EGR2_HUMAN
ID EGR2_HUMAN Reviewed; 476 AA.
AC P11161; B2R724; B3KRD7; Q68CZ5; Q8IV26; Q9UNA6;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2003, sequence version 3.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=E3 SUMO-protein ligase EGR2;
DE EC=2.3.2.- {ECO:0000269|PubMed:21836637};
DE AltName: Full=AT591;
DE AltName: Full=E3 SUMO-protein transferase ERG2 {ECO:0000305};
DE AltName: Full=Early growth response protein 2;
DE Short=EGR-2;
DE AltName: Full=Zinc finger protein Krox-20;
GN Name=EGR2; Synonyms=KROX20;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RX PubMed=3140236; DOI=10.1073/pnas.85.19.7164;
RA Joseph L.J., le Beau M.M., Jamieson G.A. Jr., Acharya S., Shows T.B.,
RA Rowley J.D., Sukhatme V.P.;
RT "Molecular cloning, sequencing, and mapping of EGR2, a human early growth
RT response gene encoding a protein with 'zinc-binding finger' structure.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:7164-7168(1988).
RN [2]
RP ERRATUM OF PUBMED:3140236, AND SEQUENCE REVISION TO C-TERMINUS.
RA Joseph L.J., le Beau M.M., Jamieson G.A. Jr., Acharya S., Shows T.B.,
RA Rowley J.D., Sukhatme V.P.;
RL Proc. Natl. Acad. Sci. U.S.A. 86:515-515(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), VARIANTS CHN1 ASN-268 AND
RP 382-ARG-TYR-383, AND VARIANT CMT1D TRP-409.
RX PubMed=9537424; DOI=10.1038/ng0498-382;
RA Warner L.E., Mancias P., Butler I.J., McDonald C.M., Keppen L., Koob K.G.,
RA Lupski J.R.;
RT "Mutations in the early growth response 2 (EGR2) gene are associated with
RT hereditary myelinopathies.";
RL Nat. Genet. 18:382-384(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND SHORT).
RC TISSUE=Brain, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Endometrium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21.
RX PubMed=2111009; DOI=10.1093/nar/18.9.2749;
RA Rangnekar V.M., Aplin A.C., Sukhatme V.P.;
RT "The serum and TPA responsive promoter and intron-exon structure of EGR2, a
RT human early growth response gene encoding a zinc finger protein.";
RL Nucleic Acids Res. 18:2749-2757(1990).
RN [10]
RP INTERACTION WITH HCFC1, AND MUTAGENESIS OF 162-ASP--TYR-165.
RX PubMed=14532282; DOI=10.1074/jbc.m303470200;
RA Luciano R.L., Wilson A.C.;
RT "HCF-1 functions as a coactivator for the zinc finger protein Krox20.";
RL J. Biol. Chem. 278:51116-51124(2003).
RN [11]
RP INTERACTION WITH WWP2.
RX PubMed=19651900; DOI=10.1128/mcb.00407-09;
RA Chen A., Gao B., Zhang J., McEwen T., Ye S.Q., Zhang D., Fang D.;
RT "The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell
RT death by catalyzing EGR2 ubiquitination.";
RL Mol. Cell. Biol. 29:5348-5356(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP FUNCTION AS SUMO LIGASE, CATALYTIC ACTIVITY, AND INTERACTION WITH UBC9.
RX PubMed=21836637; DOI=10.1038/embor.2011.152;
RA Garcia-Gutierrez P., Juarez-Vicente F., Gallardo-Chamizo F., Charnay P.,
RA Garcia-Dominguez M.;
RT "The transcription factor Krox20 is an E3 ligase that sumoylates its Nab
RT coregulators.";
RL EMBO Rep. 12:1018-1023(2011).
RN [14]
RP VARIANT CMT1D VAL-355.
RA Di Maria E., Bellone E., Soriani S., Varese A., Lamba Doria L., Grandis M.,
RA Schenone A., Levi G., Ajmar F., Mandich P.;
RT "EGR2 gene mutation in a patient affected with Charcot-Marie-Tooth type
RT 1.";
RL Eur. J. Hum. Genet. Suppl. 7:99-99(1999).
RN [15]
RP VARIANT CMT1D VAL-355.
