MESP2_HUMAN
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 03-AUG-2022, entry version 129.
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 variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=DAA00304.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 AlphaFoldDB; Q0VG99; -.
DR SMR; Q0VG99; -.
DR BioGRID; 126951; 8.
DR IntAct; Q0VG99; 4.
DR STRING; 9606.ENSP00000342392; -.
DR iPTMnet; Q0VG99; -.
DR PhosphoSitePlus; Q0VG99; -.
DR BioMuta; MESP2; -.
DR DMDM; 290457624; -.
DR PaxDb; Q0VG99; -.
DR PeptideAtlas; Q0VG99; -.
DR PRIDE; Q0VG99; -.
DR Antibodypedia; 28666; 108 antibodies from 27 providers.
DR DNASU; 145873; -.
DR Ensembl; ENST00000341735.5; ENSP00000342392.3; ENSG00000188095.6.
DR GeneID; 145873; -.
DR KEGG; hsa:145873; -.
DR MANE-Select; ENST00000341735.5; ENSP00000342392.3; NM_001039958.2; NP_001035047.1.
DR UCSC; uc002bon.4; human.
DR CTD; 145873; -.
DR DisGeNET; 145873; -.
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 VEuPathDB; HostDB:ENSG00000188095; -.
DR eggNOG; KOG4029; Eukaryota.
DR GeneTree; ENSGT00530000063712; -.
DR HOGENOM; CLU_064749_0_0_1; -.
DR InParanoid; Q0VG99; -.
DR OMA; PYCPGMQ; -.
DR OrthoDB; 1072866at2759; -.
DR PhylomeDB; Q0VG99; -.
DR TreeFam; TF325707; -.
DR PathwayCommons; Q0VG99; -.
DR SignaLink; Q0VG99; -.
DR BioGRID-ORCS; 145873; 12 hits in 1090 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:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; 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:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
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:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0032525; P:somite rostral/caudal axis specification; IBA:GO_Central.
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; 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 28..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 152..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 179..204
FT /note="13 X 2 AA tandem repeats of G-Q"
FT REGION 222..295
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 351..376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 29..43
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 175..205
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 257..279
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 280..294
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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
