PRRX1_HUMAN
ID PRRX1_HUMAN Reviewed; 245 AA.
AC P54821; B5BUM7; O60807;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Paired mesoderm homeobox protein 1;
DE AltName: Full=Homeobox protein PHOX1;
DE AltName: Full=Paired-related homeobox protein 1;
DE Short=PRX-1;
GN Name=PRRX1; Synonyms=PMX1;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 19-197 (ISOFORM 2).
RX PubMed=1509260; DOI=10.1126/science.257.5073.1089;
RA Grueneberg D.A., Natesan S., Alexandre C., Gilman M.Z.;
RT "Human and Drosophila homeodomain proteins that enhance the DNA-binding
RT activity of serum response factor.";
RL Science 257:1089-1095(1992).
RN [5]
RP VARIANT AGOTC SER-113.
RX PubMed=21294718; DOI=10.1111/j.1399-0004.2010.01531.x;
RA Sergi C., Kamnasaran D.;
RT "PRRX1 is mutated in a fetus with agnathia-otocephaly.";
RL Clin. Genet. 79:293-295(2011).
CC -!- FUNCTION: Acts as a transcriptional regulator of muscle creatine kinase
CC (MCK) and so has a role in the establishment of diverse mesodermal
CC muscle types. The protein binds to an A/T-rich element in the muscle
CC creatine enhancer (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P54821; Q9BW66: CINP; NbExp=3; IntAct=EBI-12828023, EBI-739784;
CC P54821; P51687: SUOX; NbExp=3; IntAct=EBI-12828023, EBI-3921347;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=PMX1-B;
CC IsoId=P54821-1; Sequence=Displayed;
CC Name=2; Synonyms=PMX1-A;
CC IsoId=P54821-2; Sequence=VSP_002278;
CC -!- DISEASE: Agnathia-otocephaly complex (AGOTC) [MIM:202650]: A rare
CC condition characterized by mandibular hypoplasia or agnathia,
CC ventromedial auricular malposition (melotia) and/or auricular fusion
CC (synotia), and microstomia with oroglossal hypoplasia or aglossia.
CC Holoprosencephaly is the most commonly identified association, but
CC skeletal, genitourinary, and cardiovascular anomalies, and situs
CC inversus have been reported. The disorder is almost always lethal.
CC {ECO:0000269|PubMed:21294718}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the paired homeobox family. {ECO:0000305}.
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DR EMBL; AB451463; BAG70277.1; -; mRNA.
DR EMBL; Z97200; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC074993; AAH74993.1; -; mRNA.
DR EMBL; M95929; AAA60085.1; -; mRNA.
DR CCDS; CCDS1290.1; -. [P54821-1]
DR CCDS; CCDS1291.1; -. [P54821-2]
DR RefSeq; NP_008833.1; NM_006902.4. [P54821-2]
DR RefSeq; NP_073207.1; NM_022716.3. [P54821-1]
DR AlphaFoldDB; P54821; -.
DR SMR; P54821; -.
DR BioGRID; 111405; 7.
DR CORUM; P54821; -.
DR IntAct; P54821; 2.
DR STRING; 9606.ENSP00000239461; -.
DR GlyGen; P54821; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P54821; -.
DR PhosphoSitePlus; P54821; -.
DR BioMuta; PRRX1; -.
DR DMDM; 6174916; -.
DR jPOST; P54821; -.
DR MassIVE; P54821; -.
DR PaxDb; P54821; -.
DR PeptideAtlas; P54821; -.
DR PRIDE; P54821; -.
DR ProteomicsDB; 56732; -. [P54821-1]
DR ProteomicsDB; 56733; -. [P54821-2]
DR Antibodypedia; 34372; 436 antibodies from 31 providers.
DR DNASU; 5396; -.
DR Ensembl; ENST00000239461.11; ENSP00000239461.6; ENSG00000116132.12. [P54821-1]
DR Ensembl; ENST00000367760.7; ENSP00000356734.3; ENSG00000116132.12. [P54821-2]
DR GeneID; 5396; -.
DR KEGG; hsa:5396; -.
DR MANE-Select; ENST00000239461.11; ENSP00000239461.6; NM_022716.4; NP_073207.1.
