TRIB3_RAT
ID TRIB3_RAT Reviewed; 349 AA.
AC Q9WTQ6; Q5BKD1;
DT 01-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Tribbles homolog 3;
DE Short=TRB-3;
DE AltName: Full=Neuronal cell death-inducible putative kinase;
GN Name=Trib3; Synonyms=Nipk;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Neuron;
RX PubMed=10329375; DOI=10.1006/bbrc.1999.0576;
RA Mayumi-Matsuda K., Kojima S., Suzuki H., Sakata T.;
RT "Identification of a novel kinase-like gene induced during neuronal cell
RT death.";
RL Biochem. Biophys. Res. Commun. 258:260-264(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION.
RX PubMed=15469416; DOI=10.1042/bj20041425;
RA Iynedjian P.B.;
RT "Lack of evidence for a role of TRB3/NIPK as inhibitor of PKB-mediated
RT insulin signaling in primary hepatocytes.";
RL Biochem. J. 386:113-118(2005).
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 (By similarity).
CC Disrupts insulin signaling by binding directly to Akt kinases and
CC blocking their activation (PubMed:15469416). May bind directly to and
CC mask the 'Thr-308' phosphorylation site in AKT1 (By similarity).
CC Interacts with the NF-kappa-B transactivator p65 RELA and inhibits its
CC phosphorylation and thus its transcriptional activation activity.
CC Interacts with MAPK kinases and regulates activation of MAP kinases (By
CC similarity). Can inhibit APOBEC3A editing of nuclear DNA (By
CC similarity). {ECO:0000250|UniProtKB:Q8K4K2,
CC ECO:0000250|UniProtKB:Q96RU7, ECO:0000269|PubMed:15469416}.
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 -!- TISSUE SPECIFICITY: Detected only in the lung. Not detected in the
CC heart, brain, spleen, liver, skeletal muscle, kidney and testis.
CC -!- INDUCTION: Expression induced during programmed cell death evoked in
CC neuronal cells by NGF-depletion.
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}.
CC -!- CAUTION: The role of this protein in Akt activation has been
CC demonstrated by Du et al for the mouse ortholog but PubMed:15469416 has
CC not been able to reproduce the result in rat hepatocytes.
CC {ECO:0000305}.
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DR EMBL; AB020967; BAA77582.1; -; mRNA.
DR EMBL; BC091120; AAH91120.1; -; mRNA.
DR RefSeq; NP_653356.1; NM_144755.2.
DR AlphaFoldDB; Q9WTQ6; -.
DR SMR; Q9WTQ6; -.
DR BioGRID; 251567; 1.
DR STRING; 10116.ENSRNOP00000009840; -.
DR PaxDb; Q9WTQ6; -.
DR Ensembl; ENSRNOT00000009840; ENSRNOP00000009840; ENSRNOG00000007319.
DR GeneID; 246273; -.
DR KEGG; rno:246273; -.
DR UCSC; RGD:708432; rat.
DR CTD; 57761; -.
DR RGD; 708432; Trib3.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00950000182986; -.
DR HOGENOM; CLU_000288_13_1_1; -.
DR InParanoid; Q9WTQ6; -.
DR OMA; YFLFERC; -.
DR OrthoDB; 1362510at2759; -.
DR PhylomeDB; Q9WTQ6; -.
DR TreeFam; TF329785; -.
DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR Reactome; R-RNO-165158; Activation of AKT2.
DR Reactome; R-RNO-199418; Negative regulation of the PI3K/AKT network.
DR Reactome; R-RNO-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-RNO-5218920; VEGFR2 mediated vascular permeability.
DR PRO; PR:Q9WTQ6; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000007319; Expressed in jejunum and 15 other tissues.
DR Genevisible; Q9WTQ6; RN.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0003714; F:transcription corepressor activity; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0055106; F:ubiquitin-protein transferase regulator activity; ISO:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; ISO:RGD.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; ISO:RGD.
DR GO; GO:0012501; P:programmed cell death; NAS:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0010506; P:regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0010827; P:regulation of glucose transmembrane transport; ISO:RGD.
DR GO; GO:0043405; P:regulation of MAP kinase activity; ISS:UniProtKB.
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..349
FT /note="Tribbles homolog 3"
FT /id="PRO_0000131868"
FT DOMAIN 63..310
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..122
FT /note="Interaction with DDIT3/CHOP"
FT /evidence="ECO:0000250"
FT REGION 35..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 317..349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 317..332
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 349 AA; 38602 MW; 3050F9BFE946D815 CRC64;
MRATSLAASA DVPCRKKPLE FDDNIDVECP VLKRVRDEPE PGPTPSLPPA SDLSPAVAPA
TRLGPYILLE REQGNCTYRA LHCPTGTEYT CKVYPASEAQ AVLAPYARLP THQHVARPTE
VLLGSQLLYT FFTKTHGDLH SLVRSRRGIP EPEAAALFRQ MASAVAHCHK HGLILRDLKL
RRFVFSNCER TKLVLENLED ACVMTGPDDS LWDKHACPAY VGPEILSSRP SYSGRAADVW
SLGVALFTML AGRYPFQDSE PALLFGKIRR GTFALPEGLS ASARCLIRCL LRREPSERLV
ALGILLHPWL REDCSQVSPP RSDRREMDQV VPDGPQLEEA EEGEVGLYG
