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Q68CJ9 (CR3L3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Gene names
Name:CREB3L3
Synonyms:CREBH
ORF Names:HYST1481
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length461 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.7 Ref.8

Subunit structure

Binds DNA as a dimer By similarity. Probably homodimerizes. Probably forms a heterodimer with ATF6. Interacts with ATF6. Ref.8

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.7

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.9 Ref.10

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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ATF6P188502EBI-852194,EBI-852157

Alternative products

This entry describes 3 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.
Isoform 3 (identifier: Q68CJ9-4)

The sequence of this isoform differs from the canonical sequence as follows:
     193-194: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 461461Cyclic AMP-responsive element-binding protein 3-like protein 3
PRO_0000288074
Chain1 – ?Processed cyclic AMP-responsive element-binding protein 3-like protein 3PRO_0000296216

Regions

Topological domain1 – 322322Cytoplasmic Potential
Transmembrane323 – 34321Helical; Signal-anchor for type II membrane protein; Potential
Topological domain344 – 461118Lumenal Potential
Domain243 – 30664bZIP
Region245 – 27430Basic motif By similarity
Region285 – 30622Leucine-zipper By similarity

Sites

Site363 – 3642Cleavage; by PS1 By similarity

Amino acid modifications

Glycosylation3791O-linked (GalNAc...) Ref.10
Glycosylation4101N-linked (GlcNAc...) Potential
Glycosylation4131N-linked (GlcNAc...) Ref.9
Glycosylation4201N-linked (GlcNAc...) Ref.9
Glycosylation4271N-linked (GlcNAc...) Ref.9

Natural variations

Alternative sequence531Missing in isoform 2.
VSP_025637
Alternative sequence193 – 1942Missing in isoform 3.
VSP_054876

Experimental info

Mutagenesis3611R → A: Decreases proteolytic cleavage upon ER stress. Ref.8
Sequence conflict4371L → P in BAD18804. Ref.3

Sequences

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

Last modified May 29, 2007. Version 2.
Checksum: C40F5AA626661F80

FASTA46149,077
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 53E643AF4D09C329
Show »

FASTA46048,949
Isoform 3 [UniParc].

Checksum: EBED4351D3DD72C3
Show »

FASTA45948,821

References

« Hide '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. 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 1).
Tissue: Ileal mucosa and Thalamus.
[4]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]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. expand/collapse author list , 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].
[6]"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).
Tissue: Brain.
[7]"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.
[8]"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.
[9]"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.
[10]"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, IDENTIFICATION BY 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.
AC016586 Genomic DNA. No translation available.
CH471139 Genomic DNA. Translation: EAW69260.1.
BC101508 mRNA. Translation: AAI01509.1.
BC101504 mRNA. Translation: AAI01505.1.
BC143609 mRNA. Translation: AAI43610.1.
CCDSCCDS12121.1. [Q68CJ9-1]
CCDS62500.1. [Q68CJ9-2]
RefSeqNP_001258924.1. NM_001271995.1. [Q68CJ9-2]
NP_001258925.1. NM_001271996.1.
NP_001258926.1. NM_001271997.1.
NP_115996.1. NM_032607.2. [Q68CJ9-1]
UniGeneHs.247744.

3D structure databases

ProteinModelPortalQ68CJ9.
SMRQ68CJ9. Positions 249-294.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124213. 10 interactions.
IntActQ68CJ9. 7 interactions.
MINTMINT-2877373.
STRING9606.ENSP00000078445.

PTM databases

PhosphoSiteQ68CJ9.

Polymorphism databases

DMDM148886847.

Proteomic databases

PaxDbQ68CJ9.
PRIDEQ68CJ9.

Protocols and materials databases

DNASU84699.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000078445; ENSP00000078445; ENSG00000060566. [Q68CJ9-1]
ENST00000595923; ENSP00000469355; ENSG00000060566. [Q68CJ9-2]
ENST00000602257; ENSP00000472399; ENSG00000060566.
GeneID84699.
KEGGhsa:84699.
UCSCuc002lzl.4. human. [Q68CJ9-1]
uc002lzm.4. human. [Q68CJ9-2]

Organism-specific databases

CTD84699.
GeneCardsGC19P004153.
HGNCHGNC:18855. CREB3L3.
HPAHPA040671.
MIM611998. gene.
neXtProtNX_Q68CJ9.
Orphanet70470. Hyperlipoproteinemia type 5.
PharmGKBPA134882161.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG288874.
HOGENOMHOG000059566.
HOVERGENHBG090496.
InParanoidQ68CJ9.
KOK09048.
OMADLEMWSP.
OrthoDBEOG7KM5SZ.
PhylomeDBQ68CJ9.
TreeFamTF316079.

Gene expression databases

ArrayExpressQ68CJ9.
BgeeQ68CJ9.
CleanExHS_CREB3L3.
GenevestigatorQ68CJ9.

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

GenomeRNAi84699.
NextBio35481244.
PROQ68CJ9.
SOURCESearch...

Entry information

Entry nameCR3L3_HUMAN
AccessionPrimary (citable) accession number: Q68CJ9
Secondary accession number(s): B2R7S6 expand/collapse secondary AC list , B7ZL69, Q6ZMC5, Q96TB9
Entry history
Integrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 29, 2007
Last modified: July 9, 2014
This is version 97 of the entry and version 2 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 chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM