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Q03014 (HHEX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hematopoietically-expressed homeobox protein HHEX

Short name=Homeobox protein HEX
Alternative name(s):
Homeobox protein PRH
Gene names
Name:HHEX
Synonyms:HEX, PRH, PRHX
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length270 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Recognizes the DNA sequence 5'-ATTAA-3'. Transcriptional repressor. May play a role in hematopoietic differentiation. Establishes anterior identity at two levels; acts early to enhance canonical WNT-signaling by repressing expression of TLE4, and acts later to inhibit NODAL-signaling by directly targeting NODAL By similarity.

Subcellular location

Nucleus Probable.

Tissue specificity

Liver and promyelocytic leukemia cell line HL-60. Ref.1 Ref.2 Ref.7

Developmental stage

Expressed during hematopoiesis.

Sequence similarities

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processDifferentiation
Transcription
Transcription regulation
Wnt signaling pathway
   Cellular componentNucleus
   DomainHomeobox
   LigandDNA-binding
   Molecular functionDevelopmental protein
Repressor
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell differentiation

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

DNA conformation change

Inferred from direct assay PubMed 18755198. Source: BHF-UCL

Wnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

anterior/posterior pattern specification

Inferred from sequence or structural similarity. Source: UniProtKB

cell differentiation

Inferred by curator PubMed 10871399. Source: BHF-UCL

cell proliferation

Inferred from direct assay PubMed 12554669. Source: BHF-UCL

common bile duct development

Inferred from electronic annotation. Source: Ensembl

embryonic heart tube development

Inferred from electronic annotation. Source: Ensembl

endoderm development

Inferred from electronic annotation. Source: Ensembl

forebrain morphogenesis

Inferred from electronic annotation. Source: Ensembl

gall bladder development

Inferred from electronic annotation. Source: Ensembl

hepatic duct development

Inferred from electronic annotation. Source: Ensembl

hepatoblast differentiation

Inferred from electronic annotation. Source: Ensembl

hepatocyte differentiation

Inferred from electronic annotation. Source: Ensembl

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

interkinetic nuclear migration

Inferred from electronic annotation. Source: Ensembl

mRNA export from nucleus

Inferred from direct assay PubMed 12554669. Source: BHF-UCL

multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

myeloid leukocyte differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of angiogenesis

Inferred from sequence or structural similarity PubMed 15016828. Source: BHF-UCL

negative regulation of cyclin-dependent protein serine/threonine kinase activity

Inferred from direct assay PubMed 12554669. Source: BHF-UCL

negative regulation of transcription by competitive promoter binding

Traceable author statement PubMed 19324893. Source: BHF-UCL

negative regulation of transcription by transcription factor localization

Inferred by curator PubMed 18713067. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 10871399PubMed 15016828. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 10871399PubMed 15016828. Source: BHF-UCL

negative regulation of vascular endothelial growth factor receptor signaling pathway

Inferred from sequence or structural similarity PubMed 15016828. Source: BHF-UCL

pancreas development

Inferred from electronic annotation. Source: Ensembl

poly(A)+ mRNA export from nucleus

Inferred from mutant phenotype PubMed 12554669. Source: BHF-UCL

positive regulation of Wnt signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 12655000. Source: BHF-UCL

primary lung bud formation

Inferred from electronic annotation. Source: Ensembl

primitive streak formation

Inferred from electronic annotation. Source: Ensembl

protein localization to nucleus

Inferred from direct assay PubMed 18713067. Source: BHF-UCL

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

response to peptide hormone

Inferred from electronic annotation. Source: Ensembl

response to wounding

Inferred from electronic annotation. Source: Ensembl

thyroid gland development

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

vasculogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 12554669PubMed 12826010. Source: BHF-UCL

nucleus

Inferred from direct assay PubMed 12554669PubMed 12588764PubMed 12826010. Source: BHF-UCL

protein-DNA complex

Inferred from direct assay PubMed 18755198. Source: BHF-UCL

   Molecular_functionDNA binding, bending

Inferred from direct assay PubMed 18755198. Source: BHF-UCL

TBP-class protein binding

Traceable author statement PubMed 19324893. Source: BHF-UCL

chromatin binding

Inferred from electronic annotation. Source: Ensembl

eukaryotic initiation factor 4E binding

Inferred from direct assay PubMed 12554669. Source: BHF-UCL

protein binding

Inferred from physical interaction PubMed 10597310PubMed 12826010. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction PubMed 16540119. Source: BHF-UCL

repressing transcription factor binding

Inferred from direct assay PubMed 15187083. Source: BHF-UCL

sequence-specific DNA binding

Inferred from direct assay PubMed 10871399. Source: BHF-UCL

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

transcription factor binding

Inferred from physical interaction PubMed 15016828. Source: BHF-UCL

transcription regulatory region DNA binding

Inferred from direct assay PubMed 18755198. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 270270Hematopoietically-expressed homeobox protein HHEX
PRO_0000049074

