CR3L3_MOUSE
ID CR3L3_MOUSE Reviewed; 479 AA.
AC Q91XE9; Q8BWS0;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Cyclic AMP-responsive element-binding protein 3-like protein 3;
DE Short=cAMP-responsive element-binding protein 3-like protein 3;
DE AltName: Full=Transcription factor CREB-H;
DE Contains:
DE RecName: Full=Processed cyclic AMP-responsive element-binding protein 3-like protein 3;
GN Name=Creb3l3; Synonyms=Crebh;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=C57BL/10; TISSUE=Liver;
RX PubMed=15800215; DOI=10.1093/nar/gki332;
RA Chin K.-T., Zhou H.-J., Wong C.-M., Lee J.M.-F., Chan C.-P., Qiang B.-Q.,
RA Yuan J.-G., Ng I.-O., Jin D.-Y.;
RT "The liver-enriched transcription factor CREB-H is a growth suppressor
RT protein underexpressed in hepatocellular carcinoma.";
RL Nucleic Acids Res. 33:1859-1873(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Ovary, and Uterus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; 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 [4]
RP INDUCTION.
RX PubMed=16469704; DOI=10.1016/j.cell.2005.11.040;
RA Zhang K., Shen X., Wu J., Sakaki K., Saunders T., Rutkowski D.T.,
RA Back S.H., Kaufman R.J.;
RT "Endoplasmic reticulum stress activates cleavage of CREBH to induce a
RT systemic inflammatory response.";
RL Cell 124:587-599(2006).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=21666694; DOI=10.1038/nm.2347;
RA Lee J.H., Giannikopoulos P., Duncan S.A., Wang J., Johansen C.T.,
RA Brown J.D., Plutzky J., Hegele R.A., Glimcher L.H., Lee A.H.;
RT "The transcription factor cyclic AMP-responsive element-binding protein H
RT regulates triglyceride metabolism.";
RL Nat. Med. 17:812-815(2011).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, AND
RP INTERACTION WITH SYNV1.
RX PubMed=30389664; DOI=10.15252/embj.201898942;
RA Wei J., Chen L., Li F., Yuan Y., Wang Y., Xia W., Zhang Y., Xu Y., Yang Z.,
RA Gao B., Jin C., Melo-Cardenas J., Green R.M., Pan H., Wang J., He F.,
RA Zhang K., Fang D.;
RT "HRD1-ERAD controls production of the hepatokine FGF21 through CREBH
RT polyubiquitination.";
RL EMBO J. 37:0-0(2018).
CC -!- FUNCTION: Transcription factor that may act during endoplasmic
CC reticulum (ER) stress by activating unfolded protein response target
CC genes. Activated in response to cAMP stimulation. Binds to the cAMP
CC response element (CRE). Activates transcription through box-B element
CC (By similarity). Activates transcription through CRE. May function
CC synergistically with ATF6. In acute inflammatory response, may activate
CC expression of acute phase response (APR) genes. May be involved in
CC growth suppression. Regulates FGF21 transcription (PubMed:30389664).
CC Plays a crucial role in the regulation of triglyceride metabolism and
CC is required for the maintenance of normal plasma triglyceride
CC concentrations (PubMed:21666694). {ECO:0000250,
CC ECO:0000269|PubMed:15800215, ECO:0000269|PubMed:21666694,
CC ECO:0000269|PubMed:30389664}.
CC -!- SUBUNIT: Binds DNA as a dimer. May form homodimers (By similarity).
CC Interacts with ATF6 (By similarity). Interacts with SYNV1/HRD1; this
CC interaction leads to CREB3L3 ubiquitination and proteasomal degradation
CC (PubMed:30389664). {ECO:0000250, ECO:0000250|UniProtKB:Q68CJ9,
CC ECO:0000269|PubMed:30389664}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q68CJ9}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q68CJ9}.
CC -!- SUBCELLULAR LOCATION: [Processed cyclic AMP-responsive element-binding
CC protein 3-like protein 3]: Nucleus {ECO:0000250|UniProtKB:Q68CJ9}.
CC Note=Under ER stress the cleaved N-terminal cytoplasmic domain
CC translocates into the nucleus. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in adult liver (at protein level) and
CC small intestine. {ECO:0000269|PubMed:15800215,
CC ECO:0000269|PubMed:21666694, ECO:0000269|PubMed:30389664}.
CC -!- INDUCTION: By IL6. Pro-inflammatory cytokines and lipopolysaccharide
CC activate the UPR and induce cleavage of CREBH in the liver
CC (PubMed:16469704). Down-regulated in the liver during fasting-
CC refeeding. This down-regulation may occur at the postranscriptional
CC level and may be mediated by SYNV1/HRD1, which induces CREB3L3
CC ubiquitination and proteasomal degradation (PubMed:30389664).
CC {ECO:0000269|PubMed:16469704, ECO:0000269|PubMed:30389664}.
CC -!- PTM: Following ER stress a fragment containing the cytoplasmic
CC transcription factor domain is released by proteolysis. The cleavage
CC seems to be performed sequentially by site-1 and site-2 proteases (By
CC similarity). {ECO:0000250}.
CC -!- PTM: N-glycosylation is required for optimal proteolytic activation.
