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UniProtKB - Q68CJ9 (CR3L3_HUMAN)

Protein

Cyclic AMP-responsive element-binding protein 3-like protein 3

Gene

CREB3L3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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). Seems to function synergistically with ATF6. In acute inflammatory response, may activate expression of acute phase response (APR) genes. May be involved in growth suppression.By similarity3 Publications

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation, Unfolded protein response

Enzyme and pathway databases

ReactomeiR-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 3
Short name:
cAMP-responsive element-binding protein 3-like protein 3
Alternative name(s):
Transcription factor CREB-H
Cleaved into the following chain:
Processed cyclic AMP-responsive element-binding protein 3-like protein 3
Gene namesi
Name:CREB3L3
Synonyms:CREBH
ORF Names:HYST1481
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000060566.13
HGNCiHGNC:18855 CREB3L3
MIMi611998 gene
neXtProtiNX_Q68CJ9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 322CytoplasmicSequence analysisAdd BLAST322
Transmembranei323 – 343Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini344 – 461LumenalSequence analysisAdd BLAST118

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi361R → A: Decreases proteolytic cleavage upon ER stress. 1 Publication1

Organism-specific databases

DisGeNETi84699
MalaCardsiCREB3L3
OpenTargetsiENSG00000060566
Orphaneti70470 Hyperlipoproteinemia type 5
PharmGKBiPA134882161

Polymorphism and mutation databases

DMDMi148886847

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002880741 – 461Cyclic AMP-responsive element-binding protein 3-like protein 3Add BLAST461
ChainiPRO_00002962161 – ?Processed cyclic AMP-responsive element-binding protein 3-like protein 3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei173PhosphoserineCombined sources1
Glycosylationi379O-linked (GalNAc...) serine1 Publication1
Glycosylationi410N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi413N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi420N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi427N-linked (GlcNAc...) asparagine1 Publication1

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei363 – 364Cleavage; by PS1By similarity2

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ68CJ9
PeptideAtlasiQ68CJ9
PRIDEiQ68CJ9
ProteomicsDBi66003
66004 [Q68CJ9-2]

PTM databases

GlyConnecti804
iPTMnetiQ68CJ9
PhosphoSitePlusiQ68CJ9
UniCarbKBiQ68CJ9

Expressioni

Tissue specificityi

Exclusively expressed in liver. Underexpressed in hepatocellular carcinoma tissues.2 Publications

Gene expression databases

BgeeiENSG00000060566 Expressed in 70 organ(s), highest expression level in right lobe of liver
CleanExiHS_CREB3L3
GenevisibleiQ68CJ9 HS

Organism-specific databases

HPAiHPA040671
HPA056228

Interactioni

Subunit structurei

Binds DNA as a dimer (By similarity). Probably homodimerizes. Probably forms a heterodimer with ATF6. Interacts with ATF6.By similarity1 Publication

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi124213, 16 interactors
IntActiQ68CJ9, 30 interactors
STRINGi9606.ENSP00000078445

Structurei

3D structure databases

ProteinModelPortaliQ68CJ9
SMRiQ68CJ9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini243 – 306bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni245 – 274Basic motifPROSITE-ProRule annotationAdd BLAST30
Regioni285 – 306Leucine-zipperPROSITE-ProRule annotationAdd BLAST22

Sequence similaritiesi

Belongs to the bZIP family. ATF subfamily.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0709 Eukaryota
ENOG410ZZQM LUCA
GeneTreeiENSGT00520000055538
HOGENOMiHOG000059566
HOVERGENiHBG090496
InParanoidiQ68CJ9
KOiK09048
OMAiDLEMWSP
OrthoDBiEOG091G07QR
PhylomeDBiQ68CJ9
TreeFamiTF316079

Family and domain databases

InterProiView protein in InterPro
IPR004827 bZIP
IPR029806 CREBH
PANTHERiPTHR22952:SF98 PTHR22952:SF98, 1 hit
PfamiView protein in Pfam
PF00170 bZIP_1, 1 hit
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit
PS00036 BZIP_BASIC, 1 hit

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q68CJ9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Length:461
Mass (Da):49,077
Last modified:May 29, 2007 - v2
Checksum:iC40F5AA626661F80
GO
Isoform 2 (identifier: Q68CJ9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     53-53: Missing.

Show »
Length:460
Mass (Da):48,949
Checksum:i53E643AF4D09C329
GO
Isoform 3 (identifier: Q68CJ9-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     193-194: Missing.

Note: No experimental confirmation available.
Show »
Length:459
Mass (Da):48,821
Checksum:iEBED4351D3DD72C3
GO
Isoform 4 (identifier: Q68CJ9-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     239-337: YEERVLKKIR...LLSFALIILP → DVSLHCSESG...AQRCCLPRGC
     338-461: Missing.

