{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P08152","uniProtkbId":"EGR2_MOUSE","entryAudit":{"firstPublicDate":"1988-08-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1997-11-01","entryVersion":221,"sequenceVersion":3},"annotationScore":5.0,"organism":{"scientificName":"Mus musculus","commonName":"Mouse","taxonId":10090,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Glires","Rodentia","Myomorpha","Muroidea","Muridae","Murinae","Mus","Mus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"E3 SUMO-protein ligase EGR2"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P11161"}],"value":"2.3.2.-"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"E3 SUMO-protein transferase ERG2"}},{"fullName":{"value":"Early growth response protein 2"},"shortNames":[{"value":"EGR-2"}]},{"fullName":{"value":"Zinc finger protein Krox-20"}}]},"genes":[{"geneName":{"value":"Egr2"},"synonyms":[{"value":"Egr-2"},{"value":"Krox-20"},{"value":"Zfp-25"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10068633"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11509834"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11823429"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16054051"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1674431"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17938205"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1969796"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31852952"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7935840"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8093858"}],"value":"Sequence-specific DNA-binding transcription factor (PubMed:11823429, PubMed:1674431, PubMed:1969796, PubMed:31852952). Plays a role in hindbrain segmentation by regulating the expression of a subset of homeobox containing genes and in Schwann cell myelination by regulating the expression of genes involved in the formation and maintenance of myelin (PubMed:11823429, PubMed:1674431, PubMed:1969796, PubMed:31852952, PubMed:8093858). Binds to two EGR2-consensus sites EGR2A (5'-CTGTAGGAG-3') and EGR2B (5'-ATGTAGGTG-3') in the HOXB3 enhancer and promotes HOXB3 transcriptional activation (PubMed:11823429). Binds to specific DNA sites located in the promoter region of HOXA4, HOXB2 and ERBB2 (PubMed:17938205, PubMed:1969796, PubMed:8093858). Regulates hindbrain segmentation by controlling the expression of Hox genes, such as HOXA4, HOXB3 and HOXB2, and thereby specifying odd and even rhombomeres (PubMed:11823429, PubMed:1674431). Promotes the expression of HOXB3 in the rhombomere r5 and of HOXB3 in r3 and r5 in the hindbrain (PubMed:11823429, PubMed:8093858). Regulates myelination in the peripheral nervous system after birth, possibly by regulating the expression of myelin proteins, such as MPZ, and by promoting the differentiation of Schwann cells (PubMed:10068633, PubMed:7935840). Involved in the development of the jaw openener musculature, probably by playing a role in its innervation through trigeminal motor neurons (PubMed:11509834). May play a role in adipogenesis, possibly by regulating the expression of CEBPB (PubMed:16054051)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P11161"}],"value":"E3 SUMO-protein ligase helping SUMO1 conjugation to its coregulators NAB1 and NAB2, whose sumoylation down-regulates EGR2 transcriptional activity"}],"commentType":"FUNCTION"},{"texts":[{"value":"Protein modification; protein sumoylation"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P11161"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17938205"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19651900"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32736174"}],"value":"Interacts with HCFC1 (By similarity). Interacts with WWP2 (PubMed:19651900). Interacts with UBC9 (By similarity). Interacts with CITED1 (PubMed:17938205). Interacts (via phosphorylated form) with SFN (PubMed:17938205). Interacts with DTX1; this interaction is important for optimum expression of CBL (PubMed:32736174)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P08152","intActId":"EBI-7070449"},"interactantTwo":{"uniProtKBAccession":"Q8C5D8-1","geneName":"Pias2","intActId":"EBI-8064899"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P08152","intActId":"EBI-7070449"},"interactantTwo":{"uniProtKBAccession":"P63280","geneName":"Ube2i","intActId":"EBI-80180"},"numberOfExperiments":2,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17938205"}],"value":"Nucleus","id":"SL-0191"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"Long"},"isoformIds":["P08152-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"Short"},"isoformIds":["P08152-2"],"sequenceIds":["VSP_006864"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17938205"}],"value":"Expressed mainly in the thymus"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17938205"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7935840"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8093858"}],"value":"Before 8 dpc, expressed in the future rhombomere r3 