The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Functional site class:
SUMO interaction site
Functional site description:
Non-covalent binding to SUMO proteins is mediated via the SUMO-interacting motif (SIM). SUMO-interacting proteins predominantly function in the nucleus. The SIM is essential for a variety of cellular processes including transcriptional regulation, sub-nuclear localization, nuclear body assembly, and anti-viral response. Viral proteins are also known to utilize such processes via their SIMs upon host cell invasion.
ELMs with same tags:
ELMs with same func. site: LIG_SUMO_SIM_anti_2  LIG_SUMO_SIM_par_1 
ELM Description:
This SUMO interacting motif variant is for SIMs bound as a beta-augmented strand in the parallel orientation. The SIM peptide inserts into a groove on the SUMO surface so that the motif has a hydrophobic core of four residues (preference V, I or L), the 3rd position being more variable. At the variable 3rd position, in addition to hydrophobic residues, acidic residues (D or E) and the phosphorylatable residue serine are allowed. A stretch of 1 to 5 acidic or phosphorylatable residues is considered necessary C-terminally from the hydrophobic core. Another negative stretch N-terminal to the core appears more optional, though both are usually present. These acidic stretches complement positively-charged residues on the SUMO surface. The length of the acidic stretch may be involved in determining the orientation of binding. When the longer acidic stretch is C-terminal, the beta strand seems usually to be parallel. The two crystal structures of PIAS2 (2ASQ, Song,2005, O75928) and Daxx (2KQS, Chang,2011, O75928) support this theory: They both bind in parallel orientation and have a C-terminal acidic stretch. The crystal structure of RanBP2 (1Z5S, Reverter,2005, P49792) can be contrasted: It binds as an anti-parallel beta strand and has an N-terminal acidic patch. Because of the high similarity of the motif patterns for the parallel and antiparallel orientations, many SIMs will be detected by both of the motifs in ELM. Quite possibly, some SIM peptides may be able to bind to SUMO in both orientations.
Pattern: [DEST]{0,5}.[VILPTM][VIL][DESTVILMA][VIL].{0,1}[DEST]{1,10}
Pattern Probability: 0.0045452
Present in taxon: Eukaryota
Interaction Domain:
Rad60-SLD (PF11976) Ubiquitin-2 like Rad60 SUMO-like (Stochiometry: 1 : 1)
PDB Structure: 2KQS
o See 33 Instances for LIG_SUMO_SIM_par_1
o Abstract
A SUMO-Interacting Motif or SIM (also known as SBM, for SUMO-Binding Motif) is a short linear motif that mediates non-covalent binding of SIM-containing proteins to SUMO. Known instances of SIM function in the nucleus. SIM-containing proteins are involved in cellular functions such as transcriptional regulation, subnuclear localization, nuclear body formation, DNA repair regulation, myeloid formation, tumor suppressor activation, control of differentiation/proliferation, targeting substrates for ubiquitin-mediated proteasomal degradation, and enhancement of sumoylation efficiency. It is of note that eukaryotic cells also utilize SIMs for anti-viral response (e.g. SIM is essential for PML’s (P29590) restriction activity of HSV-1 viral replication (Cuchet,2010)), whereas viruses in turn use SIM for transcriptional control of the host cell (e.g. SIM is essential for the trans-activation function of IE2 (Q6SWV3) protein of HCMV (Kim,2010)). Different SIM motif patterns have been suggested in the literature, but most of these match a limited number of known SIMs (Zhao,2014). The minimal region common to all known SIM instances and required for SIM function is a hydrophobic patch consisting of 3 to 4 hydrophobic residues (I, V, or L) with an optionally single variable residue at the 2nd or 3rd positions. At the variable position, beside hydrophobic residues, acidic- and phosphorylatable residues are alsoallowed. The hydrophobic core is extended at least on one side by a variable length stretch of residues composed of phosphorylatable residues (mainly Serine) and acidic residues. Acidic residues and phosphorylated Serine/Threonine residues increase the affinity of binding to SUMO due to interactions with basic residues of SUMO on the SIM interaction interface. Moreover, phosphorylation of the SIM provides a potential for regulation of sumoylation efficiency and fine-tuning the affinity of binding to SUMO, for instance S737 and S739 in Daxx (Q9UER7) (Chang,2011). Structural analyses of SIM complexed with SUMO have reported similar but slightly different binding patterns. All structurally solved instances of SIM bind as an extra beta strand in a hydrophobic pocket formed by the second beta strand and the single alpha helix of SUMO. The SIMs can bind in both directions to the hydrophobic pocket and therefore bind by either parallel or antiparallel beta-augmentation to the beta sheet of SUMO. RanBP2 (1Z5S) (Reverter,2005) and M-IR2 (2LAS) (Namanja,2012) bind in antiparallel orientation, PIAS2 (2ASQ) (Song,2005) and Daxx (2KQS) (Chang,2011) bind parallel to the second beta strand. The size of the interaction interface with SUMO differs slightly between SIMs. All known structures of SIMs commonly interact with the residues F36, K39, T42, K46, S50 and R54 of SUMO, while each SIM may additionally interact with other residues.
o 17 selected references:

