Q8C878 (UBA3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NEDD8-activating enzyme E1 catalytic subunit
EC=6.3.2.-

Alternative name(s):
NEDD8-activating enzyme E1C
Ubiquitin-activating enzyme E1C
Ubiquitin-like modifier-activating enzyme 3
Short name=Ubiquitin-activating enzyme 3

Gene names

Name:	Uba3
Synonyms:	Ube1c

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	462 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Down-regulates steroid receptor activity. Necessary for cell cycle progression. Ref.5
Enzyme regulation	Binding of TP53BP2 to the regulatory subunit NAE1 decreases activity By similarity.
Pathway	Protein modification; protein neddylation.
Subunit structure	Heterodimer of UBA3 and NAE1. Interacts with NEDD8, UBE2F and UBE2M. Binds ESR1 and ESR2 with bound steroid ligand By similarity. Interacts with TBATA. Ref.6
Involvement in disease	Defects in Uba3 are a cause of embryonic lethality. Mouse embryos deficient in Uba3 die at the preimplantation stage.
Miscellaneous	Arg-211 acts as a selectivity gate, preventing misactivation of ubiquitin by this NEDD8-specific E1 complex By similarity.
Sequence similarities	Belongs to the ubiquitin-activating E1 family. UBA3 subfamily.

Ontologies

Keywords
Biological process	Cell cycle Ubl conjugation pathway
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	endomitotic cell cycle Inferred from mutant phenotype Ref.5. Source: MGI negative regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara protein neddylation Inferred from electronic annotation. Source: UniProtKB-UniPathway regulation of cell cycle Inferred from mutant phenotype Ref.5. Source: MGI
Cellular_component	nucleus Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW NEDD8 activating enzyme activity Traceable author statement Ref.5. Source: MGI acid-amino acid ligase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q8C878-1)

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: Q8C878-2)

The sequence of this isoform differs from the canonical sequence as follows:
     396-462: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 462	462	NEDD8-activating enzyme E1 catalytic subunit		PRO_0000194942
Regions
	Nucleotide binding	100 – 124	25	ATP By similarity
	Nucleotide binding	148 – 171	24	ATP By similarity
	Region	53 – 70	18	Interaction with UBE2M N-terminus By similarity
	Region	157 – 161	5	Interaction with UBE2M N-terminus By similarity
	Region	192 – 217	26	Interaction with UBE2M N-terminus By similarity
	Region	227 – 229	3	Interaction with NEDD8 By similarity
	Region	242 – 248	7	Interaction with NAE1 By similarity
	Region	292 – 295	4	Interaction with NAE1 By similarity
	Region	331 – 338	8	Interaction with UBE2M N-terminus By similarity
	Region	352 – 357	6	Interaction with NEDD8 By similarity
	Region	368 – 462	95	Interaction with UBE2M core domain By similarity
Sites
	Active site	237	1	Glycyl thioester intermediate By similarity
	Site	211	1	Determines specificity for NEDD8 By similarity
Natural variations
	Alternative sequence	396 – 462	67	Missing in isoform 2.		VSP_010787
Experimental info
	Sequence conflict	147	1	K → E in BAB29346. Ref.1
	Sequence conflict	334	1	S → G in BAB29346. Ref.1
	Sequence conflict	397	1	M → I in BAC33258. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 4034CE39E6E9A14E	FASTA	462	51,737
	10 20 30 40 50 60 MADGEEPEKK RRRIEELLAE KMAVDGGCGD TGDWEGRWNH VKKFLERSGP FTHPDFEPST 70 80 90 100 110 120 ESLQFLLDTC KVLVIGAGGL GCELLKNLAL SGFRQIHVID MDTIDVSNLN RQFLFRPKDV 130 140 150 160 170 180 GRPKAEVAAE FLNDRVPNCN VVPHFNKIQD FNDTFYRQFH IIVCGLDSII ARRWINGMLI 190 200 210 220 230 240 SLLNYEDGVL DPSSIVPLID GGTEGFKGNA RVILPGMTAC IECTLELYPP QVNFPMCTIA 250 260 270 280 290 300 SMPRLPEHCI EYVRMLQWPK EQPFGDGVPL DGDDPEHIQW IFQKSIERAS QYNIRGVTYR 310 320 330 340 350 360 LTQGVVKRII PAVASTNAVI AAVCATEVFK IATSAYIPLN NYLVFNDVDG LYTYTFEAER 370 380 390 400 410 420 KENCPACSQL PQNIQFSPSA KLQEVLDYLT NSASLQMKSP AITATLEGKN RTLYLQSVTS 430 440 450 460 IEERTRPNLS KTLKELGLVD GQELAVADVT TPQTVLFKLH FT
	Isoform 2 [UniParc]. Checksum: 01E494E63C4166CB	FASTA	395	44,326
	10 20 30 40 50 60 MADGEEPEKK RRRIEELLAE KMAVDGGCGD TGDWEGRWNH VKKFLERSGP FTHPDFEPST 70 80 90 100 110 120 ESLQFLLDTC KVLVIGAGGL GCELLKNLAL SGFRQIHVID MDTIDVSNLN RQFLFRPKDV 130 140 150 160 170 180 GRPKAEVAAE FLNDRVPNCN VVPHFNKIQD FNDTFYRQFH IIVCGLDSII ARRWINGMLI 190 200 210 220 230 240 SLLNYEDGVL DPSSIVPLID GGTEGFKGNA RVILPGMTAC IECTLELYPP QVNFPMCTIA 250 260 270 280 290 300 SMPRLPEHCI EYVRMLQWPK EQPFGDGVPL DGDDPEHIQW IFQKSIERAS QYNIRGVTYR 310 320 330 340 350 360 LTQGVVKRII PAVASTNAVI AAVCATEVFK IATSAYIPLN NYLVFNDVDG LYTYTFEAER 370 380 390 KENCPACSQL PQNIQFSPSA KLQEVLDYLT NSASL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Embryonic head, Kidney and Placenta.
[2]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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] OF 3-462 (ISOFORM 1).
[4]	"Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway." Gong L., Yeh E.T.H. J. Biol. Chem. 274:12036-12042(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 9-462 (ISOFORM 1). Tissue: Liver.
[5]	"The NEDD8 system is essential for cell cycle progression and morphogenetic pathway in mice." Tateishi K., Omata M., Tanaka K., Chiba T. J. Cell Biol. 155:571-580(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 9-462 (ISOFORM 1), FUNCTION. Strain: C57BL/6.
[6]	"Tbata modulates thymic stromal cell proliferation and thymus function." Flomerfelt F.A., El Kassar N., Gurunathan C., Chua K.S., League S.C., Schmitz S., Gershon T.R., Kapoor V., Yan X.Y., Schwartz R.H., Gress R.E. J. Exp. Med. 207:2521-2532(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TBATA.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK014433 mRNA. Translation: BAB29346.1. AK032514 mRNA. Translation: BAC27905.1. AK048148 mRNA. Translation: BAC33258.1. AK159381 mRNA. Translation: BAE35036.1. AK168859 mRNA. Translation: BAE40680.1. CH466523 Genomic DNA. Translation: EDK99352.1. BC002002 mRNA. Translation: AAH02002.1. AF077330 mRNA. Translation: AAC27323.1. AY029181 mRNA. Translation: AAK33015.1.
IPI	IPI00226943. IPI00453622.
RefSeq	NP_001104576.1. NM_001111106.1. NP_035796.2. NM_011666.2.
UniGene	Mm.277626.
3D structure databases
ProteinModelPortal	Q8C878.
SMR	Q8C878. Positions 33-462.
ModBase	Search...
PTM databases
PhosphoSite	Q8C878.
Proteomic databases
PaxDb	Q8C878.
PRIDE	Q8C878.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000089287; ENSMUSP00000086701; ENSMUSG00000030061.
GeneID	22200.
KEGG	mmu:22200.
UCSC	uc009dam.2. mouse.
Organism-specific databases
CTD	9039.
MGI	MGI:1341217. Uba3.
Phylogenomic databases
eggNOG	COG0476.
GeneTree	ENSGT00550000074831.
HOGENOM	HOG000166793.
HOVERGEN	HBG082736.
InParanoid	Q3TG68.
KO	K10686.
OMA	DHIQWIF.
Enzyme and pathway databases
UniPathway	UPA00885.
Gene expression databases
ArrayExpress	Q8C878.
Bgee	Q8C878.
CleanEx	MM_UBA3.
Genevestigator	Q8C878.
GermOnline	ENSMUSG00000030061. Mus musculus.
Family and domain databases
Gene3D	1.10.10.520. 1 hit. 3.10.20.260. 1 hit. 3.40.50.720. 2 hits.
InterPro	IPR014929. E2_binding. IPR009036. Molybdenum_cofac_synth_MoeB. IPR016040. NAD(P)-bd_dom. IPR000594. ThiF_NAD_FAD-bd. IPR023318. Ub_act_enz_dom_a. IPR000127. UBact_repeat. IPR019572. Ubiquitin-activating_enzyme. IPR018074. UBQ-activ_enz_E1_AS. [Graphical view]
Pfam	PF08825. E2_bind. 1 hit. PF00899. ThiF. 1 hit. PF10585. UBA_e1_thiolCys. 1 hit. PF02134. UBACT. 1 hit. [Graphical view]
SUPFAM	SSF69572. MoeB. 1 hit.
PROSITE	PS00536. UBIQUITIN_ACTIVAT_1. False negative. PS00865. UBIQUITIN_ACTIVAT_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	302185.
SOURCE	Search...

Entry information

Entry name

UBA3_MOUSE

Accession

Primary (citable) accession number: Q8C878
Secondary accession number(s): O88598, Q3TG68, Q9D6B7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	July 27, 2011
Last modified:	May 29, 2013
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program