TRIB1 (tribbles pseudokinase 1)

Gene

• Entrez ID: 10221
• Gene name: Tribbles pseudokinase 1
• Gene symbol: TRIB1
• Synonyms: C8FW, GIG-2, GIG2, SKIP1, TRB-1, TRB1
• Chromosome: 8
• Chromosome location: 8q24.13

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT003109	hsa-miR-122-5p	Luciferase reporter assay, qRT-PCR	19296470
MIRT016950	hsa-miR-335-5p	Microarray	18185580
MIRT027398	hsa-miR-99a-5p	Sequencing	20371350
MIRT027398	hsa-miR-99a-5p	PAR-CLIP	26701625
MIRT027499	hsa-miR-98-5p	Microarray	19088304
MIRT028892	hsa-miR-26b-5p	Microarray	19088304
MIRT438014	hsa-miR-224-5p	Microarray/In situ hybridization, Luciferase reporter assay, Western blot , qRT-PCR	24382668
MIRT465295	hsa-miR-3658	PAR-CLIP	23592263
MIRT465296	hsa-miR-5006-5p	PAR-CLIP	23592263
MIRT465297	hsa-miR-3653-3p	PAR-CLIP	23592263
MIRT465298	hsa-miR-4694-5p	PAR-CLIP	23592263
MIRT465299	hsa-miR-4755-3p	PAR-CLIP	23592263
MIRT465300	hsa-miR-6086	PAR-CLIP	23592263
MIRT465301	hsa-miR-377-5p	PAR-CLIP	23592263
MIRT465302	hsa-miR-655-5p	PAR-CLIP	23592263
MIRT465303	hsa-miR-6507-5p	PAR-CLIP	23592263
MIRT465304	hsa-miR-3934-5p	PAR-CLIP	23592263
MIRT553403	hsa-let-7c-3p	PAR-CLIP	21572407
MIRT553403	hsa-let-7c-3p	PAR-CLIP	20371350
MIRT553404	hsa-miR-331-5p	PAR-CLIP	21572407
MIRT553404	hsa-miR-331-5p	PAR-CLIP	20371350
MIRT553405	hsa-miR-524-5p	PAR-CLIP	21572407
MIRT553406	hsa-miR-520d-5p	PAR-CLIP	21572407
MIRT553407	hsa-miR-3163	PAR-CLIP	21572407
MIRT553407	hsa-miR-3163	PAR-CLIP	20371350
MIRT553408	hsa-miR-4678	PAR-CLIP	21572407
MIRT553408	hsa-miR-4678	PAR-CLIP	20371350
MIRT553409	hsa-miR-1277-5p	PAR-CLIP	21572407
MIRT553409	hsa-miR-1277-5p	PAR-CLIP	20371350
MIRT553410	hsa-miR-548m	PAR-CLIP	21572407
MIRT553410	hsa-miR-548m	PAR-CLIP	20371350
MIRT573048	hsa-miR-887-5p	PAR-CLIP	20371350
MIRT573049	hsa-miR-6779-5p	PAR-CLIP	20371350
MIRT573050	hsa-miR-6780a-5p	PAR-CLIP	20371350
MIRT573051	hsa-miR-3689c	PAR-CLIP	20371350
MIRT573052	hsa-miR-3689b-3p	PAR-CLIP	20371350
MIRT573053	hsa-miR-3689a-3p	PAR-CLIP	20371350
MIRT573054	hsa-miR-1273h-5p	PAR-CLIP	20371350
MIRT573055	hsa-miR-30b-3p	PAR-CLIP	20371350
MIRT573056	hsa-miR-6788-5p	PAR-CLIP	20371350
MIRT573057	hsa-miR-30c-2-3p	PAR-CLIP	20371350
MIRT573058	hsa-miR-30c-1-3p	PAR-CLIP	20371350
MIRT573059	hsa-miR-4425	PAR-CLIP	20371350
MIRT573060	hsa-miR-4303	PAR-CLIP	20371350
MIRT573061	hsa-miR-8085	PAR-CLIP	20371350
MIRT573062	hsa-miR-6878-5p	PAR-CLIP	20371350
MIRT573063	hsa-miR-6731-5p	PAR-CLIP	20371350
MIRT573064	hsa-miR-3670	PAR-CLIP	20371350
MIRT573065	hsa-miR-6751-3p	PAR-CLIP	20371350
MIRT573066	hsa-miR-1199-5p	PAR-CLIP	20371350
MIRT573067	hsa-miR-4653-5p	PAR-CLIP	20371350
MIRT573068	hsa-miR-4766-5p	PAR-CLIP	20371350
MIRT573069	hsa-miR-3921	PAR-CLIP	20371350
MIRT573070	hsa-miR-1306-3p	PAR-CLIP	20371350
MIRT573071	hsa-miR-759	PAR-CLIP	20371350
MIRT573072	hsa-miR-148b-5p	PAR-CLIP	20371350
MIRT573073	hsa-miR-6874-3p	PAR-CLIP	20371350
MIRT573074	hsa-miR-6854-5p	PAR-CLIP	20371350
MIRT641197	hsa-miR-514b-5p	HITS-CLIP	23824327
MIRT641197	hsa-miR-514b-5p	HITS-CLIP	19536157
MIRT641198	hsa-miR-513c-5p	HITS-CLIP	23824327
MIRT641198	hsa-miR-513c-5p	HITS-CLIP	19536157
MIRT641199	hsa-miR-6749-3p	HITS-CLIP	23824327
MIRT641199	hsa-miR-6749-3p	HITS-CLIP	19536157
MIRT641200	hsa-miR-642a-5p	HITS-CLIP	23824327
MIRT641200	hsa-miR-642a-5p	HITS-CLIP	19536157
MIRT641201	hsa-miR-6852-3p	HITS-CLIP	23824327
MIRT641201	hsa-miR-6852-3p	HITS-CLIP	19536157
MIRT641202	hsa-miR-3909	HITS-CLIP	23824327
MIRT641202	hsa-miR-3909	HITS-CLIP	19536157
MIRT641203	hsa-miR-6744-3p	HITS-CLIP	23824327
MIRT641203	hsa-miR-6744-3p	HITS-CLIP	19536157
MIRT641204	hsa-miR-4757-5p	HITS-CLIP	23824327
MIRT641204	hsa-miR-4757-5p	HITS-CLIP	19536157
MIRT641205	hsa-miR-942-5p	HITS-CLIP	23824327
MIRT641205	hsa-miR-942-5p	HITS-CLIP	19536157
MIRT641206	hsa-miR-4469	HITS-CLIP	23824327
MIRT641206	hsa-miR-4469	HITS-CLIP	19536157
MIRT641207	hsa-miR-372-5p	HITS-CLIP	23824327
MIRT641207	hsa-miR-372-5p	HITS-CLIP	19536157
MIRT641208	hsa-miR-371a-5p	HITS-CLIP	23824327
MIRT641208	hsa-miR-371a-5p	HITS-CLIP	19536157
MIRT641209	hsa-miR-616-5p	HITS-CLIP	23824327
MIRT641209	hsa-miR-616-5p	HITS-CLIP	19536157
MIRT641210	hsa-miR-373-5p	HITS-CLIP	23824327
MIRT641210	hsa-miR-373-5p	HITS-CLIP	19536157
MIRT641211	hsa-miR-371b-5p	HITS-CLIP	23824327
MIRT641211	hsa-miR-371b-5p	HITS-CLIP	19536157
MIRT641212	hsa-miR-877-3p	HITS-CLIP	23824327
MIRT641212	hsa-miR-877-3p	HITS-CLIP	19536157
MIRT641213	hsa-miR-2276-5p	HITS-CLIP	23824327
MIRT641213	hsa-miR-2276-5p	HITS-CLIP	19536157
MIRT641214	hsa-miR-6892-3p	HITS-CLIP	23824327
MIRT641214	hsa-miR-6892-3p	HITS-CLIP	19536157
MIRT641215	hsa-miR-520h	HITS-CLIP	23824327
MIRT641215	hsa-miR-520h	HITS-CLIP	19536157
MIRT641216	hsa-miR-520g-3p	HITS-CLIP	23824327
MIRT641216	hsa-miR-520g-3p	HITS-CLIP	19536157
MIRT641217	hsa-miR-3973	HITS-CLIP	23824327
MIRT641217	hsa-miR-3973	HITS-CLIP	19536157
MIRT735790	hsa-miR-100-5p	PAR-CLIP	26701625
MIRT735800	hsa-miR-101-3p	PAR-CLIP	26701625
MIRT737068	hsa-miR-1287-3p	PAR-CLIP	26701625
MIRT737628	hsa-miR-144-3p	PAR-CLIP	26701625
MIRT744294	hsa-miR-4426	PAR-CLIP	26701625
MIRT745427	hsa-miR-449b-3p	PAR-CLIP	26701625
MIRT746453	hsa-miR-4647	PAR-CLIP	26701625
MIRT746707	hsa-miR-4662b	PAR-CLIP	26701625
MIRT760961	hsa-miR-99b-5p	PAR-CLIP	26701625

