Q68CJ9 (CR3L3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclic AMP-responsive element-binding protein 3-like protein 3
Short name=cAMP-responsive element-binding protein 3-like protein 3

Alternative name(s):
Transcription factor CREB-H

Cleaved into the following chain:

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

Gene names

Name:	CREB3L3
Synonyms:	CREBH
ORF Names:	HYST1481

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	461 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	Transcription factor that may act during endoplasmic reticulum stress by activating unfolded protein response target genes. Activated in response to cAMP stimulation. In vitro, binds to the cAMP response element (CRE) and box-B element. Activates transcription through box-B element. Activates transcription through CRE By similarity. Seems to function synergistically with ATF6. In acute inflammatory response, may activate expression of acute phase response (APR) genes. May be involved in growth suppression. Ref.1 Ref.6 Ref.7
Subunit structure	Binds DNA as a dimer By similarity. Probably homodimerizes. Probably forms a heterodimer with ATF6. Interacts with ATF6. Ref.7
Subcellular location	Endoplasmic reticulum membrane; Single-pass type II membrane protein Ref.1. Processed cyclic AMP-responsive element-binding protein 3-like protein 3: Nucleus. Note: Under ER stress the cleaved N-terminal cytoplasmic domain translocates into the nucleus. Ref.1
Tissue specificity	Exclusively expressed in liver. Underexpressed in hepatocellular carcinoma tissues. Ref.1 Ref.6
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). N- and O-glycosylated. N-glycosylation is required for optimal proteolytic activation. O-glycosylated with core 1 or possibly core 8 glycans. Ref.8 Ref.9
Sequence similarities	Belongs to the bZIP family. ATF subfamily. Contains 1 bZIP (basic-leucine zipper) domain.
Sequence caution	The sequence BAD18804.1 differs from that shown. Reason: Frameshift at position 445. The sequence BAD18804.1 differs from that shown. Reason: Aberrant splicing.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Unfolded protein response
Cellular component	Endoplasmic reticulum Membrane Nucleus
Coding sequence diversity	Alternative splicing
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	DNA-binding
Molecular function	Activator
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	response to unfolded protein Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA 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. Source: HPA
Molecular_function	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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATF6	P18850	2	EBI-852194,EBI-852157

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q68CJ9-1)

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: Q68CJ9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     53-53: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 461	461	Cyclic AMP-responsive element-binding protein 3-like protein 3		PRO_0000288074
	Chain	1 – ?		Processed cyclic AMP-responsive element-binding protein 3-like protein 3		PRO_0000296216
Regions
	Topological domain	1 – 322	322	Cytoplasmic Potential
	Transmembrane	323 – 343	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	344 – 461	118	Lumenal Potential
	Domain	243 – 306	64	bZIP
	Region	245 – 274	30	Basic motif By similarity
	Region	285 – 306	22	Leucine-zipper By similarity
Sites
	Site	363 – 364	2	Cleavage; by PS1 By similarity
Amino acid modifications
	Glycosylation	379	1	O-linked (GalNAc...) Ref.9
	Glycosylation	410	1	N-linked (GlcNAc...) Potential
	Glycosylation	413	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	420	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	427	1	N-linked (GlcNAc...) Ref.8
Natural variations
	Alternative sequence	53	1	Missing in isoform 2.		VSP_025637
Experimental info
	Mutagenesis	361	1	R → A: Decreases proteolytic cleavage upon ER stress. Ref.7
	Sequence conflict	437	1	L → P in BAD18804. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 29, 2007. Version 2. Checksum: C40F5AA626661F80	FASTA	461	49,077
	10 20 30 40 50 60 MNTDLAAGKM ASAACSMDPI DSFELLDLLF DRQDGILRHV ELGEGWGHVK DQQVLPNPDS 70 80 90 100 110 120 DDFLSSILGS GDSLPSSPLW SPEGSDSGIS EDLPSDPQDT PPRSGPATSP AGCHPAQPGK 130 140 150 160 170 180 GPCLSYHPGN SCSTTTPGPV IQVPEASVTI DLEMWSPGGR ICAEKPADPV DLSPRCNLTV 190 200 210 220 230 240 KDLLLSGSSG DLQQHHLGAS YLLRPGAGHC QELVLTEDEK KLLAKEGITL PTQLPLTKYE 250 260 270 280 290 300 ERVLKKIRRK IRNKQSAQES RKKKKEYIDG LETRMSACTA QNQELQRKVL HLEKQNLSLL 310 320 330 340 350 360 EQLKKLQAIV VQSTSKSAQT GTCVAVLLLS FALIILPSIS PFGPNKTESP GDFAPVRVFS 370 380 390 400 410 420 RTLHNDAASR VAADAVPGSE APGPRPEADT TREESPGSPG ADWGFQDTAN LTNSTEELDN 430 440 450 460 ATLVLRNATE GLGQVALLDW VAPGPSTGSG RAGLEAAGDE L
	Isoform 2 [UniParc]. Checksum: 53E643AF4D09C329	FASTA	460	48,949
	10 20 30 40 50 60 MNTDLAAGKM ASAACSMDPI DSFELLDLLF DRQDGILRHV ELGEGWGHVK DQVLPNPDSD 70 80 90 100 110 120 DFLSSILGSG DSLPSSPLWS PEGSDSGISE DLPSDPQDTP PRSGPATSPA GCHPAQPGKG 130 140 150 160 170 180 PCLSYHPGNS CSTTTPGPVI QVPEASVTID LEMWSPGGRI CAEKPADPVD LSPRCNLTVK 190 200 210 220 230 240 DLLLSGSSGD LQQHHLGASY LLRPGAGHCQ ELVLTEDEKK LLAKEGITLP TQLPLTKYEE 250 260 270 280 290 300 RVLKKIRRKI RNKQSAQESR KKKKEYIDGL ETRMSACTAQ NQELQRKVLH LEKQNLSLLE 310 320 330 340 350 360 QLKKLQAIVV QSTSKSAQTG TCVAVLLLSF ALIILPSISP FGPNKTESPG DFAPVRVFSR 370 380 390 400 410 420 TLHNDAASRV AADAVPGSEA PGPRPEADTT REESPGSPGA DWGFQDTANL TNSTEELDNA 430 440 450 460 TLVLRNATEG LGQVALLDWV APGPSTGSGR AGLEAAGDEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"CREB-H: a novel mammalian transcription factor belonging to the CREB/ATF family and functioning via the box-B element with a liver-specific expression." Omori Y., Imai J., Watanabe M., Komatsu T., Suzuki Y., Kataoka K., Watanabe S., Tanigami A., Sugano S. Nucleic Acids Res. 29:2154-2162(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas." Yamada S., Ohira M., Horie H., Ando K., Takayasu H., Suzuki Y., Sugano S., Hirata T., Goto T., Matsunaga T., Hiyama E., Hayashi Y., Ando H., Suita S., Kaneko M., Sasaki F., Hashizume K., Ohnuma N., Nakagawara A. Oncogene 23:5901-5911(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	"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 1). Tissue: Ileal mucosa and Thalamus.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 1). Tissue: Brain.
[6]	"The liver-enriched transcription factor CREB-H is a growth suppressor protein underexpressed in hepatocellular carcinoma." Chin K.-T., Zhou H.-J., Wong C.-M., Lee J.M.-F., Chan C.-P., Qiang B.-Q., Yuan J.-G., Ng I.-O., Jin D.-Y. Nucleic Acids Res. 33:1859-1873(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[7]	"Endoplasmic reticulum stress activates cleavage of CREBH to induce a systemic inflammatory response." Zhang K., Shen X., Wu J., Sakaki K., Saunders T., Rutkowski D.T., Back S.H., Kaufman R.J. Cell 124:587-599(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PROTEOLYTIC CLEAVAGE, SELF-ASSOCIATION, INTERACTION WITH ATF6, MUTAGENESIS OF ARG-361.
[8]	"N-linked glycosylation is required for optimal proteolytic activation of membrane-bound transcription factor CREB-H." Chan C.P., Mak T.Y., Chin K.T., Ng I.O., Jin D.Y. J. Cell Sci. 123:1438-1448(2010) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-413; ASN-420 AND ASN-427.
[9]	"Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD." Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G. Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT SER-379, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB050902 mRNA. Translation: BAB47242.1. AB073612 mRNA. Translation: BAD38649.1. AK172839 mRNA. Translation: BAD18804.1. Sequence problems. AK313099 mRNA. Translation: BAG35923.1. CH471139 Genomic DNA. Translation: EAW69260.1. BC101508 mRNA. Translation: AAI01509.1. BC101504 mRNA. Translation: AAI01505.1.
IPI	IPI00045957. IPI00441894. IPI00847524.
RefSeq	NP_001258924.1. NM_001271995.1. NP_001258925.1. NM_001271996.1. NP_001258926.1. NM_001271997.1. NP_115996.1. NM_032607.2.
UniGene	Hs.247744.
3D structure databases
ProteinModelPortal	Q68CJ9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q68CJ9. 7 interactions.
MINT	MINT-2877373.
STRING	9606.ENSP00000078445.
PTM databases
PhosphoSite	Q68CJ9.
Polymorphism databases
DMDM	148886847.
Proteomic databases
PaxDb	Q68CJ9.
PRIDE	Q68CJ9.
Protocols and materials databases
DNASU	84699.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000078445; ENSP00000078445; ENSG00000060566. ENST00000595923; ENSP00000469355; ENSG00000060566.
GeneID	84699.
KEGG	hsa:84699.
UCSC	uc002lzl.3. human. uc002lzm.3. human. uc010xic.2. human.
Organism-specific databases
CTD	84699.
GeneCards	GC19P004153.
HGNC	HGNC:18855. CREB3L3.
HPA	HPA040671.
MIM	611998. gene.
neXtProt	NX_Q68CJ9.
Orphanet	70470. Hyperlipoproteinemia type 5.
PharmGKB	PA134882161.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG288874.
HOGENOM	HOG000059566.
HOVERGEN	HBG090496.
InParanoid	Q68CJ9.
KO	K09048.
OMA	IDLEMWS.
Gene expression databases
ArrayExpress	Q68CJ9.
Bgee	Q68CJ9.
CleanEx	HS_CREB3L3.
Genevestigator	Q68CJ9.
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
GenomeRNAi	84699.
NextBio	74780.
SOURCE	Search...

Entry information

Entry name

CR3L3_HUMAN

Accession

Primary (citable) accession number: Q68CJ9
Secondary accession number(s): B2R7S6, Q6ZMC5, Q96TB9

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 29, 2007
Last sequence update:	May 29, 2007
Last modified:	May 29, 2013
This is version 86 of the entry and version 2 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.