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Protein

Ras-related protein Rap-1b

Gene

RAP1B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

GTP-binding protein that possesses intrinsic GTPase activity. Contributes to the polarizing activity of KRIT1 and CDH5 in the establishment and maintenance of correct endothelial cell polarity and vascular lumen. Required for the localization of phosphorylated PRKCZ, PARD3 and TIAM1 to the cell junction. Plays a role in the establishment of basal endothelial barrier function.3 Publications

Enzyme regulationi

Activated by binding to the GTPase-activating protein RAP1GAP. Activated by guanine nucleotide-exchange factor (GEF) EPAC2 in a cAMP-dependent manner.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi10 – 18GTP2 Publications9
Nucleotide bindingi57 – 61GTP2 Publications5
Nucleotide bindingi116 – 119GTP2 Publications4
Nucleotide bindingi147 – 149GTP2 Publications3

GO - Molecular functioni

  • GDP binding Source: UniProtKB
  • GTPase activity Source: UniProtKB
  • GTP binding Source: UniProtKB
  • protein complex binding Source: MGI

GO - Biological processi

  • cell proliferation Source: Ensembl
  • cellular response to cAMP Source: UniProtKB
  • establishment of endothelial barrier Source: UniProtKB
  • negative regulation of synaptic vesicle exocytosis Source: Ensembl
  • positive regulation of ERK1 and ERK2 cascade Source: Ensembl
  • Rap protein signal transduction Source: UniProtKB
  • regulation of cell junction assembly Source: UniProtKB
  • regulation of establishment of cell polarity Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000127314-MONOMER.
ReactomeiR-HSA-354192. Integrin alphaIIb beta3 signaling.
R-HSA-354194. GRB2:SOS provides linkage to MAPK signaling for Integrins.
R-HSA-372708. p130Cas linkage to MAPK signaling for integrins.
R-HSA-392517. Rap1 signalling.
R-HSA-5674135. MAP2K and MAPK activation.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-6802946. Signaling by moderate kinase activity BRAF mutants.
R-HSA-6802948. Signaling by high-kinase activity BRAF mutants.
R-HSA-6802949. Signaling by RAS mutants.
R-HSA-6802952. Signaling by BRAF and RAF fusions.
R-HSA-6802955. Paradoxical activation of RAF signaling by kinase inactive BRAF.
R-HSA-8875555. MET activates RAP1 and RAC1.
SignaLinkiP61224.
SIGNORiP61224.

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-related protein Rap-1b
Alternative name(s):
GTP-binding protein smg p21B
Gene namesi
Name:RAP1B
ORF Names:OK/SW-cl.11
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:9857. RAP1B.

Subcellular locationi

GO - Cellular componenti

  • cell-cell junction Source: UniProtKB
  • cytosol Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • intracellular Source: LIFEdb
  • lipid particle Source: UniProtKB
  • membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi12G → V: Constitutively activated. 1
Mutagenesisi25Q → A: Impairs interaction with KRIT1. 1
Mutagenesisi32Y → A: 25-fold reduction in RAP1GAP-stimulated GTPase activity. 1 Publication1
Mutagenesisi32Y → F: 2-fold reduction in RAP1GAP-stimulated GTPase activity. 1 Publication1
Mutagenesisi37E → A: Strong reduction in nucleotide exchange with EPAC2. 1 Publication1
Mutagenesisi38D → A: Impairs interaction with KRIT1. 1
Mutagenesisi63Q → E: Abolishes complex formation with RAP1GAP. Loss GTPase activity. 1 Publication1
Mutagenesisi64F → A: Abolishes complex formation with RAP1GAP. Loss GTPase activity. 1 Publication1
Mutagenesisi179S → A: Abolishes phosphorylation by PKA. 1 Publication1

Organism-specific databases

DisGeNETi5908.
OpenTargetsiENSG00000127314.
PharmGKBiPA34219.

Polymorphism and mutation databases

BioMutaiRAP1B.
DMDMi47117723.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000302091 – 181Ras-related protein Rap-1bAdd BLAST181
PropeptideiPRO_0000030210182 – 184Removed in mature form3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei39ADP-ribosylserine; by botulinum toxin1 Publication1
Modified residuei179Phosphoserine; by PKA1 Publication1
Modified residuei181Cysteine methyl ester1 Publication1
Lipidationi181S-geranylgeranyl cysteine1 Publication1

Keywords - PTMi

ADP-ribosylation, Lipoprotein, Methylation, Phosphoprotein, Prenylation

Proteomic databases

EPDiP61224.
MaxQBiP61224.
PaxDbiP61224.
PeptideAtlasiP61224.
PRIDEiP61224.
TopDownProteomicsiP61224-1. [P61224-1]
P61224-2. [P61224-2]

2D gel databases

OGPiP09526.

