Reviewed, UniProtKB/Swiss-Prot P15336 (ATF2_HUMAN)

Names and origin

Protein names

Recommended name:
    Cyclic AMP-dependent transcription factor ATF-2
      Short name=cAMP-dependent transcription factor ATF-2
Alternative name(s):
    Activating transcription factor 2
    cAMP response element-binding protein CRE-BP1
    HB16
    Cyclic AMP-responsive element-binding protein 2
      Short name=cAMP-responsive element-binding protein 2
      Short name=CREB-2

Gene names

Name:	ATF2
Synonyms:	CREB2, CREBP1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	505 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Transcriptional activator, probably constitutive, which binds to the cAMP-responsive element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Interaction with JUN redirects JUN to bind to CRES preferentially over the 12-O-tetradecanoylphorbol-13-acetate response elements (TRES) as part of an ATF2-c-Jun complex.
Subunit structure	Binds DNA as a dimer and can form a homodimer in the absence of DNA. Can form a heterodimer with JUN. Interacts with SMAD3 and SMAD4. Binds through its N-terminal region to UTF1 which acts as a coactivator of ATF2 transcriptional activity. Ref.5
Subcellular location	Nucleus.
Tissue specificity	Abundant expression seen in the brain.
Post-translational modification	Phosphorylation of Thr-69 and Thr-71 by MAPK14 causes increased transcriptional activity. Also phosphorylated and activated by JNK. Ref.6 Ref.7 Ref.8 Ref.9
Sequence similarities	Belongs to the bZIP family. ATF subfamily. Contains 1 bZIP domain. Contains 1 C2H2-type zinc finger.
Caution	It is uncertain whether Met-1 or Met-19 is the initiator.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from Experiment. Source: Reactome nucleus Inferred from direct assay. Source: MGI
Molecular function	RNA polymerase II transcription factor activity Traceable author statement. Source: ProtInc protein dimerization activity Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription coactivator activity Ref.1 Traceable author statement. Source: ProtInc transcription factor activity Inferred from direct assay. Source: MGI zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MAPK11	Q15759	1	EBI-1170906,EBI-298304
MAPK13	O15264	1	EBI-1170906,EBI-2116951
MAPK8	P45983-1	1	EBI-1170906,EBI-288687
MAPK9	P45984-1	1	EBI-1170906,EBI-713586
pmk-1	Q17446	1	EBI-1170906,EBI-312987	From a different organism.
VRK1	Q99986	1	EBI-1170906,EBI-1769146

Alternative products

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

Isoform 1 (identifier: P15336-1)

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: P15336-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-176: Missing.
     177-185: TSSDSSVII → MSTAYFQMM

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 505

505

Cyclic AMP-dependent transcription factor ATF-2

PRO_0000076577

Regions

Domain

380 – 408

29

Leucine-zipper

Zinc finger

25 – 49

25

C2H2-type

DNA binding

351 – 374

24

Basic motif

Amino acid modifications

Modified residue

69

1

Phosphothreonine; by MAPK14 Ref.7 Ref.9

Modified residue

71

1

Phosphothreonine; by MAPK14 Ref.7 Ref.9

Modified residue

112

1

Phosphoserine Ref.6 Ref.7 Ref.9

Modified residue

328

1

Phosphoserine Ref.8

Natural variations

Alternative sequence

1 – 176

176

Missing in isoform 2.

VSP_000587

Alternative sequence

177 – 185

9

TSSDSSVII → MSTAYFQMM in isoform 2.

VSP_000588

Natural variant

352

1

D → H in a breast cancer sample; somatic mutation. Ref.11

VAR_035999

Experimental info

Sequence conflict

209

1

V → L in AAB64017. Ref.2

Sequence conflict

223

1

N → S in CAA33886. Ref.1

Sequence conflict

311

1

R → L in AAB64017. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

505

Helix Strand Turn

Details...

