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Protein

Ras-related protein Rab-7a

Gene

RAB7A

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

Functioni

Key regulator in endo-lysosomal trafficking. Governs early-to-late endosomal maturation, microtubule minus-end as well as plus-end directed endosomal migration and positioning, and endosome-lysosome transport through different protein-protein interaction cascades. Plays a central role, not only in endosomal traffic, but also in many other cellular and physiological events, such as growth-factor-mediated cell signaling, nutrient-transportor mediated nutrient uptake, neurotrophin transport in the axons of neurons and lipid metabolism. Also involved in regulation of some specialized endosomal membrane trafficking, such as maturation of melanosomes, pathogen-induced phagosomes (or vacuoles) and autophagosomes. Plays a role in the maturation and acidification of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis. Plays a role in the fusion of phagosomes with lysosomes. Plays important roles in microbial pathogen infection and survival, as well as in participating in the life cycle of viruses. Microbial pathogens possess survival strategies governed by RAB7A, sometimes by employing RAB7A function (e.g. Salmonella) and sometimes by excluding RAB7A function (e.g. Mycobacterium). In concert with RAC1, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. Controls the endosomal trafficking and neurite outgrowth signaling of NTRK1/TRKA (PubMed:11179213, PubMed:12944476, PubMed:14617358, PubMed:20028791, PubMed:21255211). Regulates the endocytic trafficking of the EGF-EGFR complex by regulating its lysosomal degradation. Involved in the ADRB2-stimulated lipolysis through lipophagy, a cytosolic lipase-independent autophagic pathway (By similarity). Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413).By similarity5 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi15 – 22GTP2 Publications8
Nucleotide bindingi34 – 40GTP2 Publications7
Nucleotide bindingi63 – 67GTP2 Publications5
Nucleotide bindingi125 – 128GTP2 Publications4
Nucleotide bindingi156 – 157GTP2 Publications2

GO - Molecular functioni

  • GDP binding Source: BHF-UCL
  • GTPase activity Source: BHF-UCL
  • GTP binding Source: BHF-UCL
  • retromer complex binding Source: ParkinsonsUK-UCL

GO - Biological processi

Keywordsi

Biological processAutophagy, Lipid degradation, Lipid metabolism, Protein transport, Transport
LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-2132295 MHC class II antigen presentation
R-HSA-6798695 Neutrophil degranulation
R-HSA-8854214 TBC/RABGAPs
R-HSA-8873719 RAB geranylgeranylation
R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs
SignaLinkiP51149

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-related protein Rab-7a
Gene namesi
Name:RAB7A
Synonyms:RAB7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000075785.12
HGNCiHGNC:9788 RAB7A
MIMi602298 gene
neXtProtiNX_P51149

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

Cytoplasmic vesicle, Endosome, Lipid droplet, Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Charcot-Marie-Tooth disease 2B (CMT2B)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced.
See also OMIM:600882
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_018722129L → F in CMT2B; increases GTP hydrolysis; decreases affinity for GTP and GDP; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 3 PublicationsCorresponds to variant dbSNP:rs121909078EnsemblClinVar.1
Natural variantiVAR_037887157K → N in CMT2B; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 2 PublicationsCorresponds to variant dbSNP:rs121909081EnsemblClinVar.1
Natural variantiVAR_037888161N → T in CMT2B; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 2 PublicationsCorresponds to variant dbSNP:rs121909080EnsemblClinVar.1
Natural variantiVAR_018723162V → M in CMT2B; increases GTP hydrolysis; decreases affinity for GTP and GDP; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 3 PublicationsCorresponds to variant dbSNP:rs121909079EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi8L → A: Abolishes interaction with RILP and reduces its localization to late endosomal/lysosomal compartments. 1 Publication1
Mutagenesisi10K → A: Abolishes interaction with RILP and localization to late endosomal/lysosomal compartments. 1 Publication1
Mutagenesisi22T → N: Abolishes localization on late endosomes, lysosomes and phagosomes and reduces phagosomal fusions. Abolishes association of RILP with the phagosomes. No loss of interaction with CLN5. 2 Publications1
Mutagenesisi67Q → L: Does not abolish localization on late endosomes, lysosomes and phagosomes and does not reduce phagosomal fusions. No loss of interaction with CLN5. 2 Publications1
Mutagenesisi180V → A: Abolishes interaction with RILP and localization to late endosomal/lysosomal compartments. 1 Publication1
Mutagenesisi182L → A: Does not abolish interaction with RILP and localization to late endosomal/lysosomal compartments. Does not abolish interaction with RILP and localization to late endosomal/lysosomal compartments; when associated with A-183. 1 Publication1
Mutagenesisi183Y → A: Does not abolish interaction with RILP and localization to late endosomal/lysosomal compartments. Does not abolish interaction with RILP and localization to late endosomal/lysosomal compartments; when associated with A-182. 1 Publication1

Keywords - Diseasei

Charcot-Marie-Tooth disease, Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi7879
GeneReviewsiRAB7A
MalaCardsiRAB7A
MIMi600882 phenotype
OpenTargetsiENSG00000075785
Orphaneti99936 Autosomal dominant Charcot-Marie-Tooth disease type 2B
PharmGKBiPA162400619

Chemistry databases

DrugBankiDB04315 Guanosine-5'-Diphosphate

Polymorphism and mutation databases

BioMutaiRAB7A
DMDMi1709999

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001211212 – 207Ras-related protein Rab-7aAdd BLAST206

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylthreonineCombined sources1
Modified residuei72PhosphoserineCombined sources1
Lipidationi205S-geranylgeranyl cysteineBy similarity1
Modified residuei207Cysteine methyl esterBy similarity1
Lipidationi207S-geranylgeranyl cysteineBy similarity1

Keywords - PTMi

Acetylation, Lipoprotein, Methylation, Phosphoprotein, Prenylation

Proteomic databases

EPDiP51149
MaxQBiP51149
PaxDbiP51149
PeptideAtlasiP51149
PRIDEiP51149
ProteomicsDBi56284
TopDownProteomicsiP51149

PTM databases

iPTMnetiP51149
PhosphoSitePlusiP51149
SwissPalmiP51149

Expressioni

Tissue specificityi

Widely expressed; high expression found in skeletal muscle.1 Publication

Gene expression databases

BgeeiENSG00000075785 Expressed in 233 organ(s), highest expression level in frontal cortex
CleanExiHS_RAB7A
ExpressionAtlasiP51149 baseline and differential
GenevisibleiP51149 HS

Organism-specific databases

HPAiCAB037131
HPA006964

Interactioni

Subunit structurei

The GTP-bound form interacts with RAC1 (By similarity). Interacts with NTRK1/TRKA (By similarity). Interacts with C9orf72 (By similarity). Interacts with CHM, the substrate-binding subunit of the Rab geranylgeranyltransferase complex (By similarity). Interacts with RILP (PubMed:11179213, PubMed:14668488, PubMed:15933719, PubMed:20028791, PubMed:22431521). Interacts with PSMA7 (PubMed:14998988). Interacts with RNF115 (PubMed:16925951). Interacts with FYCO1 (PubMed:20100911). Interacts with the PIK3C3/VPS34-PIK3R4 complex (PubMed:14617358). The GTP-bound form interacts with OSBPL1A (PubMed:16176980). Interacts with CLN3 (PubMed:22261744). Does not interact with HPS4 and the BLOC-3 complex (heterodimer of HPS1 and HPS4) (PubMed:20048159). Interacts with CLN5 (PubMed:22431521). Interacts with PLEKHM1 (via N- and C-terminus) (By similarity).By similarity12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RILPQ96NA22EBI-1056089,EBI-2856119

Protein-protein interaction databases

BioGridi113624, 178 interactors
DIPiDIP-39879N
IntActiP51149, 112 interactors
MINTiP51149
STRINGi9606.ENSP00000265062

Structurei

Secondary structure

1207
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP51149
SMRiP51149
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP51149

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi37 – 45Effector regionBy similarity9

Sequence similaritiesi

Belongs to the small GTPase superfamily. Rab family.Curated

Phylogenomic databases

eggNOGiKOG0394 Eukaryota
ENOG410XNZV LUCA
GeneTreeiENSGT00760000119125
HOGENOMiHOG000233968
HOVERGENiHBG009351
InParanoidiP51149
KOiK07897
OMAiSAKRAQQ
OrthoDBiEOG091G0JIV
PhylomeDBiP51149
TreeFamiTF105605

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51419 RAB, 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 6 potential isoforms that are computationally mapped.iShow all

P51149-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTSRKKVLLK VIILGDSGVG KTSLMNQYVN KKFSNQYKAT IGADFLTKEV
60 70 80 90 100
MVDDRLVTMQ IWDTAGQERF QSLGVAFYRG ADCCVLVFDV TAPNTFKTLD
110 120 130 140 150
SWRDEFLIQA SPRDPENFPF VVLGNKIDLE NRQVATKRAQ AWCYSKNNIP
160 170 180 190 200
YFETSAKEAI NVEQAFQTIA RNALKQETEV ELYNEFPEPI KLDKNDRAKA

SAESCSC
Length:207
Mass (Da):23,490
Last modified:October 1, 1996 - v1
Checksum:iA2AF33B16A672971
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9IZZ0C9IZZ0_HUMAN
Ras-related protein Rab-7a
RAB7A
116Annotation score:
C9J592C9J592_HUMAN
Ras-related protein Rab-7a
RAB7A
150Annotation score:
C9J4V0C9J4V0_HUMAN
Ras-related protein Rab-7a
RAB7A
134Annotation score:
C9J7D1C9J7D1_HUMAN
Ras-related protein Rab-7a
RAB7A
91Annotation score:
C9J8S3C9J8S3_HUMAN
Ras-related protein Rab-7a
RAB7A
160Annotation score:
C9J4S4C9J4S4_HUMAN
Ras-related protein Rab-7a
RAB7A
98Annotation score:

Sequence cautioni

The sequence BAA91390 differs from that shown. Reason: Erroneous translation. Wrong choice of frame.Curated
The sequence BAF83410 differs from that shown. Reason: Erroneous translation. Wrong choice of frame.Curated
The sequence EAW79303 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti47T → I in AAD02565 (Ref. 3) Curated1
Sequence conflicti108I → V in AAA86640 (PubMed:9126495).Curated1
Sequence conflicti127I → V in AAA86640 (PubMed:9126495).Curated1
Sequence conflicti180V → E in AAD02565 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03788632K → E. Corresponds to variant dbSNP:rs11549759Ensembl.1
Natural variantiVAR_018722129L → F in CMT2B; increases GTP hydrolysis; decreases affinity for GTP and GDP; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 3 PublicationsCorresponds to variant dbSNP:rs121909078EnsemblClinVar.1
Natural variantiVAR_037887157K → N in CMT2B; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 2 PublicationsCorresponds to variant dbSNP:rs121909081EnsemblClinVar.1
Natural variantiVAR_037888161N → T in CMT2B; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 2 PublicationsCorresponds to variant dbSNP:rs121909080EnsemblClinVar.1
Natural variantiVAR_018723162V → M in CMT2B; increases GTP hydrolysis; decreases affinity for GTP and GDP; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 3 PublicationsCorresponds to variant dbSNP:rs121909079EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X93499 mRNA Translation: CAA63763.1
U44104 mRNA Translation: AAA86640.1
AF050175 Genomic DNA Translation: AAD02565.1
AF498942 mRNA Translation: AAM21090.1
AK000826 mRNA Translation: BAA91390.1 Sequence problems.
AK290721 mRNA Translation: BAF83410.1 Sequence problems.
BC008721 mRNA Translation: AAH08721.2
CH471052 Genomic DNA Translation: EAW79303.1 Sequence problems.
CCDSiCCDS3052.1
PIRiJC5268
RefSeqiNP_004628.4, NM_004637.5
UniGeneiHs.684374
Hs.744853

Genome annotation databases

EnsembliENST00000265062; ENSP00000265062; ENSG00000075785
GeneIDi7879
KEGGihsa:7879
UCSCiuc003eks.2 human

Similar proteinsi

Cross-referencesi

Web resourcesi

Inherited peripheral neuropathies mutation db
Leiden Muscular Dystrophy pages RAB7A, member RAS oncogene family (RAB7A)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X93499 mRNA Translation: CAA63763.1
U44104 mRNA Translation: AAA86640.1
AF050175 Genomic DNA Translation: AAD02565.1
AF498942 mRNA Translation: AAM21090.1
AK000826 mRNA Translation: BAA91390.1 Sequence problems.
AK290721 mRNA Translation: BAF83410.1 Sequence problems.
BC008721 mRNA Translation: AAH08721.2
CH471052 Genomic DNA Translation: EAW79303.1 Sequence problems.
CCDSiCCDS3052.1
PIRiJC5268
RefSeqiNP_004628.4, NM_004637.5
UniGeneiHs.684374
Hs.744853

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1T91X-ray1.90A/B/C/D1-207[»]
1YHNX-ray3.00A1-207[»]
3LAWX-ray2.80A/B/C/D/E1-207[»]
ProteinModelPortaliP51149
SMRiP51149
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113624, 178 interactors
DIPiDIP-39879N
IntActiP51149, 112 interactors
MINTiP51149
STRINGi9606.ENSP00000265062

Chemistry databases

DrugBankiDB04315 Guanosine-5'-Diphosphate

PTM databases

iPTMnetiP51149
PhosphoSitePlusiP51149
SwissPalmiP51149

Polymorphism and mutation databases

BioMutaiRAB7A
DMDMi1709999

Proteomic databases

EPDiP51149
MaxQBiP51149
PaxDbiP51149
PeptideAtlasiP51149
PRIDEiP51149
ProteomicsDBi56284
TopDownProteomicsiP51149

Protocols and materials databases

DNASUi7879
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265062; ENSP00000265062; ENSG00000075785
GeneIDi7879
KEGGihsa:7879
UCSCiuc003eks.2 human

Organism-specific databases

CTDi7879
DisGeNETi7879
EuPathDBiHostDB:ENSG00000075785.12
GeneCardsiRAB7A
GeneReviewsiRAB7A
HGNCiHGNC:9788 RAB7A
HPAiCAB037131
HPA006964
MalaCardsiRAB7A
MIMi600882 phenotype
602298 gene
neXtProtiNX_P51149
OpenTargetsiENSG00000075785
Orphaneti99936 Autosomal dominant Charcot-Marie-Tooth disease type 2B
PharmGKBiPA162400619
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0394 Eukaryota
ENOG410XNZV LUCA
GeneTreeiENSGT00760000119125
HOGENOMiHOG000233968
HOVERGENiHBG009351
InParanoidiP51149
KOiK07897
OMAiSAKRAQQ
OrthoDBiEOG091G0JIV
PhylomeDBiP51149
TreeFamiTF105605

Enzyme and pathway databases

ReactomeiR-HSA-2132295 MHC class II antigen presentation
R-HSA-6798695 Neutrophil degranulation
R-HSA-8854214 TBC/RABGAPs
R-HSA-8873719 RAB geranylgeranylation
R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs
SignaLinkiP51149

Miscellaneous databases

ChiTaRSiRAB7A human
EvolutionaryTraceiP51149
GeneWikiiRAB7A
GenomeRNAii7879
PROiPR:P51149
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000075785 Expressed in 233 organ(s), highest expression level in frontal cortex
CleanExiHS_RAB7A
ExpressionAtlasiP51149 baseline and differential
GenevisibleiP51149 HS

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR005225 Small_GTP-bd_dom
IPR001806 Small_GTPase
PfamiView protein in Pfam
PF00071 Ras, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
PS51419 RAB, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRAB7A_HUMAN
AccessioniPrimary (citable) accession number: P51149
Secondary accession number(s): A8K3V6, Q9NWJ0, Q9UPB0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: September 12, 2018
This is version 199 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, Reference proteome
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Main funding by: National Institutes of Health

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