at 0-3 somites, followed by expression in rhombomere r5 in 4-7 somites at 8 dpc, and maintained until 12 somites (PubMed:8093858). Expressed in migrating neural crest cells from r5/r6 (PubMed:8093858). Expressed in boundary cap cells that surround nerve exit points from the central nervous system at 10.5 dpc (PubMed:7935840, PubMed:8093858). Up to 14.5 dpc, expressed in motor and sensory roots of cranial and spinal nerves (PubMed:7935840). After 15.5 dpc, expressed in the entire peripheral nervous system (PubMed:7935840). Expressed in the embryonic nervous system (PubMed:17938205). Expressed in myelinating Schwann cells 2 weeks after birth (PubMed:7935840)"}],"commentType":"DEVELOPMENTAL STAGE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"3129290"}],"value":"Activated during G0/G1 transition in cultured cells"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19651900"}],"value":"Ubiquitinated by WWP2 leading to proteasomal degradation"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28576496"}],"value":"Acetylated at Lys-247. May be deacetylated by HDAC6, HDAC10 or SIRT1"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10068633"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11509834"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11823429"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7935840"}],"value":"Failure to promote expression of the Hoxb3 reporter in rhombomere r5 in the hindbrain (PubMed:11823429). Changed morphology of the sciatic nerves, with a higher density of Schwann cells, and a reduction in major components of compacted myelin, including lipidic components, as well as myelin proteins Mpz and Mbp (PubMed:7935840). Schwann cells in the sciatic nerves exhibit increased expression of Scip, reduced expression of Mpz, elevated mitotic activity and increased apoptosis at postnatal day P12 (PubMed:10068633). Total absence of myelin along the axons of sciatic nerves at postnatal day P15 (PubMed:7935840). Does not seem to affect the myelination in the central nervous system (PubMed:7935840). Signs of atrophy in the jaw openener anterior digastric (AD) and mylohoid (MY) muscles at 15 dpc with smaller diameter fibers, fibers with triangular shape, increased amount of connective tissue surrounding the fibers, suggesting a lack of neural innervation (PubMed:11509834). Reduced volume of the delineated trigeminal motor nucleus and restructuring of the brainstem at 15 dpc (PubMed:11509834). Reduced volume in both AD and MY musculature and reduced milk indigestion after birth (PubMed:11509834)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the EGR C2H2-type zinc-finger protein family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":470,"modifier":"EXACT"}},"description":"E3 SUMO-protein ligase EGR2","featureId":"PRO_0000047120"},{"type":"Zinc finger","location":{"start":{"value":337,"modifier":"EXACT"},"end":{"value":361,"modifier":"EXACT"}},"description":"C2H2-type 1","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00042"}]},{"type":"Zinc finger","location":{"start":{"value":367,"modifier":"EXACT"},"end":{"value":389,"modifier":"EXACT"}},"description":"C2H2-type 2","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00042"}]},{"type":"Zinc finger","location":{"start":{"value":395,"modifier":"EXACT"},"end":{"value":417,"modifier":"EXACT"}},"description":"C2H2-type 3","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00042"}]},{"type":"Region","location":{"start":{"value":126,"modifier":"EXACT"},"end":{"value":153,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":159,"modifier":"EXACT"},"end":{"value":178,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":185,"modifier":"EXACT"},"end":{"value":210,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":275,"modifier":"EXACT"},"end":{"value":345,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":408,"modifier":"EXACT"},"end":{"value":470,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":126,"modifier":"EXACT"},"end":{"value":141,"modifier":"EXACT"}},"description":"Low complexity","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":190,"modifier":"EXACT"},"end":{"value":202,"modifier":"EXACT"}},"description":"Low complexity","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":275,"modifier":"EXACT"},"end":{"value":291,"modifier":"EXACT"}},"description":"Gly residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":412,"modifier":"EXACT"},"end":{"value":422,"modifier":"EXACT"}},"description":"Basic residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":426,"modifier":"EXACT"},"end":{"value":439,"modifier":"EXACT"}},"description":"Low complexity","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":440,"modifier":"EXACT"},"end":{"value":450,"modifier":"EXACT"}},"description":"Gly residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Modified residue","location":{"start":{"value":247,"modifier":"EXACT"},"end":{"value":247,"modifier":"EXACT"}},"description":"N6-acetyllysine; 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