ID   HME1_HUMAN              Reviewed;         392 AA.
AC   Q05925; Q4ZG44;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   25-NOV-2008, sequence version 3.
DT   24-JAN-2024, entry version 190.
DE   RecName: Full=Homeobox protein engrailed-1;
DE            Short=Homeobox protein en-1;
DE            Short=Hu-En-1;
GN   Name=EN1;
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 288.
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=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [4]
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   [5]
RP   INVOLVEMENT IN ENDOVESL AND ENDOVESLB.
RX   PubMed=33568816; DOI=10.1038/s41586-021-03208-9;
RA   Allou L., Balzano S., Magg A., Quinodoz M., Royer-Bertrand B.,
RA   Schoepflin R., Chan W.L., Speck-Martins C.E., Carvalho D.R., Farage L.,
RA   Lourenco C.M., Albuquerque R., Rajagopal S., Nampoothiri S.,
RA   Campos-Xavier B., Chiesa C., Niel-Buetschi F., Wittler L., Timmermann B.,
RA   Spielmann M., Robson M.I., Ringel A., Heinrich V., Cova G., Andrey G.,
RA   Prada-Medina C.A., Pescini-Gobert R., Unger S., Bonafe L., Grote P.,
RA   Rivolta C., Mundlos S., Superti-Furga A.;
RT   "Non-coding deletions identify Maenli lncRNA as a limb-specific En1
RT   regulator.";
RL   Nature 592:93-98(2021).
CC   -!- FUNCTION: Required for proper formation of the apical ectodermal ridge
CC       and correct dorsal-ventral patterning in the limb.
CC       {ECO:0000250|UniProtKB:P09065}.
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- DISEASE: ENDOVE syndrome, limb-only type (ENDOVESL) [MIM:619217]: An
CC       autosomal recessive disorder characterized by severe shortening and
CC       deformation of the legs and feet, 3/4 syndactyly of the hands, and
CC       toenails partially displaced to plantar surface. Radiographs show
CC       normal femora but severely shortened tibiae, triangular fibulae and
CC       malformed or absent bones in the feet. In addition, genitourinary
CC       anomalies have been observed. {ECO:0000269|PubMed:33568816}. Note=The
CC       gene represented in this entry is involved in disease pathogenesis.
CC       Homozygous structural variants on chromosome 2 located 300 kb upstream
CC       of EN1 result in altered EN1 expression with pathological consequences.
CC       {ECO:0000269|PubMed:33568816}.
CC   -!- DISEASE: ENDOVE syndrome, limb-brain type (ENDOVESLB) [MIM:619218]: An
CC       autosomal recessive disorder characterized by marked mesomelic
CC       shortening of the lower limbs, severe hypoplasia of the tibia and
CC       fibula, absent talus, and rudimentary and short foot bones. Hands show
CC       short and malformed fingers with a missing digit, and nails are absent
CC       on some fingers. Affected individuals manifest neurologic symptoms
CC       including seizures and generalized hypotonia. Brain imaging reveals
CC       absence of the cerebellum and hypoplasia of the brain stem.
CC       {ECO:0000269|PubMed:33568816}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the engrailed homeobox family. {ECO:0000305}.
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DR   EMBL; L12699; AAA53502.2; -; Genomic_DNA.
DR   EMBL; L12698; AAA53502.2; JOINED; Genomic_DNA.
DR   EMBL; AC012665; AAX88967.1; -; Genomic_DNA.
DR   EMBL; CH471103; EAW95206.1; -; Genomic_DNA.
DR   CCDS; CCDS2123.1; -.
DR   PIR; B48423; B48423.
DR   RefSeq; NP_001417.3; NM_001426.3.
DR   AlphaFoldDB; Q05925; -.
DR   SMR; Q05925; -.
DR   BioGRID; 108334; 136.
DR   IntAct; Q05925; 79.
DR   STRING; 9606.ENSP00000295206; -.
DR   iPTMnet; Q05925; -.
DR   PhosphoSitePlus; Q05925; -.
DR   BioMuta; EN1; -.
DR   DMDM; 215274149; -.
DR   jPOST; Q05925; -.
DR   MassIVE; Q05925; -.
DR   MaxQB; Q05925; -.
DR   PaxDb; 9606-ENSP00000295206; -.
DR   PeptideAtlas; Q05925; -.
DR   ProteomicsDB; 58357; -.
DR   Antibodypedia; 33365; 298 antibodies from 30 providers.
DR   DNASU; 2019; -.
DR   Ensembl; ENST00000295206.7; ENSP00000295206.5; ENSG00000163064.7.
DR   GeneID; 2019; -.
DR   KEGG; hsa:2019; -.
DR   MANE-Select; ENST00000295206.7; ENSP00000295206.5; NM_001426.4; NP_001417.3.
DR   UCSC; uc002tlm.4; human.
DR   AGR; HGNC:3342; -.
DR   CTD; 2019; -.
DR   DisGeNET; 2019; -.
DR   GeneCards; EN1; -.
DR   HGNC; HGNC:3342; EN1.
DR   HPA; ENSG00000163064; Group enriched (adipose tissue, brain, skeletal muscle, skin).
DR   MalaCards; EN1; -.
DR   MIM; 131290; gene.
DR   MIM; 619217; phenotype.
DR   MIM; 619218; phenotype.
DR   neXtProt; NX_Q05925; -.
DR   OpenTargets; ENSG00000163064; -.
DR   PharmGKB; PA27779; -.
DR   VEuPathDB; HostDB:ENSG00000163064; -.
DR   eggNOG; KOG0493; Eukaryota.
DR   GeneTree; ENSGT00940000160811; -.
DR   HOGENOM; CLU_051739_0_1_1; -.
DR   InParanoid; Q05925; -.
DR   OMA; CPDSNCR; -.
DR   OrthoDB; 2897502at2759; -.
DR   PhylomeDB; Q05925; -.
DR   TreeFam; TF106461; -.
DR   PathwayCommons; Q05925; -.
DR   SignaLink; Q05925; -.
DR   SIGNOR; Q05925; -.
DR   BioGRID-ORCS; 2019; 6 hits in 1173 CRISPR screens.
DR   GeneWiki; EN1_(gene); -.
DR   GenomeRNAi; 2019; -.
DR   Pharos; Q05925; Tbio.
DR   PRO; PR:Q05925; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; Q05925; Protein.
DR   Bgee; ENSG00000163064; Expressed in substantia nigra pars reticulata and 58 other cell types or tissues.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR   GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR   GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR   GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR   GO; GO:0021549; P:cerebellum development; IEA:Ensembl.
DR   GO; GO:0071542; P:dopaminergic neuron differentiation; TAS:ParkinsonsUK-UCL.
DR   GO; GO:0009953; P:dorsal/ventral pattern formation; IEA:Ensembl.
DR   GO; GO:0042756; P:drinking behavior; IEA:Ensembl.
DR   GO; GO:1990403; P:embryonic brain development; IEA:Ensembl.
DR   GO; GO:0035115; P:embryonic forelimb morphogenesis; IEA:Ensembl.
DR   GO; GO:0030901; P:midbrain development; IEA:Ensembl.
DR   GO; GO:0030917; P:midbrain-hindbrain boundary development; IEA:Ensembl.
DR   GO; GO:0061743; P:motor learning; IEA:Ensembl.
DR   GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR   GO; GO:0048666; P:neuron development; IEA:Ensembl.
DR   GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR   GO; GO:0043473; P:pigmentation; IEA:Ensembl.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0009954; P:proximal/distal pattern formation; IEA:Ensembl.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0042220; P:response to cocaine; IEA:Ensembl.
DR   GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR   GO; GO:0035176; P:social behavior; IEA:Ensembl.
DR   CDD; cd00086; homeodomain; 1.
DR   Gene3D; 1.10.10.60; Homeodomain-like; 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   PANTHER; PTHR24341; HOMEOBOX PROTEIN ENGRAILED; 1.
DR   PANTHER; PTHR24341:SF4; HOMEOBOX PROTEIN ENGRAILED-1; 1.
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; Homeodomain-like; 1.
DR   PROSITE; PS00033; ENGRAILED; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   Genevisible; Q05925; HS.
PE   3: Inferred from homology;
KW   Developmental protein; DNA-binding; Dwarfism; Homeobox; Nucleus;
KW   Reference proteome.
FT   CHAIN           1..392
FT                   /note="Homeobox protein engrailed-1"
FT                   /id="PRO_0000196062"
FT   DNA_BIND        303..362
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          1..100
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          132..164
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          219..251
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          282..306
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        29..48
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        50..89
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        18
FT                   /note="A -> G (in Ref. 1; AAA53502)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   392 AA;  40115 MW;  BDFE6279E9C27BFD CRC64;
     MEEQQPEPKS QRDSALGAAA AATPGGLSLS LSPGASGSSG SGSDGDSVPV SPQPAPPSPP
     AAPCLPPLAH HPHLPPHPPP PPPQHLAAPA HQPQPAAQLH RTTNFFIDNI LRPDFGCKKE
     QPPPQLLVAA AARGGAGGGG RVERDRGQTA AGRDPVHPLG TRAPGAASLL CAPDANCGPP
     DGSQPAAAGA GASKAGNPAA AAAAAAAAVA AAAAAAAAKP SDTGGGGSGG GAGSPGAQGT
     KYPEHGNPAI LLMGSANGGP VVKTDSQQPL VWPAWVYCTR YSDRPSSGPR TRKLKKKKNE
     KEDKRPRTAF TAEQLQRLKA EFQANRYITE QRRQTLAQEL SLNESQIKIW FQNKRAKIKK
     ATGIKNGLAL HLMAQGLYNH STTTVQDKDE SE
//