UniProtKB - Q68CJ9 (CR3L3_HUMAN)
Protein
Cyclic AMP-responsive element-binding protein 3-like protein 3
Gene
CREB3L3
Organism
Homo sapiens (Human)
Status
Functioni
Transcription factor that may act during endoplasmic reticulum stress by activating unfolded protein response target genes. Activated in response to cAMP stimulation. In vitro, binds to the cAMP response element (CRE) and box-B element. Activates transcription through box-B element. Activates transcription through CRE (By similarity). May function synergistically with ATF6. In acute inflammatory response, may activate expression of acute phase response (APR) genes. May be involved in growth suppression. Regulates FGF21 transcription (By similarity).By similarity3 Publications
GO - Molecular functioni
- cAMP response element binding Source: InterPro
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: NTNU_SB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- protein heterodimerization activity Source: ParkinsonsUK-UCL
- protein homodimerization activity Source: ParkinsonsUK-UCL
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: NTNU_SB
- transcription regulatory region sequence-specific DNA binding Source: ParkinsonsUK-UCL
GO - Biological processi
- endoplasmic reticulum unfolded protein response Source: Reactome
- positive regulation of acute inflammatory response Source: ParkinsonsUK-UCL
- positive regulation of transcription by RNA polymerase II Source: NTNU_SB
- positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
Keywordsi
Molecular function | Activator, DNA-binding |
Biological process | Transcription, Transcription regulation, Unfolded protein response |
Enzyme and pathway databases
PathwayCommonsi | Q68CJ9 |
Reactomei | R-HSA-8874211, CREB3 factors activate genes R-HSA-8963889, Assembly of active LPL and LIPC lipase complexes |
Names & Taxonomyi
Protein namesi | Recommended name: Cyclic AMP-responsive element-binding protein 3-like protein 3Short name: cAMP-responsive element-binding protein 3-like protein 3 Alternative name(s): Transcription factor CREB-H Cleaved into the following chain: |
Gene namesi | Name:CREB3L3 Synonyms:CREBH ORF Names:HYST1481 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000060566.13 |
HGNCi | HGNC:18855, CREB3L3 |
MIMi | 611998, gene |
neXtProti | NX_Q68CJ9 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Single-pass type II membrane protein 1 Publication
Nucleus
- Nucleus 1 Publication
Note: Under ER stress the cleaved N-terminal cytoplasmic domain translocates into the nucleus.
Cytosol
- cytosol Source: Reactome
Endoplasmic reticulum
- endoplasmic reticulum Source: ParkinsonsUK-UCL
- endoplasmic reticulum membrane Source: Reactome
Golgi apparatus
- Golgi membrane Source: Reactome
Nucleus
- nuclear chromatin Source: NTNU_SB
- nucleoplasm Source: Reactome
- nucleus Source: ParkinsonsUK-UCL
Other locations
- integral component of membrane Source: UniProtKB-KW
- membrane Source: ParkinsonsUK-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 322 | CytoplasmicSequence analysisAdd BLAST | 322 | |
Transmembranei | 323 – 343 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 344 – 461 | LumenalSequence analysisAdd BLAST | 118 |
Keywords - Cellular componenti
Endoplasmic reticulum, Membrane, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 294 | K → R: Loss of ubiquitination by SYNV1/HRD1. 1 Publication | 1 | |
Mutagenesisi | 361 | R → A: Decreases proteolytic cleavage upon ER stress. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 84699 |
OpenTargetsi | ENSG00000060566 |
PharmGKBi | PA134882161 |
Miscellaneous databases
Pharosi | Q68CJ9, Tbio |
Polymorphism and mutation databases
BioMutai | CREB3L3 |
DMDMi | 148886847 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000288074 | 1 – 461 | Cyclic AMP-responsive element-binding protein 3-like protein 3Add BLAST | 461 | |
ChainiPRO_0000296216 | 1 – ? | Processed cyclic AMP-responsive element-binding protein 3-like protein 3 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 173 | PhosphoserineCombined sources | 1 | |
Cross-linki | 294 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Glycosylationi | 379 | O-linked (GalNAc...) serine1 Publication | 1 | |
Glycosylationi | 410 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 413 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 420 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 427 | N-linked (GlcNAc...) asparagine1 Publication | 1 |
Post-translational modificationi
Controlled by regulated intramembrane proteolysis (RIP). Following ER stress a fragment containing the cytoplasmic transcription factor domain is released by proteolysis. The cleavage seems to be performed sequentially by site-1 and site-2 proteases (PS1 and PS2).1 Publication
N- and O-glycosylated. N-glycosylation is required for optimal proteolytic activation. O-glycosylated with core 1 or possibly core 8 glycans.2 Publications
Ubiquitinated at Lys-294 by SYNV1/HRD1 via 'Lys-27'-linked ubiquitin.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 363 – 364 | Cleavage; by PS1By similarity | 2 |
Keywords - PTMi
Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
MassIVEi | Q68CJ9 |
PaxDbi | Q68CJ9 |
PeptideAtlasi | Q68CJ9 |
PRIDEi | Q68CJ9 |
ProteomicsDBi | 66003 [Q68CJ9-1] 66004 [Q68CJ9-2] |
PTM databases
GlyConnecti | 804, 1 O-Linked glycan (1 site) |
GlyGeni | Q68CJ9, 6 sites, 1 O-linked glycan (2 sites) |
iPTMneti | Q68CJ9 |
PhosphoSitePlusi | Q68CJ9 |
UniCarbKBi | Q68CJ9 |
Expressioni
Tissue specificityi
Exclusively expressed in liver. Underexpressed in hepatocellular carcinoma tissues.2 Publications
Gene expression databases
Bgeei | ENSG00000060566, Expressed in right lobe of liver and 91 other tissues |
Genevisiblei | Q68CJ9, HS |
Organism-specific databases
HPAi | ENSG00000060566, Group enriched (intestine, liver) |
Interactioni
Subunit structurei
Binary interactionsi
Hide detailsQ68CJ9
GO - Molecular functioni
- protein heterodimerization activity Source: ParkinsonsUK-UCL
- protein homodimerization activity Source: ParkinsonsUK-UCL
Protein-protein interaction databases
BioGRIDi | 124213, 34 interactors |
IntActi | Q68CJ9, 28 interactors |
STRINGi | 9606.ENSP00000078445 |
Miscellaneous databases
RNActi | Q68CJ9, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 243 – 306 | bZIPPROSITE-ProRule annotationAdd BLAST | 64 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 245 – 274 | Basic motifPROSITE-ProRule annotationAdd BLAST | 30 | |
Regioni | 285 – 306 | Leucine-zipperPROSITE-ProRule annotationAdd BLAST | 22 |
Sequence similaritiesi
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0709, Eukaryota |
GeneTreei | ENSGT00940000159261 |
