P18847 (ATF3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclic AMP-dependent transcription factor ATF-3
Short name=cAMP-dependent transcription factor ATF-3

Alternative name(s):
Activating transcription factor 3

Gene names

Name:

ATF3

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

General annotation (Comments)

Function	This protein binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Represses transcription from promoters with ATF sites. It may repress transcription by stabilizing the binding of inhibitory cofactors at the promoter. Isoform 2 activates transcription presumably by sequestering inhibitory cofactors away from the promoters.
Subunit structure	Binds DNA as a homodimer or a heterodimer.
Subcellular location	Nucleus Ref.2.
Sequence similarities	Belongs to the bZIP family. ATF subfamily. Contains 1 bZIP (basic-leucine zipper) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
Molecular function	Repressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of signaling protein activity involved in unfolded protein response Traceable author statement. Source: Reactome gluconeogenesis Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleolus Inferred from direct assay. Source: HPA nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Traceable author statement Ref.1. Source: ProtInc transcription corepressor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-712767,EBI-712767
FHL2	Q14192	3	EBI-712767,EBI-701903
RELA	Q04206	4	EBI-712767,EBI-73886

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P18847-1)

Also known as: ATF3;

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: P18847-2)

Also known as: ATF3-delta-Zip;

The sequence of this isoform differs from the canonical sequence as follows:
     116-181: KESEKLESVNAELKAQIEELKNEKQHLIYMLNLHRPTCIVRAQNGRTPEDERNLFIQQIKEGTLQS → LQY

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 3 (identifier: P18847-3)

Also known as: ATF3-delta-Zip2a/TF3-delta-Zip2b;

The sequence of this isoform differs from the canonical sequence as follows:
     117-181: ESEKLESVNA...QQIKEGTLQS → LPRPFWVQKTCIWAVDSCK

Note: Stress-induced isoform, counteracts the transcriptional repression of isoform 1.

Isoform 4 (identifier: P18847-4)

Also known as: ATF3-delta-Zip2c;

The sequence of this isoform differs from the canonical sequence as follows:
     14-42: Missing.
     117-181: ESEKLESVNA...QQIKEGTLQS → LPRPFWVQKTCIWAVDSCK

