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P35548 (MSX2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox protein MSX-2
Alternative name(s):
Homeobox protein Hox-8
Gene names
Name:MSX2
Synonyms:HOX8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length267 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.11

Subunit structure

Interacts with MINT By similarity. Interacts with XRCC6 (Ku70) and XRCC5 (Ku80). Ref.11

Subcellular location

Nucleus.

Involvement in disease

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. Ref.13 Ref.14

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. Ref.12

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. Ref.2

Sequence similarities

Belongs to the Msh homeobox family.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processOsteogenesis
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseCraniosynostosis
Disease mutation
   DomainHomeobox
   LigandDNA-binding
   Molecular functionDevelopmental protein
Repressor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway involved in heart development

Inferred from electronic annotation. Source: Ensembl

activation of meiosis

Inferred from electronic annotation. Source: Ensembl

anagen

Inferred from electronic annotation. Source: Ensembl

anterior/posterior pattern specification

Inferred from electronic annotation. Source: Ensembl

bone trabecula formation

Inferred from electronic annotation. Source: Ensembl

branching involved in mammary gland duct morphogenesis

Inferred from electronic annotation. Source: Ensembl

cellular response to estradiol stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

chondrocyte development

Inferred from electronic annotation. Source: Ensembl

cranial suture morphogenesis

Traceable author statement PubMed 8968743. Source: BHF-UCL

embryonic forelimb morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic hindlimb morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic nail plate morphogenesis

Inferred from electronic annotation. Source: Ensembl

enamel mineralization

Inferred from electronic annotation. Source: Ensembl

endochondral bone growth

Inferred from electronic annotation. Source: Ensembl

epithelial to mesenchymal transition involved in endocardial cushion formation

Inferred from electronic annotation. Source: Ensembl

frontal suture morphogenesis

Inferred from electronic annotation. Source: Ensembl

negative regulation of CREB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of keratinocyte differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of transcription regulatory region DNA binding

Inferred from sequence or structural similarity. Source: BHF-UCL

osteoblast development

Inferred from electronic annotation. Source: Ensembl

osteoblast differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

outflow tract septum morphogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of BMP signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of catagen

Inferred from electronic annotation. Source: Ensembl

positive regulation of mesenchymal cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

signal transduction involved in regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

wound healing, spreading of epidermal cells

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

nucleus

Inferred from direct assay. Source: HPA

transcription factor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionRNA polymerase II core promoter proximal region sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding

Inferred from direct assay PubMed 9073066. Source: MGI

transcription cofactor activity

Inferred from sequence or structural similarity. Source: BHF-UCL

transcription regulatory region DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 267267Homeobox protein MSX-2
PRO_0000049099

Regions

DNA binding142 – 20160Homeobox

Natural variations

Natural variant1291M → T. Ref.1 Ref.2 Ref.3 Ref.5 Ref.7 Ref.8 Ref.9 Ref.14
Corresponds to variant rs4242182 [ dbSNP | Ensembl ].
VAR_010898
Natural variant1481P → H in CRS2; gain of function. Ref.2
VAR_003755
Natural variant1541L → P in PFM1. Ref.13
VAR_010786
Natural variant159 – 1602Missing in PFM1; loss of function.
VAR_010200
Natural variant1721R → H in PFM1; loss of function. Ref.13 Ref.14
VAR_010201

Experimental info

Mutagenesis1471T → A: Does not bind DNA but still suppresses OCFRE activation. Ref.11
Sequence conflict281P → L in CAA49156. Ref.1
Sequence conflict321E → A in CAA49156. Ref.1
Sequence conflict62 – 654ASPL → SPAV in CAA49156. Ref.1
Sequence conflict671A → P in CAA49156. Ref.1
Sequence conflict691S → G in CAA49156. Ref.1
Sequence conflict751T → H in CAA49156. Ref.1
Sequence conflict851G → R in CAA49156. Ref.1
Sequence conflict1071E → G in CAA49156. Ref.1
Sequence conflict1941R → S in CAA49156. Ref.1
Sequence conflict2371G → A in CAA49156. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P35548 [UniParc].

Last modified November 2, 2010. Version 3.
Checksum: 5B61B75F4A7C4AFD

FASTA26728,897
        10         20         30         40         50         60 
MASPSKGNDL FSPDEEGPAV VAGPGPGPGG AEGAAEERRV KVSSLPFSVE ALMSDKKPPK 

        70         80         90        100        110        120 
EASPLPAESA SAGATLRPLL LSGHGAREAH SPGPLVKPFE TASVKSENSE DGAAWMQEPG 

       130        140        150        160        170        180 
RYSPPPRHMS PTTCTLRKHK TNRKPRTPFT TSQLLALERK FRQKQYLSIA ERAEFSSSLN 

       190        200        210        220        230        240 
LTETQVKIWF QNRRAKAKRL QEAELEKLKM AAKPMLPSSF SLPFPISSPL QAASIYGASY 

       250        260 
PFHRPVLPIP PVGLYATPVG YGMYHLS 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"Parietal foramina with cleidocranial dysplasia is caused by mutation in MSX2."
Garcia-Minaur S., Mavrogiannis L.A., Rannan-Eliya S.V., Hendry M.A., Liston W.A., Porteous M.E.M., Wilkie A.O.M.
Eur. J. Hum. Genet. 11:892-895(2003) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA49068.
RefSeqNP_002440.2. NM_002449.4.
UniGeneHs.89404.

3D structure databases

ProteinModelPortalP35548.
SMRP35548. Positions 143-200.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110594. 21 interactions.
IntActP35548. 1 interaction.
STRING9606.ENSP00000239243.

PTM databases

PhosphoSiteP35548.

Polymorphism databases

DMDM311033429.

Proteomic databases

PaxDbP35548.
PRIDEP35548.

Protocols and materials databases

DNASU4488.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000239243; ENSP00000239243; ENSG00000120149.
GeneID4488.
KEGGhsa:4488.
UCSCuc003mcy.3. human.

Organism-specific databases

CTD4488.
GeneCardsGC05P174084.
H-InvDBHIX0005431.
HGNCHGNC:7392. MSX2.
HPAHPA005652.
MIM123101. gene.
168500. phenotype.
168550. phenotype.
604757. phenotype.
neXtProtNX_P35548.
Orphanet1541. Craniosynostosis, Boston type.
60015. Parietal foramina.
251290. Parietal foramina with cleidocranial dysplasia.
PharmGKBPA31197.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG298790.
HOGENOMHOG000231922.
HOVERGENHBG005205.
InParanoidP35548.
KOK09341.
OMAPPKEMSS.
OrthoDBEOG70GMGK.
PhylomeDBP35548.
TreeFamTF350699.

Gene expression databases

ArrayExpressP35548.
BgeeP35548.
CleanExHS_MSX2.
GenevestigatorP35548.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSPR00024. HOMEOBOX.
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMsh_homeobox_2.
GenomeRNAi4488.
NextBio17363.
PROP35548.
SOURCESearch...

Entry information

Entry nameMSX2_HUMAN
AccessionPrimary (citable) accession number: P35548
Secondary accession number(s): D3DQN1, Q53XM4, Q9UD60
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: November 2, 2010
Last modified: March 19, 2014
This is version 143 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM