ID   MESP2_HUMAN             Reviewed;         397 AA.
AC   Q0VG99; Q7RTU2;
DT   24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT   02-MAR-2010, sequence version 2.
DT   12-AUG-2020, entry version 120.
DE   RecName: Full=Mesoderm posterior protein 2;
DE   AltName: Full=Class C basic helix-loop-helix protein 6;
DE            Short=bHLHc6;
GN   Name=MESP2; Synonyms=BHLHC6, SCDO2;
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 GENOMIC DNA].
RX   PubMed=16572171; DOI=10.1038/nature04601;
RA   Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA   Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA   FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA   Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA   Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA   DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA   Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA   Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA   Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA   O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA   Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA   Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT   "Analysis of the DNA sequence and duplication history of human chromosome
RT   15.";
RL   Nature 440:671-675(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [3]
RP   IDENTIFICATION.
RX   PubMed=14516699; DOI=10.1016/s0925-4773(03)00130-8;
RA   McLellan A.S., Langlands K., Kealey T.;
RT   "Exhaustive identification of human class II basic helix-loop-helix
RT   proteins by virtual library screening.";
RL   Mech. Dev. 119:S285-S291(2002).
RN   [4]
RP   INVOLVEMENT IN SCDO2, AND POLYMORPHISM.
RX   PubMed=15122512; DOI=10.1086/421053;
RA   Whittock N.V., Sparrow D.B., Wouters M.A., Sillence D., Ellard S.,
RA   Dunwoodie S.L., Turnpenny P.D.;
RT   "Mutated MESP2 causes spondylocostal dysostosis in humans.";
RL   Am. J. Hum. Genet. 74:1249-1254(2004).
RN   [5]
RP   VARIANTS GLY-66; VAL-125 AND PHE-224, AND CHARACTERIZATION OF VARIANT
RP   VAL-125.
RX   PubMed=18485326; DOI=10.1016/j.ajhg.2008.04.014;
RA   Cornier A.S., Staehling-Hampton K., Delventhal K.M., Saga Y., Caubet J.-F.,
RA   Sasaki N., Ellard S., Young E., Ramirez N., Carlo S.E., Torres J.,
RA   Emans J.B., Turnpenny P.D., Pourquie O.;
RT   "Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin
RT   syndrome.";
RL   Am. J. Hum. Genet. 82:1334-1341(2008).
CC   -!- FUNCTION: Transcription factor with important role in somitogenesis.
CC       Defines the rostrocaudal patterning of the somite by participating in
CC       distinct Notch pathways. Regulates also the FGF signaling pathway.
CC       Specifies the rostral half of the somites. Generates rostro-caudal
CC       polarity of somites by down-regulating in the presumptive rostral
CC       domain DLL1, a Notch ligand. Participates in the segment border
CC       formation by activating in the anterior presomitic mesoderm LFNG, a
CC       negative regulator of DLL1-Notch signaling. Acts as a strong suppressor
CC       of Notch activity. Together with MESP1 is involved in the
CC       epithelialization of somitic mesoderm and in the development of cardiac
CC       mesoderm.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}.
CC   -!- PTM: Degraded by the proteasome. {ECO:0000250}.
CC   -!- POLYMORPHISM: The number of GQ repeats at position 179 is polymorphic.
CC       {ECO:0000269|PubMed:15122512}.
CC   -!- DISEASE: Spondylocostal dysostosis 2, autosomal recessive (SCDO2)
CC       [MIM:608681]: A condition of variable severity associated with
CC       vertebral and rib segmentation defects. The main skeletal malformations
CC       include fusion of vertebrae, hemivertebrae, fusion of certain ribs, and
CC       other rib malformations. Deformity of the chest and spine (severe
CC       scoliosis, kyphoscoliosis and lordosis) is a natural consequence of the
CC       malformation and leads to a dwarf-like appearance. As the thorax is
CC       small, infants frequently have respiratory insufficiency and repeated
CC       respiratory infections resulting in life-threatening complications in
CC       the first year of life. {ECO:0000269|PubMed:15122512}. Note=The disease
CC       is caused by mutations affecting the gene represented in this entry.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=DAA00304.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; AC079075; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC111413; AAI11414.1; -; mRNA.
DR   EMBL; BK000142; DAA00304.1; ALT_SEQ; Genomic_DNA.
DR   CCDS; CCDS42078.1; -.
DR   RefSeq; NP_001035047.1; NM_001039958.1.
DR   SMR; Q0VG99; -.
DR   BioGRID; 126951; 3.
DR   IntAct; Q0VG99; 3.
DR   STRING; 9606.ENSP00000342392; -.
DR   iPTMnet; Q0VG99; -.
DR   PhosphoSitePlus; Q0VG99; -.
DR   BioMuta; MESP2; -.
DR   DMDM; 290457624; -.
DR   PaxDb; Q0VG99; -.
DR   PRIDE; Q0VG99; -.
DR   ProteomicsDB; 58841; -.
DR   Antibodypedia; 28666; 101 antibodies.
DR   Ensembl; ENST00000341735; ENSP00000342392; ENSG00000188095.
DR   GeneID; 145873; -.
DR   KEGG; hsa:145873; -.
DR   UCSC; uc002bon.4; human.
DR   CTD; 145873; -.
DR   DisGeNET; 145873; -.
DR   EuPathDB; HostDB:ENSG00000188095.4; -.
DR   GeneCards; MESP2; -.
DR   GeneReviews; MESP2; -.
DR   HGNC; HGNC:29659; MESP2.
DR   HPA; ENSG00000188095; Low tissue specificity.
DR   MalaCards; MESP2; -.
