CREB3_HUMAN
ID CREB3_HUMAN Reviewed; 371 AA.
AC O43889; D0PTW6; O14671; O14919; Q5TCV1; Q96GK8; Q9H2W3; Q9UE77;
DT 09-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 2.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Cyclic AMP-responsive element-binding protein 3;
DE Short=CREB-3;
DE Short=cAMP-responsive element-binding protein 3;
DE AltName: Full=Leucine zipper protein;
DE AltName: Full=Luman;
DE AltName: Full=Transcription factor LZIP-alpha;
DE Contains:
DE RecName: Full=Processed cyclic AMP-responsive element-binding protein 3;
DE Short=N-terminal Luman;
DE Short=Transcriptionally active form;
GN Name=CREB3; Synonyms=LZIP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION (ISOFORM 1), DNA-BINDING
RP (ISOFORM 1), INTERACTION WITH HCFC1 (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Cervix carcinoma;
RX PubMed=9271389; DOI=10.1128/mcb.17.9.5117;
RA Lu R., Yang P., O'Hare P., Misra V.;
RT "Luman, a new member of the CREB/ATF family, binds to herpes simplex virus
RT VP16-associated host cellular factor.";
RL Mol. Cell. Biol. 17:5117-5126(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH HCFC1 (ISOFORM
RP 1).
RC TISSUE=Cervix carcinoma;
RX PubMed=9389645; DOI=10.1101/gad.11.23.3122;
RA Freiman R.N., Herr W.;
RT "Viral mimicry: common mode of association with HCF by VP16 and the
RT cellular protein LZIP.";
RL Genes Dev. 11:3122-3127(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), FUNCTION IN CELL
RP PROLIFERATION (MICROBIAL INFECTION), HOMODIMERIZATION, INTERACTION WITH HCV
RP CORE PROTEIN (MICROBIAL INFECTION), DNA-BINDING, AND SUBCELLULAR LOCATION.
RC TISSUE=Fetal liver;
RX PubMed=10675342; DOI=10.1093/emboj/19.4.729;
RA Jin D.-Y., Wang H.-L., Zhou Y., Chun A.C.S., Kibler K.V., Hou Y.-D.,
RA Kung H.-F., Jeang K.-T.;
RT "Hepatitis C virus core protein-induced loss of LZIP function correlates
RT with cellular transformation.";
RL EMBO J. 19:729-740(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING (ISOFORM 1),
RP FUNCTION IN LKN-1-STIMULATED CHEMOTAXIS SIGNALING (ISOFORM 1), FUNCTION IN
RP GLUCOCORTICOID-INDUCED TRANSCRIPTIONAL REPRESSION (ISOFORM 2), SUBCELLULAR
RP LOCATION (ISOFORMS 1 AND 2), TISSUE SPECIFICITY (ISOFORMS 1 AND 2), AND
RP MUTAGENESIS OF 16-LEU-LEU-17 AND 57-LEU-LEU-58.
RX PubMed=19779205; DOI=10.1210/me.2009-0009;
RA Kang H., Kim Y.S., Ko J.;
RT "A novel isoform of human LZIP negatively regulates the transactivation of
RT the glucocorticoid receptor.";
RL Mol. Endocrinol. 23:1746-1757(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Hayashi M., Tanaka T.;
RT "Novel activation and inhibitory domains of LZIP isoforms, retinoic acid-
RT inducible genes in P19 embryonal carcinoma cell, differentially activate
RT transcription in mouse development.";
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RA Ben-Yosef T., Francomano C.A.;
RT "Complete nucleotide sequence and genomic structure of the human cAMP
RT responsive element binding protein 3 (Luman) gene (CREB3).";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas, and Skin;
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 [9]
RP FUNCTION IN HSV-1 INFECTION (MICROBIAL INFECTION), MUTAGENESIS OF TYR-81,
RP AND SUBCELLULAR LOCATION (ISOFORM 1).
RX PubMed=10623756; DOI=10.1128/jvi.74.2.934-943.2000;
RA Lu R., Misra V.;
RT "Potential role for luman, the cellular homologue of herpes simplex virus
RT VP16 (alpha gene trans-inducing factor), in herpesvirus latency.";
RL J. Virol. 74:934-943(2000).
RN [10]
RP INTERACTION WITH HCFC1.
RX PubMed=10629049; DOI=10.1128/mcb.20.3.919-928.2000;
RA Mahajan S.S., Wilson A.C.;
RT "Mutations in host cell factor 1 separate its role in cell proliferation
RT from recruitment of VP16 and LZIP.";
RL Mol. Cell. Biol. 20:919-928(2000).
RN [11]
RP FUNCTION IN TRANSCRIPTIONAL REGULATION (ISOFORM 1), INTERACTION WITH HCFC1,
RP REGION, AND MUTAGENESIS OF 12-LEU-LEU-13; 16-LEU-LEU-17 AND 78-ASP--TYR-81.
RX PubMed=10984507; DOI=10.1073/pnas.190062797;
RA Luciano R.L., Wilson A.C.;
RT "N-terminal transcriptional activation domain of LZIP comprises two LxxLL
RT motifs and the host cell factor-1 binding motif.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:10757-10762(2000).
RN [12]
RP GLYCOSYLATION, SUBCELLULAR LOCATION, TOPOLOGY, PROTEOLYTIC PROCESSING,
RP CLEAVAGE SITE, AND MUTAGENESIS OF ARG-252; ARG-264 AND ARG-267.
RX PubMed=12138176; DOI=10.1128/mcb.22.16.5639-5649.2002;
RA Raggo C., Rapin N., Stirling J., Gobeil P., Smith-Windsor E., O'Hare P.,
RA Misra V.;
RT "Luman, the cellular counterpart of herpes simplex virus VP16, is processed
RT by regulated intramembrane proteolysis.";
RL Mol. Cell. Biol. 22:5639-5649(2002).
RN [13]
RP FUNCTION IN LKN-1-STIMULATED CHEMOTAXIS SIGNALING, AND INTERACTION WITH
RP CCR1.
RX PubMed=15001559; DOI=10.1096/fj.03-0867fje;
RA Ko J., Jang S.W., Kim Y.S., Kim I.S., Sung H.J., Kim H.-H., Park J.Y.,
RA Lee Y.H., Kim J., Na D.S.;
RT "Human LZIP binds to CCR1 and differentially affects the chemotactic
RT activities of CCR1-dependent chemokines.";
RL FASEB J. 18:890-892(2004).
RN [14]
RP FUNCTION IN THE UNFOLDED PROTEIN RESPONSE, DNA-BINDING, AND INDUCTION.
RX PubMed=15845366; DOI=10.1016/j.bbrc.2005.03.141;
RA DenBoer L.M., Hardy-Smith P.W., Hogan M.R., Cockram G.P., Audas T.E.,
RA Lu R.;
RT "Luman is capable of binding and activating transcription from the unfolded
RT protein response element.";
RL Biochem. Biophys. Res. Commun. 331:113-119(2005).
RN [15]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH CREBZF AND HCFC1,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 78-ASP--TYR-81 AND ASN-160.
RX PubMed=15705566; DOI=10.1074/jbc.m500728200;
RA Misra V., Rapin N., Akhova O., Bainbridge M., Korchinski P.;
RT "Zhangfei is a potent and specific inhibitor of the host cell factor-
RT binding transcription factor Luman.";
RL J. Biol. Chem. 280:15257-15266(2005).
RN [16]
RP FUNCTION IN HIV-1 INFECTIVITY (MICROBIAL INFECTION), INTERACTION WITH HIV-1
RP TAT (MICROBIAL INFECTION), INTERACTION WITH HIV-1 TMGP41 (MICROBIAL
RP INFECTION), AND PROTEOLYTIC PROCESSING.
RX PubMed=17054986; DOI=10.1016/j.jmb.2006.09.080;
RA Blot G., Lopez-Verges S., Treand C., Kubat N.J., Delcroix-Genete D.,
RA Emiliani S., Benarous R., Berlioz-Torrent C.;
RT "Luman, a new partner of HIV-1 TMgp41, interferes with Tat-mediated
RT transcription of the HIV-1 LTR.";
RL J. Mol. Biol. 364:1034-1047(2006).
RN [17]
RP FUNCTION IN THE UNFOLDED PROTEIN RESPONSE, DNA-BINDING, GLYCOSYLATION,
RP PROTEOLYTIC PROCESSING, AND INDUCTION.
RX PubMed=16940180; DOI=10.1128/mcb.01046-06;
RA Liang G., Audas T.E., Li Y., Cockram G.P., Dean J.D., Martyn A.C.,
RA Kokame K., Lu R.;
RT "Luman/CREB3 induces transcription of the endoplasmic reticulum (ER) stress
RT response protein Herp through an ER stress response element.";
RL Mol. Cell. Biol. 26:7999-8010(2006).
RN [18]
RP FUNCTION IN LKN-1-STIMULATED CHEMOTAXIS SIGNALING, AND INDUCTION.
RX PubMed=17296613; DOI=10.1074/jbc.m607962200;
RA Jang S.W., Kim Y.S., Kim Y.R., Sung H.J., Ko J.;
RT "Regulation of human LZIP expression by NF-kappaB and its involvement in
RT monocyte cell migration induced by Lkn-1.";
RL J. Biol. Chem. 282:11092-11100(2007).
RN [19]
RP FUNCTION IN TRANSCRIPTIONAL ACTIVATION AND IN PROMOTING CHEMOTAXIS, AND
RP DNA-BINDING.
RX PubMed=18587271; DOI=10.3858/emm.2008.40.3.332;
RA Sung H.J., Kim Y.S., Kang H., Ko J.;
RT "Human LZIP induces monocyte CC chemokine receptor 2 expression leading to
RT enhancement of monocyte chemoattractant protein 1/CCL2-induced cell
RT migration.";
RL Exp. Mol. Med. 40:332-338(2008).
RN [20]
RP INTERACTION WITH CREBRF, PROTEOLYTIC PROCESSING, INDUCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=18391022; DOI=10.1128/mcb.01439-07;
RA Audas T.E., Li Y., Liang G., Lu R.;
RT "A novel protein, Luman/CREB3 recruitment factor, inhibits Luman activation
RT of the unfolded protein response.";
RL Mol. Cell. Biol. 28:3952-3966(2008).
RN [21]
RP INTERACTION WITH DCSTAMP AND OS9, PROTEOLYTIC PROCESSING, INDUCTION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=20546900; DOI=10.1016/j.molimm.2010.04.019;
RA Eleveld-Trancikova D., Sanecka A., van Hout-Kuijer M.A., Looman M.W.,
RA Hendriks I.A., Jansen B.J., Adema G.J.;
RT "DC-STAMP interacts with ER-resident transcription factor LUMAN which
RT becomes activated during DC maturation.";
RL Mol. Immunol. 47:1963-1973(2010).
CC -!- FUNCTION: Endoplasmic reticulum (ER)-bound sequence-specific
CC transcription factor that directly binds DNA and activates
CC transcription (PubMed:9271389, PubMed:19779205, PubMed:10984507,
CC PubMed:15845366, PubMed:16940180). Plays a role in the unfolded protein
CC response (UPR), promoting cell survival versus ER stress-induced
CC apoptotic cell death (PubMed:15845366, PubMed:16940180). Also involved
CC in cell proliferation, migration and differentiation, tumor suppression
CC and inflammatory gene expression. Acts as a positive regulator of LKN-
CC 1/CCL15-induced chemotaxis signaling of leukocyte cell migration
CC (PubMed:19779205, PubMed:15001559, PubMed:17296613). Associates with
CC chromatin to the HERPUD1 promoter (PubMed:16940180). Also induces
CC transcriptional activation of chemokine receptors (PubMed:18587271,
CC PubMed:17296613). {ECO:0000269|PubMed:10984507,
CC ECO:0000269|PubMed:15001559, ECO:0000269|PubMed:15845366,
CC ECO:0000269|PubMed:16940180, ECO:0000269|PubMed:17296613,
CC ECO:0000269|PubMed:18587271, ECO:0000269|PubMed:19779205,
CC ECO:0000269|PubMed:9271389}.
CC -!- FUNCTION: (Microbial infection) Plays a role in human immunodeficiency
CC virus type 1 (HIV-1) virus protein expression.
CC {ECO:0000269|PubMed:17054986}.
CC -!- FUNCTION: [Isoform 1]: (Microbial infection) May play a role as a
CC cellular tumor suppressor that is targeted by the hepatitis C virus
CC (HCV) core protein. {ECO:0000269|PubMed:10675342}.
CC -!- FUNCTION: [Isoform 1]: (Microbial infection) Plays a role in herpes
CC simplex virus-1 (HSV-1) latent infection and reactivation from latency.
CC Represses the VP16-mediated transactivation of immediate early genes of
CC the HSV-1 virus by sequestering host cell factor-1 HCFC1 in the ER
CC membrane of sensory neurons, thereby preventing the initiation of the
CC replicative cascade leading to latent infection.
CC {ECO:0000269|PubMed:10623756, ECO:0000269|PubMed:15705566}.
CC -!- FUNCTION: [Isoform 2]: Functions as a negative transcriptional
CC regulator in ligand-induced transcriptional activation of the
CC glucocorticoid receptor NR3C1 by recruiting and activating histone
CC deacetylases (HDAC1, HDAC2 and HDAC6). Also decreases the acetylation
CC level of histone H4. Does not promote the chemotactic activity of
CC leukocyte cells. {ECO:0000269|PubMed:19779205}.
CC -!- FUNCTION: [Processed cyclic AMP-responsive element-binding protein 3]:
CC This is the transcriptionally active form that translocates to the
CC nucleus and activates unfolded protein response (UPR) target genes
CC during endoplasmic reticulum (ER) stress response. Binds the cAMP
CC response element (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP
CC sequences present in many promoters to activate transcription of the
CC genes. Binds to the unfolded protein response element (UPRE) consensus
CC sequences sites. Binds DNA to the 5'-CCAC[GA]-3'half of ERSE II (5'-
CC ATTGG-N-CCACG-3'). {ECO:0000269|PubMed:16940180}.
CC -!- FUNCTION: [Processed cyclic AMP-responsive element-binding protein 3]:
CC (Microbial infection) Activates transcription of genes required for
CC reactivation of the latent HSV-1 virus. It's transcriptional activity
CC is inhibited by CREBZF in a HCFC1-dependent manner, by the viral
CC transactivator protein VP16. Binds DNA to the cAMP response element
CC (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP sequences present in
CC many viral promoters. {ECO:0000269|PubMed:10623756}.
CC -!- FUNCTION: [Processed cyclic AMP-responsive element-binding protein 3]:
CC (Microbial infection) It's transcriptional activity is inhibited by
CC CREBZF in a HCFC1-dependent manner, by the viral transactivator HCV
CC core protein. {ECO:0000269|PubMed:10675342}.
CC -!- SUBUNIT: Homodimer (PubMed:10675342). Isoform 1 interacts with HCFC1;
CC the interaction is required to stimulate CREB3 transcriptional activity
CC (PubMed:9271389, PubMed:9389645, PubMed:10629049, PubMed:10984507).
CC Isoform 1 interacts with CREBZF; the interaction occurs only in
CC combination with HCFC1 (PubMed:15705566). Isoform 1 interacts (via
CC central part and transmembrane region) with DCSTAMP (via C-terminus
CC cytoplasmic domain) (PubMed:20546900). Isoform 1 interacts with OS9
CC (PubMed:20546900). Isoform 1 interacts (via leucine-zipper domain) with
CC CREBRF (via leucine-zipper domain); the interaction occurs only after
CC CREB3 activation and promotes CREB3 degradation (PubMed:18391022).
CC Isoform 1 interacts (via C-terminal domain) with CCR1
CC (PubMed:15001559). {ECO:0000269|PubMed:10629049,
CC ECO:0000269|PubMed:10675342, ECO:0000269|PubMed:10984507,
CC ECO:0000269|PubMed:15001559, ECO:0000269|PubMed:15705566,
CC ECO:0000269|PubMed:18391022, ECO:0000269|PubMed:20546900,
CC ECO:0000269|PubMed:9271389, ECO:0000269|PubMed:9389645}.
CC -!- SUBUNIT: (Microbial infection) Interacts with the HCV core protein;
CC homodimerization is prevented by the HCV core protein
CC (PubMed:10675342). Isoform 1 interacts (via leucine-zipper and
CC transmembrane domains) with HIV-1 TMgp41 (via cytoplasmic domain); the
CC interaction reduces CREB3 stability (PubMed:17054986). Processed cyclic
CC AMP-responsive element-binding protein 3 interacts with HIV-1 Tat
CC (PubMed:17054986). {ECO:0000269|PubMed:10675342,
CC ECO:0000269|PubMed:17054986}.
CC -!- INTERACTION:
CC O43889; Q92685: ALG3; NbExp=4; IntAct=EBI-625002, EBI-2848814;
CC O43889; O43889: CREB3; NbExp=2; IntAct=EBI-625002, EBI-625002;
CC O43889; Q68CJ9: CREB3L3; NbExp=3; IntAct=EBI-625002, EBI-852194;
CC O43889; Q9NS37: CREBZF; NbExp=3; IntAct=EBI-625002, EBI-632965;
CC O43889; P35638: DDIT3; NbExp=2; IntAct=EBI-625002, EBI-742651;
CC O43889; P51610: HCFC1; NbExp=5; IntAct=EBI-625002, EBI-396176;
CC O43889; P05412: JUN; NbExp=4; IntAct=EBI-625002, EBI-852823;
CC O43889; O00268: TAF4; NbExp=2; IntAct=EBI-625002, EBI-1034261;
CC O43889-2; Q15109: AGER; NbExp=3; IntAct=EBI-625022, EBI-1646426;
CC O43889-2; Q92685: ALG3; NbExp=4; IntAct=EBI-625022, EBI-2848814;
CC O43889-2; Q9BVK2: ALG8; NbExp=3; IntAct=EBI-625022, EBI-3921603;
CC O43889-2; P05090: APOD; NbExp=4; IntAct=EBI-625022, EBI-715495;
CC O43889-2; P29972: AQP1; NbExp=3; IntAct=EBI-625022, EBI-745213;
CC O43889-2; P41181: AQP2; NbExp=3; IntAct=EBI-625022, EBI-12701138;
CC O43889-2; P55087: AQP4; NbExp=3; IntAct=EBI-625022, EBI-10104898;
