Reviewed, UniProtKB/Swiss-Prot P05412 (JUN_HUMAN)

Names and origin

Protein names

Recommended name:
    Transcription factor AP-1
Alternative name(s):
    Activator protein 1
      Short name=AP1
    Proto-oncogene c-jun
    V-jun avian sarcoma virus 17 oncogene homolog
    p39

Gene names

Name:

JUN

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

General annotation (Comments)

Function	Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'.
Subunit structure	Heterodimer with either FOS or BATF3. Interacts with HIVEP3 By similarity. Interacts with SMAD3/SMAD4 heterodimers. Interacts with MYBBP1A, SPIB and TCF20. Interacts with COPS5; indirectly leading to its phosphorylation. Interacts with DSIPI; this interaction inhibits the binding of active AP1 to its target DNA.
Subcellular location	Nucleus.
Post-translational modification	Phosphorylation enhances the transcriptional activity. Phosphorylated by PRKDC. Ref.7 Ref.13 Ref.14
Sequence similarities	Belongs to the bZIP family. Jun subfamily. Contains 1 bZIP domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Proto-oncogene
Ligand	DNA-binding
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	SMAD protein nuclear translocation Inferred from direct assay. Source: UniProtKB SMAD protein signal transduction Inferred from direct assay. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from Experiment. Source: Reactome nuclear chromosome Traceable author statement. Source: ProtInc
Molecular function	R-SMAD binding Inferred from physical interaction. Source: UniProtKB RNA polymerase II transcription factor activity Traceable author statement. Source: ProtInc Rho GTPase activator activity Inferred from direct assay. Source: UniProtKB promoter binding Inferred from direct assay. Source: UniProtKB protein dimerization activity Inferred from electronic annotation. Source: InterPro transcription factor activity Ref.2 Inferred from direct assay. Source: UniProtKB transcription factor binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EDF1	O60869-1	1	EBI-852823,EBI-781310
jnk-1	Q8WQG9	2	EBI-852823,EBI-321822	From a different organism.
MAPK8	P45983	2	EBI-852823,EBI-286483
MAPK8	P45983-1	2	EBI-852823,EBI-288687
MAPK9	P45984-1	1	EBI-852823,EBI-713586
VRK1	Q99986	3	EBI-852823,EBI-1769146

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 331

331

Transcription factor AP-1

PRO_0000076429

Regions

Domain

280 – 308

29

Leucine-zipper

DNA binding

257 – 276

20

Basic motif

Amino acid modifications

Modified residue

58

1

Phosphoserine Ref.14

Modified residue

63

1

Phosphoserine; by MAPK8 Ref.14

Modified residue

73

1

Phosphoserine; by MAPK8 Ref.13 Ref.14

Modified residue

239

1

Phosphothreonine Ref.14

Modified residue

243

1

Phosphoserine Ref.14

Natural variations

Natural variant

297

1

T → M: dbSNP rs9989.

VAR_012070

Experimental info

Sequence conflict

11

1

D → G AA sequence Ref.2

Sequence conflict

14

1

L → F AA sequence Ref.2

Sequence conflict

80

1

I → V AA sequence Ref.2

Secondary structure

1

.

.

.

331

Helix Strand Turn

Details...

Helix

255 – 306

52

Sequences

	Sequence		Length	Mass (Da)
	P05412-1 [UniParc]. Last modified October 1, 1989. Version 2. Checksum: 0695E23AC4D33561	FASTA	331	35,676
	10 20 30 40 50 60 MTAKMETTFY DDALNASFLP SESGPYGYSN PKILKQSMTL NLADPVGSLK PHLRAKNSDL 70 80 90 100 110 120 LTSPDVGLLK LASPELERLI IQSSNGHITT TPTPTQFLCP KNVTDEQEGF AEGFVRALAE 130 140 150 160 170 180 LHSQNTLPSV TSAAQPVNGA GMVAPAVASV AGGSGSGGFS ASLHSEPPVY ANLSNFNPGA 190 200 210 220 230 240 LSSGGGAPSY GAAGLAFPAQ PQQQQQPPHH LPQQMPVQHP RLQALKEEPQ TVPEMPGETP 250 260 270 280 290 300 PLSPIDMESQ ERIKAERKRM RNRIAASKCR KRKLERIARL EEKVKTLKAQ NSELASTANM 310 320 330 LREQVAQLKQ KVMNHVNSGC QLMLTQQLQT F

