P28360 · MSX1_HUMAN
- ProteinHomeobox protein MSX-1
- GeneMSX1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids303 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Acts as a transcriptional repressor (By similarity).
Capable of transcription autoinactivation (By similarity).
Binds to the consensus sequence 5'-C/GTAAT-3' in downstream activin regulatory elements (DARE) in the gene promoter, thereby repressing the transcription of CGA/alpha-GSU and GNRHR (By similarity).
Represses transcription of myoblast differentiation factors (By similarity).
Binds to core enhancer regions in target gene promoters of myoblast differentiation factors with binding specificity facilitated by interaction with PIAS1 (By similarity).
Recruits histone H3 methyltransferases such as EHMT2/G9a to gene promoter regions which leads to inhibition of myoblast differentiation via transcriptional repression of differentiation factors (By similarity).
Regulates, in a stage-specific manner, a developmental program of gene expression in the fetal tooth bud that controls odontoblast differentiation and proliferation of dental mesenchymal cells (By similarity).
At the bud stage, required for mesenchymal molar tooth bud development via facilitating reciprocal signaling between dental epithelial and mesenchymal cells (By similarity).
May also regulate expression of Wnt antagonists such as DKK2 and SFPR2 in the developing tooth mesenchyme (By similarity).
Required for BMP4 expression in dental mesenchyme cells (By similarity).
Also, in response to BMP4, required for BMP4 expression in neighboring dental epithelial cells (By similarity).
Required for maximal FGF4-induced expression of SDC1 in dental mesenchyme cells (By similarity).
Also in response to SDC1, required for SDC1 expression in neighboring dental epithelial cells (By similarity).
At the early bell stage, acts to drive proliferation of dental mesenchyme cells, however during the late bell stage acts as an homeostatic regulator of the cell cycle (By similarity).
Regulates proliferation and inhibits premature mesenchymal odontogenesis during the bell stage via inhibition of the Wnt signaling component CTNNB1 and subsequent repression of the odontoblast differentiation factors BMP2, BMP4, LEF1, ALPL and BGLAP/OCN (By similarity).
Additionally, required for correct development and fusion of the palatal shelves and embryonic mandibular formation (By similarity).
Plays a role in embryonic bone formation of the middle ear, skull and nasal bones (By similarity).
Required for correct formation and thickness of the nail plate (By similarity).
May play a role in limb-pattern formation (By similarity).
Capable of transcription autoinactivation (By similarity).
Binds to the consensus sequence 5'-C/GTAAT-3' in downstream activin regulatory elements (DARE) in the gene promoter, thereby repressing the transcription of CGA/alpha-GSU and GNRHR (By similarity).
Represses transcription of myoblast differentiation factors (By similarity).
Binds to core enhancer regions in target gene promoters of myoblast differentiation factors with binding specificity facilitated by interaction with PIAS1 (By similarity).
Recruits histone H3 methyltransferases such as EHMT2/G9a to gene promoter regions which leads to inhibition of myoblast differentiation via transcriptional repression of differentiation factors (By similarity).
Regulates, in a stage-specific manner, a developmental program of gene expression in the fetal tooth bud that controls odontoblast differentiation and proliferation of dental mesenchymal cells (By similarity).
At the bud stage, required for mesenchymal molar tooth bud development via facilitating reciprocal signaling between dental epithelial and mesenchymal cells (By similarity).
May also regulate expression of Wnt antagonists such as DKK2 and SFPR2 in the developing tooth mesenchyme (By similarity).
Required for BMP4 expression in dental mesenchyme cells (By similarity).
Also, in response to BMP4, required for BMP4 expression in neighboring dental epithelial cells (By similarity).
Required for maximal FGF4-induced expression of SDC1 in dental mesenchyme cells (By similarity).
Also in response to SDC1, required for SDC1 expression in neighboring dental epithelial cells (By similarity).
At the early bell stage, acts to drive proliferation of dental mesenchyme cells, however during the late bell stage acts as an homeostatic regulator of the cell cycle (By similarity).
Regulates proliferation and inhibits premature mesenchymal odontogenesis during the bell stage via inhibition of the Wnt signaling component CTNNB1 and subsequent repression of the odontoblast differentiation factors BMP2, BMP4, LEF1, ALPL and BGLAP/OCN (By similarity).
Additionally, required for correct development and fusion of the palatal shelves and embryonic mandibular formation (By similarity).
Plays a role in embryonic bone formation of the middle ear, skull and nasal bones (By similarity).
Required for correct formation and thickness of the nail plate (By similarity).
May play a role in limb-pattern formation (By similarity).
Features
Showing features for dna binding.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
DNA binding | 172-231 | Homeobox | ||||
Sequence: NRKPRTPFTTAQLLALERKFRQKQYLSIAERAEFSSSLSLTETQVKIWFQNRRAKAKRLQ |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameHomeobox protein MSX-1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP28360
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Interaction with EHMT2/G9a is required for localization to the nuclear periphery (By similarity).
Interaction with PIAS1 is required for localization to the nuclear periphery (By similarity).
Interaction with PIAS1 is required for localization to the nuclear periphery (By similarity).
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Tooth agenesis, selective, 1 (STHAG1)
- Note
- DescriptionA form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). STHAG1 can be associated with orofacial cleft in some patients.
- See alsoMIM:106600
Natural variants in STHAG1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_015712 | 67 | M>K | in STHAG1; dbSNP:rs121913130 | |
VAR_003754 | 202 | R>P | in STHAG1; dbSNP:rs121913129 |
Ectodermal dysplasia 3, Witkop type (ECTD3)
- Note
- DescriptionA form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ECTD3 is characterized by abnormalities largely limited largely to teeth (some of which are missing) and nails (which are poorly formed early in life, especially toenails). This condition is distinguished from anhidrotic ectodermal dysplasia by autosomal dominant inheritance and little involvement of hair and sweat glands. The teeth are not as severely affected.
- See alsoMIM:189500
Natural variants in ECTD3
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_088427 | 208-303 | missing | in ECTD3; dbSNP:rs104893853 |
Non-syndromic orofacial cleft 5 (OFC5)
- Note
- DescriptionA birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum.
- See alsoMIM:608874
Natural variants in OFC5
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_018391 | 84 | E>V | in OFC5; cleft palate only; dbSNP:rs28928890 | |
VAR_018392 | 97 | G>D | in OFC5; cleft palate only | |
VAR_018393 | 120 | V>G | in OFC5; cleft palate only; dbSNP:rs759548721 | |
VAR_018394 | 122 | G>E | in OFC5; bilateral cleft palate; dbSNP:rs28933081 | |
VAR_018395 | 157 | R>S | in OFC5; unilateral cleft palate; dbSNP:rs150284621 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_015712 | 67 | in STHAG1; dbSNP:rs121913130 | |||
Sequence: M → K | ||||||
Natural variant | VAR_018391 | 84 | in OFC5; cleft palate only; dbSNP:rs28928890 | |||
Sequence: E → V | ||||||
Natural variant | VAR_018392 | 97 | in OFC5; cleft palate only | |||
Sequence: G → D | ||||||
Natural variant | VAR_018393 | 120 | in OFC5; cleft palate only; dbSNP:rs759548721 | |||
Sequence: V → G | ||||||
Natural variant | VAR_018394 | 122 | in OFC5; bilateral cleft palate; dbSNP:rs28933081 | |||
Sequence: G → E | ||||||
Natural variant | VAR_018395 | 157 | in OFC5; unilateral cleft palate; dbSNP:rs150284621 | |||
Sequence: R → S | ||||||
Natural variant | VAR_003754 | 202 | in STHAG1; dbSNP:rs121913129 | |||
Sequence: R → P | ||||||
Natural variant | VAR_088427 | 208-303 | in ECTD3; dbSNP:rs104893853 | |||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 447 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, cross-link, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000049086 | 1-303 | UniProt | Homeobox protein MSX-1 | |||
Sequence: MAPAADMTSLPLGVKVEDSAFGKPAGGGAGQAPSAAAATAAAMGADEEGAKPKVSPSLLPFSVEALMADHRKPGAKESALAPSEGVQAAGGSAQPLGVPPGSLGAPDAPSSPRPLGHFSVGGLLKLPEDALVKAESPEKPERTPWMQSPRFSPPPARRLSPPACTLRKHKTNRKPRTPFTTAQLLALERKFRQKQYLSIAERAEFSSSLSLTETQVKIWFQNRRAKAKRLQEAELEKLKMAAKPMLPPAAFGLSFPLGGPAAVAAAAGASLYGASGPFQRAALPVAPVGLYTAHVGYSMYHLT | |||||||
Cross-link | 15 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K | |||||||
Cross-link | 133 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 136 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 152 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 160 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Sumoylated by PIAS1, desumoylated by SENP1 (By similarity).