CC O43889-2; P09871: C1S; NbExp=3; IntAct=EBI-625022, EBI-2810045;
CC O43889-2; P06681: C2; NbExp=3; IntAct=EBI-625022, EBI-2835920;
CC O43889-2; P32246: CCR1; NbExp=7; IntAct=EBI-625022, EBI-608322;
CC O43889-2; Q9UJ71: CD207; NbExp=3; IntAct=EBI-625022, EBI-2873235;
CC O43889-2; Q9BXR6: CFHR5; NbExp=3; IntAct=EBI-625022, EBI-11579371;
CC O43889-2; Q8N6F1-2: CLDN19; NbExp=3; IntAct=EBI-625022, EBI-12256978;
CC O43889-2; Q8IUR6: CREBRF; NbExp=4; IntAct=EBI-625022, EBI-1042699;
CC O43889-2; P78329: CYP4F2; NbExp=3; IntAct=EBI-625022, EBI-1752413;
CC O43889-2; Q9H295: DCSTAMP; NbExp=6; IntAct=EBI-625022, EBI-6095316;
CC O43889-2; Q15125: EBP; NbExp=3; IntAct=EBI-625022, EBI-3915253;
CC O43889-2; P50402: EMD; NbExp=3; IntAct=EBI-625022, EBI-489887;
CC O43889-2; P37268: FDFT1; NbExp=3; IntAct=EBI-625022, EBI-714550;
CC O43889-2; Q01740: FMO1; NbExp=3; IntAct=EBI-625022, EBI-12701460;
CC O43889-2; P31513: FMO3; NbExp=4; IntAct=EBI-625022, EBI-12361463;
CC O43889-2; P17302: GJA1; NbExp=4; IntAct=EBI-625022, EBI-1103439;
CC O43889-2; A0A0C4DFT7: GYPA; NbExp=3; IntAct=EBI-625022, EBI-12044847;
CC O43889-2; P51610: HCFC1; NbExp=4; IntAct=EBI-625022, EBI-396176;
CC O43889-2; P24593: IGFBP5; NbExp=4; IntAct=EBI-625022, EBI-720480;
CC O43889-2; Q8TAF8: LHFPL5; NbExp=4; IntAct=EBI-625022, EBI-2820517;
CC O43889-2; Q6FG55: LTA; NbExp=3; IntAct=EBI-625022, EBI-11984863;
CC O43889-2; Q99735: MGST2; NbExp=3; IntAct=EBI-625022, EBI-11324706;
CC O43889-2; Q99519: NEU1; NbExp=3; IntAct=EBI-625022, EBI-721517;
CC O43889-2; P26678: PLN; NbExp=3; IntAct=EBI-625022, EBI-692836;
CC O43889-2; P60201-2: PLP1; NbExp=3; IntAct=EBI-625022, EBI-12188331;
CC O43889-2; Q01453: PMP22; NbExp=3; IntAct=EBI-625022, EBI-2845982;
CC O43889-2; P05155: SERPING1; NbExp=3; IntAct=EBI-625022, EBI-1223454;
CC O43889-2; P11686: SFTPC; NbExp=3; IntAct=EBI-625022, EBI-10197617;
CC O43889-2; Q9BZD2: SLC29A3; NbExp=3; IntAct=EBI-625022, EBI-12701374;
CC O43889-2; P11166: SLC2A1; NbExp=3; IntAct=EBI-625022, EBI-717153;
CC O43889-2; P14672: SLC2A4; NbExp=3; IntAct=EBI-625022, EBI-367146;
CC O43889-2; Q9BRI3: SLC30A2; NbExp=3; IntAct=EBI-625022, EBI-8644112;
CC O43889-2; P82251: SLC7A9; NbExp=3; IntAct=EBI-625022, EBI-3936589;
CC O43889-2; O43759-2: SYNGR1; NbExp=3; IntAct=EBI-625022, EBI-12187159;
CC O43889-2; Q8TAA9: VANGL1; NbExp=3; IntAct=EBI-625022, EBI-682393;
CC O43889-2; Q9Y397: ZDHHC9; NbExp=3; IntAct=EBI-625022, EBI-12690113;
CC O43889-2; P29846; Xeno; NbExp=8; IntAct=EBI-625022, EBI-909718;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10623756, ECO:0000269|PubMed:12138176,
CC ECO:0000269|PubMed:18391022}; Single-pass type II membrane protein
CC {ECO:0000255, ECO:0000269|PubMed:12138176}. Golgi apparatus
CC {ECO:0000269|PubMed:10623756}. Note=Colocalizes with HCFC1 in neuronal
CC cell bodies of the trigeminal ganglia (PubMed:10623756). Colocalizes
CC with DCSTAMP in the ER membrane of immature dendritic cell (DC)
CC (PubMed:20546900). Colocalizes with CANX, CCR1, HCFC1 in the ER
CC membrane (PubMed:10623756). {ECO:0000269|PubMed:10623756,
CC ECO:0000269|PubMed:20546900}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. Note=(Microbial
CC infection) Sequestered into the cytoplasm by the HCV core protein.
CC {ECO:0000269|PubMed:10675342}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus
CC {ECO:0000269|PubMed:19779205}. Cytoplasm {ECO:0000269|PubMed:19779205}.
CC Note=Predominantly in the nucleus (PubMed:19779205). Not associated
CC with membranes (PubMed:19779205). {ECO:0000269|PubMed:19779205}.
CC -!- SUBCELLULAR LOCATION: [Processed cyclic AMP-responsive element-binding
CC protein 3]: Nucleus. Note=Upon RIP activation the transcriptional
CC active processed cyclic AMP-responsive element-binding protein 3 form
CC translocates into the nucleus. Detected in the nucleus upon dendritic
CC cell maturation and RIP activation. Colocalizes with CREBRF in nuclear
CC foci. Colocalizes with CREBZF in promyelocytic leukemia protein nuclear
CC bodies (PML-NB). {ECO:0000269|PubMed:10675342,
CC ECO:0000269|PubMed:15705566, ECO:0000269|PubMed:18391022,
CC ECO:0000269|PubMed:20546900}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=LZIP;
CC IsoId=O43889-2; Sequence=Displayed;
CC Name=2; Synonyms=small LZIP, sLZIP;
CC IsoId=O43889-3; Sequence=VSP_059386;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed (PubMed:9271389,
CC PubMed:19779205). Expressed in dendritic cells (DC). Weakly expressed
CC in monocytes (at protein level) (PubMed:20546900).
CC {ECO:0000269|PubMed:19779205, ECO:0000269|PubMed:20546900,
CC ECO:0000269|PubMed:9271389}.
CC -!- INDUCTION: Up-regulated upon differentiation of monocytes towards
CC immature dendritic cells (DC). Down-regulated upon DC maturation. Up-
CC regulated by endoplasmic reticulum stress triggered by thapsigargin
CC (Tg) or tunicamycin (Tm). Up-regulated by CCR1-dependent chemokines in
CC an immediate early response and biphasic manner and by NF-kappa-B.
CC {ECO:0000269|PubMed:15845366, ECO:0000269|PubMed:16940180,
CC ECO:0000269|PubMed:17296613, ECO:0000269|PubMed:18391022,
CC ECO:0000269|PubMed:20546900}.
CC -!- PTM: First proteolytically cleaved by site-1 protease (S1P) that
CC generates membrane-associated N-terminus and a luminal C-terminus
CC forms. The membrane-associated N-terminus form is further
CC proteolytically processed probably by the site-2 protease (S2P) through
CC a regulated intramembrane proteolysis (RIP), releasing the
CC transcriptional active processed cyclic AMP-responsive element-binding
CC protein 3 form, which is transported to the nucleus. The proteolytic
CC cleavage is strongly induced during dendritic cell (DC) maturation and
CC inhibited by DCSTAMP. That form is rapidly degraded.
CC {ECO:0000269|PubMed:12138176, ECO:0000269|PubMed:16940180,
CC ECO:0000269|PubMed:17054986, ECO:0000269|PubMed:18391022,
CC ECO:0000269|PubMed:20546900}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:12138176,
CC ECO:0000269|PubMed:16940180}.
CC -!- MISCELLANEOUS: [Isoform 2]: Does not contain a helical transmembrane
CC domain. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the bZIP family. ATF subfamily. {ECO:0000305}.
CC -!- CAUTION: All experiments concerning the proteolytic cleavage are done
CC with isoform 1. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC04325.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; AF009368; AAB69652.1; -; mRNA.
DR EMBL; AF029674; AAB84166.1; -; mRNA.
DR EMBL; U59629; AAD09210.1; -; Genomic_DNA.
DR EMBL; FJ263669; ACN32251.1; -; mRNA.
DR EMBL; U88528; AAC04325.1; ALT_SEQ; mRNA.
DR EMBL; AF211847; AAG43527.1; -; Genomic_DNA.
DR EMBL; AF211848; AAG43528.1; -; mRNA.
DR EMBL; AL133410; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009402; AAH09402.1; -; mRNA.
DR EMBL; BC010158; AAH10158.1; -; mRNA.
DR CCDS; CCDS6588.1; -. [O43889-2]
DR RefSeq; NP_006359.3; NM_006368.4. [O43889-2]
DR AlphaFoldDB; O43889; -.
DR SMR; O43889; -.
DR BioGRID; 115751; 240.
DR ComplexPortal; CPX-6541; bZIP transcription factor complex, ATF4-CREB3.
DR ComplexPortal; CPX-7109; bZIP transcription factor complex, BATF3-CREB3.
DR DIP; DIP-33935N; -.
DR ELM; O43889; -.
DR IntAct; O43889; 231.
DR MINT; O43889; -.
DR STRING; 9606.ENSP00000342136; -.
DR GlyGen; O43889; 2 sites.
DR iPTMnet; O43889; -.
DR PhosphoSitePlus; O43889; -.
DR BioMuta; CREB3; -.
DR jPOST; O43889; -.
DR MassIVE; O43889; -.
DR PeptideAtlas; O43889; -.
