proline-, glutamic acid- & leucine-rich protein 1 (modulator of nongenomic activity of estrogen receptor, transcription factor HMX3, PELP1, HMX3, MNAR)

Function: - coactivator of estrogen receptor-mediated transcription - corepressor of other nuclear hormone receptors & sequence- specific transcription factors - role in estrogen receptor (ER) genomic activity when resides in the nuclear compartment by activating the ER target genes - facilitates ER nongenomic signaling via SRC & PI3K interaction in the cytosol - role in E2-mediated cell cycle progression by interacting with RB1 - role in ER/growth factor cross-talk (putative) - interacts with several growth factor signaling components including EGFR & HRS - involved in nuclear receptor signaling via its interaction with AR & NR3C1 - interacts with HRS, RXRA, SUMO₂, HDAC2, RB1 & STAT3 - interacts with PI3K, SRC & EGFR in cytoplas - interacts with ESR1 & ESR2; interaction is enhanced by 17-beta-estradiol - interacts with CREBBP, EP300, AR & NR3C1 (ligand-dependent) - forms 2 complexes in presence of 17-beta-estradio a) forms complex with SRC & ESR b) forms complex with LCK & ESR1 - interacts with histone H1 & H3, greater affinity for H1 - phosphorylated upon DNA damage, probably by ATM or ATR Structure: - Glu-rich region mediates histones interaction - LXXLL motifs are required for association with nuclear receptor ESR1 Compartment: - nucleus, cytoplasm - also found in plasma membrane Alternative splicing: named isoforms=2 Expression: - Isoform 1 is widely expressed Pathology: - may promote tumorigenesis via its interaction with & modulation of several oncogenes including SRC, PI3K, STAT3 & EGFR - role in cancer cell metastasis via its ability to modulate E2-mediated cytoskeleton changes & cell migration via its interaction with SRC & PI3K - isoform 2 is expressed in breast cancer cell lines - in a subset of breast tumors mainly in cytoplasm - localization is widely deregulated in endometrial cancers with predominantly in cytoplasm of high-grade endometrial tumors

Properties

SIZE: MW = 120 kD entity length = 1130 aa COMPARTMENT: cytoplasm cell nucleus MOTIF: LXXLL motif 1 {33-37} LXXLL motif 2 {69-73} LXXLL motif 3 {111-115} LXXLL motif 4 {155-159} LXXLL motif 5 {177-181} LXXLL motif 6 {264-268} LXXLL motif 7 {271-275} LXXLL motif 8 {364-368} LXXLL motif 9 {459-463} Ser phosphorylation site {S481} LXXLL motif 10 {579-583} LXXLL motif 11 {584-588} proline-rich region SITE: 633-872 MOTIF: proline residue (SEVERAL) Thr phosphorylation site {T745} glutamate-rich region {888-1101} MOTIF: glutamate residue (SEVERAL) proline-rich region SITE: 977-1083 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S1033} Ser phosphorylation site {S1043}

Database Correlations

UniProt Q8IZL8 PFAM correlations

References

UniProt :accession Q8IZL8