CR3L3_HUMAN
ID CR3L3_HUMAN Reviewed; 461 AA.
AC Q68CJ9; B2R7S6; B7ZL69; M0QYW7; Q6ZMC5; Q96TB9;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 163.
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; ORFNames=HYST1481;
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, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=11353085; DOI=10.1093/nar/29.10.2154;
RA Omori Y., Imai J., Watanabe M., Komatsu T., Suzuki Y., Kataoka K.,
RA Watanabe S., Tanigami A., Sugano S.;
RT "CREB-H: a novel mammalian transcription factor belonging to the CREB/ATF
RT family and functioning via the box-B element with a liver-specific
RT expression.";
RL Nucleic Acids Res. 29:2154-2162(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=15221005; DOI=10.1038/sj.onc.1207782;
RA Yamada S., Ohira M., Horie H., Ando K., Takayasu H., Suzuki Y., Sugano S.,
RA Hirata T., Goto T., Matsunaga T., Hiyama E., Hayashi Y., Ando H., Suita S.,
RA Kaneko M., Sasaki F., Hashizume K., Ohnuma N., Nakagawara A.;
RT "Expression profiling and differential screening between hepatoblastomas
RT and the corresponding normal livers: identification of high expression of
RT the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas.";
RL Oncogene 23:5901-5911(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Ileal mucosa, and Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
RC TISSUE=Brain;
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 [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
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 [8]
RP FUNCTION, PROTEOLYTIC CLEAVAGE, SELF-ASSOCIATION, INTERACTION WITH ATF6,
RP AND MUTAGENESIS OF ARG-361.
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 [9]
RP GLYCOSYLATION AT ASN-413; ASN-420 AND ASN-427.
RX PubMed=20356926; DOI=10.1242/jcs.067819;
RA Chan C.P., Mak T.Y., Chin K.T., Ng I.O., Jin D.Y.;
RT "N-linked glycosylation is required for optimal proteolytic activation of
RT membrane-bound transcription factor CREB-H.";
RL J. Cell Sci. 123:1438-1448(2010).
RN [10]
RP GLYCOSYLATION AT SER-379, STRUCTURE OF CARBOHYDRATES, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=22171320; DOI=10.1074/mcp.m111.013649;
RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
RT "Human urinary glycoproteomics; attachment site specific analysis of N- and
RT O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 11:1-17(2012).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-173, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-294, AND UBIQUITINATION AT
RP LYS-294.
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).
RN [13]
RP FUNCTION, INVOLVEMENT IN HYTG2, VARIANTS HYTG2 46-TRP--LEU-461 DEL;
RP LEU-166; MET-180; ASN-182 AND LYS-240, CHARACTERIZATION OF VARIANTS HYTG2
RP 46-TRP--LEU-461 DEL; LEU-166; MET-180; ASN-182 AND LYS-240, AND VARIANT
RP ARG-105.
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 [14]
RP INVOLVEMENT IN HYTG2.
RX PubMed=26427795; DOI=10.1161/atvbaha.115.306170;
RA Cefalu A.B., Spina R., Noto D., Valenti V., Ingrassia V., Giammanco A.,
RA Panno M.D., Ganci A., Barbagallo C.M., Averna M.R.;
RT "Novel CREB3L3 nonsense mutation in a family with dominant
RT hypertriglyceridemia.";
RL Arterioscler. Thromb. Vasc. Biol. 35:2694-2699(2015).
CC -!- FUNCTION: Transcription factor that may act during endoplasmic
CC reticulum stress by activating unfolded protein response target genes.
CC Activated in response to cAMP stimulation. In vitro, binds to the cAMP
CC response element (CRE) and box-B element. Activates transcription
CC through box-B element. Activates transcription through CRE (By
CC similarity). May function synergistically with ATF6. In acute
CC inflammatory response, may activate expression of acute phase response
CC (APR) genes. May be involved in growth suppression. Regulates FGF21
CC transcription (By similarity). Plays a crucial role in the regulation
CC of triglyceride metabolism and is required for the maintenance of
CC normal plasma triglyceride concentrations (PubMed:21666694).
CC {ECO:0000250, ECO:0000250|UniProtKB:Q91XE9,
CC ECO:0000269|PubMed:11353085, ECO:0000269|PubMed:15800215,
CC ECO:0000269|PubMed:16469704, ECO:0000269|PubMed:21666694}.
CC -!- SUBUNIT: Binds DNA as a dimer (By similarity). May form homodimers
CC (PubMed:16469704). Interacts with ATF6 (PubMed:16469704). Interacts
CC with SYNV1/HRD1; this interaction leads to CREB3L3 ubiquitination and
CC proteasomal degradation (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q91XE9, ECO:0000269|PubMed:16469704}.
CC -!- INTERACTION:
CC Q68CJ9; P18850: ATF6; NbExp=2; IntAct=EBI-852194, EBI-852157;
CC Q68CJ9; Q96LK0: CEP19; NbExp=3; IntAct=EBI-852194, EBI-741885;
CC Q68CJ9; O43889: CREB3; NbExp=3; IntAct=EBI-852194, EBI-625002;
CC Q68CJ9; Q96BA8: CREB3L1; NbExp=2; IntAct=EBI-852194, EBI-6942903;
CC Q68CJ9; Q68CJ9: CREB3L3; NbExp=2; IntAct=EBI-852194, EBI-852194;
CC Q68CJ9; Q8NBI2: CYB561A3; NbExp=3; IntAct=EBI-852194, EBI-10269179;
CC Q68CJ9; Q9C005: DPY30; NbExp=3; IntAct=EBI-852194, EBI-744973;
CC Q68CJ9; Q969F0: FATE1; NbExp=3; IntAct=EBI-852194, EBI-743099;
CC Q68CJ9; O00155: GPR25; NbExp=3; IntAct=EBI-852194, EBI-10178951;
CC Q68CJ9; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-852194, EBI-348259;
CC Q68CJ9; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-852194, EBI-12070086;
CC Q68CJ9; Q16649: NFIL3; NbExp=2; IntAct=EBI-852194, EBI-3951858;
CC Q68CJ9; Q02094: RHAG; NbExp=3; IntAct=EBI-852194, EBI-14772355;
CC Q68CJ9; Q96GQ5: RUSF1; NbExp=3; IntAct=EBI-852194, EBI-8636004;
CC Q68CJ9; O43765: SGTA; NbExp=3; IntAct=EBI-852194, EBI-347996;
CC Q68CJ9; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-852194, EBI-744081;
CC Q68CJ9; Q9NVC3: SLC38A7; NbExp=3; IntAct=EBI-852194, EBI-10314552;
CC Q68CJ9; Q9NUM3: SLC39A9; NbExp=3; IntAct=EBI-852194, EBI-2823239;
CC Q68CJ9; Q13190: STX5; NbExp=3; IntAct=EBI-852194, EBI-714206;
CC Q68CJ9; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-852194, EBI-11955057;
CC Q68CJ9; Q8WW34-2: TMEM239; NbExp=3; IntAct=EBI-852194, EBI-11528917;
CC Q68CJ9; Q9Y228: TRAF3IP3; NbExp=3; IntAct=EBI-852194, EBI-765817;
CC Q68CJ9; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-852194, EBI-751210;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11353085}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:11353085}.
CC -!- SUBCELLULAR LOCATION: [Processed cyclic AMP-responsive element-binding
CC protein 3-like protein 3]: Nucleus {ECO:0000269|PubMed:30389664}.
CC Note=Under ER stress the cleaved N-terminal cytoplasmic domain
CC translocates into the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q68CJ9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q68CJ9-2; Sequence=VSP_025637;
CC Name=3;
CC IsoId=Q68CJ9-4; Sequence=VSP_054876;
CC Name=4;
CC IsoId=Q68CJ9-5; Sequence=VSP_055635, VSP_055636;
CC -!- TISSUE SPECIFICITY: Exclusively expressed in liver. Underexpressed in
CC hepatocellular carcinoma tissues. {ECO:0000269|PubMed:11353085,
CC ECO:0000269|PubMed:15800215}.
