UniProt functional annotation for P05412



	UniProt functional annotation for P05412

UniProt code: P05412.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3' (PubMed:10995748, PubMed:22083952). Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation (PubMed:17210646). Involved in activated KRAS-mediated transcriptional activation of USP28 in colorectal cancer (CRC) cells (PubMed:24623306). Binds to the USP28 promoter in colorectal cancer (CRC) cells (PubMed:24623306). {ECO:0000269|PubMed:10995748, ECO:0000269|PubMed:17210646, ECO:0000269|PubMed:22083952, ECO:0000269|PubMed:24623306}.

Subunit: Heterodimer with either FOS or BATF3 or ATF7 (PubMed:10376527, PubMed:12087103, PubMed:15467742). The ATF7/JUN heterodimer is essential for ATF7 transactivation activity (PubMed:10376527). Interacts with DSIPI; the interaction inhibits the binding of active AP1 to its target DNA (By similarity). Interacts with HIVEP3 and MYBBP1A (By similarity). Interacts with SP1, SPIB and TCF20 (PubMed:10196196, PubMed:16478997, PubMed:8663478). Interacts with COPS5; the interaction leads indirectly to its phosphorylation (PubMed:8837781). Component of the SMAD3/SMAD4/JUN/FOS/complex which forms at the AP1 promoter site (PubMed:10995748). The SMAD3/SMAD4 heterodimer acts synergistically with the JUN/FOS heterodimer to activate transcription in response to TGF-beta (PubMed:9732876). Interacts (via its basic DNA binding and leucine zipper domains) with SMAD3 (via an N-terminal domain); the interaction is required for TGF- beta-mediated transactivation of the SMAD3/SMAD4/JUN/FOS/complex (PubMed:10995748). Interacts with methylated RNF187 (PubMed:20852630, PubMed:23624934). Binds to HIPK3. Interacts (when phosphorylated) with FBXW7 (PubMed:14739463). Found in a complex with PRR7 and FBXW7 (PubMed:27458189). Interacts with PRR7 and FBXW7; the interaction inhibits ubiquitination-mediated JUN degradation promoting its phosphorylation and transcriptional activity (PubMed:27458189). Interacts with RBM39 (By similarity). Interacts with PAGE4 (PubMed:24263171, PubMed:24559171, PubMed:26242913). {ECO:0000250|UniProtKB:P05627, ECO:0000250|UniProtKB:P17325, ECO:0000269|PubMed:10196196, ECO:0000269|PubMed:10376527, ECO:0000269|PubMed:10995748, ECO:0000269|PubMed:12087103, ECO:0000269|PubMed:14739463, ECO:0000269|PubMed:15467742, ECO:0000269|PubMed:16478997, ECO:0000269|PubMed:20852630, ECO:0000269|PubMed:23624934, ECO:0000269|PubMed:24263171, ECO:0000269|PubMed:24559171, ECO:0000269|PubMed:26242913, ECO:0000269|PubMed:27458189, ECO:0000269|PubMed:8663478, ECO:0000269|PubMed:8837781, ECO:0000269|PubMed:9732876}.

Subcellular location: Nucleus.

Tissue specificity: Expressed in the developing and adult prostate and prostate cancer cells. {ECO:0000269|PubMed:24263171, ECO:0000269|PubMed:24559171}.

Ptm: Ubiquitinated by the SCF(FBXW7), leading to its degradation (PubMed:14739463, PubMed:27458189). Ubiquitination takes place following phosphorylation, that promotes interaction with FBXW7 (PubMed:14739463). {ECO:0000269|PubMed:14739463, ECO:0000269|PubMed:27458189}.

Ptm: Phosphorylated by CaMK4 and PRKDC; phosphorylation enhances the transcriptional activity. Phosphorylated by HIPK3. Phosphorylated by DYRK2 at Ser-243; this primes the protein for subsequent phosphorylation by GSK3B at Thr-239. Phosphorylated at Thr-239, Ser-243 and Ser-249 by GSK3B; phosphorylation reduces its ability to bind DNA. Phosphorylated by PAK2 at Thr-2, Thr-8, Thr-89, Thr-93 and Thr-286 thereby promoting JUN-mediated cell proliferation and transformation. Phosphorylated by PLK3 following hypoxia or UV irradiation, leading to increase DNA-binding activity. {ECO:0000269|PubMed:14739463, ECO:0000269|PubMed:17210646, ECO:0000269|PubMed:17804415, ECO:0000269|PubMed:1846781, ECO:0000269|PubMed:18650425, ECO:0000269|PubMed:21177766, ECO:0000269|PubMed:22307329, ECO:0000269|PubMed:8464713, ECO:0000269|PubMed:8855261}.

Ptm: Acetylated at Lys-271 by EP300. {ECO:0000269|PubMed:11689449}.

Similarity: Belongs to the bZIP family. Jun subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3' (PubMed:10995748, PubMed:22083952). Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation (PubMed:17210646). Involved in activated KRAS-mediated transcriptional activation of USP28 in colorectal cancer (CRC) cells (PubMed:24623306). Binds to the USP28 promoter in colorectal cancer (CRC) cells (PubMed:24623306). {ECO:0000269\|PubMed:10995748, ECO:0000269\|PubMed:17210646, ECO:0000269\|PubMed:22083952, ECO:0000269\|PubMed:24623306}.


Subunit:		Heterodimer with either FOS or BATF3 or ATF7 (PubMed:10376527, PubMed:12087103, PubMed:15467742). The ATF7/JUN heterodimer is essential for ATF7 transactivation activity (PubMed:10376527). Interacts with DSIPI; the interaction inhibits the binding of active AP1 to its target DNA (By similarity). Interacts with HIVEP3 and MYBBP1A (By similarity). Interacts with SP1, SPIB and TCF20 (PubMed:10196196, PubMed:16478997, PubMed:8663478). Interacts with COPS5; the interaction leads indirectly to its phosphorylation (PubMed:8837781). Component of the SMAD3/SMAD4/JUN/FOS/complex which forms at the AP1 promoter site (PubMed:10995748). The SMAD3/SMAD4 heterodimer acts synergistically with the JUN/FOS heterodimer to activate transcription in response to TGF-beta (PubMed:9732876). Interacts (via its basic DNA binding and leucine zipper domains) with SMAD3 (via an N-terminal domain); the interaction is required for TGF- beta-mediated transactivation of the SMAD3/SMAD4/JUN/FOS/complex (PubMed:10995748). Interacts with methylated RNF187 (PubMed:20852630, PubMed:23624934). Binds to HIPK3. Interacts (when phosphorylated) with FBXW7 (PubMed:14739463). Found in a complex with PRR7 and FBXW7 (PubMed:27458189). Interacts with PRR7 and FBXW7; the interaction inhibits ubiquitination-mediated JUN degradation promoting its phosphorylation and transcriptional activity (PubMed:27458189). Interacts with RBM39 (By similarity). Interacts with PAGE4 (PubMed:24263171, PubMed:24559171, PubMed:26242913). {ECO:0000250\|UniProtKB:P05627, ECO:0000250\|UniProtKB:P17325, ECO:0000269\|PubMed:10196196, ECO:0000269\|PubMed:10376527, ECO:0000269\|PubMed:10995748, ECO:0000269\|PubMed:12087103, ECO:0000269\|PubMed:14739463, ECO:0000269\|PubMed:15467742, ECO:0000269\|PubMed:16478997, ECO:0000269\|PubMed:20852630, ECO:0000269\|PubMed:23624934, ECO:0000269\|PubMed:24263171, ECO:0000269\|PubMed:24559171, ECO:0000269\|PubMed:26242913, ECO:0000269\|PubMed:27458189, ECO:0000269\|PubMed:8663478, ECO:0000269\|PubMed:8837781, ECO:0000269\|PubMed:9732876}.
Subcellular location:		Nucleus.
Tissue specificity:		Expressed in the developing and adult prostate and prostate cancer cells. {ECO:0000269\|PubMed:24263171, ECO:0000269\|PubMed:24559171}.
Ptm:		Ubiquitinated by the SCF(FBXW7), leading to its degradation (PubMed:14739463, PubMed:27458189). Ubiquitination takes place following phosphorylation, that promotes interaction with FBXW7 (PubMed:14739463). {ECO:0000269\|PubMed:14739463, ECO:0000269\|PubMed:27458189}.
Ptm:		Phosphorylated by CaMK4 and PRKDC; phosphorylation enhances the transcriptional activity. Phosphorylated by HIPK3. Phosphorylated by DYRK2 at Ser-243; this primes the protein for subsequent phosphorylation by GSK3B at Thr-239. Phosphorylated at Thr-239, Ser-243 and Ser-249 by GSK3B; phosphorylation reduces its ability to bind DNA. Phosphorylated by PAK2 at Thr-2, Thr-8, Thr-89, Thr-93 and Thr-286 thereby promoting JUN-mediated cell proliferation and transformation. Phosphorylated by PLK3 following hypoxia or UV irradiation, leading to increase DNA-binding activity. {ECO:0000269\|PubMed:14739463, ECO:0000269\|PubMed:17210646, ECO:0000269\|PubMed:17804415, ECO:0000269\|PubMed:1846781, ECO:0000269\|PubMed:18650425, ECO:0000269\|PubMed:21177766, ECO:0000269\|PubMed:22307329, ECO:0000269\|PubMed:8464713, ECO:0000269\|PubMed:8855261}.
Ptm:		Acetylated at Lys-271 by EP300. {ECO:0000269\|PubMed:11689449}.
Similarity:		Belongs to the bZIP family. Jun subfamily. {ECO:0000305}.