P16220 (CREB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclic AMP-responsive element-binding protein 1
Short name=CREB-1
Short name=cAMP-responsive element-binding protein 1

Gene names

Name:

CREB1

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	341 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells.
Subunit structure	Interacts with PPRC1. Binds DNA as a dimer. This dimer is stabilized by magnesium ions. Interacts, through the bZIP domain, with the coactivators TORC1/CRTC1, TORC2/CRTC2 and TORC3/CRTC3. When phosphorylated on Ser-133, binds CREBBP By similarity. Interacts with CREBL2; regulates CREB1 phosphorylation, stability and transcriptional activity By similarity. Interacts (phosphorylated form) with TOX3. Interacts with ARRB1. Binds to HIPK2. Interacts with SGK1. Ref.9 Ref.10 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.26 Ref.27
Subcellular location	Nucleus Ref.16.
Post-translational modification	Stimulated by phosphorylation. Phosphorylation of both Ser-133 and Ser-142 in the SCN regulates the activity of CREB and participates in circadian rhythm generation. Phosphorylation of Ser-133 allows CREBBP binding By similarity. CREBL2 positively regulates phosphorylation at Ser-133 thereby stimulating CREB1 transcriptional activity By similarity. Phosphorylated upon calcium influx by CaMK4 and CaMK2 on Ser-133. CaMK4 is much more potent than CaMK2 in activating CREB. Phosphorylated by CaMK2 on Ser-142. Phosphorylation of Ser-142 blocks CREB-mediated transcription even when Ser-133 is phosphorylated. Phosphorylated by CaMK1 By similarity. Phosphorylation of Ser-271 by HIPK2 in response to genotoxic stress promotes CREB1 activity, facilitating the recruitment of the coactivator CBP. Phosphorylated at Ser-133 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli. Ref.11 Ref.12 Ref.13 Ref.14 Ref.20 Ref.26 Sumoylated with SUMO1. Sumoylation on Lys-304, but not on Lys-285, is required for nuclear localization of this protein. Sumoylation is enhanced under hypoxia, promoting nuclear localization and stabilization. Ref.16
Involvement in disease	Angiomatoid fibrous histiocytoma (AFH) [MIM:612160]: A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis. Note: The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving CREB1 is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type. A CREB1 mutation has been found in a patient with multiple congenital anomalies consisting of agenesis of the corpus callosum, cerebellar hypoplasia, severe neonatal respiratory distress refractory to surfactant, thymus hypoplasia, and thyroid follicular hypoplasia (Ref.29).
Sequence similarities	Belongs to the bZIP family. Contains 1 bZIP (basic-leucine zipper) domain. Contains 1 KID (kinase-inducible) domain.

Ontologies

Keywords
Biological process	Differentiation Host-virus interaction Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Ligand	DNA-binding
Molecular function	Activator
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome TRIF-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome activation of phospholipase C activity Traceable author statement. Source: Reactome axon guidance Traceable author statement. Source: Reactome epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome innate immune response Traceable author statement. Source: Reactome lactation Inferred from electronic annotation. Source: Compara negative regulation of transcription by competitive promoter binding Inferred from direct assay PubMed 19861239. Source: BHF-UCL nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome phosphatidylinositol-mediated signaling Traceable author statement. Source: Reactome pituitary gland development Inferred from electronic annotation. Source: Compara positive regulation of fat cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of hormone secretion Inferred from electronic annotation. Source: Compara positive regulation of lipid biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of multicellular organism growth Inferred from electronic annotation. Source: Compara protein phosphorylation Inferred from direct assay PubMed 8798441. Source: MGI protein stabilization Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell size Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara stress-activated MAPK cascade Traceable author statement. Source: Reactome synaptic transmission Traceable author statement. Source: Reactome toll-like receptor 1 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 2 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 3 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nuclear euchromatin Inferred from direct assay PubMed 19861239. Source: BHF-UCL nucleoplasm Traceable author statement. Source: Reactome transcription factor complex Inferred from electronic annotation. Source: Compara
Molecular_function	RNA polymerase II distal enhancer sequence-specific DNA binding Inferred from direct assay PubMed 19861239. Source: BHF-UCL RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 19861239. Source: BHF-UCL RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Inferred from direct assay PubMed 19861239. Source: BHF-UCL cAMP response element binding Inferred from direct assay PubMed 19861239. Source: BHF-UCL transcription cofactor activity Traceable author statement PubMed 8552098. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MEIS1	O00470	9	EBI-711855,EBI-1210694
TSSK4	Q6SA08	5	EBI-711855,EBI-1202583

Alternative products

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

Isoform CREB-A (identifier: P16220-1)

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 CREB-B (identifier: P16220-2)

The sequence of this isoform differs from the canonical sequence as follows:
     88-101: Missing.

Isoform 3 (identifier: P16220-3)

Also known as: htCREB;

The sequence of this isoform differs from the canonical sequence as follows:
     162-272: Missing.

Note: Highly expressed in adult testis and sperm.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 341	341	Cyclic AMP-responsive element-binding protein 1		PRO_0000076597
Regions
	Domain	101 – 160	60	KID
	Domain	283 – 341	59	bZIP
	Region	284 – 309	26	Basic motif By similarity
	Region	311 – 332	22	Leucine-zipper By similarity
Sites
	Site	314	1	Required for binding TORCs
Amino acid modifications
	Modified residue	133	1	Phosphoserine; by CaMK1, CaMK2, CaMK4, PKB/AKT1 or PKB/AKT2, RPS6KA3, RPS6KA4, RPS6KA5 and SGK1 Ref.11 Ref.12 Ref.13 Ref.14 Ref.20
	Modified residue	142	1	Phosphoserine; by CaMK2 By similarity
	Modified residue	271	1	Phosphoserine; by HIPK2 Ref.26
	Cross-link	285		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) Ref.16
	Cross-link	304		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) Ref.16
Natural variations
	Alternative sequence	88 – 101	14	Missing in isoform CREB-B.		VSP_000596
	Alternative sequence	162 – 272	111	Missing in isoform 3.		VSP_043914
	Natural variant	116	1	D → G Found in a patient with multiple congenital anomalies; does not affect CREB1 phosphorylation at S-133; fails to interact with CREBBP. Ref.29		VAR_068077
Experimental info
	Mutagenesis	133	1	S → A: Does not interact with TOX3 and inhibits induction of transcription by TOX3. Loss of phosphorylation by CaMK4. Ref.11 Ref.27
	Mutagenesis	155	1	K → R: No effect on sumoylation. Ref.16
	Mutagenesis	271	1	S → A: Impaired phosphorylation by HIPK2 and subsequent transactivation. Ref.26
	Mutagenesis	271	1	S → E: Potentiated transactivation. Ref.26
	Mutagenesis	285	1	K → R: Decreased sumoylation, in vivo and in vitro. Ref.16
	Mutagenesis	304	1	K → R: Decreased sumoylation, in vivo and in vitro. Loss of nuclear localization. Ref.16
	Sequence conflict	4	1	E → D in CAA42620. Ref.5
	Sequence conflict	8	1	E → D in CAA42620. Ref.5
	Sequence conflict	160	1	T → A in CAA42620. Ref.5
	Sequence conflict	167	1	T → A in CAA42620. Ref.5
	Sequence conflict	169	1	T → A in CAA42620. Ref.5
	Sequence conflict	176	1	Q → R in CAA42620. Ref.5
	Sequence conflict	184	1	A → T in CAA42620. Ref.5
	Sequence conflict	188	1	G → R in CAA42620. Ref.5
	Sequence conflict	195	1	N → S in CAA42620. Ref.5
	Sequence conflict	210	1	T → A in CAA42620. Ref.5
	Sequence conflict	292	1	K → E in AAQ24858. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform CREB-A [UniParc]. Last modified May 1, 1992. Version 2. Checksum: D5E989AE40BF69AF	FASTA	341	36,688
	10 20 30 40 50 60 MTMESGAENQ QSGDAAVTEA ENQQMTVQAQ PQIATLAQVS MPAAHATSSA PTVTLVQLPN 70 80 90 100 110 120 GQTVQVHGVI QAAQPSVIQS PQVQTVQSSC KDLKRLFSGT QISTIAESED SQESVDSVTD 130 140 150 160 170 180 SQKRREILSR RPSYRKILND LSSDAPGVPR IEEEKSEEET SAPAITTVTV PTPIYQTSSG 190 200 210 220 230 240 QYIAITQGGA IQLANNGTDG VQGLQTLTMT NAAATQPGTT ILQYAQTTDG QQILVPSNQV 250 260 270 280 290 300 VVQAASGDVQ TYQIRTAPTS TIAPGVVMAS SPALPTQPAE EAARKREVRL MKNREAAREC 310 320 330 340 RRKKKEYVKC LENRVAVLEN QNKTLIEELK ALKDLYCHKS D
	Isoform CREB-B [UniParc]. Checksum: F5BA8200EE5184B7	FASTA	327	35,136
	10 20 30 40 50 60 MTMESGAENQ QSGDAAVTEA ENQQMTVQAQ PQIATLAQVS MPAAHATSSA PTVTLVQLPN 70 80 90 100 110 120 GQTVQVHGVI QAAQPSVIQS PQVQTVQIST IAESEDSQES VDSVTDSQKR REILSRRPSY 130 140 150 160 170 180 RKILNDLSSD APGVPRIEEE KSEEETSAPA ITTVTVPTPI YQTSSGQYIA ITQGGAIQLA 190 200 210 220 230 240 NNGTDGVQGL QTLTMTNAAA TQPGTTILQY AQTTDGQQIL VPSNQVVVQA ASGDVQTYQI 250 260 270 280 290 300 RTAPTSTIAP GVVMASSPAL PTQPAEEAAR KREVRLMKNR EAARECRRKK KEYVKCLENR 310 320 VAVLENQNKT LIEELKALKD LYCHKSD
	Isoform 3 (htCREB) [UniParc]. Checksum: 9FD8CA28F7632FBD	FASTA	230	25,445