PTM databases

iPTMnetiP61224.
PhosphoSitePlusiP61224.
SwissPalmiP61224.

Expressioni

Gene expression databases

BgeeiENSG00000127314.
CleanExiHS_RAP1B.
ExpressionAtlasiP61224. baseline and differential.
GenevisibleiP61224. HS.

Organism-specific databases

HPAiCAB015334.
CAB016402.

Interactioni

Subunit structurei

Heterodimer with RAP1GAP. Interacts with EPAC2, SGSM1, SGSM2 and SGSM3. Interacts with KRIT1.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RALGDSQ129672EBI-358143,EBI-365861
RAP1GAPP477363EBI-358143,EBI-722307
RASSF5Q8WWW03EBI-358143,EBI-367390
UBCP0CG482EBI-358143,EBI-3390054

GO - Molecular functioni

  • protein complex binding Source: MGI

Protein-protein interaction databases

BioGridi111843. 70 interactors.
DIPiDIP-35407N.
IntActiP61224. 53 interactors.
MINTiMINT-1133272.
STRINGi9606.ENSP00000250559.

Structurei

Secondary structure

1184
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi2 – 9Combined sources8
Helixi16 – 25Combined sources10
Turni27 – 29Combined sources3
Beta strandi36 – 46Combined sources11
Beta strandi49 – 58Combined sources10
Beta strandi60 – 62Combined sources3
Beta strandi63 – 65Combined sources3
Helixi68 – 74Combined sources7
Beta strandi76 – 83Combined sources8
Helixi87 – 91Combined sources5
Helixi93 – 104Combined sources12
Beta strandi105 – 107Combined sources3
Beta strandi111 – 116Combined sources6
Helixi121 – 123Combined sources3
Helixi128 – 137Combined sources10
Beta strandi142 – 145Combined sources4
Turni148 – 151Combined sources4
Helixi154 – 166Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BRWX-ray3.40D1-167[»]
3CF6X-ray2.20R1-167[»]
4DXAX-ray1.95A1-167[»]
4HDOX-ray1.67B1-167[»]
4HDQX-ray1.95B1-167[»]
4M8NX-ray3.29E/F/G/H1-166[»]
4MGIX-ray2.80R1-167[»]
4MGKX-ray2.70R1-167[»]
4MGYX-ray2.60R1-167[»]
4MGZX-ray3.00R1-167[»]
4MH0X-ray2.40R1-167[»]
5KHOX-ray2.78C/D1-167[»]
ProteinModelPortaliP61224.
SMRiP61224.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP61224.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni25 – 67Interaction with KRIT11 PublicationAdd BLAST43

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi32 – 40Effector regionCurated9

Sequence similaritiesi

Belongs to the small GTPase superfamily. Ras family.Curated

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133678.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiP61224.
KOiK07836.
OMAiRDSTHPR.
OrthoDBiEOG091G0OOG.
PhylomeDBiP61224.
TreeFamiTF313014.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P61224-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MREYKLVVLG SGGVGKSALT VQFVQGIFVE KYDPTIEDSY RKQVEVDAQQ
60 70 80 90 100
CMLEILDTAG TEQFTAMRDL YMKNGQGFAL VYSITAQSTF NDLQDLREQI
110 120 130 140 150
LRVKDTDDVP MILVGNKCDL EDERVVGKEQ GQNLARQWNN CAFLESSAKS
160 170 180
KINVNEIFYD LVRQINRKTP VPGKARKKSS CQLL
Length:184
Mass (Da):20,825
Last modified:May 10, 2004 - v1
Checksum:iCE976895E5965224
GO
Isoform 2 (identifier: P61224-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     62-108: Missing.

Show »
Length:137
Mass (Da):15,356
Checksum:iA142020053FE1BC5
GO
Isoform 3 (identifier: P61224-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     43-61: Missing.

Show »
Length:165
Mass (Da):18,778
Checksum:i5F70CFF192C43A4A
GO
Isoform 4 (identifier: P61224-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     20-61: Missing.

