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Protein

Cyclic AMP-responsive element-binding protein 3-like protein 2

Gene

Creb3l2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor involved in unfolded protein response (UPR). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in chondrogenesis by activating the transcription of SEC23A, which promotes the transport and secretion of cartilage matrix proteins, and possibly that of ER biogenesis-related genes (PubMed:19767744). In a neuroblastoma cell line, protects cells from ER stress-induced death (PubMed:17178827). In vitro activates transcription of target genes via direct binding to the CRE site (PubMed:17178827).2 Publications

GO - Molecular functioni

  • cAMP response element binding Source: UniProtKB
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  • cartilage development Source: UniProtKB
  • chondrocyte differentiation Source: UniProtKB
  • endoplasmic reticulum unfolded protein response Source: InterPro
  • ER to Golgi vesicle-mediated transport Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • response to endoplasmic reticulum stress Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Transcription, Transcription regulation, Unfolded protein response

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclic AMP-responsive element-binding protein 3-like protein 2
Short name:
cAMP-responsive element-binding protein 3-like protein 2
Cleaved into the following chain:
Gene namesi
Name:Creb3l2
Synonyms:Bbf2h7
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:2442695. Creb3l2.

Subcellular locationi

Processed cyclic AMP-responsive element-binding protein 3-like protein 2 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 378CytoplasmicSequence analysisAdd BLAST378
Transmembranei379 – 399Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini400 – 521LumenalSequence analysisAdd BLAST122

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mutant mice are born at the expected Mendelian rate, but die by suffocation shortly after birth because of an immature chest cavity. They exhibit severe chondrodysplasia. The cartilage shows a lack of typical columnar structure in the proliferating zone and a decrease in the size of the hypertrophic zone, resulting in a significant reduction of extracellular matrix proteins. Proliferating chondrocytes show abnormally expanded ER, containing aggregated type II collagen and cartilage oligomeric matrix protein (COMP). Displays significant decrease in Sec23a levels.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi427R → A: Loss of S1P cleavage. 1 Publication1
Mutagenesisi427R → A: Loss of S1P cleavage; when associated with V-430. 1 Publication1
Mutagenesisi430L → V: Loss of S1P cleavage. 1 Publication1
Mutagenesisi430L → V: Loss of S1P cleavage; when associated with A-427. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002880681 – 521Cyclic AMP-responsive element-binding protein 3-like protein 2Add BLAST521
ChainiPRO_00002962101 – ?Processed cyclic AMP-responsive element-binding protein 3-like protein 2

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei93PhosphoserineBy similarity1
Cross-linki178Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei191PhosphoserineBy similarity1
Glycosylationi481N-linked (GlcNAc...)Sequence analysis1
Glycosylationi505N-linked (GlcNAc...)Sequence analysis1
Glycosylationi518N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Upon ER stress, translocated to the Golgi apparatus, where it is processed by regulated intramembrane proteolysis (RIP) to release the cytosol-facing N-terminal transcription factor domain. The cleavage is performed sequentially by site-1 and site-2 proteases (S1P/MBTPS1 and S2P/MBTPS2).1 Publication
N-glycosylated.1 Publication
Ubiquitinated by HRD1/SYVN1; undergoes 'Lys-48'-linked ubiquitination, followed by rapid proteasomal degradation under normal conditions. Upon ER stress, SYVN1 E3 ubiquitin-protein ligase dissociates from its substrate, ubiquitination does not occur and CREB3L2 is stabilized.1 Publication

Keywords - PTMi

Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8BH52.
PeptideAtlasiQ8BH52.
PRIDEiQ8BH52.

PTM databases

iPTMnetiQ8BH52.
PhosphoSitePlusiQ8BH52.

Expressioni

Tissue specificityi

Widely expressed, including in lung, bladder, ovary, testis and spleen (PubMed:17178827). Highly expressed in chondrocytes (PubMed:19767744).2 Publications

Inductioni

Up-regulated by ER stress at the transcript and protein levels, the increase at the protein level is much higher than at the transcript level. This induction is accompanied by increased proteolytic cleavage that releases the N-terminal transcription factor domain. Up-regulated in brain areas undergoing ischemic injury, in neurons, but not astrocytes. Up-regulated by SOX9 during chondrocyte differentiation, possibly through SOX9-induced mild ER stress (PubMed:19767744).2 Publications

Gene expression databases

BgeeiENSMUSG00000038648.
CleanExiMM_CREB3L2.
GenevisibleiQ8BH52. MM.

Interactioni

Subunit structurei

Binds DNA as a dimer.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000040208.

Structurei

3D structure databases

ProteinModelPortaliQ8BH52.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini294 – 357bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni296 – 325Basic motifPROSITE-ProRule annotationAdd BLAST30
Regioni336 – 357Leucine-zipperPROSITE-ProRule annotationAdd BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi427 – 430S1P recognitionBy similarity4

Sequence similaritiesi

Belongs to the bZIP family. ATF subfamily.Curated
Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0709. Eukaryota.
ENOG410ZZQM. LUCA.
GeneTreeiENSGT00520000055538.
HOGENOMiHOG000060150.
HOVERGENiHBG057480.
InParanoidiQ8BH52.
KOiK09048.
OMAiHFTEFLD.
OrthoDBiEOG091G081Z.
PhylomeDBiQ8BH52.
TreeFamiTF316079.