	10 20 30 40 50 60 MTMESGAENQ QSGDAAVTEA ENQQMTVQAQ PQIATLAQVS MPAAHATSSA PTVTLVQLPN 70 80 90 100 110 120 GQTVQVHGVI QAAQPSVIQS PQVQTVQSSC KDLKRLFSGT QISTIAESED SQESVDSVTD 130 140 150 160 170 180 SQKRREILSR RPSYRKILND LSSDAPGVPR IEEEKSEEET SALPTQPAEE AARKREVRLM 190 200 210 220 230 KNREAARECR RKKKEYVKCL ENRVAVLENQ NKTLIEELKA LKDLYCHKSD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Two distinct forms of active transcription factor CREB (cAMP response element binding protein)." Berkowitz L.A., Gilman M.Z. Proc. Natl. Acad. Sci. U.S.A. 87:5258-5262(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CREB-A).
[2]	"Multiple cDNA clones encoding nuclear proteins that bind to the tax-dependent enhancer of HTLV-1: all contain a leucine zipper structure and basic amino acid domain." Yoshimura T., Fujisawa J., Yoshida M. EMBO J. 9:2537-2542(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CREB-A).
[3]	"Diversification of cyclic AMP-responsive enhancer binding proteins-generated by alternative exon splicing." Waeber G., Meyer T.E., Hoeffler J.P., Habener J.F. Trans. Assoc. Am. Physicians 103:28-37(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CREB-A).
[4]	"Cyclic AMP-responsive DNA-binding protein: structure based on a cloned placental cDNA." Hoeffler J.P., Meyer T.E., Yun Y., Jameson J.L., Habener J.F. Science 242:1430-1433(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CREB-B).
[5]	"Nucleotide and derived amino-acid sequences of the CRE-binding proteins from rat C6 glioma and HeLa cells." Short M.L., Manohar C.F., Furtado M.R., Ghadge G.D., Wolinsky S.M., Thimmapaya B., Jungmann R.A. Nucleic Acids Res. 19:4290-4290(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CREB-B).
[6]	"Cloning and expression of a novel CREB mRNA splice variant in human testis." Huang X., Zhang J., Lu L., Yin L., Xu M., Wang Y., Zhou Z., Sha J. Reproduction 128:775-782(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Testis.
[7]	"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 CREB-A). Tissue: Eye.
[8]	"The promoter of the gene encoding 3',5'-cyclic adenosine monophosphate (cAMP) response element binding protein contains cAMP response elements: evidence for positive autoregulation of gene transcription." Meyer T.E., Waeber G., Lin J., Beckmann W., Habener J.F. Endocrinology 132:770-780(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-8.
[9]	"HBV X protein alters the DNA binding specificity of CREB and ATF-2 by protein-protein interactions." Maguire H.F., Hoeffler J.P., Siddiqui A. Science 252:842-844(1991) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HBV PROTEIN X.
[10]	"Human T-cell lymphotropic virus type I (HTLV-I) transcriptional activator, Tax, enhances CREB binding to HTLV-I 21-base-pair repeats by protein-protein interaction." Zhao L.J., Giam C.-Z. Proc. Natl. Acad. Sci. U.S.A. 89:7070-7074(1992) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HTLV-1 TAX-1.
[11]	"Calcium/calmodulin-dependent protein kinase types II and IV differentially regulate CREB-dependent gene expression." Matthews R.P., Guthrie C.R., Wailes L.M., Zhao X., Means A.R., McKnight G.S. Mol. Cell. Biol. 14:6107-6116(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-133, MUTAGENESIS OF SER-133.
[12]	"Transcriptional activation of egr-1 by granulocyte-macrophage colony-stimulating factor but not interleukin 3 requires phosphorylation of cAMP response element-binding protein (CREB) on serine 133." Lee H.-J.J., Mignacca R.C., Sakamoto K.M. J. Biol. Chem. 270:15979-15983(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-133.
[13]	"CREB is a regulatory target for the protein kinase Akt/PKB." Du K., Montminy M. J. Biol. Chem. 273:32377-32379(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-133.
