Q9NZC4 (EHF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ETS homologous factor
Short name=hEHF

Alternative name(s):
ETS domain-containing transcription factor
Epithelium-specific Ets transcription factor 3
Short name=ESE-3

Gene names

Name:	EHF
Synonyms:	ESE3, ESE3B, ESEJ

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	300 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Transcriptional activator that may play a role in regulating epithelial cell differentiation and proliferation. May act as a repressor for a specific subset of ETS/AP-1-responsive genes and as a modulator of the nuclear response to mitogen-activated protein kinase signaling cascades. Binds to DNA sequences containing the consensus nucleotide core sequence GGAA. Involved in regulation of TNFRSF10B/DR5 expression through Ets-binding sequences on the TNFRSF10B/DR5 promoter. May contribute to development and carcinogenesis by acting as a tumor suppressor gene or anti-oncogene. Ref.1 Ref.2 Ref.3 Ref.10 Ref.11
Subcellular location	Nucleus Ref.3 Ref.10.
Tissue specificity	Expressed exclusively in tissues with a high content of epithelial cells. Highly expressed in salivary gland, mammary gland, prostate, and lung. Weakly expressed in kidney and colon. Not detected in heart, brain, placenta, liver, skeletal muscle, spleen, thymus, testis, ovary, small intestine or peripheral blood leukocytes. Ref.1 Ref.2 Ref.3 Ref.10
Induction	By IL1B/interleukin-1 beta and TNF in bronchial smooth muscle cells and fibroblasts. By IL10/interleukin-10 and IFNG/IFN-gamma in monocyte-derived dendritic cells. Ref.10 Ref.12
Domain	The PNT domain acts as a transcriptional activator By similarity. UniProtKB O70273
Sequence similarities	Belongs to the ETS family. Contains 1 ETS DNA-binding domain. Contains 1 PNT (pointed) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell proliferation Traceable author statement Ref.2. Source: UniProtKB epithelial cell differentiation Inferred from expression pattern Ref.2. Source: UniProtKB multicellular organismal development Traceable author statement Ref.2. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from direct assay Ref.2. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred by curator Ref.2. Source: UniProtKB
Molecular_function	DNA binding Inferred from direct assay Ref.2. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 Ref.1 Ref.2 Ref.3 (identifier: Q9NZC4-1)

Also known as: ESE-3B;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 Ref.2 (identifier: Q9NZC4-2)

Also known as: ESE-3A;

The sequence of this isoform differs from the canonical sequence as follows:
     159-181: Missing.

Isoform 3 (identifier: Q9NZC4-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGLPERRGLVLLLSLAEILFKIM

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 300	300	ETS homologous factor		PRO_0000257969
Regions
	Domain	29 – 115	87	PNT
	DNA binding	207 – 289	83	ETS
Natural variations
	Alternative sequence	1	1	M → MGLPERRGLVLLLSLAEILF KIM in isoform 3.		VSP_046373
	Alternative sequence	159 – 181	23	Missing in isoform 2. Ref.2		VSP_052190
	Natural variant	96	1	A → V. Corresponds to variant rs9804460 [ dbSNP | Ensembl ].		VAR_048941
Experimental info
	Sequence conflict	40	1	G → S in AAD30990. Ref.2
	Sequence conflict	40	1	G → S in AAD30991. Ref.2
	Sequence conflict	163	1	S → G in AAD30991. Ref.2
	Sequence conflict	169	1	A → V in AAD30991. Ref.2
	Sequence conflict	196	1	K → E in AAF06998. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ESE-3B) [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 5CABB38BAF852ED0	FASTA	300	34,892
	10 20 30 40 50 60 MILEGGGVMN LNPGNNLLHQ PPAWTDSYST CNVSSGFFGG QWHEIHPQYW TKYQVWEWLQ 70 80 90 100 110 120 HLLDTNQLDA NCIPFQEFDI NGEHLCSMSL QEFTRAAGTA GQLLYSNLQH LKWNGQCSSD 130 140 150 160 170 180 LFQSTHNVIV KTEQTEPSIM NTWKDENYLY DTNYGSTVDL LDSKTFCRAQ ISMTTTSHLP 190 200 210 220 230 240 VAESPDMKKE QDPPAKCHTK KHNPRGTHLW EFIRDILLNP DKNPGLIKWE DRSEGVFRFL 250 260 270 280 290 300 KSEAVAQLWG KKKNNSSMTY EKLSRAMRYY YKREILERVD GRRLVYKFGK NARGWRENEN
	Isoform 2 (ESE-3A) [UniParc]. Checksum: 3BF620E8F1164811	FASTA	277	32,345
	10 20 30 40 50 60 MILEGGGVMN LNPGNNLLHQ PPAWTDSYST CNVSSGFFGG QWHEIHPQYW TKYQVWEWLQ 70 80 90 100 110 120 HLLDTNQLDA NCIPFQEFDI NGEHLCSMSL QEFTRAAGTA GQLLYSNLQH LKWNGQCSSD 130 140 150 160 170 180 LFQSTHNVIV KTEQTEPSIM NTWKDENYLY DTNYGSTVAE SPDMKKEQDP PAKCHTKKHN 190 200 210 220 230 240 PRGTHLWEFI RDILLNPDKN PGLIKWEDRS EGVFRFLKSE AVAQLWGKKK NNSSMTYEKL 250 260 270 SRAMRYYYKR EILERVDGRR LVYKFGKNAR GWRENEN
	Isoform 3 [UniParc]. Checksum: 62D08E04E9C0FFDE	FASTA	322	37,356
	10 20 30 40 50 60 MGLPERRGLV LLLSLAEILF KIMILEGGGV MNLNPGNNLL HQPPAWTDSY STCNVSSGFF 70 80 90 100 110 120 GGQWHEIHPQ YWTKYQVWEW LQHLLDTNQL DANCIPFQEF DINGEHLCSM SLQEFTRAAG 130 140 150 160 170 180 TAGQLLYSNL QHLKWNGQCS SDLFQSTHNV IVKTEQTEPS IMNTWKDENY LYDTNYGSTV 190 200 210 220 230 240 DLLDSKTFCR AQISMTTTSH LPVAESPDMK KEQDPPAKCH TKKHNPRGTH LWEFIRDILL 250 260 270 280 290 300 NPDKNPGLIK WEDRSEGVFR FLKSEAVAQL WGKKKNNSSM TYEKLSRAMR YYYKREILER 310 320 VDGRRLVYKF GKNARGWREN EN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human chromosomal localization, tissue/tumor expression, and regulatory function of the ets family gene EHF." Kleinbaum L.A., Duggan C., Ferreira E., Coffey G.P., Buttice G., Burton F.H. Biochem. Biophys. Res. Commun. 264:119-126(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ALTERNATIVE SPLICING (ISOFORM 2), TISSUE SPECIFICITY. Tissue: Prostate.
[2]	"ESE-3, a novel member of an epithelium-specific ets transcription factor subfamily, demonstrates different target gene specificity from ESE-1." Kas K., Finger E., Grall F., Gu X., Akbarali Y., Boltax J., Weiss A., Oettgen P., Kapeller R., Libermann T.A. J. Biol. Chem. 275:2986-2998(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY. Tissue: Prostate.
[3]	"The epithelium-specific ETS protein EHF/ESE-3 is a context-dependent transcriptional repressor downstream of MAPK signaling cascades." Tugores A., Le J., Sorokina I., Snijders A.J., Duyao M., Reddy P.S., Carlee L., Ronshaugen M., Mushegian A., Watanaskul T., Chu S., Buckler A., Emtage S., McCormick M.K. J. Biol. Chem. 276:20397-20406(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]	"Up-regulation of the epithelial-specific transcription factor Genes hEHF and ESX in advanced prostate cancer." Mitchell S.C., Levin E., Hubert R., Yeramian C., Saffran D.C., Afar D.E.H. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	"New human ESE3B coding sequence from H441 cells." Lei W., Harrod K.S. Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]	"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] (ISOFORM 3). Tissue: Trachea.
[7]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.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].