Show »
Length:142
Mass (Da):16,033
Checksum:iEA48A041F34E0074
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti8V → F in AAH95467 (PubMed:15489334).Curated1
Sequence conflicti16K → N in AAH78173 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04530320 – 61Missing in isoform 4. 1 PublicationAdd BLAST42
Alternative sequenceiVSP_04530443 – 61Missing in isoform 3. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_04530562 – 108Missing in isoform 2. 1 PublicationAdd BLAST47

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X08004 mRNA. Translation: CAB46488.1.
AL080212 mRNA. Translation: CAB45777.1.
AB062128 mRNA. Translation: BAB93460.1.
AF493913 mRNA. Translation: AAM12627.1.
AK298818 mRNA. Translation: BAG60950.1.
AK301401 mRNA. Translation: BAG62936.1.
AK301428 mRNA. Translation: BAG62956.1.
AK312371 mRNA. Translation: BAG35289.1.
CR407689 mRNA. Translation: CAG28617.1.
BT020093 mRNA. Translation: AAV38896.1.
EF581377 Genomic DNA. Translation: ABQ52130.1.
AC015550 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW97189.1.
BC000176 mRNA. Translation: AAH00176.1.
BC078173 mRNA. Translation: AAH78173.1.
BC095467 mRNA. Translation: AAH95467.1.
CCDSiCCDS58252.1. [P61224-2]
CCDS58253.1. [P61224-3]
CCDS58254.1. [P61224-4]
CCDS8984.1. [P61224-1]
PIRiS01952. TVHUR1.
RefSeqiNP_001010942.1. NM_001010942.2. [P61224-1]
NP_001238846.1. NM_001251917.1. [P61224-4]
NP_001238847.1. NM_001251918.1. [P61224-4]
NP_001238850.1. NM_001251921.1. [P61224-3]
NP_001238851.1. NM_001251922.1. [P61224-2]
NP_056461.1. NM_015646.5. [P61224-1]
UniGeneiHs.369920.

Genome annotation databases

EnsembliENST00000250559; ENSP00000250559; ENSG00000127314. [P61224-1]
ENST00000341355; ENSP00000441275; ENSG00000127314. [P61224-1]
ENST00000393436; ENSP00000377085; ENSG00000127314. [P61224-1]
ENST00000450214; ENSP00000399986; ENSG00000127314. [P61224-4]
ENST00000537460; ENSP00000439966; ENSG00000127314. [P61224-1]
ENST00000539091; ENSP00000444830; ENSG00000127314. [P61224-4]
ENST00000540209; ENSP00000446318; ENSG00000127314. [P61224-3]
ENST00000542145; ENSP00000440014; ENSG00000127314. [P61224-2]
GeneIDi5908.
KEGGihsa:5908.
UCSCiuc001sub.5. human. [P61224-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X08004 mRNA. Translation: CAB46488.1.
AL080212 mRNA. Translation: CAB45777.1.
AB062128 mRNA. Translation: BAB93460.1.
AF493913 mRNA. Translation: AAM12627.1.
AK298818 mRNA. Translation: BAG60950.1.
AK301401 mRNA. Translation: BAG62936.1.
AK301428 mRNA. Translation: BAG62956.1.
AK312371 mRNA. Translation: BAG35289.1.
CR407689 mRNA. Translation: CAG28617.1.
BT020093 mRNA. Translation: AAV38896.1.
EF581377 Genomic DNA. Translation: ABQ52130.1.
AC015550 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW97189.1.
BC000176 mRNA. Translation: AAH00176.1.
BC078173 mRNA. Translation: AAH78173.1.
BC095467 mRNA. Translation: AAH95467.1.
CCDSiCCDS58252.1. [P61224-2]
CCDS58253.1. [P61224-3]
CCDS58254.1. [P61224-4]
CCDS8984.1. [P61224-1]
PIRiS01952. TVHUR1.
RefSeqiNP_001010942.1. NM_001010942.2. [P61224-1]
NP_001238846.1. NM_001251917.1. [P61224-4]
NP_001238847.1. NM_001251918.1. [P61224-4]
NP_001238850.1. NM_001251921.1. [P61224-3]
NP_001238851.1. NM_001251922.1. [P61224-2]
NP_056461.1. NM_015646.5. [P61224-1]
UniGeneiHs.369920.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BRWX-ray3.40D1-167[»]
3CF6X-ray2.20R1-167[»]
4DXAX-ray1.95A1-167[»]
4HDOX-ray1.67B1-167[»]
4HDQX-ray1.95B1-167[»]
4M8NX-ray3.29E/F/G/H1-166[»]
4MGIX-ray2.80R1-167[»]
4MGKX-ray2.70R1-167[»]
4MGYX-ray2.60R1-167[»]
4MGZX-ray3.00R1-167[»]
4MH0X-ray2.40R1-167[»]
5KHOX-ray2.78C/D1-167[»]
ProteinModelPortaliP61224.
SMRiP61224.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111843. 70 interactors.
DIPiDIP-35407N.
IntActiP61224. 53 interactors.
MINTiMINT-1133272.
STRINGi9606.ENSP00000250559.

