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Protein

Ran GTPase-activating protein 1

Gene

RANGAP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

GTPase activator for RAN (PubMed:8146159, PubMed:8896452, PubMed:16428860). Converts cytoplasmic GTP-bound RAN to GDP-bound RAN, which is essential for RAN-mediated nuclear import and export (PubMed:8896452, PubMed:27160050). Mediates dissociation of cargo from nuclear export complexes containing XPO1, RAN and RANBP2 after nuclear export (PubMed:27160050).4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei562Hydrophobic interaction with UBE2IBy similarity1
Sitei565Hydrophobic interaction with UBE2IBy similarity1

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • GTPase activator activity Source: UniProtKB
  • Ran GTPase binding Source: UniProtKB
  • RNA binding Source: FlyBase
  • ubiquitin protein ligase binding Source: Ensembl

GO - Biological processi

Keywordsi

Molecular functionGTPase activation

Enzyme and pathway databases

ReactomeiR-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-165054 Rev-mediated nuclear export of HIV RNA
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-4615885 SUMOylation of DNA replication proteins
R-HSA-5663220 RHO GTPases Activate Formins
R-HSA-68877 Mitotic Prometaphase
SIGNORiP46060

Protein family/group databases

TCDBi1.I.1.1.3 the eukaryotic nuclear pore complex (e-npc) family

Names & Taxonomyi

Protein namesi
Recommended name:
Ran GTPase-activating protein 1
Short name:
RanGAP1
Gene namesi
Name:RANGAP1
Synonyms:KIAA1835, SD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100401.19
HGNCiHGNC:9854 RANGAP1
MIMi602362 gene
neXtProtiNX_P46060

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Kinetochore, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi91R → A: Abolishes RAN GTPase activation. 1 Publication1
Mutagenesisi356S → A: No effect on phosphorylation. 1 Publication1
Mutagenesisi358S → A: Strongly decreased phosphorylation. No effect on sumoylation. 1 Publication1
Mutagenesisi524K → R: Loss of cross-link to SUMO1. Abolishes association with nuclear pores during interphase, and with mitotic spindles during mitosis. 1 Publication1

Organism-specific databases

DisGeNETi5905
OpenTargetsiENSG00000100401
PharmGKBiPA34216

Polymorphism and mutation databases

BioMutaiRANGAP1
DMDMi1172922

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000567372 – 587Ran GTPase-activating protein 1Add BLAST586

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine1 Publication1
Cross-linki8Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternate
Cross-linki8Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Cross-linki15Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei24PhosphoserineCombined sources1
Cross-linki279Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei301PhosphoserineCombined sources1
Modified residuei358PhosphoserineCombined sources1 Publication1
Modified residuei409Phosphothreonine; by CDK21 Publication1
Modified residuei428PhosphoserineCombined sources1 Publication1
Modified residuei435PhosphoserineCombined sources1
Modified residuei436PhosphothreonineCombined sources1
Modified residuei442PhosphoserineCombined sources1 Publication1
Cross-linki452Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei524N6-acetyllysine; alternateCombined sources1
Cross-linki524Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources1 Publication
Cross-linki524Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Cross-linki586Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Phosphorylation 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, UBE2I, on nuclear pore complex (NPC) diassembly and during mitosis.1 Publication
Sumoylated (PubMed:11854305, PubMed:15037602, PubMed:26304119, PubMed:27160050). Sumoylation is necessary for targeting to the nuclear envelope (NE), and for association with mitotic spindles and kinetochores during mitosis (PubMed:11854305). Also required for interaction with RANBP2 and is mediated by UBE2I (PubMed:27160050).1 Publication5 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP46060
MaxQBiP46060
PaxDbiP46060
PeptideAtlasiP46060
PRIDEiP46060
ProteomicsDBi55712

