P28360 (MSX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homeobox protein MSX-1

Alternative name(s):
Homeobox protein Hox-7
Msh homeobox 1-like protein

Gene names

Name:	MSX1
Synonyms:	HOX7

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	297 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a transcriptional repressor. May play a role in limb-pattern formation. Acts in cranofacial development and specifically in odontogenesis. Expression in the developing nail bed mesenchyme is important for nail plate thickness and integrity. Ref.3 Ref.7
Subcellular location	Nucleus.
Tissue specificity	Expressed in the developing nail bed mesenchyme. Ref.7
Post-translational modification	Sumoylated by PIAS1, desumoylated by SENP1 By similarity.
Involvement in disease	Tooth agenesis selective 1 (STHAG1) [MIM:106600]: A 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). Tooth agenesis selective type 1 can be associated with orofacial cleft in some patients. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 MSX1 is deleted in some patients with Wolf-Hirschhorn syndrome (WHS). WHS results from sub-telomeric deletions in the short arm of chromosome 4. Ectodermal dysplasia 3, Witkop type (ECTD3) [MIM:189500]: A 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Non-syndromic orofacial cleft 5 (OFC5) [MIM:608874]: A 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3
Sequence similarities	Belongs to the Msh homeobox family. Contains 1 homeobox DNA-binding domain.
Sequence caution	The sequence AAH21285.4 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Disease	Disease mutation Ectodermal dysplasia
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Developmental protein Repressor
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway involved in heart development Inferred from electronic annotation. Source: Compara anterior/posterior pattern specification Inferred from electronic annotation. Source: Compara apoptotic nuclear changes Inferred from direct assay PubMed 15705871. Source: BHF-UCL bone morphogenesis Inferred from electronic annotation. Source: Compara cartilage morphogenesis Inferred from electronic annotation. Source: Compara cell morphogenesis Inferred from direct assay PubMed 15705871. Source: BHF-UCL embryonic forelimb morphogenesis Inferred from electronic annotation. Source: Compara embryonic hindlimb morphogenesis Inferred from electronic annotation. Source: Compara embryonic nail plate morphogenesis Inferred from mutant phenotype Ref.7. Source: BHF-UCL epithelial to mesenchymal transition involved in endocardial cushion formation Inferred from electronic annotation. Source: Compara face morphogenesis Inferred from mutant phenotype PubMed 10742093PubMed 11332647PubMed 12651933. Source: BHF-UCL forebrain development Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara mammary gland epithelium development Inferred from electronic annotation. Source: Compara mesenchymal cell proliferation Inferred from electronic annotation. Source: Compara midbrain development Inferred from electronic annotation. Source: Compara middle ear morphogenesis Inferred from electronic annotation. Source: Compara muscle organ development Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of cell growth Inferred from direct assay PubMed 15705871. Source: BHF-UCL negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of striated muscle cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara negative regulation of transcription regulatory region DNA binding Inferred from electronic annotation. Source: Compara odontogenesis of dentin-containing tooth Inferred from mutant phenotype PubMed 10742093Ref.7Ref.8. Source: BHF-UCL palate development Inferred from electronic annotation. Source: Compara positive regulation of BMP signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of DNA damage response, signal transduction by p53 class mediator Inferred by curator PubMed 15705871. Source: BHF-UCL positive regulation of apoptotic process Inferred from direct assay PubMed 15705871. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara protein localization to nucleus Inferred from direct assay PubMed 15705871. Source: BHF-UCL protein stabilization Inferred from direct assay PubMed 15705871. Source: BHF-UCL regulation of odontogenesis Inferred from electronic annotation. Source: Compara signal transduction involved in regulation of gene expression Inferred from electronic annotation. Source: Compara stem cell differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	nucleus Inferred from direct assay PubMed 15705871. Source: BHF-UCL transcription factor complex Inferred from electronic annotation. Source: Compara
Molecular_function	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara sequence-specific DNA binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 297	297	Homeobox protein MSX-1		PRO_0000049086
Regions
	DNA binding	166 – 225	60	Homeobox
	Compositional bias	29 – 36	8	Poly-Ala
	Compositional bias	255 – 263	9	Poly-Ala
Amino acid modifications
	Cross-link	9		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	127		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Natural variations
	Natural variant	61	1	M → K in STHAG1. Ref.9		VAR_015712
	Natural variant	78	1	E → V in OFC5; cleft palate only. Ref.3		VAR_018391
	Natural variant	91	1	G → D in OFC5; cleft palate only. Ref.3		VAR_018392
