Q03014 (HHEX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	270 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Differentiation Transcription Transcription regulation Wnt signaling pathway
Cellular component	Nucleus
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Developmental protein Repressor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL DNA conformation change Inferred from direct assay PubMed 18755198. Source: BHF-UCL Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW anterior/posterior pattern specification Inferred from sequence or structural similarity. Source: UniProtKB cell cycle Inferred from direct assay PubMed 12554669. Source: BHF-UCL cell proliferation Inferred from direct assay PubMed 12554669. Source: BHF-UCL common bile duct development Inferred from electronic annotation. Source: Compara embryonic heart tube development Inferred from electronic annotation. Source: Compara embryonic organ development Inferred from electronic annotation. Source: Compara endoderm development Inferred from electronic annotation. Source: Compara forebrain morphogenesis Inferred from electronic annotation. Source: Compara gall bladder development Inferred from electronic annotation. Source: Compara hepatic duct development Inferred from electronic annotation. Source: Compara hepatoblast differentiation Inferred from electronic annotation. Source: Compara hepatocyte differentiation Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara interkinetic nuclear migration Inferred from electronic annotation. Source: Compara multicellular organism growth Inferred from electronic annotation. Source: Compara myeloid leukocyte differentiation Inferred from electronic annotation. Source: Compara negative regulation of angiogenesis Inferred from sequence or structural similarity PubMed 15016828. 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 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: Compara poly(A)+ mRNA export from nucleus Inferred from mutant phenotype PubMed 12554669. Source: BHF-UCL positive regulation of Wnt receptor 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: Compara primitive streak formation Inferred from electronic annotation. Source: Compara protein localization to nucleus Inferred from direct assay PubMed 18713067. Source: BHF-UCL regulation of cell proliferation Inferred from electronic annotation. Source: Compara response to peptide hormone stimulus Inferred from electronic annotation. Source: Compara response to wounding Inferred from electronic annotation. Source: Compara thyroid gland development Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW vasculogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm 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_function	DNA 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: Compara eukaryotic initiation factor 4E binding Inferred from direct assay PubMed 12554669. 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 regulatory region DNA binding Inferred from direct assay PubMed 18755198. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 270

270

Hematopoietically-expressed homeobox protein HHEX

PRO_0000049074

Regions

DNA binding

137 – 196

60

Homeobox

Compositional bias

1 – 133

133

Pro-rich

Experimental info

Sequence conflict

115

1

L → V in AAA02988. Ref.2

Sequence conflict

171

1

A → T in AAH14336. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

270

Helix Strand Turn

Details...

Helix

146 – 158

13

Helix

164 – 173

10

Helix

178 – 194

17

Sequences

	Sequence		Length	Mass (Da)
	Q03014 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: 9C16BB6D494475FC	FASTA	270	30,022
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.

IPI

IPI00008771.

PIR

JN0767.

RefSeq

NP_002720.1. NM_002729.4.

UniGene

Hs.118651.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2E1O	NMR	-	A	138-194	[»]

ProteinModelPortal

Q03014.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q03014. 4 interactions.

MINT

MINT-1439118.

STRING

9606.ENSP00000282728.

PTM databases

PhosphoSite

Q03014.

Polymorphism databases

DMDM

547658.

Proteomic databases

PaxDb

Q03014.

PRIDE

Q03014.

Protocols and materials databases

DNASU

3087.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000282728; ENSP00000282728; ENSG00000152804.

GeneID

3087.

KEGG

hsa:3087.

UCSC

uc001kid.3. human.

Organism-specific databases

CTD

3087.

GeneCards

GC10P094439.

HGNC

HGNC:4901. HHEX.

HPA

HPA051894.

MIM

604420. gene.

neXtProt

NX_Q03014.

PharmGKB

PA29274.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG252905.

HOGENOM

HOG000049110.

HOVERGEN

HBG055460.

InParanoid

Q03014.

KO

K08024.

OMA

DNSCDQR.

OrthoDB

EOG4XKV7W.

PhylomeDB

Q03014.

Gene expression databases

ArrayExpress

Q03014.

Bgee

Q03014.

CleanEx

HS_HHEX.

Genevestigator

Q03014.

GermOnline

ENSG00000152804. 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

EvolutionaryTrace

Q03014.

GenomeRNAi

3087.

NextBio

12253.

SOURCE

Search...

Entry information

Entry name

HHEX_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 134 of the entry and version 1 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.