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P46061 (RAGP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ran GTPase-activating protein 1

Short name=RanGAP1
Gene names
Name:Rangap1
Synonyms:Fug1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length589 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.9

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. Chromosomecentromerekinetochore By similarity. Cytoplasmcytoskeletonspindle 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.9

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.9

Sequence similarities

Belongs to the RNA1 family.

Contains 6 LRR (leucine-rich) repeats.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 589588Ran GTPase-activating protein 1
PRO_0000056738

Regions

Repeat48 – 7124LRR 1
Repeat111 – 13424LRR 2
Repeat207 – 23024LRR 3
Repeat235 – 25824LRR 4
Repeat292 – 31524LRR 5
Repeat320 – 34324LRR 6
Motif525 – 5284SUMO conjugation By similarity
Compositional bias359 – 39941Asp/Glu-rich (highly acidic)

Sites

Site5641Hydrophobic interaction with UBC9 By similarity
Site5671Hydrophobic interaction with UBC9 By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue3581Phosphoserine By similarity
Modified residue4111Phosphothreonine; by CDK2 By similarity
Modified residue4301Phosphoserine By similarity
Modified residue4371Phosphoserine By similarity
Modified residue4381Phosphothreonine By similarity
Modified residue4441Phosphoserine Ref.7 Ref.10
Modified residue5261N6-acetyllysine; alternate By similarity
Cross-link8Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-link526Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate Ref.5 Ref.6 Ref.9

Experimental info

Mutagenesis4111T → D: Greatly reduced phosphorylation by CDK1 or CDK2. Completely abolished phosphorylation by CDK1 or CDK2; when associated with D-444. Ref.7
Mutagenesis4441S → D: Little change in phosphorylation by CDK1 or CDK2. Completely abolished phosphorylation by CDK1 or CDK2; when associated with D-411. Ref.7
Mutagenesis5121N → A: No effect on UBC9 binding nor on sumoylation. Ref.11
Mutagenesis5161T → A: No effect on UBC9 binding nor on sumoylation. Ref.11
Mutagenesis5171R → A: No effect on UBC9 binding nor on sumoylation. Ref.11
Mutagenesis5201I → A: No effect on UBC9 binding nor on sumoylation.
Mutagenesis5211H → A: No effect on UBC9 binding nor on sumoylation. Ref.11
Mutagenesis5221M → A: No effect on UBC9 binding nor on sumoylation. Ref.11
Mutagenesis5241L → A: No sumoylation. Ref.11
Mutagenesis5251L → A: Disrupted binding of UCB9, and no sumoylation. Ref.11
Mutagenesis5261K → A: No UBC9 binding nor sumoylation. Ref.5 Ref.6 Ref.9 Ref.11
Mutagenesis5261K → 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.9 Ref.11
Mutagenesis5281E → A: No UBC9 binding nor sumoylation. Ref.11
Mutagenesis5291D → A: No effect on UBC9 binding nor on sumoylation. Ref.11
Mutagenesis5311I → A: No effect on UBC9 binding nor on sumoylation. Ref.11
Mutagenesis5371L → A: No effect on UBC9 binding nor on sumoylation. Ref.11
Mutagenesis5601L → A: No effect on UBC9 binding nor on sumoylation. Ref.11
Mutagenesis5631A → L: No effect on UBC9 binding nor on sumoylation. Ref.11
Mutagenesis5641F → A: No UBC9 binding nor sumoylation. Not targeted to nuclear core complexes; when associated with R-526. Ref.6 Ref.11
Mutagenesis5671K → A: No UBC9 binding nor sumoylation. Ref.11
Mutagenesis5691N → A: No effect on UBC9 binding nor on sumoylation. Ref.11
Sequence conflict1811A → R in AAA17681. Ref.1
Sequence conflict4131S → L in AAB60517. Ref.2

Secondary structure

.................... 589
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P46061 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 775ADE3A53EFD558

FASTA58963,531
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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]"Phosphoproteomic analysis of the developing mouse brain."
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.
Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic brain.
[9]"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.
[10]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[11]"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.
PIRA36983.
T52070.
RefSeqNP_001139646.1. NM_001146174.1.
NP_035371.4. NM_011241.4.
UniGeneMm.270975.
Mm.475271.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1KPSX-ray2.50B/D420-589[»]
ProteinModelPortalP46061.
SMRP46061. Positions 21-370, 434-589.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202583. 10 interactions.
DIPDIP-17024N.
IntActP46061. 3 interactions.
MINTMINT-4132270.
STRING10090.ENSMUSP00000057771.

PTM databases

PhosphoSiteP46061.

Proteomic databases

PaxDbP46061.
PRIDEP46061.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000052374; ENSMUSP00000057771; ENSMUSG00000022391.
ENSMUST00000170134; ENSMUSP00000126849; ENSMUSG00000022391.
ENSMUST00000171115; ENSMUSP00000130046; ENSMUSG00000022391.
GeneID19387.
KEGGmmu:19387.
UCSCuc007wxb.2. mouse.

Organism-specific databases

CTD5905.
MGIMGI:103071. Rangap1.

Phylogenomic databases

eggNOGCOG5238.
GeneTreeENSGT00440000039203.
HOVERGENHBG017720.
InParanoidQ6NZB5.
KOK14319.
OMAAEAFGII.
OrthoDBEOG70W3DV.
TreeFamTF318283.

Gene expression databases

ArrayExpressP46061.
BgeeP46061.
CleanExMM_RANGAP1.
GenevestigatorP46061.

Family and domain databases

Gene3D1.25.40.200. 1 hit.
InterProIPR009109. Ran_GTPase_activating_1_C.
IPR027038. RanGap.
[Graphical view]
PANTHERPTHR24113. PTHR24113. 1 hit.
PfamPF07834. RanGAP1_C. 1 hit.
[Graphical view]
SUPFAMSSF69099. SSF69099. 1 hit.
ProtoNetSearch...

Other

ChiTaRSRANGAP1. mouse.
EvolutionaryTraceP46061.
NextBio296501.
PROP46061.
SOURCESearch...

Entry information

Entry nameRAGP1_MOUSE
AccessionPrimary (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: April 16, 2014
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot