O43889 (CREB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Leucin zipper proitein
Luman
Transcription factor LZIP-alpha

Cleaved into the following chain:

1. Processed cyclic AMP-responsive element-binding protein 3
   Short name=N-terminal Luman
   Short name=Transcriptionally active form

Gene names

Name:	CREB3
Synonyms:	LZIP

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	395 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	Endoplasmic reticulum (ER)-bound transcription factor that plays a role in the unfolded protein response (UPR). Involved in cell proliferation and migration, tumor suppression and inflammatory gene expression. Plays also a role in the human immunodeficiency virus type 1 (HIV-1) virus protein expression and in the herpes simplex virus-1 (HSV-1) latent infection and reactivation from latency. Isoform 2 plays a role in the unfolded protein response (UPR). Isoform 2 acts as a positive regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell migration. Isoform 2 may play a role as a cellular tumor suppressor that is targeted by the hepatitis C virus (HSV) core protein. Isoform 2 represses the VP16-mediated transactivation of immediate early genes of the HSV-1 virus by sequestring host cell factor-1 HCFC1 in the ER membrane of sensory neurons, thereby preventing the initiation of the replicative cascade leading to latent infection. Isoform 3 functions as a negative transcriptional regulator in ligand-induced transcriptional activation of the glucocorticoid receptor NR3C1 by recruiting and activating histone deacetylases (HDAC1, HDAC2 and HDAC6). Isoform 3 decreases the acetylation level of histone H4. Isoform 3 does not promote the chemotactic activity of leukocyte cells. Ref.1 Ref.3 Ref.4 Ref.9 Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Processed cyclic AMP-responsive element-binding protein 3: acts as a transcription factor that activates unfolded protein response (UPR) target genes during endoplasmic reticulum (ER) stress response. Promotes cell survival against ER stress-induced apoptotic cell death during UPR. Activates transcription from CRE and C/EBP-containing reporter genes. Induces transcriptional activation of chemokine receptors. Activates transcription of genes required for reactivation of the latent HSV-1 virus. Down-regulates Tat-dependent transcription of the HIV-1 LTR by interacting with HIV-1 Tat. It's transcriptional activity is inhibited by CREBZF in a HCFC1-dependent manner, by the viral transactivator protein VP16 and by the HCV core protein. Binds DNA to the cAMP response element (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP sequences present in many viral and cellular promoters. Binds to the unfolded protein respons element (UPRE) consensus sequences sites. Binds DNA to the 5'-CCAC[GA]-3'half of ERSE II (5'-ATTGG-N-CCACG-3'). Associates with chromatin to the HERPUD1 promoter. Ref.1 Ref.3 Ref.4 Ref.9 Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21
Subunit structure	Homodimer; homodimerization is prevented by the HCV core protein. Interacts with HCFC1; the interaction is required to stimulate CREB3 transcriptional activity. Isoform 2 interacts with CREBZF; the interaction occurs only in combination with HCFC1. Isoform 2 interacts (via central part and transmembrane region) with TM7SF4 (via C-terminus cytoplasmic domain). Isoform 2 interacts with OS9. Isoform 2 interacts (via leucine-zipper domain) with CREBRF (via leucine-zipper domain); the interaction occurs only after CREB3 activation and promotes CREB3 degradation. Isoform 2 interacts (via C-terminal domain) with CCR1. Isoform 2 interacts (via leucine-zipper and transmembrane domains) with HIV-1 ENV (via cytoplasmic domain). Isoform 2 interacts (via leucine-zipper and transmembrane domains) with HIV-1 TMgp41 (via cytoplasmic domain); the interaction reduces CREB3 stability. Interacts with the HCV core protein. Processed cyclic AMP-responsive element-binding protein 3 interacts with HIV-1 Tat. Ref.2 Ref.3 Ref.10 Ref.11 Ref.13 Ref.15 Ref.16 Ref.20 Ref.21
Subcellular location	Isoform 2: Endoplasmic reticulum membrane; Single-pass type II membrane protein. Membrane. Note: Colocalizes with HCFC1 in neuronal cell bodies of the trigeminal ganglia By similarity. Colocalizes with TM7SF4 in the ER membrane of immature dendritic cell (DC). Colocalizes with CANX, CCR1, HCFC1 in the ER membrane. Sequestred into the cytoplasm by the HCV core protein. Ref.3 Ref.4 Ref.9 Ref.12 Ref.13 Ref.15 Ref.16 Ref.20 Ref.21 Isoform 3: Nucleus. Cytoplasm. Note: Predominantly in the nucleus. Ref.3 Ref.4 Ref.9 Ref.12 Ref.13 Ref.15 Ref.16 Ref.20 Ref.21 Processed cyclic AMP-responsive element-binding protein 3: Nucleus. Note: Upon RIP activation the transcriptional active processed cyclic AMP-responsive element-binding protein 3 form translocates into the nucleus. Detected in the nucleus upon dendritic cell maturation and RIP activation. Colocalizes with CREBRF in nuclear foci. Colocalizes with CREBZF in promyelocytic leukemia protein nuclear bodies (PML-NB). Ref.3 Ref.4 Ref.9 Ref.12 Ref.13 Ref.15 Ref.16 Ref.20 Ref.21
Tissue specificity	Expressed in dendritic cells (DC). Weakly expressed in monocytes (at protein level). Ubiquitous. Ref.1 Ref.2 Ref.3 Ref.4 Ref.21
Induction	Up-regulated upon differentiation of monocytes towards immature dendritic cells (DC). Down-regulated upon DC maturation. Up-regulated by endoplasmic reticulum stress triggered by thapsigargin (Tg) or tunicamycin (Tm). Up-regulated by CCR1-dependent chemokines in an immediate early response and biphasic manner and by NF-kappa-B. Ref.14 Ref.17 Ref.18 Ref.20 Ref.21
Post-translational modification	The ER membrane embedded cyclic AMP-responsive element-binding protein 3 form is first proteolytically cleaved by site-1 protease (S1P) that generates membrane-associated N-terminus and a luminal C-terminus forms. The membrane-associated N-terminus form is further proteolytically processed probably by the site-2 protease (S2P) through a regulated intramembrane proteolysis (RIP), releasing the transcriptional active processed cyclic AMP-responsive element-binding protein 3 form, which is transported to the nucleus. The proteolytic cleavage is strongly induced during dendritic cell (DC) maturation and inhibited by TM7SF4. Ref.12 Ref.14 Ref.16 Ref.17 Ref.20 Ref.21 The processed cyclic AMP-responsive element-binding protein 3 is rapidly degraded. N-glycosylated. Ref.12 Ref.17
Sequence similarities	Belongs to the bZIP family. ATF subfamily. Contains 1 bZIP (basic-leucine zipper) domain.
Caution	All experiments concerning the proteolytic cleavage are done with isoform 2.

Ontologies

Keywords
Biological process	Chemotaxis Host-virus interaction Transcription Transcription regulation Unfolded protein response
Cellular component	Cytoplasm Endoplasmic reticulum Membrane Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal-anchor Transmembrane Transmembrane helix
Ligand	DNA-binding
Molecular function	Activator Repressor
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chemotaxis Inferred from electronic annotation. Source: UniProtKB-KW cytoplasmic sequestering of transcription factor Inferred from direct assay PubMed 20091349. Source: UniProtKB establishment of viral latency Inferred from direct assay PubMed 20091349. Source: UniProtKB induction of positive chemotaxis Inferred from direct assay Ref.4. Source: UniProtKB negative regulation of cell cycle Non-traceable author statement Ref.9. Source: UniProtKB negative regulation of ligand-dependent nuclear receptor transcription coactivator activity Inferred from direct assay Ref.4. Source: UniProtKB positive regulation of calcium ion transport Inferred from mutant phenotype Ref.13. Source: UniProtKB positive regulation of cell migration Inferred from mutant phenotype Ref.13. Source: UniProtKB positive regulation of deacetylase activity Inferred from direct assay Ref.4. Source: UniProtKB positive regulation of defense response to virus by host Inferred from direct assay PubMed 20091349. Source: UniProtKB positive regulation of monocyte chemotaxis Inferred from direct assay Ref.18. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.18PubMed 98051186. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response Inferred from direct assay Ref.17Ref.20. Source: UniProtKB regulation of cell growth Inferred from direct assay PubMed 20141198. Source: UniProtKB regulation of cell proliferation Inferred from mutant phenotype Ref.3. Source: UniProtKB release from viral latency Inferred from direct assay PubMed 20091349. Source: UniProtKB response to unfolded protein Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from direct assay Ref.1. Source: UniProtKB virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi membrane Inferred from direct assay PubMed 20091349. Source: UniProtKB cytosol Inferred from mutant phenotype Ref.13. Source: UniProtKB endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to endoplasmic reticulum membrane Inferred from direct assay Ref.21. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuronal cell body Inferred from direct assay PubMed 20091349. Source: UniProtKB nuclear body Inferred from direct assay Ref.20. Source: UniProtKB nucleus Inferred from direct assay Ref.21Ref.4. Source: UniProtKB
Molecular_function	CCR1 chemokine receptor binding Inferred from direct assay Ref.13. Source: UniProtKB RNA polymerase II regulatory region sequence-specific DNA binding Inferred from direct assay Ref.14Ref.17. Source: UniProtKB cAMP response element binding protein binding Inferred from direct assay Ref.1. Source: UniProtKB chromatin binding Inferred from direct assay Ref.17. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.3PubMed 20141198. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.3PubMed 20091349PubMed 20141198PubMed 97415590. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	P29846	8	EBI-625022,EBI-909718	From a different organism.
CCR1	P32246	7	EBI-625022,EBI-608322
CREBRF	Q8IUR6	4	EBI-625022,EBI-1042699
DCSTAMP	Q9H295	6	EBI-625022,EBI-6095316
HCFC1	P51610	5	EBI-625002,EBI-396176
JUN	P05412	4	EBI-625002,EBI-852823

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O43889-1)

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: O43889-2)

Also known as: LZIP;

The sequence of this isoform differs from the canonical sequence as follows:
     93-116: Missing.

Isoform 3 (identifier: O43889-3)

Also known as: smal LZIP; sLZIP;

The sequence of this isoform differs from the canonical sequence as follows:
     93-116: Missing.
     253-269: Missing.

