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Protein

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

Gene

CREB3L2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (By similarity). 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).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-8874211 CREB3 factors activate genes
SIGNORiQ70SY1

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
Alternative name(s):
BBF2 human homolog on chromosome 7
Cleaved into the following chain:
Gene namesi
Name:CREB3L2
Synonyms:BBF2H7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000182158.14
HGNCiHGNC:23720 CREB3L2
MIMi608834 gene
neXtProtiNX_Q70SY1

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 – 379CytoplasmicSequence analysisAdd BLAST379
Transmembranei380 – 400Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini401 – 520LumenalSequence analysisAdd BLAST120

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving CREB3L2 is found in low grade fibromyxoid sarcoma (LGFMS). Translocation t(7;16)(q33;p11) with FUS.

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi64764
MalaCardsiCREB3L2
OpenTargetsiENSG00000182158
Orphaneti79105 Myxofibrosarcoma
PharmGKBiPA134914841

Polymorphism and mutation databases

BioMutaiCREB3L2
DMDMi296439387

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002880671 – 520Cyclic AMP-responsive element-binding protein 3-like protein 2Add BLAST520
ChainiPRO_00002962091 – ?Processed cyclic AMP-responsive element-binding protein 3-like protein 2

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei93PhosphoserineCombined sources1
Cross-linki178Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei191PhosphoserineCombined sources1
Glycosylationi480N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi504N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi517N-linked (GlcNAc...) asparagineSequence 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).By similarity
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

MaxQBiQ70SY1
PaxDbiQ70SY1
PeptideAtlasiQ70SY1
PRIDEiQ70SY1
ProteomicsDBi68563
68564 [Q70SY1-2]
68565 [Q70SY1-3]

PTM databases

iPTMnetiQ70SY1
PhosphoSitePlusiQ70SY1

Expressioni

Tissue specificityi

Widely expressed with highest levels in placenta, lung, spleen and intestine, and lowest levels in heart, brain, skeletal muscle, thymus, colon and leukocytes. In fetal tissues, the weakest expression is detected in brain and heart.1 Publication

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.1 Publication

Gene expression databases

BgeeiENSG00000182158 Expressed in 236 organ(s), highest expression level in placenta
CleanExiHS_CREB3L2
ExpressionAtlasiQ70SY1 baseline and differential
GenevisibleiQ70SY1 HS

Organism-specific databases

HPAiHPA015068
HPA015534

Interactioni

Subunit structurei

Binds DNA as a dimer.By similarity

Protein-protein interaction databases

BioGridi122277, 17 interactors
IntActiQ70SY1, 11 interactors
STRINGi9606.ENSP00000329140

Structurei

3D structure databases

ProteinModelPortaliQ70SY1
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 recognition1 Publication4

Sequence similaritiesi

Belongs to the bZIP family. ATF subfamily.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0709 Eukaryota
ENOG410ZZQM LUCA
GeneTreeiENSGT00520000055538
HOGENOMiHOG000060150
HOVERGENiHBG057480
InParanoidiQ70SY1
KOiK09048
OMAiVDLPHFI
OrthoDBiEOG091G081Z
PhylomeDBiQ70SY1
TreeFamiTF316079

Family and domain databases

InterProiView protein in InterPro
IPR029804 BBF2H7
IPR004827 bZIP
PANTHERiPTHR22952:SF96 PTHR22952:SF96, 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 (3+)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q70SY1-1) [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
MEVLESGEQG VLQWDRKLSE LSEPGDGEAL MYHTHFSELL DEFSQNVLGQ
60 70 80 90 100
LLNDPFLSEK SVSMEVEPSP TSPAPLIQAE HSYSLCEEPR AQSPFTHITT
110 120 130 140 150
SDSFNDDEVE SEKWYLSTDF PSTSIKTEPV TDEPPPGLVP SVTLTITAIS
160 170 180 190 200
TPLEKEEPPL EMNTGVDSSC QTIIPKIKLE PHEVDQFLNF SPKEAPVDHL
210 220 230 240 250
HLPPTPPSSH GSDSEGSLSP NPRLHPFSLP QTHSPSRAAP RAPSALSSSP
260 270 280 290 300
LLTAPHKLQG SGPLVLTEEE KRTLIAEGYP IPTKLPLSKS 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 SQHSLQEPYT ASVVRSRNLL IYEEHSPPEE SSSPGSAGEL
460 470 480 490 500
GGWDRGSSLL RVSGLESRPD VDLPHFIISN ETSLEKSVLL ELQQHLVSAK
510 520
LEGNETLKVV ELDRRVNTTF
Length:520
Mass (Da):57,415
Last modified:May 18, 2010 - v3
Checksum:i64699072EEB454D3
GO
Isoform 2 (identifier: Q70SY1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     424-520: VRSRNLLIYE...ELDRRVNTTF → GKTACGKLGR...FCESPMFKKW

Note: No experimental confirmation available.
Show »
Length:460
Mass (Da):50,843
Checksum:i8762472720C306F0
GO
Isoform 3 (identifier: Q70SY1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     195-248: APVDHLHLPP...APRAPSALSS → GLSALPVSLW...FLKNKNFASK
     249-520: Missing.

Note: No experimental confirmation available.
Show »
Length:248
Mass (Da):27,722
Checksum:i8AF3A941E7068506
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WU77A0A087WU77_HUMAN
Cyclic AMP-responsive element-bindi...
CREB3L2
150Annotation score:
A0A087WUP1A0A087WUP1_HUMAN
Cyclic AMP-responsive element-bindi...
CREB3L2
175Annotation score:
C9JPH0C9JPH0_HUMAN
Cyclic AMP-responsive element-bindi...
CREB3L2
185Annotation score:
H7C1W8H7C1W8_HUMAN
Cyclic AMP-responsive element-bindi...
CREB3L2
239Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_062385100Missing 3 Publications1
Natural variantiVAR_062386130V → I3 PublicationsCorresponds to variant dbSNP:rs273957Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_025634195 – 248APVDH…SALSS → GLSALPVSLWVMDMVSGSTE REYGERAGMSLYHRCCSWLY EIALFLKNKNFASK in isoform 3. 1 PublicationAdd BLAST54
Alternative sequenceiVSP_025635249 – 520Missing in isoform 3. 1 PublicationAdd BLAST272
Alternative sequenceiVSP_025636424 – 520VRSRN…VNTTF → GKTACGKLGRVLFYFPRAGF LSLPKGIFCESPMFKKW in isoform 2. 1 PublicationAdd BLAST97

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ549092 mRNA Translation: CAD79342.1
AJ549387 mRNA Translation: CAD79347.1
AK131517 mRNA Translation: BAD18659.1
CH236950 Genomic DNA Translation: EAL24050.1
BC063666 mRNA Translation: AAH63666.1
BC110813 mRNA Translation: AAI10814.1
CCDSiCCDS34760.1 [Q70SY1-1]
CCDS59083.1 [Q70SY1-3]
RefSeqiNP_001240704.1, NM_001253775.1 [Q70SY1-3]
NP_919047.2, NM_194071.3 [Q70SY1-1]
UniGeneiHs.490273

Genome annotation databases

EnsembliENST00000330387; ENSP00000329140; ENSG00000182158 [Q70SY1-1]
ENST00000452463; ENSP00000410314; ENSG00000182158 [Q70SY1-3]
ENST00000456390; ENSP00000403550; ENSG00000182158 [Q70SY1-2]
GeneIDi64764
KEGGihsa:64764
UCSCiuc003vtw.4 human [Q70SY1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ549092 mRNA Translation: CAD79342.1
AJ549387 mRNA Translation: CAD79347.1
AK131517 mRNA Translation: BAD18659.1
CH236950 Genomic DNA Translation: EAL24050.1
BC063666 mRNA Translation: AAH63666.1
BC110813 mRNA Translation: AAI10814.1
CCDSiCCDS34760.1 [Q70SY1-1]
CCDS59083.1 [Q70SY1-3]
RefSeqiNP_001240704.1, NM_001253775.1 [Q70SY1-3]
NP_919047.2, NM_194071.3 [Q70SY1-1]
UniGeneiHs.490273

3D structure databases

ProteinModelPortaliQ70SY1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122277, 17 interactors
IntActiQ70SY1, 11 interactors
STRINGi9606.ENSP00000329140

PTM databases

iPTMnetiQ70SY1
PhosphoSitePlusiQ70SY1

Polymorphism and mutation databases

BioMutaiCREB3L2
DMDMi296439387

Proteomic databases

MaxQBiQ70SY1
PaxDbiQ70SY1
PeptideAtlasiQ70SY1
PRIDEiQ70SY1
ProteomicsDBi68563
68564 [Q70SY1-2]
68565 [Q70SY1-3]

Protocols and materials databases

DNASUi64764
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000330387; ENSP00000329140; ENSG00000182158 [Q70SY1-1]
ENST00000452463; ENSP00000410314; ENSG00000182158 [Q70SY1-3]
ENST00000456390; ENSP00000403550; ENSG00000182158 [Q70SY1-2]
GeneIDi64764
KEGGihsa:64764
UCSCiuc003vtw.4 human [Q70SY1-1]

Organism-specific databases

CTDi64764
DisGeNETi64764
EuPathDBiHostDB:ENSG00000182158.14
GeneCardsiCREB3L2
HGNCiHGNC:23720 CREB3L2
HPAiHPA015068
HPA015534
MalaCardsiCREB3L2
MIMi608834 gene
neXtProtiNX_Q70SY1
OpenTargetsiENSG00000182158
Orphaneti79105 Myxofibrosarcoma
PharmGKBiPA134914841
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0709 Eukaryota
ENOG410ZZQM LUCA
GeneTreeiENSGT00520000055538
HOGENOMiHOG000060150
HOVERGENiHBG057480
InParanoidiQ70SY1
KOiK09048
OMAiVDLPHFI
OrthoDBiEOG091G081Z
PhylomeDBiQ70SY1
TreeFamiTF316079

Enzyme and pathway databases

ReactomeiR-HSA-8874211 CREB3 factors activate genes
SIGNORiQ70SY1

Miscellaneous databases

ChiTaRSiCREB3L2 human
GenomeRNAii64764
PROiPR:Q70SY1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182158 Expressed in 236 organ(s), highest expression level in placenta
CleanExiHS_CREB3L2
ExpressionAtlasiQ70SY1 baseline and differential
GenevisibleiQ70SY1 HS

Family and domain databases

InterProiView protein in InterPro
IPR029804 BBF2H7
IPR004827 bZIP
PANTHERiPTHR22952:SF96 PTHR22952:SF96, 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 nameiCR3L2_HUMAN
AccessioniPrimary (citable) accession number: Q70SY1
Secondary accession number(s): Q6P454, Q6ZMR6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 18, 2010
Last modified: November 7, 2018
This is version 138 of the entry and version 3 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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