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Protein

Tribbles homolog 1

Gene

Trib1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Adapter protein involved in protein degradation by interacting with COP1 ubiquitin ligase (PubMed:23515163, PubMed:20410507). Promotes CEBPA degradation and inhibits its function (PubMed:20410507). Controls macrophage, eosinophil and neutrophil differentiation via the COP1-binding domain (PubMed:24003916, PubMed:23515163). Regulates myeloid cell differentiation by altering the expression of CEBPA in a COP1-dependent manner (PubMed:23515163). Interacts with MAPK kinases and regulates activation of MAP kinases, but has no kinase activity (By similarity).By similarity3 Publications

GO - Molecular functioni

  • mitogen-activated protein kinase kinase binding Source: MGI
  • protein kinase inhibitor activity Source: MGI
  • 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: MGI
  • negative regulation of DNA binding transcription factor activity Source: BHF-UCL
  • negative regulation of lipopolysaccharide-mediated signaling pathway Source: MGI
  • negative regulation of neutrophil differentiation Source: CACAO
  • negative regulation of protein kinase activity Source: MGI
  • negative regulation of smooth muscle cell migration Source: MGI
  • negative regulation of smooth muscle cell proliferation Source: MGI
  • positive regulation of eosinophil differentiation Source: CACAO
  • positive regulation of macrophage differentiation Source: CACAO
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL
  • positive regulation of ubiquitin-protein transferase activity Source: BHF-UCL
  • regulation of MAP kinase activity Source: UniProtKB
  • response to lipopolysaccharide Source: BHF-UCL

Keywordsi

Molecular functionProtein kinase inhibitor

Names & Taxonomyi

Protein namesi
Recommended name:
Tribbles homolog 1
Short name:
TRB-1
Gene namesi
Name:Trib1Imported
Synonyms:Trb1Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:2443397 Trib1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001318601 – 372Tribbles homolog 1Add BLAST372

Proteomic databases

PaxDbiQ8K4K4
PRIDEiQ8K4K4

PTM databases

iPTMnetiQ8K4K4
PhosphoSitePlusiQ8K4K4

Expressioni

Gene expression databases

BgeeiENSMUSG00000032501
CleanExiMM_TRIB1
GenevisibleiQ8K4K4 MM

Interactioni

Subunit structurei

Monomer. Interacts (via protein kinase domain) with CEBPA. Interacts with COP1.By similarity

GO - Molecular functioni

  • mitogen-activated protein kinase kinase binding Source: MGI
  • transcription factor binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi229263, 3 interactors
IntActiQ8K4K4, 1 interactor
STRINGi10090.ENSMUSP00000068834

Structurei

3D structure databases

ProteinModelPortaliQ8K4K4
SMRiQ8K4K4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 338Protein kinasePROSITE-ProRule annotationAdd BLAST338

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi355 – 360COP1-binding1 Publication6

Domaini

The COP1-binding motif (355-360) is required for regulation activity (PubMed:24003916).1 Publication
The C-terminus (351-372) is required for interaction with COP1 (By similarity).By similarity
The protein kinase active site is incompatible with ATP binding and is inactive (By similarity).By similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0583 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00900000140868
HOGENOMiHOG000231872
HOVERGENiHBG067729
InParanoidiQ8K4K4
KOiK08814
OMAiCHQSAIV
OrthoDBiEOG091G07JM
PhylomeDBiQ8K4K4
TreeFamiTF329785

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR024105 TRB1
IPR024104 Tribbles/Ser_Thr_kinase_40
PANTHERiPTHR22961 PTHR22961, 1 hit
PTHR22961:SF17 PTHR22961:SF17, 1 hit
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView 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 11 Publication (identifier: Q8K4K4-1) [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.

« Hide

        10         20         30         40         50
MRVGPVRFAL SGASQPRGPG LLFPAARGTP AKRLLDTDDA GAVAAKCPRL
60 70 80 90 100
SECSSPPDYL SPPGSPCSPQ PPPSTQGTGG SCVSSPGPSR IADYLLLPLA
110 120 130 140 150
EREHVSRALC IHTGRELRCK EFPIKHYQDK IRPYIQLPSH SNITGIVEVL
160 170 180 190 200
LGESKAYVFF EKDFGDMHSY VRSRKRLREE EAARLFKQIV SAVAHCHQSA
210 220 230 240 250
IVLGDLKLRK FVFSTEERTQ LRLESLEDTH IIKGEDDALS DKHGCPAYVS
260 270 280 290 300
PEILNTTGTY SGKAADVWSL GVMLYTLLVG RYPFHDSDPS ALFSKIRRGQ
310 320 330 340 350
FCIPEHVSPK ARCLIRSLLR REPSERLTAP QILLHPWFEY VLEPGYVDSE
360 370
IGTSDQIVPE YQEDSDISSF FC
Length:372
Mass (Da):41,281
Last modified:December 6, 2005 - v2
Checksum:iAD29BB4E640B4B62
GO
Isoform 2Curated (identifier: Q8K4K4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     219-372: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:218
Mass (Da):23,907
Checksum:iF3A5AFE16E3450A8
GO

Sequence cautioni

The sequence BAC28245 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC37854 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti224E → G in AAM45478 (PubMed:15299019).Curated1
Sequence conflicti278L → W in AAM45478 (PubMed:15299019).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_051888219 – 372Missing in isoform 2. 1 PublicationAdd BLAST154

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF358866 mRNA Translation: AAM45478.1
AK028626 mRNA Translation: BAC26038.1
AK033358 mRNA Translation: BAC28245.1 Different initiation.
AK040738 mRNA Translation: BAC30688.1
AK041212 mRNA Translation: BAC30865.1
AK080228 mRNA Translation: BAC37854.1 Different initiation.
AK162876 mRNA Translation: BAE37097.1
BC006800 mRNA Translation: AAH06800.1
CCDSiCCDS27499.1 [Q8K4K4-1]
RefSeqiNP_653132.1, NM_144549.4 [Q8K4K4-1]
UniGeneiMm.40298

Genome annotation databases

EnsembliENSMUST00000067543; ENSMUSP00000068834; ENSMUSG00000032501 [Q8K4K4-1]
ENSMUST00000118228; ENSMUSP00000112828; ENSMUSG00000032501 [Q8K4K4-2]
GeneIDi211770
KEGGimmu:211770
UCSCiuc007vxw.1 mouse [Q8K4K4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiTRIB1_MOUSE
AccessioniPrimary (citable) accession number: Q8K4K4
Secondary accession number(s): Q8BFS7
, Q8BJR9, Q8BZX3, Q91W04
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: December 6, 2005
Last modified: April 25, 2018
This is version 126 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health