SUMO1

Summary

SUMO1 (small ubiquitin like modifier 1, HGNC:12502) is a protein-coding gene on chromosome 2q33.1, encoding Small ubiquitin-related modifier 1 (P63165). Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer.

This gene encodes a protein that is a member of the SUMO (small ubiquitin-like modifier) protein family. It functions in a manner similar to ubiquitin in that it is bound to target proteins as part of a post-translational modification system. However, unlike ubiquitin which targets proteins for degradation, this protein is involved in a variety of cellular processes, such as nuclear transport, transcriptional regulation, apoptosis, and protein stability. It is not active until the last four amino acids of the carboxy-terminus have been cleaved off. Several pseudogenes have been reported for this gene. Alternate transcriptional splice variants encoding different isoforms have been characterized.

Source: NCBI Gene 7341 — RefSeq curated summary.

At a glance

• Gene–disease (curated): orofacial cleft 10 (Limited, GenCC)
• Clinical variants (ClinVar): 31 total — 1 pathogenic
• Phenotypes (HPO): 27
• Druggable target: yes
• MANE Select transcript: NM_003352

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12502
Approved symbol	SUMO1
Name	small ubiquitin like modifier 1
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	PIC1, GMP1, SMT3C, SUMO-1, SMT3H3, OFC10
Ensembl gene	ENSG00000116030
Ensembl biotype	protein_coding
OMIM	601912
Entrez	7341

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 14 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000392244, ENST00000392245, ENST00000392246, ENST00000409181, ENST00000409205, ENST00000409368, ENST00000409498, ENST00000409627, ENST00000409712, ENST00000469034, ENST00000871845, ENST00000871846, ENST00000871847, ENST00000933956, ENST00000933957, ENST00000933958

RefSeq mRNA: 6 — MANE Select: NM_003352 NM_001005781, NM_001005782, NM_001371392, NM_001371393, NM_001371394, NM_003352

CCDS: CCDS2352, CCDS46493, CCDS92928, CCDS92929

Canonical transcript exons

ENST00000392246 — 5 exons

Exon	Start	End
ENSE00001390654	202206182	202207321
ENSE00001771214	202238440	202238597
ENSE00003461703	202210735	202210806
ENSE00003530310	202214357	202214434
ENSE00003637683	202220032	202220106

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 98.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.9743 / max 614.8629, expressed in 1818 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33272	39.4081	1816
33271	1.6066	994
202536	0.9596	648

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	98.69	gold quality
cortical plate	UBERON:0005343	98.49	gold quality
ventricular zone	UBERON:0003053	98.39	gold quality
monocyte	CL:0000576	98.00	gold quality
mononuclear cell	CL:0000842	97.77	gold quality
leukocyte	CL:0000738	97.67	gold quality
adrenal tissue	UBERON:0018303	97.61	gold quality
rectum	UBERON:0001052	97.56	gold quality
gall bladder	UBERON:0002110	97.32	gold quality
right adrenal gland cortex	UBERON:0035827	97.31	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.28	gold quality
colonic epithelium	UBERON:0000397	97.27	gold quality
right adrenal gland	UBERON:0001233	97.14	gold quality
anterior cingulate cortex	UBERON:0009835	96.99	gold quality
left adrenal gland	UBERON:0001234	96.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.94	gold quality
cingulate cortex	UBERON:0003027	96.87	gold quality
left adrenal gland cortex	UBERON:0035825	96.75	gold quality
right frontal lobe	UBERON:0002810	96.55	gold quality
cerebellar hemisphere	UBERON:0002245	96.54	gold quality
cerebellar cortex	UBERON:0002129	96.47	gold quality
frontal pole	UBERON:0002795	96.31	gold quality
stromal cell of endometrium	CL:0002255	96.30	gold quality
right lobe of liver	UBERON:0001114	96.30	gold quality
popliteal artery	UBERON:0002250	96.24	gold quality
tibial artery	UBERON:0007610	96.24	gold quality
calcaneal tendon	UBERON:0003701	96.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.21	gold quality
descending thoracic aorta	UBERON:0002345	96.19	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.16	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	5.89
E-MTAB-6819	no	1293.05
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, BCL6, DLX3, EGR1, ESR1, FOXN1, GATA4, HSF1, HSF2, MEF2A, MYB, NR1H4, PGR, PRDM1, PROX1, RCOR2, RORA, RUNX1, SP1, SP3, STAT5A, TP53, YBX1, ZBTB16

miRNA regulators (miRDB)

90 targeting SUMO1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-1284	99.67	73.56	1353

Literature-anchored findings (GeneRIF, showing 40)

• role in modulating nuclear receptor interaction domain of GRIP1 (PMID:12060666)
• post-translationally modifies glucocorticoid receptor in a ligand-enhanced fashion (PMID:12144530)
• binding of proteins SALL1, UBE2I and SUMO-1 (PMID:12200128)
• p14ARF promotes accumulation of (H)Mdm2 conjugated to the small ubiquitin-like protein SUMO-1. (PMID:12297306)
• role in modifying aryl hydrocarbon receptor nuclear transporter at Lys245 (PMID:12354770)
• SUMO1 has a role in PIASy-enhanced modification of C-EPB alpha (PMID:12511558)
• Overexpression of SUMO-1 enhanced PR-mediated gene transcription even in the presence of non-sumoylated mutants of SRC-1. (PMID:12529333)
• SUMO-1 has a role in modifying cAMP-response element-binding protein (CREB) in prolonged hypoxia (PMID:12552083)
• examination of the role of the phosphorylation event in regulating SUMO-1 modification of HSF1 (PMID:12646186)
• HSF1 is modified by SUMO-1 and SUMO-2 in a stress-inducible manner. (PMID:12665592)
• SRF is modified by SUMO-1 chiefly at lysine(147) within the DNA-binding domain. (PMID:12788062)
• PIAS1 was found to strongly stimulate sumoylation of STAT1 at Lys703 by SUMO-1 conjugation to STAT1; results suggest a negative regulatory function for sumoylation. (PMID:12855578)
• PIAS1 conjugates SUMO-1 to human mineralocorticoid receptor. (PMID:14500761)
• Smad4 is covalently modified by SUMO-1 and facilitates Smad-dependent transcriptional activation (PMID:14514699)
• PLZF colocalizes with SUMO-1 in the nucleus; lysine 242 in the RD2 domain of human PLZF was identified as the sumoylation site (PMID:14527952)
• SENP1 localization is influenced by expression and localization of SUMO-1-conjugated target proteins within the cell. (PMID:14563852)
• recruitment of SUMO-1 modified proteins into insoluble nuclear inclusions and proteasomal dysfunction may be involved in the pathogenesis neuronal intranuclear inclusion disease (PMID:14637113)
• Dnmt3a interacts with multiple components of the sumoylation machinery, all of which are involved in conjugating the small ubiquitin-like modifier polypeptide, SUMO-1, to its target proteins (PMID:14752048)
• SUMO-1 promotes histone deacetylase-mediated transcriptional repression. (PMID:14992729)
• Regulates protein function by binding to diverse proteins within the cell. (PMID:15016812)
• In interphase, a significant fraction of vertebrate SUMO1-modified RanGAP1 forms a stable complex with the nucleoporin RanBP2/Nup358 at nuclear pore complexes. (PMID:15037602)
• These results suggest that the PPARgamma-dependent transactivation pathway seems to be modulated by SUMO-1 modification and may serve as a novel target for apoptosis-induction therapy in cancer cells. (PMID:15123625)
• SUMO modification of Human Cytomegalovirus (HCMV) IE1-72 kDa contributes to efficient HCMV replication by promoting the accumulation of IE2-86 kDa. (PMID:15220454)
• SUMO-1 conjugation at the Lys-19 residue is crucial for enhancing the transactivation activity of EBV Rta (PMID:15229220)
• CENPC target sites that can be sumoylated by SUMO-2 were shown to be equally susceptible to SUMO-1 attachments which include specific sites on SUMO-2 itself, Ubc9, and the recombinant CENP-C fragments. (PMID:15272016)
• GATA4 is a SUMO-1-targeted transcription factor and together with PIAS1 is a potent regulator of cardiac gene activity (PMID:15337742)
• the RanGAP1 consensus sumoylation site and SUMO-1 C terminus are both conformationally flexible (PMID:15355965)
• SUMO-1 shows patterns of utilization that are clearly discrete from the patterns of SUMO-2 and -3 throughout the cell cycle (PMID:15456902)
• sumoylation is involved in negative regulation of the transactivating function of PPARgamma2 (PMID:15507114)
• reversible SUMO modification at hsTAF5 contributes to the dynamic regulation of TFIID promoter-binding activity in human cells (PMID:15637059)
• structures of heterodimeric Sae1/Sae2-Mg.ATP and Sae1/Sae2-SUMO-1-Mg.ATP complexes (PMID:15660128)
• SUMO1 represses transcriptional activity of SOX3. (PMID:15788563)
• SUMO1 conjugation to the C-terminal K330 of thymine DNA glycosylase modulates the DNA binding function of the N terminus to induce dissociation of the glycosylase from the AP site while it leaves the catalytic properties of the enzyme unaffected. (PMID:15823533)
• ERM is subject to SUMO modification and this post-translational modification causes inhibition of transcription-enhancing activity (PMID:15857832)
• OZF interacts with UBC9, the E2 enzyme involved in the covalent conjugation of the small ubiquitin-like modifier 1 (SUMO-1). Conjugation of SUMO-1 to a Kruppel zinc finger motif. (PMID:15881673)
• In cell culture experiments, we found that the nuclear and perinuclear accumulation of SUMO-1 aggregates could be induced in glioma cells by chemical inhibition of proteasomal protein degradation. (PMID:15882793)
• sumoylation-deficient MDMX mutant undergoes normal ubiquitination and degradation by MDM2, normal nuclear translocation and degradation after DNA damage, and inhibits p53 with wild type efficiency (PMID:15907800)
• Data show that sumoylated LRH-1 is exclusively localized in promyelocytic leukemia protein nuclear bodies, and that this association is a dynamic process regulated in part by SUMO-1. (PMID:15923626)
• Nup358/RanBP2 acts as an E3 by binding both SUMO and Ubc9 to position the SUMO-E2-thioester in an optimal orientation to enhance conjugation (PMID:15931224)
• HIPK2 effector function on JNK is modulated through dynamic SUMO-1 modification (PMID:15958389)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sumo1	ENSDARG00000044267
mus_musculus	Sumo1	ENSMUSG00000026021
rattus_norvegicus	LOC120102380	ENSRNOG00000016133

Protein

Protein identifiers

Small ubiquitin-related modifier 1 — P63165 (reviewed: P63165)

Alternative names: GAP-modifying protein 1, SMT3 homolog 3, Sentrin, Ubiquitin-homology domain protein PIC1, Ubiquitin-like protein SMT3C, Ubiquitin-like protein UBL1

All UniProt accessions (6): P63165, B8ZZ67, B8ZZJ0, B8ZZN6, B9A032, F8WBI1

UniProt curated annotations — full annotation on UniProt →

Function. Ubiquitin-like protein that can be covalently attached to proteins as a monomer or 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 E3 ligases 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. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Covalently attached to the voltage-gated potassium channel KCNB1; this modulates the gating characteristics of KCNB1. Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development. Covalently attached to ZFHX3.

Subunit / interactions. Covalently attached to KCNB1; UBE2I increases cross-linking with KCNB1 and PIAS1 decreases cross-links with KCNB1. Interacts with SAE2, RANBP2, PIAS1 and PIAS2. Interacts with PRKN. Covalently attached to a number of proteins such as IKFZ1, PML, RANGAP1, HIPK2, SP100, p53, p73-alpha, MDM2, JUN, DNMT3B and TDG. Also interacts with HIF1A, HIPK2, HIPK3, CHD3, EXOSC9, RAD51 and RAD52. Interacts with USP25 (via ts SIM domain); the interaction weakly sumoylates USP25. Interacts with SIMC1, CASP8AP2, RNF111 and SOBP (via SIM domains). Interacts with BHLHE40/DEC1. Interacts with RWDD3. Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3. Interacts with MTA1. Interacts with SENP2. Interacts with HINT1. Interacts with TINCR (via SUMO-interacting motif); the interaction increases TINCR protein stability. (Microbial infection) Interacts with Epstein-barr virus BGLF4. (Microbial infection) Interacts (via N-terminus) with Tula hantavirus nucleoprotein. (Microbial infection) Interacts (via N-terminus) with Hantaan hantavirus nucleoprotein.

Subcellular location. Nucleus membrane. Nucleus speckle. Cytoplasm. Nucleus. PML body. Cell membrane.

Post-translational modifications. Cleavage of precursor form by SENP1 or SENP2 is necessary for function. Polymeric SUMO1 chains undergo polyubiquitination by RNF4.

Disease relevance. Non-syndromic orofacial cleft 10 (OFC10) [MIM:613705] A birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving SUMO1 is the cause of OFC10. Translocation t(2;8)(q33.1;q24.3). The breakpoint occurred in the SUMO1 gene and resulted in haploinsufficiency confirmed by protein assays.

Similarity. Belongs to the ubiquitin family. SUMO subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P63165-1	1	yes
P63165-2	2

RefSeq proteins (6): NP_001005781, NP_001005782, NP_001358321, NP_001358322, NP_001358323, NP_003343* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR022617	Rad60/SUMO-like_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR046332	SUMO1_Ubl	Domain

Pfam: PF11976

UniProt features (40 total): cross-link 11, strand 8, helix 5, modified residue 4, mutagenesis site 2, region of interest 2, initiator methionine 1, chain 1, propeptide 1, splice variant 1, sequence conflict 1, domain 1, turn 1, site 1

Structure

Experimental structures (PDB)

68 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6UYR	X-RAY DIFFRACTION	1.3
4WJQ	X-RAY DIFFRACTION	1.35
6V7Q	X-RAY DIFFRACTION	1.35
6V7P	X-RAY DIFFRACTION	1.4
2UYZ	X-RAY DIFFRACTION	1.4
6UYZ	X-RAY DIFFRACTION	1.4
6UYV	X-RAY DIFFRACTION	1.4
6UYP	X-RAY DIFFRACTION	1.42
4WJO	X-RAY DIFFRACTION	1.46
6V7S	X-RAY DIFFRACTION	1.47
4WJN	X-RAY DIFFRACTION	1.5
6UYQ	X-RAY DIFFRACTION	1.5
6V7R	X-RAY DIFFRACTION	1.55
9QTG	X-RAY DIFFRACTION	1.55
6UYS	X-RAY DIFFRACTION	1.59
6UYY	X-RAY DIFFRACTION	1.6
6UYO	X-RAY DIFFRACTION	1.64
6UYU	X-RAY DIFFRACTION	1.66
6UYT	X-RAY DIFFRACTION	1.66
4WJP	X-RAY DIFFRACTION	1.7
6UYX	X-RAY DIFFRACTION	1.7
8DJH	X-RAY DIFFRACTION	1.77
9GNX	X-RAY DIFFRACTION	1.9
8DJI	X-RAY DIFFRACTION	1.97
6XOG	X-RAY DIFFRACTION	1.98
5ELJ	X-RAY DIFFRACTION	1.98
6XOI	X-RAY DIFFRACTION	2
9Q9E	X-RAY DIFFRACTION	2.05
6WW3	X-RAY DIFFRACTION	2.1
1WYW	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P63165-F1	79.28	0.40

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 36 (interaction with pias2)

Post-translational modifications (15): 32, 7, 7, 16, 17, 23, 25, 37, 39, 45, 46, 97, 2, 2, 9

Mutagenesis-validated functional residues (2):

Position	Phenotype
36	abolishes binding to pias2.
97	abolishes sumoylation of zbed1.

Function

Pathways and Gene Ontology

Reactome pathways

62 pathways

ID	Pathway
R-HSA-3065676	SUMO is conjugated to E1 (UBA2:SAE1)
R-HSA-3065678	SUMO is transferred from E1 to E2 (UBE2I, UBC9)
R-HSA-3065679	SUMO is proteolytically processed
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-3232118	SUMOylation of transcription factors
R-HSA-3232142	SUMOylation of ubiquitinylation proteins
R-HSA-3899300	SUMOylation of transcription cofactors
R-HSA-4085377	SUMOylation of SUMOylation proteins
R-HSA-4090294	SUMOylation of intracellular receptors
R-HSA-4551638	SUMOylation of chromatin organization proteins
R-HSA-4570464	SUMOylation of RNA binding proteins
R-HSA-4615885	SUMOylation of DNA replication proteins
R-HSA-4655427	SUMOylation of DNA methylation proteins
R-HSA-4755510	SUMOylation of immune response proteins
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5696395	Formation of Incision Complex in GG-NER
R-HSA-877312	Regulation of IFNG signaling
R-HSA-8866904	Negative regulation of activity of TFAP2 (AP-2) family transcription factors
R-HSA-9615933	Postmitotic nuclear pore complex (NPC) reformation
R-HSA-9683610	Maturation of nucleoprotein
R-HSA-9694631	Maturation of nucleoprotein
R-HSA-9793242	SUMOylation of nuclear envelope proteins
R-HSA-9833482	PKR-mediated signaling
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity
R-HSA-9918432	Maturation of DENV proteins
R-HSA-9937850	NuRD complex assembly
R-HSA-1169410	Antimicrobial mechanism of IFN-stimulated genes
R-HSA-1266738	Developmental Biology
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1640170	Cell Cycle

MSigDB gene sets: 461 (showing top): REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, MORF_MTA1, PID_HDAC_CLASSI_PATHWAY, E2F_Q4, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, MORF_MBD4, E2F4DP1_01, GOBP_CIRCULATORY_SYSTEM_PROCESS, MORF_RAB5A, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, KAAB_FAILED_HEART_ATRIUM_DN, GAANYNYGACNY_UNKNOWN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN

GO Biological Process (25): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA repair (GO:0006281), protein sumoylation (GO:0016925), PML body organization (GO:0030578), positive regulation of protein-containing complex assembly (GO:0031334), regulation of protein stability (GO:0031647), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), cellular response to heat (GO:0034605), negative regulation of protein import into nucleus (GO:0042308), negative regulation of action potential (GO:0045759), negative regulation of DNA-templated transcription (GO:0045892), protein stabilization (GO:0050821), roof of mouth development (GO:0060021), negative regulation of transcription initiation by RNA polymerase II (GO:0060633), cellular response to cadmium ion (GO:0071276), regulation of cardiac muscle cell contraction (GO:0086004), protein localization to nuclear pore (GO:0090204), regulation of calcium ion transmembrane transport (GO:1903169), regulation of DNA-templated transcription (GO:0006355), obsolete negative regulation of transcription by transcription factor localization (GO:0010621), regulation of protein localization (GO:0032880), negative regulation of DNA binding (GO:0043392), obsolete negative regulation of DNA-binding transcription factor activity (GO:0043433), negative regulation of potassium ion transmembrane transporter activity (GO:1901017), negative regulation of delayed rectifier potassium channel activity (GO:1902260)

GO Molecular Function (11): RNA binding (GO:0003723), potassium channel regulator activity (GO:0015459), enzyme binding (GO:0019899), protein tag activity (GO:0031386), ubiquitin protein ligase binding (GO:0031625), small protein activating enzyme binding (GO:0044388), ubiquitin-like protein ligase binding (GO:0044389), transporter activator activity (GO:0141109), ubiquitin-specific protease binding (GO:1990381), protein binding (GO:0005515), transcription factor binding (GO:0008134)

GO Cellular Component (18): XY body (GO:0001741), nucleus (GO:0005634), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear body (GO:0016604), PML body (GO:0016605), nuclear speck (GO:0016607), nuclear membrane (GO:0031965), nuclear stress granule (GO:0097165), glutamatergic synapse (GO:0098978), presynaptic cytosol (GO:0099523), postsynaptic cytosol (GO:0099524), cytoplasm (GO:0005737), voltage-gated potassium channel complex (GO:0008076), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	11
Processing and activation of SUMO	3
DNA Double Strand Break Response	1
Global Genome Nucleotide Excision Repair (GG-NER)	1
Interferon gamma signaling	1
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1
Nuclear Envelope (NE) Reassembly	1
Translation of Structural Proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA-templated transcription	2
protein binding	2
enzyme binding	2
nuclear envelope	2
nuclear lumen	2
intracellular membraneless organelle	2
nuclear ribonucleoprotein granule	2
cytosol	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA metabolic process	1
DNA damage response	1
peptidyl-lysine modification	1
protein modification by small protein conjugation	1
nuclear body organization	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
regulation of biological quality	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
response to heat	1
cellular response to stress	1
protein import into nucleus	1
regulation of protein import into nucleus	1
negative regulation of nucleocytoplasmic transport	1
negative regulation of intracellular protein transport	1
negative regulation of protein localization to nucleus	1
action potential	1
negative regulation of biological process	1
regulation of action potential	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
regulation of protein stability	1
anatomical structure development	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

469 interactions, top by confidence:

A	B	Type	Score
SUMO1	RANGAP1	psi-mi:“MI:0915”(physical association)	0.960
RANGAP1	SUMO1	psi-mi:“MI:0915”(physical association)	0.960
RANGAP1	SUMO1	psi-mi:“MI:0195”(covalent binding)	0.960
RANGAP1	SUMO1	psi-mi:“MI:0407”(direct interaction)	0.960
UBE2I	SUMO1	psi-mi:“MI:0914”(association)	0.950
UBE2I	SUMO1	psi-mi:“MI:0195”(covalent binding)	0.950
UBE2I	SUMO1	psi-mi:“MI:0407”(direct interaction)	0.950
SUMO1	UBE2I	psi-mi:“MI:0407”(direct interaction)	0.950
SUMO1	SENP1	psi-mi:“MI:0407”(direct interaction)	0.870
SUMO1	UBA2	psi-mi:“MI:0915”(physical association)	0.850
UBA2	SUMO1	psi-mi:“MI:0915”(physical association)	0.850
UBA2	SUMO1	psi-mi:“MI:0407”(direct interaction)	0.850
SUMO1	PML	psi-mi:“MI:0407”(direct interaction)	0.830
SUMO1	ARK2N	psi-mi:“MI:0915”(physical association)	0.790
ARK2N	SUMO1	psi-mi:“MI:0915”(physical association)	0.790
PIAS2	SUMO1	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (512): SUMO1 (Biochemical Activity), SUMO1 (Biochemical Activity), SUMO1 (Biochemical Activity), SUMO1 (Biochemical Activity), SUMO1 (Reconstituted Complex), SUMO1 (Biochemical Activity), SUMO1 (Biochemical Activity), SUMO1 (Two-hybrid), SUMO1 (Two-hybrid), SUMO1 (Two-hybrid), SUMO1 (Two-hybrid), SUMO1 (Two-hybrid), SUMO1 (Two-hybrid), SUMO1 (Two-hybrid), SUMO1 (Two-hybrid)

ESM2 similar proteins: A7WLH8, A7WLI0, B3H5R8, G2XKQ0, O13351, O57686, P29504, P55852, P55853, P55854, P55857, P61955, P61956, P61957, P61958, P61959, P62982, P62983, P63165, P63166, Q12306, Q17QV3, Q28H04, Q2EF74, Q2PFW2, Q3E8A8, Q5E9D1, Q5EAX4, Q5I0H3, Q5R6J4, Q5XIF4, Q5ZHQ1, Q5ZJM9, Q6DEP7, Q6DHL4, Q6DI05, Q6DK72, Q6EEV6, Q6GPW2, Q6LDZ8

Diamond homologs: A7WLH8, A7WLI0, B3H5R8, G2XKQ0, O13351, O57686, P55852, P55853, P55854, P55857, P61955, P61956, P61957, P61958, P61959, P63165, P63166, Q0P4K8, Q12306, Q17QV3, Q28H04, Q2EF74, Q2PFW2, Q5E9D1, Q5EAX4, Q5I0H3, Q5R6J4, Q5XIF4, Q5ZHQ1, Q5ZJM9, Q6DEP7, Q6DHL4, Q6DI05, Q6DK72, Q6EEV6, Q6GPW2, Q6LDZ8, Q6NV25, Q7SZ22, Q7SZR5

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
BCL6	“down-regulates quantity by repression”	SUMO1	“transcriptional regulation”
SUMO1	up-regulates	PML	sumoylation
SUMO1	“up-regulates activity”	PML	sumoylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SUMOylation of transcription factors	5	51.9×	1e-06
Postmitotic nuclear pore complex (NPC) reformation	6	44.5×	2e-07
Nuclear import of Rev protein	7	42.8×	2e-08
SUMOylation of ubiquitinylation proteins	8	42.6×	2e-09
Transport of Ribonucleoproteins into the Host Nucleus	6	38.9×	4e-07
SUMOylation of SUMOylation proteins	6	35.6×	6e-07
Rev-mediated nuclear export of HIV RNA	6	34.6×	6e-07
IPs transport between nucleus and cytosol	5	34.6×	7e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein sumoylation	9	44.2×	3e-10
nucleocytoplasmic transport	6	35.6×	3e-06
mRNA transport	5	19.9×	5e-04
protein import into nucleus	9	19.6×	2e-07
protein-containing complex assembly	6	10.3×	2e-03
chromatin remodeling	7	7.7×	2e-03
DNA damage response	7	5.7×	8e-03
positive regulation of gene expression	9	5.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

31 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	14
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
7629	46,XX,t(2;8)(q33.1;q24.3)	Pathogenic

SpliceAI

935 predictions. Top by Δscore:

