Q9UBE0 (SAE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
SUMO-activating enzyme subunit 1

Alternative name(s):
Ubiquitin-like 1-activating enzyme E1A

Gene names

Name:	SAE1
Synonyms:	AOS1, SUA1, UBLE1A

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	346 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.1 Ref.2 Ref.3 Ref.9 Ref.10 Ref.15 Ref.16
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.1 Ref.2 Ref.3 Ref.9
Subcellular location	Nucleus Ref.9.
Tissue specificity	Expression level increases during S phase and drops in G2 phase (at protein level). Ref.9
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.12
Sequence similarities	Belongs to the ubiquitin-activating E1 family.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Nucleus
Molecular function	Ligase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	protein sumoylation Inferred from direct assay Ref.16. Source: UniProtKB protein ubiquitination Traceable author statement Ref.3. Source: UniProtKB
Cellular component	nucleus Non-traceable author statement Ref.3. Source: UniProtKB
Molecular function	ATP-dependent protein binding Inferred from direct assay Ref.3. Source: UniProtKB enzyme activator activity Traceable author statement. Source: ProtInc ligase activity Inferred from electronic annotation. Source: UniProtKB-KW nucleotide binding Inferred from electronic annotation. Source: InterPro protein C-terminus binding Inferred from direct assay Ref.3. Source: UniProtKB protein heterodimerization activity Inferred from physical interaction Ref.16. Source: UniProtKB ubiquitin activating enzyme activity Traceable author statement Ref.3. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
UBA2	Q9UBT2	3	EBI-743154,EBI-718569

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 346

346

SUMO-activating enzyme subunit 1

PRO_0000194966

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.13

Modified residue

185

1

Phosphoserine Ref.12

Experimental info

Mutagenesis

21

1

R → A: Abolishes ATP-dependent activation of SUMO proteins. Ref.16

Mutagenesis

24 – 26

3

RLW → AAA: Abolishes ATP-dependent activation of SUMO proteins. Ref.16

Sequence conflict

158

1

V → A in AAF29104. Ref.4

Sequence conflict

178 – 180

3

KTK → ETD in AAF29104. Ref.4

Sequence conflict

186

1

Q → H in AAF29104. Ref.4

Sequence conflict

273

1

R → G in AAD12785. Ref.1

Secondary structure

1

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346

Helix Strand Turn

Details...

Helix

13 – 26

14

Helix

28 – 35

8

Beta strand

38 – 42

5

Helix

46 – 58

13

Beta strand

61 – 66

6

Helix

76 – 78

3

Helix

91 – 101

11

Beta strand

106 – 111

6

Helix

115 – 117

3

Helix

120 – 123

4

Beta strand

127 – 133

7

Helix

136 – 148

13

Beta strand

152 – 160

9

Beta strand

162 – 168

7

Beta strand

170 – 177

8

Beta strand

206 – 212

7

Helix

216 – 219

4

Helix

227 – 233

7

Helix

239 – 252

14

Beta strand

253 – 255

3

Helix

259 – 261

3

Helix

262 – 278

17

Turn

279 – 281

3

Helix

284 – 286

3

Helix

289 – 293

5

Helix

300 – 319

20

Beta strand

327 – 332

6

Turn

333 – 336

4

Beta strand

337 – 341

5

Sequences

	Sequence		Length	Mass (Da)
	Q9UBE0 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: E2B10A69FF2ED746	FASTA	346	38,450
	10 20 30 40 50 60 MVEKEEAGGG ISEEEAAQYD RQIRLWGLEA QKRLRASRVL LVGLKGLGAE IAKNLILAGV 70 80 90 100 110 120 KGLTMLDHEQ VTPEDPGAQF LIRTGSVGRN RAEASLERAQ NLNPMVDVKV DTEDIEKKPE 130 140 150 160 170 180 SFFTQFDAVC LTCCSRDVIV KVDQICHKNS IKFFTGDVFG YHGYTFANLG EHEFVEEKTK 190 200 210 220 230 240 VAKVSQGVED GPDTKRAKLD SSETTMVKKK VVFCPVKEAL EVDWSSEKAK AALKRTTSDY 250 260 270 280 290 300 FLLQVLLKFR TDKGRDPSSD TYEEDSELLL QIRNDVLDSL GISPDLLPED FVRYCFSEMA 310 320 330 340 PVCAVVGGIL AQEIVKALSQ RDPPHNNFFF FDGMKGNGIV ECLGPK

