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Protein

GTP-binding protein Rit1

Gene

RIT1

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

Functioni

Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF-dependent neuronal differentiation. Involved in ELK1 transactivation through the Ras-MAPK signaling cascade that mediates a wide variety of cellular functions, including cell proliferation, survival, and differentiation.2 Publications

Enzyme regulationi

Alternates between an inactive form bound to GDP and an active form bound to GTP.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi28 – 35GTPBy similarity8
Nucleotide bindingi75 – 79GTPBy similarity5
Nucleotide bindingi134 – 137GTPBy similarity4

GO - Molecular functioni

  • calmodulin binding Source: ProtInc
  • GTPase activity Source: ParkinsonsUK-UCL
  • GTP binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • Ras protein signal transduction Source: UniProtKB
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000143622-MONOMER.
ReactomeiR-HSA-187706. Signalling to p38 via RIT and RIN.
SIGNORiQ92963.

Names & Taxonomyi

Protein namesi
Recommended name:
GTP-binding protein Rit1
Alternative name(s):
Ras-like protein expressed in many tissues
Ras-like without CAAX protein 1
Gene namesi
Name:RIT1
Synonyms:RIBB, RIT, ROC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:10023. RIT1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Noonan syndrome 8 (NS8)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells.
See also OMIM:615355
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07015057A → G in NS8; results in increased ELK1 transcriptional activation; results in increased MAPK-ERK signaling. 2 PublicationsCorresponds to variant rs672601334dbSNPEnsembl.1
Natural variantiVAR_07015181E → G in NS8; results in increased ELK1 transcriptional activation. 1 Publication1
Natural variantiVAR_07015282F → L in NS8; results in increased ELK1 transcriptional activation. 1 PublicationCorresponds to variant rs730881014dbSNPEnsembl.1
Natural variantiVAR_07015690M → I in NS8; results in increased MAPK-ERK signaling. 2 PublicationsCorresponds to variant rs483352822dbSNPEnsembl.1
Natural variantiVAR_07015795G → A in NS8; results in increased ELK1 transcriptional activation. 1 PublicationCorresponds to variant rs672601335dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi35S → N: Dominant negative. Loss of interaction with AFDN, RLF and RALGDS. 1 Publication1
Mutagenesisi53T → S: Loss of interaction with AFDN, RLF and RALGDS; when associated with L-79. 1 Publication1
Mutagenesisi55E → G: Loss of interaction with AFDN, but not with RLF and RALGDS; when associated with L-79. 1 Publication1
Mutagenesisi79Q → L: Constitutively active. Dramatic reduction of the rate of GTP hydrolysis. Loss of interaction with AFDN, RLF and RALGDS; when associated with S-53. Loss of interaction with AFDN; when associated with G-55. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi6016.
MalaCardsiRIT1.
MIMi615355. phenotype.
OpenTargetsiENSG00000143622.
Orphaneti648. Noonan syndrome.
PharmGKBiPA35528.

Polymorphism and mutation databases

BioMutaiRIT1.
DMDMi38258628.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000827251 – 219GTP-binding protein Rit1Add BLAST219

Proteomic databases

EPDiQ92963.
MaxQBiQ92963.
PaxDbiQ92963.
PeptideAtlasiQ92963.
PRIDEiQ92963.

PTM databases

iPTMnetiQ92963.
PhosphoSitePlusiQ92963.

Expressioni

Tissue specificityi

Expressed in many tissues.

Gene expression databases

BgeeiENSG00000143622.
CleanExiHS_RIT1.
ExpressionAtlasiQ92963. baseline and differential.
GenevisibleiQ92963. HS.

Organism-specific databases

HPAiHPA053249.

Interactioni

Subunit structurei

Interacts with AFDN, the C-terminal domain of RALGDS and RLF, but not with RIN1 and PIK3CA. RLF binds exclusively to the active GTP-bound form. Strongly interacts with BRAF, but only weakly with RAF1. BARF and RAF1 association is dependent upon the GTP-bound state. Interacts with RGL3 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
RLFQ131293EBI-365845,EBI-958266

GO - Molecular functioni

  • calmodulin binding Source: ProtInc

Protein-protein interaction databases

BioGridi111948. 14 interactors.
IntActiQ92963. 10 interactors.
STRINGi9606.ENSP00000357306.