Note: Does not contain a helical transmembrane domain.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 395	395	Cyclic AMP-responsive element-binding protein 3		PRO_0000076602
	Chain	1 – ?		Processed cyclic AMP-responsive element-binding protein 3		PRO_0000296204
Regions
	Topological domain	1 – 254	254	Cytoplasmic Potential
	Transmembrane	255 – 271	17	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	272 – 395	124	Lumenal Potential
	Domain	174 – 237	64	bZIP
	Region	1 – 92	92	Transcription activation (acidic)
	Region	176 – 208	33	Basic motif By similarity
	Region	216 – 237	22	Leucine-zipper By similarity
	Motif	13 – 17	5	LXXLL motif 1
	Motif	54 – 58	5	LXXLL motif 2
	Motif	78 – 81	4	HCFC1-binding-motif (HBM)
	Compositional bias	340 – 385	46	Pro-rich
Sites
	Site	287 – 288	2	Cleavage; by PS1 Probable
	Site	290 – 291	2	Cleavage; by PS1 Probable
Amino acid modifications
	Glycosylation	331	1	N-linked (GlcNAc...) Potential
	Glycosylation	372	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	93 – 116	24	Missing in isoform 2 and isoform 3.		VSP_011838
	Alternative sequence	253 – 269	17	Missing in isoform 3.		VSP_043805
Experimental info
	Mutagenesis	12 – 13	2	LL → AA: Does not inhibit interaction with HCFC1. Reduces transcriptional activation. Inhibits strongly transcriptional activation; when associated with 56-A-A-57 and 78-A--A-81 (isoform 2). Ref.4
	Mutagenesis	16 – 17	2	LL → AA: Does not affect the transcriptional activation of the glucocorticoid receptor NR3C1; when associated with 57-A-A-58 (isoform 3). Ref.4
	Mutagenesis	57 – 58	2	LL → AA: Does not affect the transcriptional activation of the glucocorticoid receptor NR3C1; when associated with 16-A-A-17 (isoform 3). Ref.4
	Mutagenesis	57 – 58	2	LL → AA: Does not inhibit interaction with HCFC1. Reduces transcriptional activation. Inhibits strongly transcriptional activation; when associated with 12-A-A-13 and 78-A--A-81 (isoform 2). Ref.4
	Mutagenesis	78 – 81	4	DHTY → AAAA: Inhibits interaction with HCFC1. Reduces transcriptional activation. Inhibits strongly transcriptional activation; when associated with 12-A-A-13 and 56-A-A-57. Colocalizes with HCFC1 in the nucleus (isoform 2). Ref.4 Ref.9 Ref.11 Ref.15
	Mutagenesis	81	1	Y → A: Does not retain HCFC1 in the cytoplasm, does not interact with HCFC1, does not activate promoter and fail to protect cells from a productive infection by HSV-1. Ref.4 Ref.9
	Mutagenesis	184	1	N → G: Does not bind to DNA but retains its ability to interact with HCFC1. Reduces transcriptional activation of unfolded protein respons elements (UPRE)-containing promoter. Colocalizes with HCFC1 in the ER membrane. Ref.4 Ref.15
