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Q9UBT2 (SAE2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
SUMO-activating enzyme subunit 2

EC=6.3.2.-
Alternative name(s):
Anthracycline-associated resistance ARX
Ubiquitin-like 1-activating enzyme E1B
Ubiquitin-like modifier-activating enzyme 2
Gene names
Name:UBA2
Synonyms:SAE2, UBLE1B
ORF Names:HRIHFB2115
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length640 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

The heterodimer acts as a E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2. Ref.11 Ref.12 Ref.16 Ref.22 Ref.23 Ref.24

Pathway

Protein modification; protein sumoylation.

Subunit structure

Heterodimer of SAE1 and UBA2/SAE2. The heterodimer corresponds to the two domains that are encoded on a single polypeptide chain in ubiquitin-activating enzyme E1. Interacts with UBE2I. Ref.11 Ref.16 Ref.22 Ref.23 Ref.24

Subcellular location

Cytoplasm. Nucleus. Note: Shuttles between the cytoplasm and the nucleus, sumoylation is required either for nuclear translocation or nuclear retention. Ref.11 Ref.21

Post-translational modification

Sumoylated with SUMO1 and SUMO2/3 and by UBC9. Sumoylation at Lys-236 inhibits enzymatic activity. Sumoylation at the C-terminal lysine cluster plays an essential role in nuclear trafficking. Ref.20 Ref.21

Sequence similarities

Belongs to the ubiquitin-activating E1 family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SAE1Q9UBE03EBI-718569,EBI-743154

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 640640SUMO-activating enzyme subunit 2
PRO_0000194968

Regions

Nucleotide binding24 – 296ATP
Nucleotide binding56 – 594ATP
Nucleotide binding95 – 962ATP
Nucleotide binding117 – 1226ATP

Sites

Active site1731Glycyl thioester intermediate Ref.22 Ref.24
Metal binding1581Zinc
Metal binding1611Zinc
Metal binding4411Zinc
Metal binding4441Zinc
Binding site481ATP
Binding site721ATP

Amino acid modifications

Modified residue2711N6-acetyllysine; alternate Ref.17
Modified residue5071Phosphoserine Ref.18
Modified residue5921Phosphoserine Ref.14
Modified residue6131N6-acetyllysine; alternate By similarity
Cross-link190Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.20
Cross-link236Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) Ref.20
Cross-link257Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.20
Cross-link271Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate Ref.20
Cross-link275Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.20
Cross-link611Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.21
Cross-link613Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate Ref.21
Cross-link617Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.21
Cross-link623Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.21

Natural variations

Natural variant3071L → R. Ref.1 Ref.2
Corresponds to variant rs1043062 [ dbSNP | Ensembl ].
VAR_017689

Experimental info

Mutagenesis561N → A: Abolishes ATP-dependent activation of SUMO proteins. Ref.24
Mutagenesis571L → A: Strongly reduces ATP-dependent activation of SUMO proteins. Ref.24
Mutagenesis591R → A: Strongly reduces ATP-dependent activation of SUMO proteins. Ref.24
Mutagenesis721K → A: Abolishes ATP-dependent activation of SUMO proteins. Ref.24
Mutagenesis1171D → A: Abolishes ATP-dependent activation of SUMO proteins. Ref.24
Mutagenesis1731C → A: Loss of enzyme activity. Ref.24
Mutagenesis1741T → A: Slightly reduced enzyme activity. Ref.24
Mutagenesis1841H → Q: No effect on enzyme activity. Ref.24
Mutagenesis2351I → A: Strongly reduced interaction with UBE2I; when associated with A-238. Ref.23
Mutagenesis2381I → A: Strongly reduced interaction with UBE2I; when associated with A-235. Ref.23
Mutagenesis4841Missing: Strongly reduced interaction with UBE2I. Ref.16
Mutagenesis4851G → GGGG: Strongly reduced interaction with UBE2I. Ref.16
Sequence conflict2291S → C in AAD12784. Ref.1
Sequence conflict2291S → C in AAD23914. Ref.2
Sequence conflict3411E → G in CAB66839. Ref.5
Sequence conflict4561V → L in BAD92109. Ref.9

Secondary structure

.......................................................................................................... 640
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UBT2 [UniParc].

Last modified February 16, 2004. Version 2.
Checksum: C12D15293BBF90EB

FASTA64071,224
        10         20         30         40         50         60 
MALSRGLPRE LAEAVAGGRV LVVGAGGIGC ELLKNLVLTG FSHIDLIDLD TIDVSNLNRQ 

        70         80         90        100        110        120 
FLFQKKHVGR SKAQVAKESV LQFYPKANIV AYHDSIMNPD YNVEFFRQFI LVMNALDNRA 

       130        140        150        160        170        180 
ARNHVNRMCL AADVPLIESG TAGYLGQVTT IKKGVTECYE CHPKPTQRTF PGCTIRNTPS 

       190        200        210        220        230        240 
EPIHCIVWAK YLFNQLFGEE DADQEVSPDR ADPEAAWEPT EAEARARASN EDGDIKRIST 

       250        260        270        280        290        300 
KEWAKSTGYD PVKLFTKLFK DDIRYLLTMD KLWRKRKPPV PLDWAEVQSQ GEETNASDQQ 

       310        320        330        340        350        360 
NEPQLGLKDQ QVLDVKSYAR LFSKSIETLR VHLAEKGDGA ELIWDKDDPS AMDFVTSAAN 

       370        380        390        400        410        420 
LRMHIFSMNM KSRFDIKSMA GNIIPAIATT NAVIAGLIVL EGLKILSGKI DQCRTIFLNK 

       430        440        450        460        470        480 
QPNPRKKLLV PCALDPPNPN CYVCASKPEV TVRLNVHKVT VLTLQDKIVK EKFAMVAPDV 

       490        500        510        520        530        540 
QIEDGKGTIL ISSEEGETEA NNHKKLSEFG IRNGSRLQAD DFLQDYTLLI NILHSEDLGK 

       550        560        570        580        590        600 
DVEFEVVGDA PEKVGPKQAE DAAKSITNGS DDGAQPSTST AQEQDDVLIV DSDEEDSSNN 

       610        620        630        640 
ADVSEEERSR KRKLDEKENL SAKRSRIEQK EELDDVIALD 

« Hide

References

« Hide 'large scale' references
[1]"In vitro SUMO-1 modification requires two enzymatic steps, E1 and E2."
Okuma T., Honda R., Ichikawa G., Tsumagari N., Yasuda H.
Biochem. Biophys. Res. Commun. 254:693-698(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-307.
Tissue: Cervix carcinoma.
[2]"Molecular cloning and characterization of human AOS1 and UBA2, components of the sentrin-activating enzyme complex."
Gong L., Li B., Millas S., Yeh E.T.H.
FEBS Lett. 448:185-189(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-307.
Tissue: Placenta.
[3]"Identification of the enzyme required for activation of the small ubiquitin-like protein SUMO-1."
Desterro J.M.P., Rodriguez M.S., Kemp G.D., Hay R.T.
J. Biol. Chem. 274:10618-10624(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]Slapak C., Mizunuma N., Terashima M., Yamauchi T., Kufe D.
Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[6]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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].
Tissue: Skin.
[9]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 346-640.
Tissue: Brain.
[10]"Selection system for genes encoding nuclear-targeted proteins."
Ueki N., Oda T., Kondo M., Yano K., Noguchi T., Muramatsu M.-A.
Nat. Biotechnol. 16:1338-1342(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 536-640.
Tissue: Fetal brain.
[11]"Expression and regulation of the mammalian SUMO-1 E1 enzyme."
Azuma Y., Tan S.-H., Cavenagh M.M., Ainsztein A.M., Saitoh H., Dasso M.
FASEB J. 15:1825-1827(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, DIMERIZATION, FUNCTION.
[12]"Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9."
Tatham M.H., Jaffray E., Vaughan O.A., Desterro J.M.P., Botting C.H., Naismith J.H., Hay R.T.
J. Biol. Chem. 276:35368-35374(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"A general approach for investigating enzymatic pathways and substrates for ubiquitin-like modifiers."
Li T., Santockyte R., Shen R.-F., Tekle E., Wang G., Yang D.C.H., Chock P.B.
Arch. Biochem. Biophys. 453:70-74(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY.
[14]"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-592, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Conformational transition associated with E1-E2 interaction in small ubiquitin-like modifications."
Wang J., Lee B., Cai S., Fukui L., Hu W., Chen Y.
J. Biol. Chem. 284:20340-20348(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBE2I, FUNCTION, MUTAGENESIS OF ASP-484 AND GLY-485.
[17]"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-271, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"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-507, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[19]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"Small ubiquitin-like modifier (SUMO) modification of E1 Cys domain inhibits E1 Cys domain enzymatic activity."
Truong K., Lee T.D., Chen Y.
J. Biol. Chem. 287:15154-15163(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-190; LYS-236; LYS-257; LYS-271 AND LYS-275.
[21]"Sumoylation of SAE2 C terminus regulates SAE nuclear localization."
Truong K., Lee T.D., Li B., Chen Y.
J. Biol. Chem. 287:42611-42619(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, SUMOYLATION AT LYS-611; LYS-613; LYS-617 AND LYS-623.
[22]"Structures of the SUMO E1 provide mechanistic insights into SUMO activation and E2 recruitment to E1."
Lois L.M., Lima C.D.
EMBO J. 24:439-451(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH SAE1; SUMO1; ZINC IONS AND ATP, FUNCTION, SUBUNIT, ACTIVE SITE.
[23]"The intrinsic affinity between E2 and the Cys domain of E1 in ubiquitin-like modifications."
Wang J., Hu W., Cai S., Lee B., Song J., Chen Y.
Mol. Cell 27:228-237(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 166-382 IN COMPLEX WITH UBE2I, MUTAGENESIS OF ILE-235 AND ILE-238, FUNCTION, INTERACTION WITH UBE2I.
[24]"Active site remodelling accompanies thioester bond formation in the SUMO E1."
Olsen S.K., Capili A.D., Lu X., Tan D.S., Lima C.D.
Nature 463:906-912(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) IN COMPLEX WITH SAE1; SUMO1 AND REACTION INTERMEDIATE, FUNCTION, ACTIVE SITE, SUBUNIT, MUTAGENESIS OF ASN-56; LEU-57; ARG-59; LYS-72; ASP-117; CYS-173; THR-174 AND HIS-184.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF090384 mRNA. Translation: AAD12784.1.
AF079566 mRNA. Translation: AAD23914.1.
AF110957 mRNA. Translation: AAD24434.1.
U35832 mRNA. Translation: AAC99992.1.
AL136905 mRNA. Translation: CAB66839.1.
BT009781 mRNA. Translation: AAP88783.1.
CR456756 mRNA. Translation: CAG33037.1.
BC003153 mRNA. Translation: AAH03153.1.
AB208872 mRNA. Translation: BAD92109.1.
AB015337 mRNA. Translation: BAA34795.1.
PIRT46936.
RefSeqNP_005490.1. NM_005499.2.
UniGeneHs.631580.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Y8QX-ray2.25B/D1-640[»]
1Y8RX-ray2.75B/E1-640[»]
2PX9NMR-A166-382[»]
3KYCX-ray2.45B1-640[»]
3KYDX-ray2.61B1-549[»]
DisProtDP00486.
ProteinModelPortalQ9UBT2.
SMRQ9UBT2. Positions 4-591, 607-640.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115365. 62 interactions.
DIPDIP-35136N.
IntActQ9UBT2. 5 interactions.
MINTMINT-1405216.
STRING9606.ENSP00000246548.