Structurei

Secondary structure

1219
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi22 – 27Combined sources6
Helixi34 – 43Combined sources10
Beta strandi56 – 62Combined sources7
Beta strandi64 – 67Combined sources4
Beta strandi69 – 75Combined sources7
Beta strandi95 – 101Combined sources7
Helixi105 – 109Combined sources5
Helixi111 – 121Combined sources11
Beta strandi129 – 134Combined sources6
Helixi139 – 141Combined sources3
Helixi146 – 155Combined sources10
Beta strandi160 – 162Combined sources3
Helixi165 – 167Combined sources3
Helixi171 – 182Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4KLZX-ray2.30A19-189[»]
ProteinModelPortaliQ92963.
SMRiQ92963.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the small GTPase superfamily. Ras family.Curated

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133678.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiQ92963.
KOiK07832.
OMAiPKRTMDS.
OrthoDBiEOG091G0UAU.
PhylomeDBiQ92963.
TreeFamiTF315072.

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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q92963-1) [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
MDSGTRPVGS CCSSPAGLSR EYKLVMLGAG GVGKSAMTMQ FISHRFPEDH
60 70 80 90 100
DPTIEDAYKI RIRIDDEPAN LDILDTAGQA EFTAMRDQYM RAGEGFIICY
110 120 130 140 150
SITDRRSFHE VREFKQLIYR VRRTDDTPVV LVGNKSDLKQ LRQVTKEEGL
160 170 180 190 200
ALAREFSCPF FETSAAYRYY IDDVFHALVR EIRRKEKEAV LAMEKKSKPK
210
NSVWKRLKSP FRKKKDSVT
Length:219
Mass (Da):25,145
Last modified:February 1, 1997 - v1
Checksum:i7F957871F836AE92
GO
Isoform 2 (identifier: Q92963-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.

Show »
Length:183
Mass (Da):21,633
Checksum:i61CFC2E07B180267
GO
Isoform 3 (identifier: Q92963-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MERWLFLGATEEGPKRTM

Note: No experimental confirmation available.
Show »
Length:236
Mass (Da):27,148
Checksum:iB6B991C6D3668388
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07014935S → T Probable disease-associated mutation found in patients with features of Noonan syndrome. 1 Publication1
Natural variantiVAR_07015057A → G in NS8; results in increased ELK1 transcriptional activation; results in increased MAPK-ERK signaling. 2 PublicationsCorresponds to variant rs672601334dbSNPEnsembl.1
Natural variantiVAR_07015181E → G in NS8; results in increased ELK1 transcriptional activation. 1 Publication1
Natural variantiVAR_07015282F → L in NS8; results in increased ELK1 transcriptional activation. 1 PublicationCorresponds to variant rs730881014dbSNPEnsembl.1
Natural variantiVAR_07015382F → V Probable disease-associated mutation found in patients with features of Noonan syndrome. 1 Publication1
Natural variantiVAR_07015483T → P Probable disease-associated mutation found in patients with features of Noonan syndrome. 1
Natural variantiVAR_07015589Y → H Probable disease-associated mutation found in patients with features of Noonan syndrome. 1 Publication1
Natural variantiVAR_07015690M → I in NS8; results in increased MAPK-ERK signaling. 2 PublicationsCorresponds to variant rs483352822dbSNPEnsembl.1
Natural variantiVAR_07015795G → A in NS8; results in increased ELK1 transcriptional activation. 1 PublicationCorresponds to variant rs672601335dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0453061 – 36Missing in isoform 2. 1 PublicationAdd BLAST36
Alternative sequenceiVSP_0471141M → MERWLFLGATEEGPKRTM in isoform 3. Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U71203 mRNA. Translation: AAB42213.1.
Y07566 mRNA. Translation: CAA68851.1.
U78165 mRNA. Translation: AAB64246.1.
AF084462 mRNA. Translation: AAD13021.1.
AF493923 mRNA. Translation: AAM12637.1.
AK298768 mRNA. Translation: BAG60910.1.
AK314239 mRNA. Translation: BAG36908.1.
CR407639 mRNA. Translation: CAG28567.1.
AL139128, AL355388 Genomic DNA. Translation: CAH69943.1.
AL355388, AL139128 Genomic DNA. Translation: CAH72621.1.
CH471121 Genomic DNA. Translation: EAW53024.1.
BC104186 mRNA. Translation: AAI04187.1.
BC104187 mRNA. Translation: AAI04188.1.
CCDSiCCDS1123.1. [Q92963-1]
CCDS58036.1. [Q92963-2]
CCDS58037.1. [Q92963-3]
RefSeqiNP_001243749.1. NM_001256820.1. [Q92963-2]
NP_001243750.1. NM_001256821.1. [Q92963-3]
NP_008843.1. NM_006912.5. [Q92963-1]
UniGeneiHs.491234.

