ID   ESX1_HUMAN              Reviewed;         406 AA.
AC   Q8N693; B0QYU3; Q7Z6K7;
DT   07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 3.
DT   27-MAR-2024, entry version 164.
DE   RecName: Full=Homeobox protein ESX1;
DE   AltName: Full=Extraembryonic, spermatogenesis, homeobox 1;
DE   Contains:
DE     RecName: Full=Homeobox protein ESX1-N;
DE   Contains:
DE     RecName: Full=Homeobox protein ESX1-C;
GN   Name=ESX1; Synonyms=ESX1L, ESX1R;
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], AND TISSUE SPECIFICITY.
RC   TISSUE=Germ cell;
RX   PubMed=11374906; DOI=10.1006/geno.2001.6532;
RA   Fohn L.E., Behringer R.R.;
RT   "ESX1L, a novel X chromosome-linked human homeobox gene expressed in the
RT   placenta and testis.";
RL   Genomics 74:105-108(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PROTEOLYTIC PROCESSING, SUBCELLULAR
RP   LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=15235584; DOI=10.1038/sj.onc.1207884;
RA   Ozawa H., Ashizawa S., Naito M., Yanagihara M., Ohnishi N., Maeda T.,
RA   Matsuda Y., Jo Y., Higashi H., Kakita A., Hatakeyama M.;
RT   "Paired-like homeodomain protein ESXR1 possesses a cleavable C-terminal
RT   region that inhibits cyclin degradation.";
RL   Oncogene 23:6590-6602(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15772651; DOI=10.1038/nature03440;
RA   Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA   Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA   Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA   Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA   Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA   Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA   Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA   Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA   Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA   Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA   Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA   Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA   Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA   Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA   Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA   Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA   Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA   Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA   Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA   Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA   Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA   Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA   Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA   Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA   Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA   Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA   Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA   Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA   Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA   McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA   Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA   Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA   Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA   Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA   Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA   Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA   Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA   Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA   Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA   d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA   Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA   Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA   Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA   Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA   Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA   Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA   Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA   Rogers J., Bentley D.R.;
RT   "The DNA sequence of the human X chromosome.";
RL   Nature 434:325-337(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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
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   FUNCTION.
RX   PubMed=15897875; DOI=10.1038/sj.onc.1208736;
RA   Yanagihara M., Ishikawa S., Naito M., Nakajima J., Aburatani H.,
RA   Hatakeyama M.;
RT   "Paired-like homeoprotein ESXR1 acts as a sequence-specific transcriptional
RT   repressor of the human K-ras gene.";
RL   Oncogene 24:5878-5887(2005).
CC   -!- FUNCTION: May coordinately regulate cell cycle progression and
CC       transcription during spermatogenesis. Inhibits degradation of
CC       polyubiquitinated cyclin A and cyclin B1 and thereby arrests the cell
CC       cycle at early M phase. ESXR1-N acts as a transcriptional repressor.
CC       Binds to the sequence 5'-TAATGTTATTA-3' which is present within the
CC       first intron of the KRAS gene and inhibits its expression. ESXR1-C has
CC       the ability to inhibit cyclin turnover. {ECO:0000269|PubMed:15235584,
CC       ECO:0000269|PubMed:15897875}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15235584}. Nucleus
CC       {ECO:0000255|PROSITE-ProRule:PRU00108, ECO:0000269|PubMed:15235584}.
CC       Note=ESXR1-N localizes specifically to the nucleus while ESXR1-C
CC       localizes specifically to the cytoplasm.
CC   -!- TISSUE SPECIFICITY: Expressed in placenta and testis. Expressed in
CC       testicular germ cell tumors. {ECO:0000269|PubMed:11374906,
CC       ECO:0000269|PubMed:15235584}.
CC   -!- PTM: Undergoes proteolytic cleavage; produces a 45 kDa N-terminal
CC       homeodomain-containing fragment (ESXR1-N) and a 20 kDa C-terminal
CC       fragment (ESXR1-C). {ECO:0000269|PubMed:15235584}.
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DR   EMBL; AY114148; AAM62141.1; -; mRNA.
DR   EMBL; AL049631; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471120; EAX02755.1; -; Genomic_DNA.
DR   EMBL; BC042633; AAH42633.1; -; mRNA.
DR   EMBL; BC053599; AAH53599.1; -; mRNA.
DR   CCDS; CCDS14516.1; -.
DR   RefSeq; NP_703149.1; NM_153448.3.
DR   AlphaFoldDB; Q8N693; -.
DR   BioGRID; 123270; 3.
DR   IntAct; Q8N693; 3.
DR   MINT; Q8N693; -.
DR   STRING; 9606.ENSP00000361669; -.
DR   GlyGen; Q8N693; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q8N693; -.
DR   PhosphoSitePlus; Q8N693; -.
DR   BioMuta; ESX1; -.
DR   DMDM; 116241356; -.
DR   EPD; Q8N693; -.
DR   MassIVE; Q8N693; -.
DR   PaxDb; 9606-ENSP00000361669; -.
DR   PeptideAtlas; Q8N693; -.
DR   ProteomicsDB; 72146; -.
DR   Antibodypedia; 15003; 150 antibodies from 28 providers.
DR   DNASU; 80712; -.
DR   Ensembl; ENST00000372588.4; ENSP00000361669.4; ENSG00000123576.5.
