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Prospero homeobox protein 1 (Homeobox prospero-like protein PROX1) (PROX-1)

 PROX1_MOUSE             Reviewed;         737 AA.
P48437; O88478; Q3UPV1; Q543D8;
01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
27-APR-2001, sequence version 2.
22-NOV-2017, entry version 148.
RecName: Full=Prospero homeobox protein 1;
AltName: Full=Homeobox prospero-like protein PROX1;
Short=PROX-1;
Name=Prox1;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
PubMed=9703987; DOI=10.1006/bbrc.1998.8989;
Tomarev S.I., Zinovieva R.D., Chang B., Hawes N.L.;
"Characterization of the mouse Prox1 gene.";
Biochem. Biophys. Res. Commun. 248:684-689(1998).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=C57BL/6J; TISSUE=Eye, and Heart;
PubMed=16141072; DOI=10.1126/science.1112014;
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
Hayashizaki Y.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Retina;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
NUCLEOTIDE SEQUENCE [MRNA] OF 573-737, AND TISSUE SPECIFICITY.
PubMed=7908825; DOI=10.1016/0925-4773(93)90012-M;
Oliver G., Sosa-Pineda B., Geisendorf S., Spana E.P., Doe C.Q.,
Gruss P.;
"Prox 1, a prospero-related homeobox gene expressed during mouse
development.";
Mech. Dev. 44:3-16(1993).
[5]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179; SER-511 AND
SER-514, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
ANALYSIS].
TISSUE=Liver;
PubMed=17242355; DOI=10.1073/pnas.0609836104;
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
"Large-scale phosphorylation analysis of mouse liver.";
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
[6]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-511, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=18630941; DOI=10.1021/pr800223m;
Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
"Specific phosphopeptide enrichment with immobilized titanium ion
affinity chromatography adsorbent for phosphoproteome analysis.";
J. Proteome Res. 7:3957-3967(2008).
[7]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179; SER-291; SER-295;
SER-511 AND SER-514, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
SCALE ANALYSIS].
TISSUE=Brain, Heart, Kidney, Liver, Pancreas, and Spleen;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
expression.";
Cell 143:1174-1189(2010).
[8]
REVIEW.
PubMed=22733308; DOI=10.1007/s10555-012-9390-8;
Elsir T., Smits A., Lindstroem M.S., Nister M.;
"Transcription factor PROX1: its role in development and cancer.";
Cancer Metastasis Rev. 31:793-805(2012).
[9]
FUNCTION, INDUCTION, SUBCELLULAR LOCATION, INTERACTION WITH RORA AND
RORG, AND DOMAIN.
PubMed=23723244; DOI=10.1093/nar/gkt447;
Takeda Y., Jetten A.M.;
"Prospero-related homeobox 1 (Prox1) functions as a novel modulator of
retinoic acid-related orphan receptors alpha- and gamma-mediated
transactivation.";
Nucleic Acids Res. 41:6992-7008(2013).
-!- FUNCTION: Transcription factor involved in developmental processes
such as cell fate determination, gene transcriptional regulation
and progenitor cell regulation in a number of organs. Plays a
critical role in embryonic development and functions as a key
regulatory protein in neurogenesis and the development of the
heart, eye lens, liver, pancreas and the lymphatic system.
Involved in the regulation of the circadian rhythm. Represses:
transcription of the retinoid-related orphan receptor RORG,
transcriptional activator activity of RORA and RORG and the
expression of RORA/G-target genes including core clock components:
ARNTL/BMAL1, NPAS2 and CRY1 and metabolic genes: AVPR1A and
ELOVL3. {ECO:0000269|PubMed:23723244,
ECO:0000303|PubMed:22733308}.
-!- SUBUNIT: Interacts with RORA and RORG (via AF-2 motif).
{ECO:0000269|PubMed:23723244}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23723244}.
Note=RORG promotes its nuclear localization.
{ECO:0000269|PubMed:23723244}.
-!- TISSUE SPECIFICITY: Expressed in the young neurons of the
subventricular region of the CNS, developing eye lens and
pancreas. It is also found in the developing liver, heart and
skeletal muscle. In the eye, expressed in the lens and retina at
postnatal day 10. In the retina, localized to the inner nuclear
layer. In the lens, localized to epithelial and fiber cells.
{ECO:0000269|PubMed:7908825, ECO:0000269|PubMed:9703987}.
-!- INDUCTION: Expressed in a circadian manner in the liver with a
peak at ZT4. {ECO:0000269|PubMed:23723244}.
-!- DOMAIN: The Prospero-type homeodomain and the adjacent Prospero
domain act as a single structural unit, the Homeo-Prospero domain
(Potential). The Prospero-type homeodomain is essential for
repression of RORG transcriptional activator activity
(PubMed:23723244). {ECO:0000255|PROSITE-ProRule:PRU01162,
ECO:0000269|PubMed:23723244}.
-!- SIMILARITY: Belongs to the Prospero homeodomain family.
{ECO:0000255|PROSITE-ProRule:PRU01162}.
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EMBL; AF061576; AAC32824.1; -; mRNA.
EMBL; AK052889; BAC35190.1; -; mRNA.
EMBL; AK143179; BAE25293.1; -; mRNA.
EMBL; BC051411; AAH51411.1; -; mRNA.
CCDS; CCDS35822.1; -.
PIR; JE0269; JE0269.
RefSeq; NP_032963.1; NM_008937.2.
RefSeq; XP_006497191.1; XM_006497128.3.
UniGene; Mm.132579; -.
UniGene; Mm.392678; -.
ProteinModelPortal; P48437; -.
SMR; P48437; -.
BioGrid; 202396; 2.
DIP; DIP-58960N; -.
IntAct; P48437; 2.
MINT; MINT-4108644; -.
STRING; 10090.ENSMUSP00000010319; -.
iPTMnet; P48437; -.
PhosphoSitePlus; P48437; -.
MaxQB; P48437; -.
PaxDb; P48437; -.
PeptideAtlas; P48437; -.
PRIDE; P48437; -.
Ensembl; ENSMUST00000010319; ENSMUSP00000010319; ENSMUSG00000010175.
Ensembl; ENSMUST00000175916; ENSMUSP00000135703; ENSMUSG00000010175.
Ensembl; ENSMUST00000177288; ENSMUSP00000135066; ENSMUSG00000010175.
GeneID; 19130; -.
KEGG; mmu:19130; -.
UCSC; uc007ebc.2; mouse.
CTD; 5629; -.
MGI; MGI:97772; Prox1.
eggNOG; KOG3779; Eukaryota.
eggNOG; ENOG410ZE21; LUCA.
GeneTree; ENSGT00530000063507; -.
HOGENOM; HOG000115708; -.
HOVERGEN; HBG053693; -.
InParanoid; P48437; -.
KO; K20211; -.
OMA; SCFMSRN; -.
OrthoDB; EOG091G02KS; -.
PhylomeDB; P48437; -.
TreeFam; TF316638; -.
PRO; PR:P48437; -.
Proteomes; UP000000589; Chromosome 1.
Bgee; ENSMUSG00000010175; -.
CleanEx; MM_PROX1; -.
Genevisible; P48437; MM.
GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0001046; F:core promoter sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0050692; F:DBD domain binding; ISO:MGI.
GO; GO:0003677; F:DNA binding; ISO:MGI.
GO; GO:0050693; F:LBD domain binding; ISO:MGI.
GO; GO:0016922; F:ligand-dependent nuclear receptor binding; ISO:MGI.
GO; GO:0000981; F:RNA polymerase II transcription factor activity, sequence-specific DNA binding; IDA:MGI.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
GO; GO:0003714; F:transcription corepressor activity; ISO:MGI.
GO; GO:0003705; F:transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; IDA:BHF-UCL.
GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; NAS:BHF-UCL.
GO; GO:0044212; F:transcription regulatory region DNA binding; ISO:MGI.
GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IBA:GO_Central.
GO; GO:0090425; P:acinar cell differentiation; IMP:MGI.
GO; GO:0060414; P:aorta smooth muscle tissue morphogenesis; IMP:BHF-UCL.
GO; GO:0055009; P:atrial cardiac muscle tissue morphogenesis; IMP:BHF-UCL.
GO; GO:0061114; P:branching involved in pancreas morphogenesis; IMP:MGI.
GO; GO:0001709; P:cell fate determination; IMP:MGI.
GO; GO:0021707; P:cerebellar granule cell differentiation; IMP:BHF-UCL.
GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
GO; GO:0021542; P:dentate gyrus development; IMP:BHF-UCL.
GO; GO:0060059; P:embryonic retina morphogenesis in camera-type eye; IEP:BHF-UCL.
GO; GO:0060214; P:endocardium formation; IMP:BHF-UCL.
GO; GO:0045446; P:endothelial cell differentiation; IMP:MGI.
GO; GO:0002194; P:hepatocyte cell migration; IMP:MGI.
GO; GO:0070365; P:hepatocyte differentiation; IEP:BHF-UCL.
GO; GO:0072574; P:hepatocyte proliferation; IMP:MGI.
GO; GO:0048839; P:inner ear development; IMP:MGI.
GO; GO:0001822; P:kidney development; IEA:Ensembl.
GO; GO:0070309; P:lens fiber cell morphogenesis; IMP:BHF-UCL.
GO; GO:0002089; P:lens morphogenesis in camera-type eye; IMP:BHF-UCL.
GO; GO:0030324; P:lung development; IEA:Ensembl.
GO; GO:0001945; P:lymph vessel development; IMP:MGI.
GO; GO:0001946; P:lymphangiogenesis; ISO:MGI.
GO; GO:0060836; P:lymphatic endothelial cell differentiation; IMP:MGI.
GO; GO:0070858; P:negative regulation of bile acid biosynthetic process; ISO:MGI.
GO; GO:0008285; P:negative regulation of cell proliferation; IMP:MGI.
GO; GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; ISO:MGI.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:MGI.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0045071; P:negative regulation of viral genome replication; ISO:MGI.
GO; GO:0097150; P:neuronal stem cell population maintenance; IMP:BHF-UCL.
GO; GO:0046619; P:optic placode formation involved in camera-type eye formation; IEP:BHF-UCL.
GO; GO:0045787; P:positive regulation of cell cycle; IMP:BHF-UCL.
GO; GO:1901978; P:positive regulation of cell cycle checkpoint; IMP:MGI.
GO; GO:0008284; P:positive regulation of cell proliferation; IMP:BHF-UCL.
GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:MGI.
GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:MGI.
GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:MGI.
GO; GO:2000979; P:positive regulation of forebrain neuron differentiation; IMP:BHF-UCL.
GO; GO:0060421; P:positive regulation of heart growth; IMP:BHF-UCL.
GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IMP:BHF-UCL.
GO; GO:0060298; P:positive regulation of sarcomere organization; IMP:BHF-UCL.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:MGI.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
GO; GO:0010468; P:regulation of gene expression; IMP:BHF-UCL.
GO; GO:0060849; P:regulation of transcription involved in lymphatic endothelial cell fate commitment; ISO:MGI.
GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
GO; GO:0030240; P:skeletal muscle thin filament assembly; IMP:BHF-UCL.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0048845; P:venous blood vessel morphogenesis; IMP:BHF-UCL.
GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:BHF-UCL.
GO; GO:0055005; P:ventricular cardiac myofibril assembly; IMP:BHF-UCL.
GO; GO:0060412; P:ventricular septum morphogenesis; IMP:BHF-UCL.
Gene3D; 1.10.10.500; -; 1.
InterPro; IPR023082; Homeo_prospero_dom.
InterPro; IPR037131; Homeo_prospero_dom_sf.
InterPro; IPR009057; Homeobox-like_sf.
InterPro; IPR007738; Prox1.
PANTHER; PTHR12198:SF6; PTHR12198:SF6; 1.
Pfam; PF05044; HPD; 1.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS51818; HOMEO_PROSPERO; 1.
1: Evidence at protein level;
Biological rhythms; Complete proteome; Developmental protein;
DNA-binding; Homeobox; Isopeptide bond; Nucleus; Phosphoprotein;
Reference proteome; Repressor; Transcription;
Transcription regulation; Ubl conjugation.
CHAIN 1 737 Prospero homeobox protein 1.
/FTId=PRO_0000208881.
DOMAIN 577 635 Prospero-type homeo.
{ECO:0000255|PROSITE-ProRule:PRU01162}.
DOMAIN 636 735 Prospero. {ECO:0000255|PROSITE-
ProRule:PRU01162}.
REGION 1 28 Interaction with RORG.
{ECO:0000269|PubMed:23723244}.
REGION 577 735 Homeo-Prospero. {ECO:0000255|PROSITE-
ProRule:PRU01162}.
REGION 723 729 Essential for nuclear localization,
interaction with RORG, repression of RORG
transcriptional activator activity.
{ECO:0000269|PubMed:23723244}.
COMPBIAS 215 219 Poly-Gln.
MOD_RES 177 177 Phosphoserine.
{ECO:0000250|UniProtKB:Q92786}.
MOD_RES 179 179 Phosphoserine.
{ECO:0000244|PubMed:17242355,
ECO:0000244|PubMed:21183079}.
MOD_RES 199 199 Phosphoserine.
{ECO:0000250|UniProtKB:Q92786}.
MOD_RES 291 291 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 295 295 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 511 511 Phosphoserine.
{ECO:0000244|PubMed:17242355,
ECO:0000244|PubMed:18630941,
ECO:0000244|PubMed:21183079}.
MOD_RES 514 514 Phosphoserine.
{ECO:0000244|PubMed:17242355,
ECO:0000244|PubMed:21183079}.
MOD_RES 557 557 Phosphoserine.
{ECO:0000250|UniProtKB:Q92786}.
CROSSLNK 324 324 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000250|UniProtKB:Q92786}.
CONFLICT 685 685 A -> V (in Ref. 2; BAC35190).
{ECO:0000305}.
SEQUENCE 737 AA; 83126 MW; 834DF6963FF5C9B5 CRC64;
MPDHDSTALL SRQTKRRRVD IGVKRTVGTA SAFFAKARAT FFSAMNPQGS EQDVEYSVVQ
HADGEKSNVL RKLLKRANSY EDAMMPFPGA TIISQLLKNN MNKNGGTEPS FQASGLSSTG
SEVHQEDICS NSSRDSPPEC LSPFGRPTMS QFDVDRLCDE HLRAKRARVE NIIRGMSHSP
SVALRGNENE REMAPQSVSP RESYRENKRK QKLPQQQQQS FQQLVSARKE QKREERRQLK
QQLEDMQKQL RQLQEKFYQV YDSTDSENDE DGDLSEDSMR SEILDARAQD SVGRSDNEMC
ELDPGQFIDR ARALIREQEM AENKPKREGS NKERDHGPNS LQPEGKHLAE TLKQELNTAM
SQVVDTVVKV FSAKPSRQVP QVFPPLQIPQ ARFAVNGENH NFHTANQRLQ CFGDVIIPNP
LDTFGSVQMP SSTDQTEALP LVVRKNSSEQ SASGPATGGH HQPLHQSPLS ATAGFTTPSF
RHPFPLPLMA YPFQSPLGAP SGSFSGKDRA SPESLDLTRD TTSLRTKMSS HHLSHHPCSP
AHPPSTAEGL SLSLIKSECG DLQDMSDISP YSGSAMQEGL SPNHLKKAKL MFFYTRYPSS
NMLKTYFSDV KFNRCITSQL IKWFSNFREF YYIQMEKYAR QAINDGVTST EELSITRDCE
LYRALNMHYN KANDFEVPER FLEVAQITLR EFFNAIIAGK DVDPSWKKAI YKVICKLDSE
VPEIFKSPNC LQELLHE


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