P20339 (RAB5A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ras-related protein Rab-5A

Gene names

Name:	RAB5A
Synonyms:	RAB5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	215 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for the fusion of plasma membranes and early endosomes. Contributes to the regulation of filopodia extension. Ref.15
Enzyme regulation	Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP.
Subunit structure	Binds EEA1. Interacts with RIN1 and GAPVD1, which regulate its pathway, probably by acting as a GEF. Interacts with RINL. Interacts with ALS2CL, RABEP1, SUN2, ZFYVE20 and RUFY1. Interacts with SGSM1 and SGSM3 By similarity. Interacts with PIK3CB By similarity. Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.16 Ref.17
Subcellular location	Cell membrane; Lipid-anchor; Cytoplasmic side By similarity. Early endosome membrane; Lipid-anchor By similarity. Melanosome. Cytoplasmic vesicle By similarity. Cell projection › ruffle By similarity. Note: Enriched in stage I melanosomes. Ref.18
Sequence similarities	Belongs to the small GTPase superfamily. Rab family.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis Protein transport Transport
Cellular component	Cell membrane Cell projection Cytoplasmic vesicle Endosome Membrane
Ligand	GTP-binding Nucleotide-binding
PTM	Lipoprotein Prenylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW nervous system development Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of exocytosis Inferred from mutant phenotype PubMed 19966785. Source: UniProtKB protein transport Inferred from electronic annotation. Source: UniProtKB-KW receptor internalization involved in canonical Wnt receptor signaling pathway Inferred from mutant phenotype PubMed 16890161. Source: BHF-UCL regulation of filopodium assembly Inferred from direct assay Ref.15. Source: UniProtKB small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	actin cytoskeleton Inferred from electronic annotation. Source: Compara early endosome Inferred from direct assay Ref.22. Source: UniProtKB early endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endocytic vesicle Inferred from electronic annotation. Source: Compara endosome membrane Traceable author statement. Source: Reactome melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell membrane raft Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell ruffle Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	GDP binding Inferred from direct assay Ref.22. Source: UniProtKB GTP binding Inferred from direct assay Ref.22. Source: UniProtKB GTPase activity Inferred from direct assay Ref.22. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EEA1	Q15075	3	EBI-399437,EBI-298113
PIK3R1	P23727	5	EBI-399437,EBI-520244	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 215

215

Ras-related protein Rab-5A

PRO_0000121104

Regions

Nucleotide binding

27 – 35

9

GTP

Nucleotide binding

75 – 79

5

GTP

Nucleotide binding

133 – 136

4

GTP

Nucleotide binding

163 – 165

3

GTP

Motif

49 – 57

9

Effector region By similarity

Amino acid modifications

Lipidation

212

1

S-geranylgeranyl cysteine Ref.2

Lipidation

213

1

S-geranylgeranyl cysteine Ref.2

Experimental info

Mutagenesis

54

1

G → Q: Strongly decreases ZFYVE20 binding affinity. Ref.16

Mutagenesis

56

1

A → E: Strongly decreases ZFYVE20 binding affinity. Ref.16

Mutagenesis

57

1

F → A: Strongly decreases RABEP1 and ZFYVE20 binding affinity. Ref.16 Ref.22

Mutagenesis

74

1

W → A: Strongly decreases RABEP1 binding affinity. Ref.22

Mutagenesis

79

1

Q → L: Loss of GTPase activity. Does not inhibit filopodia formation. Ref.15 Ref.22

Mutagenesis

82

1

Y → A: Strongly decreases RABEP1 binding affinity. Ref.22

Mutagenesis

89

1

Y → A: Strongly decreases RABEP1 binding affinity. Ref.22

Mutagenesis

116

1

K → E: No effect on RABEP1 binding affinity. Ref.22

Mutagenesis

120

1

R → E: No effect on RABEP1 binding affinity. Ref.22

Sequence conflict

81

1

R → G in AAA60245. Ref.1

Sequence conflict

197

1

R → G in AAA60245. Ref.1

Secondary structure

1

.

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215

Helix Strand Turn

Details...

Beta strand

17 – 26

10

Beta strand

28 – 32

5

Helix

33 – 42

10

Beta strand

53 – 64

12

Beta strand

67 – 76

10

Helix

80 – 85

6

Helix

86 – 90

5

Beta strand

94 – 101

8

Helix

105 – 121

17

Beta strand

127 – 133

7

Helix

135 – 140

6

Helix

145 – 154

10

Beta strand

158 – 161

4

Turn

164 – 166

3

Helix

170 – 179

10

Sequences

	Sequence		Length	Mass (Da)
	P20339 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: EC03DDF96BBEF821	FASTA	215	23,659
	10 20 30 40 50 60 MASRGATRPN GPNTGNKICQ FKLVLLGESA VGKSSLVLRF VKGQFHEFQE STIGAAFLTQ 70 80 90 100 110 120 TVCLDDTTVK FEIWDTAGQE RYHSLAPMYY RGAQAAIVVY DITNEESFAR AKNWVKELQR 130 140 150 160 170 180 QASPNIVIAL SGNKADLANK RAVDFQEAQS YADDNSLLFM ETSAKTSMNV NEIFMAIAKK 190 200 210 LPKNEPQNPG ANSARGRGVD LTEPTQPTRN QCCSN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human Rab genes encode a family of GTP-binding proteins related to yeast YPT1 and SEC4 products involved in secretion." Zahraoui A., Touchot N., Chardin P., Tavitian A. J. Biol. Chem. 264:12394-12401(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Rab geranylgeranyl transferase catalyzes the geranylgeranylation of adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5A." Farnsworth C.C., Seabra M.C., Ericsson L.H., Gelb M.H., Glomset J.A. Proc. Natl. Acad. Sci. U.S.A. 91:11963-11967(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ISOPRENYLATION AT CYS-212 AND CYS-213, MASS SPECTROMETRY.
[3]	"Identification of a new oncogene in human cancers." Kim J.W. Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Puhl H.L. III, Ikeda S.R., Aronstam R.S. Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cervix and Placenta.
[9]	"Direct interaction of EEA1 with Rab5b." Callaghan J.M., Nixon S., Bucci C., Toh B.-H., Stenmark H. Eur. J. Biochem. 265:361-366(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EEA1.
[10]	"A novel membrane-anchored Rab5 interacting protein required for homotypic endosome fusion." Hoffenberg S., Liu X., Nikolova L., Hall H.S., Dai W., Baughn R.E., Dickey B.F., Barbieri M.A., Aballay A., Stahl P.D., Knoll B.J. J. Biol. Chem. 275:24661-24669(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SUN2.
[11]	"Rabenosyn-5, a novel Rab5 effector, is complexed with hVPS45 and recruited to endosomes through a FYVE finger domain." Nielsen E., Christoforidis S., Uttenweiler-Joseph S., Miaczynska M., Dewitte F., Wilm M., Hoflack B., Zerial M. J. Cell Biol. 151:601-612(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZFYVE20. Tissue: Cervix carcinoma.
[12]	"Ras-activated endocytosis is mediated by the Rab5 guanine nucleotide exchange activity of RIN1." Tall G.G., Barbieri M.A., Stahl P.D., Horazdovsky B.F. Dev. Cell 1:73-82(2001) [PubMed] [Europe PMC] [Abstract] Cited for: ACTIVATION BY RIN1.
[13]	"ALS2CL, the novel protein highly homologous to the carboxy-terminal half of ALS2, binds to Rab5 and modulates endosome dynamics." Hadano S., Otomo A., Suzuki-Utsunomiya K., Kunita R., Yanagisawa Y., Showguchi-Miyata J., Mizumura H., Ikeda J.-E. FEBS Lett. 575:64-70(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ALS2CL.
[14]	"Rabip4' is an effector of rab5 and rab4 and regulates transport through early endosomes." Fouraux M.A., Deneka M., Ivan V., van der Heijden A., Raymackers J., van Suylekom D., van Venrooij W.J., van der Sluijs P., Pruijn G.J.M. Mol. Biol. Cell 15:611-624(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RUFY1.
[15]	"Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs." Gauthier-Campbell C., Bredt D.S., Murphy T.H., El-Husseini A. Mol. Biol. Cell 15:2205-2217(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLN-79.
[16]	"Structural basis of family-wide Rab GTPase recognition by rabenosyn-5." Eathiraj S., Pan X., Ritacco C., Lambright D.G. Nature 436:415-419(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZFYVE20, MUTAGENESIS OF GLY-54; ALA-56 AND PHE-57.
[17]	"Rab5-activating protein 6, a novel endosomal protein with a role in endocytosis." Hunker C.M., Galvis A., Kruk I., Giambini H., Veisaga M.L., Barbieri M.A. Biochem. Biophys. Res. Commun. 340:967-975(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GAPVD1.
[18]	"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes." Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F. J. Proteome Res. 5:3135-3144(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Melanoma.
[19]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[20]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]	"High resolution crystal structures of human Rab5a and five mutants with substitutions in the catalytically important phosphate-binding loop." Zhu G., Liu J., Terzyan S., Zhai P., Li G., Zhang X.C. J. Biol. Chem. 278:2452-2460(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS).
[22]	"Structural basis of Rab5-Rabaptin5 interaction in endocytosis." Zhu G., Zhai P., Liu J., Terzyan S., Li G., Zhang X.C. Nat. Struct. Mol. Biol. 11:975-983(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 15-184 IN COMPLEX WITH GTP ANALOG; GDP AND RABEP1, MUTAGENESIS OF PHE-57; TRP-74; GLN-79; TYR-82; TYR-89; LYS-116 AND ARG-120.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M28215 mRNA. Translation: AAA60245.1.
AF464088 mRNA. Translation: AAO15677.1.
AF498936 mRNA. Translation: AAM21084.1.
AK312618 mRNA. Translation: BAG35504.1.
CR536492 mRNA. Translation: CAG38731.1.
CH471055 Genomic DNA. Translation: EAW64301.1.
BC001267 mRNA. Translation: AAH01267.1.
BC018288 mRNA. Translation: AAH18288.1.