	Natural variant	114	1	V → G in OFC5; cleft palate only. Ref.3		VAR_018393
	Natural variant	116	1	G → E in OFC5; bilateral cleft palate. Ref.3 Corresponds to variant rs28933081 [ dbSNP | Ensembl ].		VAR_018394
	Natural variant	151	1	R → S in OFC5; unilateral cleft palate. Ref.3		VAR_018395
	Natural variant	196	1	R → P in STHAG1; severely impairs DNA-binding. Ref.8		VAR_003754
Experimental info
	Sequence conflict	39	1	A → T in AAA58665. Ref.2
	Sequence conflict	91 – 93	3	GVP → ASR in AAA58665. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P28360 [UniParc]. Last modified September 19, 2002. Version 2. Checksum: D22C3BED8E88107E	FASTA	297	30,940
	10 20 30 40 50 60 MTSLPLGVKV EDSAFGKPAG GGAGQAPSAA AATAAAMGAD EEGAKPKVSP SLLPFSVEAL 70 80 90 100 110 120 MADHRKPGAK ESALAPSEGV QAAGGSAQPL GVPPGSLGAP DAPSSPRPLG HFSVGGLLKL 130 140 150 160 170 180 PEDALVKAES PEKPERTPWM QSPRFSPPPA RRLSPPACTL RKHKTNRKPR TPFTTAQLLA 190 200 210 220 230 240 LERKFRQKQY LSIAERAEFS SSLSLTETQV KIWFQNRRAK AKRLQEAELE KLKMAAKPML 250 260 270 280 290 PPAAFGLSFP LGGPAAVAAA AGASLYGASG PFQRAALPVA PVGLYTAHVG YSMYHLT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and sequence of the human homeobox gene HOX7." Hewitt J.E., Clarke L.E., Iven A., Williamson R. Genomics 11:670-678(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Lymphocyte.
[2]	"Characterization of the human HOX 7 cDNA and identification of polymorphic markers." Padanilam B.J., Stadler S.H., Mills K.A., McLeod L.B., Solursh M., Lee B.M., Ramirez F., Buetow K.H., Murray J.C. Hum. Mol. Genet. 1:407-410(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Ectomesenchyme.
[3]	"Complete sequencing shows a role for MSX1 in non-syndromic cleft lip and palate." Jezewski P.A., Vieira A.R., Nishimura C., Ludwig B., Johnson M., O'Brien S.E., Daack-Hirsch S., Schultz R.E., Weber A., Nepomucena B., Romitti P.A., Christensen K., Orioli I.M., Castilla E.E., Machida J., Natsume N., Murray J.C. J. Med. Genet. 40:399-407(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, VARIANTS OFC5 VAL-78; ASP-91; GLY-114; GLU-116 AND SER-151.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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]. Tissue: Neuroblastoma and Pancreatic carcinoma.
[6]	"The human homeobox gene HOX7 maps to chromosome 4p16.1 and may be implicated in Wolf-Hirschhorn syndrome." Ivens A., Flavin N., Williamson R., Dixon M., Bates G., Buckingham M., Robert B. Hum. Genet. 84:473-476(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 185-245, INVOLVEMENT IN WOLF-HIRSCHORN SYNDROME.
[7]	"A nonsense mutation in MSX1 causes Witkop syndrome." Jumlongras D., Bei M., Stimson J.M., Wang W.-F., DePalma S.R., Seidman C.E., Felbor U., Maas R., Seidman J.G., Olsen B.R. Am. J. Hum. Genet. 69:67-74(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, INVOLVEMENT IN ECTD3.
[8]	"A human MSX1 homeodomain missense mutation causes selective tooth agenesis." Vastardis H., Karimbux N., Guthua S.W., Seidman J.G., Seidman C.E. Nat. Genet. 13:417-421(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT STHAG1 PRO-196.
[9]	"The role of MSX1 in human tooth agenesis." Lidral A.C., Reising B.C. J. Dent. Res. 81:274-278(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT STHAG1 LYS-61.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M76732, M76731 Genomic DNA. Translation: AAA58665.1. M97676 mRNA. Translation: AAA52683.1. AF426432 Genomic DNA. Translation: AAL17870.1. AC092437 Genomic DNA. No translation available. BC021285 mRNA. Translation: AAH21285.4. Different initiation. BC067353 mRNA. Translation: AAH67353.1.
IPI	IPI00002939.
PIR	A40560. I54320.
RefSeq	NP_002439.2. NM_002448.3.
UniGene	Hs.424414.
3D structure databases
ProteinModelPortal	P28360.
ModBase	Search...
Protein-protein interaction databases
IntAct	P28360. 3 interactions.
STRING	9606.ENSP00000372170.
PTM databases
PhosphoSite	P28360.
Polymorphism databases
DMDM	23503066.
Proteomic databases
PaxDb	P28360.
PRIDE	P28360.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000382723; ENSP00000372170; ENSG00000163132.
GeneID	4487.
KEGG	hsa:4487.
UCSC	uc003gif.3. human.
Organism-specific databases
CTD	4487.
GeneCards	GC04P004861.
HGNC	HGNC:7391. MSX1.
HPA	CAB026198.
MIM	106600. phenotype. 142983. gene. 189500. phenotype. 608874. phenotype.
neXtProt	NX_P28360.
Orphanet	199306. Cleft lip/palate. 2227. Hypodontia. 2228. Hypodontia - dysplasia of nails. 99798. Oligodontia.
PharmGKB	PA31196.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG298790.
HOGENOM	HOG000231922.
HOVERGEN	HBG005205.
InParanoid	P28360.
KO	K09341.
PhylomeDB	P28360.
Gene expression databases
ArrayExpress	P28360.
Bgee	P28360.
CleanEx	HS_MSX1.
Genevestigator	P28360.
GermOnline	ENSG00000163132. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.60. 1 hit.
InterPro	IPR017970. Homeobox_CS. IPR020479. Homeobox_metazoa. IPR001356. Homeodomain. IPR009057. Homeodomain-like. [Graphical view]
Pfam	PF00046. Homeobox. 1 hit. [Graphical view]
PRINTS	PR00024. HOMEOBOX.
SMART	SM00389. HOX. 1 hit. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 1 hit.
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	4487.
NextBio	17359.
SOURCE	Search...

Entry information

Entry name

MSX1_HUMAN

Accession

Primary (citable) accession number: P28360
Secondary accession number(s): Q96NY4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	September 19, 2002
Last modified:	May 1, 2013
This is version 148 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.