BioPAX pathway converted from "Expression of ADD1 (Adducin alpha)" in the Reactome database.LEFT-TO-RIGHTExpression of ADD1 (Adducin alpha)The ADD1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.Authored: May, B, 2011-10-13Reviewed: D'Eustachio, P, Matthews, L, Gillespie, ME, 2008-12-02 16:25:31Reviewed: Urano, F, 2010-04-30Edited: May, B, 2011-10-13ADD1 geneReactome DB_ID: 5642279nucleoplasmGENE ONTOLOGYGO:0005654ENSEMBL:ENSG00000087274 ADD1ADD1ADDAHomo sapiensNCBI Taxonomy9606ENSEMBLENSG00000087274Reactome Database ID Release 755642279Database 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=5642279ReactomeR-HSA-56422791Reactome 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-5642279.1Reactomehttp://www.reactome.orgADD1Adducin alphaAlpha adducinReactome DB_ID: 201623cytosolGENE ONTOLOGYGO:0005829UniProt:P35611 ADD1ADD1ADDAFUNCTION Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to calmodulin.SUBUNIT Heterodimer of an alpha and a beta subunit or an alpha and a gamma subunit.TISSUE SPECIFICITY Expressed in all tissues. Found in much higher levels in reticulocytes than the beta subunit.DOMAIN Each subunit is comprised of three regions: a NH2-terminal protease-resistant globular head region, a short connecting subdomain, and a protease-sensitive tail region.SIMILARITY Belongs to the aldolase class II family. Adducin subfamily.UniProtP356111EQUAL737EQUALReactome Database ID Release 75201623Database 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=201623ReactomeR-HSA-2016231Reactome 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-201623.1Reactome Database ID Release 751791076Database 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=1791076ReactomeR-HSA-17910764Reactome 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-1791076.416539657Pubmed2006XBP1 induces WFS1 through an endoplasmic reticulum stress response element-like motif in SH-SY5Y cellsKakiuchi, CIshiwata, MHayashi, AKato, TJ Neurochem 97:545-55ACTIVATIONReactome Database ID Release 751791249Database 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=1791249ReactomeR-HSA-17912491Reactome 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-1791249.1XBP1-2XBP1(S)XBP1 isoform 2XBP-1SReactome DB_ID: 381096UniProt:P17861-2 XBP1XBP1TREB5XBP2FUNCTION Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). Required for cardiac myogenesis and hepatogenesis during embryonic development, and the development of secretory tissues such as exocrine pancreas and salivary gland (By similarity). Involved in terminal differentiation of B lymphocytes to plasma cells and production of immunoglobulins (PubMed:11460154). Modulates the cellular response to ER stress in a PIK3R-dependent manner (PubMed:20348923). Binds to the cis-acting X box present in the promoter regions of major histocompatibility complex class II genes (PubMed:8349596). Involved in VEGF-induced endothelial cell (EC) proliferation and retinal blood vessel formation during embryonic development but also for angiogenesis in adult tissues under ischemic conditions. Functions also as a major regulator of the UPR in obesity-induced insulin resistance and type 2 diabetes for the management of obesity and diabetes prevention (By similarity).SUBUNIT Isoform 2 interacts with SIRT1. Isoform 2 interacts with PIK3R1 and PIK3R2; the interactions are direct and induce translocation of XBP1 isoform 2 into the nucleus and the unfolded protein response (UPR) XBP1-dependent target genes activation in a ER stress- and/or insulin-dependent but PI3K-independent manner. Isoform 2 interacts with FOXO1; the interaction is direct and leads to FOXO1 ubiquitination and degradation via the proteasome pathway in hepatocytes (By similarity). Isoform 1 interacts with HM13 (PubMed:25239945). Isoform 1 interacts with RNF139; the interaction induces ubiquitination and degradation of isoform 1 (PubMed:25239945). Isoform 1 interacts (via luminal domain) with DERL1; the interaction obviates the need for ectodomain shedding prior HM13/SPP-mediated XBP1 isoform 1 cleavage (PubMed:25239945). Isoform 1 interacts with isoform 2; the interaction sequesters isoform 2 from the nucleus and enhances isoform 2 degradation in the cytoplasm (PubMed:16461360, PubMed:25239945). Isoform 1 interacts with HDAC3 and AKT1; the interactions occur in endothelial cell (EC) under disturbed flow (PubMed:25190803). Isoform 1 interacts with the oncoprotein FOS (PubMed:1903538). Isoform 2 interacts with ATF6; the interaction occurs in a ER stress-dependent manner and is required for DNA binding to the unfolded protein response element (UPRE) (PubMed:17765680). Isoform 2 interacts with PIK3R1; the interaction is direct and induces translocation of XBP1 isoform 2 into the nucleus and the unfolded protein response (UPR) XBP1-dependent target genes activation in a ER stress- and/or insulin-dependent but PI3K-independent manner (PubMed:20348923).TISSUE SPECIFICITY Expressed in plasma cells in rheumatoid synovium (PubMed:11460154). Over-expressed in primary breast cancer and metastatic breast cancer cells (PubMed:25280941). Isoform 1 and isoform 2 are expressed at higher level in proliferating as compared to confluent quiescent endothelial cells (PubMed:19416856).INDUCTION Isoform 1 is up-regulated at the recovery phase of the endoplasmic reticulum (ER) stress response and isoform 2 is up-regulated early during the ER stress response and gradually decreased at later phase of ER stress (PubMed:16461360). Isoform 1 and isoform 2 are down-regulated by laminar flow but up-regulated by disturbed flow in umbilical vein endothelial cells in vitro (at protein level) (PubMed:19416856). Down-regulated by the B-cell-specific transcription factor PAX5 (PubMed:8627152). Up-regulated by interleukin IL-6 in myeloma cells (PubMed:10375612). Up-regulated during plasma-cell differentiation, either through the CD40 receptor signaling pathway or mitogens such as lipopolysaccharide (LPS) (PubMed:11460154). Isoform 1 and isoform 2 are down-regulated by laminar flow but up-regulated by disturbed flow in umbilical vein endothelial cells in vitro (PubMed:25190803). Isoform 2 is up-regulated early during the ER stress response in a ATF6-dependent manner (PubMed:11779464, PubMed:17110785, PubMed:16461360). Isoform 2 is up-regulated by endostatin in a ERN1-dependent manner (PubMed:23184933). Isoform 2 is transiently up-regulated by the mitogenic vascular endothelial growth factor (VEGF) in endothelial cells (PubMed:23529610).DOMAIN Isoform 1 and isoform 2 N-terminus domains are necessary for nuclear localization targeting. Isoform 1 C-terminus domain confers localization to the cytoplasm and is sufficient to impose rapid degradation (By similarity). Isoform 1 transmembrane signal-anchor domain is necessary for its own mRNA to be recruited to the endoplasmic reticulum (ER) which will undergo unconventional ERN1-dependent splicing in response to ER stress (PubMed:19394296, PubMed:21233347). Isoform 1 N-terminus and C-terminus regions are necessary for DNA-binding and weak transcriptional activity, respectively. Isoform 2 N-terminus and C-terminus regions are necessary for DNA-binding and strong transcriptional activity upon ER stress, respectively (PubMed:11779464, PubMed:8657566). Isoform 2 C-terminus region contains a nuclear exclusion signal (NES) at positions 186 through 208. Isoform 2 C-terminus region contains a degradation domain at positions 209 through 261 (PubMed:16461360).PTM X-box-binding protein 1, cytoplasmic form and luminal form are produced by intramembrane proteolytic cleavage of ER membrane-anchored isoform 1 triggered by HM13/SPP in a DERL1-RNF139-dependent and VCP/p97-independent manner. X-box-binding protein 1, luminal form is ubiquitinated leading to proteasomal degradation (PubMed:25239945).SIMILARITY Belongs to the bZIP family.UniProt IsoformP17861-21EQUAL261EQUALReactome Database ID Release 75381096Database 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=381096ReactomeR-HSA-3810961Reactome 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-381096.1