UniProtKB - Q96RU8 (TRIB1_HUMAN)
Protein
Tribbles homolog 1
Gene
TRIB1
Organism
Homo sapiens (Human)
Status
Functioni
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).By similarity1 Publication2 Publications
GO - Molecular functioni
- mitogen-activated protein kinase kinase binding Source: BHF-UCL
- protein kinase inhibitor activity Source: BHF-UCL
- transcription factor binding Source: BHF-UCL
- ubiquitin protein ligase binding Source: BHF-UCL
- ubiquitin-protein transferase regulator activity Source: BHF-UCL
GO - Biological processi
- JNK cascade Source: BHF-UCL
- negative regulation of DNA-binding transcription factor activity Source: BHF-UCL
- negative regulation of lipopolysaccharide-mediated signaling pathway Source: BHF-UCL
- negative regulation of neutrophil differentiation Source: Ensembl
- negative regulation of protein kinase activity Source: BHF-UCL
- negative regulation of smooth muscle cell migration Source: BHF-UCL
- negative regulation of smooth muscle cell proliferation Source: BHF-UCL
- positive regulation of eosinophil differentiation Source: Ensembl
- positive regulation of macrophage differentiation Source: Ensembl
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL
- regulation of MAP kinase activity Source: UniProtKB
- response to lipopolysaccharide Source: BHF-UCL
Keywordsi
Molecular function | Protein kinase inhibitor |
Enzyme and pathway databases
PathwayCommonsi | Q96RU8 |
Reactomei | R-HSA-9031628, NGF-stimulated transcription |
SignaLinki | Q96RU8 |
Names & Taxonomyi
Protein namesi | Recommended name: Tribbles homolog 1Short name: TRB-1 Alternative name(s): G-protein-coupled receptor-induced gene 2 protein Short name: GIG-2 SKIP1 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000173334.3 |
HGNCi | HGNC:16891, TRIB1 |
MIMi | 609461, gene |
neXtProti | NX_Q96RU8 |
Subcellular locationi
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 355 | D → A: Decreased interaction with COP1. 1 Publication | 1 | |
Mutagenesisi | 356 | Q → A: Decreased interaction with COP1. 1 Publication | 1 | |
Mutagenesisi | 357 | I → A: Decreased interaction with COP1. 1 Publication | 1 | |
Mutagenesisi | 358 | V → I or A: Loss of interaction with COP1. 1 Publication | 1 | |
Mutagenesisi | 359 | P → A: Strongly decreased interaction with COP1. 1 Publication | 1 | |
Mutagenesisi | 360 | E → A: Decreased interaction with COP1. 1 Publication | 1 | |
Mutagenesisi | 361 | Y → A: No effect on interaction with COP1. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 10221 |
OpenTargetsi | ENSG00000173334 |
PharmGKBi | PA134963922 |
Miscellaneous databases
Pharosi | Q96RU8, Tbio |
Polymorphism and mutation databases
BioMutai | TRIB1 |
DMDMi | 83305929 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000131859 | 1 – 372 | Tribbles homolog 1Add BLAST | 372 |
Proteomic databases
EPDi | Q96RU8 |
jPOSTi | Q96RU8 |
MassIVEi | Q96RU8 |
MaxQBi | Q96RU8 |
PaxDbi | Q96RU8 |
PeptideAtlasi | Q96RU8 |
PRIDEi | Q96RU8 |
ProteomicsDBi | 4625 78041 [Q96RU8-1] |
PTM databases
iPTMneti | Q96RU8 |
PhosphoSitePlusi | Q96RU8 |
Expressioni
Tissue specificityi
Expressed in most human tissues with the highest levels in skeletal muscle, thyroid gland, pancreas, peripheral blood leukocytes, and bone marrow.1 Publication
Gene expression databases
Bgeei | ENSG00000173334, Expressed in thyroid gland and 235 other tissues |
ExpressionAtlasi | Q96RU8, baseline and differential |
Genevisiblei | Q96RU8, HS |
Organism-specific databases
HPAi | ENSG00000173334, Tissue enhanced (bone marrow, thyroid gland) |
Interactioni
Subunit structurei
Binary interactionsi
Hide detailsQ96RU8
With | #Exp. | IntAct |
---|---|---|
STK40 [Q8N2I9] | 3 | EBI-492555,EBI-716112 |
Isoform 1 [Q96RU8-1]
With | #Exp. | IntAct |
---|---|---|
CEBPA - isoform 1 [P49715-1] | 2 | EBI-16180744,EBI-16180754 |
GO - Molecular functioni
- mitogen-activated protein kinase kinase binding Source: BHF-UCL
- transcription factor binding Source: BHF-UCL
- ubiquitin protein ligase binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 115516, 30 interactors |
DIPi | DIP-34542N |
IntActi | Q96RU8, 24 interactors |
MINTi | Q96RU8 |
STRINGi | 9606.ENSP00000312150 |
Miscellaneous databases
RNActi | Q96RU8, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q96RU8 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1 – 338 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 338 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 355 – 360 | COP1-bindingBy similarity | 6 |
Domaini
The protein kinase active site is incompatible with ATP binding and is inactive (PubMed:26455797).1 Publication
The C-terminus (351-372) is required for interaction with COP1 (PubMed:27041596).1 Publication
The COP1-binding motif (355-360) is required for regulation activity (By similarity).By similarity
Sequence similaritiesi
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Tribbles subfamily.Curated
Phylogenomic databases
eggNOGi | KOG0583, Eukaryota |
GeneTreei | ENSGT00950000182986 |
HOGENOMi | CLU_000288_13_1_1 |
InParanoidi | Q96RU8 |
OMAi | FFERDFG |
OrthoDBi | 1362510at2759 |
PhylomeDBi | Q96RU8 |
TreeFami | TF329785 |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR024105, TRB1 IPR024104, Tribbles/Ser_Thr_kinase_40 |
PANTHERi | PTHR22961, PTHR22961, 1 hit PTHR22961:SF17, PTHR22961:SF17, 1 hit |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50011, PROTEIN_KINASE_DOM, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: Q96RU8-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MRVGPVRSAM SGASQPRGPA LLFPATRGVP AKRLLDADDA AAVAAKCPRL
60 70 80 90 100
SECSSPPDYL SPPGSPCSPQ PPPAAPGAGG GSGSAPGPSR IADYLLLPLA
110 120 130 140 150
EREHVSRALC IHTGRELRCK VFPIKHYQDK IRPYIQLPSH SNITGIVEVI
160 170 180 190 200
LGETKAYVFF EKDFGDMHSY VRSRKRLREE EAARLFKQIV SAVAHCHQSA
210 220 230 240 250
IVLGDLKLRK FVFSTEERTQ LRLESLEDTH IMKGEDDALS DKHGCPAYVS
260 270 280 290 300
PEILNTTGTY SGKAADVWSL GVMLYTLLVG RYPFHDSDPS ALFSKIRRGQ
310 320 330 340 350
FCIPEHISPK ARCLIRSLLR REPSERLTAP EILLHPWFES VLEPGYIDSE
360 370
IGTSDQIVPE YQEDSDISSF FC
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketE5RFH4 | E5RFH4_HUMAN | Tribbles homolog 1 | TRIB1 | 141 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 149 – 150 | VI → SV in CAA04119 (PubMed:9342215).Curated | 2 | |
Sequence conflicti | 163 | D → S (PubMed:15299019).Curated | 1 | |
Sequence conflicti | 163 | D → S (PubMed:9342215).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_042364 | 173 | S → R1 PublicationCorresponds to variant dbSNP:rs56285697Ensembl. | 1 | |
Natural variantiVAR_042365 | 215 | T → M1 PublicationCorresponds to variant dbSNP:rs34349706Ensembl. | 1 | |
Natural variantiVAR_042366 | 267 | V → I1 PublicationCorresponds to variant dbSNP:rs56056430Ensembl. | 1 | |
Natural variantiVAR_042367 | 298 | R → C1 PublicationCorresponds to variant dbSNP:rs55953723Ensembl. | 1 | |
Natural variantiVAR_042368 | 360 | E → A1 PublicationCorresponds to variant dbSNP:rs35454769Ensembl. | 1 | |
Natural variantiVAR_042369 | 360 | E → D1 PublicationCorresponds to variant dbSNP:rs16900603EnsemblClinVar. | 1 | |
Natural variantiVAR_042370 | 371 | F → L in a lung large cell carcinoma sample; somatic mutation. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_054894 | 1 – 166 | Missing in isoform 2. 1 PublicationAdd BLAST | 166 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF250310 mRNA Translation: AAK58174.1 AF205437 mRNA Translation: AAG35663.1 AK297539 mRNA Translation: BAG59938.1 AL832388 mRNA Translation: CAI46181.1 FJ515869 Genomic DNA Translation: ACS13752.1 AC091114 Genomic DNA No translation available. CH471060 Genomic DNA Translation: EAW92085.1 BC063292 mRNA Translation: AAH63292.1 AJ000480 mRNA Translation: CAA04119.1 |
CCDSi | CCDS6357.1 [Q96RU8-1] CCDS64971.1 [Q96RU8-2] |
RefSeqi | NP_001269914.1, NM_001282985.1 [Q96RU8-2] NP_079471.1, NM_025195.3 [Q96RU8-1] |
Genome annotation databases
Ensembli | ENST00000311922; ENSP00000312150; ENSG00000173334 [Q96RU8-1] ENST00000520847; ENSP00000429063; ENSG00000173334 [Q96RU8-2] |
GeneIDi | 10221 |
KEGGi | hsa:10221 |
UCSCi | uc003yrx.4, human [Q96RU8-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF250310 mRNA Translation: AAK58174.1 AF205437 mRNA Translation: AAG35663.1 AK297539 mRNA Translation: BAG59938.1 AL832388 mRNA Translation: CAI46181.1 FJ515869 Genomic DNA Translation: ACS13752.1 AC091114 Genomic DNA No translation available. CH471060 Genomic DNA Translation: EAW92085.1 BC063292 mRNA Translation: AAH63292.1 AJ000480 mRNA Translation: CAA04119.1 |
CCDSi | CCDS6357.1 [Q96RU8-1] CCDS64971.1 [Q96RU8-2] |
RefSeqi | NP_001269914.1, NM_001282985.1 [Q96RU8-2] NP_079471.1, NM_025195.3 [Q96RU8-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5CEK | X-ray | 2.80 | A | 83-343 | [»] | |
5CEM | X-ray | 2.10 | A | 83-371 | [»] | |
5IGO | X-ray | 1.60 | U/V/W/X | 354-361 | [»] | |
5IGQ | X-ray | 3.90 | U | 354-364 | [»] | |
V/W/X/Y/Z | 354-361 | [»] | ||||
6DC0 | X-ray | 2.80 | A/B | 90-343 | [»] | |
SMRi | Q96RU8 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 115516, 30 interactors |
DIPi | DIP-34542N |
IntActi | Q96RU8, 24 interactors |
MINTi | Q96RU8 |
STRINGi | 9606.ENSP00000312150 |
PTM databases
iPTMneti | Q96RU8 |
PhosphoSitePlusi | Q96RU8 |
Polymorphism and mutation databases
BioMutai | TRIB1 |
DMDMi | 83305929 |
Proteomic databases
EPDi | Q96RU8 |
jPOSTi | Q96RU8 |
MassIVEi | Q96RU8 |
MaxQBi | Q96RU8 |
PaxDbi | Q96RU8 |
PeptideAtlasi | Q96RU8 |
PRIDEi | Q96RU8 |
ProteomicsDBi | 4625 78041 [Q96RU8-1] |
Protocols and materials databases
Antibodypediai | 27210, 369 antibodies |
DNASUi | 10221 |
Genome annotation databases
Ensembli | ENST00000311922; ENSP00000312150; ENSG00000173334 [Q96RU8-1] ENST00000520847; ENSP00000429063; ENSG00000173334 [Q96RU8-2] |
GeneIDi | 10221 |
KEGGi | hsa:10221 |
UCSCi | uc003yrx.4, human [Q96RU8-1] |
Organism-specific databases
CTDi | 10221 |
DisGeNETi | 10221 |
EuPathDBi | HostDB:ENSG00000173334.3 |
GeneCardsi | TRIB1 |
HGNCi | HGNC:16891, TRIB1 |
HPAi | ENSG00000173334, Tissue enhanced (bone marrow, thyroid gland) |
MIMi | 609461, gene |
neXtProti | NX_Q96RU8 |
OpenTargetsi | ENSG00000173334 |
PharmGKBi | PA134963922 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0583, Eukaryota |
GeneTreei | ENSGT00950000182986 |
HOGENOMi | CLU_000288_13_1_1 |
InParanoidi | Q96RU8 |
OMAi | FFERDFG |
OrthoDBi | 1362510at2759 |
PhylomeDBi | Q96RU8 |
TreeFami | TF329785 |
Enzyme and pathway databases
PathwayCommonsi | Q96RU8 |
Reactomei | R-HSA-9031628, NGF-stimulated transcription |
SignaLinki | Q96RU8 |
Miscellaneous databases
BioGRID-ORCSi | 10221, 28 hits in 877 CRISPR screens |
ChiTaRSi | TRIB1, human |
GeneWikii | TRIB1 |
GenomeRNAii | 10221 |
Pharosi | Q96RU8, Tbio |
PROi | PR:Q96RU8 |
RNActi | Q96RU8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000173334, Expressed in thyroid gland and 235 other tissues |
ExpressionAtlasi | Q96RU8, baseline and differential |
Genevisiblei | Q96RU8, HS |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR024105, TRB1 IPR024104, Tribbles/Ser_Thr_kinase_40 |
PANTHERi | PTHR22961, PTHR22961, 1 hit PTHR22961:SF17, PTHR22961:SF17, 1 hit |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50011, PROTEIN_KINASE_DOM, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TRIB1_HUMAN | |
Accessioni | Q96RU8Primary (citable) accession number: Q96RU8 Secondary accession number(s): B4DMM6 Q9H2Y8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 6, 2005 |
Last sequence update: | December 6, 2005 | |
Last modified: | December 2, 2020 | |
This is version 159 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human and mouse protein kinases
Human and mouse protein kinases: classification and index