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Q8C878

- UBA3_MOUSE

UniProt

Q8C878 - UBA3_MOUSE

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Protein

NEDD8-activating enzyme E1 catalytic subunit

Gene

Uba3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.1 Publication

Enzyme regulationi

Binding of TP53BP2 to the regulatory subunit NAE1 decreases activity.By similarity

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei211 – 2111Determines specificity for NEDD8By similarity
Active sitei237 – 2371Glycyl thioester intermediatePROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi100 – 12425ATPBy similarityAdd
BLAST
Nucleotide bindingi148 – 17124ATPBy similarityAdd
BLAST

GO - Molecular functioni

  1. acid-amino acid ligase activity Source: InterPro
  2. ATP binding Source: UniProtKB-KW
  3. NEDD8 activating enzyme activity Source: RefGenome

GO - Biological processi

  1. endomitotic cell cycle Source: MGI
  2. mitotic cell cycle Source: MGI
  3. protein neddylation Source: RefGenome
  4. regulation of cell cycle Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Cell cycle, Ubl conjugation pathway

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_199115. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00885.

Names & Taxonomyi

Protein namesi
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 namesi
Name:Uba3
Synonyms:Ube1c
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 6

Organism-specific databases

MGIiMGI:1341217. Uba3.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: RefGenome
  2. nucleus Source: RefGenome
Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Defects in Uba3 are a cause of embryonic lethality. Mouse embryos deficient in Uba3 die at the preimplantation stage.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 462461NEDD8-activating enzyme E1 catalytic subunitPRO_0000194942Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ8C878.
PaxDbiQ8C878.
PRIDEiQ8C878.

PTM databases

PhosphoSiteiQ8C878.

Expressioni

Gene expression databases

BgeeiQ8C878.
CleanExiMM_UBA3.
ExpressionAtlasiQ8C878. baseline and differential.
GenevestigatoriQ8C878.

Interactioni

Subunit structurei

Heterodimer of UBA3 and NAE1. Interacts with NEDD8, UBE2F and UBE2M. Binds ESR1 and ESR2 with bound steroid ligand (By similarity). Interacts with TBATA.By similarity1 Publication

Protein-protein interaction databases

BioGridi204409. 2 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ8C878.
SMRiQ8C878. Positions 33-462.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni53 – 7018Interaction with UBE2M N-terminusBy similarityAdd
BLAST
Regioni157 – 1615Interaction with UBE2M N-terminusBy similarity
Regioni192 – 21726Interaction with UBE2M N-terminusBy similarityAdd
BLAST
Regioni227 – 2293Interaction with NEDD8By similarity
Regioni242 – 2487Interaction with NAE1By similarity
Regioni292 – 2954Interaction with NAE1By similarity
Regioni331 – 3388Interaction with UBE2M N-terminusBy similarity
Regioni352 – 3576Interaction with NEDD8By similarity
Regioni368 – 46295Interaction with UBE2M core domainBy similarityAdd
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0476.
GeneTreeiENSGT00550000074831.
HOGENOMiHOG000166793.
HOVERGENiHBG082736.
InParanoidiQ8C878.
KOiK10686.
OMAiDHIQWIF.
TreeFamiTF300499.

Family and domain databases

Gene3Di1.10.10.520. 1 hit.
3.10.20.260. 1 hit.
3.40.50.720. 2 hits.
InterProiIPR014929. 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]
PfamiPF08825. E2_bind. 1 hit.
PF00899. ThiF. 1 hit.
PF10585. UBA_e1_thiolCys. 1 hit.
PF02134. UBACT. 1 hit.
[Graphical view]
SUPFAMiSSF69572. SSF69572. 1 hit.
PROSITEiPS00865. UBIQUITIN_ACTIVAT_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q8C878-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MADGEEPEKK RRRIEELLAE KMAVDGGCGD TGDWEGRWNH VKKFLERSGP
60 70 80 90 100
FTHPDFEPST ESLQFLLDTC KVLVIGAGGL GCELLKNLAL SGFRQIHVID
110 120 130 140 150
MDTIDVSNLN RQFLFRPKDV GRPKAEVAAE FLNDRVPNCN VVPHFNKIQD
160 170 180 190 200
FNDTFYRQFH IIVCGLDSII ARRWINGMLI SLLNYEDGVL DPSSIVPLID
210 220 230 240 250
GGTEGFKGNA RVILPGMTAC IECTLELYPP QVNFPMCTIA SMPRLPEHCI
260 270 280 290 300
EYVRMLQWPK EQPFGDGVPL DGDDPEHIQW IFQKSIERAS QYNIRGVTYR
310 320 330 340 350
LTQGVVKRII PAVASTNAVI AAVCATEVFK IATSAYIPLN NYLVFNDVDG
360 370 380 390 400
LYTYTFEAER KENCPACSQL PQNIQFSPSA KLQEVLDYLT NSASLQMKSP
410 420 430 440 450
AITATLEGKN RTLYLQSVTS IEERTRPNLS KTLKELGLVD GQELAVADVT
460
TPQTVLFKLH FT
Length:462
Mass (Da):51,737
Last modified:July 27, 2011 - v2
Checksum:i4034CE39E6E9A14E
GO
Isoform 2 (identifier: Q8C878-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:395
Mass (Da):44,326
Checksum:i01E494E63C4166CB
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti147 – 1471K → E in BAB29346. (PubMed:16141072)Curated
Sequence conflicti334 – 3341S → G in BAB29346. (PubMed:16141072)Curated
Sequence conflicti397 – 3971M → I in BAC33258. (PubMed:16141072)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei396 – 46267Missing in isoform 2. 1 PublicationVSP_010787Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS51860.1. [Q8C878-1]
RefSeqiNP_001104576.1. NM_001111106.1.
NP_035796.2. NM_011666.2. [Q8C878-1]
XP_006505974.1. XM_006505911.1.
XP_006505975.1. XM_006505912.1.
XP_006505976.1. XM_006505913.1.
UniGeneiMm.277626.

Genome annotation databases

EnsembliENSMUST00000089287; ENSMUSP00000086701; ENSMUSG00000030061. [Q8C878-1]
GeneIDi22200.
KEGGimmu:22200.
UCSCiuc009dam.2. mouse. [Q8C878-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS51860.1. [Q8C878-1 ]
RefSeqi NP_001104576.1. NM_001111106.1.
NP_035796.2. NM_011666.2. [Q8C878-1 ]
XP_006505974.1. XM_006505911.1.
XP_006505975.1. XM_006505912.1.
XP_006505976.1. XM_006505913.1.
UniGenei Mm.277626.

3D structure databases

ProteinModelPortali Q8C878.
SMRi Q8C878. Positions 33-462.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 204409. 2 interactions.

PTM databases

PhosphoSitei Q8C878.

Proteomic databases

MaxQBi Q8C878.
PaxDbi Q8C878.
PRIDEi Q8C878.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000089287 ; ENSMUSP00000086701 ; ENSMUSG00000030061 . [Q8C878-1 ]
GeneIDi 22200.
KEGGi mmu:22200.
UCSCi uc009dam.2. mouse. [Q8C878-1 ]

Organism-specific databases

CTDi 9039.
MGIi MGI:1341217. Uba3.

Phylogenomic databases

eggNOGi COG0476.
GeneTreei ENSGT00550000074831.
HOGENOMi HOG000166793.
HOVERGENi HBG082736.
InParanoidi Q8C878.
KOi K10686.
OMAi DHIQWIF.
TreeFami TF300499.

Enzyme and pathway databases

UniPathwayi UPA00885 .
Reactomei REACT_199115. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

NextBioi 302185.
PROi Q8C878.
SOURCEi Search...

Gene expression databases

Bgeei Q8C878.
CleanExi MM_UBA3.
ExpressionAtlasi Q8C878. baseline and differential.
Genevestigatori Q8C878.

Family and domain databases

Gene3Di 1.10.10.520. 1 hit.
3.10.20.260. 1 hit.
3.40.50.720. 2 hits.
InterProi 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 ]
Pfami PF08825. E2_bind. 1 hit.
PF00899. ThiF. 1 hit.
PF10585. UBA_e1_thiolCys. 1 hit.
PF02134. UBACT. 1 hit.
[Graphical view ]
SUPFAMi SSF69572. SSF69572. 1 hit.
PROSITEi PS00865. UBIQUITIN_ACTIVAT_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: INTERACTION WITH TBATA.

Entry informationi

Entry nameiUBA3_MOUSE
AccessioniPrimary (citable) accession number: Q8C878
Secondary accession number(s): O88598, Q3TG68, Q9D6B7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: July 27, 2011
Last modified: October 29, 2014
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Arg-211 acts as a selectivity gate, preventing misactivation of ubiquitin by this NEDD8-specific E1 complex.By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3