P61956 (SUMO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Small ubiquitin-related modifier 2
Short name=SUMO-2

Alternative name(s):
HSMT3
SMT3 homolog 2
SUMO-3
Sentrin-2
Ubiquitin-like protein SMT3A
Short name=Smt3A

Gene names

Name:	SUMO2
Synonyms:	SMT3A, SMT3H2

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	95 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ubiquitin-like protein that can be covalently attached to proteins as a monomer or as a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by an E3 ligase such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Polymeric SUMO2 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. Ref.7 Ref.15 Ref.16
Subunit structure	Homotrimer Potential. Crystal packing analysis suggests a possible trimeric assembly, of which the biological significance remains to be determined. Interacts with SAE2 and UBE2I. Covalently attached to a number of proteins. Interacts with PELP1. Interacts with USP25; the interaction sumoylates USP25. Ref.11 Ref.14 Ref.15 Ref.20
Subcellular location	Nucleus. Note: Nuclear bodies. Ref.7 Ref.10
Tissue specificity	Broadly expressed. Ref.7
Post-translational modification	Polymeric chains can be formed through Lys-11 cross-linking. Polymeric SUMO2 chains undergo 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination by RNF4. Cleavage of precursor form by SENP1 or SENP2 is necessary for function.
Sequence similarities	Belongs to the ubiquitin family. SUMO subfamily. Contains 1 ubiquitin-like domain.
Caution	Frequently wrongly assigned as SMT3B in many databases and publications. However, according to initial nomenclature, SUMO2 corresponds to SMT3A (Ref.8).

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
PTM	Acetylation Isopeptide bond Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay Ref.16. Source: UniProtKB protein sumoylation Inferred from direct assay. Source: UniProtKB
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ubiquitin protein ligase binding Inferred from physical interaction Ref.16. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MYB	P10242	3	EBI-473220,EBI-298355
PIAS4	Q8N2W9	3	EBI-473220,EBI-473160

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 93

93

Small ubiquitin-related modifier 2

PRO_0000035949

Propeptide

94 – 95

2

PRO_0000035950

Regions

Domain

16 – 95

80

Ubiquitin-like

Amino acid modifications

Modified residue

11

1

N6-acetyllysine Ref.17

Cross-link

11

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate Ref.9 Ref.16 Ref.18

Cross-link

11

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate

Cross-link

93

Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins)

Natural variations

Natural variant

16

1

D → N. Ref.6
Corresponds to variant rs17850328 [ dbSNP | Ensembl ].

VAR_047508

Experimental info

Mutagenesis

11

1

K → R: Abolishes the formation of poly(SUMO) chains. Ref.9

Sequence conflict

55

1

V → M in AAD45399. Ref.1

Sequence conflict

55

1

V → M in CAA67897. Ref.2

Sequence conflict

55

1

V → M in BAG34779. Ref.3

Sequence conflict

55

1

V → M in EAW89249. Ref.5

Sequence conflict

55

1

V → M in AAH08450. Ref.6

Sequence conflict

55

1

V → M in AAH16775. Ref.6

Sequence conflict

55

1

V → M in AAH22340. Ref.6

Sequence conflict

55

1

V → M in AAH62713. Ref.6

Sequence conflict

55

1

V → M in AAH68465. Ref.6

Sequence conflict

55

1

V → M in AAH70159. Ref.6

Sequence conflict

55

1

V → M in AAH71645. Ref.6

Sequence conflict

55

1

V → M in AAH71646. Ref.6

Sequence conflict

55

1

V → M in AAI07854. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

95

Helix Strand Turn

Details...

Beta strand

18 – 23

6

Beta strand

27 – 34

8

Helix

41 – 51

11

Turn

55 – 57

3

Beta strand

59 – 62

4

Turn

73 – 77

5

Beta strand

82 – 87

6

Sequences

	Sequence		Length	Mass (Da)
	P61956 [UniParc]. Last modified February 8, 2011. Version 2. Checksum: E49DF4AF49BEF08B	FASTA	95	10,839
	10 20 30 40 50 60 MADEKPKEGV KTENNDHINL KVAGQDGSVV QFKIKRHTPL SKLMKAYCER QGLSVRQIRF 70 80 90 RFDGQPINET DTPAQLEMED EDTIDVFQQQ TGGVY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of human homolog HSMT3 to yeast SMT3 suppressor of MIF2 mutations in a centromere protein gene." Mannen H., Tseng H.M., Cho C.L., Li S.S.-L. Biochem. Biophys. Res. Commun. 222:178-180(1996) [PubMed: 8630065] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"SMT3A, a human homologue of the S. cerevisiae SMT3 gene, maps to chromosome 21qter and defines a novel gene family." Lapenta V., Chiurazzi P., van der Spek P.J., Pizzuti A., Hanaoka F., Brahe C. Genomics 40:362-367(1997) [PubMed: 9119407] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"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]. Tissue: Cerebellum.
[4]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed: 16625196] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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].
[6]	"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], VARIANT ASN-16. Tissue: Blood vessel, Bone, Bone marrow, Brain, Lung and Testis.
[7]	"Characterization of a second member of the sentrin family of ubiquitin-like proteins." Kamitani T., Kito K., Nguyen H.P., Fukuda-Kamitani T., Yeh E.T.H. J. Biol. Chem. 273:11349-11353(1998) [PubMed: 9556629] [Abstract] Cited for: FUNCTION, PROTEOLYTIC CLEAVAGE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[8]	"Functional heterogeneity of small ubiquitin-related protein modifiers SUMO-1 versus SUMO-2/3." Saitoh H., Hinchey J. J. Biol. Chem. 275:6252-6258(2000) [PubMed: 10692421] [Abstract] Cited for: IDENTIFICATION.
[9]	"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: SUMOYLATION AT LYS-11, MUTAGENESIS OF LYS-11.
[10]	"Molecular features of human ubiquitin-like SUMO genes and their encoded proteins." Su H.-L., Li S.S.-L. Gene 296:65-73(2002) [PubMed: 12383504] [Abstract] Cited for: SUBCELLULAR LOCATION.
[11]	"Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and conjugation." Tatham M.H., Kim S., Yu B., Jaffray E., Song J., Zheng J., Rodriguez M.S., Hay R.T., Chen Y. Biochemistry 42:9959-9969(2003) [PubMed: 12924945] [Abstract] Cited for: INTERACTION WITH UBE2I.
[12]	"A basis for SUMO protease specificity provided by analysis of human Senp2 and a Senp2-SUMO complex." Reverter D., Lima C.D. Structure 12:1519-1531(2004) [PubMed: 15296745] [Abstract] Cited for: CLEAVAGE.
[13]	"Mapping residues of SUMO precursors essential in differential maturation by SUMO-specific protease, SENP1." Xu Z., Au S.W.N. Biochem. J. 386:325-330(2005) [PubMed: 15487983] [Abstract] Cited for: CLEAVAGE.
[14]	"NXP-2 association with SUMO-2 depends on lysines required for transcriptional repression." Rosendorff A., Sakakibara S., Lu S., Kieff E., Xuan Y., DiBacco A., Shi Y., Shi Y., Gill G. Proc. Natl. Acad. Sci. U.S.A. 103:5308-5313(2006) [PubMed: 16567619] [Abstract] Cited for: INTERACTION WITH PELP1.
[15]	"Mechanism and consequences for paralog-specific sumoylation of ubiquitin-specific protease 25." Meulmeester E., Kunze M., Hsiao H.H., Urlaub H., Melchior F. Mol. Cell 30:610-619(2008) [PubMed: 18538659] [Abstract] Cited for: FUNCTION IN SUMOYLATION OF USP25, INTERACTION WITH USP25.
[16]	"RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation." Tatham M.H., Geoffroy M.C., Shen L., Plechanovova A., Hattersley N., Jaffray E.G., Palvimo J.J., Hay R.T. Nat. Cell Biol. 10:538-546(2008) [PubMed: 18408734] [Abstract] Cited for: FUNCTION, POLYUBIQUITINATION AT LYS-11 BY RNF4.
[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., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-11, MASS SPECTROMETRY.
[18]	"In vivo identification of sumoylation sites by a signature tag and cysteine-targeted affinity purification." Blomster H.A., Imanishi S.Y., Siimes J., Kastu J., Morrice N.A., Eriksson J.E., Sistonen L. J. Biol. Chem. 285:19324-19329(2010) [PubMed: 20388717] [Abstract] Cited for: SUMOYLATION AT LYS-11. 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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]	"Crystal structures of the human SUMO-2 protein at 1.6 A and 1.2 A resolution: implication on the functional differences of SUMO proteins." Huang W.-C., Ko T.-P., Li S.S.-L., Wang A.H.-J. Eur. J. Biochem. 271:4114-4122(2004) [PubMed: 15479240] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 9-93, SUBUNIT.
[21]	"Solution structure of human SUMO-2 (SMT3B), a ubiquitin-like protein." RIKEN structural genomics initiative (RSGI) Submitted (AUG-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 1-93.
[22]	"Crystal structure of SUMO-3-modified thymine-DNA glycosylase." Baba D., Maita N., Jee J.-G., Uchimura Y., Saitoh H., Sugasawa K., Hanaoka F., Tochio H., Hiroaki H., Shirakawa M. J. Mol. Biol. 359:137-147(2006) [PubMed: 16626738] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-93 CONJUGATED TO TDG.
[23]	"Solution structure of human small ubiquitin-like modifier protein isoform 2 (SUMO-2)." Chang C.K., Wang Y.H., Chung T.L., Chang C.F., Li S.S.L., Huang T.H. Submitted (OCT-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 1-95.
+	Additional computationally mapped references.

Web resources

Wikipedia

SUMO protein entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L76416 mRNA. Translation: AAD45399.1.
X99585 mRNA. Translation: CAA67897.1.
AK311837 mRNA. Translation: BAG34779.1.
AC022211 Genomic DNA. No translation available.
CH471099 Genomic DNA. Translation: EAW89249.1.
BC008450 mRNA. Translation: AAH08450.1.
BC016775 mRNA. Translation: AAH16775.1.
BC022340 mRNA. Translation: AAH22340.1.
BC062713 mRNA. Translation: AAH62713.1.
BC068465 mRNA. Translation: AAH68465.1.
BC070159 mRNA. Translation: AAH70159.1.
BC071645 mRNA. Translation: AAH71645.1.
BC071646 mRNA. Translation: AAH71646.1.
BC107853 mRNA. Translation: AAI07854.1.

IPI

IPI00299149.

PIR

JC4760.

RefSeq

NP_001005849.1. NM_001005849.1.
NP_008868.3. NM_006937.3.

UniGene

Hs.380973.
Hs.546298.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WM2	X-ray	1.60	A	12-89	[»]
1WM3	X-ray	1.20	A	17-88	[»]
1WZ0	NMR	-	A	1-91	[»]
1Z5Q	model	-	B	15-93	[»]
2AWT	NMR	-	A	1-95	[»]
2CKH	X-ray	3.20	B	15-93	[»]
2D07	X-ray	2.10	B	1-93	[»]
2IO0	X-ray	2.30	B	15-95	[»]
2IO3	X-ray	3.20	B	15-93	[»]
2IYD	X-ray	3.20	B	15-95	[»]
2RPQ	NMR	-	A	1-93	[»]

ProteinModelPortal

P61956.

SMR

P61956. Positions 1-95.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29253N.

IntAct

P61956. 36 interactions.

MINT

MINT-1373938.

STRING

P61956.

PTM databases

PhosphoSite

P61956.

Polymorphism databases

DMDM

48429130.

Proteomic databases

PRIDE

P61956.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000420826; ENSP00000405965; ENSG00000188612.

GeneID

6613.

KEGG

hsa:6613.

UCSC

uc002jne.1. human.

Organism-specific databases

CTD

6613.

GeneCards

GC17M073163.

H-InvDB

HIX0014166.
HIX0056267.

HGNC

HGNC:11125. SUMO2.

HPA

CAB037314.

MIM

603042. gene.

neXtProt

NX_P61956.

PharmGKB

PA134914683.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG20741.

GeneTree

ENSGT00390000018808.

HOGENOM

HBG436396.

HOVERGEN

HBG053025.

OMA

TETEHIN.

OrthoDB

EOG46HGC8.

PhylomeDB

P61956.

Gene expression databases

ArrayExpress

P61956.

Bgee

P61956.

CleanEx

HS_SUMO2.

Genevestigator

P61956.

GermOnline

ENSG00000188612. Homo sapiens.

Family and domain databases

InterPro

IPR022617. SUMO.
IPR000626. Ubiquitin.
IPR019955. Ubiquitin_supergroup.
[Graphical view]

KO

K12160.

Pfam

PF11976. Rad60-SLD. 1 hit.
[Graphical view]

SMART

SM00213. UBQ. 1 hit.
[Graphical view]

PROSITE

PS50053. UBIQUITIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

25747.

PMAP-CutDB

P61956.

SOURCE

Search...

Entry information

Entry name

SUMO2_HUMAN

Accession

Primary (citable) accession number: P61956
Secondary accession number(s): B2R4I2 , P55855, Q32Q42, Q6IPZ6, Q96HK1

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2004
Last sequence update:	February 8, 2011
Last modified:	January 25, 2012
This is version 95 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.