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: 9920803] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], DIMERIZATION, FUNCTION. 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: 10217437] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], DIMERIZATION, FUNCTION. 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: 10187858] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-11; 109-117 AND 186-193, DIMERIZATION, FUNCTION. Tissue: Cervix carcinoma.
[4]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. , Gu J., Chen S.-J., Chen Z. Genome Res. 10:1546-1560(2000) [PubMed: 11042152] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Umbilical cord blood.
[5]	"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 (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon, Lung and Placenta.
[9]	"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: 11481243] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DIMERIZATION, FUNCTION.
[10]	"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: 11451954] [Abstract] Cited for: FUNCTION.
[11]	"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: 16620772] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY.
[12]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[13]	"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: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[14]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"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: 15660128] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH UBA2; SUMO1 AND ATP, FUNCTION.
[16]	"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: 20164921] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) IN COMPLEX WITH UBA2 AND SUMO1, FUNCTION, MUTAGENESIS OF ARG-21 AND 24-ARG--TRP-26.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF090385 mRNA. Translation: AAD12785.2.
AF046025 mRNA. Translation: AAD23902.2.
AF110956 mRNA. Translation: AAD24433.1.
AF161489 mRNA. Translation: AAF29104.1.
BT007290 mRNA. Translation: AAP35954.1.
AK315624 mRNA. Translation: BAG37992.1.
CH471126 Genomic DNA. Translation: EAW57461.1.
BC000344 mRNA. Translation: AAH00344.1.
BC003611 mRNA. Translation: AAH03611.1.
BC018271 mRNA. Translation: AAH18271.1.

IPI

IPI00033130.

RefSeq

NP_005491.1. NM_005500.2.

UniGene

Hs.515500.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Y8Q	X-ray	2.25	A/C	1-346	[»]
1Y8R	X-ray	2.75	A/D	1-346	[»]
3KYC	X-ray	2.45	A	1-346	[»]
3KYD	X-ray	2.61	A	1-346	[»]

ProteinModelPortal

Q9UBE0.

SMR

Q9UBE0. Positions 25-345.

DisProt

DP00485.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34587N.

IntAct

Q9UBE0. 6 interactions.

MINT

MINT-1205002.

STRING

Q9UBE0.

PTM databases

PhosphoSite

Q9UBE0.

Polymorphism databases

DMDM

42559897.

Proteomic databases

PeptideAtlas

Q9UBE0.

PRIDE

Q9UBE0.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000270225; ENSP00000270225; ENSG00000142230.

GeneID

10055.

KEGG

hsa:10055.

UCSC

uc002pgc.1. human.

Organism-specific databases

CTD

10055.

GeneCards

GC19P047634.

H-InvDB

HIX0015267.

HGNC

HGNC:30660. SAE1.

MIM

613294. gene.

neXtProt

NX_Q9UBE0.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13812.

GeneTree

ENSGT00550000075007.

HOGENOM

HBG714097.

HOVERGEN

HBG080782.

InParanoid

Q9UBE0.

OMA

GSGIVEC.

OrthoDB

EOG4FTW0X.

PhylomeDB

Q9UBE0.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q9UBE0.

Bgee

Q9UBE0.

CleanEx

HS_SAE1.

Genevestigator

Q9UBE0.

GermOnline

ENSG00000142230. Homo sapiens.

Family and domain databases

InterPro

IPR009036. Molybdenum_cofac_synth_MoeB.
IPR016040. NAD(P)-bd_dom.
IPR000594. ThiF_NAD_FAD-bd.
IPR000011. UBQ/SUMO-activ_enz_E1-like.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

KO

K10684.

Pfam

PF00899. ThiF. 1 hit.
[Graphical view]

PRINTS

PR01849. UBIQUITINACT.

SUPFAM

SSF69572. MoeB. 1 hit.

ProtoNet

Search...

Other

NextBio

37989.

SOURCE

Search...

Entry information

Entry name

SAE1_HUMAN

Accession

Primary (citable) accession number: Q9UBE0
Secondary accession number(s): B2RDP5, O95717, Q9P020

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 16, 2004
Last sequence update:	May 1, 2000
Last modified:	January 25, 2012
This is version 102 of the entry and version 1 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.