Q99581 (FEV_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein FEV

Alternative name(s):
Fifth Ewing variant protein
PC12 ETS domain-containing transcription factor 1
Short name=PC12 ETS factor 1
Short name=Pet-1

Gene names

Name:	FEV
Synonyms:	PET1

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	238 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Functions as a transcriptional regulator. According to Ref.5, it functions as a transcriptional repressor. Functions in the differentiation and the maintenance of the central serotonergic neurons. May play a role in cell growth. Ref.5
Subcellular location	Nucleus Ref.5.
Tissue specificity	In brain, exclusively expressed in the major serotonergic neurons of the dorsal and median raphe nuclei located in the midbrain and pons. Also detected in prostate and small intestine. Ref.1 Ref.6 Ref.7
Involvement in disease	Sudden infant death syndrome (SIDS) [MIM:272120]: SIDS is the sudden death of an infant younger than 1 year that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of clinical history. Pathophysiologic mechanisms for SIDS may include respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory instability, and inborn errors of metabolism, but definitive pathogenic mechanisms precipitating an infant sudden death remain elusive. Note: Disease susceptibility may be associated with variations affecting the gene represented in this entry. Ref.9 A chromosomal aberration involving FEV is found in Ewing tumors. Translocation t(2;21;22)(q23;q22;q12) that forms a EWSR1-FEV fusion protein with a potential oncogenic activity.
Sequence similarities	Belongs to the ETS family. Contains 1 ETS DNA-binding domain.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Chromosomal rearrangement
Ligand	DNA-binding
Molecular function	Developmental protein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	neuron fate specification Inferred from electronic annotation. Source: Compara neuron maturation Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara transcription from RNA polymerase II promoter Traceable author statement Ref.1. Source: ProtInc
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	double-stranded DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Traceable author statement Ref.1. Source: ProtInc transcription corepressor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 238

238

Protein FEV

PRO_0000344204

Regions

DNA binding

47 – 127

81

ETS

Region

129 – 238

110

May mediate active transcriptional repression

Compositional bias

132 – 210

79

Ala-rich

Sites

Site

18 – 19

2

Breakpoint for insertion to form EWS-FEV fusion protein

Secondary structure

1

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238

Helix Strand Turn

Details...

Helix

49 – 57

9

Helix

60 – 62

3

Turn

63 – 65

3

Beta strand

74 – 76

3

Helix

80 – 90

11

Helix

98 – 105

8

Helix

107 – 110

4

Beta strand

113 – 116

4

Beta strand

121 – 126

6

Helix

128 – 135

8

Sequences

	Sequence		Length	Mass (Da)
	Q99581 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 057E4A76FBDD6E0A	FASTA	238	25,030
	10 20 30 40 50 60 MRQSGASQPL LINMYLPDPV GDGLFKDGKN PSWGPLSPAV QKGSGQIQLW QFLLELLADR 70 80 90 100 110 120 ANAGCIAWEG GHGEFKLTDP DEVARRWGER KSKPNMNYDK LSRALRYYYD KNIMSKVHGK 130 140 150 160 170 180 RYAYRFDFQG LAQACQPPPA HAHAAAAAAA AAAAAQDGAL YKLPAGLAPL PFPGLSKLNL 190 200 210 220 230 MAASAGVAPA GFSYWPGPGP AATAAAATAA LYPSPSLQPP PGPFGAVAAA SHLGGHYH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A new member of the ETS family fused to EWS in Ewing tumors." Peter M., Couturier J., Pacquement H., Michon J., Thomas G., Magdelenat H., Delattre O. Oncogene 14:1159-1164(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHROMOSOMAL TRANSLOCATION WITH EWSR1, TISSUE SPECIFICITY.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: Brain.
[5]	"FEV acts as a transcriptional repressor through its DNA-binding ETS domain and alanine-rich domain." Maurer P., T'Sas F., Coutte L., Callens N., Brenner C., Van Lint C., de Launoit Y., Baert J.-L. Oncogene 22:3319-3329(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]	"The Ets transcription factor Fev is specifically expressed in the human central serotonergic neurons." Maurer P., Rorive S., de Kerchove d'Exaerde A., Schiffmann S.N., Salmon I., de Launoit Y. Neurosci. Lett. 357:215-218(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"Regional distribution and cellular localization of the ETS-domain transcription factor, FEV, mRNA in the human postmortem brain." Iyo A.H., Porter B., Deneris E.S., Austin M.C. Synapse 57:223-228(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"Expression of EWS-ETS fusions in NIH3T3 cells reveals significant differences to Ewing's sarcoma." Braunreiter C.L., Hancock J.D., Coffin C.M., Boucher K.M., Lessnick S.L. Cell Cycle 5:2753-2759(2006) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF THE EWSR1-FEV FUSION PROTEIN.
[9]	"Sudden infant death syndrome: rare mutation in the serotonin system FEV gene." Rand C.M., Berry-Kravis E.M., Zhou L., Fan W., Weese-Mayer D.E. Pediatr. Res. 62:180-182(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SIDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y08976 mRNA. Translation: CAA70169.1.
AC097468 Genomic DNA. Translation: AAX88917.1.
CH471063 Genomic DNA. Translation: EAW70664.1.
BC023511 mRNA. Translation: AAH23511.1.

IPI

IPI00013984.

RefSeq

NP_059991.1. NM_017521.2.

UniGene

Hs.234759.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2YPR	X-ray	2.64	A/B	42-141	[»]
3ZP5	X-ray	2.00	A	42-141	[»]

ProteinModelPortal

Q99581.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000295727.

PTM databases

PhosphoSite

Q99581.

Polymorphism databases

DMDM

74762701.

Proteomic databases

PaxDb

Q99581.

PRIDE

Q99581.

Protocols and materials databases

DNASU

54738.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000295727; ENSP00000295727; ENSG00000163497.

GeneID

54738.

KEGG

hsa:54738.

UCSC

uc002vji.1. human.

Organism-specific databases

CTD

54738.

GeneCards

GC02M219845.

HGNC

HGNC:18562. FEV.

MIM

272120. phenotype.
607150. gene.

neXtProt

NX_Q99581.

PharmGKB

PA134875093.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG287001.

HOGENOM

HOG000234879.

HOVERGEN

HBG095796.

InParanoid

Q99581.

KO

K09437.

OMA

LMFNMYL.

OrthoDB

EOG4J3WJC.

PhylomeDB

Q99581.

Gene expression databases

Bgee

Q99581.

CleanEx

HS_FEV.

Genevestigator

Q99581.

Family and domain databases

Gene3D

1.10.10.10. 1 hit.

InterPro

IPR000418. Ets_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

Pfam

PF00178. Ets. 1 hit.
[Graphical view]

PRINTS

PR00454. ETSDOMAIN.

SMART

SM00413. ETS. 1 hit.
[Graphical view]

PROSITE

PS00345. ETS_DOMAIN_1. 1 hit.
PS00346. ETS_DOMAIN_2. 1 hit.
PS50061. ETS_DOMAIN_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

54738.

NextBio

57329.

SOURCE

Search...

Entry information

Entry name

FEV_HUMAN

Accession

Primary (citable) accession number: Q99581

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 22, 2008
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 118 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.