UniProtKB - Q96RU8 (TRIB1_HUMAN)
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Protein
Tribbles homolog 1
Gene
TRIB1
Organism
Homo sapiens (Human)
Status
Functioni
Adapter protein involved in protein degradation by interacting with RFWD2/COP1 ubiquitin ligase (PubMed:27041596). The RFWD2-binding motif is masked by autoinhibitory interactions with the protein kinase domain (PubMed:26455797). Serves to alter RFWD2 substrate specificity by directing the activity of RFWD2 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 RFWD2-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 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 sequence-specific DNA binding transcription factor 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
| 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
| HGNCi | HGNC:16891. TRIB1. |
Subcellular locationi
GO - Cellular componenti
Pathology & Biotechi
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 355 | D → A: Decreased interaction with RFWD2. 1 Publication | 1 | |
| Mutagenesisi | 356 | Q → A: Decreased interaction with RFWD2. 1 Publication | 1 | |
| Mutagenesisi | 357 | I → A: Decreased interaction with RFWD2. 1 Publication | 1 | |
| Mutagenesisi | 358 | V → I or A: Loss of interaction with RFWD2. 1 Publication | 1 | |
| Mutagenesisi | 359 | P → A: Strongly decreased interaction with RFWD2. 1 Publication | 1 | |
| Mutagenesisi | 360 | E → A: Decreased interaction with RFWD2. 1 Publication | 1 | |
| Mutagenesisi | 361 | Y → A: No effect on interaction with RFWD2. 1 Publication | 1 |
Organism-specific databases
| DisGeNETi | 10221. |
| OpenTargetsi | ENSG00000173334. |
| PharmGKBi | PA134963922. |
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. |
| MaxQBi | Q96RU8. |
| PaxDbi | Q96RU8. |
| PeptideAtlasi | Q96RU8. |
| PRIDEi | Q96RU8. |
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. |
| CleanExi | HS_TRIB1. |
| ExpressionAtlasi | Q96RU8. baseline and differential. |
| Genevisiblei | Q96RU8. HS. |
Organism-specific databases
| HPAi | HPA063982. |
Interactioni
Subunit structurei
Monomer (PubMed:26455797). Interacts (via protein kinase domain) with CEBPA (PubMed:20410507, PubMed:26455797). Interacts with RFWD2 (PubMed:20410507, PubMed:27041596).3 Publications
Binary interactionsi
| With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| STK40 | Q8N2I9 | 2 | EBI-492555,EBI-716112 |
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. 23 interactors. |
| DIPi | DIP-34542N. |
| IntActi | Q96RU8. 15 interactors. |
| STRINGi | 9606.ENSP00000312150. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Beta strandi | 89 – 91 | Combined sources | 3 | |
| Beta strandi | 94 – 98 | Combined sources | 5 | |
| Beta strandi | 103 – 110 | Combined sources | 8 | |
| Turni | 111 – 113 | Combined sources | 3 | |
| Beta strandi | 116 – 123 | Combined sources | 8 | |
| Helixi | 124 – 130 | Combined sources | 7 | |
| Helixi | 132 – 135 | Combined sources | 4 | |
| Beta strandi | 137 – 139 | Combined sources | 3 | |
| Turni | 141 – 143 | Combined sources | 3 | |
| Beta strandi | 146 – 151 | Combined sources | 6 | |
| Beta strandi | 153 – 160 | Combined sources | 8 | |
| Helixi | 167 – 174 | Combined sources | 8 | |
| Helixi | 179 – 198 | Combined sources | 20 | |
| Helixi | 208 – 210 | Combined sources | 3 | |
| Beta strandi | 211 – 215 | Combined sources | 5 | |
| Beta strandi | 221 – 223 | Combined sources | 3 | |
| Beta strandi | 240 – 243 | Combined sources | 4 | |
| Helixi | 251 – 254 | Combined sources | 4 | |
| Helixi | 262 – 279 | Combined sources | 18 | |
| Helixi | 289 – 297 | Combined sources | 9 | |
| Beta strandi | 305 – 307 | Combined sources | 3 | |
| Helixi | 309 – 318 | Combined sources | 10 | |
| Helixi | 323 – 325 | Combined sources | 3 | |
| Helixi | 329 – 332 | Combined sources | 4 | |
| Helixi | 336 – 341 | Combined sources | 6 | |
| Beta strandi | 360 – 362 | Combined sources | 3 |
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 | [»] | ||||
| ProteinModelPortali | Q96RU8. | |||||
| SMRi | Q96RU8. | |||||
| ModBasei | Search... | |||||
| MobiDBi | 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. COG0515. LUCA. |
| GeneTreei | ENSGT00880000137914. |
| HOGENOMi | HOG000231872. |
| HOVERGENi | HBG067729. |
| InParanoidi | Q96RU8. |
| KOi | K08814. |
| OMAi | CHQSAIV. |
| OrthoDBi | EOG091G07JM. |
| PhylomeDBi | Q96RU8. |
| TreeFami | TF329785. |
Family and domain databases
| InterProi | View protein in InterPro IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_dom. IPR024105. TRB1. IPR024104. Tribbles/Ser_Thr_kinase_40. |
| PANTHERi | PTHR22961. PTHR22961. 1 hit. PTHR22961:SF18. PTHR22961:SF18. 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. |
Sequences (2)i
Sequence statusi: Complete.
This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q96RU8-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
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
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:rs16900603Ensembl. | 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] |
| UniGenei | Hs.444947. |
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
Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:| 100% | UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry. |
| 90% | UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence). |
| 50% | UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster. |
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: | June 7, 2017 | |
| This is version 136 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, Complete proteome, Reference proteomeDocuments
- 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 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 - Human and mouse protein kinases
Human and mouse protein kinases: classification and index - SIMILARITY comments
Index of protein domains and families
