Reviewed, UniProtKB/Swiss-Prot Q15276 (RABE1_HUMAN)

Names and origin

Protein names

Recommended name:
    Rab GTPase-binding effector protein 1
Alternative name(s):
    Rabaptin-5
    Rabaptin-5alpha
    Rabaptin-4
    Renal carcinoma antigen NY-REN-17

Gene names

Name:	RABEP1
Synonyms:	RABPT5, RABPT5A

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	862 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Rab effector protein acting as linker between gamma-adaptin, RAB4A and RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Stimulates RABGEF1 mediated nucleotide exchange on RAB5A. Ref.1 Ref.2 Ref.9 Ref.11
Subunit structure	Homodimer when bound to RAB5A. Heterodimer with RABGEF1. The heterodimer binds RAB4A and RAB5A that have been activated by GTP-binding. Binds TSC2, GGA1, GGA2, GGA3, AP1G1 and AP1G2. Ref.19
Subcellular location	Cytoplasm. Early endosome. Recycling endosome Ref.1 Ref.2 Ref.11 Ref.10.
Post-translational modification	Proteolytic cleavage by caspases in apoptotic cells causes loss of endosome fusion activity.
Sequence similarities	Belongs to the rabaptin family.

Ontologies

Keywords
Biological process	Apoptosis Endocytosis Protein transport Transport
Cellular component	Cytoplasm Endosome
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW endocytosis Ref.1 Traceable author statement. Source: ProtInc membrane fusion Ref.1 Traceable author statement. Source: ProtInc protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	early endosome Ref.1 Traceable author statement. Source: ProtInc recycling endosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	GTPase activator activity Inferred from electronic annotation. Source: InterPro growth factor activity Inferred from electronic annotation. Source: InterPro protein homodimerization activity Ref.19 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GGA1	Q9UJY5	4	EBI-447043,EBI-447141
GGA2	Q9UJY4	2	EBI-447043,EBI-447646
GGA3	Q9NZ52	1	EBI-447043,EBI-447404
YWHAG	P61981	1	EBI-447043,EBI-359832
YWHAQ	P27348	1	EBI-447043,EBI-359854

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q15276-1)

Also known as: Rabaptin-5;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q15276-2)

Also known as: Rabaptin-4;

The sequence of this isoform differs from the canonical sequence as follows:
     758-790: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 862

861

Rab GTPase-binding effector protein 1

PRO_0000187556

Regions

Coiled coil

11 – 345

335

Potential

Coiled coil

534 – 816

283

Potential

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.16

Modified residue

282

1

N6-acetyllysine Ref.18

Modified residue

407

1

Phosphoserine Ref.16 Ref.12 Ref.14 Ref.17

Modified residue

408

1

Phosphothreonine Ref.16 Ref.13

Modified residue

410

1

Phosphoserine Ref.16 Ref.14 Ref.13

Natural variations

Alternative sequence

758 – 790

33

Missing in isoform 2.

VSP_010451

Natural variant

640

1

E → G: dbSNP rs3026099.

VAR_028106

Experimental info

Mutagenesis

812

1

D → K: No effect on RAB5A binding affinty. Ref.19

Mutagenesis

815

1

E → K: No effect on RAB5A binding affinty. Ref.19

Mutagenesis

818

1

Q → W: Strongly decreases RAB5A binding affinty. Ref.19

Mutagenesis

820

1

D → K: Strongly decreases RAB5A binding affinty. Ref.19

Mutagenesis

821

1

F → R: Strongly decreases RAB5A binding affinty. Ref.19

Mutagenesis

822

1

V → D: Strongly decreases RAB5A binding affinty. Ref.19

Mutagenesis

826

1

Q → A: Strongly decreases RAB5A binding affinty. Ref.19

Mutagenesis

829

1

Q → A: Strongly decreases RAB5A binding affinty. Ref.19

Sequence conflict

149

1

S → Y Ref.1

Sequence conflict

149

1

S → Y Ref.2

Secondary structure

1

.

