UniProt functional annotation for P63165



	UniProt functional annotation for P63165

UniProt code: P63165.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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 (PubMed:19223394). 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 (PubMed:24651376). {ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:18538659, ECO:0000269|PubMed:19223394, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:24651376, ECO:0000269|PubMed:9019411, ECO:0000269|PubMed:9162015}.

Subunit: Covalently attached to KCNB1; UBE2I increases cross-linking with KCNB1 and PIAS1 decreases cross-links with KCNB1 (PubMed:19223394, PubMed:15931224). Interacts with SAE2, RANBP2, PIAS1 and PIAS2 (PubMed:10961991, PubMed:15608651, PubMed:15660128, PubMed:16204249, PubMed:15931224). Interacts with PRKN (PubMed:16955485). Covalently attached to a number of proteins such as IKFZ1, PML, RANGAP1, HIPK2, SP100, p53, p73-alpha, MDM2, JUN, DNMT3B and TDG (PubMed:10961991, PubMed:15931224, PubMed:15959518, PubMed:17099698). Also interacts with HIF1A, HIPK2, HIPK3, CHD3, EXOSC9, RAD51 and RAD52 (PubMed:10961991, PubMed:12565818). Interacts with USP25 (via ts SIM domain); the interaction weakly sumoylates USP25 (PubMed:18538659). Interacts with SIMC1, CASP8AP2, RNF111 AND SOBP (via SIM domains) (PubMed:23086935). Interacts with BHLHE40/DEC1 (PubMed:21829689). Interacts with RWDD3 (PubMed:17956732). Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3 (PubMed:12924945, PubMed:17956732). Interacts with MTA1 (PubMed:21965678). Interacts with SENP2 (PubMed:15296745). {ECO:0000269|PubMed:10961991, ECO:0000269|PubMed:12565818, ECO:0000269|PubMed:12924945, ECO:0000269|PubMed:15296745, ECO:0000269|PubMed:15608651, ECO:0000269|PubMed:15660128, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:15959518, ECO:0000269|PubMed:16204249, ECO:0000269|PubMed:16955485, ECO:0000269|PubMed:17099698, ECO:0000269|PubMed:17956732, ECO:0000269|PubMed:18538659, ECO:0000269|PubMed:19223394, ECO:0000269|PubMed:21829689, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:23086935}.

Subunit: (Microbial infection) Interacts with Epstein-barr virus BGLF4. {ECO:0000269|PubMed:22398289}.

Subcellular location: Nucleus membrane {ECO:0000269|PubMed:10574707, ECO:0000269|PubMed:12383504}. Nucleus speckle {ECO:0000250|UniProtKB:P63166}. Cytoplasm {ECO:0000269|PubMed:12383504, ECO:0000269|PubMed:9162015}. Nucleus, PML body {ECO:0000269|PubMed:10574707, ECO:0000269|PubMed:12383504, ECO:0000269|PubMed:22406621}. Cell membrane {ECO:0000269|PubMed:19223394}. Nucleus {ECO:0000269|PubMed:24651376, ECO:0000269|PubMed:9162015}. Note=Recruited by BCL11A into the nuclear body (By similarity). In the presence of ZFHX3, sequesterd to nuclear body (NB)-like dots in the nucleus some of which overlap or closely associate with PML body (PubMed:24651376). {ECO:0000250|UniProtKB:P63166, ECO:0000269|PubMed:24651376}.

Ptm: Cleavage of precursor form by SENP1 or SENP2 is necessary for function. {ECO:0000269|PubMed:15487983}.

Ptm: Polymeric SUMO1 chains undergo polyubiquitination by RNF4. {ECO:0000269|PubMed:18408734}.

Disease: 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. {ECO:0000269|PubMed:16990542}. Note=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. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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 (PubMed:19223394). 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 (PubMed:24651376). {ECO:0000269\|PubMed:18408734, ECO:0000269\|PubMed:18538659, ECO:0000269\|PubMed:19223394, ECO:0000269\|PubMed:21965678, ECO:0000269\|PubMed:24651376, ECO:0000269\|PubMed:9019411, ECO:0000269\|PubMed:9162015}.


Subunit:		Covalently attached to KCNB1; UBE2I increases cross-linking with KCNB1 and PIAS1 decreases cross-links with KCNB1 (PubMed:19223394, PubMed:15931224). Interacts with SAE2, RANBP2, PIAS1 and PIAS2 (PubMed:10961991, PubMed:15608651, PubMed:15660128, PubMed:16204249, PubMed:15931224). Interacts with PRKN (PubMed:16955485). Covalently attached to a number of proteins such as IKFZ1, PML, RANGAP1, HIPK2, SP100, p53, p73-alpha, MDM2, JUN, DNMT3B and TDG (PubMed:10961991, PubMed:15931224, PubMed:15959518, PubMed:17099698). Also interacts with HIF1A, HIPK2, HIPK3, CHD3, EXOSC9, RAD51 and RAD52 (PubMed:10961991, PubMed:12565818). Interacts with USP25 (via ts SIM domain); the interaction weakly sumoylates USP25 (PubMed:18538659). Interacts with SIMC1, CASP8AP2, RNF111 AND SOBP (via SIM domains) (PubMed:23086935). Interacts with BHLHE40/DEC1 (PubMed:21829689). Interacts with RWDD3 (PubMed:17956732). Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3 (PubMed:12924945, PubMed:17956732). Interacts with MTA1 (PubMed:21965678). Interacts with SENP2 (PubMed:15296745). {ECO:0000269\|PubMed:10961991, ECO:0000269\|PubMed:12565818, ECO:0000269\|PubMed:12924945, ECO:0000269\|PubMed:15296745, ECO:0000269\|PubMed:15608651, ECO:0000269\|PubMed:15660128, ECO:0000269\|PubMed:15931224, ECO:0000269\|PubMed:15959518, ECO:0000269\|PubMed:16204249, ECO:0000269\|PubMed:16955485, ECO:0000269\|PubMed:17099698, ECO:0000269\|PubMed:17956732, ECO:0000269\|PubMed:18538659, ECO:0000269\|PubMed:19223394, ECO:0000269\|PubMed:21829689, ECO:0000269\|PubMed:21965678, ECO:0000269\|PubMed:23086935}.
Subunit:		(Microbial infection) Interacts with Epstein-barr virus BGLF4. {ECO:0000269\|PubMed:22398289}.
Subcellular location:		Nucleus membrane {ECO:0000269\|PubMed:10574707, ECO:0000269\|PubMed:12383504}. Nucleus speckle {ECO:0000250\|UniProtKB:P63166}. Cytoplasm {ECO:0000269\|PubMed:12383504, ECO:0000269\|PubMed:9162015}. Nucleus, PML body {ECO:0000269\|PubMed:10574707, ECO:0000269\|PubMed:12383504, ECO:0000269\|PubMed:22406621}. Cell membrane {ECO:0000269\|PubMed:19223394}. Nucleus {ECO:0000269\|PubMed:24651376, ECO:0000269\|PubMed:9162015}. Note=Recruited by BCL11A into the nuclear body (By similarity). In the presence of ZFHX3, sequesterd to nuclear body (NB)-like dots in the nucleus some of which overlap or closely associate with PML body (PubMed:24651376). {ECO:0000250\|UniProtKB:P63166, ECO:0000269\|PubMed:24651376}.
Ptm:		Cleavage of precursor form by SENP1 or SENP2 is necessary for function. {ECO:0000269\|PubMed:15487983}.
Ptm:		Polymeric SUMO1 chains undergo polyubiquitination by RNF4. {ECO:0000269\|PubMed:18408734}.
Disease:		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. {ECO:0000269\|PubMed:16990542}. Note=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. {ECO:0000305}.