ESX1_HUMAN
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 03-AUG-2022, entry version 155.
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 iPTMnet; Q8N693; -.
DR PhosphoSitePlus; Q8N693; -.
DR BioMuta; ESX1; -.
DR DMDM; 116241356; -.
DR EPD; Q8N693; -.
DR MassIVE; Q8N693; -.
DR PaxDb; Q8N693; -.
DR PeptideAtlas; Q8N693; -.
DR PRIDE; Q8N693; -.
DR ProteomicsDB; 72146; -.
DR Antibodypedia; 15003; 134 antibodies from 27 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 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; YGAEAEN; -.
DR OrthoDB; 1270742at2759; -.
DR PhylomeDB; Q8N693; -.
DR TreeFam; TF315976; -.
DR PathwayCommons; Q8N693; -.
DR SignaLink; Q8N693; -.
DR BioGRID-ORCS; 80712; 11 hits in 718 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 right testis and 19 other tissues.
DR Genevisible; Q8N693; HS.
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:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
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 InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR013847; POU.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00028; POUDOMAIN.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
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