DR UCSC; uc001ghe.4; human. [P54821-1]
DR CTD; 5396; -.
DR DisGeNET; 5396; -.
DR GeneCards; PRRX1; -.
DR HGNC; HGNC:9142; PRRX1.
DR HPA; ENSG00000116132; Low tissue specificity.
DR MalaCards; PRRX1; -.
DR MIM; 167420; gene.
DR MIM; 202650; phenotype.
DR neXtProt; NX_P54821; -.
DR OpenTargets; ENSG00000116132; -.
DR Orphanet; 990; Agnathia-holoprosencephaly-situs inversus syndrome.
DR PharmGKB; PA33466; -.
DR VEuPathDB; HostDB:ENSG00000116132; -.
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00940000159466; -.
DR InParanoid; P54821; -.
DR OMA; YAHIMER; -.
DR OrthoDB; 1413050at2759; -.
DR PhylomeDB; P54821; -.
DR TreeFam; TF351612; -.
DR PathwayCommons; P54821; -.
DR SignaLink; P54821; -.
DR SIGNOR; P54821; -.
DR BioGRID-ORCS; 5396; 11 hits in 1092 CRISPR screens.
DR ChiTaRS; PRRX1; human.
DR GeneWiki; PRRX1; -.
DR GenomeRNAi; 5396; -.
DR Pharos; P54821; Tbio.
DR PRO; PR:P54821; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P54821; protein.
DR Bgee; ENSG00000116132; Expressed in calcaneal tendon and 187 other tissues.
DR ExpressionAtlas; P54821; baseline and differential.
DR Genevisible; P54821; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:ARUK-UCL.
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; IEA:Ensembl.
DR GO; GO:0071837; F:HMG box domain binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:GO_Central.
DR GO; GO:0016251; F:RNA polymerase II general transcription initiation factor activity; IEA:Ensembl.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:ARUK-UCL.
DR GO; GO:0048844; P:artery morphogenesis; IEA:Ensembl.
DR GO; GO:0051216; P:cartilage development; IEA:Ensembl.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl.
DR GO; GO:0030326; P:embryonic limb morphogenesis; IEA:Ensembl.
DR GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl.
DR GO; GO:0010463; P:mesenchymal cell proliferation; IEA:Ensembl.
DR GO; GO:0042474; P:middle ear morphogenesis; IEA:Ensembl.
DR GO; GO:0048664; P:neuron fate determination; IEA:Ensembl.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; IEA:Ensembl.
DR GO; GO:0100026; P:positive regulation of DNA repair by transcription from RNA polymerase II promoter; IDA:ARUK-UCL.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Ensembl.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0070570; P:regulation of neuron projection regeneration; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060021; P:roof of mouth development; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0072089; P:stem cell proliferation; IEA:Ensembl.
DR CDD; cd00086; homeodomain; 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; PTHR46385; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF03826; OAR; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
DR PROSITE; PS50803; OAR; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Developmental protein; Disease variant;
KW DNA-binding; Homeobox; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..245
FT /note="Paired mesoderm homeobox protein 1"
FT /id="PRO_0000049251"
FT DNA_BIND 94..153
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 63..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:0000250|UniProtKB:P63013"
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:1509260"
FT /id="VSP_002278"
FT VARIANT 113
FT /note="F -> S (in AGOTC; dbSNP:rs387906667)"
FT /evidence="ECO:0000269|PubMed:21294718"
FT /id="VAR_066414"
SQ SEQUENCE 245 AA; 27296 MW; 7CA4B7FD9492FC19 CRC64;
MTSSYGHVLE RQPALGGRLD SPGNLDTLQA KKNFSVSHLL DLEEAGDMVA AQADENVGEA
GRSLLESPGL TSGSDTPQQD NDQLNSEEKK KRKQRRNRTT FNSSQLQALE RVFERTHYPD
AFVREDLARR VNLTEARVQV WFQNRRAKFR RNERAMLANK NASLLKSYSG DVTAVEQPIV
PRPAPRPTDY LSWGTASPYS AMATYSATCA NNSPAQGINM ANSIANLRLK AKEYSLQRNQ
VPTVN
