Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins playing a key role in the regulation of 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 endosom (updated: April 7, 2021)

Protein identification was indicated in the following studies:

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

Publication	Identification ¹	Uniprot mapping ²	Not mapped / Obsolete	TrEMBL	Swiss-Prot
Goodman (2013)	2289 (gene list)	2278	53	20599	2269
Lange (2014)	1234	1234	7	28	1224
Hegedus (2015)	2638	2622	0	235	2387
Wilson (2016)	1658	1528	170	291	1068
d'Alessandro (2017)	1826	1817	2	0	1815
Bryk (2017)	2090	2060	10	108	1942
Chu (2018)	1853	1804	55	362	1387

¹ as available in the article and/or in supplementary material
² uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Protein sequence (FASTA)

Protein coevolution profile (FreeContact)

Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology.

Total structural coverage: 100%

Model score: 100

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Variant	Description
	dbSNP:rs11549759
	CMT2B
	CMT2B
	CMT2B
	CMT2B

Biological Process

Antigen processing and presentation of exogenous peptide antigen via MHC class II

Autophagosome assembly

Bone resorption

Early endosome to late endosome transport

Endocytosis

Endosome to lysosome transport

Endosome to plasma membrane protein transport

Epidermal growth factor catabolic process

Establishment of vesicle localization

Intracellular protein transport

Lipid catabolic process

Lipophagy

Multi-organism intercellular transport

Multi-organism intracellular transport

Negative regulation of exosomal secretion

Negative regulation of intralumenal vesicle formation

Neutrophil degranulation

Phagosome acidification

Phagosome maturation

Phagosome-lysosome fusion

Positive regulation of exosomal secretion

Positive regulation of protein catabolic process

Positive regulation of viral process

Protein targeting to lysosome

Protein to membrane docking

Protein transport

Rab protein signal transduction

Regulation of autophagosome assembly

Retrograde transport, endosome to Golgi

Suppression by symbiont of host defense-related programmed cell death

Viral release from host cell

Cellular Component

Alveolar lamellar body

Autophagosome membrane

Cytosol

Endomembrane system

Endosome membrane

Extracellular exosome

Extrinsic component of lysosome membrane

Golgi apparatus

Intracellular membrane-bounded organelle

Late endosome

Late endosome membrane

Lipid droplet

Lysosomal membrane

Lysosome

Melanosome

Melanosome membrane

Obsolete cell

Phagocytic vesicle

Phagocytic vesicle membrane

Phagophore assembly site membrane

Plasma membrane

Secretory granule membrane

Terminal bouton

Vacuolar membrane

Molecular Function

G protein activity

GDP binding

GTP binding

GTPase activity

Rac GTPase binding

Retromer complex binding

The reference OMIM entry for this protein is 600882

Charcot-marie-tooth disease, axonal, type 2b; cmt2b
Charcot-marie-tooth disease, autosomal dominant, type 2b
Charcot-marie-tooth neuropathy, type 2b
Hereditary motor and sensory neuropathy iib; hmsn iib
Hmsn2b

A number sign (#) is used with this entry because this form of Charcot-Marie-Tooth (

CMT

) disease can be caused by mutation in the small GTPase late endosomal protein RAB7 (602298). Hereditary sensory and autonomic neuropathy type I (HSAN1; 162400), caused by mutation in the SPTLC1 gene (605712) on chromosome 9q22, is a similar disorder with overlapping phenotypic features. For a phenotypic description and a discussion of genetic heterogeneity of axonal

CMT

, see

CMT

2A1 (118210).

CLINICAL FEATURES

In a single large kindred with an autosomal dominant peripheral sensory neuropathy, Kwon et al. (1995) demonstrated linkage of the disorder to the interval between microsatellite markers D3S1769 and D3S1744. Kwon et al. (1995) considered this to be a form of Charcot-Marie-Tooth disease, which they designated

CMT

2B. They noted that genetic studies of

CMT

2 are more complicated than those in

CMT

1 because of difficulties in establishing the diagnosis. Whereas in

CMT

1 both the clinical and the electrophysiologic findings of nerve conduction are present early in life,

CMT

2 often has its onset later in life and the neuropathic findings are those seen in common disorders such as diabetes mellitus or toxic exposures. Diagnosis of

CMT

2 relies not on a single test but on the combination of clinical history and medical examination by appropriate physical and electrodiagnostic studies. Houlden et al. (2004) reported a family with an autosomal dominant ulcero-mutilating neuropathy affecting 3 individuals over 3 generations. The proband was a 56-year-old man who developed a painful ulcer on the left sole at age 16 years. The lesion never healed, and he had numerous operations on his foot, including amputation of the second digit. He later developed progressive right foot pain with swelling and deformity. Other features included mild scoliosis, absent ankle reflexes, decreased distal sensation, lateral-gaze nystagmus, and cerebellar degeneration on MRI. The patient also reported spontaneous lancinating pain in the left foot. Muscle tone, power, and coordination were normal. Nerve conduction studies and sural nerve biopsy showed a chronic sensory axonal neuropathy with axonal degeneration and prominent regeneration. Genetic studies identified a heterozygous mutation in the RAB7 gene (602298.0003). Houlden et al. (2004) commented that the findings expanded the phenotypic spectrum of

CMT

2B; in particular, the lack of motor symptoms and lancinating pain were suggestive of HSAN1. In addition, there was evidence of central nervous system involvement with nystagmus and cerebellar atrophy.

MAPPING

Auer-Grumbach et al. (2000) studied a large Austrian family with typical features of

CMT

2B, including prominent large and small fiber sensory loss and distal muscle weakness and atrophy. Linkage analysis from 19 family members refined the localization of the

CMT

2B locus to a 10-cM interval on chromosome 3q13-q22 between markers D3S1589 and D3S1549. - Genetic Heterogeneity Auer-Grumbach et al. (2000) reported a second large Austrian family with an autosomal dominant ulcero-mutilating neuropathy that did not show linkage to the

CMT

2B locus on 3q13-q22 or the HSAN1 locus on 9q22. There were 12 definitely affected members and 16 probably affected members spanning 5 generations. Age at onset ranged from 15 to 30 years, ... More on the omim web site

Subscribe to this protein entry history

April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600882 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed

Ras-related protein Rab-7a (RAB7A)