.

.

.

.

.

.

862

Helix Strand Turn

Details...

Helix

553 – 639

87

Helix

805 – 836

32

Helix

841 – 847

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Rabaptin-5) [UniParc]. Last modified October 17, 2006. Version 2. Checksum: CAAF91638B8ED516	FASTA	862	99,290
	10 20 30 40 50 60 MAQPGPASQP DVSLQQRVAE LEKINAEFLR AQQQLEQEFN QKRAKFKELY LAKEEDLKRQ 70 80 90 100 110 120 NAVLQAAQDD LGHLRTQLWE AQAEMENIKA IATVSENTKQ EAIDEVKRQW REEVASLQAV 130 140 150 160 170 180 MKETVRDYEH QFHLRLEQER TQWAQYRESA EREIADLRRR LSEGQEEENL ENEMKKAQED 190 200 210 220 230 240 AEKLRSVVMP MEKEIAALKD KLTEAEDKIK ELEASKVKEL NHYLEAEKSC RTDLEMYVAV 250 260 270 280 290 300 LNTQKSVLQE DAEKLRKELH EVCHLLEQER QQHNQLKHTW QKANDQFLES QRLLMRDMQR 310 320 330 340 350 360 MEIVLTSEQL RQVEELKKKD QEDDEQQRLN KRKDHKKADV EEEIKIPVVC ALTQEESSAQ 370 380 390 400 410 420 LSNEEEHLDS TRGSVHSLDA GLLLPSGDPF SKSDNDMFKD GLRRAQSTDS LGTSGSLQSK 430 440 450 460 470 480 ALGYNYKAKS AGNLDESDFG PLVGADSVSE NFDTASLGSL QMPSGFMLTK DQERAIKAMT 490 500 510 520 530 540 PEQEETASLL SSVTQGMESA YVSPSGYRLV SETEWNLLQK EVHNAGNKLG RRCDMCSNYE 550 560 570 580 590 600 KQLQGIQIQE AETRDQVKKL QLMLRQANDQ LEKTMKDKQE LEDFIKQSSE DSSHQISALV 610 620 630 640 650 660 LRAQASEILL EELQQGLSQA KRDVQEQMAV LMQSREQVSE ELVRLQKDND SLQGKHSLHV 670 680 690 700 710 720 SLQQAEDFIL PDTTEALREL VLKYREDIIN VRTAADHVEE KLKAEILFLK EQIQAEQCLK 730 740 750 760 770 780 ENLEETLQLE IENCKEEIAS ISSLKAELER IKVEKGQLES TLREKSQQLE SLQEIKISLE 790 800 810 820 830 840 EQLKKETAAK ATVEQLMFEE KNKAQRLQTE LDVSEQVQRD FVKLSQTLQV QLERIRQADS 850 860 LERIRAILND TKLTDINQLP ET
	Isoform 2 (Rabaptin-4). Checksum: 5B9D6E6BDF9627CD	FASTA	829	95,479
	10 20 30 40 50 60 MAQPGPASQP DVSLQQRVAE LEKINAEFLR AQQQLEQEFN QKRAKFKELY LAKEEDLKRQ 70 80 90 100 110 120 NAVLQAAQDD LGHLRTQLWE AQAEMENIKA IATVSENTKQ EAIDEVKRQW REEVASLQAV 130 140 150 160 170 180 MKETVRDYEH QFHLRLEQER TQWAQYRESA EREIADLRRR LSEGQEEENL ENEMKKAQED 190 200 210 220 230 240 AEKLRSVVMP MEKEIAALKD KLTEAEDKIK ELEASKVKEL NHYLEAEKSC RTDLEMYVAV 250 260 270 280 290 300 LNTQKSVLQE DAEKLRKELH EVCHLLEQER QQHNQLKHTW QKANDQFLES QRLLMRDMQR 310 320 330 340 350 360 MEIVLTSEQL RQVEELKKKD QEDDEQQRLN KRKDHKKADV EEEIKIPVVC ALTQEESSAQ 370 380 390 400 410 420 LSNEEEHLDS TRGSVHSLDA GLLLPSGDPF SKSDNDMFKD GLRRAQSTDS LGTSGSLQSK 430 440 450 460 470 480 ALGYNYKAKS AGNLDESDFG PLVGADSVSE NFDTASLGSL QMPSGFMLTK DQERAIKAMT 490 500 510 520 530 540 PEQEETASLL SSVTQGMESA YVSPSGYRLV SETEWNLLQK EVHNAGNKLG RRCDMCSNYE 550 560 570 580 590 600 KQLQGIQIQE AETRDQVKKL QLMLRQANDQ LEKTMKDKQE LEDFIKQSSE DSSHQISALV 610 620 630 640 650 660 LRAQASEILL EELQQGLSQA KRDVQEQMAV LMQSREQVSE ELVRLQKDND SLQGKHSLHV 670 680 690 700 710 720 SLQQAEDFIL PDTTEALREL VLKYREDIIN VRTAADHVEE KLKAEILFLK EQIQAEQCLK 730 740 750 760 770 780 ENLEETLQLE IENCKEEIAS ISSLKAELER IKVEKGQATV EQLMFEEKNK AQRLQTELDV 790 800 810 820 SEQVQRDFVK LSQTLQVQLE RIRQADSLER IRAILNDTKL TDINQLPET

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Rabaptin-5 is a direct effector of the small GTPase Rab5 in endocytic membrane fusion." Stenmark H., Vitale G., Ulrich O., Zerial M. Cell 83:423-432(1995) [PubMed: 8521472] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAB5A. Tissue: Cervix carcinoma.
[2]	"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAB4A AND RAB5A. Tissue: Cervix carcinoma.
[3]	"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] (ISOFORM 1). Tissue: Testis.
[4]	Lubec G., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 807-819, MASS SPECTROMETRY. Tissue: Fetal brain cortex.
[5]	"A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function." Horiuchi H., Lippe R., McBride H.M., Rubino M., Woodman P., Stenmark H., Rybin V., Wilm M., Ashman K., Mann M., Zerial M. Cell 90:1149-1159(1997) [PubMed: 9323142] [Abstract] Cited for: INTERACTION WITH RABGEF1.
[6]	"Cleavage of rabaptin-5 blocks endosome fusion during apoptosis." Cosulich S.C., Horiuchi H., Zerial M., Clarke P.R., Woodman P.G. EMBO J. 16:6182-6191(1997) [PubMed: 9321397] [Abstract] Cited for: PROTEOLYTIC CLEAVAGE BY CASPASES IN APOPTOTIC CELLS.
[7]	"The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis." Xiao G.-H., Shoarinejad F., Jin F., Golemis E.A., Yeung R.S. J. Biol. Chem. 272:6097-6100(1997) [PubMed: 9045618] [Abstract] Cited for: INTERACTION WITH TSC2.
[8]	"Antigens recognized by autologous antibody in patients with renal-cell carcinoma." Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J. Int. J. Cancer 83:456-464(1999) [PubMed: 10508479] [Abstract] Cited for: IDENTIFICATION AS A RENAL CANCER ANTIGEN. Tissue: Renal cell carcinoma.
[9]	"Functional synergy between Rab5 effector Rabaptin-5 and exchange factor Rabex-5 when physically associated in a complex." Lippe R., Miaczynska M., Rybin V., Runge A., Zerial M. Mol. Biol. Cell 12:2219-2228(2001) [PubMed: 11452015] [Abstract] Cited for: FUNCTION, INTERACTION WITH RABGEF1.
[10]	"Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5 complex." Mattera R., Arighi C.N., Lodge R., Zerial M., Bonifacino J.S. EMBO J. 22:78-88(2003) [PubMed: 12505986] [Abstract] Cited for: INTERACTION WITH GGA1; GGA2; GGA3; AP1G1 AND AP1G2, SUBCELLULAR LOCATION.
[11]	"Rabaptin-5alpha/rabaptin-4 serves as a linker between rab4 and gamma(1)-adaptin in membrane recycling from endosomes." Deneka M., Neeft M., Popa I., van Oort M., Sprong H., Oorschot V., Klumperman J., Schu P., van der Sluijs P. EMBO J. 22:2645-2657(2003) [PubMed: 12773381] [Abstract] Cited for: FUNCTION, INTERACTION WITH RAB4A AND AP1G1, SUBCELLULAR LOCATION.
[12]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-408 AND SER-410, MASS SPECTROMETRY. Tissue: Platelet.
[14]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407 AND SER-410, MASS SPECTROMETRY.
[15]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[16]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407; THR-408 AND SER-410, MASS SPECTROMETRY.
[17]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, MASS SPECTROMETRY. Tissue: T-cell.
[18]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-282, MASS SPECTROMETRY.
[19]	"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: 15378032] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) OF 789-862 IN COMPLEX WITH RAB5A, SUBUNIT, MUTAGENESIS OF ASP-812; GLU-815; GLN-818; ASO-820; PHE-821; VAL-822; GLN-826 AND GLN-829.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X91141 mRNA. Translation: CAA62580.1.
AF098638 mRNA. Translation: AAC70781.1.
BC041700 mRNA. Translation: AAH41700.1.

IPI

IPI00293009.
IPI00412712.

RefSeq

NP_001077054.1.
NP_004694.2.

UniGene

Hs.584784
Hs.592121

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TU3	X-ray	2.31	F/G/H/I/J	789-862	[»]
1X79	X-ray	2.41	B/C	551-661	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29350N.

IntAct

Q15276. 11 interactions.

STRING

Q15276.

PTM databases

PhosphoSite

Q15276.

Proteomic databases

PRIDE

Q15276.

Genome annotation databases

Ensembl

ENST00000262477; ENSP00000262477; ENSG00000029725; Homo sapiens. [Genome view]

GeneID

9135.

KEGG

hsa:9135.

NMPDR

fig|9606.3.peg.12951.

UCSC

uc002gbl.2. human.
uc002gbm.2. human.

Organism-specific databases

CTD

9135.

GeneCards

GC17P005127.

H-InvDB

HIX0013466.

HGNC

HGNC:17677. RABEP1.

HPA

CAB004549.
HPA019669.
HPA024235.
HPA024691.

MIM

603616. gene.

PharmGKB

PA134884097.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19092.

HOGENOM

HBG402862.

HOVERGEN

Q15276.

InParanoid

Q15276.

OMA

EIENCKE.

OrthoDB

EOG9G4K9B.

PhylomeDB

Q15276.

Gene expression databases

ArrayExpress

Q15276.

Bgee

Q15276.

CleanEx

HS_RABEP1.

Genevestigator

Q15276.

GermOnline

ENSG00000029725. Homo sapiens.

Family and domain databases

InterPro

IPR003914. Rabaptin.
IPR018514. Rabaptin_coiled-coil.
IPR015390. Rabaptin_Rab5-bd.
[Graphical view]

Pfam

PF09311. Rab5-bind. 1 hit.
PF03528. Rabaptin. 2 hits.
[Graphical view]

PRINTS

PR01432. RABAPTIN.

ProtoNet

Search...

Other Resources

NextBio

34253.

PMAP-CutDB

Q15276.

SOURCE

Search...

Entry information

Entry name

RABE1_HUMAN

Accession

Primary (citable) accession number: Q15276
Secondary accession number(s): O95369, Q8IVX3

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 24, 2004
Last sequence update:	October 17, 2006
Last modified:	January 19, 2010
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.