Reviewed, UniProtKB/Swiss-Prot Q9UBE0 (SAE1_HUMAN)

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) [Complete proteome]

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 dimeric enzyme acts as a E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins and formation of a thioester with a conserved cysteine residue on SAE2. Ref.1 Ref.2 Ref.3 Ref.9 Ref.10 Ref.15
Pathway	Protein modification; protein sumoylation.
Subunit structure	Heterodimer of SAE1 and SAE2. The complex binds SUMO proteins via SAE2. 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
Gene Ontology (GO)
Biological process	modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW protein ubiquitination Ref.3 Traceable author statement. Source: UniProtKB
Cellular component	nucleus Ref.3 Non-traceable author statement. Source: UniProtKB
Molecular function	ATP-dependent protein binding Ref.3 Inferred from direct assay. Source: UniProtKB enzyme activator activity Ref.1 Traceable author statement. Source: ProtInc ligase activity Inferred from electronic annotation. Source: UniProtKB-KW protein C-terminus binding Ref.3 Inferred from direct assay. Source: UniProtKB protein heterodimerization activity Ref.3 Traceable author statement. Source: UniProtKB ubiquitin activating enzyme activity Ref.3 Traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CYP1B1	Q16678	1	EBI-743154,EBI-1055133
FKBP4	Q02790	1	EBI-743154,EBI-1047444
SUMO3	P55854	1	EBI-743154,EBI-474067
UBA2	Q9UBT2	1	EBI-743154,EBI-718569
UBE2I	P63279	1	EBI-743154,EBI-80168

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.14

Modified residue

185

1

Phosphoserine Ref.12

Experimental info

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

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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)
	Q9UBE0-1 [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.
[13]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[14]	"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.
[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 SAE2 AND ATP, X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) IN COMPLEX WITH SAE2; SUMO1 AND ATP, FUNCTION.
+	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.

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	[»]

DisProt

DP00485.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UBE0. 12 interactions.

STRING

Q9UBE0.

PTM databases

PhosphoSite

Q9UBE0.

Proteomic databases

PeptideAtlas

Q9UBE0.

PRIDE

Q9UBE0.

Genome annotation databases

Ensembl

ENST00000270225; ENSP00000270225; ENSG00000142230; Homo sapiens. [Genome view]

GeneID

10055.

UCSC

uc002pgc.1. human.

Organism-specific databases

CTD

10055.

GeneCards

GC19P052328.

H-InvDB

HIX0015267.

HGNC

HGNC:30660. SAE1.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13812.

HOGENOM

HBG714097.

HOVERGEN

Q9UBE0.

InParanoid

Q9UBE0.

OMA

GSGIVEC.

PhylomeDB

Q9UBE0.

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-activ_enz_E1-like.
[Graphical view]

Gene3D

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

Pfam

PF00899. ThiF. 1 hit.
[Graphical view]

PRINTS

PR01849. UBIQUITINACT.

ProtoNet

Search...

Other Resources

NextBio

37989.

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 19, 2010
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.