RX PubMed=10502832;
RX DOI=10.1002/(sici)1098-1004(199910)14:4<353::aid-humu17>3.0.co;2-4;
RA Bellone E., Di Maria E., Soriani S., Varese A., Lamba Doria L., Ajmar F.,
RA Mandich P.;
RT "A novel mutation (D305V) in the early growth response 2 gene is associated
RT with severe Charcot-Marie-Tooth type 1 disease.";
RL Hum. Mutat. 14:353-354(1999).
RN [16]
RP VARIANT DSS TRP-359.
RX PubMed=10371530; DOI=10.1212/wnl.52.9.1827;
RA Timmerman V., De Jonghe P., Ceuterick C., De Vriendt E., Lofgren A.,
RA Nelis E., Warner L.E., Lupski J.R., Martin J.-J., Van Broeckhoven C.;
RT "Novel missense mutation in the early growth response 2 gene associated
RT with Dejerine-Sottas syndrome phenotype.";
RL Neurology 52:1827-1832(1999).
RN [17]
RP VARIANT CMT1D HIS-381.
RX PubMed=10762521; DOI=10.1212/wnl.54.8.1696;
RA Pareyson D., Taroni F., Botti S., Morbin M., Baratta S., Lauria G.,
RA Ciano C., Sghirlanzoni A.;
RT "Cranial nerve involvement in CMT disease type 1 due to early growth
RT response 2 gene mutation.";
RL Neurology 54:1696-1698(2000).
RN [18]
RP VARIANT CMT1D CYS-381.
RX PubMed=11239949; DOI=10.1016/s0022-510x(00)00504-9;
RA Yoshihara T., Kanda F., Yamamoto M., Ishihara H., Misu K., Hattori N.,
RA Chihara K., Sobue G.;
RT "A novel missense mutation in the early growth response 2 gene associated
RT with late-onset Charcot-Marie-Tooth disease type 1.";
RL J. Neurol. Sci. 184:149-153(2001).
RN [19]
RP VARIANT CMT1D TYR-383.
RX PubMed=12736090; DOI=10.1016/s0022-510x(03)00028-5;
RA Numakura C., Shirahata E., Yamashita S., Kanai M., Kijima K., Matsuki T.,
RA Hayasaka K.;
RT "Screening of the early growth response 2 gene in Japanese patients with
RT Charcot-Marie-Tooth disease type 1.";
RL J. Neurol. Sci. 210:61-64(2003).
RN [20]
RP VARIANT CMT1D TRP-359.
RX PubMed=15241803; DOI=10.1002/humu.9261;
RA Choi B.-O., Lee M.S., Shin S.H., Hwang J.H., Choi K.-G., Kim W.-K.,
RA Sunwoo I.N., Kim N.K., Chung K.W.;
RT "Mutational analysis of PMP22, MPZ, GJB1, EGR2 and NEFL in Korean Charcot-
RT Marie-Tooth neuropathy patients.";
RL Hum. Mutat. 24:185-186(2004).
RN [21]
RP VARIANT CMT1D TRP-359.
RX PubMed=15947997; DOI=10.1007/s10048-005-0217-4;
RA Chung K.W., Sunwoo I.N., Kim S.M., Park K.D., Kim W.-K., Kim T.S., Koo H.,
RA Cho M., Lee J., Choi B.O.;
RT "Two missense mutations of EGR2 R359W and GJB1 V136A in a Charcot-Marie-
RT Tooth disease family.";
RL Neurogenetics 6:159-163(2005).
RN [22]
RP VARIANT DSS LYS-412, CHARACTERIZATION OF VARIANTS CHN1 ASN-268; DSS LYS-412
RP AND DSS/CMT1D TRP-359, AND FUNCTION.
RX PubMed=17717711; DOI=10.1007/s10048-007-0094-0;
RA Szigeti K., Wiszniewski W., Saifi G.M., Sherman D.L., Sule N.,
RA Adesina A.M., Mancias P., Papasozomenos S.C., Miller G., Keppen L.,
RA Daentl D., Brophy P.J., Lupski J.R.;
RT "Functional, histopathologic and natural history study of neuropathy
RT associated with EGR2 mutations.";
RL Neurogenetics 8:257-262(2007).
RN [23]
RP INVOLVEMENT IN CHN1.
RX PubMed=22522483; DOI=10.1002/ana.23527;
RA Funalot B., Topilko P., Arroyo M.A., Sefiani A., Hedley-Whyte E.T.,
RA Yoldi M.E., Richard L., Touraille E., Laurichesse M., Khalifa E.,
RA Chauzeix J., Ouedraogo A., Cros D., Magdelaine C., Sturtz F.G.,
RA Urtizberea J.A., Charnay P., Bragado F.G., Vallat J.M.;
RT "Homozygous deletion of an EGR2 enhancer in congenital amyelinating
RT neuropathy.";
RL Ann. Neurol. 71:719-723(2012).
RN [24]
RP VARIANT CMT1D ASN-387.
RX PubMed=22734907; DOI=10.1111/j.1529-8027.2012.00403.x;
RA Shiga K., Noto Y., Mizuta I., Hashiguchi A., Takashima H., Nakagawa M.;
RT "A novel EGR2 mutation within a family with a mild demyelinating form of
RT Charcot-Marie-Tooth disease.";
RL J. Peripher. Nerv. Syst. 17:206-209(2012).
RN [25]
RP VARIANT CMT1D GLY-412.
RX PubMed=22546699; DOI=10.1016/j.nmd.2012.04.002;
RA Safka Brozkova D., Nevsimalova S., Mazanec R., Rautenstrauss B., Seeman P.;
RT "Charcot-Marie-Tooth neuropathy due to a novel EGR2 gene mutation with mild
RT phenotype--usefulness of human mapping chip linkage analysis in a Czech
RT family.";
RL Neuromuscul. Disord. 22:742-746(2012).
RN [26]
RP VARIANT CMT1D GLY-412, AND CHARACTERIZATION OF VARIANT CMT1D GLY-412.
RX PubMed=30843326; DOI=10.1111/jns.12314;
RA Tozza S., Magri S., Pennisi E.M., Schirinzi E., Pisciotta C.,
RA Balistreri F., Severi D., Ricci G., Siciliano G., Taroni F., Santoro L.,
RA Manganelli F.;
RT "A novel family with axonal Charcot-Marie-Tooth disease caused by a
RT mutation in the EGR2 gene.";
RL J. Peripher. Nerv. Syst. 24:219-223(2019).
RN [27]
RP VARIANT DSS GLY-411.
RX PubMed=31852952; DOI=10.1038/s41598-019-55875-4;
RA Grosz B.R., Golovchenko N.B., Ellis M., Kumar K., Nicholson G.A.,
RA Antonellis A., Kennerson M.L.;
RT "A de novo EGR2 variant, c.1232A > G p.Asp411Gly, causes severe early-onset
RT Charcot-Marie-Tooth Neuropathy Type 3 (Dejerine-Sottas Neuropathy).";
RL Sci. Rep. 9:19336-19336(2019).
CC -!- FUNCTION: Sequence-specific DNA-binding transcription factor
CC (PubMed:17717711). Plays a role in hindbrain segmentation by regulating
CC the expression of a subset of homeobox containing genes and in Schwann
CC cell myelination by regulating the expression of genes involved in the
CC formation and maintenance of myelin (By similarity). Binds to two EGR2-
CC consensus sites EGR2A (5'-CTGTAGGAG-3') and EGR2B (5'-ATGTAGGTG-3') in
CC the HOXB3 enhancer and promotes HOXB3 transcriptional activation (By
CC similarity). Binds to specific DNA sites located in the promoter region
CC of HOXA4, HOXB2 and ERBB2 (By similarity). Regulates hindbrain
CC segmentation by controlling the expression of Hox genes, such as HOXA4,
CC HOXB3 and HOXB2, and thereby specifying odd and even rhombomeres (By
CC similarity). Promotes the expression of HOXB3 in the rhombomere r5 in
CC the hindbrain (By similarity). Regulates myelination in the peripheral
CC nervous system after birth, possibly by regulating the expression of
CC myelin proteins, such as MPZ, and by promoting the differentiation of
CC Schwann cells (By similarity). Involved in the development of the jaw
CC openener musculature, probably by playing a role in its innervation
CC through trigeminal motor neurons (By similarity). May play a role in
CC adipogenesis, possibly by regulating the expression of CEBPB (By
CC similarity). {ECO:0000250|UniProtKB:P08152,
CC ECO:0000269|PubMed:17717711}.
CC -!- FUNCTION: E3 SUMO-protein ligase helping SUMO1 conjugation to its
CC coregulators NAB1 and NAB2, whose sumoylation down-regulates EGR2
CC transcriptional activity. {ECO:0000269|PubMed:21836637}.
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC -!- SUBUNIT: Interacts with HCFC1 (PubMed:14532282). Interacts with WWP2
CC (PubMed:19651900). Interacts with UBC9 (PubMed:21836637). Interacts
CC with CITED1 (By similarity). Interacts (via phosphorylated form) with
CC SFN (By similarity). {ECO:0000250|UniProtKB:P08152,
CC ECO:0000269|PubMed:14532282, ECO:0000269|PubMed:19651900,
CC ECO:0000269|PubMed:21836637}.
CC -!- INTERACTION:
CC P11161; P46937: YAP1; NbExp=2; IntAct=EBI-625282, EBI-1044059;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P08152}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P11161-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P11161-2; Sequence=VSP_006863;
CC -!- PTM: Ubiquitinated by WWP2 leading to proteasomal degradation.
CC {ECO:0000250|UniProtKB:P08152}.
CC -!- PTM: Acetylated at Lys-247. May be deacetylated by HDAC6, HDAC10 or
CC SIRT1. {ECO:0000250|UniProtKB:P08152}.
CC -!- DISEASE: Neuropathy, congenital hypomyelinating, 1, autosomal recessive
CC (CHN1) [MIM:605253]: A severe degenerating neuropathy that results from
CC a congenital impairment in myelin formation. It is clinically
CC characterized by early onset of hypotonia, areflexia, distal muscle
CC weakness, and very slow nerve conduction velocities (as low as 3m/s).
CC Some patients manifest nearly complete absence of spontaneous limb
CC movements, respiratory distress at birth, and complete absence of
CC myelin shown by electron microscopy of peripheral nerves.
CC {ECO:0000269|PubMed:17717711, ECO:0000269|PubMed:22522483,
CC ECO:0000269|PubMed:9537424}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. Patients affected by the
CC amyelinating form carry a causative, homozygous deletion encompassing a
CC myelin-specific enhancer of EGR2 (PubMed:22522483).
CC {ECO:0000269|PubMed:22522483}.
CC -!- DISEASE: Charcot-Marie-Tooth disease 1D (CMT1D) [MIM:607678]: A
CC dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder
CC of the peripheral nervous system, characterized by progressive weakness
CC and atrophy, initially of the peroneal muscles and later of the distal
CC muscles of the arms. Charcot-Marie-Tooth disease is classified in two
CC main groups on the basis of electrophysiologic properties and
CC histopathology: primary peripheral demyelinating neuropathies
CC (designated CMT1 when they are dominantly inherited) and primary
CC peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are
CC characterized by severely reduced nerve conduction velocities (less
CC than 38 m/sec), segmental demyelination and remyelination with onion
CC bulb formations on nerve biopsy, slowly progressive distal muscle
CC atrophy and weakness, absent deep tendon reflexes, and hollow feet.
CC {ECO:0000269|PubMed:10502832, ECO:0000269|PubMed:10762521,
CC ECO:0000269|PubMed:11239949, ECO:0000269|PubMed:12736090,
CC ECO:0000269|PubMed:15241803, ECO:0000269|PubMed:15947997,
CC ECO:0000269|PubMed:17717711, ECO:0000269|PubMed:22546699,
CC ECO:0000269|PubMed:22734907, ECO:0000269|PubMed:30843326,
CC ECO:0000269|PubMed:9537424, ECO:0000269|Ref.14}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Dejerine-Sottas syndrome (DSS) [MIM:145900]: A severe
CC degenerating neuropathy of the demyelinating Charcot-Marie-Tooth
CC disease category, with onset by age 2 years. Characterized by motor and
CC sensory neuropathy with very slow nerve conduction velocities,
CC increased cerebrospinal fluid protein concentrations, hypertrophic
CC nerve changes, delayed age of walking as well as areflexia. There are
CC both autosomal dominant and autosomal recessive forms of Dejerine-
CC Sottas syndrome. {ECO:0000269|PubMed:10371530,
CC ECO:0000269|PubMed:17717711, ECO:0000269|PubMed:31852952}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the EGR C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA52372.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAA52372.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db;
CC URL="https://uantwerpen.vib.be/CMTMutations";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; J04076; AAA52372.1; ALT_SEQ; mRNA.
