The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Functional site class:
Sumoylation site
Functional site description:
Sumoylation is a common PTM of nuclear proteins that affects their functional status. SUMO belongs to the large multiprotein family of Ubiquitin-like proteins. The sumoylation modification is achieved by a typical E1-, E2- and E3-ligase based system. Many transcription factors, chromatin proteins and proteins involved in other nuclear functions as well as the nuclear pores are sumoylated. Sumoylation is known to cause dramatic rearrangements of the subnuclear location of modified proteins.
ELMs with same tags:
ELMs with same func. site: LIG_KEPE_1  LIG_KEPE_2  LIG_KEPE_3  MOD_SUMO_for_1  MOD_SUMO_rev_2 
ELM Description:
Motif recognised for modification by SUMO-1
Pattern: [VILMAFP](K).E
Pattern Probability: 0.0019140
Present in taxon: Eukaryota
Interaction Domain:
UQ_con (PF00179) Ubiquitin-conjugating enzyme (Stochiometry: 1 : 1)
PDB Structure: 1KPS
o See 45 Instances for MOD_SUMO_for_1
o Abstract
The SUMO proteins are Small Ubiquitin-related MOdifiers that are covalently conjugated onto lysine residues within target proteins (Tang,2008, Anckar,2007, Geiss-Friedlander,2007). Invertebrates have a single SUMO gene, whereas the SUMO family in vertebrates has three members; SUMO-1, SUMO-2, and SUMO-3. The SUMO proteins are synthesized as inactive precursors, which are processed by SUMO-specific carboxy-terminal hydrolases, resulting in novel double-glycine C-termini. The mature SUMO proteins are then activated by the Aos1/Uba2 activating enzyme (E1) and transferred to the Ubc9 conjugating enzyme (E2). Eventually, the SUMO protein is covalently linked to the target protein by the formation of an isopeptide bond between the carboxyl terminus of SUMO and an epsilon-amino group of a lysine residue of the target protein. The reaction is aided by an E3 ligase, e.g. mammalian PIAS1. This process, termed sumoylation, is reversible by certain SENP family desumoylating proteases.
Most sumoylated proteins are nuclear, and three main functional roles of SUMO have been proposed. (i) Protein targeting: sumoylation has been shown to be important for nuclear import of the RanGAP1 protein, and for recruiting proteins to subnuclear protein complexes (e.g. promyelocytic leukemia protein (PML) to PML nuclear bodies). (ii) Enhancement of protein stability by potential competition with (and inhibition of) ubiquitination. (iii) Transcriptional control (e.g. negative regulation of transcription from the androgen receptor).
A core motif (PhiKxE) has been identified as the sumoylation target for SUMO-1 (Endter,2001, Poukka,2000, Sternsdorf,1999). SUMO-2/3 themselves contain a PhiKxE site, in contrast to SUMO-1, and can thus form polymeric chains (shown in vitro, and in vivo for SUMO-2) (Tatham,2001). The Crystal structure of a complex between SUMO-1, E2 Ligase UBC9, E3 Ligase RanGAP1 and the target protein RanBP2 (3UIP, Gareau,2012) shows, that the hydrophobic residue (leucine) and glutamic acid bind to the E2 ligase UBC9 and stabilize lysine, which fits into the catalytic pocket of UBC9. The E3 ligase RanGAP1 binds SUMO-1 with a SIM (SUMO interacting motif) LIG_SUMO_SIM_par_1 motif and stabilizes the N-terminus of SUMO-1 which also fits into the catalytic pocket of UBC9 where the covalent binding of SUMO-1 to RanBP2 takes place.
A number of reports in the literature suggest modified versions of the core motif (PhiKxE):
(i) KEPE motif (LIG_KEPE_1, LIG_KEPE_2 and LIG_KEPE_3): A bioinformatics survey of nuclear proteins revealed a common extended SUMO site, termed the KEPE motif (Diella,2008) in transcriptional and chromatin proteins. The function of the KEPE motif remains to be determined.
(ii) PDSM motif: A Phosphorylation-Dependent Sumo Motif (PhiKxExxSP) has been found (Hietakangas,2006) which consists of the core motif with a phosphorylation site. It was found to regulate sumoylation of the transcription regulators GATA-1, MEF2a and HFSs (Hietakangas,2006).
(iii) NDSM motif: Another extended version of the core motif is the NDSM (Negatively charged amino acid-Dependent Sumoylation Motif), which has clusters of acidic residues downstream from the core motif (Yang,2006). These acidic clusters help to increase the efficiency of sumoylation, for example for the transcription factor ELK-1.
Beside these modified versions of the core motif, multiple high throughput mass spectrometry studies (Matic,2010, Tammsalu,2014, Impens,2014, Hendriks,2014) have shown that an inverted version (E/DxK) of the motif is also used, but less commonly. Yung-Kang Lee et al. (Lee,2007) confirmed the inverted SUMOylation site in TRIM28 by a combination of proteomic screening and site- directed mutagenesis. These finding have also been confirmed by another study (Ivanov,2007). Currently there is no crystal structure of the inverted motif available. There are also some sumoylation sites that do not fit to either the canonical or the reverse motif. ELM annotators have noted that these seem to always be at sites in folded globular domains, raising the possibility that there is a structural motif at these sites, in contrast to the more typical short linear motifs.
o 9 selected references:

o 8 GO-Terms:

