BioPAX pathway converted from "MBTPS2 (S2P) cleaves CREB3L4" in the Reactome database.3.4.24MBTPS2 (S2P) cleaves CREB3L4MBTPS2 (S2P) cleaves CREB3L4CREB3L4 (CREB4) is cleaved near the cytoplasmic face of the transmembrane domain (Stirling and O'Hare 2006, Ben-Aicha et al. 2007). Based on homology with the mouse homolog and other CREB3 proteins, MBTPS2 (S2P) cleaves CREB3L4 and the cleavage is inferred to occur at approximately amino acid 297. The cleavage releases the N-terminal domain to the cytosol.Authored: May, Bruce, 2016-05-21Reviewed: Schröder, M, 2017-02-25Edited: May, Bruce, 2016-05-21Reactome DB_ID: 88741801Golgi membraneGO0000139UniProt:Q8TEY5 CREB3L4CREB3L4JALCREB3L4AIBZIPCREB4FUNCTION Transcriptional activator that may play a role in the unfolded protein response. Binds to the UPR element (UPRE) but not to CRE element. Preferentially binds DNA with to the consensus sequence 5'-T[GT]ACGT[GA][GT]-3' and has transcriptional activation activity from UPRE. Binds to NF-kappa-B site and has transcriptional activation activity from NF-kappa-B-containing regulatory elements (By similarity).SUBUNIT Binds DNA as a dimer.TISSUE SPECIFICITY According to PubMed:11830526, exclusively expressed in the prostate. Expressed in breast and prostate cancer cell lines. Expressed in prostatic luminal epithelial cells (at protein level). Expression is significantly more abundant in prostate cancer than in benign prostatic tissue (prostatic hyperplasia). According to PubMed:12111373, also expressed in brain, pancreas and skeletal muscle, and at lower levels in small intestine, testis, leukocyte and thymus.INDUCTION By androgens.PTM N-glycosylated in the C-terminal region.PTM Controlled by regulated intramembrane proteolysis (RIP). Following ER stress a fragment containing the cytoplasmic transcription factor domain is released by proteolysis. The cleavage seems to be performed sequentially by site-1 and site-2 proteases (PS1 and PS2). PS1 cleavage may be suppressed by a determinant in the C-terminal region (By similarity).SIMILARITY Belongs to the bZIP family. ATF subfamily.Reactomehttp://www.reactome.orgHomo sapiensNCBI Taxonomy9606UniProtQ8TEY5Chain Coordinates1EQUAL338EQUALReactome DB_ID: 88742211298EQUAL338EQUALReactome DB_ID: 88741881cytosolGO00058291EQUAL297EQUALPHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 381131UniProt:O43462 MBTPS2MBTPS2S2PMBTPS2FUNCTION Involved in regulated intramembrane proteolysis (RIP) that is the cleavage of membrane-spanning regulatory proteins by proteases within the plane of the membrane. It cleaves sterol-regulatory element-binding proteins (SREBPs) within the first transmembrane segment, thereby releasing the N-terminal segment with a portion of the transmembrane segment attached. Mature N-terminal fragments shuttle to the nucleus and activate gene transcription (PubMed:9659902, PubMed:27380894). Involved in RIP-mediated regulation of bone formation (PubMed:27380894).TISSUE SPECIFICITY Expressed in heart, brain, placenta, lung, liver, muscle, kidney and pancreas.SIMILARITY Belongs to the peptidase M50A family.UniProtO434621EQUAL519EQUALGO0004222GO molecular functionReactome Database ID Release 71381068Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=381068Reactome Database ID Release 718874195Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8874195ReactomeR-HSA-88741952Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8874195.217712038Pubmed2007Transcriptional profiling of genes that are regulated by the endoplasmic reticulum-bound transcription factor AIbZIP/CREB3L4 in prostate cellsBen Aicha, SoniaLessard, JuliePelletier, MélissaFournier, AndréaCalvo, EzequielLabrie, CPhysiol. Genomics 31:295-30516236796Pubmed2006CREB4, a transmembrane bZip transcription factor and potential new substrate for regulation and cleavage by S1PStirling, JulieO'Hare, PeterMol. Biol. Cell 17:413-26