Chemistry

ChEMBLCHEMBL2095174.

PTM databases

PhosphoSiteQ9UBT2.

Polymorphism databases

DMDM42559898.

Proteomic databases

PaxDbQ9UBT2.
PeptideAtlasQ9UBT2.
PRIDEQ9UBT2.

Protocols and materials databases

DNASU10054.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000246548; ENSP00000246548; ENSG00000126261.
GeneID10054.
KEGGhsa:10054.
UCSCuc002nvk.3. human.

Organism-specific databases

CTD10054.
GeneCardsGC19P034919.
HGNCHGNC:30661. UBA2.
HPAHPA041436.
MIM613295. gene.
neXtProtNX_Q9UBT2.
PharmGKBPA162407583.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0476.
HOGENOMHOG000216514.
HOVERGENHBG060266.
InParanoidQ9UBT2.
KOK10685.
OMAYACLFSK.
OrthoDBEOG7S7SDB.
PhylomeDBQ9UBT2.
TreeFamTF300765.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
UniPathwayUPA00886.

Gene expression databases

ArrayExpressQ9UBT2.
BgeeQ9UBT2.
CleanExHS_UBA2.
GenevestigatorQ9UBT2.

Family and domain databases

Gene3D1.10.3240.10. 1 hit.
3.40.50.720. 2 hits.
InterProIPR009036. Molybdenum_cofac_synth_MoeB.
IPR016040. NAD(P)-bd_dom.
IPR000594. ThiF_NAD_FAD-bd.
IPR028077. UAE_UbL_dom.
IPR023280. Ub-like_act_enz_cat_cys_dom.
IPR000127. UBact_repeat.
IPR019572. Ubiquitin-activating_enzyme.
IPR018074. UBQ-activ_enz_E1_AS.
[Graphical view]
PfamPF00899. ThiF. 1 hit.
PF14732. UAE_UbL. 1 hit.
PF10585. UBA_e1_thiolCys. 1 hit.
PF02134. UBACT. 1 hit.
[Graphical view]
SUPFAMSSF69572. SSF69572. 2 hits.
PROSITEPS00536. UBIQUITIN_ACTIVAT_1. 1 hit.
PS00865. UBIQUITIN_ACTIVAT_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSUBA2. human.
EvolutionaryTraceQ9UBT2.
GeneWikiUBA2.
GenomeRNAi10054.
NextBio37985.
PROQ9UBT2.
SOURCESearch...

Entry information

Entry nameSAE2_HUMAN
AccessionPrimary (citable) accession number: Q9UBT2
Secondary accession number(s): O95605 expand/collapse secondary AC list , Q59H87, Q6IBP6, Q9NTJ1, Q9UED2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 16, 2004
Last sequence update: February 16, 2004
Last modified: April 16, 2014
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM