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Q9UBX0 (HESX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox expressed in ES cells 1
Alternative name(s):
Homeobox protein ANF
Short name=hAnf
Gene names
Name:HESX1
Synonyms:HANF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length185 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for the normal development of the forebrain, eyes and other anterior structures such as the olfactory placodes and pituitary gland. Possible transcriptional repressor. Binds to the palindromic PIII sequence, 5'-AGCTTGAGTCTAATTGAATTAACTGTAC-3'. HESX1 and PROP1 bind as heterodimers on this palindromic site, and, in vitro, HESX1 can antagonize PROP1 activation By similarity.

Subunit structure

Can form heterodimers with PROP1 in binding to DNA By similarity. Interacts with TLE1. Ref.4

Subcellular location

Nucleus Probable.

Developmental stage

Strongly expressed in Rathke pouch in seven-week-old embryo.

Involvement in disease

Septooptic dysplasia (SOD) [MIM:182230]: A clinically heterogeneous disorder defined by any combination of optic nerve hypoplasia, pituitary gland hypoplasia with panhypopopituitarism, and midline abnormalities of the brain, including absence of the corpus callosum and septum pellucidum.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.6

Growth hormone deficiency with pituitary anomalies (GHDPA) [MIM:182230]: A disease characterized by low or absent growth hormone levels, in the presence of a hypoplastic anterior pituitary lobe and ectopic or absent posterior pituitary lobe.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.8

Pituitary hormone deficiency, combined, 5 (CPHD5) [MIM:182230]: Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD5 is characterized by complete or partial deficiencies of growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle stimulating hormone and adrenocorticotropic hormone.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7

Sequence similarities

Belongs to the ANF homeobox family.

Contains 1 homeobox DNA-binding domain.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 185185Homeobox expressed in ES cells 1
PRO_0000048922

Regions

DNA binding108 – 16760Homeobox Ref.5

Natural variations

Natural variant61Q → H in CPHD5. Ref.6
VAR_063230
Natural variant261I → T in CPHD5; the mutated protein is associated with impaired transcriptional repression but not DNA binding. Ref.7
VAR_063231
Natural variant1251N → S. Ref.1
Corresponds to variant rs9878928 [ dbSNP | Ensembl ].
VAR_010400
Natural variant1491E → K in GHDPA; unable to repress PROP1-mediated activation. Ref.8
VAR_063232
Natural variant1601R → C in SOD; loss of DNA-binding. Ref.1
Corresponds to variant rs28936702 [ dbSNP | Ensembl ].
VAR_010225
Natural variant1701S → L in SOD; mild. Ref.6
VAR_063233
Natural variant1811T → A in GHDPA. Ref.6
VAR_063234

Secondary structure

....... 185
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UBX0 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 1F23D319EB4FDBF0

FASTA18521,409
        10         20         30         40         50         60 
MSPSLQEGAQ LGENKPSTCS FSIERILGLD QKKDCVPLMK PHRPWADTCS SSGKDGNLCL 

        70         80         90        100        110        120 
HVPNPPSGIS FPSVVDHPMP EERASKYENY FSASERLSLK RELSWYRGRR PRTAFTQNQI 

       130        140        150        160        170        180 
EVLENVFRVN CYPGIDIRED LAQKLNLEED RIQIWFQNRR AKLKRSHRES QFLMAKKNFN 


TNLLE 

« Hide

References

« Hide 'large scale' references
[1]"Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse."
Dattani M.T., Martinez-Barbera J.-P., Thomas P.Q., Brickman J.M., Gupta R., Maartensson I.-L., Toresson H., Fox M., Wales J.K.H., Hindmarsh P.C., Krauss S., Beddington R.S.P., Robinson I.C.A.F.
Nat. Genet. 19:125-133(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SOD CYS-160, VARIANT SER-125.
Tissue: Fibrosarcoma.
[2]"Anf: a novel class of vertebrate homeobox genes expressed at the anterior end of the main embryonic axis."
Kazanskaya O.V., Severtzova E.A., Barth K.A., Ermakova G.V., Lukyanov S.A., Benyumov A.O., Pannese M., Boncinelli E., Wilson S.W., Zaraisky A.G.
Gene 200:25-34(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Teratocarcinoma.
[3]"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].
[4]"Temporal regulation of a paired-like homeodomain repressor/TLE corepressor complex and a related activator is required for pituitary organogenesis."
Dasen J.S., Martinez-Barbera J.-P., Herman T.S., O'Connell S., Olson L., Ju B., Tollkuhn J., Baek S.H., Rose D.W., Rosenfeld M.G.
Genes Dev. 15:3193-3207(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TLE1.
[5]"Role of conserved salt bridges in homeodomain stability and DNA binding."
Torrado M., Revuelta J., Gonzalez C., Corzana F., Bastida A., Asensio J.L.
J. Biol. Chem. 284:23765-23779(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 108-174, DNA-BINDING.
[6]"Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia."
Thomas P.Q., Dattani M.T., Brickman J.M., McNay D., Warne G., Zacharin M., Cameron F., Hurst J., Woods K., Dunger D., Stanhope R., Forrest S., Robinson I.C., Beddington R.S.
Hum. Mol. Genet. 10:39-45(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SOD LEU-170, VARIANT GHDPA ALA-181, VARIANT CPHD5 HIS-6.
[7]"A homozygous mutation in HESX1 is associated with evolving hypopituitarism due to impaired repressor-corepressor interaction."
Carvalho L.R., Woods K.S., Mendonca B.B., Marcal N., Zamparini A.L., Stifani S., Brickman J.M., Arnhold I.J., Dattani M.T.
J. Clin. Invest. 112:1192-1201(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPHD5 THR-26, CHARACTERIZATION OF VARIANT CPHD5 THR-26.
[8]"HESX1 mutations are an uncommon cause of septooptic dysplasia and hypopituitarism."
McNay D.E.G., Turton J.P., Kelberman D., Woods K.S., Brauner R., Papadimitriou A., Keller E., Keller A., Haufs N., Krude H., Shalet S.M., Dattani M.T.
J. Clin. Endocrinol. Metab. 92:691-697(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GHDPA LYS-149, CHARACTERIZATION OF VARIANT GHDPA LYS-149.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF059734 Genomic DNA. Translation: AAC24523.1.
U82811 mRNA. Translation: AAB88275.1.
U65437 Genomic DNA. Translation: AAB39561.1.
BC069515 mRNA. Translation: AAH69515.1.
BC093979 mRNA. Translation: AAH93979.1.
BC112089 mRNA. Translation: AAI12090.1.
CCDSCCDS2881.1.
RefSeqNP_003856.1. NM_003865.2.
XP_005265583.1. XM_005265526.2.
XP_006713442.1. XM_006713379.1.
UniGeneHs.171980.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2K40NMR-A108-174[»]
ProteinModelPortalQ9UBX0.
SMRQ9UBX0. Positions 108-174.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114347. 5 interactions.
IntActQ9UBX0. 2 interactions.
MINTMINT-8417673.
STRING9606.ENSP00000295934.

Polymorphism databases

DMDM12230168.

Proteomic databases

PaxDbQ9UBX0.
PRIDEQ9UBX0.

Protocols and materials databases

DNASU8820.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000295934; ENSP00000295934; ENSG00000163666.
GeneID8820.
KEGGhsa:8820.
UCSCuc003din.4. human.

Organism-specific databases

CTD8820.
GeneCardsGC03M057207.
HGNCHGNC:4877. HESX1.
HPAHPA024187.
MIM182230. phenotype.
262600. phenotype.
601802. gene.
neXtProtNX_Q9UBX0.
Orphanet95494. Combined pituitary hormone deficiencies, genetic forms.
226307. Hypothyroidism due to deficient transcription factors involved in pituitary development or function.
478. Kallmann syndrome.
95496. Pituitary stalk interruption syndrome.
3157. Septo-optic dysplasia.
PharmGKBPA29255.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG326168.
HOGENOMHOG000112889.
HOVERGENHBG004226.
InParanoidQ9UBX0.
KOK09354.
OMAHPMPEER.
OrthoDBEOG7WMCMW.
PhylomeDBQ9UBX0.
TreeFamTF335506.

Gene expression databases

ArrayExpressQ9UBX0.
BgeeQ9UBX0.
CleanExHS_HESX1.
GenevestigatorQ9UBX0.

Family and domain databases

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

Other

ChiTaRSHESX1. human.
EvolutionaryTraceQ9UBX0.
GeneWikiHESX1.
GenomeRNAi8820.
NextBio33086.
PROQ9UBX0.
SOURCESearch...

Entry information

Entry nameHESX1_HUMAN
AccessionPrimary (citable) accession number: Q9UBX0
Secondary accession number(s): Q52LC5, Q99667
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: May 1, 2000
Last modified: July 9, 2014
This is version 128 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 3

Human chromosome 3: entries, gene names and cross-references to MIM