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Q70SY1

- CR3L2_HUMAN

UniProt

Q70SY1 - CR3L2_HUMAN

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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: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

  1. cAMP response element binding Source: UniProtKB
  2. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: Ensembl
  3. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: Ensembl
  4. transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  1. cartilage development Source: UniProtKB
  2. chondrocyte differentiation Source: UniProtKB
  3. ER to Golgi vesicle-mediated transport Source: Ensembl
  4. positive regulation of transcription, DNA-templated Source: UniProtKB
  5. response to endoplasmic reticulum stress Source: UniProtKB
  6. response to unfolded protein Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

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
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
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:23720. CREB3L2.

Subcellular locationi

Endoplasmic reticulum membrane 1 Publication; Single-pass type II membrane protein 1 Publication
Chain 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.

GO - Cellular componenti

  1. endoplasmic reticulum Source: UniProtKB
  2. integral component of membrane Source: UniProtKB-KW
  3. nucleus Source: UniProtKB
Complete GO annotation...

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

Orphaneti79105. Myxofibrosarcoma.
PharmGKBiPA134914841.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 520520Cyclic AMP-responsive element-binding protein 3-like protein 2PRO_0000288067Add
BLAST
Chaini1 – ?Processed cyclic AMP-responsive element-binding protein 3-like protein 2PRO_0000296209

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei191 – 1911Phosphoserine1 Publication
Glycosylationi480 – 4801N-linked (GlcNAc...)Sequence Analysis
Glycosylationi504 – 5041N-linked (GlcNAc...)Sequence Analysis
Glycosylationi517 – 5171N-linked (GlcNAc...)Sequence Analysis

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

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ70SY1.
PaxDbiQ70SY1.
PRIDEiQ70SY1.

PTM databases

PhosphoSiteiQ70SY1.

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

Gene expression databases

BgeeiQ70SY1.
CleanExiHS_CREB3L2.
ExpressionAtlasiQ70SY1. baseline and differential.
GenevestigatoriQ70SY1.

Organism-specific databases

HPAiHPA015068.

Interactioni

Subunit structurei

Binds DNA as a dimer.By similarity

Protein-protein interaction databases

BioGridi122277. 18 interactions.
IntActiQ70SY1. 11 interactions.
STRINGi9606.ENSP00000329140.

Structurei

3D structure databases

ProteinModelPortaliQ70SY1.
SMRiQ70SY1. Positions 264-352.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 379379CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini401 – 520120LumenalSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei380 – 40021Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini294 – 35764bZIPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni296 – 32530Basic motifPROSITE-ProRule annotationAdd
BLAST
Regioni336 – 35722Leucine-zipperPROSITE-ProRule annotationAdd
BLAST

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

eggNOGiNOG294764.
GeneTreeiENSGT00520000055538.
HOGENOMiHOG000060150.
HOVERGENiHBG057480.
InParanoidiQ70SY1.
KOiK09048.
OMAiHFTEFLD.
OrthoDBiEOG7327QN.
PhylomeDBiQ70SY1.
TreeFamiTF316079.

Family and domain databases

InterProiIPR004827. bZIP.
[Graphical view]
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]

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. Align

Isoform 1 (identifier: Q70SY1) [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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti100 – 1001Missing.3 Publications
VAR_062385
Natural varianti130 – 1301V → I.3 Publications
Corresponds to variant rs273957 [ dbSNP | Ensembl ].
VAR_062386

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei195 – 24854APVDH…SALSS → GLSALPVSLWVMDMVSGSTE REYGERAGMSLYHRCCSWLY EIALFLKNKNFASK in isoform 3. 1 PublicationVSP_025634Add
BLAST
Alternative sequencei249 – 520272Missing in isoform 3. 1 PublicationVSP_025635Add
BLAST
Alternative sequencei424 – 52097VRSRN…VNTTF → GKTACGKLGRVLFYFPRAGF LSLPKGIFCESPMFKKW in isoform 2. 1 PublicationVSP_025636Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
UCSCiuc003vtv.3. human. [Q70SY1-1]
uc003vtx.2. human. [Q70SY1-2]
uc003vty.4. human. [Q70SY1-3]

Polymorphism databases

DMDMi296439387.

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS34760.1. [Q70SY1-1 ]
CCDS59083.1. [Q70SY1-3 ]
RefSeqi NP_001240704.1. NM_001253775.1. [Q70SY1-3 ]
NP_919047.2. NM_194071.3. [Q70SY1-1 ]
UniGenei Hs.490273.

3D structure databases

ProteinModelPortali Q70SY1.
SMRi Q70SY1. Positions 264-352.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 122277. 18 interactions.
IntActi Q70SY1. 11 interactions.
STRINGi 9606.ENSP00000329140.

PTM databases

PhosphoSitei Q70SY1.

Polymorphism databases

DMDMi 296439387.

Proteomic databases

MaxQBi Q70SY1.
PaxDbi Q70SY1.
PRIDEi Q70SY1.

Protocols and materials databases

DNASUi 64764.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000330387 ; ENSP00000329140 ; ENSG00000182158 . [Q70SY1-1 ]
ENST00000452463 ; ENSP00000410314 ; ENSG00000182158 . [Q70SY1-3 ]
ENST00000456390 ; ENSP00000403550 ; ENSG00000182158 . [Q70SY1-2 ]
GeneIDi 64764.
KEGGi hsa:64764.
UCSCi uc003vtv.3. human. [Q70SY1-1 ]
uc003vtx.2. human. [Q70SY1-2 ]
uc003vty.4. human. [Q70SY1-3 ]

Organism-specific databases

CTDi 64764.
GeneCardsi GC07M137559.
HGNCi HGNC:23720. CREB3L2.
HPAi HPA015068.
MIMi 608834. gene.
neXtProti NX_Q70SY1.
Orphaneti 79105. Myxofibrosarcoma.
PharmGKBi PA134914841.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG294764.
GeneTreei ENSGT00520000055538.
HOGENOMi HOG000060150.
HOVERGENi HBG057480.
InParanoidi Q70SY1.
KOi K09048.
OMAi HFTEFLD.
OrthoDBi EOG7327QN.
PhylomeDBi Q70SY1.
TreeFami TF316079.

Miscellaneous databases

ChiTaRSi CREB3L2. human.
GenomeRNAii 64764.
NextBioi 66755.
PROi Q70SY1.
SOURCEi Search...

Gene expression databases

Bgeei Q70SY1.
CleanExi HS_CREB3L2.
ExpressionAtlasi Q70SY1. baseline and differential.
Genevestigatori Q70SY1.

Family and domain databases

InterProi IPR004827. bZIP.
[Graphical view ]
Pfami PF00170. bZIP_1. 1 hit.
[Graphical view ]
SMARTi SM00338. BRLZ. 1 hit.
[Graphical view ]
PROSITEi PS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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.
    , 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.
    , 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. 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.

Entry informationi

Entry nameiCR3L2_HUMAN
AccessioniPrimary (citable) accession number: Q70SY1
Secondary accession number(s): Q6P454, Q6ZMR6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 18, 2010
Last modified: October 29, 2014
This is version 102 of the entry and version 3 of the sequence. [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. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3