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Q70SY1 (CR3L2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Gene names
Name:CREB3L2
Synonyms:BBF2H7
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length520 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional activator which is processed and activated during endoplasmic reticulum stress late phase. Binds to the cAMP response element (CRE) and activates transcription through CRE. Regulates the transcription of unfolded protein response target genes, preventing accumulation of unfolded proteins in damaged neurons. Also regulates the expression of SEC23A, accelerating protein trafficking from the ER to the Golgi thereby playing a key role in chondrocyte differentiation and formation of epiphyseal cartilage By similarity. Ref.7

Subunit structure

Binds DNA as a dimer By similarity.

Subcellular location

Endoplasmic reticulum membrane; Single-pass type II membrane protein Ref.7.

Processed cyclic AMP-responsive element-binding protein 3-like protein 2: Nucleus. Note: Under ER stress the cleaved N-terminal cytoplasmic domain translocates into the nucleus. Ref.7

Tissue specificity

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. Ref.1

Post-translational modification

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).

Involvement in disease

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

Sequence similarities

Belongs to the bZIP family. ATF subfamily.

Contains 1 bZIP (basic-leucine zipper) domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
Unfolded protein response
   Cellular componentEndoplasmic reticulum
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
Polymorphism
   DiseaseProto-oncogene
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandDNA-binding
   Molecular functionActivator
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processER to Golgi vesicle-mediated transport

Inferred from electronic annotation. Source: Ensembl

cartilage development

Inferred from sequence or structural similarity. Source: UniProtKB

chondrocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.7. Source: UniProtKB

response to endoplasmic reticulum stress

Inferred from expression pattern Ref.7. Source: UniProtKB

response to unfolded protein

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentendoplasmic reticulum

Inferred from direct assay Ref.7. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from direct assay Ref.7. Source: UniProtKB

   Molecular_functioncAMP response element binding

Inferred from mutant phenotype Ref.7. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

transcription regulatory region DNA binding

Inferred from mutant phenotype Ref.7. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q70SY1-1)

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.
Isoform 2 (identifier: Q70SY1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     424-520: VRSRNLLIYE...ELDRRVNTTF → GKTACGKLGR...FCESPMFKKW
Note: No experimental confirmation available.
Isoform 3 (identifier: Q70SY1-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 520520Cyclic AMP-responsive element-binding protein 3-like protein 2
PRO_0000288067
Chain1 – ?Processed cyclic AMP-responsive element-binding protein 3-like protein 2PRO_0000296209

Regions

Topological domain1 – 379379Cytoplasmic Potential
Transmembrane380 – 40021Helical; Signal-anchor for type II membrane protein; Potential
Topological domain401 – 520120Lumenal Potential
Domain294 – 35764bZIP
Region296 – 32530Basic motif By similarity
Region336 – 35722Leucine-zipper By similarity

Amino acid modifications

Modified residue1911Phosphoserine Ref.6
Glycosylation4801N-linked (GlcNAc...) Potential
Glycosylation5041N-linked (GlcNAc...) Potential
Glycosylation5171N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence195 – 24854APVDH…SALSS → GLSALPVSLWVMDMVSGSTE REYGERAGMSLYHRCCSWLY EIALFLKNKNFASK in isoform 3.
VSP_025634
Alternative sequence249 – 520272Missing in isoform 3.
VSP_025635
Alternative sequence424 – 52097VRSRN…VNTTF → GKTACGKLGRVLFYFPRAGF LSLPKGIFCESPMFKKW in isoform 2.
VSP_025636
Natural variant1001Missing. Ref.1 Ref.3 Ref.4
VAR_062385
Natural variant1301V → I. Ref.1 Ref.3 Ref.4
Corresponds to variant rs273957 [ dbSNP | Ensembl ].
VAR_062386

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 18, 2010. Version 3.
Checksum: 64699072EEB454D3

FASTA52057,415
        10         20         30         40         50         60 
MEVLESGEQG VLQWDRKLSE LSEPGDGEAL MYHTHFSELL DEFSQNVLGQ LLNDPFLSEK 

        70         80         90        100        110        120 
SVSMEVEPSP TSPAPLIQAE HSYSLCEEPR AQSPFTHITT SDSFNDDEVE SEKWYLSTDF 

       130        140        150        160        170        180 
PSTSIKTEPV TDEPPPGLVP SVTLTITAIS TPLEKEEPPL EMNTGVDSSC QTIIPKIKLE 

       190        200        210        220        230        240 
PHEVDQFLNF SPKEAPVDHL HLPPTPPSSH GSDSEGSLSP NPRLHPFSLP QTHSPSRAAP 

       250        260        270        280        290        300 
RAPSALSSSP LLTAPHKLQG SGPLVLTEEE KRTLIAEGYP IPTKLPLSKS EEKALKKIRR 