	Mutagenesis	276	1	R → A: Does not inhibit proteolytic cleavage and transcriptional activation. Ref.4 Ref.12
	Mutagenesis	288	1	R → G: Inhibits proteolytic cleavage and transcriptional activation. Ref.4 Ref.12
	Mutagenesis	291	1	R → G: Inhibits proteolytic cleavage and transcriptional activation. Ref.4 Ref.12
	Sequence conflict	21	1	G → E in AAG43527. Ref.6
	Sequence conflict	254	1	C → G in AAD09210. Ref.3
	Sequence conflict	270	1	M → I in AAH09402. Ref.8
	Sequence conflict	286	1	L → C in AAD09210. Ref.3
	Sequence conflict	357	1	F → S in AAB69652. Ref.1
	Sequence conflict	362	1	C → V in AAD09210. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 1C412AA0D51CB7B2	FASTA	395	43,917
	10 20 30 40 50 60 MELELDAGDQ DLLAFLLEES GDLGTAPDEA VRAPLDWALP LSEVPSDWEV DDLLCSLLSP 70 80 90 100 110 120 PASLNILSSS NPCLVHHDHT YSLPRETVSM DLGECEISLT GRTGFMGLAI HTFPFAESES 130 140 150 160 170 180 CRKEGTQMTP QHMEELAEQE IARLVLTDEE KSLLEKEGLI LPETLPLTKT EEQILKRVRR 190 200 210 220 230 240 KIRNKRSAQE SRRKKKVYVG GLESRVLKYT AQNMELQNKV QLLEEQNLSL LDQLRKLQAM 250 260 270 280 290 300 VIEISNKTSS SSTCILVLLV SFCLLLVPAM YSSDTRGSLP AEHGVLSRQL RALPSEDPYQ 310 320 330 340 350 360 LELPALQSEV PKDSTHQWLD GSDCVLQAPG NTSCLLHYMP QAPSAEPPLE WPFPDLFSEP 370 380 390 LCRGPILPLQ ANLTRKGGWL PTGSPSVILQ DRYSG
	Isoform 2 (LZIP) [UniParc]. Checksum: 82152E496B924EEC	FASTA	371	41,379
	10 20 30 40 50 60 MELELDAGDQ DLLAFLLEES GDLGTAPDEA VRAPLDWALP LSEVPSDWEV DDLLCSLLSP 70 80 90 100 110 120 PASLNILSSS NPCLVHHDHT YSLPRETVSM DLESESCRKE GTQMTPQHME ELAEQEIARL 130 140 150 160 170 180 VLTDEEKSLL EKEGLILPET LPLTKTEEQI LKRVRRKIRN KRSAQESRRK KKVYVGGLES 190 200 210 220 230 240 RVLKYTAQNM ELQNKVQLLE EQNLSLLDQL RKLQAMVIEI SNKTSSSSTC ILVLLVSFCL 250 260 270 280 290 300 LLVPAMYSSD TRGSLPAEHG VLSRQLRALP SEDPYQLELP ALQSEVPKDS THQWLDGSDC 310 320 330 340 350 360 VLQAPGNTSC LLHYMPQAPS AEPPLEWPFP DLFSEPLCRG PILPLQANLT RKGGWLPTGS 370 PSVILQDRYS G
	Isoform 3 (smal LZIP) (sLZIP) [UniParc]. Checksum: BC8F014103A52111	FASTA	354	39,580
	10 20 30 40 50 60 MELELDAGDQ DLLAFLLEES GDLGTAPDEA VRAPLDWALP LSEVPSDWEV DDLLCSLLSP 70 80 90 100 110 120 PASLNILSSS NPCLVHHDHT YSLPRETVSM DLESESCRKE GTQMTPQHME ELAEQEIARL 130 140 150 160 170 180 VLTDEEKSLL EKEGLILPET LPLTKTEEQI LKRVRRKIRN KRSAQESRRK KKVYVGGLES 190 200 210 220 230 240 RVLKYTAQNM ELQNKVQLLE EQNLSLLDQL RKLQAMVIEI SNKTSSSSMY SSDTRGSLPA 250 260 270 280 290 300 EHGVLSRQLR ALPSEDPYQL ELPALQSEVP KDSTHQWLDG SDCVLQAPGN TSCLLHYMPQ 310 320 330 340 350 APSAEPPLEW PFPDLFSEPL CRGPILPLQA NLTRKGGWLP TGSPSVILQD RYSG

References

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[1]	"Luman, a new member of the CREB/ATF family, binds to herpes simplex virus VP16-associated host cellular factor." Lu R., Yang P., O'Hare P., Misra V. Mol. Cell. Biol. 17:5117-5126(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), NUCLEAR FUNCTION IN TRANSCRIPTIONAL REGULATION, DNA-BINDING, TISSUE SPECIFICITY. Tissue: Cervix carcinoma.
[2]	"Viral mimicry: common mode of association with HCF by VP16 and the cellular protein LZIP." Freiman R.N., Herr W. Genes Dev. 11:3122-3127(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH HCFC1, TISSUE SPECIFICITY. Tissue: Cervix carcinoma.
[3]	"Hepatitis C virus core protein-induced loss of LZIP function correlates with cellular transformation." Jin D.-Y., Wang H.-L., Zhou Y., Chun A.C.S., Kibler K.V., Hou Y.-D., Kung H.-F., Jeang K.-T. EMBO J. 19:729-740(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), FUNCTION IN CELL PROLIFERATION, HOMODIMERIZATION, INTERACTION WITH HCV CORE PROTEIN, DNA-BINDING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Fetal liver.
[4]	"A novel isoform of human LZIP negatively regulates the transactivation of the glucocorticoid receptor." Kang H., Kim Y.S., Ko J. Mol. Endocrinol. 23:1746-1757(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION IN LKN-1-STIMULATED CHEMOTAXIS SIGNALING (ISOFORM 2), FUNCTION IN GLUCOCORTICOID-INDUCED TRANSCRIPTIONAL REPRESSION (ISOFORM 3), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF 16-LEU-LEU-17 AND 57-LEU-LEU-58.
[5]	"Novel activation and inhibitory domains of LZIP isoforms, retinoic acid-inducible genes in P19 embryonal carcinoma cell, differentially activate transcription in mouse development." Hayashi M., Tanaka T. Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[6]	"Complete nucleotide sequence and genomic structure of the human cAMP responsive element binding protein 3 (Luman) gene (CREB3)." Ben-Yosef T., Francomano C.A. Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2).
[7]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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 2). Tissue: Pancreas and Skin.
[9]	"Potential role for luman, the cellular homologue of herpes simplex virus VP16 (alpha gene trans-inducing factor), in herpesvirus latency." Lu R., Misra V. J. Virol. 74:934-943(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN HSV-1 INFECTION (ISOFORM 2), MUTAGENESIS OF TYR-81, SUBCELLULAR LOCATION.
[10]	"Mutations in host cell factor 1 separate its role in cell proliferation from recruitment of VP16 and LZIP." Mahajan S.S., Wilson A.C. Mol. Cell. Biol. 20:919-928(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HCFC1.
[11]	"N-terminal transcriptional activation domain of LZIP comprises two LxxLL motifs and the host cell factor-1 binding motif." Luciano R.L., Wilson A.C. Proc. Natl. Acad. Sci. U.S.A. 97:10757-10762(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN TRANSCRIPTIONAL REGULATION (ISOFORM 2), INTERACTION WITH HCFC1, TRANSCRIPTIONAL ACTIVATION DOMAIN, MUTAGENESIS OF 12-LEU-LEU-13; 16-LEU-LEU-17 AND 78-ASP--TYR-81.
[12]	"Luman, the cellular counterpart of herpes simplex virus VP16, is processed by regulated intramembrane proteolysis." Raggo C., Rapin N., Stirling J., Gobeil P., Smith-Windsor E., O'Hare P., Misra V. Mol. Cell. Biol. 22:5639-5649(2002) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, CLEAVAGE SITE, MUTAGENESIS OF ARG-276; ARG-288 AND ARG-291.
[13]	"Human LZIP binds to CCR1 and differentially affects the chemotactic activities of CCR1-dependent chemokines." Ko J., Jang S.W., Kim Y.S., Kim I.S., Sung H.J., Kim H.-H., Park J.Y., Lee Y.H., Kim J., Na D.S. FASEB J. 18:890-892(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN LKN-1-STIMULATED CHEMOTAXIS SIGNALING (ISOFORM 2), INTERACTION WITH CCR1, SUBCELLULAR LOCATION.
[14]	"Luman is capable of binding and activating transcription from the unfolded protein response element." DenBoer L.M., Hardy-Smith P.W., Hogan M.R., Cockram G.P., Audas T.E., Lu R. Biochem. Biophys. Res. Commun. 331:113-119(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN THE UNFOLDED PROTEIN RESPONSE (ISOFORM 2), DNA-BINDING, ABSENCE OF PROTEOLYTIC CLEAVAGE, INDUCTION.
[15]	"Zhangfei is a potent and specific inhibitor of the host cell factor-binding transcription factor Luman." Misra V., Rapin N., Akhova O., Bainbridge M., Korchinski P. J. Biol. Chem. 280:15257-15266(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION (ISOFORM 2), INTERACTION WITH CREBZF AND HCFC1, SUBCELLULAR LOCATION, MUTAGENESIS OF 78-ASP--TYR-81 AND ASN-184.
[16]	"Luman, a new partner of HIV-1 TMgp41, interferes with Tat-mediated transcription of the HIV-1 LTR." Blot G., Lopez-Verges S., Treand C., Kubat N.J., Delcroix-Genete D., Emiliani S., Benarous R., Berlioz-Torrent C. J. Mol. Biol. 364:1034-1047(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN HIV-1 INFECTIVITY (ISOFORM 2), INTERACTION WITH HIV-1 ENV, INTERACTION WITH HIV-1 TMGP41, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING.
[17]	"Luman/CREB3 induces transcription of the endoplasmic reticulum (ER) stress response protein Herp through an ER stress response element." Liang G., Audas T.E., Li Y., Cockram G.P., Dean J.D., Martyn A.C., Kokame K., Lu R. Mol. Cell. Biol. 26:7999-8010(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN THE UNFOLDED PROTEIN RESPONSE (ISOFORM 2), DNA-BINDING, GLYCOSYLATION, PROTEOLYTIC PROCESSING, INDUCTION.
[18]	"Regulation of human LZIP expression by NF-kappaB and its involvement in monocyte cell migration induced by Lkn-1." Jang S.W., Kim Y.S., Kim Y.R., Sung H.J., Ko J. J. Biol. Chem. 282:11092-11100(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN LKN-1-STIMULATED CHEMOTAXIS SIGNALING (ISOFORM 2), INDUCTION.
[19]	"Human LZIP induces monocyte CC chemokine receptor 2 expression leading to enhancement of monocyte chemoattractant protein 1/CCL2-induced cell migration." Sung H.J., Kim Y.S., Kang H., Ko J. Exp. Mol. Med. 40:332-338(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN TRANSCRIPTIONAL ACTIVATION AND IN PROMOTING CHEMOTAXIS, DNA-BINDING.
[20]	"A novel protein, Luman/CREB3 recruitment factor, inhibits Luman activation of the unfolded protein response." Audas T.E., Li Y., Liang G., Lu R. Mol. Cell. Biol. 28:3952-3966(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CREBRF, PROTEOLYTIC PROCESSING, INDUCTION, SUBCELLULAR LOCATION.
[21]	"DC-STAMP interacts with ER-resident transcription factor LUMAN which becomes activated during DC maturation." Eleveld-Trancikova D., Sanecka A., van Hout-Kuijer M.A., Looman M.W., Hendriks I.A., Jansen B.J., Adema G.J. Mol. Immunol. 47:1963-1973(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH OS9 AND TM7SF4, PROTEOLYTIC PROCESSING, INDUCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF009368 mRNA. Translation: AAB69652.1. AF029674 mRNA. Translation: AAB84166.1. U59629 Genomic DNA. Translation: AAD09210.1. FJ263669 mRNA. Translation: ACN32251.1. U88528 mRNA. Translation: AAC04325.1. AF211847 Genomic DNA. Translation: AAG43527.1. AF211848 mRNA. Translation: AAG43528.1. AL133410 Genomic DNA. Translation: CAI10980.1. BC009402 mRNA. Translation: AAH09402.1. BC010158 mRNA. Translation: AAH10158.1.
IPI	IPI00014590. IPI00413475.
RefSeq	NP_006359.3. NM_006368.4.
UniGene	Hs.522110.
3D structure databases
ProteinModelPortal	O43889.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43889. 22 interactions.
MINT	MINT-1446829.
STRING	9606.ENSP00000342136.
PTM databases
PhosphoSite	O43889.
Proteomic databases
PaxDb	O43889.
PRIDE	O43889.
Protocols and materials databases
DNASU	10488.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000353704; ENSP00000342136; ENSG00000107175.
GeneID	10488.
KEGG	hsa:10488.
UCSC	uc003zxv.3. human. uc010mla.3. human.
Organism-specific databases
CTD	10488.
GeneCards	GC09P035722.
HGNC	HGNC:2347. CREB3.
MIM	606443. gene.
neXtProt	NX_O43889.
PharmGKB	PA26865.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG254445.
HOGENOM	HOG000133026.
HOVERGEN	HBG051114.
InParanoid	O43889.
KO	K09048.
OMA	HDHTYSL.
OrthoDB	EOG46WZ8N.
Gene expression databases
ArrayExpress	O43889.
Bgee	O43889.
CleanEx	HS_CREB3.
Genevestigator	O43889.
GermOnline	ENSG00000107175. Homo sapiens.
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	CREB3. human.
GenomeRNAi	10488.
NextBio	39796.
SOURCE	Search...

Entry information

Entry name

CREB3_HUMAN

Accession

Primary (citable) accession number: O43889
Secondary accession number(s): D0PTW6 , O14671, O14919, Q5TCV1, Q96GK8, Q9H2W3, Q9UE77

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 9, 2004
Last sequence update:	June 1, 1998
Last modified:	May 1, 2013
This is version 124 of the entry and version 1 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.