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P35548

- MSX2_HUMAN

UniProt

P35548 - MSX2_HUMAN

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Protein
Homeobox protein MSX-2
Gene
MSX2, HOX8
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Acts as a transcriptional regulator in bone development. Represses the ALPL promoter activity and antogonizes the stimulatory effect of DLX5 on ALPL expression during osteoblast differentiation. Probable morphogenetic role. May play a role in limb-pattern formation. In osteoblasts, suppresses transcription driven by the osteocalcin FGF response element (OCFRE). Binds to the homeodomain-response element of the ALPL promoter.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi142 – 20160Homeobox
Add
BLAST

GO - Molecular functioni

  1. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: Ensembl
  2. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity Source: Ensembl
  3. protein binding Source: UniProtKB
  4. sequence-specific DNA binding Source: MGI
  5. transcription cofactor activity Source: BHF-UCL
  6. transcription regulatory region DNA binding Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  1. BMP signaling pathway involved in heart development Source: Ensembl
  2. activation of meiosis Source: Ensembl
  3. anagen Source: Ensembl
  4. anterior/posterior pattern specification Source: Ensembl
  5. bone trabecula formation Source: Ensembl
  6. branching involved in mammary gland duct morphogenesis Source: Ensembl
  7. cellular response to estradiol stimulus Source: Ensembl
  8. cellular response to growth factor stimulus Source: Ensembl
  9. chondrocyte development Source: Ensembl
  10. cranial suture morphogenesis Source: BHF-UCL
  11. embryonic forelimb morphogenesis Source: Ensembl
  12. embryonic hindlimb morphogenesis Source: Ensembl
  13. embryonic nail plate morphogenesis Source: Ensembl
  14. enamel mineralization Source: Ensembl
  15. endochondral bone growth Source: Ensembl
  16. epithelial to mesenchymal transition involved in endocardial cushion formation Source: Ensembl
  17. frontal suture morphogenesis Source: Ensembl
  18. negative regulation of CREB transcription factor activity Source: Ensembl
  19. negative regulation of apoptotic process Source: Ensembl
  20. negative regulation of cell proliferation Source: Ensembl
  21. negative regulation of fat cell differentiation Source: Ensembl
  22. negative regulation of keratinocyte differentiation Source: Ensembl
  23. negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  24. negative regulation of transcription regulatory region DNA binding Source: BHF-UCL
  25. negative regulation of transcription, DNA-templated Source: UniProtKB
  26. osteoblast development Source: Ensembl
  27. osteoblast differentiation Source: UniProtKB
  28. outflow tract septum morphogenesis Source: Ensembl
  29. positive regulation of BMP signaling pathway Source: Ensembl
  30. positive regulation of catagen Source: Ensembl
  31. positive regulation of mesenchymal cell apoptotic process Source: Ensembl
  32. positive regulation of osteoblast differentiation Source: Ensembl
  33. signal transduction involved in regulation of gene expression Source: Ensembl
  34. wound healing, spreading of epidermal cells Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Repressor

Keywords - Biological processi

Osteogenesis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein MSX-2
Alternative name(s):
Homeobox protein Hox-8
Gene namesi
Name:MSX2
Synonyms:HOX8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:7392. MSX2.

Subcellular locationi

GO - Cellular componenti

  1. nucleus Source: UniProtKB-SubCell
  2. transcription factor complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Parietal foramina 1 (PFM1) [MIM:168500]: Autosomal dominant disease characterized by oval defects of the parietal bones caused by deficient ossification around the parietal notch, which is normally obliterated during the fifth fetal month.
Note: The disease is caused by mutations affecting the gene represented in this entry.2 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti154 – 1541L → P in PFM1. 1 Publication
VAR_010786
Natural varianti159 – 1602Missing in PFM1; loss of function.
VAR_010200
Natural varianti172 – 1721R → H in PFM1; loss of function. 2 Publications
VAR_010201
Parietal foramina with cleidocranial dysplasia (PFMCCD) [MIM:168550]: Combines skull defects in the form of enlarged parietal foramina and deficient ossification of the clavicles.
Note: The disease is caused by mutations affecting the gene represented in this entry.1 Publication
Craniosynostosis 2 (CRS2) [MIM:604757]: A primary abnormality of skull growth involving premature fusion of one or more cranial sutures. The growth velocity of the skull often cannot match that of the developing brain resulting in an abnormal head shape and, in some cases, increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability. CRS2 is characterized by either fronto-orbital recession, or frontal bossing, or turribrachycephaly, or cloverleaf skull. Associated features include severe headache, high incidence of visual problems (myopia or hyperopia), and short first metatarsals. Intelligence is normal.
Note: The disease is caused by mutations affecting the gene represented in this entry.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti148 – 1481P → H in CRS2; gain of function. 1 Publication
VAR_003755

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi147 – 1471T → A: Does not bind DNA but still suppresses OCFRE activation. 1 Publication

Keywords - Diseasei

Craniosynostosis, Disease mutation

Organism-specific databases

MIMi168500. phenotype.
168550. phenotype.
604757. phenotype.
Orphaneti1541. Craniosynostosis, Boston type.
60015. Parietal foramina.
251290. Parietal foramina with cleidocranial dysplasia.
PharmGKBiPA31197.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 267267Homeobox protein MSX-2
PRO_0000049099Add
BLAST

Proteomic databases

MaxQBiP35548.
PaxDbiP35548.
PRIDEiP35548.

PTM databases

PhosphoSiteiP35548.

Expressioni

Gene expression databases

ArrayExpressiP35548.
BgeeiP35548.
CleanExiHS_MSX2.
GenevestigatoriP35548.

Organism-specific databases

HPAiHPA005652.

Interactioni

Subunit structurei

Interacts with MINT By similarity. Interacts with XRCC6 (Ku70) and XRCC5 (Ku80).1 Publication

Protein-protein interaction databases

BioGridi110594. 21 interactions.
IntActiP35548. 1 interaction.
STRINGi9606.ENSP00000239243.

Structurei

3D structure databases

ProteinModelPortaliP35548.
SMRiP35548. Positions 143-200.

Family & Domainsi

Sequence similaritiesi

Belongs to the Msh homeobox family.

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiNOG298790.
HOGENOMiHOG000231922.
HOVERGENiHBG005205.
InParanoidiP35548.
KOiK09341.
OMAiPPKEMSS.
OrthoDBiEOG70GMGK.
PhylomeDBiP35548.
TreeFamiTF350699.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSiPR00024. HOMEOBOX.
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P35548-1 [UniParc]FASTAAdd to Basket

« Hide

MASPSKGNDL FSPDEEGPAV VAGPGPGPGG AEGAAEERRV KVSSLPFSVE    50
ALMSDKKPPK EASPLPAESA SAGATLRPLL LSGHGAREAH SPGPLVKPFE 100
TASVKSENSE DGAAWMQEPG RYSPPPRHMS PTTCTLRKHK TNRKPRTPFT 150
TSQLLALERK FRQKQYLSIA ERAEFSSSLN LTETQVKIWF QNRRAKAKRL 200
QEAELEKLKM AAKPMLPSSF SLPFPISSPL QAASIYGASY PFHRPVLPIP 250
PVGLYATPVG YGMYHLS 267
Length:267
Mass (Da):28,897
Last modified:November 2, 2010 - v3
Checksum:i5B61B75F4A7C4AFD
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti129 – 1291M → T.8 Publications
Corresponds to variant rs4242182 [ dbSNP | Ensembl ].
VAR_010898
Natural varianti148 – 1481P → H in CRS2; gain of function. 1 Publication
VAR_003755
Natural varianti154 – 1541L → P in PFM1. 1 Publication
VAR_010786
Natural varianti159 – 1602Missing in PFM1; loss of function.
VAR_010200
Natural varianti172 – 1721R → H in PFM1; loss of function. 2 Publications
VAR_010201

