Q70SY1 (CR3L2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

1. Processed cyclic AMP-responsive element-binding protein 3-like protein 2

Gene names

Name:	CREB3L2
Synonyms:	BBF2H7

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	520 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Transcription Transcription regulation Unfolded protein response
Cellular component	Endoplasmic reticulum Membrane Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Proto-oncogene
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	DNA-binding
Molecular function	Activator
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ER to Golgi vesicle-mediated transport Inferred from electronic annotation. Source: Compara chondrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription, DNA-dependent 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-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum Inferred from direct assay Ref.7. Source: UniProtKB endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	cAMP 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
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 520	520	Cyclic AMP-responsive element-binding protein 3-like protein 2		PRO_0000288067
	Chain	1 – ?		Processed cyclic AMP-responsive element-binding protein 3-like protein 2		PRO_0000296209
Regions
	Topological domain	1 – 379	379	Cytoplasmic Potential
	Transmembrane	380 – 400	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	401 – 520	120	Lumenal Potential
	Domain	294 – 357	64	bZIP
	Region	296 – 325	30	Basic motif By similarity
	Region	336 – 357	22	Leucine-zipper By similarity
Amino acid modifications
	Modified residue	191	1	Phosphoserine Ref.6
	Glycosylation	480	1	N-linked (GlcNAc...) Potential
	Glycosylation	504	1	N-linked (GlcNAc...) Potential
	Glycosylation	517	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	195 – 248	54	APVDH…SALSS → GLSALPVSLWVMDMVSGSTE REYGERAGMSLYHRCCSWLY EIALFLKNKNFASK in isoform 3.		VSP_025634
	Alternative sequence	249 – 520	272	Missing in isoform 3.		VSP_025635
	Alternative sequence	424 – 520	97	VRSRN…VNTTF → GKTACGKLGRVLFYFPRAGF LSLPKGIFCESPMFKKW in isoform 2.		VSP_025636
	Natural variant	100	1	Missing. Ref.1 Ref.3 Ref.4		VAR_062385
	Natural variant	130	1	V → I. Ref.1 Ref.3 Ref.4 Corresponds to variant rs273957 [ dbSNP | Ensembl ].		VAR_062386

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 3. Checksum: 64699072EEB454D3	FASTA	520	57,415
	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
	Isoform 2 [UniParc]. Checksum: 8762472720C306F0	FASTA	460	50,843
	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 ASVGKTACGK LGRVLFYFPR AGFLSLPKGI FCESPMFKKW
	Isoform 3 [UniParc]. Checksum: 8AF3A941E7068506	FASTA	248	27,722
	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 SPKEGLSALP VSLWVMDMVS GSTEREYGER AGMSLYHRCC SWLYEIALFL KNKNFASK

References

	« Hide 'large scale' referencesShow '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. , 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]	"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, MASS SPECTROMETRY. 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.
IPI	IPI00375520. IPI00440514. IPI00847963.
RefSeq	NP_001240704.1. NM_001253775.1. NP_919047.2. NM_194071.3.
UniGene	Hs.724212.
3D structure databases
HSSP	HSSP built from PDB template 1T2K based on UniProtKB P15336.
ProteinModelPortal	Q70SY1.
SMR	Q70SY1. Positions 300-345.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q70SY1. 11 interactions.
STRING	9606.ENSP00000329140.
PTM databases
PhosphoSite	Q70SY1.
Polymorphism databases
DMDM	296439387.
Proteomic databases
PaxDb	Q70SY1.
PRIDE	Q70SY1.
Protocols and materials databases
DNASU	64764.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000330387; ENSP00000329140; ENSG00000182158. ENST00000452463; ENSP00000410314; ENSG00000182158. ENST00000456390; ENSP00000403550; ENSG00000182158.
GeneID	64764.
KEGG	hsa:64764.
UCSC	uc003vtv.3. human. uc003vtx.2. human. uc003vty.4. human.
Organism-specific databases
CTD	64764.
GeneCards	GC07M137559.
HGNC	HGNC:23720. CREB3L2.
HPA	HPA015068.
MIM	608834. gene.
neXtProt	NX_Q70SY1.
Orphanet	79105. Myxofibrosarcoma.
PharmGKB	PA134914841.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG294764.
HOGENOM	HOG000060150.
HOVERGEN	HBG057480.
InParanoid	Q70SY1.
KO	K09048.
OMA	ETEALMY.
OrthoDB	EOG405S1B.
PhylomeDB	Q70SY1.
Gene expression databases
ArrayExpress	Q70SY1.
Bgee	Q70SY1.
CleanEx	HS_CREB3L2.
Genevestigator	Q70SY1.
Family and domain databases
InterPro	IPR004827. bZIP. IPR008917. Euk_TF_DNA-bd. [Graphical view]
Pfam	PF00170. bZIP_1. 1 hit. [Graphical view]
SMART	SM00338. BRLZ. 1 hit. [Graphical view]
SUPFAM	SSF47454. Euk_transcr_DNA. 1 hit.
PROSITE	PS50217. BZIP. 1 hit. PS00036. BZIP_BASIC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CREB3L2. human.
GenomeRNAi	64764.
NextBio	66755.
SOURCE	Search...

Entry information

Entry name

CR3L2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 90 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.