DR   GeneID; 80712; -.
DR   KEGG; hsa:80712; -.
DR   MANE-Select; ENST00000372588.4; ENSP00000361669.4; NM_153448.4; NP_703149.1.
DR   UCSC; uc004ely.4; human.
DR   AGR; HGNC:14865; -.
DR   CTD; 80712; -.
DR   DisGeNET; 80712; -.
DR   GeneCards; ESX1; -.
DR   HGNC; HGNC:14865; ESX1.
DR   HPA; ENSG00000123576; Tissue enriched (testis).
DR   MIM; 300154; gene.
DR   neXtProt; NX_Q8N693; -.
DR   OpenTargets; ENSG00000123576; -.
DR   PharmGKB; PA27892; -.
DR   VEuPathDB; HostDB:ENSG00000123576; -.
DR   eggNOG; KOG0490; Eukaryota.
DR   GeneTree; ENSGT00940000163297; -.
DR   HOGENOM; CLU_044595_0_0_1; -.
DR   InParanoid; Q8N693; -.
DR   OMA; FDEAQYP; -.
DR   OrthoDB; 3042435at2759; -.
DR   PhylomeDB; Q8N693; -.
DR   TreeFam; TF315976; -.
DR   PathwayCommons; Q8N693; -.
DR   SignaLink; Q8N693; -.
DR   BioGRID-ORCS; 80712; 13 hits in 796 CRISPR screens.
DR   GeneWiki; ESX1; -.
DR   GenomeRNAi; 80712; -.
DR   Pharos; Q8N693; Tbio.
DR   PRO; PR:Q8N693; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; Q8N693; Protein.
DR   Bgee; ENSG00000123576; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 21 other cell types or tissues.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
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:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IMP:NTNU_SB.
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:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR   GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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; IPR013847; POU.
DR   PANTHER; PTHR24329; HOMEOBOX PROTEIN ARISTALESS; 1.
DR   PANTHER; PTHR24329:SF340; HOMEOBOX PROTEIN ESX1; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   PRINTS; PR00028; POUDOMAIN.
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; Q8N693; HS.
PE   1: Evidence at protein level;
KW   Cytoplasm; DNA-binding; Homeobox; Nucleus; Reference proteome; Repeat;
KW   Repressor; Transcription; Transcription regulation.
FT   CHAIN           1..406
FT                   /note="Homeobox protein ESX1"
FT                   /id="PRO_0000048876"
FT   CHAIN           1..?
FT                   /note="Homeobox protein ESX1-N"
FT                   /id="PRO_0000386625"
FT   CHAIN           ?..406
FT                   /note="Homeobox protein ESX1-C"
FT                   /id="PRO_0000386626"
FT   REPEAT          244..252
FT                   /note="1"
FT   REPEAT          253..261
FT                   /note="2"
FT   REPEAT          262..270
FT                   /note="3"
FT   REPEAT          271..279
FT                   /note="4"
FT   REPEAT          280..288
FT                   /note="5"
FT   REPEAT          289..297
FT                   /note="6"
FT   REPEAT          298..306
FT                   /note="7"
FT   REPEAT          307..315
FT                   /note="8"
FT   REPEAT          316..324
FT                   /note="9"
FT   REPEAT          325..333
FT                   /note="10"
FT   REPEAT          334..342
FT                   /note="11"
FT   REPEAT          343..351
FT                   /note="12"
FT   REPEAT          352..360
FT                   /note="13"
FT   REPEAT          361..369
FT                   /note="14"
FT   REPEAT          370..378
FT                   /note="15"
FT   DNA_BIND        139..198
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          1..21
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          33..142
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          244..378
FT                   /note="15 X 9 AA tandem repeats of P-P-x-x-P-x-P-P-x"
FT   REGION          341..364
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           138..143
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        53..67
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        68..88
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         314
FT                   /note="T -> P (in dbSNP:rs9697856)"
FT                   /id="VAR_059352"
FT   CONFLICT        320
FT                   /note="P -> R (in Ref. 5; AAH42633/AAH53599)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        338..339
FT                   /note="RV -> PL (in Ref. 5; AAH42633/AAH53599)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   406 AA;  44297 MW;  7013E3986F1148FA CRC64;
     MESLRGYTHS DIGYRSLAVG EDIEEVNDEK LTVTSLMARG GEDEENTRSK PEYGTEAENN
     VGTEGSVPSD DQDREGGGGH EPEQQQEEPP LTKPEQQQEE PPLLELKQEQ EEPPQTTVEG
     PQPAEGPQTA EGPQPPERKR RRRTAFTQFQ LQELENFFDE SQYPDVVARE RLAARLNLTE
     DRVQVWFQNR RAKWKRNQRV LMLRNTATAD LAHPLDMFLG GAYYAAPALD PALCVHLVPQ
     LPRPPVLPVP PMPPRPPMVP MPPRPPIAPM PPMAPVPPGS RMAPVPPGPR MAPVPPWPPM
     APVPPWPPMA PVPTGPPMAP VPPGPPMARV PPGPPMARVP PGPPMAPLPP GPPMAPLPPG
     PPMAPLPPGP PMAPLPPRSH VPHTGLAPVH ITWAPVINSY YACPFF
//