O60447 (EVI5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ecotropic viral integration site 5 protein homolog
Short name=EVI-5

Alternative name(s):
Neuroblastoma stage 4S gene protein

Gene names

Name:	EVI5
Synonyms:	NB4S

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

General annotation (Comments)

Function	Functions as a regulator of cell cycle progression by stabilizing the FBXO5 protein and promoting cyclin-A accumulation during interphase. May play a role in cytokinesis. Ref.4
Subunit structure	Dimeric and monomeric. Interacts with alpha- and gamma-tubulin. Interacts with FBXO5. Interacts with the chromosome passenger complex (CPC) which is at least composed of AURKB/aurora-B, BIRC5/survivin, CDCA8/borealin and INCENP. Ref.3 Ref.4 Ref.5
Subcellular location	Nucleus. Cytoplasm › cytoskeleton › centrosome. Cytoplasm › cytoskeleton › spindle. Note: Associates with the mitotic spindle through anaphase and remains within the midzone and midbody until completion of cytokinesis. Ref.3 Ref.4 Ref.5
Tissue specificity	Expressed in various cell lines (at protein level). Expressed in a wide range of tissues including brain and adrenal. Ref.1 Ref.3
Induction	Down-regulated during mitosis through proteasomal degradation. Ref.4
Post-translational modification	Probably phosphorylated by PLK1; may be required for degradation during mitosis. Ref.4 Ubiquitinated. Degradation during prophase is ubiquitin-dependent. Ref.4
Involvement in disease	A chromosomal aberration involving EVI5 is found is a patient with stage 4S neuroblastoma. Translocation t(1;10)(p22;q21) that forms a EVI5-TRNG10 fusion protein. TRNG10 is a probable structural transcript which is normally not translated. Ref.1
Miscellaneous	Depletion of EVI5 by RNAi causes cell cycle arrest and mitotic abnormalities.
Sequence similarities	Contains 1 Rab-GAP TBC domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division
Cellular component	Cytoplasm Cytoskeleton Nucleus
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Domain	Coiled coil
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Traceable author statement Ref.1. Source: ProtInc multicellular organismal development Traceable author statement Ref.1. Source: ProtInc positive regulation of Rab GTPase activity Inferred from electronic annotation. Source: GOC
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW microtubule organizing center Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell spindle Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	Rab GTPase activator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FBXO5	Q9UKT4	6	EBI-852291,EBI-852298
PLK1	P53350	2	EBI-852291,EBI-476768