Variant	Effect	Δscore
2:202207317:CCCAG:C	acceptor_gain	1.0000
2:202207318:CCAG:C	acceptor_gain	1.0000
2:202207318:CCAGC:C	acceptor_gain	1.0000
2:202207319:CAG:C	acceptor_gain	1.0000
2:202207319:CAGC:C	acceptor_gain	1.0000
2:202210733:A:AC	donor_gain	1.0000
2:202210734:C:CC	donor_gain	1.0000
2:202210803:CACC:C	acceptor_gain	1.0000
2:202210805:CC:C	acceptor_gain	1.0000
2:202210806:CC:C	acceptor_gain	1.0000
2:202214338:AATAC:A	donor_gain	1.0000
2:202214352:CGAA:C	donor_loss	1.0000
2:202214353:GAACC:G	donor_loss	1.0000
2:202214354:AACC:A	donor_loss	1.0000
2:202214355:A:C	donor_loss	1.0000
2:202214356:C:A	donor_loss	1.0000
2:202214356:CCTGT:C	donor_gain	1.0000
2:202214430:CTATC:C	acceptor_gain	1.0000
2:202214433:TC:T	acceptor_gain	1.0000
2:202214434:CC:C	acceptor_gain	1.0000
2:202214435:C:CC	acceptor_gain	1.0000
2:202220027:CTCA:C	donor_loss	1.0000
2:202220028:TCACC:T	donor_loss	1.0000
2:202220029:CA:C	donor_loss	1.0000
2:202220030:A:AC	donor_gain	1.0000
2:202220031:C:CA	donor_loss	1.0000
2:202220031:C:CC	donor_gain	1.0000
2:202220031:CCTGT:C	donor_gain	1.0000
2:202220104:CTC:C	acceptor_gain	1.0000
2:202220106:CCTG:C	acceptor_loss	1.0000

AlphaMissense

670 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:202207296:A:T	I88N	1.000
2:202210781:A:G	F64S	1.000
2:202214382:A:T	L47H	1.000
2:202214414:G:C	F36L	1.000
2:202214414:G:T	F36L	1.000
2:202214415:A:G	F36S	1.000
2:202214416:A:G	F36L	1.000
2:202220048:A:T	L24H	1.000
2:202207296:A:C	I88S	0.999
2:202207314:A:C	M82R	0.999
2:202207314:A:G	M82T	0.999
2:202210742:G:T	P77Q	0.999
2:202210760:A:T	I71N	0.999
2:202210769:C:A	G68V	0.999
2:202210770:C:G	G68R	0.999
2:202210778:A:G	L65P	0.999
2:202210780:A:C	F64L	0.999
2:202210780:A:T	F64L	0.999
2:202210782:A:G	F64L	0.999
2:202210784:C:A	R63M	0.999
2:202214378:T:A	K48N	0.999
2:202214378:T:G	K48N	0.999
2:202214382:A:G	L47P	0.999
2:202214391:A:G	L44P	0.999
2:202214406:T:A	K39I	0.999
2:202214407:T:C	K39E	0.999
2:202220042:A:T	V26D	0.999
2:202220048:A:G	L24P	0.999
2:202207272:C:T	G96E	0.998
2:202207290:A:T	V90D	0.998

dbSNP variants (sampled 300 via entrez): RS1000063219 (2:202209383 T>C), RS1000326462 (2:202227399 G>A), RS1000399970 (2:202225109 T>C), RS1000412490 (2:202218336 C>T), RS1000440611 (2:202234135 T>C,G), RS1000442971 (2:202237456 A>G), RS1000519252 (2:202231879 G>A), RS1000559464 (2:202214817 A>G), RS1000574676 (2:202232085 G>A,C), RS1000614960 (2:202227089 G>A), RS1000622330 (2:202207043 G>A,T), RS1000641399 (2:202226136 A>G), RS1000665275 (2:202220858 T>C), RS1000698047 (2:202221200 T>A,C), RS1000708089 (2:202224866 G>A)

Disease associations

OMIM: gene MIM:601912 | disease phenotypes: MIM:613705

GenCC curated gene-disease

Disease	Classification	Inheritance
orofacial cleft 10	Limited	Unknown

Mondo (1): orofacial cleft 10 (MONDO:0013378)

Orphanet (0):

HPO phenotypes

27 total (27 of 27 shown, HPO-id order):

HPO	Term
HP:0000202	Orofacial cleft
HP:0000677	Oligodontia
HP:0000679	Taurodontia
HP:0000684	Delayed eruption of teeth
HP:0000685	Hypoplasia of teeth
HP:0000687	Widely spaced teeth
HP:0000689	Dental malocclusion
HP:0000690	Agenesis of maxillary lateral incisor
HP:0000691	Microdontia
HP:0000696	Delayed eruption of permanent teeth
HP:0003577	Congenital onset
HP:0003745	Sporadic
HP:0005216	Impaired mastication
HP:0006289	Agenesis of central incisor
HP:0006297	Enamel hypoplasia
HP:0006336	Short dental root
HP:0006342	Peg-shaped maxillary lateral incisors
HP:0006344	Abnormal primary molar morphology
HP:0006482	Abnormal dental morphology
HP:0011051	Agenesis of premolar
HP:0011053	Agenesis of mandibular premolar
HP:0011056	Agenesis of first permanent molar tooth
HP:0011078	Abnormality of canine
HP:0011219	Short face
HP:0012472	Eclabion
HP:0100333	Unilateral cleft lip
HP:0100334	Unilateral cleft palate

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566605	Orofacial Cleft 10 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2146296 (SINGLE PROTEIN), CHEMBL6066555 (PROTEIN COMPLEX), CHEMBL6066556 (PROTEIN COMPLEX), CHEMBL6066558 (PROTEIN FAMILY)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

15 potent at pChembl≥5 of 28 total, top 15 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.85	IC50	1420	nM	CHEMBL5276705
5.80	IC50	1600	nM	CHEMBL2009952
5.75	Kd	1800	nM	CHEMBL3580707
5.73	IC50	1880	nM	CHEMBL5276705
5.73	IC50	1860	nM	CHEMBL5315679
5.68	IC50	2080	nM	CHEMBL5175111
5.63	IC50	2320	nM	CHEMBL2009952
5.50	IC50	3200	nM	CHEMBL3580708
5.47	IC50	3420	nM	CHEMBL5175111
5.44	IC50	3620	nM	CHEMBL5290662
5.39	IC50	4100	nM	CHEMBL6030623
5.37	IC50	4320	nM	CHEMBL5290662
5.29	IC50	5170	nM	CHEMBL5315679
5.12	IC50	7500	nM	CHEMBL3580707
5.12	IC50	7500	nM	CHEMBL5278967

CTD chemical–gene interactions

66 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	decreases expression, affects cotreatment, increases localization, increases reaction, increases ubiquitination (+5 more)	8
Tretinoin	increases expression, increases reaction, decreases reaction, affects localization, decreases expression	4
sodium arsenite	decreases expression, increases abundance, increases expression	3
Arsenic	affects binding, increases reaction, increases expression, decreases reaction, decreases expression (+1 more)	3
cobaltous chloride	decreases expression, affects binding, decreases abundance, increases reaction, increases expression	2
Resveratrol	affects binding, decreases reaction, increases reaction, affects reaction, decreases expression (+1 more)	2
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases expression	2
aristolochic acid I	decreases expression	1
CB-5083	affects binding, increases reaction, decreases reaction	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
daidzein	affects cotreatment, increases expression	1
quinomethionate	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
1,12-benzoperylene	increases expression	1
bisphenol A	decreases expression	1
daidzin	affects cotreatment, increases expression	1
arsenite	affects binding, increases reaction	1
antimony trioxide	increases reaction, affects localization, affects binding	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
genistin	affects cotreatment, increases expression	1
hinokiflavone	increases localization	1
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide	affects reaction, decreases expression, decreases reaction, increases expression	1
glycitein	affects cotreatment, increases expression	1
CD 437	decreases expression	1
monomethylarsonous acid	affects cotreatment, increases localization	1
CPG-oligonucleotide	increases expression	1
glycitin	affects cotreatment, increases expression	1

ChEMBL screening assays

13 unique, capped per target: 11 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2114737	Functional	PubChem BioAssay. Dose response confirmation of uHTS inhibitor hits of SUMO1-mediated protein-protein interactions using a fluorescence polarization assay. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL3582505	Binding	Binding affinity to recombinant His-tagged human SUMO1 expressed in Escherichia coli BL21 (DE3) assessed as inhibition of interaction with biotinylated DAXX-SIM peptide after 1 hr by AlphaLISA method	Discovery of small molecule inhibitors targeting the SUMOSIM interaction using a protein interface consensus approach — Medchemcomm

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TR20	HAP1 SUMO1 (-) 1	Cancer cell line	Male
CVCL_TR21	HAP1 SUMO1 (-) 2	Cancer cell line	Male
CVCL_TR22	HAP1 SUMO1 (-) 3	Cancer cell line	Male
CVCL_TR23	HAP1 SUMO1 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.