Sumoylation of Lys-15 and Lys-133 not required for interaction with H1-5, transcriptional repression, inhibition of myoblast differentiation, or binding to gene promoters (By similarity).
Sumoylation of Lys-15 and Lys-133 not required for interaction with H1-5, transcriptional repression, inhibition of myoblast differentiation, or binding to gene promoters (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Interacts with CREBBP/CBP, TBP and SP1; interaction with these transcription activators may inhibit autoinactivation (By similarity).
Interacts (via homeobox domain) with EHMT2/G9a (By similarity).
Interacts with EHMT1/GLP (By similarity).
Interacts (via C-terminus) with PIAS1 (via N-terminus); the interaction is required for the localization of both proteins to the nuclear periphery and specific binding of MSX1 to the core enhancer region in target gene promoters (PubMed:16600910).
Interacts with H1-5 (By similarity).
Interacts (via homeobox domain) with EHMT2/G9a (By similarity).
Interacts with EHMT1/GLP (By similarity).
Interacts (via C-terminus) with PIAS1 (via N-terminus); the interaction is required for the localization of both proteins to the nuclear periphery and specific binding of MSX1 to the core enhancer region in target gene promoters (PubMed:16600910).
Interacts with H1-5 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P28360 | RBPMS Q93062-3 | 3 | EBI-3919342, EBI-740343 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 18-55 | Disordered | ||||
Sequence: DSAFGKPAGGGAGQAPSAAAATAAAMGADEEGAKPKVS | ||||||
Region | 69-117 | Disordered | ||||
Sequence: DHRKPGAKESALAPSEGVQAAGGSAQPLGVPPGSLGAPDAPSSPRPLGH | ||||||
Region | 133-174 | Disordered | ||||
Sequence: KAESPEKPERTPWMQSPRFSPPPARRLSPPACTLRKHKTNRK | ||||||
Region | 173-271 | Required for interaction with EHMT2 | ||||
Sequence: RKPRTPFTTAQLLALERKFRQKQYLSIAERAEFSSSLSLTETQVKIWFQNRRAKAKRLQEAELEKLKMAAKPMLPPAAFGLSFPLGGPAAVAAAAGASL |
Sequence similarities
Belongs to the Msh homeobox family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length303
- Mass (Da)31,496
- Last updated2013-11-13 v3
- Checksum1B5F01B35920E64F
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 28 | in Ref. 4; BAF83325 | ||||
Sequence: G → D | ||||||
Sequence conflict | 45 | in Ref. 2; AAA58665 | ||||
Sequence: A → T | ||||||
Sequence conflict | 97-99 | in Ref. 2; AAA58665 | ||||
Sequence: GVP → ASR | ||||||
Sequence conflict | 146 | in Ref. 4; BAF83325 | ||||
Sequence: M → T | ||||||
Sequence conflict | 222 | in Ref. 4; BAF83325 | ||||
Sequence: N → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M76732 EMBL· GenBank· DDBJ | AAA58665.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
M76731 EMBL· GenBank· DDBJ | AAA58665.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
M97676 EMBL· GenBank· DDBJ | AAA52683.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AF426432 EMBL· GenBank· DDBJ | AAL17870.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AK290636 EMBL· GenBank· DDBJ | BAF83325.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AC092437 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC021285 EMBL· GenBank· DDBJ | AAH21285.4 EMBL· GenBank· DDBJ | mRNA | ||
BC067353 EMBL· GenBank· DDBJ | AAH67353.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
EF065625 EMBL· GenBank· DDBJ | ABK81117.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation |