HOP_MOUSE
ID HOP_MOUSE Reviewed; 73 AA.
AC Q8R1H0; Q8C1N5; Q8CJ22;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Homeodomain-only protein;
DE AltName: Full=Homeobox-only protein;
DE AltName: Full=Odd homeobox protein 1;
DE Short=mOB1;
GN Name=Hopx; Synonyms=Hod, Hop, Ob1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION, INTERACTION WITH SRF,
RP MUTAGENESIS OF 35-LEU--GLU-39 AND 49-LYS--GLN-53, AND DISRUPTION PHENOTYPE.
RC STRAIN=NIH Swiss;
RX PubMed=12297045; DOI=10.1016/s0092-8674(02)00932-7;
RA Chen F., Kook H., Milewski R., Gitler A.D., Lu M.M., Li J., Nazarian R.,
RA Schnepp R., Jen K., Biben C., Runke G., Mackay J.P., Novotny J.,
RA Schwartz R.J., Harvey R.P., Mullins M.C., Epstein J.A.;
RT "Hop is an unusual homeobox gene that modulates cardiac development.";
RL Cell 110:713-723(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, INTERACTION WITH SRF, AND DISRUPTION PHENOTYPE.
RC STRAIN=C57BL/6J; TISSUE=Heart;
RX PubMed=12297046; DOI=10.1016/s0092-8674(02)00933-9;
RA Shin C.H., Liu Z.-P., Passier R., Zhang C.-L., Wang D.-Z., Harris T.M.,
RA Yamagishi H., Richardson J.A., Childs G., Olson E.N.;
RT "Modulation of cardiac growth and development by HOP, an unusual
RT homeodomain protein.";
RL Cell 110:725-735(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=CD-1;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Lung, Small intestine, and Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
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 INTERACTION WITH HDAC2.
RX PubMed=12975471; DOI=10.1172/jci200319137;
RA Kook H., Lepore J.J., Gitler A.D., Lu M.M., Yung W.W.-M., Mackay J.,
RA Zhou R., Ferrari V., Gruber P., Epstein J.A.;
RT "Cardiac hypertrophy and histone deacetylase-dependent transcriptional
RT repression mediated by the atypical homeodomain protein Hop.";
RL J. Clin. Invest. 112:863-871(2003).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP STRUCTURE BY NMR OF 10-73.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of mouse homeodomain-only protein Hop.";
RL Submitted (JUL-2004) to the PDB data bank.
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
CC (PubMed:12297045, PubMed:12297046). Acts as a co-chaperone for HSPA1A
CC and HSPA1B chaperone proteins and assists in chaperone-mediated protein
CC refolding (By similarity). {ECO:0000250|UniProtKB:Q9BPY8,
CC ECO:0000269|PubMed:12297045, ECO:0000269|PubMed:12297046}.
CC -!- SUBUNIT: Interacts with serum response factor (SRF) (PubMed:12297045,
CC PubMed:12297046). Component of a large complex containing histone
CC deacetylases such as HDAC2 (PubMed:12975471). Interacts with the
CC acetylated forms of HSPA1A and HSPA1B. Interacts with HSPA8 (By
CC similarity). {ECO:0000250|UniProtKB:Q9BPY8,
CC ECO:0000269|PubMed:12297045, ECO:0000269|PubMed:12297046,
CC ECO:0000269|PubMed:12975471}.
CC -!- INTERACTION:
CC Q8R1H0; P97471: Smad4; NbExp=2; IntAct=EBI-6913924, EBI-5259270;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12297045}. Cytoplasm
CC {ECO:0000269|PubMed:14516659}. Note=According to PubMed:14516659 it is
CC cytoplasmic. {ECO:0000269|PubMed:14516659}.
CC -!- TISSUE SPECIFICITY: Expressed in the embryonic and adult heart and in
CC the adult brain, liver, lung, skeletal muscle, intestine and spleen.
CC Throughout embryonic and postnatal development, it is expressed in the
CC myocardium. {ECO:0000269|PubMed:12297045, ECO:0000269|PubMed:12297046,
CC ECO:0000269|PubMed:14516659}.
CC -!- DEVELOPMENTAL STAGE: First detected at 7.75 dpc in trophoblasts within
CC extraembryonic membranes, in the lateral wings of the cardiac crescent
CC and in the anterior head folds. At 8.0 dpc, it is expressed along the
CC length of the linear heart tube and in the head folds. Expressed
CC throughout the myocardium at 9.5 dpc and in the branchial arches. At
CC 12.5 dpc, it is expressed in the heart and in the ventricular zone of
CC the neural tube. At 13.5 dpc, it is weakly expressed in the intestinal
CC epithelium. At 13.5 dpc and 15.5 dpc, it is also expressed in skeletal
CC muscle, stratified epithelium (upper aerodigestive tract and skin),
CC epithelium of developing airways, vibrissae, midbrain/hindbrain
CC junction, meninges, mesenchymal cellular condensations that preceded
CC cartilage formation and chondrocytes. {ECO:0000269|PubMed:12297045,
CC ECO:0000269|PubMed:12297046, ECO:0000269|PubMed:14516659}.
CC -!- INDUCTION: By the transcription factor NKX2-5 that acts as a direct
CC regulator. {ECO:0000269|PubMed:12297045}.
CC -!- DISRUPTION PHENOTYPE: Mice display partial embryonic lethality and
CC heart failure. {ECO:0000269|PubMed:12297045,
CC ECO:0000269|PubMed:12297046}.
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DR EMBL; AF536202; AAN16320.1; -; mRNA.
DR EMBL; AF534182; AAN05634.1; -; mRNA.
DR EMBL; AF492703; AAM46823.1; -; mRNA.
DR EMBL; AF492704; AAM46824.1; -; mRNA.
DR EMBL; AK003784; BAC25054.1; -; mRNA.
DR EMBL; AK004798; BAC25097.1; -; mRNA.
DR EMBL; AK008297; BAC25214.1; -; mRNA.
DR EMBL; AK008439; BAC25219.1; -; mRNA.
DR EMBL; AK009007; BAC25235.1; -; mRNA.
DR EMBL; BC024546; AAH24546.1; -; mRNA.
DR CCDS; CCDS39120.1; -.
DR RefSeq; NP_001153372.1; NM_001159900.1.
DR RefSeq; NP_001153373.1; NM_001159901.1.
DR RefSeq; NP_783199.1; NM_175606.3.
DR PDB; 1UHS; NMR; -; A=10-73.
DR PDB; 2HI3; NMR; -; A=1-73.
DR PDBsum; 1UHS; -.
DR PDBsum; 2HI3; -.
DR AlphaFoldDB; Q8R1H0; -.
DR BMRB; Q8R1H0; -.
DR SMR; Q8R1H0; -.
DR BioGRID; 216662; 2.
DR CORUM; Q8R1H0; -.
DR DIP; DIP-61663N; -.
DR IntAct; Q8R1H0; 9.
DR STRING; 10090.ENSMUSP00000080630; -.
DR iPTMnet; Q8R1H0; -.
DR PhosphoSitePlus; Q8R1H0; -.
DR EPD; Q8R1H0; -.
DR MaxQB; Q8R1H0; -.
DR PaxDb; Q8R1H0; -.
DR PeptideAtlas; Q8R1H0; -.
DR PRIDE; Q8R1H0; -.
DR ProteomicsDB; 273130; -.
DR Antibodypedia; 24043; 282 antibodies from 30 providers.
DR DNASU; 74318; -.
DR Ensembl; ENSMUST00000081964; ENSMUSP00000080630; ENSMUSG00000059325.
DR Ensembl; ENSMUST00000113453; ENSMUSP00000109080; ENSMUSG00000059325.
DR Ensembl; ENSMUST00000120827; ENSMUSP00000113295; ENSMUSG00000059325.
DR GeneID; 74318; -.
DR KEGG; mmu:74318; -.
DR UCSC; uc008xvv.2; mouse.
DR CTD; 84525; -.
DR MGI; MGI:1916782; Hopx.
DR VEuPathDB; HostDB:ENSMUSG00000059325; -.
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00390000017143; -.
DR HOGENOM; CLU_193231_0_0_1; -.
DR InParanoid; Q8R1H0; -.
DR OMA; EDSFKGC; -.
DR OrthoDB; 1621268at2759; -.
DR PhylomeDB; Q8R1H0; -.
DR TreeFam; TF330730; -.
DR BioGRID-ORCS; 74318; 4 hits in 75 CRISPR screens.
DR ChiTaRS; Hopx; mouse.
DR EvolutionaryTrace; Q8R1H0; -.
DR PRO; PR:Q8R1H0; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8R1H0; protein.
DR Bgee; ENSMUSG00000059325; Expressed in right lung lobe and 257 other tissues.
DR Genevisible; Q8R1H0; MM.
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:0051131; P:chaperone-mediated protein complex assembly; ISO:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0016575; P:histone deacetylation; IGI:MGI.
DR GO; GO:0048286; P:lung alveolus development; IMP:MGI.
DR GO; GO:0045596; P:negative regulation of cell differentiation; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:1903598; P:positive regulation of gap junction assembly; IMP:BHF-UCL.
DR GO; GO:0043415; P:positive regulation of skeletal muscle tissue regeneration; IMP:MGI.
DR GO; GO:0051155; P:positive regulation of striated muscle cell differentiation; IMP:MGI.
DR GO; GO:0008016; P:regulation of heart contraction; IMP:MGI.
DR GO; GO:0043393; P:regulation of protein binding; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001829; P:trophectodermal cell differentiation; IMP: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 3D-structure; Cytoplasm; Developmental protein; Homeobox; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..73
FT /note="Homeodomain-only protein"
FT /id="PRO_0000049130"
FT DNA_BIND 3..62
FT /note="Homeobox; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT MUTAGEN 35..39
FT /note="LIAAE->AAASM: In H2; induces a strong reduction in
FT interaction with SRF and subsequent ability to prevent
FT transcription of cardiac-specific genes."
FT /evidence="ECO:0000269|PubMed:12297045"
FT MUTAGEN 49..53
FT /note="KWFKQ->AAASM: In H3; does not affect the interaction
FT with SRF and keeps its ability to prevent transcription of
FT cardiac-specific genes."
FT /evidence="ECO:0000269|PubMed:12297045"
FT CONFLICT 6
FT /note="A -> P (in Ref. 4; BAC25235)"
FT /evidence="ECO:0000305"
FT CONFLICT 6
FT /note="A -> V (in Ref. 1; AAN16320)"
FT /evidence="ECO:0000305"
FT HELIX 11..22
FT /evidence="ECO:0007829|PDB:1UHS"
FT HELIX 30..40
FT /evidence="ECO:0007829|PDB:1UHS"
FT HELIX 44..62
FT /evidence="ECO:0007829|PDB:1UHS"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:2HI3"
SQ SEQUENCE 73 AA; 8282 MW; 9D9B6D7F7A11C592 CRC64;
MSAQTASGPT EDQVEILEYN FNKVNKHPDP TTLCLIAAEA GLTEEQTQKW FKQRLAEWRR
SEGLPSECRS VTD