Turn

30 – 32

3

Beta strand

35 – 38

4

Helix

39 – 50

12

Turn

51 – 55

5

Helix

355 – 412

58

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 25, 2008. Version 4. Checksum: 0190EEFAEC8891A7	FASTA	505	54,537
	10 20 30 40 50 60 MKFKLHVNSA RQYKDLWNMS DDKPFLCTAP GCGQRFTNED HLAVHKHKHE MTLKFGPARN 70 80 90 100 110 120 DSVIVADQTP TPTRFLKNCE EVGLFNELAS PFENEFKKAS EDDIKKMPLD LSPLATPIIR 130 140 150 160 170 180 SKIEEPSVVE TTHQDSPLPH PESTTSDEKE VPLAQTAQPT SAIVRPASLQ VPNVLLTSSD 190 200 210 220 230 240 SSVIIQQAVP SPTSSTVITQ APSSNRPIVP VPGPFPLLLH LPNGQTMPVA IPASITSSNV 250 260 270 280 290 300 HVPAAVPLVR PVTMVPSVPG IPGPSSPQPV QSEAKMRLKA ALTQQHPPVT NGDTVKGHGS 310 320 330 340 350 360 GLVRTQSEES RPQSLQQPAT STTETPASPA HTTPQTQSTS GRRRRAANED PDEKRRKFLE 370 380 390 400 410 420 RNRAAASRCR QKRKVWVQSL EKKAEDLSSL NGQLQSEVTL LRNEVAQLKQ LLLAHKDCPV 430 440 450 460 470 480 TAMQKKSGYH TADKDDSSED ISVPSSPHTE AIQHSSVSTS NGVSSTSKAE AVATSVLTQM 490 500 ADQSTEPALS QIVMAPSSQS QPSGS
	Isoform 2. Checksum: FA37EF544698FEFA	FASTA	329	35,044
	10 20 30 40 50 60 MSTAYFQMMQ QAVPSPTSST VITQAPSSNR PIVPVPGPFP LLLHLPNGQT MPVAIPASIT 70 80 90 100 110 120 SSNVHVPAAV PLVRPVTMVP SVPGIPGPSS PQPVQSEAKM RLKAALTQQH PPVTNGDTVK 130 140 150 160 170 180 GHGSGLVRTQ SEESRPQSLQ QPATSTTETP ASPAHTTPQT QSTSGRRRRA ANEDPDEKRR 190 200 210 220 230 240 KFLERNRAAA SRCRQKRKVW VQSLEKKAED LSSLNGQLQS EVTLLRNEVA QLKQLLLAHK 250 260 270 280 290 300 DCPVTAMQKK SGYHTADKDD SSEDISVPSS PHTEAIQHSS VSTSNGVSST SKAEAVATSV 310 320 LTQMADQSTE PALSQIVMAP SSQSQPSGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain." Maekawa T., Sakura H., Kanei-Ishii C., Sudo T., Yoshimura T., Fujisawa J., Yoshida M., Ishii S. EMBO J. 8:2023-2028(1989) [PubMed: 2529117] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal brain.
[2]	"Identification of a novel, spliced variant of CREB that is preferentially expressed in the thymus." Yang L., Lanier E.R., Kraig E. J. Immunol. 158:2522-2525(1997) [PubMed: 9058782] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Thymus.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"A cDNA for a human cyclic AMP response element-binding protein which is distinct from CREB and expressed preferentially in brain." Kara C.J., Liou H.-C., Ivashkiv L.B., Glimcher L.H. Mol. Cell. Biol. 10:1347-1357(1990) [PubMed: 2320002] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 211-505 (ISOFORMS 1/2).
[5]	"Characterization of functional domains of an embryonic stem cell coactivator UTF1 which are conserved and essential for potentiation of ATF-2 activity." Fukushima A., Okuda A., Nishimoto M., Seki N., Hori T.A., Muramatsu M. J. Biol. Chem. 273:25840-25849(1998) [PubMed: 9748258] [Abstract] Cited for: INTERACTION WITH UTF1.
[6]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"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: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-69; THR-71 AND SER-112, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-328, MASS SPECTROMETRY.
[9]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-69; THR-71 AND SER-112, MASS SPECTROMETRY.
[10]	"Solution structure of the transactivation domain of ATF-2 comprising a zinc finger-like subdomain and a flexible subdomain." Nagadoi A., Nakazawa K., Uda H., Okuno K., Maekawa T., Ishii S., Nishimura Y. J. Mol. Biol. 287:593-607(1999) [PubMed: 10092462] [Abstract] Cited for: STRUCTURE BY NMR OF 19-56.
[11]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-352.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

X15875 mRNA. Translation: CAA33886.1.
U16028 mRNA. Translation: AAB64017.1.
AC131958 Genomic DNA. Translation: AAX88876.1.
AC074291 Genomic DNA. Translation: AAY15004.1.
AC007435 Genomic DNA. No translation available.
AC096649 Genomic DNA. No translation available.
M31630 mRNA. Translation: AAA35951.1.

IPI

IPI00234446.
IPI00748604.

PIR

S05380.

RefSeq

NP_001871.2.

UniGene

Hs.592510

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BHI	NMR	-	A	19-56	[»]
1T2K	X-ray	3.00	D	354-414	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:632N.

IntAct

P15336. 12 interactions.

PTM databases

PhosphoSite

P15336.

Proteomic databases

PRIDE

P15336.

Genome annotation databases

Ensembl

ENSG00000115966. Homo sapiens. [Contig view]

GeneID

1386.

KEGG

hsa:1386.

Organism-specific databases

GeneCards

GC02M175645.

HGNC

HGNC:784. ATF2.

MIM

123811. gene.

PharmGKB

PA25084.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P15336.

HOVERGEN

P15336.

OMA

P15336. QNEVTLL.

Enzyme and pathway databases

Pathway_Interaction_DB

il12_2pathway. IL12-mediated signaling events.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta.

Reactome

REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpress

P15336.

Bgee

P15336.

CleanEx

HS_ATF2.

GermOnline

ENSG00000115966. Homo sapiens.

Family and domain databases

InterPro

IPR011616. bZIP_1.
IPR004827. TF_bZIP.
IPR016378. TF_cAMP-dep.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
[Graphical view]

Pfam

PF00170. bZIP_1. 1 hit.
PF00096. zf-C2H2. 1 hit.
[Graphical view]

PIRSF

PIRSF003153. ATF2_CRE-BP1. 1 hit.

SMART

SM00338. BRLZ. 1 hit.
SM00355. ZnF_C2H2. 1 hit.
[Graphical view]

PROSITE

PS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
PS50157. ZINC_FINGER_C2H2_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

5631.

SOURCE

Search...

Entry information

Entry name

ATF2_HUMAN

Accession

Primary (citable) accession number: P15336
Secondary accession number(s): Q13000, Q4ZFU9, Q53RY2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	November 25, 2008
Last modified:	June 16, 2009
This is version 107 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)