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Protein

Protein XRP2

Gene

RP2

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

Functioni

Acts as a GTPase-activating protein (GAP) involved in trafficking between the Golgi and the ciliary membrane. Involved in localization of proteins, such as NPHP3, to the cilium membrane by inducing hydrolysis of GTP ARL3, leading to the release of UNC119 (or UNC119B). Acts as a GTPase-activating protein (GAP) for tubulin in concert with tubulin-specific chaperone C, but does not enhance tubulin heterodimerization. Acts as guanine nucleotide dissociation inhibitor towards ADP-ribosylation factor-like proteins.4 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi98 – 99GTP2
Nucleotide bindingi115 – 118GTP4

GO - Molecular functioni

  • GTPase activator activity Source: UniProtKB
  • GTP binding Source: UniProtKB-KW
  • unfolded protein binding Source: ProtInc

GO - Biological processi

  • post-Golgi vesicle-mediated transport Source: MGI
  • protein folding Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • visual perception Source: ProtInc

Keywordsi

Molecular functionGTPase activation
Biological processProtein transport, Transport
LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-5624138 Trafficking of myristoylated proteins to the cilium

Names & Taxonomyi

Protein namesi
Recommended name:
Protein XRP2
Gene namesi
Name:RP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000102218.5
HGNCiHGNC:10274 RP2
MIMi300757 gene
neXtProtiNX_O75695

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

Cell membrane, Cell projection, Cilium, Membrane

Pathology & Biotechi

Involvement in diseasei

Retinitis pigmentosa 2 (RP2)13 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
See also OMIM:312600
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0084976Missing in RP2; loss of membrane association; enhances interaction with ARL3. 4 Publications1
Natural variantiVAR_01806967C → Y in RP2. 1 Publication1
Natural variantiVAR_01807086C → Y in RP2. 2 Publications1
Natural variantiVAR_01807195P → L in RP2; uncertain pathological significance. 2 Publications1
Natural variantiVAR_008498108C → G in RP2. 1
Natural variantiVAR_068353108C → Y in RP2. 1 Publication1
Natural variantiVAR_026058118R → C in RP2. 1 Publication1
Natural variantiVAR_008499118R → H in RP2; reduces affinity for ARL3 800-fold; loss of stimulation of tubulin GTPase activity; no effect on subcellular location. 10 PublicationsCorresponds to variant dbSNP:rs28933687Ensembl.1
Natural variantiVAR_018072118R → L in RP2. 2 PublicationsCorresponds to variant dbSNP:rs28933687Ensembl.1
Natural variantiVAR_018073137Missing in RP2. 3 Publications1
Natural variantiVAR_018074138E → G in RP2; reduces affinity for ARL3 150-fold and inhibits the GTP-hydrolysis rate of ARL3. 3 Publications1
Natural variantiVAR_018075188L → P in RP2. 1 Publication1
Natural variantiVAR_008500253L → R in RP2. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2G → A: Loss of membrane association. 1 Publication1
Mutagenesisi3C → S: Targeting to internal membranes. Loss of targeting to the plasma membrane. 1 Publication1
Mutagenesisi28S → A: Reduces affinity for mouse ARL3; when associated with A-29. 1 Publication1
Mutagenesisi29W → A: Reduces affinity for mouse ARL3; when associated with A-28. 1 Publication1
Mutagenesisi31Q → A: Does not reduce affinity for mouse ARL3; when associated with A-32. 1 Publication1
Mutagenesisi32R → A: Does not reduce affinity for mouse ARL3; when associated with A-31. 1 Publication1
Mutagenesisi101F → A: Reduces affinity for mouse ARL3. 1 Publication1
Mutagenesisi115Q → A: Reduces affinity for mouse ARL3. 1 Publication1
Mutagenesisi116Q → A: Reduces affinity and GTP-hydrolysis rate for mouse ARL3. 1 Publication1
Mutagenesisi118R → A: Reduces affinity and GTP-hydrolysis rate for mouse ARL3. 1 Publication1
Mutagenesisi120R → H: Reduces affinity for mouse ARL3; when associated with S-121. 1 Publication1
Mutagenesisi121D → S: Reduces affinity for mouse ARL3; when associated with H-120. 1
Mutagenesisi177F → A: Reduces affinity and GTP-hydrolysis rate for mouse ARL3. 1 Publication1

Keywords - Diseasei

Disease mutation, Retinitis pigmentosa

Organism-specific databases

DisGeNETi6102
GeneReviewsiRP2
MalaCardsiRP2
MIMi312600 phenotype
OpenTargetsiENSG00000102218
Orphaneti791 Retinitis pigmentosa
PharmGKBiPA34641

Polymorphism and mutation databases

BioMutaiRP2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000800472 – 350Protein XRP2Add BLAST349

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1
Lipidationi3S-palmitoyl cysteine1 Publication1 Publication1

Post-translational modificationi

Myristoylated on Gly-2; which may be required for membrane targeting.1 Publication
Palmitoylated on Cys-3; which may be required for plasma membrane targeting (Probable). Mutation of Cys-3 targets the protein to internal membranes.Curated1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Palmitate

Proteomic databases

EPDiO75695
MaxQBiO75695
PaxDbiO75695
PeptideAtlasiO75695
PRIDEiO75695

PTM databases

iPTMnetiO75695
PhosphoSitePlusiO75695
SwissPalmiO75695

Expressioni

Tissue specificityi

Ubiquitous. Expressed in the rod and cone photoreceptors, extending from the tips of the outer segment (OS) through the inner segment (IS) and outer nuclear layer (ONL) and into the synaptic terminals of the outer plexiform layer (ONL). Also detected in the bipolar, horizontal and amacrine cells in the inner nuclear layer (INL), extending to the inner plexiform layer (IPL) and though the ganglion cell layer (GCL) and into the nerve fiber layer (NFL) (at protein level).3 Publications

Gene expression databases

BgeeiENSG00000102218
CleanExiHS_RP2
ExpressionAtlasiO75695 baseline and differential
GenevisibleiO75695 HS

Organism-specific databases

HPAiHPA000234
HPA000909

Interactioni

Subunit structurei

Found in a complex with ARL3, RP2 and UNC119 (or UNC119B); RP2 induces hydrolysis of GTP ARL3 in the complex, leading to the release of UNC119 (or UNC119B). Interacts with ARL3; interaction is direct and stimulated with the activated GTP-bound form of ARL3.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Arl3Q9WUL75EBI-7996807,EBI-6860857From Mus musculus.

GO - Molecular functioni

  • unfolded protein binding Source: ProtInc

Protein-protein interaction databases

BioGridi112029, 42 interactors
DIPiDIP-29024N
ELMiO75695
IntActiO75695, 9 interactors
MINTiO75695
STRINGi9606.ENSP00000218340

Structurei

Secondary structure

1350
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi39 – 44Combined sources6
Beta strandi49 – 52Combined sources4
Beta strandi62 – 66Combined sources5
Beta strandi71 – 74Combined sources4
Beta strandi81 – 85Combined sources5
Beta strandi90 – 104Combined sources15
Beta strandi106 – 121Combined sources16
Beta strandi123 – 133Combined sources11
Beta strandi136 – 139Combined sources4
Beta strandi141 – 147Combined sources7
Helixi155 – 161Combined sources7
Beta strandi175 – 178Combined sources4
Beta strandi185 – 188Combined sources4
Helixi195 – 197Combined sources3
Helixi205 – 207Combined sources3
Turni216 – 218Combined sources3
Beta strandi235 – 240Combined sources6
Helixi246 – 259Combined sources14
Beta strandi263 – 270Combined sources8
Helixi274 – 281Combined sources8
Helixi282 – 287Combined sources6
Helixi289 – 294Combined sources6
Beta strandi297 – 304Combined sources8
Helixi307 – 318Combined sources12
Beta strandi324 – 326Combined sources3
Helixi330 – 348Combined sources19

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BX6X-ray2.10A1-350[»]
3BH6X-ray2.60B1-350[»]
3BH7X-ray1.90B1-350[»]
ProteinModelPortaliO75695
SMRiO75695
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75695

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 179C-CAP/cofactor C-likePROSITE-ProRule annotationAdd BLAST156

Sequence similaritiesi

Belongs to the TBCC family.Curated

Phylogenomic databases

eggNOGiKOG2512 Eukaryota
ENOG410Y28B LUCA
GeneTreeiENSGT00530000063741
HOGENOMiHOG000007790
HOVERGENiHBG054784
InParanoidiO75695
KOiK18272
OMAiLCCATQP
OrthoDBiEOG091G0K00
PhylomeDBiO75695
TreeFamiTF105832

Family and domain databases

Gene3Di2.160.20.70, 1 hit
3.30.70.141, 1 hit
InterProiView protein in InterPro
IPR017901 C-CAP_CF_C-like
IPR016098 CAP/MinC_C
IPR036223 CAP_C_sf
IPR006599 CARP_motif
IPR036850 NDK-like_dom_sf
IPR012945 Tubulin-bd_cofactor_C_dom
PfamiView protein in Pfam
PF07986 TBCC, 1 hit
PIRSFiPIRSF037947 Protein_XRP2_, 1 hit
SMARTiView protein in SMART
SM00673 CARP, 2 hits
SUPFAMiSSF54919 SSF54919, 1 hit
SSF69340 SSF69340, 1 hit
PROSITEiView protein in PROSITE
PS51329 C_CAP_COFACTOR_C, 1 hit

Sequencei

Sequence statusi: Complete.

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

O75695-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGCFFSKRRK ADKESRPENE EERPKQYSWD QREKVDPKDY MFSGLKDETV
60 70 80 90 100
GRLPGTVAGQ QFLIQDCENC NIYIFDHSAT VTIDDCTNCI IFLGPVKGSV
110 120 130 140 150
FFRNCRDCKC TLACQQFRVR DCRKLEVFLC CATQPIIESS SNIKFGCFQW
160 170 180 190 200
YYPELAFQFK DAGLSIFNNT WSNIHDFTPV SGELNWSLLP EDAVVQDYVP
210 220 230 240 250
IPTTEELKAV RVSTEANRSI VPISRGQRQK SSDESCLVVL FAGDYTIANA
260 270 280 290 300
RKLIDEMVGK GFFLVQTKEV SMKAEDAQRV FREKAPDFLP LLNKGPVIAL
310 320 330 340 350
EFNGDGAVEV CQLIVNEIFN GTKMFVSESK ETASGDVDSF YNFADIQMGI
Length:350
Mass (Da):39,641
Last modified:January 23, 2007 - v4
Checksum:i3C912B52C53A817E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti168N → D in CAA07577 (PubMed:9697692).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0084976Missing in RP2; loss of membrane association; enhances interaction with ARL3. 4 Publications1
Natural variantiVAR_01806967C → Y in RP2. 1 Publication1
Natural variantiVAR_01807086C → Y in RP2. 2 Publications1
Natural variantiVAR_01807195P → L in RP2; uncertain pathological significance. 2 Publications1
Natural variantiVAR_008498108C → G in RP2. 1
Natural variantiVAR_068353108C → Y in RP2. 1 Publication1
Natural variantiVAR_026058118R → C in RP2. 1 Publication1
Natural variantiVAR_008499118R → H in RP2; reduces affinity for ARL3 800-fold; loss of stimulation of tubulin GTPase activity; no effect on subcellular location. 10 PublicationsCorresponds to variant dbSNP:rs28933687Ensembl.1
Natural variantiVAR_018072118R → L in RP2. 2 PublicationsCorresponds to variant dbSNP:rs28933687Ensembl.1
Natural variantiVAR_018073137Missing in RP2. 3 Publications1
Natural variantiVAR_018074138E → G in RP2; reduces affinity for ARL3 150-fold and inhibits the GTP-hydrolysis rate of ARL3. 3 Publications1
Natural variantiVAR_053961144K → R. Corresponds to variant dbSNP:rs3126141Ensembl.1
Natural variantiVAR_018075188L → P in RP2. 1 Publication1
Natural variantiVAR_008500253L → R in RP2. 1 Publication1
Natural variantiVAR_014535282R → W Polymorphism; reduces affinity for ARL3 3-fold. 7 PublicationsCorresponds to variant dbSNP:rs1805147Ensembl.1
Natural variantiVAR_014536338D → Y1 PublicationCorresponds to variant dbSNP:rs1805148Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ007590 mRNA Translation: CAA07577.1
AL050307, AL627143 Genomic DNA Translation: CAB82030.2
BC043348 mRNA Translation: AAH43348.1
BC053530 mRNA Translation: AAH53530.1
CCDSiCCDS14270.1
RefSeqiNP_008846.2, NM_006915.2
UniGeneiHs.44766

Genome annotation databases

EnsembliENST00000218340; ENSP00000218340; ENSG00000102218
GeneIDi6102
KEGGihsa:6102
UCSCiuc004dgw.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiXRP2_HUMAN
AccessioniPrimary (citable) accession number: O75695
Secondary accession number(s): Q86XJ7, Q9NU67
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: April 25, 2018
This is version 169 of the entry and version 4 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, Reference proteome
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Main funding by: National Institutes of Health