P20338 (RAB4A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ras-related protein Rab-4A

Gene names

Name:	RAB4A
Synonyms:	RAB4

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	218 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Protein transport. Probably involved in vesicular traffic By similarity.
Subunit structure	Interacts with SGSM1, SGSM2 and SGSM3 By similarity. Interacts with RAB11FIP1, RABEP1, ZFYVE20 and RUFY1. Interacts (membrane-bound form) with NDRG1; the interaction involves NDRG1 in vesicular recycling of E-cadherin. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17
Subcellular location	Membrane; Peripheral membrane protein. Cytoplasm. Note: Generally associated with membranes. Cytoplasmic when phosphorylated by CDK1.
Post-translational modification	Phosphorylated by CDK1 kinase during mitosis. Ref.8 Ref.9
Sequence similarities	Belongs to the small GTPase superfamily. Rab family.
Caution	It is uncertain whether Met-1 or Met-6 is the initiator.
Sequence caution	The sequence AAA60244.1 differs from that shown. Reason: Frameshift at position 6.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cytoplasm Membrane
Ligand	GTP-binding Nucleotide-binding
PTM	Lipoprotein Methylation Phosphoprotein Prenylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of endocytosis Inferred from electronic annotation. Source: Compara small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	endosome Inferred from electronic annotation. Source: Compara membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	GDP binding Inferred from direct assay Ref.16Ref.17. Source: UniProtKB GTP binding Inferred from direct assay Ref.16Ref.17. Source: UniProtKB GTPase activity Inferred from direct assay Ref.16Ref.17. Source: UniProtKB protein transporter activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GDI1	P31150	2	EBI-722284,EBI-946999
GDI2	P50395	2	EBI-722284,EBI-1049143

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 218

218

Ras-related protein Rab-4A

PRO_0000121093

Regions

Nucleotide binding

20 – 28

9

GTP

Nucleotide binding

68 – 72

5

GTP

Nucleotide binding

126 – 129

4

GTP

Nucleotide binding

156 – 158

3

GTP

Motif

42 – 50

9

Effector region By similarity

Amino acid modifications

Modified residue

204

1

Phosphoserine; by CDK1

Modified residue

218

1

Cysteine methyl ester By similarity

Lipidation

216

1

S-geranylgeranyl cysteine By similarity

Lipidation

218

1

S-geranylgeranyl cysteine By similarity

Experimental info

Mutagenesis

51

1

G → A: 10-fold decrease in ZFYVE20 binding affinity. Ref.17

Mutagenesis

51

1

G → L: 10-fold decrease in ZFYVE20 binding affinity. Ref.17

Sequence conflict

162

1

N → D in AAA60244. Ref.1

Sequence conflict

208

1

A → T in AAA60244. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

218

Helix Strand Turn

Details...

Beta strand

11 – 21

11

Helix

26 – 35

10

Beta strand

46 – 57

12

Beta strand

60 – 69

10

Helix

73 – 75

3

Helix

76 – 80

5

Beta strand

87 – 94

8

Helix

98 – 102

5

Helix

104 – 114

11

Beta strand

120 – 126

7

Helix

128 – 133

6

Helix

138 – 147

10

Beta strand

151 – 154

4

Turn

157 – 159

3

Helix

163 – 179

17

Sequences

	Sequence		Length	Mass (Da)
	P20338 [UniParc]. Last modified March 6, 2013. Version 3. Checksum: 983D65E1162741B0	FASTA	218	24,390
	10 20 30 40 50 60 MSQTAMSETY DFLFKFLVIG NAGTGKSCLL HQFIEKKFKD DSNHTIGVEF GSKIINVGGK 70 80 90 100 110 120 YVKLQIWDTA GQERFRSVTR SYYRGAAGAL LVYDITSRET YNALTNWLTD ARMLASQNIV 130 140 150 160 170 180 IILCGNKKDL DADREVTFLE ASRFAQENEL MFLETSALTG ENVEEAFVQC ARKILNKIES 190 200 210 GELDPERMGS GIQYGDAALR QLRSPRRAQA PNAQECGC

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]	"Regulation of CD4 expression via recycling by HRES-1/RAB4 controls susceptibility to HIV infection." Nagy G., Ward J., Mosser D.D., Koncz A., Gergely P. Jr., Stancato C., Qian Y., Fernandez D., Niland B., Grossman C.E., Telarico T., Banki K., Perl A. J. Biol. Chem. 281:34574-34591(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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.
[4]	"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: Caudate nucleus.
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.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].
[7]	"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: Skin and Uterus.
[8]	"Phosphorylation of two small GTP-binding proteins of the Rab family by p34cdc2." Bailly E., McCaffrey M., Touchot N., Zahraoui A., Goud B., Bornens M. Nature 350:715-718(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY CDK1.
[9]	"Reversible phosphorylation-dephosphorylation determines the localization of rab4 during the cell cycle." van der Sluijs P., Hull M., Huber L.A., Male P., Goud B., Mellman I. EMBO J. 11:4379-4389(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY CDK1.
[10]	"Rabaptin4, a novel effector of the small GTPase rab4a, is recruited to perinuclear recycling vesicles." Nagelkerken B., van Anken E., van Raak M., Gerez L., Mohrmann K., van Uden N., Holthuizen J., Pelkmans L., van der Sluijs P. Biochem. J. 346:593-601(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RABEP1.
[11]	"Rab coupling protein (RCP), a novel Rab4 and Rab11 effector protein." Lindsay A.J., Hendrick A.G., Cantalupo G., Senic-Matuglia F., Goud B., Bucci C., McCaffrey M.W. J. Biol. Chem. 277:12190-12199(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAB11FIP1. Tissue: Cervix carcinoma.
[12]	"Divalent Rab effectors regulate the sub-compartmental organization and sorting of early endosomes." de Renzis S., Soennichsen B., Zerial M. Nat. Cell Biol. 4:124-133(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZFYVE20.
[13]	"Characterisation of the Rab binding properties of Rab coupling protein (RCP) by site-directed mutagenesis." Lindsay A.J., McCaffrey M.W. FEBS Lett. 571:86-92(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAB11FIP1.
[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]	"The N-Myc down regulated Gene1 (NDRG1) is a Rab4a effector involved in vesicular recycling of E-cadherin." Kachhap S.K., Faith D., Qian D.Z., Shabbeer S., Galloway N.L., Pili R., Denmeade S.R., DeMarzo A.M., Carducci M.A. PLoS ONE 2:E844-E844(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NDRG1.
[16]	"High resolution crystal structures of human Rab4a in its active and inactive conformations." Huber S.K., Scheidig A.J. FEBS Lett. 579:2821-2829(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 6-189 IN COMPLEX WITH GTP ANALOG AND GDP.
[17]	"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: X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 7-177 IN COMPLEX WITH GTP, INTERACTION WITH ZFYVE20, MUTAGENESIS OF GLY-51.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M28211 mRNA. Translation: AAA60244.1. Frameshift.
AY585832 mRNA. Translation: AAT91347.1.
AF498934 mRNA. Translation: AAM21082.1.
AK313807 mRNA. Translation: BAG36543.1.
AL162595, AL117350 Genomic DNA. Translation: CAI19037.1.
AL117350, AL162595 Genomic DNA. Translation: CAI22870.1.
CH471098 Genomic DNA. Translation: EAW69890.1.
BC002438 mRNA. Translation: AAH02438.1.
BC004309 mRNA. Translation: AAH04309.1.

IPI

IPI00480056.

PIR

E34323.

RefSeq

NP_001258927.1. NM_001271998.1.
NP_004569.2. NM_004578.3.

UniGene

Hs.296169.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YU9	X-ray	2.07	A	7-177	[»]
1Z0K	X-ray	1.92	A/C	7-177	[»]
2BMD	X-ray	1.80	A	6-189	[»]
2BME	X-ray	1.57	A/B/C/D	6-189	[»]

ProteinModelPortal

P20338.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-372N.

IntAct

P20338. 12 interactions.

MINT

MINT-1376149.

STRING

9606.ENSP00000355651.

PTM databases

PhosphoSite

P20338.

Polymorphism databases

DMDM

29337213.

Proteomic databases

PaxDb

P20338.

PRIDE

P20338.

Protocols and materials databases

DNASU

5867.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000366690; ENSP00000355651; ENSG00000168118.

GeneID

5867.

KEGG

hsa:5867.

UCSC

uc001hth.3. human.

Organism-specific databases

CTD

5867.

GeneCards

GC01P229406.

HGNC

HGNC:9781. RAB4A.

HPA

CAB004990.

MIM

179511. gene.

neXtProt

NX_P20338.

PharmGKB

PA34141.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1100.

HOVERGEN

HBG009351.

InParanoid

P20338.

KO

K07879.

OrthoDB

EOG4WM4VM.

Enzyme and pathway databases

Reactome

REACT_11123. Membrane Trafficking.

Gene expression databases

Bgee

P20338.

CleanEx

HS_RAB4A.

Genevestigator

P20338.

GermOnline

ENSG00000168118. 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

EvolutionaryTrace

P20338.

GenomeRNAi

5867.

NextBio

22786.

SOURCE

Search...

Entry information

Entry name

RAB4A_HUMAN

Accession

Primary (citable) accession number: P20338
Secondary accession number(s): Q5T7P7, Q9BQ44

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	March 6, 2013
Last modified:	May 1, 2013
This is version 147 of the entry and version 3 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.