Genome annotation databases

EnsembliENST00000368322; ENSP00000357305; ENSG00000143622. [Q92963-3]
ENST00000368323; ENSP00000357306; ENSG00000143622. [Q92963-1]
ENST00000539040; ENSP00000441950; ENSG00000143622. [Q92963-2]
GeneIDi6016.
KEGGihsa:6016.
UCSCiuc001fmh.3. human. [Q92963-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U71203 mRNA. Translation: AAB42213.1.
Y07566 mRNA. Translation: CAA68851.1.
U78165 mRNA. Translation: AAB64246.1.
AF084462 mRNA. Translation: AAD13021.1.
AF493923 mRNA. Translation: AAM12637.1.
AK298768 mRNA. Translation: BAG60910.1.
AK314239 mRNA. Translation: BAG36908.1.
CR407639 mRNA. Translation: CAG28567.1.
AL139128, AL355388 Genomic DNA. Translation: CAH69943.1.
AL355388, AL139128 Genomic DNA. Translation: CAH72621.1.
CH471121 Genomic DNA. Translation: EAW53024.1.
BC104186 mRNA. Translation: AAI04187.1.
BC104187 mRNA. Translation: AAI04188.1.
CCDSiCCDS1123.1. [Q92963-1]
CCDS58036.1. [Q92963-2]
CCDS58037.1. [Q92963-3]
RefSeqiNP_001243749.1. NM_001256820.1. [Q92963-2]
NP_001243750.1. NM_001256821.1. [Q92963-3]
NP_008843.1. NM_006912.5. [Q92963-1]
UniGeneiHs.491234.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4KLZX-ray2.30A19-189[»]
ProteinModelPortaliQ92963.
SMRiQ92963.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111948. 14 interactors.
IntActiQ92963. 10 interactors.
STRINGi9606.ENSP00000357306.

PTM databases

iPTMnetiQ92963.
PhosphoSitePlusiQ92963.

Polymorphism and mutation databases

BioMutaiRIT1.
DMDMi38258628.

Proteomic databases

EPDiQ92963.
MaxQBiQ92963.
PaxDbiQ92963.
PeptideAtlasiQ92963.
PRIDEiQ92963.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368322; ENSP00000357305; ENSG00000143622. [Q92963-3]
ENST00000368323; ENSP00000357306; ENSG00000143622. [Q92963-1]
ENST00000539040; ENSP00000441950; ENSG00000143622. [Q92963-2]
GeneIDi6016.
KEGGihsa:6016.
UCSCiuc001fmh.3. human. [Q92963-1]

Organism-specific databases

CTDi6016.
DisGeNETi6016.
GeneCardsiRIT1.
HGNCiHGNC:10023. RIT1.
HPAiHPA053249.
MalaCardsiRIT1.
MIMi609591. gene.
615355. phenotype.
neXtProtiNX_Q92963.
OpenTargetsiENSG00000143622.
Orphaneti648. Noonan syndrome.
PharmGKBiPA35528.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0395. Eukaryota.
COG1100. LUCA.
GeneTreeiENSGT00860000133678.
HOGENOMiHOG000233973.
HOVERGENiHBG009351.
InParanoidiQ92963.
KOiK07832.
OMAiPKRTMDS.
OrthoDBiEOG091G0UAU.
PhylomeDBiQ92963.
TreeFamiTF315072.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000143622-MONOMER.
ReactomeiR-HSA-187706. Signalling to p38 via RIT and RIN.
SIGNORiQ92963.

Miscellaneous databases

ChiTaRSiRIT1. human.
GeneWikiiRIT1.
GenomeRNAii6016.
PROiQ92963.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000143622.
CleanExiHS_RIT1.
ExpressionAtlasiQ92963. baseline and differential.
GenevisibleiQ92963. 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 nameiRIT1_HUMAN
AccessioniPrimary (citable) accession number: Q92963
Secondary accession number(s): B4DQE8
, O00646, O00720, Q5VY89, Q5VY90
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: February 1, 1997
Last modified: November 30, 2016
This is version 149 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

Miscellaneous

Stimulation of the NGF and EGF receptor signaling pathways results in rapid and prolonged activation.
Shows rapid uncatalyzed guanine nucleotide dissociation rates, which are much faster than those of most Ras subfamily members.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.