o 9 GO-Terms:

o 33 Instances for LIG_SUMO_SIM_par_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
P29590 PML
555 566 EAEERVVVISSSEDSDAENS TP 4 Homo sapiens (Human)
446 451 SENKKKVEVIDLTIESSSDE TP 3 Homo sapiens (Human)
Q9UT72 rfp2
37 42 GADVSEVTLLDLTRIPEFQP TP 5 Schizosaccharomyces pombe 972h-
Q9UT72 rfp2
18 25 DQRLSPEVIDLTEDIEDDGA TP 5 Schizosaccharomyces pombe 972h-
536 549 DSSTTIIIDSSDETTESPTV TP 1 Homo sapiens (Human)
115 124 KGNISETIVIDDEEDIETNG TP 1 Homo sapiens (Human)
90 95 VGSQADTNVIDLTGDDKDDL TP 3 Homo sapiens (Human)
732 740 KTSVATQCDPEEIIVLSDSD TP 6 Homo sapiens (Human)
586 598 EQDDVLIVDSDEEDSSNNAD TP 2 Homo sapiens (Human)
906 915 ASRSPVVITIDSDSDKDSEV FP 2 Homo sapiens (Human)
Q99AM3 B-cell specific latent nuclear protein
475 481 SFASGLVIVSLRSGIYVKNL FP 3 Human herpesvirus 8
153 166 REVMIIEVSSSEEEESTISE TP 1 Homo sapiens (Human)
73 81 KPNQKKLIVLSDSEVIQLSD TP 1 Homo sapiens (Human)
464 469 ENGKPGADVVDLTLDSSSSS TP 3 Homo sapiens (Human)
1012 1025 SRGQVIIISDSDDDDDERIL TP 2 Homo sapiens (Human)
965 970 ATGSDSSGVIDLTMDDEESG TP 2 Homo sapiens (Human)
276 282 LDDSDEDVILVESQDPPLPS TP 3 Homo sapiens (Human)
262 269 IGSADCNVIEIDDTLDDSDE TP 3 Homo sapiens (Human)
Q60793 Klf4
99 104 RETEEFNDLLDLDFILSNSL TP 3 Mus musculus (House mouse)
Q13330 MTA1
709 715 LPPRPPPPAPVNDEPIVIED TP 3 Homo sapiens (Human)
Q08562 ULS1
370 380 QKNSSIIILSDEDESGAGIN TP 1 Saccharomyces cerevisiae S288c
Q06265 EXOSC9
393 403 IILSDSEEEEMIILEPDKNP TP 1 Homo sapiens (Human)
P78317 RNF4
45 50 LVETAGDEIVDLTCESLEPV TP 1 Homo sapiens (Human)
P78317 RNF4
66 72 DLTHNDSVVIVDERRRPRRN TP 1 Homo sapiens (Human)
P78317 RNF4
57 62 TCESLEPVVVDLTHNDSVVI TP 1 Homo sapiens (Human)
P49792 RANBP2
2631 2637 DSPSDDDVLIVYELTPTAEQ TP 5 Homo sapiens (Human)
P40020 FIR1
758 767 DGKMVEVILLDEDEDVGLKN TP 1 Saccharomyces cerevisiae S288c
P39955 SAP1
231 237 YSDKYISEPILIDLTNDEDD TP 1 Saccharomyces cerevisiae S288c
P23497 SP100
322 332 NQASDIIVISSEDSEGSTDV TP 6 Homo sapiens (Human)
O75928 PIAS2
468 473 EASKKKVDVIDLTIESSSDE TP 6 Homo sapiens (Human)
O75925 PIAS1
458 463 SNKNKKVEVIDLTIDSSSDE TP 3 Homo sapiens (Human)
O13826 rfp1
13 18 SNGIDESSVIDLTRSPSPPV TP 5 Schizosaccharomyces pombe 972h-
O00257 CBX4
461 468 AALPQPEVILLDSDLDEPID TP 3 Homo sapiens (Human)
Please cite: ELM 2016-data update and new functionality of the eukaryotic linear motif resource. (PMID:26615199)

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