ID   PRRX1_MOUSE             Reviewed;         245 AA.
AC   P63013; P43271; Q02810; Q569N6;
DT   31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   31-AUG-2004, sequence version 1.
DT   24-JAN-2024, entry version 150.
DE   RecName: Full=Paired mesoderm homeobox protein 1;
DE   AltName: Full=Homeobox protein K-2;
DE   AltName: Full=Muscle homeobox protein {ECO:0000303|PubMed:1360403};
DE            Short=MHox {ECO:0000303|PubMed:1360403};
DE   AltName: Full=Paired-related homeobox protein 1;
DE            Short=PRX-1;
GN   Name=Prrx1; Synonyms=Pmx {ECO:0000303|PubMed:7910581}, Pmx1;
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] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, AND
RP   DEVELOPMENTAL STAGE.
RX   PubMed=1360403; DOI=10.1242/dev.115.4.1087;
RA   Cserjesi P., Lilly B., Bryson L., Wang Y., Sassoon D.A., Olson E.N.;
RT   "MHox: a mesodermally restricted homeodomain protein that binds an
RT   essential site in the muscle creatine kinase enhancer.";
RL   Development 115:1087-1101(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX   PubMed=7910581; DOI=10.1006/geno.1994.1066;
RA   Kern M.J., Argao E.A., Birkenmeier E.H., Rowe L.B., Potter S.S.;
RT   "Genomic organization and chromosome localization of the murine homeobox
RT   gene Pmx.";
RL   Genomics 19:334-340(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   STRAIN=CD-1; TISSUE=Embryo;
RX   PubMed=1383943; DOI=10.1093/nar/20.19.5189;
RA   Kern M.J., Witte D.P., Valerius M.T., Aronow B.J., Potter S.S.;
RT   "A novel murine homeobox gene isolated by a tissue specific PCR cloning
RT   strategy.";
RL   Nucleic Acids Res. 20:5189-5195(1992).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   STRAIN=C57BL/6J; 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   [5]
RP   FUNCTION, DOMAIN, AND MUTAGENESIS OF SER-223; ASN-226 AND ARG-228.
RX   PubMed=11373278; DOI=10.1074/jbc.m100239200;
RA   Norris R.A., Kern M.J.;
RT   "The identification of Prx1 transcription regulatory domains provides a
RT   mechanism for unequal compensation by the Prx1 and Prx2 loci.";
RL   J. Biol. Chem. 276:26829-26837(2001).
RN   [6]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-160, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic fibroblast;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
RN   [7]
RP   FUNCTION, INTERACTION WITH SMAD3, AND SUBCELLULAR LOCATION.
RX   PubMed=35589735; DOI=10.1038/s41467-022-30484-4;
RA   Lee K.W., Yeo S.Y., Gong J.R., Koo O.J., Sohn I., Lee W.Y., Kim H.C.,
RA   Yun S.H., Cho Y.B., Choi M.A., An S., Kim J., Sung C.O., Cho K.H.,
RA   Kim S.H.;
RT   "PRRX1 is a master transcription factor of stromal fibroblasts for
RT   myofibroblastic lineage progression.";
RL   Nat. Commun. 13:2793-2793(2022).
RN   [8]
RP   FUNCTION, IDENTIFICATION IN ADULT STEM CELLS, DEVELOPMENTAL STAGE, AND
RP   TISSUE SPECIFICITY.
RX   PubMed=36456880; DOI=10.1038/s41588-022-01227-4;
RA   Liu H., Li P., Zhang S., Xiang J., Yang R., Liu J., Shafiquzzaman M.,
RA   Biswas S., Wei Z., Zhang Z., Zhou X., Yin F., Xie Y., Goff S.P., Chen L.,
RA   Li B.;
RT   "Prrx1 marks stem cells for bone, white adipose tissue and dermis in adult
RT   mice.";
RL   Nat. Genet. 54:1946-1958(2022).
