HME1_HUMAN
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 03-AUG-2022, entry version 182.
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; Q05925; -.
DR PeptideAtlas; Q05925; -.
DR PRIDE; Q05925; -.
DR ProteomicsDB; 58357; -.
DR Antibodypedia; 33365; 256 antibodies from 29 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 CTD; 2019; -.
DR DisGeNET; 2019; -.
DR GeneCards; EN1; -.
DR HGNC; HGNC:3342; EN1.
DR HPA; ENSG00000163064; Group enriched (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; GCKKEPP; -.
DR OrthoDB; 1575614at2759; -.
DR PhylomeDB; Q05925; -.
DR TreeFam; TF106461; -.
DR PathwayCommons; Q05925; -.
DR SignaLink; Q05925; -.
DR SIGNOR; Q05925; -.
DR BioGRID-ORCS; 2019; 5 hits in 1095 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 57 other tissues.
DR Genevisible; Q05925; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0016020; C:membrane; IEA:Ensembl.
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 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 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
