Q15042 (RB3GP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Rab3 GTPase-activating protein catalytic subunit

Alternative name(s):
RAB3 GTPase-activating protein 130 kDa subunit
Rab3-GAP p130
Short name=Rab3-GAP

Gene names

Name:	RAB3GAP1
Synonyms:	KIAA0066, RAB3GAP

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	981 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	Probable catalytic subunit of a GTPase activating protein that has specificity for Rab3 subfamily (RAB3A, RAB3B, RAB3C and RAB3D). Rab3 proteins are involved in regulated exocytosis of neurotransmitters and hormones. Specifically converts active Rab3-GTP to the inactive form Rab3-GDP. Required for normal eye and brain development. May participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters. Ref.4 Ref.6
Subunit structure	The Rab3 GTPase-activating complex is a heterodimer composed of RAB3GAP and RAB3-GAP150. The Rab3 GTPase-activating complex interacts with DMXL2 By similarity.
Subcellular location	Cytoplasm. Note: In neurons, it is enriched in the synaptic soluble fraction. Ref.5
Tissue specificity	Ubiquitous. Ref.4
Involvement in disease	Warburg micro syndrome 1 (WARBM1) [MIM:600118]: A rare syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Sequence similarities	Belongs to the Rab3-GAP catalytic subunit family.
Biophysicochemical properties	Kinetic parameters: KM=75 µM for GTP-loaded RAB3A Ref.6
Sequence caution	The sequence CAH56411.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	GTPase activation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	camera-type eye development Inferred from mutant phenotype PubMed 20512159. Source: BHF-UCL face morphogenesis Inferred from mutant phenotype PubMed 20512159. Source: BHF-UCL hypothalamus development Inferred from mutant phenotype PubMed 20512159. Source: BHF-UCL
Cellular_component	centrosome Inferred from direct assay. Source: HPA cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular_function	Rab GTPase activator activity Inferred from direct assay Ref.6Ref.4. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q15042-1)

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: Q15042-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-906: Missing.
     972-981: GAFSSDTSFF → VKIIDGDV

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 981	980	Rab3 GTPase-activating protein catalytic subunit		PRO_0000191655
Natural variations
	Alternative sequence	1 – 906	906	Missing in isoform 2.		VSP_013316
	Alternative sequence	972 – 981	10	GAFSSDTSFF → VKIIDGDV in isoform 2.		VSP_013317
	Natural variant	598	1	N → S. Ref.3 Corresponds to variant rs10445686 [ dbSNP | Ensembl ].		VAR_051716
Experimental info
	Mutagenesis	619	1	R → A: No effect. Ref.6
	Mutagenesis	700	1	R → A: No effect. Ref.6
	Mutagenesis	728	1	R → A: Loss of function. Ref.6
	Mutagenesis	753	1	R → A: No effect. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 0673611C5C49641C	FASTA	981	110,524
	10 20 30 40 50 60 MAADSEPESE VFEITDFTTA SEWERFISKV EEVLNDWKLI GNSLGKPLEK GIFTSGTWEE 70 80 90 100 110 120 KSDEISFADF KFSVTHHYLV QESTDKEGKD ELLEDVVPQS MQDLLGMNND FPPRAHCLVR 130 140 150 160 170 180 WYGLREFVVI APAAHSDAVL SESKCNLLLS SVSIALGNTG CQVPLFVQIH HKWRRMYVGE 190 200 210 220 230 240 CQGPGVRTDF EMVHLRKVPN QYTHLSGLLD IFKSKIGCPL TPLPPVSIAI RFTYVLQDWQ 250 260 270 280 290 300 QYFWPQQPPD IDALVGGEVG GLEFGKLPFG ACEDPISELH LATTWPHLTE GIIVDNDVYS 310 320 330 340 350 360 DLDPIQAPHW SVRVRKAENP QCLLGDFVTE FFKICRRKES TDEILGRSAF EEEGKETADI 370 380 390 400 410 420 THALSKLTEP ASVPIHKLSV SNMVHTAKKK IRKHRGVEES PLNNDVLNTI LLFLFPDAVS 430 440 450 460 470 480 EKPLDGTTST DNNNPPSESE DYNLYNQFKS APSDSLTYKL ALCLCMINFY HGGLKGVAHL 490 500 510 520 530 540 WQEFVLEMRF RWENNFLIPG LASGPPDLRC CLLHQKLQML NCCIERKKAR DEGKKTSASD 550 560 570 580 590 600 VTNIYPGDAG KAGDQLVPDN LKETDKEKGE VGKSWDSWSD SEEEFFECLS DTEELKGNGQ 610 620 630 640 650 660 ESGKKGGPKE MANLRPEGRL YQHGKLTLLH NGEPLYIPVT QEPAPMTEDL LEEQSEVLAK 670 680 690 700 710 720 LGTSAEGAHL RARMQSACLL SDMESFKAAN PGCSLEDFVR WYSPRDYIEE EVIDEKGNVV 730 740 750 760 770 780 LKGELSARMK IPSNMWVEAW ETAKPIPARR QRRLFDDTRE AEKVLHYLAI QKPADLARHL 790 800 810 820 830 840 LPCVIHAAVL KVKEEESLEN ISSVKKIIKQ IISHSSKVLH FPNPEDKKLE EIIHQITNVE 850 860 870 880 890 900 ALIARARSLK AKFGTEKCEQ EEEKEDLERF VSCLLEQPEV LVTGAGRGHA GRIIHKLFVN 910 920 930 940 950 960 AQRAAAMTPP EEELKRMGSP EERRQNSVSD FPPPAGREFI LRTTVPRPAP YSKALPQRMY 970 980 SVLTKEDFRL AGAFSSDTSF F
	Isoform 2 [UniParc]. Checksum: 756005D70884D1F1	FASTA	73	8,344
	10 20 30 40 50 60 MTPPEEELKR MGSPEERRQN SVSDFPPPAG REFILRTTVP RPAPYSKALP QRMYSVLTKE 70 DFRLAVKIID GDV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1." Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N., Kawarabayasi Y., Ishikawa K., Tabata S. DNA Res. 1:223-229(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Bone marrow.
[2]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 439-981, VARIANT SER-598. Tissue: Placenta.
[4]	"Isolation and characterization of a GTPase activating protein specific for the Rab3 subfamily of small G proteins." Fukui K., Sasaki T., Imazumi K., Matsuura Y., Nakanishi H., Takai Y. J. Biol. Chem. 272:4655-4658(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[5]	"Localization of the Rab3 small G protein regulators in nerve terminals and their involvement in Ca2+-dependent exocytosis." Oishi H., Sasaki T., Nagano F., Ikeda W., Ohya T., Wada M., Ide N., Nakanishi H., Takai Y. J. Biol. Chem. 273:34580-34585(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[6]	"Biochemical characterization of Rab3-GTPase-activating protein reveals a mechanism similar to that of Ras-GAP." Clabecq A., Henry J.-P., Darchen F. J. Biol. Chem. 275:31786-31791(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ARG-619; ARG-700; ARG-728 AND ARG-753.
[7]	"Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome." Aligianis I.A., Johnson C.A., Gissen P., Chen D., Hampshire D., Hoffmann K., Maina E.N., Morgan N.V., Tee L., Morton J., Ainsworth J.R., Horn D., Rosser E., Cole T.R.P., Stolte-Dijkstra I., Fieggen K., Clayton-Smith J., Megarbane A. , Shield J.P., Newbury-Ecob R., Dobyns W.B., Graham J.M., Kjaer K.W., Warburg M., Bond J., Trembath R.C., Harris L.W., Takai Y., Mundlos S., Tannahill D., Woods C.G., Maher E.R. Nat. Genet. 37:221-223(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN WARBM1.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[9]	"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.
[10]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[11]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[12]	"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].
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	D31886 mRNA. Translation: BAA06684.1. AL096752 mRNA. Translation: CAH56411.1. Different initiation. BC022977 mRNA. Translation: AAH22977.1.
IPI	IPI00014235. IPI00555624.
RefSeq	NP_036365.1. NM_012233.2.
UniGene	Hs.306327.
3D structure databases
ProteinModelPortal	Q15042.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q15042. 2 interactions.
STRING	9606.ENSP00000264158.
PTM databases
PhosphoSite	Q15042.
Polymorphism databases
DMDM	62511099.
Proteomic databases
PaxDb	Q15042.
PRIDE	Q15042.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264158; ENSP00000264158; ENSG00000115839.
GeneID	22930.
KEGG	hsa:22930.
UCSC	uc002tuj.3. human.
Organism-specific databases
CTD	22930.
GeneCards	GC02P135809.
HGNC	HGNC:17063. RAB3GAP1.
HPA	HPA034495.
MIM	600118. phenotype. 602536. gene.
neXtProt	NX_Q15042.
Orphanet	2510. Micro syndrome.
PharmGKB	PA134969639.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG307494.
HOGENOM	HOG000253924.
HOVERGEN	HBG079116.
InParanoid	Q15042.
OrthoDB	EOG495ZR7.
PhylomeDB	Q15042.
Gene expression databases
ArrayExpress	Q15042.
Bgee	Q15042.
CleanEx	HS_RAB3GAP1.
Genevestigator	Q15042.
GermOnline	ENSG00000115839. Homo sapiens.
Family and domain databases
InterPro	IPR026147. Rab3-GAP_cat_su. [Graphical view]
PANTHER	PTHR21422. PTHR21422. 1 hit.
Pfam	PF13890. Rab3-GTPase_cat. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	RAB3GAP1. human.
GenomeRNAi	22930.
NextBio	43655.
SOURCE	Search...

Entry information

Entry name

RB3GP_HUMAN

Accession

Primary (citable) accession number: Q15042
Secondary accession number(s): Q659F5, Q8TBB4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 89 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.