DR PRIDE; O43889; -.
DR ProteomicsDB; 49217; -. [O43889-2]
DR ProteomicsDB; 49218; -. [O43889-3]
DR Antibodypedia; 26018; 259 antibodies from 31 providers.
DR DNASU; 10488; -.
DR Ensembl; ENST00000353704.3; ENSP00000342136.2; ENSG00000107175.12. [O43889-2]
DR GeneID; 10488; -.
DR KEGG; hsa:10488; -.
DR MANE-Select; ENST00000353704.3; ENSP00000342136.2; NM_006368.5; NP_006359.3.
DR UCSC; uc003zxv.4; human. [O43889-2]
DR CTD; 10488; -.
DR DisGeNET; 10488; -.
DR GeneCards; CREB3; -.
DR HGNC; HGNC:2347; CREB3.
DR HPA; ENSG00000107175; Low tissue specificity.
DR MIM; 606443; gene.
DR neXtProt; NX_O43889; -.
DR OpenTargets; ENSG00000107175; -.
DR PharmGKB; PA26865; -.
DR VEuPathDB; HostDB:ENSG00000107175; -.
DR eggNOG; KOG0709; Eukaryota.
DR GeneTree; ENSGT00940000160343; -.
DR HOGENOM; CLU_047257_0_0_1; -.
DR InParanoid; O43889; -.
DR OMA; CLLYHMP; -.
DR OrthoDB; 644485at2759; -.
DR PhylomeDB; O43889; -.
DR TreeFam; TF316079; -.
DR PathwayCommons; O43889; -.
DR Reactome; R-HSA-8874211; CREB3 factors activate genes.
DR SignaLink; O43889; -.
DR SIGNOR; O43889; -.
DR BioGRID-ORCS; 10488; 18 hits in 1102 CRISPR screens.
DR ChiTaRS; CREB3; human.
DR GeneWiki; CREB3; -.
DR GenomeRNAi; 10488; -.
DR Pharos; O43889; Tbio.
DR PRO; PR:O43889; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; O43889; protein.
DR Bgee; ENSG00000107175; Expressed in adenohypophysis and 188 other tissues.
DR Genevisible; O43889; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IMP:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IPI:ComplexPortal.
DR GO; GO:0035497; F:cAMP response element binding; IEA:InterPro.
DR GO; GO:0008140; F:cAMP response element binding protein binding; IDA:UniProtKB.
DR GO; GO:0031726; F:CCR1 chemokine receptor binding; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IMP:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046983; F:protein dimerization activity; TAS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0001221; F:transcription coregulator binding; IPI:UniProtKB.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0042994; P:cytoplasmic sequestering of transcription factor; IDA:UniProtKB.
DR GO; GO:0019043; P:establishment of viral latency; IDA:UniProtKB.
DR GO; GO:0050930; P:induction of positive chemotaxis; IDA:UniProtKB.
DR GO; GO:0140467; P:integrated stress response signaling; IC:ComplexPortal.
DR GO; GO:0045786; P:negative regulation of cell cycle; NAS:UniProtKB.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0090045; P:positive regulation of deacetylase activity; IDA:UniProtKB.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IDA:UniProtKB.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006990; P:positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response; IDA:ParkinsonsUK-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0019046; P:release from viral latency; IDA:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IDA:UniProtKB.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR029808; Luman.
DR PANTHER; PTHR45996:SF4; PTHR45996:SF4; 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; Alternative splicing; Chemotaxis; Cytoplasm; DNA-binding;
KW Endoplasmic reticulum; Glycoprotein; Golgi apparatus;
KW Host-virus interaction; Membrane; Nucleus; Reference proteome; Repeat;
KW Repressor; Signal-anchor; Transcription; Transcription regulation;
KW Transmembrane; Transmembrane helix; Unfolded protein response.
FT CHAIN 1..371
FT /note="Cyclic AMP-responsive element-binding protein 3"
FT /id="PRO_0000076602"
FT CHAIN 1..?
FT /note="Processed cyclic AMP-responsive element-binding
FT protein 3"
FT /id="PRO_0000296204"
FT TOPO_DOM 1..230
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:12138176"
FT TRANSMEM 231..247
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 248..371
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:12138176"
FT DOMAIN 150..213
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 1..92
FT /note="Transcription activation (acidic)"
FT /evidence="ECO:0000269|PubMed:10984507"
FT REGION 152..184
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 192..213
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT MOTIF 13..17
FT /note="LXXLL motif 1"
FT MOTIF 54..58
FT /note="LXXLL motif 2"
FT MOTIF 78..81
FT /note="HCFC1-binding-motif (HBM)"
FT SITE 263..264
FT /note="Cleavage; by PS1"
FT /evidence="ECO:0000269|PubMed:12138176"
FT SITE 266..267
FT /note="Cleavage; by PS1"
FT /evidence="ECO:0000269|PubMed:12138176"
FT CARBOHYD 307
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 348
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 229..245
FT /note="Missing (in isoform 2)"
FT /id="VSP_059386"
FT MUTAGEN 12..13
FT /note="LL->AA: Does not inhibit interaction with HCFC1.
FT Reduces transcriptional activation. Inhibits strongly
FT transcriptional activation; when associated with 56-A-A-57
FT and 78-A--A-81 (isoform 1)."
FT /evidence="ECO:0000269|PubMed:10984507"
FT MUTAGEN 16..17
FT /note="LL->AA: Does not affect the transcriptional
FT activation of the glucocorticoid receptor NR3C1; when
FT associated with 57-A-A-58 (isoform 2)."
FT /evidence="ECO:0000269|PubMed:10984507,
FT ECO:0000269|PubMed:19779205"
FT MUTAGEN 57..58
FT /note="LL->AA: Does not affect the transcriptional
FT activation of the glucocorticoid receptor NR3C1; when
FT associated with 16-A-A-17 (isoform 2)."
FT /evidence="ECO:0000269|PubMed:19779205"
FT MUTAGEN 57..58
FT /note="LL->AA: Does not inhibit interaction with HCFC1.
FT Reduces transcriptional activation. Inhibits strongly
FT transcriptional activation; when associated with 12-A-A-13
FT and 78-A--A-81 (isoform 1)."
FT /evidence="ECO:0000269|PubMed:19779205"
FT MUTAGEN 78..81
FT /note="DHTY->AAAA: Inhibits interaction with HCFC1. Reduces
FT transcriptional activation. Inhibits strongly
FT transcriptional activation; when associated with 12-A-A-13
FT and 56-A-A-57. Colocalizes with HCFC1 in the nucleus
FT (isoform 1)."
FT /evidence="ECO:0000269|PubMed:10984507,
FT ECO:0000269|PubMed:15705566"
FT MUTAGEN 81
FT /note="Y->A: Does not retain HCFC1 in the cytoplasm, does
FT not interact with HCFC1, does not activate promoter and
FT fail to protect cells from a productive infection by HSV-
FT 1."
FT /evidence="ECO:0000269|PubMed:10623756"
FT MUTAGEN 160
FT /note="N->G: Does not bind to DNA but retains its ability
FT to interact with HCFC1. Reduces transcriptional activation
FT of unfolded protein response elements (UPRE)-containing
FT promoter. Colocalizes with HCFC1 in the ER membrane."
FT /evidence="ECO:0000269|PubMed:15705566"
FT MUTAGEN 252
FT /note="R->A: Does not inhibit proteolytic cleavage and
FT transcriptional activation."
FT /evidence="ECO:0000269|PubMed:12138176"
FT MUTAGEN 264
FT /note="R->G: Inhibits proteolytic cleavage and
FT transcriptional activation."
FT /evidence="ECO:0000269|PubMed:12138176"
FT MUTAGEN 267
FT /note="R->G: Inhibits proteolytic cleavage and
FT transcriptional activation."
FT /evidence="ECO:0000269|PubMed:12138176"
FT CONFLICT 21
FT /note="G -> E (in Ref. 6; AAG43527)"
FT /evidence="ECO:0000305"
FT CONFLICT 230
FT /note="C -> G (in Ref. 3; AAD09210)"
FT /evidence="ECO:0000305"
FT CONFLICT 246
FT /note="M -> I (in Ref. 8; AAH09402)"
FT /evidence="ECO:0000305"
FT CONFLICT 262
FT /note="L -> C (in Ref. 3; AAD09210)"
FT /evidence="ECO:0000305"
FT CONFLICT 333
FT /note="F -> S (in Ref. 1; AAB69652)"
FT /evidence="ECO:0000305"
FT CONFLICT 338
FT /note="C -> V (in Ref. 3; AAD09210)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 371 AA; 41379 MW; 82152E496B924EEC CRC64;
MELELDAGDQ DLLAFLLEES GDLGTAPDEA VRAPLDWALP LSEVPSDWEV DDLLCSLLSP
PASLNILSSS NPCLVHHDHT YSLPRETVSM DLESESCRKE GTQMTPQHME ELAEQEIARL
VLTDEEKSLL EKEGLILPET LPLTKTEEQI LKRVRRKIRN KRSAQESRRK KKVYVGGLES
RVLKYTAQNM ELQNKVQLLE EQNLSLLDQL RKLQAMVIEI SNKTSSSSTC ILVLLVSFCL
LLVPAMYSSD TRGSLPAEHG VLSRQLRALP SEDPYQLELP ALQSEVPKDS THQWLDGSDC
VLQAPGNTSC LLHYMPQAPS AEPPLEWPFP DLFSEPLCRG PILPLQANLT RKGGWLPTGS
PSVILQDRYS G