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004672	Function	Protein kinase activity	TAS	20410507
GO:0004860	Function	Protein kinase inhibitor activity	IMP	15299019
GO:0005515	Function	Protein binding	IPI	25852190, 28514442
GO:0005524	Function	ATP binding	TAS	20410507
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	IDA	17452330
GO:0005737	Component	Cytoplasm	IDA	17452330
GO:0006468	Process	Protein phosphorylation	TAS	20410507
GO:0006469	Process	Negative regulation of protein kinase activity	IMP	15299019
GO:0007254	Process	JNK cascade	IMP	17452330
GO:0008134	Function	Transcription factor binding	IPI	17724128
GO:0014912	Process	Negative regulation of smooth muscle cell migration	IMP	17452330
GO:0031434	Function	Mitogen-activated protein kinase kinase binding	IBA	21873635
GO:0031434	Function	Mitogen-activated protein kinase kinase binding	IDA	15299019, 17452330
GO:0031625	Function	Ubiquitin protein ligase binding	ISS	20410507
GO:0031665	Process	Negative regulation of lipopolysaccharide-mediated signaling pathway	IMP	17452330
GO:0032436	Process	Positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IBA	21873635
GO:0032436	Process	Positive regulation of proteasomal ubiquitin-dependent protein catabolic process	ISS	20410507
GO:0032496	Process	Response to lipopolysaccharide	IMP	17452330
GO:0032496	Process	Response to lipopolysaccharide	ISS	17724128
GO:0043405	Process	Regulation of MAP kinase activity	IBA	21873635
GO:0043405	Process	Regulation of MAP kinase activity	IDA	15299019
GO:0043433	Process	Negative regulation of DNA-binding transcription factor activity	IMP	15299019
GO:0043433	Process	Negative regulation of DNA-binding transcription factor activity	ISS	17724128
GO:0045645	Process	Positive regulation of eosinophil differentiation	IEA
GO:0045651	Process	Positive regulation of macrophage differentiation	IEA
GO:0045659	Process	Negative regulation of neutrophil differentiation	IEA
GO:0048662	Process	Negative regulation of smooth muscle cell proliferation	IMP	17452330
GO:0055106	Function	Ubiquitin-protein transferase regulator activity	ISS	20410507

Other IDs

• MIM: 609461
• HGNC: 16891
• e!Ensembl: ENSG00000173334

Protein

• UniProt ID: Q96RU8
• Protein name: Tribbles homolog 1 (TRB-1) (G-protein-coupled receptor-induced gene 2 protein) (GIG-2) (SKIP1)
• Protein function: Adapter protein involved in protein degradation by interacting with COP1 ubiquitin ligase (PubMed:27041596). The COP1-binding motif is masked by autoinhibitory interactions with the protein kinase domain (PubMed:26455797). Serves to alter COP1 substrate specificity by directing the activity of COP1 toward CEBPA (PubMed:27041596). Binds selectively the recognition sequence of CEBPA (PubMed:26455797). Regulates myeloid cell differentiation by altering the expression of CEBPA in a COP1-dependent manner (By similarity). Controls macrophage, eosinophil and neutrophil differentiation via the COP1-binding domain (By similarity). Interacts with MAPK kinases and regulates activation of MAP kinases, but has no kinase activity (PubMed:15299019, PubMed:26455797).
• PDB: 5CEK, 5CEM, 5IGO, 5IGQ, 6DC0
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	105 → 338	Protein kinase domain	Domain

• Sequence:

  MRVGPVRSAMSGASQPRGPALLFPATRGVPAKRLLDADDAAAVAAKCPRLSECSSPPDYL
  SPPGSPCSPQPPPAAPGAGGGSGSAPGPSRIADYLLLPLAEREHVSRALCIHTGRELRCK
  VFPIKHYQDKIRPYIQLPSHSNITGIVEVILGETKAYVFFEKDFGDMHSYVRSRKRLREE
  EAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSTEERTQLRLESLEDTHIMKGEDDALS
  DKHGCPAYVSPEILNTTGTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQ
  FCIPEHISPKARCLIRSLLRREPSERLTAPEILLHPWFESVLEPGYIDSEIGTSDQIVPE
  YQEDSDISSFFC

• Sequence length: 372

Pathways

Reactome:

NGF-stimulated transcription

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	24097064
Lung carcinoma	Large cell carcinoma of lung	rs1805076, rs121909071, rs121913530, rs112445441, rs121913529, rs121913535, rs121913297, rs121913279, rs104886003, rs397516975, rs11554290, rs121913364, rs121913351, rs121913369, rs121913355, rs121912470, rs121913273, rs121913281, rs121913348, rs727503093, rs121913353, rs397516890, rs397516896, rs121913378, rs397516897, rs397516977, rs397516978, rs397516979, rs397516980, rs397516981, rs397516982, rs121913240, rs17851045, rs397517086, rs121913428, rs397517094, rs397517098, rs397517106, rs121913465, rs397517108, rs397517111, rs397517112, rs397517114, rs397517116, rs1554350366, rs397517127, rs397517200, rs397517202, rs121913283, rs121913370, rs121913357, rs727503106, rs121913238, rs727503108, rs397517040, rs397516976, rs1555618025, rs1057519729, rs-1, rs1584238193

Unknown
Disease name	Disease term	dbSNP ID	References
Coronary arteriosclerosis	Coronary Arteriosclerosis		24097064