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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	213 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.18
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.
Sequence caution	The sequence AAH02438.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAH04309.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAM21082.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAT91347.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence BAG36543.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAI19037.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAI22870.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence EAW69890.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

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	protein transport Inferred from electronic annotation. Source: UniProtKB-KW small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro
Molecular function	GDP binding Inferred from direct assay Ref.17Ref.18. Source: UniProtKB GTP binding Inferred from direct assay Ref.17Ref.18. Source: UniProtKB GTPase activity Inferred from direct assay Ref.17Ref.18. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 213

213

Ras-related protein Rab-4A

PRO_0000121093

Regions

Nucleotide binding

15 – 23

9

GTP

Nucleotide binding

63 – 67

5

GTP

Nucleotide binding

121 – 124

4

GTP

Nucleotide binding

151 – 153

3

GTP

Motif

37 – 45

9

Effector region By similarity

Amino acid modifications

Modified residue

199

1

Phosphoserine; by CDK1

Modified residue

213

1

Cysteine methyl ester By similarity

Lipidation

211

1

S-geranylgeranyl cysteine By similarity

Lipidation

213

1

S-geranylgeranyl cysteine By similarity

Experimental info

Mutagenesis

46

1

G → A: 10-fold decrease in ZFYVE20 binding affinity. Ref.18

Mutagenesis

46

1

G → L: 10-fold decrease in ZFYVE20 binding affinity. Ref.18

Sequence conflict

157

1

N → D in AAA60244. Ref.1

Sequence conflict

203

1

A → T in AAA60244. Ref.1

Secondary structure

1

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213

Helix Strand Turn

Details...

Beta strand

6 – 16

11

Helix

21 – 30

10

Beta strand

41 – 52

12

Beta strand

55 – 64

10

Helix

68 – 70

3

Helix

71 – 74

4

Helix

75 – 78

4

Beta strand

83 – 89

7

Helix

93 – 97

5

Helix

99 – 109

11

Beta strand

115 – 121

7

Helix

126 – 128

3

Helix

133 – 142

10

Beta strand

146 – 149

4

Turn

152 – 154

3

Helix

158 – 170

13

Sequences

	Sequence		Length	Mass (Da)
	P20338 [UniParc]. Last modified March 25, 2003. Version 2. Checksum: CEF81482DB48FAE1	FASTA	213	23,871
	10 20 30 40 50 60 MSETYDFLFK FLVIGNAGTG KSCLLHQFIE KKFKDDSNHT IGVEFGSKII NVGGKYVKLQ 70 80 90 100 110 120 IWDTAGQERF RSVTRSYYRG AAGALLVYDI TSRETYNALT NWLTDARMLA SQNIVIILCG 130 140 150 160 170 180 NKKDLDADRE VTFLEASRFA QENELMFLET SALTGENVEE AFVQCARKIL NKIESGELDP 190 200 210 ERMGSGIQYG DAALRQLRSP RRAQAPNAQE CGC

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: 2501306] [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: 16935861] [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: 14702039] [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: 16710414] [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: 15489334] [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: 1902553] [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: 1425574] [Abstract] Cited for: PHOSPHORYLATION BY CDK1.
[10]	"Rabaptin4, a novel effector of the samll 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: 10698684] [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: 11786538] [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: 11788822] [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: 15280022] [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: 14617813] [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: 17786215] [Abstract] Cited for: INTERACTION WITH NDRG1.
[16]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"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: 15907487] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 1-184 IN COMPLEX WITH GTP ANALOG AND GDP.
[18]	"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: 16034420] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 2-172 IN COMPLEX WITH GTP, INTERACTION WITH ZFYVE20, MUTAGENESIS OF GLY-46.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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

IPI

IPI00480056.

PIR

E34323.

RefSeq

NP_004569.2. NM_004578.2.

UniGene

Hs.296169.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YU9	X-ray	2.07	A	2-172	[»]
1Z0K	X-ray	1.92	A/C	2-172	[»]
2BMD	X-ray	1.80	A	1-184	[»]
2BME	X-ray	1.57	A/B/C/D	1-184	[»]

ProteinModelPortal

P20338.

SMR

P20338. Positions 2-177.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-372N.

IntAct

P20338. 9 interactions.

MINT

MINT-1376149.

STRING

P20338.

PTM databases

PhosphoSite

P20338.

Polymorphism databases

DMDM

29337213.

Proteomic databases

PRIDE

P20338.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000366690; ENSP00000355651; ENSG00000168118.

GeneID

5867.

KEGG

hsa:5867.

UCSC

uc001hth.1. 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

prNOG18178.

HOVERGEN

HBG009351.

InParanoid

P20338.

OrthoDB

EOG4WM4VM.

PhylomeDB

P20338.

Gene expression databases

ArrayExpress

P20338.

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]

KO

K07879.

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

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 25, 2003
Last modified:	January 25, 2012
This is version 135 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.