P46061 (RAGP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ran GTPase-activating protein 1
Short name=RanGAP1

Gene names

Name:	Rangap1
Synonyms:	Fug1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	589 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	GTPase activator for the nuclear Ras-related regulatory protein Ran, converting it to the putatively inactive GDP-bound state. Required for postimplantation development. Ref.5 Ref.6 Ref.8
Subunit structure	Homodimer. Interacts with TRAF6 By similarity. Forms a tight complex in association with RANBP2/NUP358 and UBE2I/UBC9, the ubiquitin-conjugating enzyme E2. Interacts with UBE2I; the interaction conjugates SUMO1 to RANGAP1, and subsequently stabilizes interactions of sumoylated RANGAP1 with RANBP2/NUP358. The SUMO1/RANGAP1/UBC9/NUP358 complex associates with nuclear pore complexes.
Subcellular location	Cytoplasm By similarity. Nucleus membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Chromosome › centromere › kinetochore By similarity. Cytoplasm › cytoskeleton › spindle By similarity. Note: Cytoplasmic during interphase. Targeted to the nuclear rim after sumoylation. During mitosis, associates with mitotic spindles. Association with kinetochores appears soon after nuclear envelope breakdown and persists until late anaphase. Mitotic location also requires sumoylation By similarity. Ref.5 Ref.6 Ref.8
Post-translational modification	Phosphorylated occurs before nuclear envelope breakdown and continues throughout mitosis. Phosphorylated by the M-phase kinase cyclin B/Cdk1, in vitro. Differential timimg of dephosphorylation occurs during phases of mitosis. The phosphorylated form remains associated with RANBP2/NUP358 and the SUMO E2-conjugating enzyme, UBC9, on nuclear pore complex (NPC) diassembly and during mitosis. Ref.7 Sumoylated with SUMO1. Sumoylation is necessary for targeting to the nuclear envelope (NE), and for association with mitotic spindles and kinetochores during mitosis. Also required for interaction with RANBP2 and is mediated by UBC9 By similarity. Ref.5 Ref.6 Ref.8
Sequence similarities	Belongs to the RNA1 family. Contains 6 LRR (leucine-rich) repeats.

Ontologies

Keywords
Cellular component	Centromere Chromosome Cytoplasm Cytoskeleton Kinetochore Membrane Nucleus
Domain	Leucine-rich repeat Repeat
Molecular function	GTPase activation
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of protein export from nucleus Inferred from electronic annotation. Source: Compara positive regulation of Ran GTPase activity Inferred from electronic annotation. Source: GOC signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	condensed chromosome kinetochore Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear membrane Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from direct assay PubMed 15923632. Source: MGI spindle Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	Ran GTPase activator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 589

588

Ran GTPase-activating protein 1

PRO_0000056738

Regions

Repeat

48 – 71

24

LRR 1

Repeat

111 – 134

24

LRR 2

Repeat

207 – 230

24

LRR 3

Repeat

235 – 258

24

LRR 4

Repeat

292 – 315

24

LRR 5

Repeat

320 – 343

24

LRR 6

Motif

525 – 528

4

SUMO conjugation By similarity

Compositional bias

359 – 399

41

Asp/Glu-rich (highly acidic)

Sites

Site

564

1

Hydrophobic interaction with UBC9 By similarity

Site

567

1

Hydrophobic interaction with UBC9 By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Modified residue

358

1

Phosphoserine By similarity

Modified residue

411

1

Phosphothreonine; by CDK2 By similarity

Modified residue

430

1

Phosphoserine By similarity

Modified residue

437

1

Phosphoserine By similarity

Modified residue

438

1

Phosphothreonine By similarity

Modified residue

444

1

Phosphoserine Ref.7 Ref.9

Modified residue

526

1

N6-acetyllysine By similarity

Cross-link

8

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Cross-link

526

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.5 Ref.6 Ref.8

Experimental info

Mutagenesis

411

1

T → D: Greatly reduced phosphorylation by CDK1 or CDK2. Completely abolished phosphorylation by CDK1 or CDK2; when associated with D-444. Ref.7

Mutagenesis

444

1

S → D: Little change in phosphorylation by CDK1 or CDK2. Completely abolished phosphorylation by CDK1 or CDK2; when associated with D-411. Ref.7

Mutagenesis

512

1

N → A: No effect on UBC9 binding nor on sumoylation. Ref.10

Mutagenesis

516

1

T → A: No effect on UBC9 binding nor on sumoylation. Ref.10

Mutagenesis

517

1

R → A: No effect on UBC9 binding nor on sumoylation. Ref.10

Mutagenesis

520

1

I → A: No effect on UBC9 binding nor on sumoylation.

Mutagenesis

521

1

H → A: No effect on UBC9 binding nor on sumoylation. Ref.10

Mutagenesis

522

1

M → A: No effect on UBC9 binding nor on sumoylation. Ref.10

Mutagenesis

524

1

L → A: No sumoylation. Ref.10

Mutagenesis

525

1

L → A: Disrupted binding of UCB9, and no sumoylation. Ref.10

Mutagenesis

526

1

K → A: No UBC9 binding nor sumoylation. Ref.5 Ref.6 Ref.8 Ref.10

Mutagenesis

526

1

K → R: Absence of sumoylation. Not targeted to the nuclear envelope rim nor to nuclear pore complexes. Disrupted sumoylation. No interaction with SUMO1; when associated with A-564 and with or without SUMO1 A-97. Ref.5 Ref.6 Ref.8 Ref.10

Mutagenesis

528

1

E → A: No UBC9 binding nor sumoylation. Ref.10

Mutagenesis

529

1

D → A: No effect on UBC9 binding nor on sumoylation. Ref.10

Mutagenesis

531

1

I → A: No effect on UBC9 binding nor on sumoylation. Ref.10

Mutagenesis

537

1

L → A: No effect on UBC9 binding nor on sumoylation. Ref.10

Mutagenesis

560

1

L → A: No effect on UBC9 binding nor on sumoylation. Ref.10

Mutagenesis

563

1

A → L: No effect on UBC9 binding nor on sumoylation. Ref.10

Mutagenesis

564

1

F → A: No UBC9 binding nor sumoylation. Not targeted to nuclear core complexes; when associated with R-526. Ref.6 Ref.10

Mutagenesis

567

1

K → A: No UBC9 binding nor sumoylation. Ref.10

Mutagenesis

569

1

N → A: No effect on UBC9 binding nor on sumoylation. Ref.10

Sequence conflict

181

1

A → R in AAA17681. Ref.1

Sequence conflict

413

1

S → L in AAB60517. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

589

Helix Strand Turn

Details...

Helix

436 – 441

6

Helix

445 – 450

6

Helix

455 – 461

7

Helix

468 – 480

13

Helix

486 – 505

20

Helix

511 – 521

11

Helix

538 – 549

12

Helix

555 – 557

3

Helix

558 – 565

8

Helix

577 – 588

12

Sequences

	Sequence		Length	Mass (Da)
	P46061 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 775ADE3A53EFD558	FASTA	589	63,531
	10 20 30 40 50 60 MASEDIAKLA ETLAKTQVAG GQLSFKGKGL KLNTAEDAKD VIKEIEEFDG LEALRLEGNT 70 80 90 100 110 120 VGVEAARVIA KALEKKSELK RCHWSDMFTG RLRSEIPPAL ISLGEGLITA GAQLVELDLS 130 140 150 160 170 180 DNAFGPDGVR GFEALLKSPA CFTLQELKLN NCGMGIGGGK ILAAALTECH RKSSAQGKPL 190 200 210 220 230 240 ALKVFVAGRN RLENDGATAL AEAFGIIGTL EEVHMPQNGI NHPGVTALAQ AFAINPLLRV 250 260 270 280 290 300 INLNDNTFTE KGGVAMAETL KTLRQVEVIN FGDCLVRSKG AVAIADAVRG GLPKLKELNL 310 320 330 340 350 360 SFCEIKRDAA LVVAEAVADK AELEKLDLNG NALGEEGCEQ LQEVMDSFNM AKVLASLSDD 370 380 390 400 410 420 EGEDEDEEEE GEEDDEEEED EEDEEDDDEE EEEQEEEEEP PQRGSGEEPA TPSRKILDPN 430 440 450 460 470 480 SGEPAPVLSS PTPTDLSTFL SFPSPEKLLR LGPKVSVLIV QQTDTSDPEK VVSAFLKVAS 490 500 510 520 530 540 VFRDDASVKT AVLDAIDALM KKAFSCSSFN SNTFLTRLLI HMGLLKSEDK IKAIPSLHGP 550 560 570 580 LMVLNHVVRQ DYFPKALAPL LLAFVTKPNG ALETCSFARH NLLQTLYNI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A murine homolog of the yeast RNA1 gene is required for postimplantation development." Degregori J., Russ A., von Melchner H., Rayburn H., Priyaranjan P., Jenkins N.A., Copeland N.G., Ruley H.E. Genes Dev. 8:265-276(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Separate domains of the Ran GTPase interact with different factors to regulate nuclear protein import and RNA processing." Ren M., Villamarin A., Shih A., Coutavas E., Moore M.S., Locurcio M., Clarke V., Oppenheim J.D., D'Eustachio P., Rush M.G. Mol. Cell. Biol. 15:2117-2124(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: BALB/c.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Liver and Visual cortex.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: 129 and C57BL/6J. Tissue: Mammary tumor.
[5]	"Molecular characterization of the SUMO-1 modification of RanGAP1 and its role in nuclear envelope association." Mahajan R., Gerace L., Melchior F. J. Cell Biol. 140:259-270(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-526, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-526.
[6]	"SUMO-1 modification and its role in targeting the Ran GTPase-activating protein, RanGAP1, to the nuclear pore complex." Matunis M.J., Wu J., Blobel G. J. Cell Biol. 140:499-509(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-526, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-526 AND PHE-564.
[7]	"RanGAP1*SUMO1 is phosphorylated at the onset of mitosis and remains associated with RanBP2 upon NPC disassembly." Swaminathan S., Kiendl F., Koerner R., Lupetti R., Hengst L., Melchior F. J. Cell Biol. 164:965-971(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-411 AND SER-444, MUTAGENESIS OF THR-411 AND SER-444.
[8]	"SUMO modification through rapamycin-mediated heterodimerization reveals a dual role for Ubc9 in targeting RanGAP1 to nuclear pore complexes." Zhu S., Zhang H., Matunis M.J. Exp. Cell Res. 312:1042-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-526, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-526.
[9]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-444, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
[10]	"Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1." Bernier-Villamor V., Sampson D.A., Matunis M.J., Lima C.D. Cell 108:345-356(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 420-589 IN COMPLEX WITH SUMO1 AND HUMAN UBE2I, MUTAGENESIS OF ASN-512; THR-516; ARG-517; HIS-521; MET-522; LEU-524; LEU-525; LYS-526; GLU-528; ASP-529; ILE-531; LEU-537; LEU-560; ALA-563; PHE-564; LYS-567 AND ASN-569.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U08110 mRNA. Translation: AAA17681.1.
U20857 Genomic RNA. Translation: AAB60517.1.
AK146670 mRNA. Translation: BAE27347.1.
AK159009 mRNA. Translation: BAE34767.1.
AK159525 mRNA. Translation: BAE35154.1.
BC066213 mRNA. Translation: AAH66213.1.
BC071200 mRNA. Translation: AAH71200.1.

IPI

IPI00467338.

PIR

A36983.
T52070.

RefSeq

NP_001139646.1. NM_001146174.1.
NP_035371.4. NM_011241.4.

UniGene

Mm.270975.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KPS	X-ray	2.50	B/D	420-589	[»]

ProteinModelPortal

P46061.

SMR

P46061. Positions 21-370, 434-589.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-17024N.

IntAct

P46061. 1 interaction.

STRING

10090.ENSMUSP00000057771.

PTM databases

PhosphoSite

P46061.

Proteomic databases

PaxDb

P46061.

PRIDE

P46061.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000052374; ENSMUSP00000057771; ENSMUSG00000022391.
ENSMUST00000170134; ENSMUSP00000126849; ENSMUSG00000022391.
ENSMUST00000171115; ENSMUSP00000130046; ENSMUSG00000022391.

GeneID

19387.

KEGG

mmu:19387.

Organism-specific databases

CTD

5905.

MGI

MGI:103071. Rangap1.

Phylogenomic databases

eggNOG

COG5238.

GeneTree

ENSGT00440000039203.

HOVERGEN

HBG017720.

InParanoid

Q6NZB5.

KO

K14319.

OMA

SFNSNAF.

OrthoDB

EOG4K0QN7.

Gene expression databases

ArrayExpress

P46061.

Bgee

P46061.

CleanEx

MM_RANGAP1.

Genevestigator

P46061.

GermOnline

ENSMUSG00000022391. Mus musculus.

Family and domain databases

Gene3D

1.25.40.200. 1 hit.

InterPro

IPR009109. Ran_GTPase_activating_1_C.
IPR027038. RanGap.
[Graphical view]

PANTHER

PTHR24113. PTHR24113. 1 hit.

Pfam

PF07834. RanGAP1_C. 1 hit.
[Graphical view]

SUPFAM

SSF69099. RanGAP1_C. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

RANGAP1. mouse.

EvolutionaryTrace

P46061.

NextBio

296501.

SOURCE

Search...

Entry information

Entry name

RAGP1_MOUSE

Accession

Primary (citable) accession number: P46061
Secondary accession number(s): Q60801, Q6NZB5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 127 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program