IPI

IPI00023510.

PIR

F34323.

RefSeq

NP_004153.2. NM_004162.4.

UniGene

Hs.475663.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1N6H	X-ray	1.51	A	15-184	[»]
1N6I	X-ray	1.60	A	15-184	[»]
1N6K	X-ray	1.55	A	15-184	[»]
1N6L	X-ray	1.60	A	15-184	[»]
1N6N	X-ray	1.60	A	15-184	[»]
1N6O	X-ray	1.80	A	15-184	[»]
1N6P	X-ray	1.54	A	15-184	[»]
1N6R	X-ray	1.55	A	15-184	[»]
1R2Q	X-ray	1.05	A	15-184	[»]
1TU3	X-ray	2.31	A/B/C/D/E	15-184	[»]
1TU4	X-ray	2.20	A/B/C/D	15-184	[»]
3MJH	X-ray	2.03	A/C	16-183	[»]

ProteinModelPortal

P20339.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-380N.

IntAct

P20339. 16 interactions.

MINT

MINT-209361.

STRING

9606.ENSP00000273047.

PTM databases

PhosphoSite

P20339.

Polymorphism databases

DMDM

1346958.

Proteomic databases

PaxDb

P20339.

PRIDE

P20339.

Protocols and materials databases

DNASU

5868.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000273047; ENSP00000273047; ENSG00000144566.

GeneID

5868.

KEGG

hsa:5868.

UCSC

uc003cbn.3. human.

Organism-specific databases

CTD

5868.

GeneCards

GC03P019963.

HGNC

HGNC:9783. RAB5A.

HPA

CAB004567.

MIM

179512. gene.

neXtProt

NX_P20339.

PharmGKB

PA34143.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1100.

HOGENOM

HOG000233968.

HOVERGEN

HBG009351.

InParanoid

P20339.

KO

K07887.

OMA

EPQNTGA.

OrthoDB

EOG4Z0B6M.

PhylomeDB

P20339.

Enzyme and pathway databases

Pathway_Interaction_DB

p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta.

Reactome

REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P20339.

Bgee

P20339.

CleanEx

HS_RAB5A.

Genevestigator

P20339.

GermOnline

ENSG00000144566. Homo sapiens.

Family and domain databases

InterPro

IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR003579. Small_GTPase_Rab_type.
[Graphical view]

Pfam

PF00071. Ras. 1 hit.
[Graphical view]

PRINTS

PR00449. RASTRNSFRMNG.

SMART

SM00175. RAB. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00231. small_GTP. 1 hit.

PROSITE

PS51419. RAB. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

RAB5A. human.

EvolutionaryTrace

P20339.

GenomeRNAi

5868.

NextBio

22790.

SOURCE

Search...

Entry information

Entry name

RAB5A_HUMAN

Accession

Primary (citable) accession number: P20339
Secondary accession number(s): Q6FI44

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1996
Last modified:	May 1, 2013
This is version 150 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.