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 181	181	Cyclic AMP-dependent transcription factor ATF-3		PRO_0000076581
Regions
	Domain	86 – 149	64	bZIP
	Region	88 – 110	23	Basic motif By similarity
	Region	114 – 142	29	Leucine-zipper By similarity
Natural variations
	Alternative sequence	14 – 42	29	Missing in isoform 4.		VSP_043182
	Alternative sequence	116 – 181	66	KESEK…GTLQS → LQY in isoform 2.		VSP_000592
	Alternative sequence	117 – 181	65	ESEKL…GTLQS → LPRPFWVQKTCIWAVDSCK in isoform 3 and isoform 4.		VSP_043150
	Natural variant	38	1	T → M. Ref.5 Corresponds to variant rs11571541 [ dbSNP | Ensembl ].		VAR_048442
Experimental info
	Sequence conflict	132	1	I → L no nucleotide entry Ref.11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ATF3) [UniParc]. Last modified November 1, 1995. Version 2. Checksum: EC5D8F065EEE2D9C	FASTA	181	20,576
	10 20 30 40 50 60 MMLQHPGQVS ASEVSASAIV PCLSPPGSLV FEDFANLTPF VKEELRFAIQ NKHLCHRMSS 70 80 90 100 110 120 ALESVTVSDR PLGVSITKAE VAPEEDERKK RRRERNKIAA AKCRNKKKEK TECLQKESEK 130 140 150 160 170 180 LESVNAELKA QIEELKNEKQ HLIYMLNLHR PTCIVRAQNG RTPEDERNLF IQQIKEGTLQ S
	Isoform 2 (ATF3-delta-Zip) [UniParc]. Checksum: E0444ABC236FA838	FASTA	118	13,266
	10 20 30 40 50 60 MMLQHPGQVS ASEVSASAIV PCLSPPGSLV FEDFANLTPF VKEELRFAIQ NKHLCHRMSS 70 80 90 100 110 ALESVTVSDR PLGVSITKAE VAPEEDERKK RRRERNKIAA AKCRNKKKEK TECLQLQY
	Isoform 3 (ATF3-delta-Zip2a/TF3-delta-Zip2b) [UniParc]. Checksum: 4A7AB87BE6374478	FASTA	135	15,250
	10 20 30 40 50 60 MMLQHPGQVS ASEVSASAIV PCLSPPGSLV FEDFANLTPF VKEELRFAIQ NKHLCHRMSS 70 80 90 100 110 120 ALESVTVSDR PLGVSITKAE VAPEEDERKK RRRERNKIAA AKCRNKKKEK TECLQKLPRP 130 FWVQKTCIWA VDSCK
	Isoform 4 (ATF3-delta-Zip2c) [UniParc]. Checksum: C0BE4D381ECB1833	FASTA	106	12,261
	10 20 30 40 50 60 MMLQHPGQVS ASEEELRFAI QNKHLCHRMS SALESVTVSD RPLGVSITKA EVAPEEDERK 70 80 90 100 KRRRERNKIA AAKCRNKKKE KTECLQKLPR PFWVQKTCIW AVDSCK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"ATF3 and ATF3 delta Zip. Transcriptional repression versus activation by alternatively spliced isoforms." Chen B.P.C., Liang G., Whelan J., Hai T. J. Biol. Chem. 269:15819-15826(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[2]	"An alternatively spliced isoform of transcriptional repressor ATF3 and its induction by stress stimuli." Hashimoto Y., Zhang C., Kawauchi J., Imoto I., Adachi M.T., Inazawa J., Amagasa T., Hai T., Kitajima S. Nucleic Acids Res. 30:2398-2406(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), SUBCELLULAR LOCATION, ALTERNATIVE SPLICING.
[3]	"Amino acid deprivation and endoplasmic reticulum stress induce expression of multiple activating transcription factor-3 mRNA species that, when overexpressed in HepG2 cells, modulate transcription by the human asparagine synthetase promoter." Pan Y., Chen H., Siu F., Kilberg M.S. J. Biol. Chem. 278:38402-38412(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), ALTERNATIVE SPLICING.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	NIEHS SNPs program Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT MET-38.
[6]	"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. , 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: Cerebellum.
[7]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[8]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	Mural R.J., Istrail S., Sutton 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. , 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].
[10]	"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 1). Tissue: Muscle.
[11]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 25-181.
[12]	Erratum Hai T., Liu F., Coukos W.J., Green M.R. Genes Dev. 4:682-682(1990)
[13]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	L19871 mRNA. Translation: AAA20506.1. AB066566 mRNA. Translation: BAB84092.1. AB078026 mRNA. Translation: BAC00495.1. AB078027 mRNA. Translation: BAC00496.1. AY313927 mRNA. Translation: AAP93896.1. BT006996 mRNA. Translation: AAP35642.1. AY426987 Genomic DNA. Translation: AAQ93358.1. AK312998 mRNA. Translation: BAG35834.1. CR450334 mRNA. Translation: CAG29330.1. AC092803 Genomic DNA. No translation available. AL590648 Genomic DNA. Translation: CAH72653.1. AL590648 Genomic DNA. Translation: CAH72654.1. AL590648 Genomic DNA. Translation: CAH72656.1. AL606913 Genomic DNA. No translation available. CH471100 Genomic DNA. Translation: EAW93385.1. CH471100 Genomic DNA. Translation: EAW93386.1. CH471100 Genomic DNA. Translation: EAW93387.1. CH471100 Genomic DNA. Translation: EAW93388.1. BC006322 mRNA. Translation: AAH06322.1.
IPI	IPI00002502. IPI00385188. IPI00413177. IPI01009242.
PIR	A54025. B54025. C34223.
RefSeq	NP_001025458.1. NM_001030287.3. NP_001035709.1. NM_001040619.2. NP_001193413.2. NM_001206484.2. NP_001193415.1. NM_001206486.2. NP_001193417.2. NM_001206488.2. NP_001665.1. NM_001674.3.
UniGene	Hs.460.
3D structure databases
ProteinModelPortal	P18847.
SMR	P18847. Positions 90-140.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-254N. DIP-344N.
IntAct	P18847. 10 interactions.
MINT	MINT-4649546.
STRING	9606.ENSP00000344352.
PTM databases
PhosphoSite	P18847.
Polymorphism databases
DMDM	1168543.
Proteomic databases
PaxDb	P18847.
PRIDE	P18847.
Protocols and materials databases
DNASU	467.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000336937; ENSP00000336908; ENSG00000162772. ENST00000341491; ENSP00000344352; ENSG00000162772. ENST00000366983; ENSP00000355950; ENSG00000162772. ENST00000366987; ENSP00000355954; ENSG00000162772. ENST00000464547; ENSP00000432208; ENSG00000162772.
GeneID	467.
KEGG	hsa:467.
UCSC	uc001hjf.3. human.
Organism-specific databases
CTD	467.
GeneCards	GC01P212738.
HGNC	HGNC:785. ATF3.
HPA	HPA001562.
MIM	603148. gene.
neXtProt	NX_P18847.
PharmGKB	PA25085.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG242494.
HOGENOM	HOG000034126.
HOVERGEN	HBG003381.
InParanoid	P18847.
KO	K09032.
OMA	LVYMLNL.
OrthoDB	EOG41NTN9.
PhylomeDB	P18847.
Enzyme and pathway databases
Pathway_Interaction_DB	smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
Reactome	REACT_116125. Disease.
Gene expression databases
ArrayExpress	P18847.
Bgee	P18847.
CleanEx	HS_ATF3.
Genevestigator	P18847.
GermOnline	ENSG00000162772. Homo sapiens.
Family and domain databases
InterPro	IPR004827. bZIP. IPR000837. Leuzip_Fos. [Graphical view]
Pfam	PF00170. bZIP_1. 1 hit. [Graphical view]
PRINTS	PR00042. LEUZIPPRFOS.
SMART	SM00338. BRLZ. 1 hit. [Graphical view]
PROSITE	PS50217. BZIP. 1 hit. PS00036. BZIP_BASIC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ATF3. human.
GenomeRNAi	467.
NextBio	1925.
SOURCE	Search...

Entry information

Entry name

ATF3_HUMAN

Accession

Primary (citable) accession number: P18847
Secondary accession number(s): Q6ICQ9, Q7Z566, Q8WYM6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 136 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.