Q9BVP2 (GNL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Guanine nucleotide-binding protein-like 3

Alternative name(s):
E2-induced gene 3 protein
Novel nucleolar protein 47
Short name=NNP47
Nucleolar GTP-binding protein 3
Nucleostemin

Gene names

Name:	GNL3
Synonyms:	E2IG3, NS

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

General annotation (Comments)

Function	May be required to maintain the proliferative capacity of stem cells. Stabilizes MDM2 by preventing its ubiquitination, and hence proteasomal degradation By similarity. Ref.2 Ref.8
Subunit structure	Interacts with MDM2; this interaction stabilizes MDM2. Interaction with MDM2 occurs in the nucleoplasm and is triggered by a nucleolar release mechanism, such as mitosis-induced nucleolar disassembly By similarity. Indirectly interacts with TP53, via MDM2-binding By similarity. Ref.8
Subcellular location	Nucleus By similarity. Nucleus › nucleolus By similarity. Note: Shuttles between the nucleus and nucleolus By similarity. Ref.6 Ref.7 Ref.8
Tissue specificity	Increased levels in lung tissue in cancer patients. Ref.2
Domain	The basic domain (B) allows nucleolar localization in the absence of GTP. The intermediate domain (I) inhibits nucleolar localization by the B domain and is required for exit from the nucleolus. Exit from the nucleolus to the nucleoplasm requires both the I and the acidic (A) domains, and may be triggered by GTP hydrolysis By similarity. In contrast to other GTP-binding proteins, this family is characterized by a circular permutation of the GTPase motifs described by a G4-G1-G3 pattern.
Sequence similarities	Belongs to the MMR1/HSR1 GTP-binding protein family. Contains 1 G (guanine nucleotide-binding) domain.
Sequence caution	The sequence AAF09482.1 differs from that shown. Reason: Frameshift at position 516.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil
Ligand	GTP-binding Nucleotide-binding
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell proliferation Inferred from electronic annotation. Source: Compara regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB ribosome biogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	nucleolus Inferred from sequence or structural similarity. Source: UniProtKB nucleoplasm Inferred from electronic annotation. Source: Compara
Molecular_function	GTP binding Inferred from sequence or structural similarity. Source: UniProtKB GTPase activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDM2	Q00987	3	EBI-641642,EBI-389668
PPP2R5A	Q15172	3	EBI-641642,EBI-641666
STAT3	P40763	2	EBI-641642,EBI-518675

Alternative products

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

Isoform 1 (identifier: Q9BVP2-1)

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: Q9BVP2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 549	549	Guanine nucleotide-binding protein-like 3		PRO_0000122444
Regions
	Domain	266 – 347	82	G
	Nucleotide binding	178 – 181	4	GTP Potential
	Nucleotide binding	261 – 268	8	GTP Potential
	Nucleotide binding	305 – 308	4	GTP Potential
	Region	2 – 46	45	Basic By similarity
	Region	282 – 456	175	Intermediate By similarity
	Region	465 – 543	79	Acidic By similarity
	Coiled coil	56 – 95	40	Potential
Amino acid modifications
	Modified residue	79	1	N6-acetyllysine Ref.10
	Modified residue	529	1	Phosphoserine Ref.9 Ref.11
Natural variations
	Alternative sequence	1 – 12	12	Missing in isoform 2.		VSP_013411
	Natural variant	39	1	R → Q. Ref.1 Ref.2 Ref.5 Corresponds to variant rs11177 [ dbSNP | Ensembl ].		VAR_022160
	Natural variant	367	1	V → M. Ref.1 Ref.2 Ref.5 Ref.12 Corresponds to variant rs2289247 [ dbSNP | Ensembl ].		VAR_022161
Experimental info
	Sequence conflict	3	1	R → K in AAV74413. Ref.2
	Sequence conflict	86	1	L → Q in AAV74413. Ref.2
	Sequence conflict	436	1	N → D in AAV74413. Ref.2
	Sequence conflict	463	1	I → M in BAB55169. Ref.3
	Sequence conflict	495	1	V → A in AAV74413. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 5, 2009. Version 2. Checksum: F3928FE1C77C77F4	FASTA	549	61,993
	10 20 30 40 50 60 MKRPKLKKAS KRMTCHKRYK IQKKVREHHR KLRKEAKKRG HKKPRKDPGV PNSAPFKEAL 70 80 90 100 110 120 LREAELRKQR LEELKQQQKL DRQKELEKKR KLETNPDIKP SNVEPMEKEF GLCKTENKAK 130 140 150 160 170 180 SGKQNSKKLY CQELKKVIEA SDVVLEVLDA RDPLGCRCPQ VEEAIVQSGQ KKLVLILNKS 190 200 210 220 230 240 DLVPKENLES WLNYLKKELP TVVFRASTKP KDKGKITKRV KAKKNAAPFR SEVCFGKEGL 250 260 270 280 290 300 WKLLGGFQET CSKAIRVGVI GFPNVGKSSI INSLKQEQMC NVGVSMGLTR SMQVVPLDKQ 310 320 330 340 350 360 ITIIDSPSFI VSPLNSSSAL ALRSPASIEV VKPMEAASAI LSQADARQVV LKYTVPGYRN 370 380 390 400 410 420 SLEFFTVLAQ RRGMHQKGGI PNVEGAAKLL WSEWTGASLA YYCHPPTSWT PPPYFNESIV 430 440 450 460 470 480 VDMKSGFNLE ELEKNNAQSI RAIKGPHLAN SILFQSSGLT NGIIEEKDIH EELPKRKERK 490 500 510 520 530 540 QEEREDDKDS DQETVDEEVD ENSSGMFAAE ETGEALSEET TAGEQSTRSF ILDKIIEEDD AYDFSTDYV
	Isoform 2 [UniParc]. Checksum: 342BCB22B4234056	FASTA	537	60,540
	10 20 30 40 50 60 MTCHKRYKIQ KKVREHHRKL RKEAKKRGHK KPRKDPGVPN SAPFKEALLR EAELRKQRLE 70 80 90 100 110 120 ELKQQQKLDR QKELEKKRKL ETNPDIKPSN VEPMEKEFGL CKTENKAKSG KQNSKKLYCQ 130 140 150 160 170 180 ELKKVIEASD VVLEVLDARD PLGCRCPQVE EAIVQSGQKK LVLILNKSDL VPKENLESWL 190 200 210 220 230 240 NYLKKELPTV VFRASTKPKD KGKITKRVKA KKNAAPFRSE VCFGKEGLWK LLGGFQETCS 250 260 270 280 290 300 KAIRVGVIGF PNVGKSSIIN SLKQEQMCNV GVSMGLTRSM QVVPLDKQIT IIDSPSFIVS 310 320 330 340 350 360 PLNSSSALAL RSPASIEVVK PMEAASAILS QADARQVVLK YTVPGYRNSL EFFTVLAQRR 370 380 390 400 410 420 GMHQKGGIPN VEGAAKLLWS EWTGASLAYY CHPPTSWTPP PYFNESIVVD MKSGFNLEEL 430 440 450 460 470 480 EKNNAQSIRA IKGPHLANSI LFQSSGLTNG IIEEKDIHEE LPKRKERKQE EREDDKDSDQ 490 500 510 520 530 ETVDEEVDEN SSGMFAAEET GEALSEETTA GEQSTRSFIL DKIIEEDDAY DFSTDYV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Effects of estrogen on global gene expression: identification of novel targets of estrogen action." Charpentier A.H., Bednarek A.K., Daniel R.L., Hawkins K.A., Laflin K.J., Gaddis S., MacLeod M.C., Aldaz C.M. Cancer Res. 60:5977-5983(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS GLN-39 AND MET-367.
[2]	"Cloning of the nucleostemin gene and its function in transforming human embryonic bone marrow mesenchymal stem cells into F6 tumor cells." Han C., Zhang X., Xu W., Wang W., Qian H., Chen Y. Int. J. Mol. Med. 16:205-213(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, VARIANTS GLN-39 AND MET-367.
