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Protein

Class A basic helix-loop-helix protein 9

Gene

BHLHA9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor, which play a role in limb development. Is an essential player in the regulatory network governing transcription of genes implicated in limb morphogenesis.2 Publications

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • protein heterodimerization activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Class A basic helix-loop-helix protein 9
Short name:
bHLHa9
Alternative name(s):
Class F basic helix-loop-helix factor 42
Short name:
bHLHf42
Gene namesi
Name:BHLHA9
Synonyms:BHLHF42
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:35126. BHLHA9.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Split-hand/foot malformation with long bone deficiency 3 (SHFLD3)1 Publication

Disease susceptibility may be associated with variations affecting the gene represented in this entry. A copy number variation (CNV) resulting in BHLHA9 duplications is a necessary but not sufficient susceptibility factor for Split-hand/foot malformation with long bone deficiency, a highly variable phenotype with reduced penetrance, particularly in females (PubMed:22147889).

Disease descriptionA disease characterized by the association of split-hand/foot malformation with long bone deficiency involving the tibia and fibula. Split-hand/foot malformation is a limb malformation involving the central rays of the autopod. Phenotypic expression is extremely variable between and within families, and even between limbs of a single patient, ranging from syndactyly and oligodactyly to the most severe monodactyly with only a single phalanx. Limb features include median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals.

See also OMIM:612576
Syndactyly, mesoaxial synostotic, with phalangeal reduction (MSSD)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn autosomal recessive, non-syndromic digit anomaly characterized by mesoaxial osseous synostosis at a metacarpal level, reduction of one or more phalanges, hypoplasia of distal phalanges of preaxial and postaxial digits, clinodactyly of fifth fingers, and preaxial fusion of toes.

See also OMIM:609432
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti71 – 711N → D in MSSD; completely abolishes the transcription activation with the dimerization partners TCF3, TCF4 and TCF12. 1 Publication
VAR_073333
Natural varianti73 – 731R → P in MSSD; completely abolishes the transcription activation with the dimerization partners TCF3, TCF4 and TCF12. 1 Publication
VAR_073334
Natural varianti75 – 751R → L in MSSD; completely abolishes the transcription activation with the dimerization partners TCF3, TCF4 and TCF12. 1 Publication
VAR_073335

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi609432. phenotype.
612576. phenotype.
Orphaneti3329. Tibial aplasia - ectrodactyly.
PharmGKBiPA164716602.

Polymorphism and mutation databases

DMDMi190358730.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 235235Class A basic helix-loop-helix protein 9PRO_0000341377Add
BLAST

Proteomic databases

PaxDbiQ7RTU4.
PRIDEiQ7RTU4.

PTM databases

PhosphoSiteiQ7RTU4.

Expressioni

Gene expression databases

BgeeiQ7RTU4.

Organism-specific databases

HPAiHPA062632.

Interactioni

Subunit structurei

Heterodimer (PubMed:25466284). Efficient DNA binding requires dimerization with another bHLH protein. Interacts with TCF3, TCF4, and TCF12 (PubMed:25466284).1 Publication

Protein-protein interaction databases

STRINGi9606.ENSP00000375248.

Structurei

3D structure databases

ProteinModelPortaliQ7RTU4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini65 – 11753bHLHPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi152 – 22069Pro-richAdd
BLAST

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG82328.
GeneTreeiENSGT00390000002453.
HOGENOMiHOG000095226.
InParanoidiQ7RTU4.
OMAiPCGHLEC.
OrthoDBiEOG7C5M9C.
PhylomeDBiQ7RTU4.
TreeFamiTF337642.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q7RTU4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLRGAPGLGL TARKGAEDSA EDLGGPCPEP GGDSGVLGAN GASCSRGEAE
60 70 80 90 100
EPAGRRRARP VRSKARRMAA NVRERKRILD YNEAFNALRR ALRHDLGGKR
110 120 130 140 150
LSKIATLRRA IHRIAALSLV LRASPAPRGP CGHLECHGPA ARGDTGDTGA
160 170 180 190 200
SPPPPAGPSL ARPDAARPSV PSAPRCASCP PHAPLARPSA VAEGPGLAQA
210 220 230
SGGSWRRCPG ASSAGPPPWP RGYLRSAPGM GHPRS
Length:235
Mass (Da):24,132
Last modified:June 10, 2008 - v2
Checksum:i1A4F0FD0E12F6E33
GO

Sequence cautioni

The sequence DAA00302.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti71 – 711N → D in MSSD; completely abolishes the transcription activation with the dimerization partners TCF3, TCF4 and TCF12. 1 Publication
VAR_073333
Natural varianti73 – 731R → P in MSSD; completely abolishes the transcription activation with the dimerization partners TCF3, TCF4 and TCF12. 1 Publication
VAR_073334
Natural varianti75 – 751R → L in MSSD; completely abolishes the transcription activation with the dimerization partners TCF3, TCF4 and TCF12. 1 Publication
VAR_073335

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC032044 Genomic DNA. No translation available.
BK000140 Genomic DNA. Translation: DAA00302.1. Different initiation.
CCDSiCCDS45560.1.
RefSeqiNP_001157877.1. NM_001164405.1.
UniGeneiHs.723790.

Genome annotation databases

EnsembliENST00000391429; ENSP00000375248; ENSG00000205899.
GeneIDi727857.
KEGGihsa:727857.
UCSCiuc021tnd.1. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC032044 Genomic DNA. No translation available.
BK000140 Genomic DNA. Translation: DAA00302.1. Different initiation.
CCDSiCCDS45560.1.
RefSeqiNP_001157877.1. NM_001164405.1.
UniGeneiHs.723790.

3D structure databases

ProteinModelPortaliQ7RTU4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000375248.

PTM databases

PhosphoSiteiQ7RTU4.

Polymorphism and mutation databases

DMDMi190358730.

Proteomic databases

PaxDbiQ7RTU4.
PRIDEiQ7RTU4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000391429; ENSP00000375248; ENSG00000205899.
GeneIDi727857.
KEGGihsa:727857.
UCSCiuc021tnd.1. human.

Organism-specific databases

CTDi727857.
GeneCardsiGC17P001175.
HGNCiHGNC:35126. BHLHA9.
HPAiHPA062632.
MIMi609432. phenotype.
612576. phenotype.
615416. gene.
neXtProtiNX_Q7RTU4.
Orphaneti3329. Tibial aplasia - ectrodactyly.
PharmGKBiPA164716602.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG82328.
GeneTreeiENSGT00390000002453.
HOGENOMiHOG000095226.
InParanoidiQ7RTU4.
OMAiPCGHLEC.
OrthoDBiEOG7C5M9C.
PhylomeDBiQ7RTU4.
TreeFamiTF337642.

Miscellaneous databases

GeneWikiiBHLHA9.
GenomeRNAii727857.
NextBioi125337.
PROiQ7RTU4.
SOURCEiSearch...

Gene expression databases

BgeeiQ7RTU4.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. "Exhaustive identification of human class II basic helix-loop-helix proteins by virtual library screening."
    McLellan A.S., Langlands K., Kealey T.
    Mech. Dev. 119:S285-S291(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION.
  3. Cited for: FUNCTION, INVOLVEMENT IN SHFLD3.
  4. "Mutations affecting the BHLHA9 DNA-binding domain cause MSSD, mesoaxial synostotic syndactyly with phalangeal reduction, Malik-Percin type."
    Malik S., Percin F.E., Bornholdt D., Albrecht B., Percesepe A., Koch M.C., Landi A., Fritz B., Khan R., Mumtaz S., Akarsu N.A., Grzeschik K.H.
    Am. J. Hum. Genet. 95:649-659(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, FUNCTION, SUBUNIT, INTERACTION WITH TCF3; TCF4 AND TCF12, INVOLVEMENT IN MSDD, VARIANTS MSSD ASP-71; PRO-73 AND LEU-75, CHARACTERIZATION OF VARIANTS MSSD ASP-71; PRO-73 AND LEU-75.

Entry informationi

Entry nameiBHA09_HUMAN
AccessioniPrimary (citable) accession number: Q7RTU4
Secondary accession number(s): A8MSH6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 10, 2008
Last sequence update: June 10, 2008
Last modified: June 24, 2015
This is version 81 of the entry and version 2 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 17
    Human chromosome 17: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.