CC -!- PTM: Controlled by regulated intramembrane proteolysis (RIP). Following
CC ER stress a fragment containing the cytoplasmic transcription factor
CC domain is released by proteolysis. The cleavage seems to be performed
CC sequentially by site-1 and site-2 proteases (PS1 and PS2).
CC {ECO:0000269|PubMed:16469704}.
CC -!- PTM: N- and O-glycosylated. N-glycosylation is required for optimal
CC proteolytic activation. O-glycosylated with core 1 or possibly core 8
CC glycans. {ECO:0000269|PubMed:20356926, ECO:0000269|PubMed:22171320}.
CC -!- PTM: Ubiquitinated at Lys-294 by SYNV1/HRD1 via 'Lys-27'-linked
CC ubiquitin. {ECO:0000269|PubMed:30389664}.
CC -!- DISEASE: Hypertriglyceridemia 2 (HYTG2) [MIM:619324]: An autosomal
CC dominant form of hypertriglyceridemia, a disorder characterized by
CC elevated plasma triglyceride levels. HYTG2 patients also have increased
CC total cholesterol levels and low levels of high density lipoprotein
CC (HDL) cholesterol. Reduced penetrance has been observed.
CC {ECO:0000269|PubMed:21666694, ECO:0000269|PubMed:26427795}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the bZIP family. ATF subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD18804.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAD18804.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
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DR EMBL; AB050902; BAB47242.1; -; mRNA.
DR EMBL; AB073612; BAD38649.1; -; mRNA.
DR EMBL; AK172839; BAD18804.1; ALT_SEQ; mRNA.
DR EMBL; AK313099; BAG35923.1; -; mRNA.
DR EMBL; AC016586; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471139; EAW69260.1; -; Genomic_DNA.
DR EMBL; BC101508; AAI01509.1; -; mRNA.
DR EMBL; BC101504; AAI01505.1; -; mRNA.
DR EMBL; BC143609; AAI43610.1; -; mRNA.
DR EMBL; BC143610; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS12121.1; -. [Q68CJ9-1]
DR CCDS; CCDS62498.1; -. [Q68CJ9-5]
DR CCDS; CCDS62499.1; -. [Q68CJ9-4]
DR CCDS; CCDS62500.1; -. [Q68CJ9-2]
DR RefSeq; NP_001258924.1; NM_001271995.1. [Q68CJ9-2]
DR RefSeq; NP_001258925.1; NM_001271996.1. [Q68CJ9-4]
DR RefSeq; NP_001258926.1; NM_001271997.1. [Q68CJ9-5]
DR RefSeq; NP_115996.1; NM_032607.2. [Q68CJ9-1]
DR AlphaFoldDB; Q68CJ9; -.
DR SMR; Q68CJ9; -.
DR BioGRID; 124213; 59.
DR IntAct; Q68CJ9; 29.
DR STRING; 9606.ENSP00000078445; -.
DR GlyConnect; 804; 1 O-Linked glycan (1 site).
DR GlyGen; Q68CJ9; 6 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; Q68CJ9; -.
DR PhosphoSitePlus; Q68CJ9; -.
DR BioMuta; CREB3L3; -.
DR DMDM; 148886847; -.
DR MassIVE; Q68CJ9; -.
DR PaxDb; Q68CJ9; -.
DR PeptideAtlas; Q68CJ9; -.
DR PRIDE; Q68CJ9; -.
DR ProteomicsDB; 66003; -. [Q68CJ9-1]
DR ProteomicsDB; 66004; -. [Q68CJ9-2]
DR Antibodypedia; 42393; 66 antibodies from 18 providers.
DR DNASU; 84699; -.
DR Ensembl; ENST00000078445.7; ENSP00000078445.1; ENSG00000060566.14. [Q68CJ9-1]
DR Ensembl; ENST00000595923.5; ENSP00000469355.1; ENSG00000060566.14. [Q68CJ9-2]
DR Ensembl; ENST00000602147.1; ENSP00000470119.1; ENSG00000060566.14. [Q68CJ9-5]
DR Ensembl; ENST00000602257.5; ENSP00000472399.1; ENSG00000060566.14. [Q68CJ9-4]
DR GeneID; 84699; -.
DR KEGG; hsa:84699; -.
DR MANE-Select; ENST00000078445.7; ENSP00000078445.1; NM_032607.3; NP_115996.1.
DR UCSC; uc002lzl.4; human. [Q68CJ9-1]
DR CTD; 84699; -.
DR DisGeNET; 84699; -.
DR GeneCards; CREB3L3; -.
DR HGNC; HGNC:18855; CREB3L3.
DR HPA; ENSG00000060566; Group enriched (intestine, liver).
DR MalaCards; CREB3L3; -.
DR MIM; 611998; gene.
DR MIM; 619324; phenotype.
DR neXtProt; NX_Q68CJ9; -.
DR OpenTargets; ENSG00000060566; -.
DR PharmGKB; PA134882161; -.
DR VEuPathDB; HostDB:ENSG00000060566; -.
DR eggNOG; KOG0709; Eukaryota.
DR GeneTree; ENSGT00940000159261; -.
DR HOGENOM; CLU_047257_1_0_1; -.
DR InParanoid; Q68CJ9; -.
DR OMA; PGTWHED; -.
DR OrthoDB; 644485at2759; -.
DR PhylomeDB; Q68CJ9; -.
DR TreeFam; TF316079; -.
DR PathwayCommons; Q68CJ9; -.
DR Reactome; R-HSA-8874211; CREB3 factors activate genes.
DR Reactome; R-HSA-8963889; Assembly of active LPL and LIPC lipase complexes.
DR SignaLink; Q68CJ9; -.
DR BioGRID-ORCS; 84699; 9 hits in 1093 CRISPR screens.
DR ChiTaRS; CREB3L3; human.
DR GenomeRNAi; 84699; -.
DR Pharos; Q68CJ9; Tbio.
DR PRO; PR:Q68CJ9; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q68CJ9; protein.
DR Bgee; ENSG00000060566; Expressed in right lobe of liver and 90 other tissues.
DR Genevisible; Q68CJ9; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISS: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; IDA:NTNU_SB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:ParkinsonsUK-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:ParkinsonsUK-UCL.
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; IDA:NTNU_SB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IEA:InterPro.
DR GO; GO:0002675; P:positive regulation of acute inflammatory response; NAS:ParkinsonsUK-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:NTNU_SB.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; IDA: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; Alternative splicing; Disease variant; DNA-binding;
KW Endoplasmic reticulum; Glycoprotein; Isopeptide bond; Membrane; Nucleus;
KW Phosphoprotein; Reference proteome; Signal-anchor; Transcription;
KW Transcription regulation; Transmembrane; Transmembrane helix;
KW Ubl conjugation; Unfolded protein response.
FT CHAIN 1..461
FT /note="Cyclic AMP-responsive element-binding protein 3-like
FT protein 3"
FT /id="PRO_0000288074"
FT CHAIN 1..?
FT /note="Processed cyclic AMP-responsive element-binding
FT protein 3-like protein 3"
FT /id="PRO_0000296216"
FT TOPO_DOM 1..322
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 323..343
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 344..461
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 243..306
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 51..120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 245..274
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 285..306
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 370..408
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 442..461
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..84
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 363..364
FT /note="Cleavage; by PS1"
FT /evidence="ECO:0000250"
FT MOD_RES 173
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 379
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:22171320"
FT CARBOHYD 410
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 413
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20356926"
FT CARBOHYD 420
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20356926"
FT CARBOHYD 427
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20356926"
FT CROSSLNK 294
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:30389664"
FT VAR_SEQ 53
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15221005"
FT /id="VSP_025637"
FT VAR_SEQ 193..194
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054876"
FT VAR_SEQ 239..337
FT /note="YEERVLKKIRRKIRNKQSAQESRKKKKEYIDGLETRMSACTAQNQELQRKVL
FT HLEKQNLSLLEQLKKLQAIVVQSTSKSAQTGTCVAVLLLSFALIILP -> DVSLHCSE
FT SGVTEESLASREAKPVPLGATEETPGHCGAVHQQVSPDRHLCRSPVAVLCPHHPPLHQP
FT FWPQQNREPWGLCACTSVLQNFAQRCCLPRGC (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055635"
FT VAR_SEQ 338..461
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055636"
FT VARIANT 46..461
FT /note="Missing (in HYTG2; risk factor; loss of
FT transactivation activity in APOA4, APOC2 or FGF21 promoter-
FT driven luciferase assays)"
FT /evidence="ECO:0000269|PubMed:21666694"
FT /id="VAR_085795"
FT VARIANT 105
FT /note="G -> R"
FT /evidence="ECO:0000269|PubMed:21666694"
FT /id="VAR_085796"
FT VARIANT 166
FT /note="P -> L (in HYTG2; unknown pathological significance;
FT no effect on transactivation activity in APOA4, APOC2 or
FT FGF21 promoter-driven luciferase assays)"
FT /evidence="ECO:0000269|PubMed:21666694"
FT /id="VAR_085797"
FT VARIANT 180
FT /note="V -> M (in HYTG2; unknown pathological significance;
FT no effect on transactivation activity in APOA4, APOC2 or
FT FGF21 promoter-driven luciferase assays)"
FT /evidence="ECO:0000269|PubMed:21666694"
FT /id="VAR_085798"
FT VARIANT 182
FT /note="D -> N (in HYTG2; unknown pathological significance;
FT no effect on transactivation activity in APOA4, APOC2 or
FT FGF21 promoter-driven luciferase assays)"
FT /evidence="ECO:0000269|PubMed:21666694"
FT /id="VAR_085799"
FT VARIANT 240
FT /note="E -> K (in HYTG2; risk factor; severely reduced
FT transactivation activity in APOA4, APOC2 or FGF21 promoter-
FT driven luciferase assays)"
FT /evidence="ECO:0000269|PubMed:21666694"
FT /id="VAR_085800"
FT MUTAGEN 294
FT /note="K->R: Loss of ubiquitination by SYNV1/HRD1."
FT /evidence="ECO:0000269|PubMed:30389664"
FT MUTAGEN 361
FT /note="R->A: Decreases proteolytic cleavage upon ER
FT stress."
FT /evidence="ECO:0000269|PubMed:16469704"
FT CONFLICT 437
FT /note="L -> P (in Ref. 3; BAD18804)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 461 AA; 49077 MW; C40F5AA626661F80 CRC64;
MNTDLAAGKM ASAACSMDPI DSFELLDLLF DRQDGILRHV ELGEGWGHVK DQQVLPNPDS
DDFLSSILGS GDSLPSSPLW SPEGSDSGIS EDLPSDPQDT PPRSGPATSP AGCHPAQPGK
GPCLSYHPGN SCSTTTPGPV IQVPEASVTI DLEMWSPGGR ICAEKPADPV DLSPRCNLTV
KDLLLSGSSG DLQQHHLGAS YLLRPGAGHC QELVLTEDEK KLLAKEGITL PTQLPLTKYE
ERVLKKIRRK IRNKQSAQES RKKKKEYIDG LETRMSACTA QNQELQRKVL HLEKQNLSLL
EQLKKLQAIV VQSTSKSAQT GTCVAVLLLS FALIILPSIS PFGPNKTESP GDFAPVRVFS
RTLHNDAASR VAADAVPGSE APGPRPEADT TREESPGSPG ADWGFQDTAN LTNSTEELDN
ATLVLRNATE GLGQVALLDW VAPGPSTGSG RAGLEAAGDE L