DR EMBL; AF139463; AAD24588.1; -; mRNA.
DR EMBL; AK091399; BAG52349.1; -; mRNA.
DR EMBL; AK312813; BAG35671.1; -; mRNA.
DR EMBL; CR749641; CAH18435.1; -; mRNA.
DR EMBL; AL133417; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471083; EAW54238.1; -; Genomic_DNA.
DR EMBL; CH471083; EAW54239.1; -; Genomic_DNA.
DR EMBL; BC035625; AAH35625.1; -; mRNA.
DR EMBL; X53700; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS44409.1; -. [P11161-2]
DR CCDS; CCDS7267.1; -. [P11161-1]
DR RefSeq; NP_000390.2; NM_000399.4. [P11161-1]
DR RefSeq; NP_001129649.1; NM_001136177.2. [P11161-1]
DR RefSeq; NP_001129650.1; NM_001136178.1. [P11161-1]
DR RefSeq; NP_001129651.1; NM_001136179.2. [P11161-2]
DR RefSeq; NP_001307966.1; NM_001321037.1. [P11161-2]
DR AlphaFoldDB; P11161; -.
DR SMR; P11161; -.
DR BioGRID; 108279; 22.
DR IntAct; P11161; 14.
DR MINT; P11161; -.
DR STRING; 9606.ENSP00000242480; -.
DR GlyGen; P11161; 13 sites, 2 O-linked glycans (13 sites).
DR iPTMnet; P11161; -.
DR PhosphoSitePlus; P11161; -.
DR BioMuta; EGR2; -.
DR DMDM; 33112654; -.
DR jPOST; P11161; -.
DR MassIVE; P11161; -.
DR PaxDb; P11161; -.
DR PeptideAtlas; P11161; -.
DR PRIDE; P11161; -.
DR ProteomicsDB; 52701; -. [P11161-1]
DR ProteomicsDB; 52702; -. [P11161-2]
DR Antibodypedia; 14464; 516 antibodies from 43 providers.
DR DNASU; 1959; -.
DR Ensembl; ENST00000242480.4; ENSP00000242480.3; ENSG00000122877.18. [P11161-1]
DR Ensembl; ENST00000411732.4; ENSP00000387634.1; ENSG00000122877.18. [P11161-2]
DR Ensembl; ENST00000637191.2; ENSP00000490154.2; ENSG00000122877.18. [P11161-1]
DR GeneID; 1959; -.
DR KEGG; hsa:1959; -.
DR MANE-Select; ENST00000242480.4; ENSP00000242480.3; NM_000399.5; NP_000390.2.
DR UCSC; uc001jmi.4; human. [P11161-1]
DR CTD; 1959; -.
DR DisGeNET; 1959; -.
DR GeneCards; EGR2; -.
DR GeneReviews; EGR2; -.
DR HGNC; HGNC:3239; EGR2.
DR HPA; ENSG00000122877; Tissue enhanced (epididymis, thyroid gland).
DR MalaCards; EGR2; -.
DR MIM; 129010; gene.
DR MIM; 145900; phenotype.
DR MIM; 605253; phenotype.
DR MIM; 607678; phenotype.
DR neXtProt; NX_P11161; -.
DR OpenTargets; ENSG00000122877; -.
DR Orphanet; 101084; Charcot-Marie-Tooth disease type 1D.
DR Orphanet; 99951; Charcot-Marie-Tooth disease type 4E.
DR Orphanet; 64748; Dejerine-Sottas syndrome.
DR PharmGKB; PA27674; -.
DR VEuPathDB; HostDB:ENSG00000122877; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000158394; -.
DR HOGENOM; CLU_043235_0_0_1; -.
DR InParanoid; P11161; -.
DR OMA; PQCQREL; -.
