HME2_HUMAN
ID HME2_HUMAN Reviewed; 333 AA.
AC P19622; A4D252; Q549U3; Q9UD58;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2002, sequence version 3.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Homeobox protein engrailed-2;
DE Short=Homeobox protein en-2;
DE Short=Hu-En-2;
GN Name=EN2;
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 [GENOMIC DNA].
RX PubMed=1363401; DOI=10.1002/dvg.1020130505;
RA Logan C., Hanks M.C., Noble-Topham S., Nallainathan D., Provart N.J.,
RA Joyner A.L.;
RT "Cloning and sequence comparison of the mouse, human, and chicken engrailed
RT genes reveal potential functional domains and regulatory regions.";
RL Dev. Genet. 13:345-358(1992).
RN [2]
RP SEQUENCE REVISION TO 229.
RA Logan C., Hanks M.C., Noble-Topham S., Nallainathan D., Provart N.J.,
RA Joyner A.L.;
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 230-333.
RX PubMed=2565873; DOI=10.1016/0888-7543(89)90324-8;
RA Poole S.J., Law M.L., Kao F.T., Lau Y.-F.C.;
RT "Isolation and chromosomal localization of the human En-2 gene.";
RL Genomics 4:225-231(1989).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 252-290.
RC TISSUE=Bone marrow;
RX PubMed=7518789; DOI=10.1016/0378-1119(94)90380-8;
RA Moretti P., Simmons P., Thomas P., Haylock D., Rathjen P., Vadas M.,
RA D'Andrea R.;
RT "Identification of homeobox genes expressed in human haemopoietic
RT progenitor cells.";
RL Gene 144:213-219(1994).
RN [8]
RP POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO AUTISM.
RX PubMed=16252243; DOI=10.1086/497705;
RA Benayed R., Gharani N., Rossman I., Mancuso V., Lazar G., Kamdar S.,
RA Bruse S.E., Tischfield S., Smith B.J., Zimmerman R.A., DiCicco-Bloom E.,
RA Brzustowicz L.M., Millonig J.H.;
RT "Support for the homeobox transcription factor gene ENGRAILED 2 as an
RT autism spectrum disorder susceptibility locus.";
RL Am. J. Hum. Genet. 77:851-868(2005).
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- DISEASE: Note=Genetic variations in EN2 may be associated with
CC susceptibility to autism.
CC -!- SIMILARITY: Belongs to the engrailed homeobox family. {ECO:0000305}.
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DR EMBL; L12701; AAA53504.2; -; Genomic_DNA.
DR EMBL; L12700; AAA53504.2; JOINED; Genomic_DNA.
DR EMBL; AC008060; AAQ96875.1; -; Genomic_DNA.
DR EMBL; CH236954; EAL23909.1; -; Genomic_DNA.
DR EMBL; BC104970; AAI04971.1; -; mRNA.
DR EMBL; BC104972; AAI04973.1; -; mRNA.
DR EMBL; J03066; AAF68670.1; -; Genomic_DNA.
DR CCDS; CCDS5940.1; -.
DR PIR; E48423; E48423.
DR RefSeq; NP_001418.2; NM_001427.3.
DR AlphaFoldDB; P19622; -.
DR BMRB; P19622; -.
DR SMR; P19622; -.
DR BioGRID; 108335; 6.
DR STRING; 9606.ENSP00000297375; -.
DR DrugBank; DB03309; N-cyclohexyltaurine.
DR iPTMnet; P19622; -.
DR PhosphoSitePlus; P19622; -.
DR BioMuta; EN2; -.
DR DMDM; 21903415; -.
DR MassIVE; P19622; -.
DR PaxDb; P19622; -.
DR PeptideAtlas; P19622; -.
DR PRIDE; P19622; -.
DR ProteomicsDB; 53681; -.
DR Antibodypedia; 18860; 279 antibodies from 30 providers.
DR DNASU; 2020; -.
DR Ensembl; ENST00000297375.4; ENSP00000297375.4; ENSG00000164778.4.
DR GeneID; 2020; -.
DR KEGG; hsa:2020; -.
DR MANE-Select; ENST00000297375.4; ENSP00000297375.4; NM_001427.4; NP_001418.2.
DR UCSC; uc003wmb.3; human.
DR CTD; 2020; -.
DR DisGeNET; 2020; -.
DR GeneCards; EN2; -.
DR HGNC; HGNC:3343; EN2.
DR HPA; ENSG00000164778; Tissue enriched (brain).
DR MIM; 131310; gene.
DR neXtProt; NX_P19622; -.
DR OpenTargets; ENSG00000164778; -.
DR Orphanet; 106; NON RARE IN EUROPE: Autism.
DR PharmGKB; PA27780; -.
DR VEuPathDB; HostDB:ENSG00000164778; -.
DR eggNOG; KOG0493; Eukaryota.
DR GeneTree; ENSGT00940000159935; -.
DR HOGENOM; CLU_051739_2_0_1; -.
DR InParanoid; P19622; -.
DR OMA; RENGDQC; -.
DR OrthoDB; 1575614at2759; -.
DR PhylomeDB; P19622; -.
DR TreeFam; TF106461; -.
DR PathwayCommons; P19622; -.
DR SignaLink; P19622; -.
DR SIGNOR; P19622; -.
DR BioGRID-ORCS; 2020; 16 hits in 1099 CRISPR screens.
DR ChiTaRS; EN2; human.
DR GeneWiki; EN2_(gene); -.
DR GenomeRNAi; 2020; -.
DR Pharos; P19622; Tbio.
DR PRO; PR:P19622; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P19622; protein.
DR Bgee; ENSG00000164778; Expressed in cerebellar cortex and 47 other tissues.
DR Genevisible; P19622; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0016020; C:membrane; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IEA:Ensembl.
DR GO; GO:1990403; P:embryonic brain development; IEA:Ensembl.
DR GO; GO:0030902; P:hindbrain development; IEA:Ensembl.
DR GO; GO:0030901; P:midbrain development; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0048666; P:neuron development; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR019549; Homeobox-engrailed_C-terminal.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR000747; Homeobox_engrailed.
DR InterPro; IPR020479; Homeobox_metazoa.
DR InterPro; IPR019737; Homoebox-engrailed_CS.
DR Pfam; PF10525; Engrail_1_C_sig; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00026; ENGRAILED.
DR PRINTS; PR00024; HOMEOBOX.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00033; ENGRAILED; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 2: Evidence at transcript level;
KW Autism; Autism spectrum disorder; Developmental protein; DNA-binding;
KW Homeobox; Nucleus; Reference proteome.
FT CHAIN 1..333
FT /note="Homeobox protein engrailed-2"
FT /id="PRO_0000196067"
FT DNA_BIND 244..303
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 95..206
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 223..250
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 192..206
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 121
FT /note="L -> F (in dbSNP:rs3735653)"
FT /id="VAR_021985"
SQ SEQUENCE 333 AA; 34211 MW; ACF5399E383D6257 CRC64;
MEENDPKPGE AAAAVEGQRQ PESSPGGGSG GGGGSSPGEA DTGRRRALML PAVLQAPGNH
QHPHRITNFF IDNILRPEFG RRKDAGTCCA GAGGGRGGGA GGEGGASGAE GGGGAGGSEQ
LLGSGSREPR QNPPCAPGAG GPLPAAGSDS PGDGEGGSKT LSLHGGAKKG GDPGGPLDGS
LKARGLGGGD LSVSSDSDSS QAGANLGAQP MLWPAWVYCT RYSDRPSSGP RSRKPKKKNP
NKEDKRPRTA FTAEQLQRLK AEFQTNRYLT EQRRQSLAQE LSLNESQIKI WFQNKRAKIK
KATGNKNTLA VHLMAQGLYN HSTTAKEGKS DSE