[9]	"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] (ISOFORM 1). Tissue: Skin.
[10]	"Constitutive and cytokine-induced expression of the ETS transcription factor ESE-3 in the lung." Silverman E.S., Baron R.M., Palmer L.J., Le L., Hallock A., Subramaniam V., Riese R.J., McKenna M.D., Gu X., Libermann T.A., Tugores A., Haley K.J., Shore S., Drazen J.M., Weiss S.T. Am. J. Respir. Cell Mol. Biol. 27:697-704(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
[11]	"ESE-3 transcription factor is involved in the expression of death receptor (DR)-5 through putative Ets sites." Lim J.H., Cho J.-Y., Park Y.B., Park J.-W., Kwon T.K. Biochem. Biophys. Res. Commun. 350:736-741(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Epithelial-specific transcription factor ESE-3 is involved in the development of monocyte-derived DCs." Appel S., Bringmann A., Grunebach F., Weck M.M., Bauer J., Brossart P. Blood 107:3265-3270(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF170583 mRNA. Translation: AAF06998.1. AF124438 mRNA. Translation: AAD30990.1. AF124439 mRNA. Translation: AAD30991.1. AF212848 mRNA. Translation: AAF61670.1. AF203977 mRNA. Translation: AAG35644.1. AY882601 mRNA. Translation: AAW80658.1. AK310867 mRNA. No translation available. AC087783 Genomic DNA. No translation available. AL157952 Genomic DNA. Translation: CAC12700.1. AL157952 Genomic DNA. Translation: CAC12701.1. CH471064 Genomic DNA. Translation: EAW68162.1. CH471064 Genomic DNA. Translation: EAW68163.1. CH471064 Genomic DNA. Translation: EAW68164.1. CH471064 Genomic DNA. Translation: EAW68165.1. CH471064 Genomic DNA. Translation: EAW68166.1. BC038995 mRNA. Translation: AAH38995.1.
IPI	IPI00034048. IPI00172578. IPI00977813.
PIR	JC7115.
RefSeq	NP_001193544.1. NM_001206615.1. NP_001193545.1. NM_001206616.1. NP_036285.2. NM_012153.5.
UniGene	Hs.653859.
3D structure databases
ProteinModelPortal	Q9NZC4.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-8247463.
STRING	9606.ENSP00000257831.
PTM databases
PhosphoSite	Q9NZC4.
Polymorphism databases
DMDM	74762761.
Proteomic databases
PaxDb	Q9NZC4.
PRIDE	Q9NZC4.
Protocols and materials databases
DNASU	26298.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000257831; ENSP00000257831; ENSG00000135373. ENST00000450654; ENSP00000399733; ENSG00000135373. ENST00000530286; ENSP00000433508; ENSG00000135373. ENST00000531794; ENSP00000435835; ENSG00000135373. ENST00000533754; ENSP00000435837; ENSG00000135373.
GeneID	26298.
KEGG	hsa:26298.
UCSC	uc001mvr.2. human. uc009yke.2. human. uc009ykf.2. human.
Organism-specific databases
CTD	26298.
GeneCards	GC11P034599.
HGNC	HGNC:3246. EHF.
MIM	605439. gene.
neXtProt	NX_Q9NZC4.
PharmGKB	PA27681.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG307806.
HOVERGEN	HBG074143.
InParanoid	Q9NZC4.
KO	K09429.
OrthoDB	EOG4Z8XWV.
Gene expression databases
ArrayExpress	Q9NZC4.
Bgee	Q9NZC4.
CleanEx	HS_EHF.
Genevestigator	Q9NZC4.
GermOnline	ENSG00000135373. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.10. 1 hit. 1.10.150.50. 1 hit.
InterPro	IPR000418. Ets_dom. IPR003118. Pointed_dom. IPR013761. SAM/pointed. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF00178. Ets. 1 hit. PF02198. SAM_PNT. 1 hit. [Graphical view]
PRINTS	PR00454. ETSDOMAIN.
SMART	SM00413. ETS. 1 hit. SM00251. SAM_PNT. 1 hit. [Graphical view]
SUPFAM	SSF47769. SAM_homology. 1 hit.
PROSITE	PS00345. ETS_DOMAIN_1. False negative. PS00346. ETS_DOMAIN_2. False negative. PS50061. ETS_DOMAIN_3. 1 hit. PS51433. PNT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	EHF. human.
GenomeRNAi	26298.
NextBio	48647.
SOURCE	Search...

Entry information

Entry name

EHF_HUMAN

Accession

Primary (citable) accession number: Q9NZC4
Secondary accession number(s): D3DR08 , D3DR10, E9PSB2, Q9H509, Q9UKF9, Q9Y5V4, Q9Y5V5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	October 1, 2000
Last modified:	May 29, 2013
This is version 105 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.