[14]	"Rsk-2 activity is necessary for epidermal growth factor-induced phosphorylation of CREB protein and transcription of c-fos gene." De Cesare D., Jacquot S., Hanauer A., Sassone-Corsi P. Proc. Natl. Acad. Sci. U.S.A. 95:12202-12207(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-133.
[15]	"TORCs: transducers of regulated CREB activity." Conkright M.D., Canettieri G., Screaton R., Guzman E., Miraglia L., Hogenesch J.B., Montminy M. Mol. Cell 12:413-423(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CRTC1.
[16]	"Small ubiquitin-related modifier-1 modification mediates resolution of CREB-dependent responses to hypoxia." Comerford K.M., Leonard M.O., Karhausen J., Carey R., Colgan S.P., Taylor C.T. Proc. Natl. Acad. Sci. U.S.A. 100:986-991(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-285 AND LYS-304, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-155; LYS-285 AND LYS-304.
[17]	"Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells." Iourgenko V., Zhang W., Mickanin C., Daly I., Jiang C., Hexham J.M., Orth A.P., Miraglia L., Meltzer J., Garza D., Chirn G.-W., McWhinnie E., Cohen D., Skelton J., Terry R., Yu Y., Bodian D., Buxton F.P. , Zhu J., Song C., Labow M.A. Proc. Natl. Acad. Sci. U.S.A. 100:12147-12152(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CRTC3.
[18]	"The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector." Screaton R.A., Conkright M.D., Katoh Y., Best J.L., Canettieri G., Jeffries S., Guzman E., Niessen S., Yates J.R. III, Takemori H., Okamoto M., Montminy M. Cell 119:61-74(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CRTC2.
[19]	"A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription." Kang J., Shi Y., Xiang B., Qu B., Su W., Zhu M., Zhang M., Bao G., Wang F., Zhang X., Yang R., Fan F., Chen X., Pei G., Ma L. Cell 123:833-847(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARRB1.
[20]	"Serum/glucocorticoid-inducible kinase can phosphorylate the cyclic AMP response element binding protein, CREB." David S., Kalb R.G. FEBS Lett. 579:1534-1538(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-133 BY SGK1, INTERACTION WITH SGK1.
[21]	"PGC-1-related coactivator: immediate early expression and characterization of a CREB/NRF-1 binding domain associated with cytochrome c promoter occupancy and respiratory growth." Vercauteren K., Pasko R.A., Gleyzer N., Marino V.M., Scarpulla R.C. Mol. Cell. Biol. 26:7409-7419(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PPRC1.
[22]	"EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma." Antonescu C.R., Dal Cin P., Nafa K., Teot L.A., Surti U., Fletcher C.D., Ladanyi M. Genes Chromosomes Cancer 46:1051-1060(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH EWSR1, ASSOCIATION WITH ANGIOMATOID FIBROUS HISTIOCYTOMA.
[23]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
[24]	"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.
[25]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[26]	"Regulation of genotoxic stress response by homeodomain-interacting protein kinase 2 through phosphorylation of cyclic AMP response element-binding protein at serine 271." Sakamoto K., Huang B.-W., Iwasaki K., Hailemariam K., Ninomiya-Tsuji J., Tsuji Y. Mol. Biol. Cell 21:2966-2974(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-271 BY HIPK2, MUTAGENESIS OF SER-271, INTERACTION WITH HIPK2.
[27]	"TOX3 is a neuronal survival factor that induces transcription depending on the presence of CITED1 or phosphorylated CREB in the transcriptionally active complex." Dittmer S., Kovacs Z., Yuan S.H., Siszler G., Kogl M., Summer H., Geerts A., Golz S., Shioda T., Methner A. J. Cell Sci. 124:252-260(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TOX3, MUTAGENESIS OF SER-133.
[28]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]	"A p.D116G mutation in CREB1 leads to novel multiple malformation syndrome resembling CrebA knockout mouse." Kitazawa S., Kondo T., Mori K., Yokoyama N., Matsuo M., Kitazawa R. Hum. Mutat. 33:651-654(2012) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN MULTIPLE CONGENITAL ANOMALIES, VARIANT GLY-116, CHARACTERIZATION OF VARIANT GLY-116.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S72459 Genomic DNA. Translation: AAB20597.1. X55545 mRNA. Translation: CAA39151.1. M34356 mRNA. Translation: AAA35717.1. M34356 mRNA. Translation: AAA35716.1. M27691 mRNA. Translation: AAA35715.1. X60003 mRNA. Translation: CAA42620.1. AY347527 mRNA. Translation: AAQ24858.1. BC010636 mRNA. Translation: AAH10636.1. S53724 Genomic DNA. Translation: AAD13869.1.
IPI	IPI00027713. IPI00218334. IPI00433048.
PIR	A35769. A37340. B35769. B37340. S22298.
RefSeq	NP_004370.1. NM_004379.3. NP_604391.1. NM_134442.3.
UniGene	Hs.516646.
3D structure databases
ProteinModelPortal	P16220.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-765N.
IntAct	P16220. 32 interactions.
MINT	MINT-1338714.
STRING	9606.ENSP00000387699.
PTM databases
PhosphoSite	P16220.
Polymorphism databases
DMDM	117434.
Proteomic databases
PaxDb	P16220.
PRIDE	P16220.
Protocols and materials databases
DNASU	1385.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000353267; ENSP00000236995; ENSG00000118260. ENST00000374397; ENSP00000363518; ENSG00000118260. ENST00000430624; ENSP00000405539; ENSG00000118260. ENST00000432329; ENSP00000387699; ENSG00000118260.
GeneID	1385.
KEGG	hsa:1385.
UCSC	uc002vcc.3. human.
Organism-specific databases
CTD	1385.
GeneCards	GC02P208394.
HGNC	HGNC:2345. CREB1.
HPA	CAB003803. HPA019150.
MIM	123810. gene. 612160. phenotype.
neXtProt	NX_P16220.
Orphanet	97338. Melanoma of soft part.
PharmGKB	PA26864.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG300199.
HOGENOM	HOG000007365.
HOVERGEN	HBG011077.
InParanoid	P16220.
KO	K05870.
OMA	QXISTIA.
OrthoDB	EOG4TB4C8.
PhylomeDB	P16220.
Enzyme and pathway databases
Pathway_Interaction_DB	hnf3bpathway. FOXA2 and FOXA3 transcription factor networks. hif1_tfpathway. HIF-1-alpha transcription factor network. lpa4_pathway. LPA4-mediated signaling events. p38_mk2pathway. p38 signaling mediated by MAPKAP kinases. smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling. ret_pathway. Signaling events regulated by Ret tyrosine kinase. p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta. pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma. mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway. lymphangiogenesis_pathway. VEGFR3 signaling in lymphatic endothelium.
Reactome	REACT_111045. Developmental Biology. REACT_111102. Signal Transduction. REACT_116125. Disease. REACT_13685. Neuronal System. REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P16220.
Bgee	P16220.
CleanEx	HS_CREB1.
Genevestigator	P16220.
GermOnline	ENSG00000118260. Homo sapiens.
Family and domain databases
InterPro	IPR004827. bZIP. IPR003102. Coactivator_CBP_pKID. IPR001630. Leuzip_CREB. [Graphical view]
Pfam	PF00170. bZIP_1. 1 hit. PF02173. pKID. 1 hit. [Graphical view]
PRINTS	PR00041. LEUZIPPRCREB.
SMART	SM00338. BRLZ. 1 hit. [Graphical view]
PROSITE	PS50217. BZIP. 1 hit. PS00036. BZIP_BASIC. 1 hit. PS50953. KID. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL5587.
DrugBank	DB00131. Adenosine monophosphate. DB01200. Bromocriptine. DB01183. Naloxone.
GenomeRNAi	1385.
NextBio	5625.
PMAP-CutDB	P16220.
SOURCE	Search...

Entry information

Entry name

CREB1_HUMAN

Accession

Primary (citable) accession number: P16220
Secondary accession number(s): P21934, Q6V963, Q9UMA7

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	May 1, 1992
Last modified:	May 1, 2013
This is version 165 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.