PLAG1
entrez
5324
canonical
uniprot
Q6DJT9
canonical
ensembl
ENSG00000181690
resolver
ensp
ENSP00000325546
resolver
ensp
ENSP00000404067
resolver
ensp
ENSP00000416537
resolver
ensp
ENSP00000610056
resolver
genesymbol
PLAG1
resolver
hgnc
HGNC:9045
resolver
uniprot
B4DLC2
resolver
uniprot
Q59GH8
resolver
uniprot
Q9Y4L2
resolver
uniprot_entry
PLAG1_HUMAN
resolver
uniprot_sec
B4DLC2
resolver
uniprot_sec
Q59GH8
resolver
uniprot_sec
Q9Y4L2
resolver
amino_acid_sequence
MATVIPGDLSEVRDTQKVPSGKRKRGETKPRKNFPCQLCDKAFNSVEKLKVHSYSHTGERPYKCIQQDCTKAFVSKYKLQRHMATHSPEKTHKCNYCEKMFHRKDHLKNHLHTHDPNKETFKCEECGKNYNTKLGFKRHLALHAATSGDLTCKVCLQTFESTGVLLEHLKSHAGKSSGGVKEKKHQCEHCDRRFYTRKDVRRHMVVHTGRKDFLCQYCAQRFGRKDHLTRHMKKSHNQELLKVKTEPVDFLDPFTCNVSVPIKDELLPVMSLPSSELLSKPFTNTLQLNLYNTPFQSMQSSGSAHQMITTLPLGMTCPIDMDTVHPSHHLSFKYPFSSTSYAISIPEKEQPLKGEIESYLMELQGGVPSSSQDSQASSSSKLGLDPQIGSLDDGAGDLSLSKSSISISDPLNTPALDFSQLFNFIPLNGPPYNPLSVGSLGMSYSQEEAHSSVSQLPPQTQDLQDPANTIGLGSLHSLSAAFTSSLSTSTTLPRFHQAFQ
uniprot
proteins
disease_involvement
DISEASE: Silver-Russell syndrome 4 (SRS4) [MIM:618907]: A form of Silver-Russell syndrome, a clinically heterogeneous condition characterized by severe intrauterine growth retardation, poor postnatal growth, craniofacial features such as a triangular shaped face and a broad forehead, body asymmetry, and a variety of minor malformations. The phenotypic expression changes during childhood and adolescence, with the facial features and asymmetry usually becoming more subtle with age. SRS4 inheritance is autosomal dominant. {ECO:0000269|PubMed:28796236}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=A chromosomal aberration involving PLAG1 is found in salivary gland pleiomorphic adenomas, the most common benign epithelial tumors of the salivary gland. Translocation t(3;8)(p21;q12) with constitutively expressed beta-catenin/CTNNB1. Fusion occurs in the 5'-regulatory regions, leading to promoter swapping between the 2 genes and activation of PLAG1 expression in adenomas. The chimeric transcript is formed by fusion of CTNNB1 exon 1 to PLAG1 exon 3. Reciprocal fusion transcript consisting of PLAG1 exon 1 and CTNNB1 exon 2-16 is also revealed in some adenomas (PubMed:10029085, PubMed:9020842). Translocation t(3;8)(p21;q12) with transcription elongation factor SII/TCEA1. The fusion transcript is composed of 5'-non-coding sequences as well as 63 nucleotides of the coding region of TCEA1 fused to the acceptor splice site of PLAG1 exon 3. The fusion transcript encodes a truncated TCEA1-PLAG1 protein of 90 AA as well as an apparently normal PLAG1 protein. Reciprocal fusion transcript PLAG1-TCEA1 is also present in one adenoma (PubMed:10029085, PubMed:16736500). Translocation t(5;8)(p13;q12) with leukemia inhibitory factor receptor LIFR. This fusion occured in the 5'-non-coding sequences of both genes, exchanging regulatory control element while preserving the coding sequences (PubMed:9525740). Translocation t(6;8)(p21.3-22;q13) with Coiled-coil-helix-coiled-coil-helix domain-containing protein 7/CHCHD7. Fusion occurs in the 5' regulatory regions, leading to promoter swapping and up-regulation of PLAG1 expression (PubMed:16736500). Ectopic expression of PLAG1 under the control of promoters of distinct translocation partner genes is a general pathogenetic mechanism for pleiomorphic adenomas with 8q aberrations. These fusion genes are likely to be found in adenomas with normal karyotype as this subgroup of tumors also exhibit PLAG1 activation (PubMed:10029085, PubMed:16736500, PubMed:9020842, PubMed:9525740). {ECO:0000269|PubMed:10029085, ECO:0000269|PubMed:16736500, ECO:0000269|PubMed:9020842, ECO:0000269|PubMed:9525740}.; DISEASE: Note=A chromosomal aberration involving PLAG1 may be a cause of lipoblastomas, which are benign tumors resulting from transformation of adipocytes, usually diagnosed in children. 8q12.1 to 8q24.1 intrachromosomal rearrangement with hyaluronic acid synthase 2/HAS2 results in promoter swapping and activation of PLAG1 expression. The breakpoint of HAS2 gene is in PLAG1 intron 1, whereas its coding sequence starts at exon 2 or exon 3. Translocation t(7;8)(p22;q13) with collagen 1A2/COL1A2. Fusion transcript COL1A2-PLAG1 as well as HAS2-PLAG1 encode a full-length PLAG1 protein. {ECO:0000269|PubMed:10987300, ECO:0000269|PubMed:15642402}.
uniprot
proteins
function
FUNCTION: Transcription factor whose activation results in up-regulation of target genes, such as IGFII, leading to uncontrolled cell proliferation: when overexpressed in cultured cells, higher proliferation rate and transformation are observed. Other target genes such as CRLF1, CRABP2, CRIP2, PIGF are strongly induced in cells with PLAG1 induction. Proto-oncogene whose ectopic expression can trigger the development of pleomorphic adenomas of the salivary gland and lipoblastomas. Overexpression is associated with up-regulation of IGFII, is frequently observed in hepatoblastoma, common primary liver tumor in childhood. Cooperates with CBFB-MYH11, a fusion gene important for myeloid leukemia. {ECO:0000269|PubMed:11888928, ECO:0000269|PubMed:14695992, ECO:0000269|PubMed:14712223}.
uniprot
proteins
mass_dalton
55909
uniprot
proteins
mutagenesis
MUTAGEN 23..24; /note="RK->AA: Inhibition of KPNA2 interaction when mutation occurs in the NLS; decreased nuclear import with localization in the nucleus but also in the cytoplasm; Complete inhibition of nuclear import when associated with a lack of zinc-finger domains."; /evidence="ECO:0000269|PubMed:11882654"; MUTAGEN 31..32; /note="RK->AA: No inhibition of KPNA2 interaction and no change in nuclear import."; /evidence="ECO:0000269|PubMed:11882654"; MUTAGEN 92; /note="H->A: Prevents formation of functional zinc-finger 3; induces drastic decrease of DNA affinity and complete modification of DNA binding specificity."; /evidence="ECO:0000269|PubMed:10646861"; MUTAGEN 227; /note="H->A: Prevents formation of functional zinc-finger 7 and inhibits DNA binding; No proliferation and transformation of cultured cells."; /evidence="ECO:0000269|PubMed:10646861, ECO:0000269|PubMed:11888928"; MUTAGEN 244; /note="K->R: Abolishes single and double sumoylation; nuclear localization conserved. Increases transcriptional activity and inhibits repression domain activity; when associated with R-263 and R-353."; /evidence="ECO:0000269|PubMed:15208321, ECO:0000269|PubMed:16207715"; MUTAGEN 263; /note="K->R: Decreases sumoylation; Abolishes double sumoylation only; Nuclear localization conserved. Increases transcriptional activity and inhibits repression domain activity; when associated with R-244 and R-353."; /evidence="ECO:0000269|PubMed:15208321, ECO:0000269|PubMed:16207715"; MUTAGEN 339; /note="T->A: No effect on transcription activation capacity."; /evidence="ECO:0000269|PubMed:9722527"; MUTAGEN 340; /note="S->A: No effect on transcription activation capacity."; /evidence="ECO:0000269|PubMed:9722527"; MUTAGEN 353; /note="K->R: No effect on sumoylation. Increases transcriptional activity and inhibits repression domain activity; when associated with R-244 and R-263."; /evidence="ECO:0000269|PubMed:15208321, ECO:0000269|PubMed:16207715
uniprot
proteins
post_translational_modification
PTM: Sumoylated with SUMO1; which inhibits transcriptional activity, but does not affect nuclear localization. Blockers of sumoylation pathway such as SENP3 and inactive UBE2I increases transcriptional capacity. Sumoylation is increased in the presence of PIAS1.; PTM: Acetylated by lysine acetyltransferase EP300; which activates transcriptional capacity. Lysine residues that are sumoylated also seem to be target for acetylation. {ECO:0000269|PubMed:16207715}.
uniprot
proteins
protein_family
Krueppel C2H2-type zinc-finger protein family
uniprot
proteins
pubmed
10029085
uniprot
proteins
pubmed
10646861
uniprot
proteins
pubmed
10987300
uniprot
proteins
pubmed
11882654
uniprot
proteins
pubmed
11888928
uniprot
proteins
pubmed
14695992
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14712223
uniprot
proteins
pubmed
15208321
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15642402
uniprot
proteins
pubmed
16207715
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
16736500
uniprot
proteins
pubmed
28796236
uniprot
proteins
pubmed
9020842
uniprot
proteins
pubmed
9525740
uniprot
proteins
pubmed
9722527
uniprot
proteins
sequence_length
500
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10646861, ECO:0000269|PubMed:11882654, ECO:0000269|PubMed:16207715}. Note=Strong nucleolar localization when sumoylation is inhibited.
uniprot
proteins