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated at Lys-290 by SYNV1/HRD1 via 'Lys-27'-linked
CC ubiquitin. {ECO:0000250|UniProtKB:Q68CJ9}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice display decreased triglyceride
CC clearance from plasma resulting in hypertriglyceridemia.
CC {ECO:0000269|PubMed:21666694}.
CC -!- SIMILARITY: Belongs to the bZIP family. ATF subfamily. {ECO:0000305}.
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DR EMBL; AF392874; AAM73673.1; -; mRNA.
DR EMBL; AK050186; BAC34115.1; -; mRNA.
DR EMBL; AK077258; BAC36714.1; -; mRNA.
DR EMBL; BC010786; AAH10786.1; -; mRNA.
DR EMBL; BC028820; AAH28820.1; -; mRNA.
DR CCDS; CCDS24043.1; -.
DR RefSeq; NP_663340.1; NM_145365.3.
DR AlphaFoldDB; Q91XE9; -.
DR SMR; Q91XE9; -.
DR BioGRID; 229005; 2.
DR CORUM; Q91XE9; -.
DR STRING; 10090.ENSMUSP00000112836; -.
DR GlyGen; Q91XE9; 3 sites.
DR iPTMnet; Q91XE9; -.
DR PhosphoSitePlus; Q91XE9; -.
DR MaxQB; Q91XE9; -.
DR PaxDb; Q91XE9; -.
DR PRIDE; Q91XE9; -.
DR ProteomicsDB; 285298; -.
DR Antibodypedia; 42393; 66 antibodies from 18 providers.
DR DNASU; 208677; -.
DR Ensembl; ENSMUST00000117422; ENSMUSP00000112836; ENSMUSG00000035041.
DR GeneID; 208677; -.
DR KEGG; mmu:208677; -.
DR UCSC; uc007gfw.1; mouse.
DR CTD; 84699; -.
DR MGI; MGI:2384786; Creb3l3.
DR VEuPathDB; HostDB:ENSMUSG00000035041; -.
DR eggNOG; KOG0709; Eukaryota.
DR GeneTree; ENSGT00940000159261; -.
DR HOGENOM; CLU_047257_1_0_1; -.
DR InParanoid; Q91XE9; -.
DR OMA; PGTWHED; -.
DR OrthoDB; 644485at2759; -.
DR PhylomeDB; Q91XE9; -.
DR TreeFam; TF316079; -.
DR Reactome; R-MMU-8874211; CREB3 factors activate genes.
DR BioGRID-ORCS; 208677; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Creb3l3; mouse.
DR PRO; PR:Q91XE9; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q91XE9; protein.
DR Bgee; ENSMUSG00000035041; Expressed in small intestine Peyer's patch and 88 other tissues.
DR Genevisible; Q91XE9; MM.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0035497; F:cAMP response element binding; IEA:InterPro.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IEA:InterPro.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR029806; CREBH.
DR PANTHER; PTHR45996:SF1; PTHR45996:SF1; 1.
DR Pfam; PF00170; bZIP_1; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 1: Evidence at protein level;
KW Activator; DNA-binding; Endoplasmic reticulum; Glycoprotein;
KW Isopeptide bond; Membrane; Nucleus; Reference proteome; Signal-anchor;
KW Transcription; Transcription regulation; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Unfolded protein response.
FT CHAIN 1..479
FT /note="Cyclic AMP-responsive element-binding protein 3-like
FT protein 3"
FT /id="PRO_0000288075"
FT CHAIN 1..?
FT /note="Processed cyclic AMP-responsive element-binding
FT protein 3-like protein 3"
FT /id="PRO_0000307123"
FT TOPO_DOM 1..317
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 318..338
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 339..479
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 239..302
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 67..144
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..270
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 281..302
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT COMPBIAS 92..114
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 359..360
FT /note="Cleavage; by PS1"
FT /evidence="ECO:0000250"
FT CARBOHYD 411
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 418
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 425
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CROSSLNK 290
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q68CJ9"
FT CONFLICT 270
FT /note="R -> L (in Ref. 2; BAC34115)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 479 AA; 52145 MW; 948A06FE79DB3779 CRC64;
MDGDIAAGKM ASPVCAMAPL DSMEVLDLLF DRQDGILRNV ELAEGWILAR EEQKVLLNSD
SDEFLNCILG PGDSDPSSPL WSPADSDSGI SEDLPSDPQD TPPRSGTEPA NTVARCHTRE
QGKGPCPSYL PSTPCPEPPR TQVQESSVAI DLDMWSTDTL YPEEPAGSPS RFNLTVKELL
LSGGSGDLQQ HSLAASQLLG PGSGHCQELV LTEDEKKLLA KEGVTLPTQL PLTKYEERVL
KKIRRKIRNK QSAQESRKKK KEYIDGLENR MSACTAQNQE LQRKVLHLEK QNLSLLEQLK
HLQALVVQST SKPAHAGTCI AVLLLSFALI ILPSISPFNS NKVDSPGDFV PVRVFSRTLH
NHAASRVAPD VTPGSEVPGP WPDVGTPHKG PSSGGLSADW GNFLEIPMLD NLTEELDNST
LVLANSTEDL GRATLLDWVA SEPLLSPGRV GLEIPGEMWL SWVPRWLRVR LVQDALGVL
