Q00994 (BEX3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein BEX3

Alternative name(s):
Brain-expressed X-linked protein 3
Nerve growth factor receptor-associated protein 1
Ovarian granulosa cell 13.0 kDa protein HGR74
p75NTR-associated cell death executor

Gene names

Name:	NGFRAP1
Synonyms:	BEX3, DXS6984E, NADE

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

General annotation (Comments)

Function	May be a signaling adapter molecule involved in p75NTR-mediated apoptosis induced by NGF. Plays a role in zinc-triggered neuronal death By similarity. May play an important role in the pathogenesis of neurogenetic diseases.
Subunit structure	Self-associates. Interacts with 14-3-3 epsilon (YWHAE). Interacts with DIABLO/SMAC By similarity. Binds to the DEATH domain of p75NTR/NGFR.
Subcellular location	Nucleus. Cytoplasm. Note: Shuttles between the cytoplasm and the nucleus. Associates with replicating mitochondria By similarity.
Tissue specificity	Found in ovarian granulosa cells, testis, prostate and seminal vesicle tissue. High levels also detected in liver. Ref.3
Domain	The nuclear export signal is required for export from the nucleus and the interactions with itself and p75NTR/NGFR By similarity.
Post-translational modification	Ubiquitinated. Degraded by the proteasome By similarity.
Miscellaneous	Binds transition metals By similarity.
Sequence similarities	Belongs to the BEX family.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	Metal-binding
PTM	Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic signaling pathway Traceable author statement. Source: Reactome extrinsic apoptotic signaling pathway via death domain receptors Inferred from electronic annotation. Source: Compara induction of apoptosis Inferred from electronic annotation. Source: Compara multicellular organismal development Traceable author statement Ref.1. Source: ProtInc neurotrophin TRK receptor signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cysteine-type endopeptidase activator activity involved in apoptotic process Traceable author statement. Source: Reactome metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TSC1	Q92574	5	EBI-741753,EBI-1047085

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q00994-1)

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 (identifier: Q00994-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 111

111

Protein BEX3

PRO_0000096688

Regions

Region

68 – 111

44

Interaction with 14-3-3 epsilon By similarity

Region

68 – 93

26

Interaction with p75NTR/NGFR By similarity

Motif

77 – 87

11

Nuclear export signal By similarity

Natural variations

Alternative sequence

1 – 10

10

Missing in isoform 2.

VSP_046343

Secondary structure

1

.

.

.

.

.

.

.

.

.

111

Helix Strand Turn

Details...

Beta strand

2 – 4

3

Turn

22 – 26

5

Beta strand

28 – 30

3

Beta strand

39 – 43

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: 29AA0573282C933E	FASTA	111	12,959
	10 20 30 40 50 60 MANIHQENEE MEQPMQNGEE DRPLGGGEGH QPAGNRRGQA RRLAPNFRWA IPNRQINDGM 70 80 90 100 110 GGDGDDMEIF MEEMREIRRK LRELQLRNCL RILMGELSNH HDHHDEFCLM P
	Isoform 2 [UniParc]. Checksum: ED263FF37D8E838F	FASTA	101	11,762
	10 20 30 40 50 60 MEQPMQNGEE DRPLGGGEGH QPAGNRRGQA RRLAPNFRWA IPNRQINDGM GGDGDDMEIF 70 80 90 100 MEEMREIRRK LRELQLRNCL RILMGELSNH HDHHDEFCLM P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of three abundant mRNAs from human ovarian granulosa cells." Rapp G., Freudenstein J., Klaudiny J., Mucha J., Wempe F., Zimmer M., Scheit K.H. DNA Cell Biol. 9:479-485(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Ovary.
[2]	"NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR." Mukai J., Hachiya T., Shoji-Hoshino S., Kimura M.T., Nadano D., Suvanto P., Hanaoka T., Li Y., Irie S., Greene L.A., Sato T.-A. J. Biol. Chem. 275:17566-17570(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION.
[3]	"Characterization of the Bex gene family in humans, mice, and rats." Alvarez E., Zhou W., Witta S.E., Freed C.R. Gene 357:18-28(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[4]	"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 1). Tissue: Cerebellum.
[5]	"A comparative gene expression profile of the whole eye from human, mouse, and guinea pig." Zhou X., Wang W., Lu F., Hu S., Jiang L., Yan D., Zhang X., Yu X., Yu J., Qu J. Mol. Vis. 13:2214-2221(2007) Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Eye.
[6]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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].
[8]	"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: Eye.
[9]	"Theoretical model for p75NTR-associated cell death executor." Arunkumar S. Submitted (JAN-2005) to the PDB data bank Cited for: 3D-STRUCTURE MODELING OF 1-111.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M38188 mRNA. Translation: AAA63232.1.
AF187064 mRNA. Translation: AAF75129.1.
AY833562 mRNA. Translation: AAX40680.1.
AK315371 mRNA. Translation: BAG37764.1.
EL953547 Genomic DNA. No translation available.
AL606763 Genomic DNA. No translation available.
CH471190 Genomic DNA. Translation: EAW54710.1.
CH471190 Genomic DNA. Translation: EAW54712.1.
BC003190 mRNA. Translation: AAH03190.1.

IPI

IPI00025492.

PIR

C35826.

RefSeq

NP_055195.1. NM_014380.1.
NP_996798.1. NM_206915.1.
NP_996800.1. NM_206917.1.

UniGene

Hs.448588.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1SA6	model	-	A	1-111	[»]

ProteinModelPortal

Q00994.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q00994. 12 interactions.

MINT

MINT-1471079.

STRING

9606.ENSP00000361718.

Polymorphism databases

DMDM

547642.

Proteomic databases

PaxDb

Q00994.

PRIDE

Q00994.

Protocols and materials databases

DNASU

27018.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000299872; ENSP00000299872; ENSG00000166681.
ENST00000361298; ENSP00000354843; ENSG00000166681.
ENST00000372634; ENSP00000361717; ENSG00000166681.
ENST00000372635; ENSP00000361718; ENSG00000166681.
ENST00000372645; ENSP00000361728; ENSG00000166681.

GeneID

27018.

KEGG

hsa:27018.

UCSC

uc004ekh.3. human.

Organism-specific databases

CTD

27018.

GeneCards

GC0XP102631.

HGNC

HGNC:13388. NGFRAP1.

HPA

HPA018886.

MIM

300361. gene.

neXtProt

NX_Q00994.

PharmGKB

PA31616.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG48134.

HOGENOM

HOG000236300.

HOVERGEN

HBG080240.

InParanoid

Q00994.

KO

K12465.

OMA

LMANIHQ.

OrthoDB

EOG4ZKJNP.

PhylomeDB

Q00994.

Enzyme and pathway databases

Pathway_Interaction_DB

p75ntrpathway. p75(NTR)-mediated signaling.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

Bgee

Q00994.

CleanEx

HS_NGFRAP1.

Genevestigator

Q00994.

GermOnline

ENSG00000166681. Homo sapiens.

Family and domain databases

InterPro

IPR007623. BEX.
IPR021156. TF_A-like/BEX-like.
[Graphical view]

Pfam

PF04538. BEX. 1 hit.
[Graphical view]

PIRSF

PIRSF008633. BEX. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

NGFRAP1. human.

GenomeRNAi

27018.

NextBio

49532.

SOURCE

Search...

Entry information

Entry name

BEX3_HUMAN

Accession

Primary (citable) accession number: Q00994
Secondary accession number(s): B2RD17 , D3DXA3, Q5JQT4, Q5JQT5

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	May 29, 2013
This is version 114 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.