DR   MIM; 605195; gene.
DR   MIM; 608681; phenotype.
DR   neXtProt; NX_Q0VG99; -.
DR   OpenTargets; ENSG00000188095; -.
DR   Orphanet; 2311; Autosomal recessive spondylocostal dysostosis.
DR   PharmGKB; PA142671469; -.
DR   eggNOG; KOG4029; Eukaryota.
DR   GeneTree; ENSGT00530000063712; -.
DR   HOGENOM; CLU_064749_0_0_1; -.
DR   InParanoid; Q0VG99; -.
DR   KO; K09076; -.
DR   OMA; LPRPSCQ; -.
DR   OrthoDB; 1072866at2759; -.
DR   PhylomeDB; Q0VG99; -.
DR   TreeFam; TF325707; -.
DR   PathwayCommons; Q0VG99; -.
DR   BioGRID-ORCS; 145873; 6 hits in 893 CRISPR screens.
DR   ChiTaRS; MESP2; human.
DR   GeneWiki; MESP2; -.
DR   GenomeRNAi; 145873; -.
DR   Pharos; Q0VG99; Tbio.
DR   PRO; PR:Q0VG99; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   RNAct; Q0VG99; protein.
DR   Bgee; ENSG00000188095; Expressed in buccal mucosa cell and 114 other tissues.
DR   ExpressionAtlas; Q0VG99; baseline and differential.
DR   Genevisible; Q0VG99; HS.
DR   GO; GO:0000790; C:nuclear chromatin; ISA:NTNU_SB.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR   GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0003007; P:heart morphogenesis; IBA:GO_Central.
DR   GO; GO:0001707; P:mesoderm formation; IBA:GO_Central.
DR   GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0032525; P:somite rostral/caudal axis specification; IBA:GO_Central.
DR   CDD; cd00083; HLH; 1.
DR   Gene3D; 4.10.280.10; -; 1.
DR   InterPro; IPR011598; bHLH_dom.
DR   InterPro; IPR036638; HLH_DNA-bd_sf.
DR   InterPro; IPR040259; Mesogenin/MesP.
DR   PANTHER; PTHR20937; PTHR20937; 1.
DR   Pfam; PF00010; HLH; 1.
DR   SMART; SM00353; HLH; 1.
DR   SUPFAM; SSF47459; SSF47459; 1.
DR   PROSITE; PS50888; BHLH; 1.
PE   1: Evidence at protein level;
KW   Developmental protein; DNA-binding; Dwarfism; Notch signaling pathway;
KW   Nucleus; Polymorphism; Reference proteome; Repeat; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..397
FT                   /note="Mesoderm posterior protein 2"
FT                   /id="PRO_0000296301"
FT   DOMAIN          81..135
FT                   /note="bHLH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT   REPEAT          179..180
FT                   /note="1"
FT   REPEAT          181..182
FT                   /note="2"
FT   REPEAT          183..184
FT                   /note="3"
FT   REPEAT          185..186
FT                   /note="4"
FT   REPEAT          187..188
FT                   /note="5"
FT   REPEAT          189..190
FT                   /note="6"
FT   REPEAT          191..192
FT                   /note="7"
FT   REPEAT          193..194
FT                   /note="8"
FT   REPEAT          195..196
FT                   /note="9"
FT   REPEAT          197..198
FT                   /note="10"
FT   REPEAT          199..200
FT                   /note="11"
FT   REPEAT          201..202
FT                   /note="12"
FT   REPEAT          203..204
FT                   /note="13"
FT   REGION          179..204
FT                   /note="13 X 2 AA tandem repeats of G-Q"
FT   VARIANT         66
FT                   /note="A -> G (in dbSNP:rs71647809)"
FT                   /evidence="ECO:0000269|PubMed:18485326"
FT                   /id="VAR_046779"
FT   VARIANT         125
FT                   /note="L -> V (in a patient with spondylocostal dysostosis;
FT                   inactive; dbSNP:rs71647806)"
FT                   /evidence="ECO:0000269|PubMed:18485326"
FT                   /id="VAR_046780"
FT   VARIANT         138
FT                   /note="V -> M (in dbSNP:rs28462216)"
FT                   /id="VAR_061257"
FT   VARIANT         224
FT                   /note="S -> F (in dbSNP:rs71647807)"
FT                   /evidence="ECO:0000269|PubMed:18485326"
FT                   /id="VAR_046781"
FT   CONFLICT        202..205
FT                   /note="Missing (in Ref. 2; AAI11414)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   397 AA;  41760 MW;  6CC8A423D23BF88B CRC64;
     MAQSPPPQSL LGHDHWIFAQ GWGWAGHWDS TSPASSSDSS GSCPCDGARG LPQPQPPSCS
     SRAAEAAATT PRRARTGPAG GQRQSASERE KLRMRTLARA LHELRRFLPP SLAPAGQSLT
     KIETLRLAIR YIGHLSAVLG LSEESLQCRR RQRGDAGSPW GCPLCPDRGP AEAQTQAEGQ
     GQGQGQGQGQ GQGQGQGQGQ GQGQGRRPGL VSAVLAEASW GSPSACPGAQ AAPERLGRGV
     HDTDPWATPP YCPKIQSPPY SSQGTTSDAS LWTPPQGCPW TQSSPEPRNP PVPWTAAPAT
     LELAAVYQGL SVSPEPCLSL GAPSLLPHPS CQRLQPQTPG RCWSHSAEVV PNSEDQGPGA
     AFQLSEASPP QSSGLRFSGC PELWQEDLEG ARLGIFY
//