Tbio MAPK8IP1 C-Jun-amino-terminal kinase-interacting protein 1

Protein Summary

Description

The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. Required for JNK activation in response to excitotoxic stress. Cytoplasmic MAPK8IP1 causes inhibition of JNK-regulated activity by retaining JNK in the cytoplasm and inhibiting JNK phosphorylation of c-Jun. May also participate in ApoER2-specific reelin signaling. Directly, or indirectly, regulates GLUT2 gene expression and beta-cell function. Appears to have a role in cell signaling in mature and developing nerve terminals. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins. Functions as an anti-apoptotic protein and whose level seems to influence the beta-cell death or survival response. Acts as a scaffold protein that coordinates with SH3RF1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the activation of MAPK8/JNK1 and differentiation of CD8(+) T-cells. This gene encodes a regulator of the pancreatic beta-cell function. It is highly similar to JIP-1, a mouse protein known to be a regulator of c-Jun amino-terminal kinase (Mapk8). This protein has been shown to prevent MAPK8 mediated activation of transcription factors, and to decrease IL-1 beta and MAP kinase kinase 1 (MEKK1) induced apoptosis in pancreatic beta cells. This protein also functions as a DNA-binding transactivator of the glucose transporter GLUT2. RE1-silencing transcription factor (REST) is reported to repress the expression of this gene in insulin-secreting beta cells. This gene is found to be mutated in a type 2 diabetes family, and thus is thought to be a susceptibility gene for type 2 diabetes. [provided by RefSeq, May 2011]

Uniprot Accession IDs

• Q9UQF2
• D3DQP4
• O43407
• JIP-1

Gene Name

• MAPK8IP1

Ensembl ID

• ENST00000241014
• ENSP00000241014
• ENSG00000121653

Symbol

• IB1
• JIP1
• PRKM8IP
• IB1
• JIP1
• JIP-1
• PRKM8IP

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	0.96
kinase perturbation	0.93
hub protein	0.88
molecular function	0.81
biological process	0.78

Protein Classes

PANTHER Classes

Protein / Signaling Molecule / C-jun-amino-terminal Kinase-interacting Protein 1

DTO Classes

Protein / Signaling / C-jun-amino-terminal Kinase-interacting Protein 1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 360.53   (req: < 5)

Gene RIFs: 27   (req: <= 3)

Antibodies: 239   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 360.53   (req: >= 5)

Gene RIFs: 27   (req: > 3)

Antibodies: 239   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 14

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (108)

Explore Interacting Targets

1 – 10 of 108

• See Interactions on String-DB

TTLL4

Tbio

Family:  Enzyme

Novelty:  0.14127442

p_int:  0.999999961

p_ni:  3.7e-8

p_wrong:  2e-9

Score:  0.228

Data Source:  BioPlex,STRINGDB

MAPK8IP2

Tbio

Family:  Enzyme

Novelty:  0.01788453

p_int:  0.999999244

p_ni:  6.87e-7

p_wrong:  6.9e-8

Score:  0.972

Data Source:  BioPlex,STRINGDB

ANK3

Tbio

Novelty:  0.00429246

p_int:  0.999997159

p_ni:  0.000002841

Score:  0.223

Data Source:  BioPlex,STRINGDB

MAPK8

Tchem

Family:  Kinase

Novelty:  0.00055723

p_int:  0.999930947

p_ni:  0.000066838

p_wrong:  0.000002215

Score:  0.997

Data Source:  BioPlex,STRINGDB

MAPK9

Tchem

Family:  Kinase

Novelty:  0.00267199

p_int:  0.999829924

p_ni:  0.000170076

Score:  0.983

Data Source:  BioPlex,STRINGDB

MAPK8IP3

Tbio

Family:  Enzyme

Novelty:  0.01127812

p_int:  0.999753312

p_ni:  0.000246688

Score:  0.944

Data Source:  BioPlex,STRINGDB

FEM1B

Tbio

Novelty:  0.06746412

p_int:  0.99918993

p_ni:  0.00081007

Data Source:  BioPlex

HOXC8

Tbio

Family:  TF

Novelty:  0.01042291

p_int:  0.99560903

p_wrong:  0.00439097

Score:  0.379

Data Source:  BioPlex,STRINGDB

ANK2

Tbio

Novelty:  0.00528351

p_int:  0.992460769

p_ni:  0.007539231

Score:  0.284

Data Source:  BioPlex,STRINGDB

SENP5

Tbio

Family:  Enzyme

Novelty:  0.0510532

p_int:  0.980890251

p_ni:  0.019109748

Data Source:  BioPlex

Nearest Tclin Targets (2)

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Downstream (2)

1 – 2 of 2

MAP2K2

Tclin

Family:  Kinase

KEGG Distance:  4

Common Pathways:  1

1: MAPK signaling pathway

MAP2K1

Tclin

Family:  Kinase

KEGG Distance:  4

Common Pathways:  1

1: MAPK signaling pathway

Pathways (9)

KEGG (1)

WikiPathways (8)

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Items per page:

5

1 – 1 of 1

Data Source	Name	Explore in Pharos	Explore in Source
KEGG	MAPK signaling pathway	295 targets	path:hsa04010

Name	Explore in Pharos	Explore in Source
MAPK signaling pathway	295 targets	path:hsa04010

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (26)

Functions (6)

Components (12)

Processes (8)

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1 – 6 of 6

GO Term	Evidence	Assigned by
kinesin binding	Inferred from Physical Interaction (IPI)	UniProtKB
MAP-kinase scaffold activity	Inferred from Physical Interaction (IPI)	UniProtKB
protein kinase inhibitor activity	Traceable Author Statement (TAS)	ProtInc
JUN kinase binding	Inferred from Electronic Annotation (IEA)	Ensembl
mitogen-activated protein kinase kinase binding	Inferred from Electronic Annotation (IEA)	Ensembl
mitogen-activated protein kinase kinase kinase binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations ()

No disease associations found

GWAS Traits (11)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 11

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
glucose measurement	EFO_0004468	2	2	2		91.9
high density lipoprotein cholesterol measurement	EFO_0004612	3	2	3		87.5
fasting blood glucose measurement	EFO_0004465	6	1	6		77.9
type II diabetes mellitus	EFO_0001360	3	3	2	1	71.4
body mass index	EFO_0004340	1	1	1		63.7

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 11

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
glucose measurement	EFO_0004468	2		91.9
high density lipoprotein cholesterol measurement	EFO_0004612	3		87.5
fasting blood glucose measurement	EFO_0004465	6		77.9
type II diabetes mellitus	EFO_0001360	2	1	71.4
body mass index	EFO_0004340	1		63.7

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UniProt Keyword Find Similar Targets

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3D-structure
Complete proteome
Cytoplasm
Diabetes mellitus
Disease mutation
Endoplasmic reticulum
Membrane
Mitochondrion
Nucleus
Phosphoprotein

GWAS Trait Find Similar Targets

No Header	No Header
body height
body mass index
fasting blood glucose measurement
glucose measurement
high density lipoprotein cholesterol measurement
mean corpuscular hemoglobin concentration
sex hormone-binding globulin measurement
smoking status measurement
triglyceride measurement
type II diabetes mellitus

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cellular phenotype
homeostasis/metabolism phenotype
liver/biliary system phenotype
mortality/aging
nervous system phenotype

IDG Resources

No IDG generated resources found

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	mitogen-activated protein kinase 8 interacting protein 1	VGNC:7508	451148
Macaque	mitogen-activated protein kinase 8 interacting protein 1		714950
Mouse	mitogen-activated protein kinase 8 interacting protein 1	MGI:1309464	19099
Rat	mitogen-activated protein kinase 8 interacting protein 1	RGD:70937	116457
Dog	mitogen-activated protein kinase 8 interacting protein 1	VGNC:49920	483640

Species	Name	OMA	EggNOG	Inparanoid
Chimp	mitogen-activated protein kinase 8 interacting protein 1
Macaque	mitogen-activated protein kinase 8 interacting protein 1
Mouse	mitogen-activated protein kinase 8 interacting protein 1
Rat	mitogen-activated protein kinase 8 interacting protein 1
Dog	mitogen-activated protein kinase 8 interacting protein 1

Publication Statistics

PubMed Score 360.53

PubMed score by year

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PubTator Score 655.33

PubTator score by year

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Related Publications

Text Mined References (57)

GeneRif Annotations (27)

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PMID	Year	Title