PTM databases

iPTMnetiP61224.
PhosphoSitePlusiP61224.
SwissPalmiP61224.

Polymorphism and mutation databases

BioMutaiRAP1B.
DMDMi47117723.

2D gel databases

OGPiP09526.

Proteomic databases

EPDiP61224.
MaxQBiP61224.
PaxDbiP61224.
PeptideAtlasiP61224.
PRIDEiP61224.
TopDownProteomicsiP61224-1. [P61224-1]
P61224-2. [P61224-2]

Protocols and materials databases

DNASUi5908.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000250559; ENSP00000250559; ENSG00000127314. [P61224-1]
ENST00000341355; ENSP00000441275; ENSG00000127314. [P61224-1]
ENST00000393436; ENSP00000377085; ENSG00000127314. [P61224-1]
ENST00000450214; ENSP00000399986; ENSG00000127314. [P61224-4]
ENST00000537460; ENSP00000439966; ENSG00000127314. [P61224-1]
ENST00000539091; ENSP00000444830; ENSG00000127314. [P61224-4]
ENST00000540209; ENSP00000446318; ENSG00000127314. [P61224-3]
ENST00000542145; ENSP00000440014; ENSG00000127314. [P61224-2]
GeneIDi5908.
KEGGihsa:5908.
UCSCiuc001sub.5. human. [P61224-1]

Organism-specific databases

CTDi5908.
DisGeNETi5908.
GeneCardsiRAP1B.
H-InvDBHIX0032084.
HGNCiHGNC:9857. RAP1B.
HPAiCAB015334.
CAB016402.
MIMi179530. gene.
neXtProtiNX_P61224.
OpenTargetsiENSG00000127314.
PharmGKBiPA34219.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133678.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiP61224.
KOiK07836.
OMAiRDSTHPR.
OrthoDBiEOG091G0OOG.
PhylomeDBiP61224.
TreeFamiTF313014.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000127314-MONOMER.
ReactomeiR-HSA-354192. Integrin alphaIIb beta3 signaling.
R-HSA-354194. GRB2:SOS provides linkage to MAPK signaling for Integrins.
R-HSA-372708. p130Cas linkage to MAPK signaling for integrins.
R-HSA-392517. Rap1 signalling.
R-HSA-5674135. MAP2K and MAPK activation.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-6802946. Signaling by moderate kinase activity BRAF mutants.
R-HSA-6802948. Signaling by high-kinase activity BRAF mutants.
R-HSA-6802949. Signaling by RAS mutants.
R-HSA-6802952. Signaling by BRAF and RAF fusions.
R-HSA-6802955. Paradoxical activation of RAF signaling by kinase inactive BRAF.
R-HSA-8875555. MET activates RAP1 and RAC1.
SignaLinkiP61224.
SIGNORiP61224.

Miscellaneous databases

ChiTaRSiRAP1B. human.
EvolutionaryTraceiP61224.
GeneWikiiRAP1B.
GenomeRNAii5908.
PROiP61224.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000127314.
CleanExiHS_RAP1B.
ExpressionAtlasiP61224. baseline and differential.
GenevisibleiP61224. HS.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51421. RAS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRAP1B_HUMAN
AccessioniPrimary (citable) accession number: P61224
Secondary accession number(s): B2R5Z2
, B4DQI8, B4DW74, B4DW94, P09526, Q502X3, Q5TZR4, Q6DCA1, Q6LES0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: May 10, 2004
Last modified: November 30, 2016
This is version 153 of the entry and version 1 of the sequence. [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. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.