Regions

DNA binding137 – 19660Homeobox
Compositional bias1 – 133133Pro-rich

Experimental info

Sequence conflict1151L → V in AAA02988. Ref.2
Sequence conflict1711A → T in AAH14336. Ref.6

Secondary structure

....... 270
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q03014 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: 9C16BB6D494475FC

FASTA27030,022
        10         20         30         40         50         60 
MQYPHPGPAA GAVGVPLYAP TPLLQPAHPT PFYIEDILGR GPAAPTPAPT LPSPNSSFTS 

        70         80         90        100        110        120 
LVSPYRTPVY EPTPIHPAFS HHSAAALAAA YGPGGFGGPL YPFPRTVNDY THALLRHDPL 

       130        140        150        160        170        180 
GKPLLWSPFL QRPLHKRKGG QVRFSNDQTI ELEKKFETQK YLSPPERKRL AKMLQLSERQ 

       190        200        210        220        230        240 
VKTWFQNRRA KWRRLKQENP QSNKKEELES LDSSCDQRQD LPSEQNKGAS LDSSQCSPSP 

       250        260        270 
ASQEDLESEI SEDSDQEVDI EGDKSYFNAG 

« Hide

References

« Hide 'large scale' references
[1]"Identification of a novel vertebrate homeobox gene expressed in haematopoietic cells."
Crompton M.R., Bartlett T.J., Macgregor A.D., Manfioletti G., Buratti E., Giancotti V., Goodwin G.H.
Nucleic Acids Res. 20:5661-5667(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]"PCR cloning of an orphan homeobox gene (PRH) preferentially expressed in myeloid and liver cells."
Hromas R.A., Collins S.J., Radich J.
Biochem. Biophys. Res. Commun. 195:976-983(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Myeloid leukemia cell.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Mammary gland.
[4]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton 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].
[6]"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: Bone marrow and Uterus.
[7]"HEX: a novel homeobox gene expressed during haematopoiesis and conserved between mouse and human."
Bedford F.K., Ashworth A., Enver T., Wiedemann L.M.
Nucleic Acids Res. 21:1245-1249(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 122-270, TISSUE SPECIFICITY.
Tissue: Leukemia and Peripheral blood monocyte.
[8]"A homology-based molecular model of the proline-rich homeodomain protein Prh, from haematopoietic cells."
Neidle S., Goodwin G.H.
FEBS Lett. 345:93-98(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: 3D-STRUCTURE MODELING OF 136-196.
[9]"Solution structure of RSGI RUH-028, a homeobox domain from human."
RIKEN structural genomics initiative (RSGI)
Submitted (NOV-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 138-194.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X67235 mRNA. Translation: CAA47661.1.
L16499 mRNA. Translation: AAA02988.1.
AK314891 mRNA. Translation: BAG37405.1.
AL590080 Genomic DNA. Translation: CAH74086.1.
CH471066 Genomic DNA. Translation: EAW50087.1.
CH471066 Genomic DNA. Translation: EAW50088.1.
BC014336 mRNA. Translation: AAH14336.1.
BC015110 mRNA. Translation: AAH15110.1.
BC050638 mRNA. Translation: AAH50638.1.
Z21533 mRNA. Translation: CAA79730.1.
CCDSCCDS7423.1.
PIRJN0767.
RefSeqNP_002720.1. NM_002729.4.
UniGeneHs.118651.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2E1ONMR-A138-194[»]
ProteinModelPortalQ03014.
SMRQ03014. Positions 141-194.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109335. 8 interactions.
IntActQ03014. 4 interactions.
MINTMINT-1439118.
STRING9606.ENSP00000282728.

PTM databases

PhosphoSiteQ03014.

Polymorphism databases

DMDM547658.

Proteomic databases

MaxQBQ03014.
PaxDbQ03014.
PRIDEQ03014.

Protocols and materials databases

DNASU3087.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000282728; ENSP00000282728; ENSG00000152804.
GeneID3087.
KEGGhsa:3087.
UCSCuc001kid.3. human.

Organism-specific databases

CTD3087.
GeneCardsGC10P094439.
HGNCHGNC:4901. HHEX.
HPAHPA051894.
MIM604420. gene.
neXtProtNX_Q03014.
PharmGKBPA29274.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG252905.
HOGENOMHOG000049110.
HOVERGENHBG055460.
InParanoidQ03014.
KOK08024.
OMADNSCDQR.
OrthoDBEOG7M0NS8.
PhylomeDBQ03014.
TreeFamTF325047.

Gene expression databases

ArrayExpressQ03014.
BgeeQ03014.
CleanExHS_HHEX.
GenevestigatorQ03014.

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

EvolutionaryTraceQ03014.
GeneWikiHHEX.
GenomeRNAi3087.
NextBio12253.
PROQ03014.
SOURCESearch...

Entry information

Entry nameHHEX_HUMAN
AccessionPrimary (citable) accession number: Q03014
Secondary accession number(s): B1AQ17, Q96CE9
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: July 9, 2014
This is version 144 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 chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM