HOP_HUMAN
ID HOP_HUMAN Reviewed; 73 AA.
AC Q9BPY8; A8K0Z2; E9PB55; G3V294; Q8N0V6; Q96CI1;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Homeodomain-only protein;
DE AltName: Full=Lung cancer-associated Y protein;
DE AltName: Full=Not expressed in choriocarcinoma protein 1;
DE AltName: Full=Odd homeobox protein 1;
GN Name=HOPX; Synonyms=HOD, HOP, LAGY, NECC1, OB1;
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] (ISOFORMS 1 AND 2).
RC TISSUE=Heart;
RX PubMed=14516659; DOI=10.1016/s0925-4773(03)00090-x;
RA Adu J., Leong F.T., Smith N.R., Leek J.P., Markham A.F., Robinson P.A.,
RA Mighell A.J.;
RT "Expression of mOb1, a novel atypical 73 amino acid K50-homeodomain
RT protein, during mouse development.";
RL Mech. Dev. 119:S43-S47(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND POSSIBLE
RP INVOLVEMENT IN CHORIOCARCINOMA.
RX PubMed=12573257; DOI=10.1016/s0888-7543(02)00011-3;
RA Asanoma K., Matsuda T., Kondo H., Kato K., Kishino T., Niikawa N., Wake N.,
RA Kato H.;
RT "NECC1, a candidate choriocarcinoma suppressor gene that encodes a
RT homeodomain consensus motif.";
RL Genomics 81:15-25(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND POSSIBLE
RP INVOLVEMENT IN LUNG CANCER.
RX PubMed=12759545; DOI=10.1159/000070306;
RA Chen Y., Petersen S., Pacyna-Gengelbach M., Pietas A., Petersen I.;
RT "Identification of a novel homeobox-containing gene, LAGY, which is
RT downregulated in lung cancer.";
RL Oncology 64:450-458(2003).
RN [4]
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 [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=B-cell;
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 [7]
RP INVOLVEMENT IN HEAD AND NECK SQUAMOUS CELL CARCINOMA.
RX PubMed=15213722; DOI=10.1038/sj.bjc.6601952;
RA Lemaire F., Millon R., Muller D., Rabouel Y., Bracco L., Abecassis J.,
RA Wasylyk B.;
RT "Loss of HOP tumour suppressor expression in head and neck squamous cell
RT carcinoma.";
RL Br. J. Cancer 91:258-261(2004).
RN [8]
RP INVOLVEMENT IN ORAL SQUAMOUS CELL CARCINOMA.
RX PubMed=15381369; DOI=10.1016/j.cancergencyto.2004.01.026;
RA Toruner G.A., Ulger C., Alkan M., Galante A.T., Rinaggio J., Wilk R.,
RA Tian B., Soteropoulos P., Hameed M.R., Schwalb M.N., Dermody J.J.;
RT "Association between gene expression profile and tumor invasion in oral
RT squamous cell carcinoma.";
RL Cancer Genet. Cytogenet. 154:27-35(2004).
RN [9]
RP FUNCTION, AND INTERACTION WITH HSPA1A; HSPA1B AND HSPA8.
RX PubMed=27708256; DOI=10.1038/ncomms12882;
RA Seo J.H., Park J.H., Lee E.J., Vo T.T., Choi H., Kim J.Y., Jang J.K.,
RA Wee H.J., Lee H.S., Jang S.H., Park Z.Y., Jeong J., Lee K.J., Seok S.H.,
RA Park J.Y., Lee B.J., Lee M.N., Oh G.T., Kim K.W.;
RT "ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding
RT and degradation.";
RL Nat. Commun. 7:12882-12882(2016).
CC -!- FUNCTION: Atypical homeodomain protein which does not bind DNA and is
CC required to modulate cardiac growth and development. Acts via its
CC interaction with SRF, thereby modulating the expression of SRF-
CC dependent cardiac-specific genes and cardiac development. Prevents SRF-
CC dependent transcription either by inhibiting SRF binding to DNA or by
CC recruiting histone deacetylase (HDAC) proteins that prevent
CC transcription by SRF. Overexpression causes cardiac hypertrophy (By
CC similarity). May act as a tumor suppressor. Acts as a co-chaperone for
CC HSPA1A and HSPA1B chaperone proteins and assists in chaperone-mediated
CC protein refolding (PubMed:27708256). {ECO:0000250|UniProtKB:Q8R1H0,
CC ECO:0000269|PubMed:27708256}.
CC -!- SUBUNIT: Interacts with serum response factor (SRF). Component of a
CC large complex containing histone deacetylases such as HDAC2 (By
CC similarity). Interacts with the acetylated forms of HSPA1A and HSPA1B.
CC Interacts with HSPA8 (PubMed:27708256). {ECO:0000250|UniProtKB:Q8R1H0,
CC ECO:0000269|PubMed:27708256}.
CC -!- INTERACTION:
CC Q9BPY8; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-10295883, EBI-79165;
CC Q9BPY8; Q99081: TCF12; NbExp=3; IntAct=EBI-10295883, EBI-722877;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8R1H0}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q8R1H0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=A;
CC IsoId=Q9BPY8-1; Sequence=Displayed;
CC Name=2; Synonyms=B;
CC IsoId=Q9BPY8-2; Sequence=VSP_012659;
CC Name=3;
CC IsoId=Q9BPY8-3; Sequence=VSP_047290;
CC Name=4;
CC IsoId=Q9BPY8-4; Sequence=VSP_047290, VSP_012659;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in the heart, brain,
CC placenta, lung, skeletal and smooth muscles, uterus, urinary bladder,
CC kidney and spleen. Down-regulated in some types of cancer such as lung
CC cancer, choriocarcinoma, head and neck squamous cell carcinoma and oral
CC squamous cell carcinoma. {ECO:0000269|PubMed:12573257,
CC ECO:0000269|PubMed:12759545}.
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DR EMBL; AF492675; AAM46827.1; -; mRNA.
DR EMBL; AF492676; AAM46828.1; -; mRNA.
DR EMBL; AF492677; AAM46829.1; -; mRNA.
DR EMBL; AF492678; AAM46830.1; -; mRNA.
DR EMBL; AF492679; AAM46831.1; -; mRNA.
DR EMBL; AF492680; AAM46832.1; -; mRNA.
DR EMBL; AF492681; AAM46833.1; -; mRNA.
DR EMBL; AB059408; BAB40926.1; -; mRNA.
DR EMBL; AB059409; BAB40927.1; -; mRNA.
DR EMBL; AB059410; BAB40928.1; -; mRNA.
DR EMBL; AF454763; AAL56613.1; -; mRNA.
DR EMBL; AK289707; BAF82396.1; -; mRNA.
DR EMBL; AC108215; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014225; AAH14225.1; -; mRNA.
DR CCDS; CCDS3507.1; -. [Q9BPY8-1]
DR CCDS; CCDS47062.1; -. [Q9BPY8-3]
DR CCDS; CCDS54767.1; -. [Q9BPY8-4]
DR RefSeq; NP_001138931.1; NM_001145459.1. [Q9BPY8-1]
DR RefSeq; NP_001138932.1; NM_001145460.1. [Q9BPY8-4]
DR RefSeq; NP_115884.4; NM_032495.5. [Q9BPY8-3]
DR RefSeq; NP_631957.1; NM_139211.4. [Q9BPY8-1]
DR RefSeq; NP_631958.1; NM_139212.3. [Q9BPY8-1]
DR RefSeq; XP_016864218.1; XM_017008729.1.
DR RefSeq; XP_016864219.1; XM_017008730.1. [Q9BPY8-1]
DR RefSeq; XP_016864220.1; XM_017008731.1. [Q9BPY8-1]
DR RefSeq; XP_016864221.1; XM_017008732.1. [Q9BPY8-1]
DR RefSeq; XP_016864222.1; XM_017008733.1. [Q9BPY8-1]
DR RefSeq; XP_016864223.1; XM_017008734.1. [Q9BPY8-1]
DR AlphaFoldDB; Q9BPY8; -.
DR SMR; Q9BPY8; -.
DR BioGRID; 124117; 34.
DR IntAct; Q9BPY8; 7.
DR MINT; Q9BPY8; -.
DR STRING; 9606.ENSP00000450527; -.
DR iPTMnet; Q9BPY8; -.
DR PhosphoSitePlus; Q9BPY8; -.
DR BioMuta; HOPX; -.
DR DMDM; 60392394; -.
DR jPOST; Q9BPY8; -.
DR MassIVE; Q9BPY8; -.
DR PaxDb; Q9BPY8; -.
DR PeptideAtlas; Q9BPY8; -.
DR PRIDE; Q9BPY8; -.
DR ProteomicsDB; 19147; -.
DR ProteomicsDB; 32566; -.
DR ProteomicsDB; 78595; -. [Q9BPY8-1]
DR ProteomicsDB; 78596; -. [Q9BPY8-2]
DR Antibodypedia; 24043; 282 antibodies from 30 providers.
DR DNASU; 84525; -.
DR Ensembl; ENST00000317745.11; ENSP00000315198.7; ENSG00000171476.22. [Q9BPY8-1]
DR Ensembl; ENST00000337881.11; ENSP00000337330.7; ENSG00000171476.22. [Q9BPY8-1]
DR Ensembl; ENST00000381255.7; ENSP00000370654.3; ENSG00000171476.22. [Q9BPY8-1]
DR Ensembl; ENST00000381260.7; ENSP00000370659.2; ENSG00000171476.22. [Q9BPY8-2]
DR Ensembl; ENST00000420433.6; ENSP00000396275.1; ENSG00000171476.22. [Q9BPY8-3]
DR Ensembl; ENST00000503639.7; ENSP00000424101.2; ENSG00000171476.22. [Q9BPY8-1]
DR Ensembl; ENST00000508121.2; ENSP00000422175.2; ENSG00000171476.22. [Q9BPY8-1]
DR Ensembl; ENST00000553379.6; ENSP00000452340.1; ENSG00000171476.22. [Q9BPY8-1]
DR Ensembl; ENST00000554144.5; ENSP00000450527.1; ENSG00000171476.22. [Q9BPY8-4]
DR Ensembl; ENST00000555760.6; ENSP00000452098.1; ENSG00000171476.22. [Q9BPY8-1]
DR Ensembl; ENST00000556376.6; ENSP00000451794.1; ENSG00000171476.22. [Q9BPY8-1]
DR Ensembl; ENST00000556614.6; ENSP00000452003.1; ENSG00000171476.22. [Q9BPY8-1]
DR GeneID; 84525; -.
DR KEGG; hsa:84525; -.
DR MANE-Select; ENST00000420433.6; ENSP00000396275.1; NM_032495.6; NP_115884.4. [Q9BPY8-3]
DR UCSC; uc003hbz.3; human. [Q9BPY8-1]
DR CTD; 84525; -.
DR DisGeNET; 84525; -.
DR GeneCards; HOPX; -.
DR HGNC; HGNC:24961; HOPX.
DR HPA; ENSG00000171476; Tissue enhanced (esophagus, skin).
DR MIM; 607275; gene.
DR neXtProt; NX_Q9BPY8; -.
DR OpenTargets; ENSG00000171476; -.
DR PharmGKB; PA162391564; -.
DR VEuPathDB; HostDB:ENSG00000171476; -.
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00390000017143; -.
DR HOGENOM; CLU_193231_0_0_1; -.
DR InParanoid; Q9BPY8; -.
DR OMA; EDSFKGC; -.
DR OrthoDB; 1567787at2759; -.
DR PhylomeDB; Q9BPY8; -.
DR PathwayCommons; Q9BPY8; -.
DR SignaLink; Q9BPY8; -.
DR SIGNOR; Q9BPY8; -.
DR BioGRID-ORCS; 84525; 9 hits in 1090 CRISPR screens.
DR ChiTaRS; HOPX; human.
DR GeneWiki; HOPX; -.
DR GenomeRNAi; 84525; -.
DR Pharos; Q9BPY8; Tbio.
DR PRO; PR:Q9BPY8; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9BPY8; protein.
DR Bgee; ENSG00000171476; Expressed in upper leg skin and 195 other tissues.
DR Genevisible; Q9BPY8; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003166; P:bundle of His development; NAS:BHF-UCL.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; IDA:CAFA.
DR GO; GO:0016575; P:histone deacetylation; IEA:Ensembl.
DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl.
DR GO; GO:0045596; P:negative regulation of cell differentiation; IDA:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:1903598; P:positive regulation of gap junction assembly; IEA:Ensembl.
DR GO; GO:0043415; P:positive regulation of skeletal muscle tissue regeneration; IEA:Ensembl.
DR GO; GO:0051155; P:positive regulation of striated muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0008016; P:regulation of heart contraction; IEA:Ensembl.
DR GO; GO:0043393; P:regulation of protein binding; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001829; P:trophectodermal cell differentiation; IDA:MGI.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR039162; HOPX.
DR PANTHER; PTHR21408; PTHR21408; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Developmental protein; Homeobox; Nucleus;
KW Proto-oncogene; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..73
FT /note="Homeodomain-only protein"
FT /id="PRO_0000049129"
FT DNA_BIND 3..62
FT /note="Homeobox; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT VAR_SEQ 1
FT /note="M -> MLIFLGCYRRRLEERAGTM (in isoform 3 and isoform
FT 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_047290"
FT VAR_SEQ 49..73
FT /note="KWFKQRLAKWRRSEGLPSECRSVTD -> GSDLISRSKIWHPESSPQREGYP
FT HDSLPCLAFDYFSLLPPQCKEMV (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14516659"
FT /id="VSP_012659"
FT CONFLICT 72
FT /note="T -> I (in Ref. 6; AAH14225)"
FT /evidence="ECO:0000305"
FT CONFLICT Q9BPY8-2:76
FT /note="P -> L (in Ref. 1; AAM46830/AAM46831)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 73 AA; 8260 MW; CE65E4D2A8972022 CRC64;
MSAETASGPT EDQVEILEYN FNKVDKHPDS TTLCLIAAEA GLSEEETQKW FKQRLAKWRR
SEGLPSECRS VTD
