TRIB3_BOVIN
ID TRIB3_BOVIN Reviewed; 357 AA.
AC Q0VCE3;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Tribbles homolog 3;
DE Short=TRB-3;
GN Name=TRIB3;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Placenta;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Inactive protein kinase which acts as a regulator of the
CC integrated stress response (ISR), a process for adaptation to various
CC stress (By similarity). Inhibits the transcriptional activity of
CC DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER
CC stress. May play a role in programmed neuronal cell death but does not
CC appear to affect non-neuronal cells (By similarity). Acts as a negative
CC feedback regulator of the ATF4-dependent transcription during the ISR:
CC while TRIB3 expression is promoted by ATF4, TRIB3 protein interacts
CC with ATF4 and inhibits ATF4 transcription activity. Disrupts insulin
CC signaling by binding directly to Akt kinases and blocking their
CC activation. May bind directly to and mask the 'Thr-308' phosphorylation
CC site in AKT1 (By similarity). Interacts with the NF-kappa-B
CC transactivator p65 RELA and inhibits its phosphorylation and thus its
CC transcriptional activation activity. Interacts with MAPK kinases and
CC regulates activation of MAP kinases (By similarity). Can inhibit
CC APOBEC3A editing of nuclear DNA (By similarity).
CC {ECO:0000250|UniProtKB:Q8K4K2, ECO:0000250|UniProtKB:Q96RU7}.
CC -!- SUBUNIT: Interacts with AKT1, AKT2, MAP2K1 and MAP2K7. Interacts with
CC ATF4 (By similarity). Interacts with DDIT3/CHOP and inhibits its
CC interaction with EP300/P300. Interacts with APOBEC3C (By similarity).
CC Interacts (via N-terminus) with APOBEC3A (By similarity). Interacts
CC with RELA (By similarity). {ECO:0000250|UniProtKB:Q8K4K2,
CC ECO:0000250|UniProtKB:Q96RU7}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8K4K2}.
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. Tribbles subfamily. {ECO:0000305}.
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DR EMBL; BC120209; AAI20210.1; -; mRNA.
DR RefSeq; NP_001069571.1; NM_001076103.1.
DR RefSeq; XP_005214869.1; XM_005214812.3.
DR AlphaFoldDB; Q0VCE3; -.
DR SMR; Q0VCE3; -.
DR STRING; 9913.ENSBTAP00000022616; -.
DR PaxDb; Q0VCE3; -.
DR PRIDE; Q0VCE3; -.
DR Ensembl; ENSBTAT00000022616; ENSBTAP00000022616; ENSBTAG00000017007.
DR GeneID; 538465; -.
DR KEGG; bta:538465; -.
DR CTD; 57761; -.
DR VEuPathDB; HostDB:ENSBTAG00000017007; -.
DR VGNC; VGNC:36310; TRIB3.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00950000182986; -.
DR HOGENOM; CLU_000288_13_1_1; -.
DR InParanoid; Q0VCE3; -.
DR OMA; YFLFERC; -.
DR OrthoDB; 1362510at2759; -.
DR TreeFam; TF329785; -.
DR Reactome; R-BTA-165158; Activation of AKT2.
DR Proteomes; UP000009136; Chromosome 13.
DR Bgee; ENSBTAG00000017007; Expressed in thymus and 83 other tissues.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0003714; F:transcription corepressor activity; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0055106; F:ubiquitin-protein transferase regulator activity; IEA:Ensembl.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IEA:Ensembl.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; IEA:Ensembl.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0032092; P:positive regulation of protein binding; IEA:Ensembl.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0010827; P:regulation of glucose transmembrane transport; IEA:Ensembl.
DR GO; GO:0043405; P:regulation of MAP kinase activity; IBA:GO_Central.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR024104; Tribbles/Ser_Thr_kinase_40.
DR InterPro; IPR024106; Tribbles_TRB3.
DR PANTHER; PTHR22961; PTHR22961; 1.
DR PANTHER; PTHR22961:SF14; PTHR22961:SF14; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; Nucleus; Protein kinase inhibitor; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..357
FT /note="Tribbles homolog 3"
FT /id="PRO_0000284059"
FT DOMAIN 68..316
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..127
FT /note="Interaction with DDIT3/CHOP"
FT /evidence="ECO:0000250"
FT REGION 1..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 333..357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 15..30
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 45..60
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 357 AA; 39657 MW; 18B65E01109CAB6E CRC64;
MRASPLAVPA NAPSRKKRLE LDDDLDTECP SQKQARSGPQ PRLPSCPLTL NPPPAPVHAP
DVTTPSRLGP YVLLEPEEGS RTYRALHCPT GTEYICKVYP ACERLAVLEP YWRLPHHGHV
ARPAEVLAGT QLLYAFFLRP HGDMHSLVRR RRRLPEPEAA ALFRQMAAAL AHCHQHGLVL
RDLKLRRFVF TDRERTKLVL ENLEDACVLT GPDDSLWDKH ACPAYVGPEI LSSRASYSGK
AADVWSLGVA LFTMLAGHYP FQDSEPALLF GKIRRGAFAL PEGLSAPARC LVRCLLRREP
TERLTASGIL LHPWLRENAI PAALPRSRHC EADQVVPEGP GLEEAEEEGE RDMGLYG
