Reviewed, UniProtKB/Swiss-Prot P18848 (ATF4_HUMAN)

Names and origin

Protein names

Recommended name:
    Cyclic AMP-dependent transcription factor ATF-4
      Short name=cAMP-dependent transcription factor ATF-4
Alternative name(s):
    Activating transcription factor 4
    DNA-binding protein TAXREB67
    Cyclic AMP-responsive element-binding protein 2
      Short name=cAMP-responsive element-binding protein 2
      Short name=CREB-2

Gene names

Name:	ATF4
Synonyms:	CREB2, TXREB

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	351 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Transcriptional activator. Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. It binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I. Ref.7
Subunit structure	Interaction with SATB2 results in enhanced DNA binding and transactivation by these transcription factors By similarity. Interacts with the C-terminal region of GABBR1 via the leucine zipper of its C-terminal bZIP domain. Interacts with the C-terminal region of GABBR2 By similarity. Binds DNA as a homo- or heterodimer. Interacts with the N-terminal region of CEP290.
Subcellular location	Cytoplasm. Cell membrane. Nucleus. Note: Colocalizes with GABBR1 in hippocampal neuron dendritic membranes By similarity.
Sequence similarities	Belongs to the bZIP family. Contains 1 bZIP domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil
Ligand	DNA-binding
Molecular function	Activator
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cellular amino acid metabolic process Traceable author statement. Source: UniProtKB gluconeogenesis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: UniProtKB response to endoplasmic reticulum stress Inferred from direct assay. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein dimerization activity Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro specific RNA polymerase II transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB transcription activator activity Inferred from mutant phenotype. Source: UniProtKB transcription factor activity Traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Cebpb	P28033	1	EBI-492498,EBI-1029979	From a different organism.
DISC1	Q9NRI5	3	EBI-492498,EBI-529989
TRIB3	Q96RU7	1	EBI-492498,EBI-492476

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 351

351

Cyclic AMP-dependent transcription factor ATF-4

PRO_0000076584

Regions

Domain

306 – 334

29

Leucine-zipper

DNA binding

280 – 300

21

Basic motif

Region

305 – 341

37

Interaction with GABBR1 By similarity

Coiled coil

280 – 340

61

Natural variations

Natural variant

22

1

Q → P: dbSNP rs4894. Ref.1 Ref.2 Ref.4

VAR_028253

Natural variant

258

1

P → A: dbSNP rs1803323.

VAR_029259

Natural variant

322

1

E → D: dbSNP rs1803324.

VAR_014768

Experimental info

Sequence conflict

284

1

K → R Ref.2

Sequence conflict

290

1

T → R Ref.5

Sequence conflict

329 – 331

3

KEI → REK Ref.5

Sequence conflict

338

1

I → L Ref.5

Secondary structure

1

.

.

.

351

Helix Strand Turn

Details...

Helix

288 – 340

53

Sequences

	Sequence		Length	Mass (Da)
	P18848-1 [UniParc]. Last modified October 17, 2006. Version 3. Checksum: 3BBB7379DC3B0D07	FASTA	351	38,590
	10 20 30 40 50 60 MTEMSFLSSE VLVGDLMSPF DQSGLGAEES LGLLDDYLEV AKHFKPHGFS SDKAKAGSSE 70 80 90 100 110 120 WLAVDGLVSP SNNSKEDAFS GTDWMLEKMD LKEFDLDALL GIDDLETMPD DLLTTLDDTC 130 140 150 160 170 180 DLFAPLVQET NKQPPQTVNP IGHLPESLTK PDQVAPFTFL QPLPLSPGVL SSTPDHSFSL 190 200 210 220 230 240 ELGSEVDITE GDRKPDYTAY VAMIPQCIKE EDTPSDNDSG ICMSPESYLG SPQHSPSTRG 250 260 270 280 290 300 SPNRSLPSPG VLCGSARPKP YDPPGEKMVA AKVKGEKLDK KLKKMEQNKT AATRYRQKKR 310 320 330 340 350 AEQEALTGEC KELEKKNEAL KERADSLAKE IQYLKDLIEE VRKARGKKRV P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of cDNAs for DNA-binding proteins which specifically bind to a tax-responsive enhancer element in the long terminal repeat of human T-cell leukemia virus type I." Tsujimoto A., Nyunoya H., Morita T., Sato T., Shimotohno K. J. Virol. 65:1420-1426(1991) [PubMed: 1847461] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-22. Tissue: Fibroblast.
[2]	"Molecular cloning of human CREB-2: an ATF/CREB transcription factor that can negatively regulate transcription from the cAMP response element." Karpinski B.A., Morle G.D., Huggenvik J., Uhler M.D., Leiden J.M. Proc. Natl. Acad. Sci. U.S.A. 89:4820-4824(1992) [PubMed: 1534408] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-22. Tissue: Leukemic T-cell.
[3]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed: 10591208] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-22. Tissue: Lung and Placenta.
[5]	"Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers." Hai T., Liu F., Coukos W.J., Green M.R. Genes Dev. 3:2083-2090(1989) [PubMed: 2516827] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 274-341.
[6]	Erratum Hai T., Liu F., Coukos W.J., Green M.R. Genes Dev. 4:682-682(1990)
[7]	"The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4." Sayer J.A., Otto E.A., O'toole J.F., Nurnberg G., Kennedy M.A., Becker C., Hennies H.C., Helou J., Attanasio M., Fausett B.V., Utsch B., Khanna H., Liu Y., Drummond I., Kawakami I., Kusakabe T., Tsuda M., Ma L. , Lee H., Larson R.G., Allen S.J., Wilkinson C.J., Nigg E.A., Shou C., Lillo C., Williams D.S., Hoppe B., Kemper M.J., Neuhaus T., Parisi M.A., Glass I.A., Petry M., Kispert A., Gloy J., Ganner A., Walz G., Zhu X., Goldman D., Nurnberg P., Swaroop A., Leroux M.R., Hildebrandt F. Nat. Genet. 38:674-681(2006) [PubMed: 16682973] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CEP290.
[8]	"Crystal structure of the CCAAT box/enhancer-binding protein beta activating transcription factor-4 basic leucine zipper heterodimer in the absence of DNA." Podust L.M., Krezel A.M., Kim Y. J. Biol. Chem. 276:505-513(2001) [PubMed: 11018027] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 279-341 IN COMPLEX WITH MOUSE CEBPB.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

D90209 mRNA. Translation: BAA14234.1.
M86842 mRNA. Translation: AAA52071.1.
AL022312 Genomic DNA. Translation: CAB45284.1.
BC008090 mRNA. Translation: AAH08090.1.
BC011994 mRNA. Translation: AAH11994.1.
BC024775 mRNA. Translation: AAH24775.1.
BC073990 mRNA. Translation: AAH73990.1.

IPI

IPI00002503.

PIR

A45377.

RefSeq

NP_001666.2.
NP_877962.1.

UniGene

Hs.496487

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CI6	X-ray	2.60	A	280-341	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:207N.
DIP:354N.

IntAct

P18848. 7 interactions.

STRING

P18848.

PTM databases

PhosphoSite

P18848.

Proteomic databases

PRIDE

P18848.

Genome annotation databases

Ensembl

ENST00000337304; ENSP00000336790; ENSG00000128272; Homo sapiens. [Genome view]
ENST00000396680; ENSP00000379912; ENSG00000128272; Homo sapiens. [Genome view]
ENST00000404241; ENSP00000384587; ENSG00000128272; Homo sapiens. [Genome view]

GeneID

468.

KEGG

hsa:468.

UCSC

uc003axz.1. human.

Organism-specific databases

CTD

468.

GeneCards

GC17M071736.
GC22P038241.

HGNC

HGNC:786. ATF4.

HPA

CAB011596.

MIM

604064. gene.

PharmGKB

PA25086.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P18848.

HOVERGEN

P18848.

OMA

SYLGSPQ.

Enzyme and pathway databases

Reactome

REACT_15380. Diabetes pathways.

Gene expression databases

Bgee

P18848.

CleanEx

HS_ATF4.

Genevestigator

P18848.

GermOnline

ENSG00000128272. Homo sapiens.

Family and domain databases

InterPro

IPR011616. bZIP_1.
IPR004827. TF_bZIP.
[Graphical view]

Pfam

PF00170. bZIP_1. 1 hit.
[Graphical view]

SMART

SM00338. BRLZ. 1 hit.
[Graphical view]

PROSITE

PS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

1935.

SOURCE

Search...

Entry information

Entry name

ATF4_HUMAN

Accession

Primary (citable) accession number: P18848
Secondary accession number(s): Q9UH31

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	October 17, 2006
Last modified:	November 3, 2009
This is version 110 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.