HOGENOMi | CLU_047257_1_0_1 |
InParanoidi | Q68CJ9 |
OMAi | AIDLDMW |
OrthoDBi | 644485at2759 |
PhylomeDBi | Q68CJ9 |
TreeFami | TF316079 |
Family and domain databases
InterProi | View protein in InterPro IPR004827, bZIP IPR029806, CREBH |
PANTHERi | PTHR45996:SF1, PTHR45996:SF1, 1 hit |
Pfami | View protein in Pfam PF00170, bZIP_1, 1 hit |
SMARTi | View protein in SMART SM00338, BRLZ, 1 hit |
PROSITEi | View protein in PROSITE PS50217, BZIP, 1 hit PS00036, BZIP_BASIC, 1 hit |
s (4)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q68CJ9-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MNTDLAAGKM ASAACSMDPI DSFELLDLLF DRQDGILRHV ELGEGWGHVK
60 70 80 90 100
DQQVLPNPDS DDFLSSILGS GDSLPSSPLW SPEGSDSGIS EDLPSDPQDT
110 120 130 140 150
PPRSGPATSP AGCHPAQPGK GPCLSYHPGN SCSTTTPGPV IQVPEASVTI
160 170 180 190 200
DLEMWSPGGR ICAEKPADPV DLSPRCNLTV KDLLLSGSSG DLQQHHLGAS
210 220 230 240 250
YLLRPGAGHC QELVLTEDEK KLLAKEGITL PTQLPLTKYE ERVLKKIRRK
260 270 280 290 300
IRNKQSAQES RKKKKEYIDG LETRMSACTA QNQELQRKVL HLEKQNLSLL
310 320 330 340 350
EQLKKLQAIV VQSTSKSAQT GTCVAVLLLS FALIILPSIS PFGPNKTESP
360 370 380 390 400
GDFAPVRVFS RTLHNDAASR VAADAVPGSE APGPRPEADT TREESPGSPG
410 420 430 440 450
ADWGFQDTAN LTNSTEELDN ATLVLRNATE GLGQVALLDW VAPGPSTGSG
460
RAGLEAAGDE L
Sequence cautioni
The sequence BAD18804 differs from that shown. Reason: Frameshift.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 437 | L → P in BAD18804 (PubMed:14702039).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_025637 | 53 | Missing in isoform 2. 1 Publication | 1 | |
Alternative sequenceiVSP_054876 | 193 – 194 | Missing in isoform 3. 1 Publication | 2 | |
Alternative sequenceiVSP_055635 | 239 – 337 | YEERV…LIILP → DVSLHCSESGVTEESLASRE AKPVPLGATEETPGHCGAVH QQVSPDRHLCRSPVAVLCPH HPPLHQPFWPQQNREPWGLC ACTSVLQNFAQRCCLPRGC in isoform 4. 1 PublicationAdd BLAST | 99 | |
Alternative sequenceiVSP_055636 | 338 – 461 | Missing in isoform 4. 1 PublicationAdd BLAST | 124 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB050902 mRNA Translation: BAB47242.1 AB073612 mRNA Translation: BAD38649.1 AK172839 mRNA Translation: BAD18804.1 Sequence problems. AK313099 mRNA Translation: BAG35923.1 AC016586 Genomic DNA No translation available. CH471139 Genomic DNA Translation: EAW69260.1 BC101508 mRNA Translation: AAI01509.1 BC101504 mRNA Translation: AAI01505.1 BC143609 mRNA Translation: AAI43610.1 BC143610 mRNA No translation available. |
CCDSi | CCDS12121.1 [Q68CJ9-1] CCDS62498.1 [Q68CJ9-5] CCDS62499.1 [Q68CJ9-4] CCDS62500.1 [Q68CJ9-2] |
RefSeqi | NP_001258924.1, NM_001271995.1 [Q68CJ9-2] NP_001258925.1, NM_001271996.1 [Q68CJ9-4] NP_001258926.1, NM_001271997.1 [Q68CJ9-5] NP_115996.1, NM_032607.2 [Q68CJ9-1] |
Genome annotation databases
Ensembli | ENST00000078445; ENSP00000078445; ENSG00000060566 [Q68CJ9-1] ENST00000595923; ENSP00000469355; ENSG00000060566 [Q68CJ9-2] ENST00000602147; ENSP00000470119; ENSG00000060566 [Q68CJ9-5] ENST00000602257; ENSP00000472399; ENSG00000060566 [Q68CJ9-4] |
GeneIDi | 84699 |
KEGGi | hsa:84699 |
UCSCi | uc002lzl.4, human [Q68CJ9-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB050902 mRNA Translation: BAB47242.1 AB073612 mRNA Translation: BAD38649.1 AK172839 mRNA Translation: BAD18804.1 Sequence problems. AK313099 mRNA Translation: BAG35923.1 AC016586 Genomic DNA No translation available. CH471139 Genomic DNA Translation: EAW69260.1 BC101508 mRNA Translation: AAI01509.1 BC101504 mRNA Translation: AAI01505.1 BC143609 mRNA Translation: AAI43610.1 BC143610 mRNA No translation available. |
CCDSi | CCDS12121.1 [Q68CJ9-1] CCDS62498.1 [Q68CJ9-5] CCDS62499.1 [Q68CJ9-4] CCDS62500.1 [Q68CJ9-2] |
RefSeqi | NP_001258924.1, NM_001271995.1 [Q68CJ9-2] NP_001258925.1, NM_001271996.1 [Q68CJ9-4] NP_001258926.1, NM_001271997.1 [Q68CJ9-5] NP_115996.1, NM_032607.2 [Q68CJ9-1] |
3D structure databases
SMRi | Q68CJ9 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 124213, 34 interactors |
IntActi | Q68CJ9, 28 interactors |
STRINGi | 9606.ENSP00000078445 |
PTM databases
GlyConnecti | 804, 1 O-Linked glycan (1 site) |
GlyGeni | Q68CJ9, 6 sites, 1 O-linked glycan (2 sites) |
iPTMneti | Q68CJ9 |
PhosphoSitePlusi | Q68CJ9 |
UniCarbKBi | Q68CJ9 |
Polymorphism and mutation databases
BioMutai | CREB3L3 |
DMDMi | 148886847 |
Proteomic databases
MassIVEi | Q68CJ9 |
PaxDbi | Q68CJ9 |
PeptideAtlasi | Q68CJ9 |
PRIDEi | Q68CJ9 |
ProteomicsDBi | 66003 [Q68CJ9-1] 66004 [Q68CJ9-2] |
Protocols and materials databases
Antibodypediai | 42393, 57 antibodies |
DNASUi | 84699 |
Genome annotation databases
Ensembli | ENST00000078445; ENSP00000078445; ENSG00000060566 [Q68CJ9-1] ENST00000595923; ENSP00000469355; ENSG00000060566 [Q68CJ9-2] ENST00000602147; ENSP00000470119; ENSG00000060566 [Q68CJ9-5] ENST00000602257; ENSP00000472399; ENSG00000060566 [Q68CJ9-4] |
GeneIDi | 84699 |
KEGGi | hsa:84699 |
UCSCi | uc002lzl.4, human [Q68CJ9-1] |
Organism-specific databases
CTDi | 84699 |
DisGeNETi | 84699 |
EuPathDBi | HostDB:ENSG00000060566.13 |
GeneCardsi | CREB3L3 |
HGNCi | HGNC:18855, CREB3L3 |
HPAi | ENSG00000060566, Group enriched (intestine, liver) |
MIMi | 611998, gene |
neXtProti | NX_Q68CJ9 |
OpenTargetsi | ENSG00000060566 |
PharmGKBi | PA134882161 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0709, Eukaryota |
GeneTreei | ENSGT00940000159261 |
HOGENOMi | CLU_047257_1_0_1 |
InParanoidi | Q68CJ9 |
OMAi | AIDLDMW |
OrthoDBi | 644485at2759 |
PhylomeDBi | Q68CJ9 |
TreeFami | TF316079 |
Enzyme and pathway databases
PathwayCommonsi | Q68CJ9 |
Reactomei | R-HSA-8874211, CREB3 factors activate genes R-HSA-8963889, Assembly of active LPL and LIPC lipase complexes |
Miscellaneous databases
BioGRID-ORCSi | 84699, 5 hits in 865 CRISPR screens |
ChiTaRSi | CREB3L3, human |
GenomeRNAii | 84699 |
Pharosi | Q68CJ9, Tbio |
PROi | PR:Q68CJ9 |
RNActi | Q68CJ9, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000060566, Expressed in right lobe of liver and 91 other tissues |
Genevisiblei | Q68CJ9, HS |
Family and domain databases
InterProi | View protein in InterPro IPR004827, bZIP IPR029806, CREBH |
PANTHERi | PTHR45996:SF1, PTHR45996:SF1, 1 hit |
Pfami | View protein in Pfam PF00170, bZIP_1, 1 hit |
SMARTi | View protein in SMART SM00338, BRLZ, 1 hit |
PROSITEi | View protein in PROSITE PS50217, BZIP, 1 hit PS00036, BZIP_BASIC, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CR3L3_HUMAN | |
Accessioni | Q68CJ9Primary (citable) accession number: Q68CJ9 Secondary accession number(s): B2R7S6 Q96TB9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 29, 2007 |
Last sequence update: | May 29, 2007 | |
Last modified: | December 2, 2020 | |
This is version 156 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM