserved Domains (4) summary

PHA03095
Location:410 → 654

PHA03095; ankyrin-like protein; Provisional

sd00045
Location:542 → 573

ANK; ANK repeat [structural motif]

pfam12796
Location:613 → 703

Ank_2; Ankyrin repeats (3 copies)

cl21453
Location:1 → 227

PKc_like; Protein Kinases, catalytic domain