       310        320        330        340        350        360 
KIKNKISAQE SRRKKKEYMD SLEKKVESCS TENLELRKKV EVLENTNRTL LQQLQKLQTL 

       370        380        390        400        410        420 
VMGKVSRTCK LAGTQTGTCL MVVVLCFAVA FGSFFQGYGP YPSATKMALP SQHSLQEPYT 

       430        440        450        460        470        480 
ASVVRSRNLL IYEEHSPPEE SSSPGSAGEL GGWDRGSSLL RVSGLESRPD VDLPHFIISN 

       490        500        510        520 
ETSLEKSVLL ELQQHLVSAK LEGNETLKVV ELDRRVNTTF 

« Hide

Isoform 2 [UniParc].

Checksum: 8762472720C306F0
Show »

FASTA46050,843
Isoform 3 [UniParc].

Checksum: 8AF3A941E7068506
Show »

FASTA24827,722

References

« Hide 'large scale' references
[1]"Fusion of the FUS and BBF2H7 genes in low grade fibromyxoid sarcoma."
Storlazzi C.T., Mertens F., Nascimento A., Isaksson M., Wejde J., Brosjoe O., Mandahl N., Panagopoulos I.
Hum. Mol. Genet. 12:2349-2358(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS THR-100 DEL AND ILE-130, TISSUE SPECIFICITY, CHROMOSOMAL TRANSLOCATION WITH FUS.
Tissue: Lung and Placenta.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Tongue.
[3]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS THR-100 DEL AND ILE-130.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), VARIANTS THR-100 DEL AND ILE-130.
Tissue: Brain and Skin.
[5]"The chimeric FUS/CREB3l2 gene is specific for low-grade fibromyxoid sarcoma."
Panagopoulos I., Storlazzi C.T., Fletcher C.D., Fletcher J.A., Nascimento A., Domanski H.A., Wejde J., Brosjo O., Rydholm A., Isaksson M., Mandahl N., Mertens F.
Genes Chromosomes Cancer 40:218-228(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH FUS.
[6]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-191, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"BBF2H7, a novel transmembrane bZIP transcription factor, is a new type of endoplasmic reticulum stress transducer."
Kondo S., Saito A., Hino S., Murakami T., Ogata M., Kanemoto S., Nara S., Yamashita A., Yoshinaga K., Hara H., Imaizumi K.
Mol. Cell. Biol. 27:1716-1729(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING.
[8]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001240704.1. NM_001253775.1.
NP_919047.2. NM_194071.3.
UniGeneHs.490273.

3D structure databases

ProteinModelPortalQ70SY1.
SMRQ70SY1. Positions 264-352.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122277. 17 interactions.
IntActQ70SY1. 11 interactions.
STRING9606.ENSP00000329140.

PTM databases

PhosphoSiteQ70SY1.

Polymorphism databases

DMDM296439387.

Proteomic databases

PaxDbQ70SY1.
PRIDEQ70SY1.

Protocols and materials databases

DNASU64764.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330387; ENSP00000329140; ENSG00000182158. [Q70SY1-1]
ENST00000452463; ENSP00000410314; ENSG00000182158. [Q70SY1-3]
ENST00000456390; ENSP00000403550; ENSG00000182158. [Q70SY1-2]
GeneID64764.
KEGGhsa:64764.
UCSCuc003vtv.3. human. [Q70SY1-1]
uc003vtx.2. human. [Q70SY1-2]
uc003vty.4. human. [Q70SY1-3]

Organism-specific databases

CTD64764.
GeneCardsGC07M137559.
HGNCHGNC:23720. CREB3L2.
HPAHPA015068.
MIM608834. gene.
neXtProtNX_Q70SY1.
Orphanet79105. Myxofibrosarcoma.
PharmGKBPA134914841.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG294764.
HOGENOMHOG000060150.
HOVERGENHBG057480.
InParanoidQ70SY1.
KOK09048.
OMAETEALMY.
OrthoDBEOG7327QN.
PhylomeDBQ70SY1.
TreeFamTF316079.

Gene expression databases

ArrayExpressQ70SY1.
BgeeQ70SY1.
CleanExHS_CREB3L2.
GenevestigatorQ70SY1.

Family and domain databases

InterProIPR004827. bZIP.
[Graphical view]
PfamPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCREB3L2. human.
GenomeRNAi64764.
NextBio66755.
PROQ70SY1.
SOURCESearch...

Entry information

Entry nameCR3L2_HUMAN
AccessionPrimary (citable) accession number: Q70SY1
Secondary accession number(s): Q6P454, Q6ZMR6
Entry history
Integrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 18, 2010
Last modified: April 16, 2014
This is version 98 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM