Reviewed, UniProtKB/Swiss-Prot P49792 (RBP2_HUMAN)

Names and origin

Protein names

Recommended name:
    E3 SUMO-protein ligase RanBP2
Alternative name(s):
    Ran-binding protein 2
    Nuclear pore complex protein Nup358
    Nucleoporin Nup358
    358 kDa nucleoporin
    p270

Gene names

Name:	RANBP2
Synonyms:	NUP358

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	3224 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I. Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates. Could also have isomerase or chaperone activity and may bind RNA or DNA. Component of the nuclear export pathway. Specific docking site for the nuclear export factor exportin-1.
Pathway	Protein modification; protein sumoylation.
Subunit structure	Forms a tight complex with RANBP1 and UBE2I. Interacts with SUMO1 but not SUMO2. Interacts with PARK2. Interacts with sumoylated RANGAP1.
Subcellular location	Nucleus › nuclear pore complex. Note= Cytoplasmic filaments.
Domain	Contains F-X-F-G repeats.
Post-translational modification	Polyubiquitinated by PARK2, which leads to proteasomal degradation.
Sequence similarities	Contains 1 PPIase cyclophilin-type domain. Contains 4 RanBD1 domains. Contains 8 RanBP2-type zinc fingers. Contains 1 TPR repeat.

Ontologies

Keywords
Biological process	Protein transport Translocation Transport Ubl conjugation pathway mRNA transport
Cellular component	Nuclear pore complex Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat TPR repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Isomerase Rotamase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	intracellular protein transmembrane transport Inferred from electronic annotation. Source: UniProtKB-KW mRNA transport Inferred from electronic annotation. Source: UniProtKB-KW protein folding Inferred from electronic annotation. Source: UniProtKB-KW protein import into nucleus Ref.2 Traceable author statement. Source: ProtInc ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from Experiment. Source: Reactome nuclear pore Ref.2 Traceable author statement. Source: ProtInc
Molecular function	Ran GTPase binding Ref.2 Traceable author statement. Source: ProtInc peptidyl-prolyl cis-trans isomerase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PARK2	O60260	6	EBI-973138,EBI-716346
TOP2A	P11388	1	EBI-973138,EBI-539628
Top2a	Q01320	1	EBI-973138,EBI-642809	From a different organism.
UBE2I	P63279	1	EBI-973138,EBI-80168

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 3224	3224	E3 SUMO-protein ligase RanBP2		PRO_0000204913
Regions
	Repeat	60 – 93	34	TPR
	Domain	1171 – 1307	137	RanBD1 1
	Domain	2012 – 2148	137	RanBD1 2
	Domain	2309 – 2445	137	RanBD1 3
	Repeat	2633 – 2685	53	1
	Repeat	2711 – 2761	51	2
	Domain	2911 – 3046	136	RanBD1 4
	Domain	3067 – 3223	157	PPIase cyclophilin-type
	Zinc finger	1351 – 1381	31	RanBP2-type 1
	Zinc finger	1415 – 1444	30	RanBP2-type 2
	Zinc finger	1479 – 1508	30	RanBP2-type 3
	Zinc finger	1543 – 1572	30	RanBP2-type 4
	Zinc finger	1606 – 1635	30	RanBP2-type 5
	Zinc finger	1665 – 1694	30	RanBP2-type 6
	Zinc finger	1724 – 1753	30	RanBP2-type 7
	Zinc finger	1781 – 1810	30	RanBP2-type 8
	Region	2631 – 2635	5	Interaction with sumoylated RANGAP1
	Region	2633 – 2761	129	2 X 50 AA approximate repeats
	Region	2633 – 2710	78	Required for E3 SUMO-ligase activity
	Region	2633 – 2685	53	Interaction with UBE2I
	Region	2686 – 2761	76	Interaction with SUMO1
Amino acid modifications
	Modified residue	19	1	Phosphothreonine
	Modified residue	21	1	Phosphoserine
	Modified residue	394	1	Phosphoserine
	Modified residue	779	1	Phosphothreonine
	Modified residue	781	1	Phosphoserine
	Modified residue	788	1	Phosphoserine
	Modified residue	796	1	Phosphoserine
	Modified residue	799	1	Phosphothreonine
	Modified residue	948	1	Phosphoserine
	Modified residue	955	1	Phosphoserine
	Modified residue	1110	1	Phosphoserine
	Modified residue	1144	1	Phosphothreonine
	Modified residue	1160	1	Phosphoserine
	Modified residue	1396	1	Phosphothreonine
	Modified residue	1399	1	Phosphothreonine
	Modified residue	1400	1	Phosphoserine
	Modified residue	1412	1	Phosphothreonine
	Modified residue	1443	1	Phosphoserine
	Modified residue	1447	1	Phosphoserine
	Modified residue	1456	1	Phosphoserine
	Modified residue	1509	1	Phosphoserine
	Modified residue	1573	1	Phosphoserine
	Modified residue	1731	1	Phosphoserine
	Modified residue	1869	1	Phosphoserine
	Modified residue	2128	1	Phosphothreonine
	Modified residue	2153	1	Phosphothreonine
	Modified residue	2246	1	Phosphoserine By similarity
	Modified residue	2251	1	Phosphoserine By similarity
	Modified residue	2270	1	Phosphoserine
	Modified residue	2276	1	Phosphoserine
	Modified residue	2280	1	Phosphoserine
	Modified residue	2290	1	Phosphoserine
	Modified residue	2293	1	Phosphothreonine By similarity
	Modified residue	2297	1	Phosphoserine By similarity
	Modified residue	2447	1	Phosphoserine
	Modified residue	2450	1	Phosphothreonine
	Modified residue	2454	1	Phosphoserine
	Modified residue	2510	1	Phosphoserine
	Modified residue	2518	1	Phosphoserine
	Modified residue	2613	1	Phosphothreonine
	Modified residue	2668	1	Phosphoserine
	Modified residue	2741	1	Phosphoserine
	Modified residue	2743	1	Phosphothreonine
	Modified residue	2807	1	Phosphoserine
	Modified residue	2900	1	Phosphoserine
	Modified residue	3207	1	Phosphoserine
	Cross-link	2592		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Natural variations
	Natural variant	548	1	V → L: dbSNP rs1057954.		VAR_029765
	Natural variant	580	1	E → K: dbSNP rs4012065.		VAR_029766
	Natural variant	581	1	C → Y: dbSNP rs1057957.		VAR_029767
	Natural variant	784	1	R → K: dbSNP rs2912838.		VAR_023939
	Natural variant	1870	1	P → L: dbSNP rs2889846.		VAR_029768
	Natural variant	1892	1	P → A: dbSNP rs12770.		VAR_014886
Experimental info
	Mutagenesis	2632	1	V → K: Abolishes interaction with sumoylated RANGAP1
	Mutagenesis	2634	1	I → K: Abolishes interaction with sumoylated RANGAP1
	Mutagenesis	2635	1	V → K: Abolishes interaction with sumoylated RANGAP1
	Mutagenesis	2640	1	P → A: No effect on SUMO E3 ligase activity
	Mutagenesis	2645	1	K → A: No effect on SUMO E3 ligase activity
	Mutagenesis	2651	1	L → A: Abolishes binding to UBE2I and SUMO E3 ligase activity
	Mutagenesis	2652	1	K → A: No effect on SUMO E3 ligase activity
	Mutagenesis	2653	1	L → A: Abolishes binding to UBE2I and SUMO E3 ligase activity
	Mutagenesis	2654	1	P → A: Impairs SUMO E3 ligase activity
	Mutagenesis	2655	1	P → A: No effect on SUMO E3 ligase activity
	Mutagenesis	2656	1	T → A: Impairs SUMO E3 ligase activity
	Mutagenesis	2657	1	F → A: Abolishes binding to UBE2I and SUMO E3 ligase activity
	Mutagenesis	2658	1	F → A: Abolishes binding to UBE2I and SUMO E3 ligase activity
	Mutagenesis	2659	1	C → S or A: Impairs SUMO E3 ligase activity
	Mutagenesis	2676	1	D → A: Impairs SUMO E3 ligase activity
	Mutagenesis	2677	1	F → A: Impairs SUMO E3 ligase activity
	Mutagenesis	2689	1	Y → A: Impairs SUMO E3 ligase activity
	Sequence conflict	777	1	H → R in AAC41758. Ref.1
	Sequence conflict	2207	1	S → A in AAA85838. Ref.5	</