Show »
Length:337
Mass (Da):35,845
Checksum:i11A7E28F406DE1FC
GO

Sequence cautioni

The sequence BAD18804 differs from that shown. Aberrant splicing.Curated
The sequence BAD18804 differs from that shown. Reason: Frameshift at position 445.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti437L → P in BAD18804 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_02563753Missing in isoform 2. 1 Publication1
Alternative sequenceiVSP_054876193 – 194Missing in isoform 3. 1 Publication2
Alternative sequenceiVSP_055635239 – 337YEERV…LIILP → DVSLHCSESGVTEESLASRE AKPVPLGATEETPGHCGAVH QQVSPDRHLCRSPVAVLCPH HPPLHQPFWPQQNREPWGLC ACTSVLQNFAQRCCLPRGC in isoform 4. 1 PublicationAdd BLAST99
Alternative sequenceiVSP_055636338 – 461Missing in isoform 4. 1 PublicationAdd BLAST124

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.
CCDSiCCDS12121.1 [Q68CJ9-1]
CCDS62498.1 [Q68CJ9-5]
CCDS62499.1 [Q68CJ9-4]
CCDS62500.1 [Q68CJ9-2]
RefSeqiNP_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]
UniGeneiHs.247744

Genome annotation databases

EnsembliENST00000078445; ENSP00000078445; ENSG00000060566 [Q68CJ9-1]
ENST00000595923; ENSP00000469355; ENSG00000060566 [Q68CJ9-2]
ENST00000602147; ENSP00000470119; ENSG00000060566 [Q68CJ9-5]
ENST00000602257; ENSP00000472399; ENSG00000060566 [Q68CJ9-4]
GeneIDi84699
KEGGihsa:84699
UCSCiuc002lzl.4 human [Q68CJ9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar 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.
CCDSiCCDS12121.1 [Q68CJ9-1]
CCDS62498.1 [Q68CJ9-5]
CCDS62499.1 [Q68CJ9-4]
CCDS62500.1 [Q68CJ9-2]
RefSeqiNP_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]
UniGeneiHs.247744

3D structure databases

ProteinModelPortaliQ68CJ9
SMRiQ68CJ9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124213, 16 interactors
IntActiQ68CJ9, 30 interactors
STRINGi9606.ENSP00000078445

PTM databases

GlyConnecti804
iPTMnetiQ68CJ9
PhosphoSitePlusiQ68CJ9
UniCarbKBiQ68CJ9

Polymorphism and mutation databases

DMDMi148886847

Proteomic databases

PaxDbiQ68CJ9
PeptideAtlasiQ68CJ9
PRIDEiQ68CJ9
ProteomicsDBi66003
66004 [Q68CJ9-2]

Protocols and materials databases

DNASUi84699
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000078445; ENSP00000078445; ENSG00000060566 [Q68CJ9-1]
ENST00000595923; ENSP00000469355; ENSG00000060566 [Q68CJ9-2]
ENST00000602147; ENSP00000470119; ENSG00000060566 [Q68CJ9-5]
ENST00000602257; ENSP00000472399; ENSG00000060566 [Q68CJ9-4]
GeneIDi84699
KEGGihsa:84699
UCSCiuc002lzl.4 human [Q68CJ9-1]

Organism-specific databases

CTDi84699
DisGeNETi84699
EuPathDBiHostDB:ENSG00000060566.13
GeneCardsiCREB3L3
HGNCiHGNC:18855 CREB3L3
HPAiHPA040671
HPA056228
MalaCardsiCREB3L3
MIMi611998 gene
neXtProtiNX_Q68CJ9
OpenTargetsiENSG00000060566
Orphaneti70470 Hyperlipoproteinemia type 5
PharmGKBiPA134882161
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0709 Eukaryota
ENOG410ZZQM LUCA
GeneTreeiENSGT00520000055538
HOGENOMiHOG000059566
HOVERGENiHBG090496
InParanoidiQ68CJ9
KOiK09048
OMAiDLEMWSP
OrthoDBiEOG091G07QR
PhylomeDBiQ68CJ9
TreeFamiTF316079

Enzyme and pathway databases

ReactomeiR-HSA-8874211 CREB3 factors activate genes
R-HSA-8963889 Assembly of active LPL and LIPC lipase complexes

Miscellaneous databases

GenomeRNAii84699
PROiPR:Q68CJ9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000060566 Expressed in 70 organ(s), highest expression level in right lobe of liver
CleanExiHS_CREB3L3
GenevisibleiQ68CJ9 HS

Family and domain databases

InterProiView protein in InterPro
IPR004827 bZIP
IPR029806 CREBH
PANTHERiPTHR22952:SF98 PTHR22952:SF98, 1 hit
PfamiView protein in Pfam
PF00170 bZIP_1, 1 hit
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit
PS00036 BZIP_BASIC, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCR3L3_HUMAN
AccessioniPrimary (citable) accession number: Q68CJ9
Secondary accession number(s): B2R7S6
, B7ZL69, M0QYW7, Q6ZMC5, Q96TB9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 29, 2007
Last modified: October 10, 2018
This is version 139 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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