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 810	810	Ecotropic viral integration site 5 protein homolog		PRO_0000256241
Regions
	Domain	163 – 348	186	Rab-GAP TBC
	Region	1 – 483	483	Interaction with alpha-tubulin, gamma-tubulin, BIRC5 and FBXO5
	Region	128 – 693	566	Dimerization
	Region	377 – 810	434	Targeting to the centrosomes
	Region	487 – 810	324	Interaction with AURKB and INCENP
	Coiled coil	406 – 716	311	Potential
	Compositional bias	28 – 128	101	Ser-rich
Sites
	Site	594	1	Breakpoint for translocation to form EVI5-TRNG10 fusion protein
Amino acid modifications
	Modified residue	776	1	Phosphoserine Ref.6
	Modified residue	778	1	Phosphoserine By similarity
Natural variations
	Natural variant	82	1	D → V. Ref.1 Corresponds to variant rs1064580 [ dbSNP | Ensembl ].		VAR_047753
	Natural variant	336	1	I → V. Ref.1 Corresponds to variant rs2391199 [ dbSNP | Ensembl ].		VAR_028890
	Natural variant	612	1	Q → H. Corresponds to variant rs11808092 [ dbSNP | Ensembl ].		VAR_028891
Experimental info
	Sequence conflict	94	1	R → I in AAC16031. Ref.1
	Sequence conflict	402	1	K → Q in AAC16031. Ref.1
	Sequence conflict	714	1	R → K in AAC16031. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O60447 [UniParc]. Last modified November 30, 2010. Version 3. Checksum: 4A2CC99A9192F632	FASTA	810	92,949
	10 20 30 40 50 60 MVTNKMTAAF RNPSGKQVAT DKVAEKLSST LSWVKNTVSH TVSQMASQVA SPSTSLHTTS 70 80 90 100 110 120 SSTTLSTPAL SPSSPSQLSP DDLELLAKLE EQNRLLETDS KSLRSVNGSR RNSGSSLVSS 130 140 150 160 170 180 SSASSNLSHL EEDSWILWGR IVNEWEDVRK KKEKQVKELV HKGIPHHFRA IVWQLLCSAQ 190 200 210 220 230 240 SMPIKDQYSE LLKMTSPCEK LIRRDIARTY PEHNFFKEKD SLGQEVLFNV MKAYSLVDRE 250 260 270 280 290 300 VGYCQGSAFI VGLLLMQMPE EEAFCVFVKL MQDYRLRELF KPSMAELGLC MYQFECMIQE 310 320 330 340 350 360 HLPELFVHFQ SQSFHTSMYA SSWFLTIFLT TFPLPIATRI FDIFMSEGLE IVFRVGLALL 370 380 390 400 410 420 QMNQAELMQL DMEGMLQHFQ KVIPHQFDGV PDKLIQAAYQ VKYNSKKMKK LEKEYTTIKT 430 440 450 460 470 480 KEMEEQVEIK RLRTENRLLK QRIETLEKHK CSSNYNEDFV LQLEKELVQA RLSEAESQCA 490 500 510 520 530 540 LKEMQDKVLD IEKRNNSLPD ENNIARLQEE LIAVKLREAE AIMGLKELRQ QVKDLEEHWQ 550 560 570 580 590 600 RHLARTTGRW KDPPKKNAMN ELQDELMTIR LREAETQAEI REIKQRMMEM ETQNQINSNH 610 620 630 640 650 660 LRRAEQEVIS LQEKVQYLSA QNKGLLTQLS EAKRKQAEIE CKNKEEVMAV RLREADSIAA 670 680 690 700 710 720 VAELRQHIAE LEIQKEEGKL QGQLNKSDSN QYIGELKDQI AELNHELRCL KGQRGFSGQP 730 740 750 760 770 780 PFDGIHIVNH LIGDDESFHS SDEDFIDNSL QETGVGFPLH GKSGSMSLDP AVADGSESET 790 800 810 EDSVLETRES NQVVQKERPP RRRESYSTTV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"NB4S, a member of the TBC1 domain family of genes, is truncated as a result of a constitutional t(1;10)(p22;q21) chromosome translocation in a patient with stage 4S neuroblastoma." Roberts T., Chernova O., Cowell J.K. Hum. Mol. Genet. 7:1169-1178(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DISEASE, CHROMOSOMAL TRANSLOCATION WITH TRNG10, VARIANTS VAL-82 AND VAL-336. Tissue: Brain.
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"EVI5 is a novel centrosomal protein that binds to alpha- and gamma-tubulin." Faitar S.L., Dabbeekeh J.T.S., Ranalli T.A., Cowell J.K. Genomics 86:594-605(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, OLIGOMERIZATION, SUBCELLULAR LOCATION, INTERACTION WITH ALPHA-TUBULIN AND GAMMA-TUBULIN.
[4]	"The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1." Eldridge A.G., Loktev A.V., Hansen D.V., Verschuren E.W., Reimann J.D.R., Jackson P.K. Cell 124:367-380(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH FBXO5, INDUCTION, UBIQUITINATION, SUBCELLULAR LOCATION, PHOSPHORYLATION BY PLK1.
[5]	"EVI5 protein associates with the INCENP-aurora B kinase-survivin chromosomal passenger complex and is involved in the completion of cytokinesis." Faitar S.L., Sossey-Alaoui K., Ranalli T.A., Cowell J.K. Exp. Cell Res. 312:2325-2335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AURKB; BIRC5 AND INCENP, SUBCELLULAR LOCATION.
[6]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-776, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF008915 mRNA. Translation: AAC16031.1. AL133332 , AC104332, AC104456, AL354890 Genomic DNA. Translation: CAC19437.2. AL354890 , AC104332, AC104456, AL133332 Genomic DNA. Translation: CAI21914.1.
IPI	IPI01018995.
RefSeq	NP_005656.4. NM_005665.4.
UniGene	Hs.594434.
3D structure databases
ProteinModelPortal	O60447.
SMR	O60447. Positions 129-402.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-38024N.
IntAct	O60447. 4 interactions.
STRING	9606.ENSP00000359356.
PTM databases
PhosphoSite	O60447.
Proteomic databases
PaxDb	O60447.
PRIDE	O60447.
Protocols and materials databases
DNASU	7813.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000370331; ENSP00000359356; ENSG00000067208. ENST00000540033; ENSP00000440826; ENSG00000067208.
GeneID	7813.
KEGG	hsa:7813.
UCSC	uc001dox.3. human.
Organism-specific databases
CTD	7813.
GeneCards	GC01M092974.
HGNC	HGNC:3501. EVI5.
HPA	HPA027339.
MIM	602942. gene.
neXtProt	NX_O60447.
PharmGKB	PA27915.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5210.
HOVERGEN	HBG081486.
InParanoid	O60447.
OrthoDB	EOG4548Z6.
Enzyme and pathway databases
Pathway_Interaction_DB	aurora_b_pathway. Aurora B signaling.
Gene expression databases
ArrayExpress	O60447.
Bgee	O60447.
CleanEx	HS_EVI5.
Genevestigator	O60447.
GermOnline	ENSG00000067208. Homo sapiens.
Family and domain databases
InterPro	IPR000195. Rab-GTPase-TBC_dom. [Graphical view]
Pfam	PF00566. RabGAP-TBC. 1 hit. [Graphical view]
SMART	SM00164. TBC. 1 hit. [Graphical view]
SUPFAM	SSF47923. RabGAP_TBC. 2 hits.
PROSITE	PS50086. TBC_RABGAP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	EVI5. human.
GenomeRNAi	7813.
NextBio	30213.
SOURCE	Search...

Entry information

Entry name

EVI5_HUMAN

Accession

Primary (citable) accession number: O60447
Secondary accession number(s): A6NKX8, Q9H1Y9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 92 of the entry and version 3 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.