ID   EMX2_HUMAN              Reviewed;         252 AA.
AC   Q04743; G3V305; Q96NN8; Q9BQF4;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   18-OCT-2001, sequence version 2.
DT   24-JAN-2024, entry version 202.
DE   RecName: Full=Homeobox protein EMX2;
DE   AltName: Full=Empty spiracles homolog 2;
DE   AltName: Full=Empty spiracles-like protein 2;
GN   Name=EMX2;
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 1).
RX   PubMed=11549315; DOI=10.1006/geno.2001.6590;
RA   Noonan F.C., Mutch D.G., Mallon M., Goodfellow P.J.;
RT   "Characterization of the homeodomain gene EMX2: sequence conservation,
RT   expression analysis and a search for mutations in endometrial cancers.";
RL   Genomics 76:37-44(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Amygdala;
RX   PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA   Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA   Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA   Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA   Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA   Klein M., Poustka A.;
RT   "Towards a catalog of human genes and proteins: sequencing and analysis of
RT   500 novel complete protein coding human cDNAs.";
RL   Genome Res. 11:422-435(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
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   [4]
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   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 95-252 (ISOFORM 1).
RX   PubMed=1352754; DOI=10.1002/j.1460-2075.1992.tb05319.x;
RA   Simeone A., Gulisano M., Acampora D., Stornaiuolo A., Rambaldi M.,
RA   Boncinelli E.;
RT   "Two vertebrate homeobox genes related to the Drosophila empty spiracles
RT   gene are expressed in the embryonic cerebral cortex.";
RL   EMBO J. 11:2541-2550(1992).
RN   [6]
RP   INVOLVEMENT IN SCHZC.
RX   PubMed=8528262; DOI=10.1038/ng0196-94;
RA   Brunelli S., Faiella A., Capra V., Nigro V., Simeone A., Cama A.,
RA   Boncinelli E.;
RT   "Germline mutations in the homeobox gene EMX2 in patients with severe
RT   schizencephaly.";
RL   Nat. Genet. 12:94-96(1996).
CC   -!- FUNCTION: Transcription factor, which in cooperation with EMX1, acts to
CC       generate the boundary between the roof and archipallium in the
CC       developing brain. May function in combination with OTX1/2 to specify
CC       cell fates in the developing central nervous system.
CC   -!- SUBUNIT: Interacts with translation initiation factor EIF4E.
CC       {ECO:0000250|UniProtKB:Q04744}.
CC   -!- INTERACTION:
CC       Q04743; P06730: EIF4E; NbExp=4; IntAct=EBI-399831, EBI-73440;
CC       Q04743; Q7L8S5: OTUD6A; NbExp=3; IntAct=EBI-399831, EBI-11960139;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q04744}. Cell
CC       projection, axon {ECO:0000250|UniProtKB:Q04744}. Note=Detected in axons
CC       within the olfactory mucosa and glomeruli in the olfactory bulb.
CC       {ECO:0000250|UniProtKB:Q04744}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q04743-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q04743-2; Sequence=VSP_045823;
CC   -!- TISSUE SPECIFICITY: Cerebral cortex.
CC   -!- DISEASE: Schizencephaly (SCHZC) [MIM:269160]: Extremely rare human
CC       congenital disorder characterized by a full-thickness cleft within the
CC       cerebral hemispheres. These clefts are lined with gray matter and most
CC       commonly involve the parasylvian regions. Large portions of the
CC       cerebral hemispheres may be absent and replaced by cerebro-spinal
CC       fluid. {ECO:0000269|PubMed:8528262}. Note=The disease is caused by
CC       variants affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the EMX homeobox family. {ECO:0000305}.
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DR   EMBL; AF301598; AAK95496.1; -; mRNA.
DR   EMBL; AL161811; CAB82104.1; -; mRNA.
DR   EMBL; AK055041; BAB70842.1; -; mRNA.
DR   EMBL; AC005871; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; X68880; CAA48751.1; -; mRNA.
DR   CCDS; CCDS53583.1; -. [Q04743-2]
DR   CCDS; CCDS7601.1; -. [Q04743-1]
DR   PIR; S22722; S22722.
DR   RefSeq; NP_001159396.1; NM_001165924.1. [Q04743-2]
DR   RefSeq; NP_004089.1; NM_004098.3. [Q04743-1]
DR   AlphaFoldDB; Q04743; -.
DR   SMR; Q04743; -.
DR   BioGRID; 108333; 33.
DR   IntAct; Q04743; 11.
DR   STRING; 9606.ENSP00000450962; -.
DR   GlyGen; Q04743; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q04743; -.
DR   PhosphoSitePlus; Q04743; -.
DR   BioMuta; EMX2; -.
DR   DMDM; 19862512; -.
DR   MassIVE; Q04743; -.
DR   PaxDb; 9606-ENSP00000450962; -.
DR   PeptideAtlas; Q04743; -.
DR   ProteomicsDB; 32794; -.
DR   ProteomicsDB; 58277; -. [Q04743-1]
DR   Antibodypedia; 18764; 353 antibodies from 32 providers.
DR   DNASU; 2018; -.
DR   Ensembl; ENST00000442245.5; ENSP00000474874.1; ENSG00000170370.12. [Q04743-2]
DR   Ensembl; ENST00000553456.5; ENSP00000450962.3; ENSG00000170370.12. [Q04743-1]
DR   GeneID; 2018; -.
DR   KEGG; hsa:2018; -.
DR   MANE-Select; ENST00000553456.5; ENSP00000450962.3; NM_004098.4; NP_004089.1.
DR   UCSC; uc001ldh.5; human. [Q04743-1]
DR   AGR; HGNC:3341; -.
DR   CTD; 2018; -.
DR   DisGeNET; 2018; -.
DR   GeneCards; EMX2; -.
DR   HGNC; HGNC:3341; EMX2.
DR   HPA; ENSG00000170370; Tissue enhanced (endometrium, epididymis).
DR   MalaCards; EMX2; -.
DR   MIM; 269160; phenotype.
DR   MIM; 600035; gene.
DR   neXtProt; NX_Q04743; -.
DR   OpenTargets; ENSG00000170370; -.
DR   Orphanet; 485275; Acquired schizencephaly.
DR   PharmGKB; PA27778; -.
DR   VEuPathDB; HostDB:ENSG00000170370; -.
DR   eggNOG; KOG0843; Eukaryota.
DR   GeneTree; ENSGT00940000157425; -.
DR   HOGENOM; CLU_049668_1_0_1; -.
DR   InParanoid; Q04743; -.
DR   OMA; RWRMETQ; -.
DR   OrthoDB; 903523at2759; -.
DR   PhylomeDB; Q04743; -.
DR   TreeFam; TF317015; -.
DR   PathwayCommons; Q04743; -.
DR   SignaLink; Q04743; -.
DR   SIGNOR; Q04743; -.
DR   BioGRID-ORCS; 2018; 14 hits in 1164 CRISPR screens.
DR   ChiTaRS; EMX2; human.
DR   GeneWiki; EMX2; -.
DR   GenomeRNAi; 2018; -.
DR   Pharos; Q04743; Tbio.
DR   PRO; PR:Q04743; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q04743; Protein.
DR   Bgee; ENSG00000170370; Expressed in corpus epididymis and 142 other cell types or tissues.
DR   ExpressionAtlas; Q04743; baseline and differential.
DR   GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
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:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
DR   GO; GO:0007420; P:brain development; IBA:GO_Central.
DR   GO; GO:0021846; P:cell proliferation in forebrain; IEA:Ensembl.
DR   GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR   GO; GO:0021796; P:cerebral cortex regionalization; IEA:Ensembl.
DR   GO; GO:0021542; P:dentate gyrus development; IEA:Ensembl.
DR   GO; GO:0021885; P:forebrain cell migration; IEA:Ensembl.
DR   GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR   GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR   GO; GO:0072197; P:ureter morphogenesis; IEA:Ensembl.
DR   CDD; cd00086; homeodomain; 1.
DR   Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR020479; Homeobox_metazoa.
DR   InterPro; IPR000047; HTH_motif.
DR   PANTHER; PTHR24339; HOMEOBOX PROTEIN EMX-RELATED; 1.
DR   PANTHER; PTHR24339:SF25; HOMEOBOX PROTEIN EMX2; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   PRINTS; PR00024; HOMEOBOX.
DR   PRINTS; PR00031; HTHREPRESSR.
DR   SMART; SM00389; HOX; 1.
DR   SUPFAM; SSF46689; Homeodomain-like; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   Genevisible; Q04743; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell projection; Developmental protein; DNA-binding;
KW   Homeobox; Nucleus; Reference proteome.
FT   CHAIN           1..252
FT                   /note="Homeobox protein EMX2"
FT                   /id="PRO_0000048868"
FT   DNA_BIND        154..213
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          212..252
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        212..227
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         137..252
FT                   /note="NDTSPESFLLHNALARKPKRIRTAFSPSQLLRLEHAFEKNHYVVGAERKQLA
FT                   HSLSLTETQVKVWFQNRRTKFKRQKLEEEGSDSQQKKKGTHHINRWRIATKQASPEEID
FT                   VTSDD -> KSMVSEPKNKVQKAEAGGRRLRFATKEKRDAPY (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_045823"
FT   CONFLICT        104
FT                   /note="S -> P (in Ref. 3; BAB70842)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   252 AA;  28303 MW;  90DAEFFC893A971C CRC64;
     MFQPAPKRCF TIESLVAKDS PLPASRSEDP IRPAALSYAN SSPINPFLNG FHSAAAAAAG
     RGVYSNPDLV FAEAVSHPPN PAVPVHPVPP PHALAAHPLP SSHSPHPLFA SQQRDPSTFY
     PWLIHRYRYL GHRFQGNDTS PESFLLHNAL ARKPKRIRTA FSPSQLLRLE HAFEKNHYVV
     GAERKQLAHS LSLTETQVKV WFQNRRTKFK RQKLEEEGSD SQQKKKGTHH INRWRIATKQ
     ASPEEIDVTS DD
//