[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] (ISOFORMS 1 AND 2).
[4]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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), VARIANTS GLN-39 AND MET-367. Tissue: Eye.
[6]	"Directed proteomic analysis of the human nucleolus." Andersen J.S., Lyon C.E., Fox A.H., Leung A.K.L., Lam Y.W., Steen H., Mann M., Lamond A.I. Curr. Biol. 12:1-11(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION.
[7]	"Functional proteomic analysis of human nucleolus." Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C., Greco A., Hochstrasser D.F., Diaz J.-J. Mol. Biol. Cell 13:4100-4109(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"A nucleolar mechanism controlling cell proliferation in stem and cancer cells." Tsai R.Y.L., McKay R.D.G. Genes Dev. 16:2991-3003(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TP53, SUBCELLULAR LOCATION.
[9]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-529, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[10]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-79, MASS SPECTROMETRY.
[11]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-529, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] MET-367, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF191018 mRNA. Translation: AAF09482.1. Frameshift. AY825265 mRNA. Translation: AAV74413.1. AK027514 mRNA. Translation: BAB55168.1. AK027516 mRNA. Translation: BAB55169.1. AK315484 mRNA. Translation: BAG37868.1. AC104446 Genomic DNA. No translation available. BC001024 mRNA. Translation: AAH01024.1.
IPI	IPI00003886. IPI00306380.
RefSeq	NP_055181.3. NM_014366.4. NP_996561.1. NM_206825.1. NP_996562.1. NM_206826.1.
UniGene	Hs.313544.
3D structure databases
ProteinModelPortal	Q9BVP2.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BVP2. 15 interactions.
MINT	MINT-1405256.
STRING	9606.ENSP00000395772.
PTM databases
PhosphoSite	Q9BVP2.
Polymorphism databases
DMDM	229462872.
2D gel databases
SWISS-2DPAGE	Q9BVP2.
Proteomic databases
PaxDb	Q9BVP2.
PRIDE	Q9BVP2.
Protocols and materials databases
DNASU	26354.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000394799; ENSP00000378278; ENSG00000163938. ENST00000418458; ENSP00000395772; ENSG00000163938.
GeneID	26354.
KEGG	hsa:26354.
UCSC	uc003dfd.3. human.
Organism-specific databases
CTD	26354.
GeneCards	GC03P052718.
H-InvDB	HIX0003367.
HGNC	HGNC:29931. GNL3.
HPA	CAB020770.
MIM	608011. gene.
neXtProt	NX_Q9BVP2.
PharmGKB	PA134952132.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1161.
HOGENOM	HOG000207716.
HOVERGEN	HBG051747.
InParanoid	Q9BVP2.
KO	K14538.
OMA	KLYCQEL.
OrthoDB	EOG4D26Q4.
Gene expression databases
ArrayExpress	Q9BVP2.
Bgee	Q9BVP2.
CleanEx	HS_GNL3.
Genevestigator	Q9BVP2.
GermOnline	ENSG00000163938. Homo sapiens.
Family and domain databases
InterPro	IPR014813. Gnl3_N_dom. IPR006073. GTP_binding_domain. [Graphical view]
Pfam	PF08701. GN3L_Grn1. 1 hit. PF01926. MMR_HSR1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	GNL3. human.
GenomeRNAi	26354.
NextBio	48693.
SOURCE	Search...

Entry information

Entry name

GNL3_HUMAN

Accession

Primary (citable) accession number: Q9BVP2
Secondary accession number(s): B2RDC1 , Q5PU80, Q96SV6, Q96SV7, Q9UJY0

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	May 5, 2009
Last modified:	May 1, 2013
This is version 108 of the entry and version 2 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.