o 45 Instances for MOD_SUMO_for_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q15596 NCOA2
238 241 FAVSQPKSIKEEGEDLQSCL TP 1 Homo sapiens (Human)
Q15596 NCOA2
730 733 TAPGSEVTIKQEPVSPKKKE TP 1 Homo sapiens (Human)
Q92754 TFAP2C
9 12 MLWKITDNVKYEEDCEDRHD TP 1 Homo sapiens (Human)
P27540 ARNT
244 247 ILDLKTGTVKKEGQQSSMRM TP 1 Homo sapiens (Human)
P32458 CDC11
411 414 KELREIEARLEKEAKIKQEE TP 1 Saccharomyces cerevisiae (Baker"s yeast)
P17676 CEBPB
173 176 PPPPPPAELKAEPGFEPADC TP 1 Homo sapiens (Human)
P04150 NR3C1
276 279 PSNVTLPQVKTEKEDFIELC TP 1 Homo sapiens (Human)
P04150 NR3C1
292 295 IELCTPGVIKQEKLGTVYCQ TP 1 Homo sapiens (Human)
Q13547 HDAC1
443 446 SNFKKAKRVKTEDEKEKDPE TP 1 Homo sapiens (Human)
Q13547 HDAC1
475 478 EKTKEEKPEAKGVKEEVKLA TP 1 Homo sapiens (Human)
Q00613 HSF1
297 300 LSSSPLVRVKEEPPSPPQSP TP 1 Homo sapiens (Human)
P27782 Lef1
24 27 CATDEMIPFKDEGDPQKEKI TP 1 Mus musculus (House mouse)
P27782 Lef1
266 269 HPAIVTPQVKQEHPHTDSDL TP 1 Mus musculus (House mouse)
P10242 MYB
502 505 LVEDLQDVIKQESDESGIVA TP 1 Homo sapiens (Human)
P10242 MYB
526 529 NGPPLLKKIKQEVESPTDKS TP 1 Homo sapiens (Human)
Q15596 NCOA2
784 787 ASNTKLIAMKTEKEEMSFEP FP 1 Homo sapiens (Human)
P15873 POL30
126 129 LMDIDADFLKIEELQYDSTL TP 1 Saccharomyces cerevisiae (Baker"s yeast)
Q07657 SHS1
425 428 PVRQLGREIKQENENLIRSI TP 1 Saccharomyces cerevisiae (Baker"s yeast)
232 235 RWYKKYKKIKVERVERENLS TP 2 Homo sapiens (Human)
P56524 HDAC4
558 561 AHAQAGVQVKQEPIESDEEE TP 1 Homo sapiens (Human)
Q07657 SHS1
436 439 ENENLIRSIKTESSPKFLNS TP 1 Saccharomyces cerevisiae (Baker"s yeast)
P55854 SUMO3
10 13 SEEKPKEGVKTENDHINLKV TP 1 Homo sapiens (Human)
P23497 SP100
296 299 SCSVRLVDIKKEKPFSNSKV TP 1 Homo sapiens (Human)
Q02447 SP3
550 553 ADSPADIRIKEEEPDPEEWQ TP 1 Homo sapiens (Human)
Q13569 TDG
329 332 QEDAKKMAVKEEKYDPGYEA TP 1 Homo sapiens (Human)
P13202 UL123
449 452 EEREDTVSVKSEPVSEIEEV TP 1 Human herpesvirus 5 strain AD169
349 352 NHPPIPRAVKPEPTNSSVEV TP 2 Homo sapiens (Human)
P04637 TP53
385 388 GQSTSRHKKLMFKTEGPDSD TP 1 Homo sapiens (Human)
P49715 CEBPA
160 163 APALRPLVIKQEPREEDEAK TP 1 Homo sapiens (Human)
P49716 CEBPD
119 122 PGPAAPRLLKREPDWGDGDA TP 1 Homo sapiens (Human)
Q15744 CEBPE
120 123 SYDPRAVAVKEEPRGPEGSR TP 1 Homo sapiens (Human)
P29590 PML
159 162 CFEAHQWFLKHEARPLAELR TP 1 Homo sapiens (Human)
P06401 PGR
387 390 DFQPPALKIKEEEEGAEASA TP 1 Homo sapiens (Human)
P32457 CDC3
3 6 MSLKEEQVSIKQDPEQEERQ TP 2 Saccharomyces cerevisiae (Baker"s yeast)
P61956 SUMO2
10 13 ADEKPKEGVKTENNDHINLK TP 1 Homo sapiens (Human)
P46061 Rangap1
525 528 RLLIHMGLLKSEDKIKAIPS TP 1 Mus musculus (House mouse)
Q14526 HIC1
332 335 GPSLLYRWMKHEPGLGSYGD TP 3 Homo sapiens (Human)
1085 1088 PANSLSSLIKTEVNGFVHVS TP 1 Homo sapiens (Human)
Q02078 MEF2A
402 405 INTNQNISIKSEPISPPRDR TP 3 Homo sapiens (Human)
P37231 PPARG
106 109 KLQEYQSAIKVEPASPPYYS TP 3 Homo sapiens (Human)
P37238 Pparg
106 109 KLQEYQSAIKVEPASPPYYS TP 4 Mus musculus (House mouse)
Q16665 HIF1A
476 479 PALNQEVALKLEPNPESLEL TP 7 Homo sapiens (Human)
Q16665 HIF1A
390 393 DTSSLFDKLKKEPDALTLLA TP 7 Homo sapiens (Human)
P29590 PML
489 492 QTQCPRKVIKMESEEGKEAR TP 9 Homo sapiens (Human)
Q16665 HIF1A
531 534 VDSDMVNEFKLELVEKLFAE TN 4 Homo sapiens (Human)
Please cite: The Eukaryotic Linear Motif Resource ELM: 10 Years and Counting (PMID:24214962)

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