CC   -!- FUNCTION: Master transcription factor of stromal fibroblasts for
CC       myofibroblastic lineage progression. Orchestrates the functional drift
CC       of fibroblasts into myofibroblastic phenotype via TGF-beta signaling by
CC       remodeling a super-enhancer landscape. Through this function, plays an
CC       essential role in wound healing process (PubMed:35589735). Acts as a
CC       transcriptional regulator of muscle creatine kinase (MCK) and so has a
CC       role in the establishment of diverse mesodermal muscle types. The
CC       protein binds to an A/T-rich element in the muscle creatine enhancer
CC       (PubMed:1360403). May play a role in homeostasis and regeneration of
CC       bone, white adipose tissue and derm (PubMed:36456880).
CC       {ECO:0000269|PubMed:1360403, ECO:0000269|PubMed:35589735,
CC       ECO:0000269|PubMed:36456880}.
CC   -!- FUNCTION: [Isoform 1]: Transcriptional activator, when transfected in
CC       fibroblastic or myoblastic cell lines. This activity may be masked by
CC       the C-terminal OAR domain. {ECO:0000269|PubMed:11373278}.
CC   -!- FUNCTION: [Isoform 2]: Transcriptional repressor, when transfected in
CC       fibroblastic or myoblastic cell lines. {ECO:0000269|PubMed:11373278}.
CC   -!- SUBUNIT: Interacts with SMAD3. {ECO:0000269|PubMed:35589735}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:35589735}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=K2-a, Prx1a {ECO:0000303|PubMed:11373278};
CC         IsoId=P63013-1, P43271-1; Sequence=Displayed;
CC       Name=2; Synonyms=K2-b, Prx1b {ECO:0000303|PubMed:11373278};
CC         IsoId=P63013-2, P43271-2; Sequence=VSP_002279;
CC   -!- TISSUE SPECIFICITY: Expressed in skeletal muscle, heart and uterus
CC       (PubMed:1360403). Detected in a limited numbers of cells in connective
CC       tissues, in bone, inguinal white adipose tissue and dermis; these cells
CC       are thought to be stem cells (PubMed:36456880).
CC       {ECO:0000269|PubMed:1360403, ECO:0000269|PubMed:36456880}.
CC   -!- DEVELOPMENTAL STAGE: First expressed at 8.5 dpc in the paraxial and
CC       intermediate mesoderm besides the lateral plate mesoderm
CC       (PubMed:36456880). At about 9 dpc, detected in the lateral mesoderm and
CC       newly formed visceral arches (PubMed:1360403). At 9.5 dpc, expressed in
CC       multiple mesoderm segments (PubMed:36456880). Strongly expressed in the
CC       visceral arches, newly formed limb buds and facial primordia.
CC       Expression in the somites is confined primarily to the dorsal
CC       dermamyotome. Also detected in the dorsal aorta. At 10.5 dpc, strong
CC       expression is maintained in the visceral arches and facial primordia,
CC       as well as in the developing limb buds and dorsal aorta. At 13.5 dpc,
CC       highest expression in the limb buds, but not in the central core of the
CC       limb, which corresponds to regions of cartilage differentiation. Lower
CC       levels in the condensing vertebrae and ribs of the axial skeleton.
CC       Detected in the mandibles, which are derived from the visceral arches.
CC       Moderate expression levels in intercostal muscles and diaphragm. Also
CC       expressed in the developing eye and the meninges of the brain, but not
CC       in the brain itself. Not detected in the developing internal organs,
CC       such as heart, liver and gut (PubMed:1360403). At 14.5 dpc, expressed
CC       in skeletal tissues and the dermis (PubMed:36456880). At 15.5 dpc,
CC       moderate expression levels in the perichondrial tissue surrounding the
CC       ribs, the intercostal muscles and the diaphragm. Strongly expressed in
CC       the distal tips of the phalanges of the digits as well as in the
CC       perichondrial tissue surrounding the developing skeleton. At this
CC       stage, expression is generally low in the embryo and is only detectable
CC       in the face, limbs and axial muscles. Expression in the neural tube
CC       (brain and spinal cord) is not be detected at any developmental stage
CC       (PubMed:1360403). At postnatal day 1, detected in the skeleton, white
CC       adipose tissue and the dermis (PubMed:36456880).
CC       {ECO:0000269|PubMed:1360403, ECO:0000269|PubMed:36456880}.
CC   -!- DOMAIN: [Isoform 1]: The C-terminal OAR domain may be masking the
CC       transactivation domains. {ECO:0000269|PubMed:11373278}.
CC   -!- DOMAIN: [Isoform 2]: The C-terminal domain encoded by the alternative
CC       exon 4 exhibits repressor activity. {ECO:0000269|PubMed:11373278}.
CC   -!- SIMILARITY: Belongs to the paired homeobox family. {ECO:0000305}.
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DR   EMBL; L06502; AAA39672.1; -; mRNA.
DR   EMBL; U03873; AAC52139.1; -; mRNA.
DR   EMBL; X59725; CAA42410.1; -; mRNA.
DR   EMBL; BC092372; AAH92372.1; -; mRNA.
DR   CCDS; CCDS15427.1; -.
DR   CCDS; CCDS15428.1; -. [P63013-2]
DR   PIR; I48902; I48902.
DR   PIR; S26076; S26076.
DR   RefSeq; NP_035257.1; NM_011127.2. [P63013-1]
DR   RefSeq; NP_783617.2; NM_175686.3. [P63013-2]
DR   RefSeq; XP_006496766.1; XM_006496703.3. [P63013-2]
DR   AlphaFoldDB; P63013; -.
DR   SMR; P63013; -.
DR   BioGRID; 202269; 2.
DR   IntAct; P63013; 2.
DR   STRING; 10090.ENSMUSP00000027878; -.
DR   GlyGen; P63013; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P63013; -.
DR   PhosphoSitePlus; P63013; -.
DR   jPOST; P63013; -.
DR   MaxQB; P63013; -.
DR   PaxDb; 10090-ENSMUSP00000027878; -.
DR   ProteomicsDB; 291820; -.
DR   ProteomicsDB; 291821; -. [P63013-2]
DR   Antibodypedia; 34372; 498 antibodies from 31 providers.
DR   DNASU; 18933; -.
DR   Ensembl; ENSMUST00000027878.14; ENSMUSP00000027878.8; ENSMUSG00000026586.17. [P63013-1]
DR   Ensembl; ENSMUST00000075805.13; ENSMUSP00000075203.7; ENSMUSG00000026586.17. [P63013-2]
DR   GeneID; 18933; -.
DR   KEGG; mmu:18933; -.
DR   UCSC; uc007dhh.1; mouse. [P63013-2]
DR   UCSC; uc007dhi.1; mouse.
DR   AGR; MGI:97712; -.
DR   CTD; 5396; -.
DR   MGI; MGI:97712; Prrx1.
DR   VEuPathDB; HostDB:ENSMUSG00000026586; -.
DR   eggNOG; KOG0490; Eukaryota.
DR   GeneTree; ENSGT00940000159466; -.
DR   InParanoid; P63013; -.
DR   OMA; YAHAMDR; -.
DR   OrthoDB; 3685623at2759; -.
DR   PhylomeDB; P63013; -.
DR   TreeFam; TF351612; -.
DR   BioGRID-ORCS; 18933; 5 hits in 79 CRISPR screens.
DR   ChiTaRS; Prrx1; mouse.
DR   PRO; PR:P63013; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; P63013; Protein.
DR   Bgee; ENSMUSG00000026586; Expressed in secondary palatal shelf and 316 other cell types or tissues.
DR   ExpressionAtlas; P63013; baseline and differential.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0003677; F:DNA binding; IDA:MGI.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:MGI.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR   GO; GO:0071837; F:HMG box domain binding; IPI:UniProtKB.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR   GO; GO:0016251; F:RNA polymerase II general transcription initiation factor activity; IDA:MGI.
DR   GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR   GO; GO:0048844; P:artery morphogenesis; IMP:MGI.
DR   GO; GO:0051216; P:cartilage development; IMP:MGI.
DR   GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IMP:MGI.
DR   GO; GO:0030326; P:embryonic limb morphogenesis; IGI:MGI.
DR   GO; GO:0048704; P:embryonic skeletal system morphogenesis; IMP:MGI.
DR   GO; GO:0042472; P:inner ear morphogenesis; IGI:MGI.
DR   GO; GO:0010463; P:mesenchymal cell proliferation; IGI:MGI.
DR   GO; GO:0042474; P:middle ear morphogenesis; IMP:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR   GO; GO:0048664; P:neuron fate determination; IDA:MGI.
DR   GO; GO:0097150; P:neuronal stem cell population maintenance; IDA:MGI.
DR   GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IGI:MGI.
DR   GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IGI:MGI.
DR   GO; GO:2000648; P:positive regulation of stem cell proliferation; IGI:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR   GO; GO:0070570; P:regulation of neuron projection regeneration; IMP:MGI.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0060021; P:roof of mouth development; IMP:MGI.
DR   GO; GO:0007224; P:smoothened signaling pathway; IGI:MGI.
DR   GO; GO:0072089; P:stem cell proliferation; IGI:MGI.
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; IPR003654; OAR_dom.
DR   InterPro; IPR043378; PRRX1/2.
DR   PANTHER; PTHR46385:SF1; PAIRED MESODERM HOMEOBOX PROTEIN 1; 1.
DR   PANTHER; PTHR46385; PAIRED MESODERM HOMEOBOX PROTEIN 1-RELATED; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   Pfam; PF03826; OAR; 1.
DR   SMART; SM00389; HOX; 1.
DR   SUPFAM; SSF46689; Homeodomain-like; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   PROSITE; PS50803; OAR; 1.
DR   Genevisible; P63013; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Developmental protein; DNA-binding;
KW   Homeobox; Nucleus; Phosphoprotein; Reference proteome.
FT   CHAIN           1..245
FT                   /note="Paired mesoderm homeobox protein 1"
FT                   /id="PRO_0000049252"
FT   DNA_BIND        94..153
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          1..24
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          54..103
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           222..235
FT                   /note="OAR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00138"
FT   COMPBIAS        67..81
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         21
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P63014"
FT   MOD_RES         160
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         197
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         200..245
FT                   /note="SAMATYSATCANNSPAQGINMANSIANLRLKAKEYSLQRNQVPTVN -> RS
FT                   SSLPRCCLHEGLHNGF (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:1360403,
FT                   ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:7910581"
FT                   /id="VSP_002279"
FT   MUTAGEN         223
FT                   /note="S->P: No effect on transcriptional activity."
FT                   /evidence="ECO:0000269|PubMed:11373278"
FT   MUTAGEN         226
FT                   /note="N->P: No effect on transcriptional activity."
FT                   /evidence="ECO:0000269|PubMed:11373278"
FT   MUTAGEN         228
FT                   /note="R->A,P: Increased transcriptional activation.No
FT                   effect on DNA binding."
FT                   /evidence="ECO:0000269|PubMed:11373278"
SQ   SEQUENCE   245 AA;  27269 MW;  FF867F0D856E1115 CRC64;
     MTSSYGHVLE RQPALGGRLD SPGNLDTLQA KKNFSVSHLL DLEEAGDMVA AQADESVGEA
     GRSLLESPGL TSGSDTPQQD NDQLNSEEKK KRKQRRNRTT FNSSQLQALE RVFERTHYPD
     AFVREDLARR VNLTEARVQV WFQNRRAKFR RNERAMLANK NASLLKSYSG DVTAVEQPIV
     PRPAPRPTDY LSWGTASPYS AMATYSATCA NNSPAQGINM ANSIANLRLK AKEYSLQRNQ
     VPTVN
//