DR OrthoDB; 1621899at2759; -.
DR PhylomeDB; P11161; -.
DR TreeFam; TF318980; -.
DR PathwayCommons; P11161; -.
DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR Reactome; R-HSA-9031628; NGF-stimulated transcription.
DR Reactome; R-HSA-9619665; EGR2 and SOX10-mediated initiation of Schwann cell myelination.
DR SignaLink; P11161; -.
DR SIGNOR; P11161; -.
DR UniPathway; UPA00886; -.
DR BioGRID-ORCS; 1959; 229 hits in 1088 CRISPR screens.
DR GeneWiki; EGR2; -.
DR GenomeRNAi; 1959; -.
DR Pharos; P11161; Tbio.
DR PRO; PR:P11161; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P11161; protein.
DR Bgee; ENSG00000122877; Expressed in gall bladder and 108 other tissues.
DR ExpressionAtlas; P11161; baseline and differential.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0071837; F:HMG box domain binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISS:BHF-UCL.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0061665; F:SUMO ligase activity; ISS:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0035904; P:aorta development; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; TAS:ProtInc.
DR GO; GO:0035284; P:brain segmentation; IEA:Ensembl.
DR GO; GO:0071310; P:cellular response to organic substance; IEA:Ensembl.
DR GO; GO:0021612; P:facial nerve structural organization; ISS:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; ISS:BHF-UCL.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0007611; P:learning or memory; IEA:Ensembl.
DR GO; GO:0008045; P:motor neuron axon guidance; IEA:Ensembl.
DR GO; GO:0042552; P:myelination; IEA:Ensembl.
DR GO; GO:0007422; P:peripheral nervous system development; TAS:ProtInc.
DR GO; GO:0031643; P:positive regulation of myelination; ISS:UniProtKB.
DR GO; GO:0014040; P:positive regulation of Schwann cell differentiation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006611; P:protein export from nucleus; ISS:UniProtKB.
DR GO; GO:0016925; P:protein sumoylation; ISS:ARUK-UCL.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IEA:Ensembl.
DR GO; GO:0030278; P:regulation of ossification; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0021660; P:rhombomere 3 formation; IEA:Ensembl.
DR GO; GO:0021659; P:rhombomere 3 structural organization; ISS:UniProtKB.
DR GO; GO:0021666; P:rhombomere 5 formation; IEA:Ensembl.
DR GO; GO:0021665; P:rhombomere 5 structural organization; ISS:UniProtKB.
DR GO; GO:0007622; P:rhythmic behavior; IEA:Ensembl.
DR GO; GO:0014037; P:Schwann cell differentiation; ISS:UniProtKB.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; ISS:UniProtKB.
DR InterPro; IPR021849; EGR_N.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF11928; DUF3446; 1.
DR Pfam; PF00096; zf-C2H2; 3.
DR SMART; SM00355; ZnF_C2H2; 3.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Alternative splicing; Charcot-Marie-Tooth disease;
KW Dejerine-Sottas syndrome; Disease variant; DNA-binding; Metal-binding;
KW Neurodegeneration; Neuropathy; Nucleus; Reference proteome; Repeat;
KW Transcription; Transcription regulation; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..476
FT /note="E3 SUMO-protein ligase EGR2"
FT /id="PRO_0000047119"
FT ZN_FING 340..364
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 370..392
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 398..420
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 127..178
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 275..300
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 318..341
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 412..476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 162..165
FT /note="HCFC1-binding-motif (HBM)"
FT COMPBIAS 127..162
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 428..476
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 247
FT /note="N6-acetyllysine; by EP300"
FT /evidence="ECO:0000250|UniProtKB:P08152"
FT VAR_SEQ 1..50
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_006863"
FT VARIANT 268
FT /note="I -> N (in CHN1; loss of large and small myelinated
FT nerve fibers; dbSNP:rs104894158)"
FT /evidence="ECO:0000269|PubMed:17717711,
FT ECO:0000269|PubMed:9537424"
FT /id="VAR_007735"
FT VARIANT 355
FT /note="D -> V (in CMT1D; dbSNP:rs1589080611)"
FT /evidence="ECO:0000269|PubMed:10502832, ECO:0000269|Ref.14"
FT /id="VAR_007736"
FT VARIANT 359
FT /note="R -> W (in DSS and CMT1D; associated with A-136 in
FT the GJB1 gene in a DSS Korean girl; loss of DNA binding and
FT loss of transactivation activity; loss of small and large
FT myelinated nerve fibers; residual fibers with thin myelin
FT sheaths; dbSNP:rs104894161)"
FT /evidence="ECO:0000269|PubMed:10371530,
FT ECO:0000269|PubMed:15241803, ECO:0000269|PubMed:15947997,
FT ECO:0000269|PubMed:17717711"
FT /id="VAR_009874"
FT VARIANT 381
FT /note="R -> C (in CMT1D; dbSNP:rs1589080524)"
FT /evidence="ECO:0000269|PubMed:11239949"
FT /id="VAR_029958"
FT VARIANT 381
FT /note="R -> H (in CMT1D; dbSNP:rs281865137)"
FT /evidence="ECO:0000269|PubMed:10762521"
FT /id="VAR_009875"
FT VARIANT 382..383
FT /note="SD -> RY (in CHN1)"
FT /id="VAR_007737"
FT VARIANT 383
FT /note="D -> Y (in CMT1D; dbSNP:rs104894160)"
FT /evidence="ECO:0000269|PubMed:12736090"
FT /id="VAR_029959"
FT VARIANT 387
FT /note="T -> N (in CMT1D; unknown pathological significance;
FT dbSNP:rs281865139)"
FT /evidence="ECO:0000269|PubMed:22734907"
FT /id="VAR_083343"
FT VARIANT 409
FT /note="R -> W (in CMT1D; dbSNP:rs104894159)"
FT /evidence="ECO:0000269|PubMed:9537424"
FT /id="VAR_007738"
FT VARIANT 411
FT /note="D -> G (in DSS)"
FT /evidence="ECO:0000269|PubMed:31852952"
FT /id="VAR_083344"
FT VARIANT 412
FT /note="E -> G (in CMT1D; loss of myelinated and
FT unmyelinated nerve fibers; dbSNP:rs749558026)"
FT /evidence="ECO:0000269|PubMed:22546699,
FT ECO:0000269|PubMed:30843326"
FT /id="VAR_083345"
FT VARIANT 412
FT /note="E -> K (in DSS; loss of DNA binding and loss of
FT transactivation activity; dbSNP:rs121434563)"
FT /evidence="ECO:0000269|PubMed:17717711"
FT /id="VAR_083346"
FT MUTAGEN 162..165
FT /note="DHLY->AAAA: Inhibits association with HCFC1."
FT /evidence="ECO:0000269|PubMed:14532282"
FT CONFLICT 68
FT /note="K -> R (in Ref. 5; CAH18435)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="K -> KPFPCPLDTLRVPPPLTPLSTIRK (in Ref. 8; AAH35625)"
FT /evidence="ECO:0000305"
FT CONFLICT 280
FT /note="V -> M (in Ref. 1; AAA52372)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 476 AA; 50302 MW; 7810D1B1B418DF1F CRC64;
MMTAKAVDKI PVTLSGFVHQ LSDNIYPVED LAATSVTIFP NAELGGPFDQ MNGVAGDGMI
NIDMTGEKRS LDLPYPSSFA PVSAPRNQTF TYMGKFSIDP QYPGASCYPE GIINIVSAGI
LQGVTSPAST TASSSVTSAS PNPLATGPLG VCTMSQTQPD LDHLYSPPPP PPPYSGCAGD
LYQDPSAFLS AATTSTSSSL AYPPPPSYPS PKPATDPGLF PMIPDYPGFF PSQCQRDLHG
TAGPDRKPFP CPLDTLRVPP PLTPLSTIRN FTLGGPSAGV TGPGASGGSE GPRLPGSSSA
AAAAAAAAAY NPHHLPLRPI LRPRKYPNRP SKTPVHERPY PCPAEGCDRR FSRSDELTRH
IRIHTGHKPF QCRICMRNFS RSDHLTTHIR THTGEKPFAC DYCGRKFARS DERKRHTKIH
LRQKERKSSA PSASVPAPST ASCSGGVQPG GTLCSSNSSS LGGGPLAPCS SRTRTP