Family and domain databases

InterProiIPR029804. BBF2H7.
IPR004827. bZIP.
[Graphical view]
PANTHERiPTHR22952:SF96. PTHR22952:SF96. 1 hit.
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q8BH52-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEVLESGEQS VLQWDRKLSE LSEPGETEAL MYHTHFSELL DEFSQNVLGQ
60 70 80 90 100
LLSDPFLSEK SESMEVEPSP TSPAPLIQAE HSYSLSEEPR TQSPFTHAAT
110 120 130 140 150
SDSFNDEEVE SEKWYLSTEF PSATIKTEPI TEEQPPGLVP SVTLTITAIS
160 170 180 190 200
TPFEKEESPL DMNAGGDSSC QTLIPKIKLE PHEVDQFLNF SPKEASVDQL
210 220 230 240 250
HLPPTPPSSH SSDSEGSLSP NPRLHPFSLS QAHSPARAMP RGPSALSTSP
260 270 280 290 300
LLTAPHKLQG SGPLVLTEEE KRTLVAEGYP IPTKLPLTKS EEKALKKIRR
310 320 330 340 350
KIKNKISAQE SRRKKKEYMD SLEKKVESCS TENLELRKKV EVLENTNRTL
360 370 380 390 400
LQQLQKLQTL VMGKVSRTCK LAGTQTGTCL MVVVLCFAVA FGSFFQGYGP
410 420 430 440 450
YPSATKMALP SQHPLSEPYT ASVVRSRNLL IYEEHAPLEE SSSPASAGEL
460 470 480 490 500
GGWDRGSSLL RASSGLEALP EVDLPHFLIS NETSLEKSVL LELQQHLVSS
510 520
KLEGNETLKV VELERRVNAT F
Length:521
Mass (Da):57,469
Last modified:March 1, 2003 - v1
Checksum:i4BDC49112F56F8BE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti264L → R in BAC29155 (PubMed:16141072).Curated1
Sequence conflicti345N → D in BAC29547 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK035695 mRNA. Translation: BAC29155.1.
AK036712 mRNA. Translation: BAC29547.1.
AK041050 mRNA. Translation: BAC30798.1.
AK041669 mRNA. Translation: BAC31028.1.
BC043466 mRNA. Translation: AAH43466.1.
BC138470 mRNA. Translation: AAI38471.1.
BC138471 mRNA. Translation: AAI38472.1.
CCDSiCCDS20006.1.
RefSeqiNP_848776.2. NM_178661.4.
UniGeneiMm.169929.
Mm.482172.

Genome annotation databases

EnsembliENSMUST00000041093; ENSMUSP00000040208; ENSMUSG00000038648.
GeneIDi208647.
KEGGimmu:208647.
UCSCiuc009bjf.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK035695 mRNA. Translation: BAC29155.1.
AK036712 mRNA. Translation: BAC29547.1.
AK041050 mRNA. Translation: BAC30798.1.
AK041669 mRNA. Translation: BAC31028.1.
BC043466 mRNA. Translation: AAH43466.1.
BC138470 mRNA. Translation: AAI38471.1.
BC138471 mRNA. Translation: AAI38472.1.
CCDSiCCDS20006.1.
RefSeqiNP_848776.2. NM_178661.4.
UniGeneiMm.169929.
Mm.482172.

3D structure databases

ProteinModelPortaliQ8BH52.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000040208.

PTM databases

iPTMnetiQ8BH52.
PhosphoSitePlusiQ8BH52.

Proteomic databases

PaxDbiQ8BH52.
PeptideAtlasiQ8BH52.
PRIDEiQ8BH52.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000041093; ENSMUSP00000040208; ENSMUSG00000038648.
GeneIDi208647.
KEGGimmu:208647.
UCSCiuc009bjf.2. mouse.

Organism-specific databases

CTDi64764.
MGIiMGI:2442695. Creb3l2.

Phylogenomic databases

eggNOGiKOG0709. Eukaryota.
ENOG410ZZQM. LUCA.
GeneTreeiENSGT00520000055538.
HOGENOMiHOG000060150.
HOVERGENiHBG057480.
InParanoidiQ8BH52.
KOiK09048.
OMAiHFTEFLD.
OrthoDBiEOG091G081Z.
PhylomeDBiQ8BH52.
TreeFamiTF316079.

Miscellaneous databases

ChiTaRSiCreb3l2. mouse.
PROiQ8BH52.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038648.
CleanExiMM_CREB3L2.
GenevisibleiQ8BH52. MM.

Family and domain databases

InterProiIPR029804. BBF2H7.
IPR004827. bZIP.
[Graphical view]
PANTHERiPTHR22952:SF96. PTHR22952:SF96. 1 hit.
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCR3L2_MOUSE
AccessioniPrimary (citable) accession number: Q8BH52
Secondary accession number(s): B2RRL0, Q8CB61, Q8CBN2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: March 1, 2003
Last modified: November 2, 2016
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.