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti28 – 281P → L in CAA49156. 1 Publication
Sequence conflicti32 – 321E → A in CAA49156. 1 Publication
Sequence conflicti62 – 654ASPL → SPAV in CAA49156. 1 Publication
Sequence conflicti67 – 671A → P in CAA49156. 1 Publication
Sequence conflicti69 – 691S → G in CAA49156. 1 Publication
Sequence conflicti75 – 751T → H in CAA49156. 1 Publication
Sequence conflicti85 – 851G → R in CAA49156. 1 Publication
Sequence conflicti107 – 1071E → G in CAA49156. 1 Publication
Sequence conflicti194 – 1941R → S in CAA49156. 1 Publication
Sequence conflicti237 – 2371G → A in CAA49156. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X69295 mRNA. Translation: CAA49156.1.
L22499, L22498 Genomic DNA. Translation: AAB42178.1.
S75308 Genomic DNA. Translation: AAD14169.1.
S75361 mRNA. Translation: AAB33867.1.
D31771 mRNA. Translation: BAA06549.1.
D89377 mRNA. Translation: BAA13949.1.
BT009814 mRNA. Translation: AAP88816.1.
AC117531 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61381.1.
CH471062 Genomic DNA. Translation: EAW61382.1.
BC015509 mRNA. Translation: AAH15509.1.
D14970 mRNA. Translation: BAA03611.1.
CCDSiCCDS4392.1.
PIRiA49068.
RefSeqiNP_002440.2. NM_002449.4.
XP_006714931.1. XM_006714868.1.
UniGeneiHs.89404.

Genome annotation databases

EnsembliENST00000239243; ENSP00000239243; ENSG00000120149.
GeneIDi4488.
KEGGihsa:4488.
UCSCiuc003mcy.3. human.

Polymorphism databases

DMDMi311033429.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X69295 mRNA. Translation: CAA49156.1 .
L22499 , L22498 Genomic DNA. Translation: AAB42178.1 .
S75308 Genomic DNA. Translation: AAD14169.1 .
S75361 mRNA. Translation: AAB33867.1 .
D31771 mRNA. Translation: BAA06549.1 .
D89377 mRNA. Translation: BAA13949.1 .
BT009814 mRNA. Translation: AAP88816.1 .
AC117531 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61381.1 .
CH471062 Genomic DNA. Translation: EAW61382.1 .
BC015509 mRNA. Translation: AAH15509.1 .
D14970 mRNA. Translation: BAA03611.1 .
CCDSi CCDS4392.1.
PIRi A49068.
RefSeqi NP_002440.2. NM_002449.4.
XP_006714931.1. XM_006714868.1.
UniGenei Hs.89404.

3D structure databases

ProteinModelPortali P35548.
SMRi P35548. Positions 143-200.
ModBasei Search...

Protein-protein interaction databases

BioGridi 110594. 21 interactions.
IntActi P35548. 1 interaction.
STRINGi 9606.ENSP00000239243.

PTM databases

PhosphoSitei P35548.

Polymorphism databases

DMDMi 311033429.

Proteomic databases

MaxQBi P35548.
PaxDbi P35548.
PRIDEi P35548.

Protocols and materials databases

DNASUi 4488.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000239243 ; ENSP00000239243 ; ENSG00000120149 .
GeneIDi 4488.
KEGGi hsa:4488.
UCSCi uc003mcy.3. human.

Organism-specific databases

CTDi 4488.
GeneCardsi GC05P174084.
GeneReviewsi MSX2.
H-InvDB HIX0005431.
HGNCi HGNC:7392. MSX2.
HPAi HPA005652.
MIMi 123101. gene.
168500. phenotype.
168550. phenotype.
604757. phenotype.
neXtProti NX_P35548.
Orphaneti 1541. Craniosynostosis, Boston type.
60015. Parietal foramina.
251290. Parietal foramina with cleidocranial dysplasia.
PharmGKBi PA31197.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG298790.
HOGENOMi HOG000231922.
HOVERGENi HBG005205.
InParanoidi P35548.
KOi K09341.
OMAi PPKEMSS.
OrthoDBi EOG70GMGK.
PhylomeDBi P35548.
TreeFami TF350699.

Miscellaneous databases

GeneWikii Msh_homeobox_2.
GenomeRNAii 4488.
NextBioi 17363.
PROi P35548.
SOURCEi Search...

Gene expression databases

ArrayExpressi P35548.
Bgeei P35548.
CleanExi HS_MSX2.
Genevestigatori P35548.

Family and domain databases

Gene3Di 1.10.10.60. 1 hit.
InterProi IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view ]
Pfami PF00046. Homeobox. 1 hit.
[Graphical view ]
PRINTSi PR00024. HOMEOBOX.
SMARTi SM00389. HOX. 1 hit.
[Graphical view ]
SUPFAMi SSF46689. SSF46689. 1 hit.
PROSITEi PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Expression of a human homeobox-containing gene is regulated by 1,25(OH)2D3 in bone cells."
    Hodgkinson J.E., Davidson C.L., Beresford J., Sharpe P.T.
    Biochim. Biophys. Acta 1174:11-16(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-129.
    Tissue: Osteoblast.
  2. "A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis."
    Jabs E.W., Ma L., Li X., Mueller U., Sparkes R.S., Luo W., Jackson C.E., Warman M.L., Mulliken J.B., Snead M., Haworth I., Maxson R.E.
    Cell 75:443-450(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-129 AND CRS2 HIS-148.
  3. "Molecular cloning and expression of homeobox-containing genes during hard tissue development."
    Iimura T.
    Kokubyo Gakkai Zasshi 61:590-604(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT THR-129.
  4. "Characterization of two length cDNA for human MSX-2 from dental pulp-derived cells."
    Iimura T., Takeda K., Goseki M., Maruoka Y., Sasaki S., Oida S.
    DNA Seq. 8:87-92(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Tooth.
  5. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-129.
  6. "The DNA sequence and comparative analysis of human chromosome 5."
    Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
    , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
    Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT THR-129.
  8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-129.
    Tissue: Pancreas.
  9. "Over-expression of HOX-8, the human homologue of the mouse Hox-8 homeobox gene, in human tumors."
    Suzuki M., Tanaka M., Iwase T., Naito Y., Sugimura H., Kino I.
    Biochem. Biophys. Res. Commun. 194:187-193(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 96-267, VARIANT THR-129.
    Tissue: Ovary tumor.
  10. "Identification of homeobox genes expressed in human haemopoietic progenitor cells."
    Moretti P., Simmons P., Thomas P., Haylock D., Rathjen P., Vadas M., D'Andrea R.
    Gene 144:213-219(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 150-188.
    Tissue: Bone marrow.
  11. "Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex."
    Willis D.M., Loewy A.P., Charlton-Kachigian N., Shao J.-S., Ornitz D.M., Towler D.A.
    J. Biol. Chem. 277:37280-37291(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH XRCC6 AND XRCC5, MUTAGENESIS OF THR-147.
    Tissue: Osteoblast.
  12. Cited for: INVOLVEMENT IN PFMCCD.
  13. "Identification of mutations in the MSX2 homeobox gene in families affected with foramina parietalia permagna."
    Wuyts W., Reardon W., Preis S., Homfray T., Rasore-Quartino A., Christians H., Willems P.J., Van Hul W.
    Hum. Mol. Genet. 9:1251-1255(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PFM1 PRO-154 AND HIS-172.
  14. "Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification."
    Wilkie A.O.M., Tang Z., Elanko N., Walsh S., Twigg S.R.F., Hurst J.A., Wall S.A., Chrzanowska K.H., Maxson R.E. Jr.
    Nat. Genet. 24:387-390(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PFM1 159-ARG-LYS-160 DEL AND HIS-172, VARIANT THR-129.

Entry informationi

Entry nameiMSX2_HUMAN
AccessioniPrimary (citable) accession number: P35548
Secondary accession number(s): D3DQN1, Q53XM4, Q9UD60
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: November 2, 2010
Last modified: July 9, 2014
This is version 147 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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