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and chromosomal localization of the functional intronless human JUN protooncogene." Hattori K., Angel P., le Beau M.M., Karin M. Proc. Natl. Acad. Sci. U.S.A. 85:9148-9152(1988) [PubMed: 3194415] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1." Bohmann D., Bos T.J., Admon A., Nishimura T., Vogt P.K., Tjian R. Science 238:1386-1392(1987) [PubMed: 2825349] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[3]	"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 (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	NIEHS SNPs program Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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]. Tissue: B-cell, Ovary, Testis and Uterus.
[7]	"c-Jun is phosphorylated by the DNA-dependent protein kinase in vitro; definition of the minimal kinase recognition motif." Bannister A.J., Gottlieb T.M., Kouzarides T., Jackson S.P. Nucleic Acids Res. 21:1289-1295(1993) [PubMed: 8464713] [Abstract] Cited for: PHOSPHORYLATION.
[8]	"Cross-talk between different enhancer elements during mitogenic induction of the human stromelysin-1 gene." Kirstein M., Sanz L., Moscat J., Diaz-Meco M.T., Saus J. J. Biol. Chem. 271:18231-18236(1996) [PubMed: 8663478] [Abstract] Cited for: INTERACTION WITH TCF20.
[9]	"A new group of conserved coactivators that increase the specificity of AP-1 transcription factors." Claret F.-X., Hibi M., Dhut S., Toda T., Karin M. Nature 383:453-457(1996) [PubMed: 8837781] [Abstract] Cited for: INTERACTION WITH COPS5.
[10]	"SPI-B activates transcription via a unique proline, serine, and threonine domain and exhibits DNA binding affinity differences from PU.1." Rao S., Matsumura A., Yoon J., Simon M.C. J. Biol. Chem. 274:11115-11124(1999) [PubMed: 10196196] [Abstract] Cited for: INTERACTION WITH SPIB.
[11]	"Correlation of transcriptional repression by p21(SNFT) with changes in DNA.NF-AT complex interactions." Bower K.E., Zeller R.W., Wachsman W., Martinez T., McGuire K.L. J. Biol. Chem. 277:34967-34977(2002) [PubMed: 12087103] [Abstract] Cited for: INTERACTION WITH BATF3.
[12]	"Transcriptional repression of MMP-1 by p21SNFT and reduced in vitro invasiveness of hepatocarcinoma cells." Bower K.E., Fritz J.M., McGuire K.L. Oncogene 23:8805-8814(2004) [PubMed: 15467742] [Abstract] Cited for: INTERACTION WITH BATF3.
[13]	"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-73, MASS SPECTROMETRY. Tissue: Epithelium.
[14]	"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 SER-58; SER-63; SER-73; THR-239 AND SER-243, MASS SPECTROMETRY.
[15]	"Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA." Glover J.N., Harrison S.C. Nature 373:257-261(1995) [PubMed: 7816143] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 257-313 OF COMPLEX WITH FOS.
[16]	"High resolution NMR solution structure of the leucine zipper domain of the c-Jun homodimer." Junius F.K., O'Donoghue S.I., Nilges M., Weiss A.S., King G.F. J. Biol. Chem. 271:13663-13667(1996) [PubMed: 8662824] [Abstract] Cited for: STRUCTURE BY NMR OF 276-314.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

J04111 Genomic DNA. Translation: AAA59197.1.
BT019759 mRNA. Translation: AAV38564.1.
AY217548 Genomic DNA. Translation: AAO22993.1.
AL136985 Genomic DNA. Translation: CAC10201.1.
BC002646 mRNA. No translation available.
BC006175 mRNA. Translation: AAH06175.1.
BC009874 mRNA. Translation: AAH09874.2.
BC068522 mRNA. Translation: AAH68522.1.

IPI

IPI00008965.

PIR

TVHUJN. A31264.

RefSeq

NP_002219.1.

UniGene

Hs.714791

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A02	X-ray	2.70	J	254-308	[»]
1FOS	X-ray	3.05	F/H	254-315	[»]
1JNM	X-ray	2.20	A/B	254-315	[»]
1JUN	NMR	-	A/B	276-314	[»]
1S9K	X-ray	3.10	E	257-308	[»]
1T2K	X-ray	3.00	C	254-314	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:1054N.
DIP:5961N.

IntAct

P05412. 9 interactions.

PTM databases

PhosphoSite

P05412.

Proteomic databases

PRIDE

P05412.

Genome annotation databases

Ensembl

ENSG00000177606. Homo sapiens. [Contig view]

GeneID

3725.

KEGG

hsa:3725.

Organism-specific databases

GeneCards

GC01M058958.

H-InvDB

HIX0000635.

HGNC

HGNC:6204. JUN.

HPA

CAB003801.
CAB007780.

MIM

165160. gene.

PharmGKB

PA30006.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P05412.

HOVERGEN

P05412.

OMA

P05412. KPHLRNK.

Enzyme and pathway databases

Pathway_Interaction_DB

bcr_5pathway. BCR signaling pathway.
nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
tcrcalciumpathway. Calcium signaling in the CD4+ TCR pathway.
cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
endothelinpathway. Endothelins.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
fgf_pathway. FGF signaling pathway.
hnf3apathway. FOXA1 transcription factor network.
hif1_tfpathway. HIF-1-alpha transcription factor network.
il1pathway. IL1-mediated signaling events.
il12_stat4pathway. IL12 signaling mediated by STAT4.
il2_1pathway. IL2-mediated signaling events.
il6_7pathway. IL6-mediated signaling events.
tcrjnkpathway. JNK signaling in the CD4+ TCR pathway.
lysophospholipid_pathway. LPA receptor mediated events.
avb3_opn_pathway. Osteopontin-mediated events.
pdgfrapathway. PDGFR-alpha signaling pathway.
ps1pathway. Presenilin action in Notch and Wnt signaling.
ar_tf_pathway. Regulation of Androgen receptor activity.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
telomerasepathway. Regulation of Telomerase.
s1p_s1p2_pathway. S1P2 pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
ret_pathway. Signaling events regulated by Ret tyrosine kinase.
p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta.

Reactome

REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpress

P05412.

Bgee

P05412.

CleanEx

HS_JUN.

GermOnline

ENSG00000177606. Homo sapiens.

Family and domain databases

InterPro

IPR011616. bZIP_1.
IPR015558. C_Jun.
IPR005643. JNK.
IPR002112. Leuzip_Jun.
IPR004827. TF_bZIP.
[Graphical view]

PANTHER

PTHR11462:SF8. C_Jun. 1 hit.

Pfam

PF00170. bZIP_1. 1 hit.
PF03957. Jun. 1 hit.
[Graphical view]

PRINTS

PR00043. LEUZIPPRJUN.

SMART

SM00338. BRLZ. 1 hit.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other Resources

DrugBank

DB01169. Arsenic trioxide.
DB01029. Irbesartan.
DB00570. Vinblastine.

NextBio

14583.

SOURCE

Search...

Entry information

Entry name

JUN_HUMAN

Accession

Primary (citable) accession number: P05412
Secondary accession number(s): Q96G93

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	October 1, 1989
Last modified:	June 16, 2009
This is version 130 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)