PTM databases

iPTMnetiP46060
PhosphoSitePlusiP46060
SwissPalmiP46060

Expressioni

Tissue specificityi

Highly expressed in brain, thymus and testis.1 Publication

Gene expression databases

BgeeiENSG00000100401 Expressed in 220 organ(s), highest expression level in right testis
CleanExiHS_RANGAP1
ExpressionAtlasiP46060 baseline and differential
GenevisibleiP46060 HS

Organism-specific databases

HPAiCAB004293
HPA050110
HPA062034

Interactioni

Subunit structurei

Homodimer (PubMed:8146159). Interacts with RAN (PubMed:7891706, PubMed:8896452, PubMed:16428860). Forms a complex with RANBP2/NUP358, NXF1 and NXT1 (PubMed:14729961). Forms a tight complex in association with RANBP2/NUP358 and UBE2I/UBC9, the ubiquitin-conjugating enzyme E2 (PubMed:15037602, PubMed:27160050, PubMed:15931224, PubMed:22194619). Interacts with UBE2I; the interaction conjugates SUMO1 to RANGAP1, and subsequently stabilizes interactions of sumoylated RANGAP1 with RANBP2/NUP358 (PubMed:15037602, PubMed:27160050, PubMed:15931224). The complex composed of RANBP2, SUMO1, RANGAP1 and UBE2I associates with nuclear pore complexes (PubMed:15037602, PubMed:15931224). Identified in a complex composed of RAN, RANBP2, sumoylated RANGAP1, UBE2I and XPO1 (PubMed:27160050). Identified in a complex composed of RAN, RANGAP1 and RANBP1 (PubMed:16428860). Interacts with TRAF6 (PubMed:18093978). Interacts with SUMO1 and SENP1 (PubMed:17099698). Interacts (when sumoylated) with MYCBP2; interaction inhibits MYCBP2 E3 ubiquitin-protein ligase activity and promotes MYCBP2 translocation to the nucleus (PubMed:26304119).11 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111840, 140 interactors
DIPiDIP-29079N
IntActiP46060, 56 interactors
MINTiP46060
STRINGi9606.ENSP00000348577

Structurei

Secondary structure

1587
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP46060
SMRiP46060
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP46060

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati48 – 71LRR 1Add BLAST24
Repeati111 – 134LRR 2Add BLAST24
Repeati207 – 230LRR 3Add BLAST24
Repeati235 – 258LRR 4Add BLAST24
Repeati292 – 319LRR 5Add BLAST28
Repeati320 – 343LRR 6Add BLAST24

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi523 – 526SUMO conjugation4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi359 – 399Asp/Glu-rich (highly acidic)Add BLAST41
Compositional biasi359 – 397Asp/Glu-rich (highly acidic)Add BLAST39

Sequence similaritiesi

Belongs to the RNA1 family.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiKOG1909 Eukaryota
COG5238 LUCA
GeneTreeiENSGT00440000039203
HOGENOMiHOG000195026
HOVERGENiHBG017720
InParanoidiP46060
KOiK14319
OMAiWGVDELD
OrthoDBiEOG091G02K4
PhylomeDBiP46060
TreeFamiTF318283

Family and domain databases

Gene3Di1.25.40.200, 1 hit
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR001611 Leu-rich_rpt
IPR032675 LRR_dom_sf
IPR009109 Ran_GTPase_activating_1_C
IPR027038 RanGap
IPR036720 RanGAP1_C_sf
PANTHERiPTHR24113 PTHR24113, 1 hit
PfamiView protein in Pfam
PF13516 LRR_6, 3 hits
PF07834 RanGAP1_C, 1 hit
SUPFAMiSSF69099 SSF69099, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

P46060-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MASEDIAKLA ETLAKTQVAG GQLSFKGKSL KLNTAEDAKD VIKEIEDFDS
60 70 80 90 100
LEALRLEGNT VGVEAARVIA KALEKKSELK RCHWSDMFTG RLRTEIPPAL
110 120 130 140 150
ISLGEGLITA GAQLVELDLS DNAFGPDGVQ GFEALLKSSA CFTLQELKLN
160 170 180 190 200
NCGMGIGGGK ILAAALTECH RKSSAQGKPL ALKVFVAGRN RLENDGATAL
210 220 230 240 250
AEAFRVIGTL EEVHMPQNGI NHPGITALAQ AFAVNPLLRV INLNDNTFTE
260 270 280 290 300
KGAVAMAETL KTLRQVEVIN FGDCLVRSKG AVAIADAIRG GLPKLKELNL
310 320 330 340 350
SFCEIKRDAA LAVAEAMADK AELEKLDLNG NTLGEEGCEQ LQEVLEGFNM
360 370 380 390 400
AKVLASLSDD EDEEEEEEGE EEEEEAEEEE EEDEEEEEEE EEEEEEEPQQ
410 420 430 440 450
RGQGEKSATP SRKILDPNTG EPAPVLSSPP PADVSTFLAF PSPEKLLRLG
460 470 480 490 500
PKSSVLIAQQ TDTSDPEKVV SAFLKVSSVF KDEATVRMAV QDAVDALMQK
510 520 530 540 550
AFNSSSFNSN TFLTRLLVHM GLLKSEDKVK AIANLYGPLM ALNHMVQQDY
560 570 580
FPKALAPLLL AFVTKPNSAL ESCSFARHSL LQTLYKV
Length:587
Mass (Da):63,542
Last modified:November 1, 1995 - v1
Checksum:i3C18068AAC06B98F
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0Y4Q3H0Y4Q3_HUMAN
Ran GTPase-activating protein 1
RANGAP1
253Annotation score:
B0QYT4B0QYT4_HUMAN
Ran GTPase-activating protein 1
RANGAP1
133Annotation score:
B0QYT5B0QYT5_HUMAN
Ran GTPase-activating protein 1
RANGAP1
100Annotation score:
B0QYT6B0QYT6_HUMAN
Ran GTPase-activating protein 1
RANGAP1
37Annotation score:

Sequence cautioni

The sequence BAB47464 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029240133E → Q. Corresponds to variant dbSNP:rs2229752Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X82260 mRNA Translation: CAA57714.1
AB058738 mRNA Translation: BAB47464.1 Different initiation.
CR456557 mRNA Translation: CAG30443.1
AL035681 Genomic DNA No translation available.
BC014044 mRNA Translation: AAH14044.1
BC041396 mRNA Translation: AAH41396.1
CCDSiCCDS14012.1
PIRiJC5300
RefSeqiNP_001265580.1, NM_001278651.1
NP_001304859.1, NM_001317930.1
NP_002874.1, NM_002883.3
XP_006724352.1, XM_006724289.3
XP_011528596.1, XM_011530294.2
XP_011528597.1, XM_011530295.2
XP_016884382.1, XM_017028893.1
XP_016884383.1, XM_017028894.1
XP_016884384.1, XM_017028895.1
XP_016884385.1, XM_017028896.1
XP_016884386.1, XM_017028897.1
UniGeneiHs.183800

Genome annotation databases

EnsembliENST00000356244; ENSP00000348577; ENSG00000100401
ENST00000405486; ENSP00000385866; ENSG00000100401
ENST00000455915; ENSP00000401470; ENSG00000100401
GeneIDi5905
KEGGihsa:5905
UCSCiuc003azs.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X82260 mRNA Translation: CAA57714.1
AB058738 mRNA Translation: BAB47464.1 Different initiation.
CR456557 mRNA Translation: CAG30443.1
AL035681 Genomic DNA No translation available.
BC014044 mRNA Translation: AAH14044.1
BC041396 mRNA Translation: AAH41396.1
CCDSiCCDS14012.1
PIRiJC5300
RefSeqiNP_001265580.1, NM_001278651.1
NP_001304859.1, NM_001317930.1
NP_002874.1, NM_002883.3
XP_006724352.1, XM_006724289.3
XP_011528596.1, XM_011530294.2
XP_011528597.1, XM_011530295.2
XP_016884382.1, XM_017028893.1
XP_016884383.1, XM_017028894.1
XP_016884384.1, XM_017028895.1
XP_016884385.1, XM_017028896.1
XP_016884386.1, XM_017028897.1
UniGeneiHs.183800

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1Z5SX-ray3.01C418-587[»]
2GRNX-ray1.80B419-587[»]
2GROX-ray1.70B419-587[»]
2GRPX-ray2.05B419-587[»]
2GRQX-ray1.70B419-587[»]
2GRRX-ray1.30B419-587[»]
2IO2X-ray2.90C418-587[»]
2IO3X-ray3.20C418-587[»]
2IY0X-ray2.77C432-587[»]
3UINX-ray2.60C419-587[»]
3UIOX-ray2.60C419-587[»]
3UIPX-ray2.29C419-587[»]
5D2MX-ray2.40C/F418-587[»]
ProteinModelPortaliP46060
SMRiP46060
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111840, 140 interactors
DIPiDIP-29079N
IntActiP46060, 56 interactors
MINTiP46060
STRINGi9606.ENSP00000348577

Protein family/group databases

TCDBi1.I.1.1.3 the eukaryotic nuclear pore complex (e-npc) family

PTM databases

iPTMnetiP46060
PhosphoSitePlusiP46060
SwissPalmiP46060

Polymorphism and mutation databases

BioMutaiRANGAP1
DMDMi1172922

Proteomic databases

EPDiP46060
MaxQBiP46060
PaxDbiP46060
PeptideAtlasiP46060
PRIDEiP46060
ProteomicsDBi55712

Protocols and materials databases

DNASUi5905
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356244; ENSP00000348577; ENSG00000100401
ENST00000405486; ENSP00000385866; ENSG00000100401
ENST00000455915; ENSP00000401470; ENSG00000100401
GeneIDi5905
KEGGihsa:5905
UCSCiuc003azs.5 human

Organism-specific databases

CTDi5905
DisGeNETi5905
EuPathDBiHostDB:ENSG00000100401.19
GeneCardsiRANGAP1
HGNCiHGNC:9854 RANGAP1
HPAiCAB004293
HPA050110
HPA062034
MIMi602362 gene
neXtProtiNX_P46060
OpenTargetsiENSG00000100401
PharmGKBiPA34216
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1909 Eukaryota
COG5238 LUCA
GeneTreeiENSGT00440000039203
HOGENOMiHOG000195026
HOVERGENiHBG017720
InParanoidiP46060
KOiK14319
OMAiWGVDELD
OrthoDBiEOG091G02K4
PhylomeDBiP46060
TreeFamiTF318283

Enzyme and pathway databases

ReactomeiR-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-165054 Rev-mediated nuclear export of HIV RNA
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-4615885 SUMOylation of DNA replication proteins
R-HSA-5663220 RHO GTPases Activate Formins
R-HSA-68877 Mitotic Prometaphase
SIGNORiP46060

Miscellaneous databases

ChiTaRSiRANGAP1 human
EvolutionaryTraceiP46060
GeneWikiiRANGAP1
GenomeRNAii5905
PROiPR:P46060
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100401 Expressed in 220 organ(s), highest expression level in right testis
CleanExiHS_RANGAP1
ExpressionAtlasiP46060 baseline and differential
GenevisibleiP46060 HS

Family and domain databases

Gene3Di1.25.40.200, 1 hit
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR001611 Leu-rich_rpt
IPR032675 LRR_dom_sf
IPR009109 Ran_GTPase_activating_1_C
IPR027038 RanGap
IPR036720 RanGAP1_C_sf
PANTHERiPTHR24113 PTHR24113, 1 hit
PfamiView protein in Pfam
PF13516 LRR_6, 3 hits
PF07834 RanGAP1_C, 1 hit
SUPFAMiSSF69099 SSF69099, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRAGP1_HUMAN
AccessioniPrimary (citable) accession number: P46060
Secondary accession number(s): Q96JJ2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 7, 2018
This is version 204 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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