Q9UBT2 (SAE2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
SUMO-activating enzyme subunit 2
EC=6.3.2.-

Alternative name(s):
Anthracycline-associated resistance ARX
Ubiquitin-like 1-activating enzyme E1B

Gene names

Name:	UBA2
Synonyms:	SAE2, UBLE1B
ORF Names:	HRIHFB2115

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	640 AA.
Sequence status	Complete.
Protein existence	Evidence 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.15 Ref.19 Ref.20 Ref.21
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.15 Ref.19 Ref.20 Ref.21
Subcellular location	Nucleus Ref.11.
Sequence similarities	Belongs to the ubiquitin-activating E1 family.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Ligase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein sumoylation Inferred from direct assay Ref.21. Source: UniProtKB
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW SUMO activating enzyme activity Inferred from direct assay Ref.21. Source: UniProtKB enzyme activator activity Traceable author statement Ref.3. Source: ProtInc ligase activity Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SAE1	Q9UBE0	3	EBI-718569,EBI-743154

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 640

640

SUMO-activating enzyme subunit 2

PRO_0000194968

Regions

Nucleotide binding

24 – 29

6

ATP

Nucleotide binding

56 – 59

4

ATP

Nucleotide binding

95 – 96

2

ATP

Nucleotide binding

117 – 122

6

ATP

Sites

Active site

173

1

Glycyl thioester intermediate Ref.19 Ref.21

Metal binding

158

1

Zinc

Metal binding

161

1

Zinc

Metal binding

441

1

Zinc

Metal binding

444

1

Zinc

Binding site

48

1

ATP

Binding site

72

1

ATP

Amino acid modifications

Modified residue

271

1

N6-acetyllysine Ref.16

Modified residue

507

1

Phosphoserine Ref.17

Modified residue

592

1

Phosphoserine Ref.14

Natural variations

Natural variant

307

1

L → R. Ref.1 Ref.2
Corresponds to variant rs1043062 [ dbSNP | Ensembl ].

VAR_017689

Experimental info

Mutagenesis

56

1

N → A: Abolishes ATP-dependent activation of SUMO proteins. Ref.21

Mutagenesis

57

1

L → A: Strongly reduces ATP-dependent activation of SUMO proteins. Ref.21

Mutagenesis

59

1

R → A: Strongly reduces ATP-dependent activation of SUMO proteins. Ref.21

Mutagenesis

72

1

K → A: Abolishes ATP-dependent activation of SUMO proteins. Ref.21

Mutagenesis

117

1

D → A: Abolishes ATP-dependent activation of SUMO proteins. Ref.21

Mutagenesis

173

1

C → A: Loss of enzyme activity. Ref.21

Mutagenesis

174

1

T → A: Slightly reduced enzyme activity. Ref.21

Mutagenesis

184

1

H → Q: No effect on enzyme activity. Ref.21

Mutagenesis

235

1

I → A: Strongly reduced interaction with UBE2I; when associated with A-238. Ref.20

Mutagenesis

238

1

I → A: Strongly reduced interaction with UBE2I; when associated with A-235. Ref.20

Mutagenesis

484

1

Missing: Strongly reduced interaction with UBE2I. Ref.15

Mutagenesis

485

1

G → GGGG: Strongly reduced interaction with UBE2I. Ref.15

Sequence conflict

229

1

S → C in AAD12784. Ref.1

Sequence conflict

229

1

S → C in AAD23914. Ref.2

Sequence conflict

341

1

E → G in CAB66839. Ref.5

Sequence conflict

456

1

V → L in BAD92109. Ref.9

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

640

Helix Strand Turn

Details...

Helix

9 – 17

9

Beta strand

19 – 23

5

Helix

27 – 39

13

Beta strand

43 – 48

6

Helix

54 – 58

5

Helix

65 – 67

3

Helix

72 – 81

10

Beta strand

88 – 94

7

Helix

103 – 106

4

Beta strand

110 – 114

5

Helix

119 – 132

14

Beta strand

136 – 142

7

Beta strand

145 – 151

7

Turn

153 – 155

3

Beta strand

168 – 171

4

Turn

172 – 176

5

Helix

182 – 197

16

Helix

202 – 204

3

Helix

213 – 215

3

Beta strand

225 – 227

3

Beta strand

234 – 236

3

Helix

241 – 246

6

Helix

251 – 259

9

Helix

261 – 266

6

Helix

270 – 272

3

Beta strand

274 – 276

3

Helix

284 – 289

6

Helix

308 – 310

3

Helix

315 – 335

21

Turn

337 – 339

3

Helix

349 – 365

17

Helix

373 – 381

9

Helix

388 – 406

19

Helix

410 – 412

3

Beta strand

414 – 418

5

Beta strand

426 – 433

8

Turn

442 – 444

3

Beta strand

445 – 447

3

Beta strand

449 – 454

6

Turn

456 – 458

3

Helix

461 – 466

6

Helix

467 – 472

6

Beta strand

479 – 486

8

Beta strand

489 – 491

3

Beta strand

493 – 498

6

Helix

501 – 503

3

Helix

506 – 509

4

Beta strand

516 – 521

6

Turn

522 – 525

4

Beta strand

526 – 534

9

Beta strand

544 – 546

3

Turn

609 – 611

3

Turn

614 – 619

6

Helix

620 – 626

7

Helix

627 – 629

3

Beta strand

636 – 638

3

Sequences

	Sequence		Length	Mass (Da)
	Q9UBT2 [UniParc]. Last modified February 16, 2004. Version 2. Checksum: C12D15293BBF90EB	FASTA	640	71,224
	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

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"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.
[16]	"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, MASS SPECTROMETRY.
[17]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"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].
[19]	"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.
[20]	"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.
[21]	"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.

IPI

IPI00023234.

PIR

T46936.

RefSeq

NP_005490.1. NM_005499.2.

UniGene

Hs.631580.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Y8Q	X-ray	2.25	B/D	1-640	[»]
1Y8R	X-ray	2.75	B/E	1-640	[»]
2PX9	NMR	-	A	166-382	[»]
3KYC	X-ray	2.45	B	1-640	[»]
3KYD	X-ray	2.61	B	1-549	[»]

DisProt

DP00486.

ProteinModelPortal

Q9UBT2.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35136N.

IntAct

Q9UBT2. 4 interactions.

MINT

MINT-1405216.

STRING

9606.ENSP00000246548.

PTM databases

PhosphoSite

Q9UBT2.

Polymorphism databases

DMDM

42559898.

Proteomic databases

PaxDb

Q9UBT2.

PeptideAtlas

Q9UBT2.

PRIDE

Q9UBT2.

Protocols and materials databases

DNASU

10054.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000246548; ENSP00000246548; ENSG00000126261.

GeneID

10054.

KEGG

hsa:10054.

UCSC

uc002nvk.3. human.

Organism-specific databases

CTD

10054.

GeneCards

GC19P034919.

HGNC

HGNC:30661. UBA2.

MIM

613295. gene.

neXtProt

NX_Q9UBT2.

PharmGKB

PA162407583.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0476.

HOGENOM

HOG000216514.

HOVERGEN

HBG060266.

InParanoid

Q9UBT2.

KO

K10685.

OMA

WAKHLFN.

OrthoDB

EOG4PRSQ8.

PhylomeDB

Q9UBT2.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

UniPathway

UPA00886.

Gene expression databases

ArrayExpress

Q9UBT2.

Bgee

Q9UBT2.

CleanEx

HS_UBA2.

Genevestigator

Q9UBT2.

GermOnline

ENSG00000126261. Homo sapiens.

Family and domain databases

Gene3D

1.10.3240.10. 1 hit.
3.40.50.720. 2 hits.

InterPro

IPR009036. Molybdenum_cofac_synth_MoeB.
IPR016040. NAD(P)-bd_dom.
IPR000594. ThiF_NAD_FAD-bd.
IPR023280. Ub-like_act_enz_cat_cys_dom.
IPR000127. UBact_repeat.
IPR019572. Ubiquitin-activating_enzyme.
IPR018074. UBQ-activ_enz_E1_AS.
[Graphical view]

Pfam

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. 1 hit.
PS00865. UBIQUITIN_ACTIVAT_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1615389.

ChiTaRS

UBA2. human.

EvolutionaryTrace

Q9UBT2.

GenomeRNAi

10054.

NextBio

37985.

SOURCE

Search...

Entry information

Entry name

SAE2_HUMAN

Accession

Primary (citable) accession number: Q9UBT2
Secondary accession number(s): O95605 , Q59H87, Q6IBP6, Q9NTJ1, Q9UED2

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 16, 2004
Last sequence update:	February 16, 2004
Last modified:	May 1, 2013
This is version 116 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.