Q9H2M9 (RBGPR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Rab3 GTPase-activating protein non-catalytic subunit

Alternative name(s):
RGAP-iso
Rab3 GTPase-activating protein 150 kDa subunit
Rab3-GAP p150
Short name=Rab3-GAP150
Rab3-GAP regulatory subunit

Gene names

Name:	RAB3GAP2
Synonyms:	KIAA0839

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	1393 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Regulatory 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. Rab3 GTPase-activating complex 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.1
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.
Tissue specificity	Ubiquitous. Ref.1
Involvement in disease	Defects in RAB3GAP2 are the cause of Martsolf syndrome (MARTS) [MIM:212720]. Martsolf syndrome is characterized by congenital cataracts, mental retardation, and hypogonadism. Inheritance is autosomal recessive. Ref.11 Defects in RAB3GAP2 are the cause of Warburg micro syndrome type 2 (WARBM2) [MIM:614225]. WARBM2 is 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. Ref.12
Sequence similarities	Belongs to the Rab3-GAP regulatory subunit family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Cataract Disease mutation Mental retardation
Molecular function	GTPase activation
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	intracellular protein transport Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA soluble fraction Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	GTPase activator activity Traceable author statement. Source: ProtInc protein heterodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PTP4A3	O75365	1	EBI-536107,EBI-1043866

Alternative products

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

Isoform 1 (identifier: Q9H2M9-1)

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: Q9H2M9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     205-206: NE → VV
     207-1393: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1393	1393	Rab3 GTPase-activating protein non-catalytic subunit		PRO_0000191662
Amino acid modifications
	Modified residue	450	1	Phosphoserine Ref.9
	Modified residue	901	1	Phosphothreonine Ref.8
Natural variations
	Alternative sequence	205 – 206	2	NE → VV in isoform 2.		VSP_013311
	Alternative sequence	207 – 1393	1187	Missing in isoform 2.		VSP_013312
	Natural variant	167 – 169	3	Missing in WARBM2.		VAR_066675
	Natural variant	863	1	T → A. Corresponds to variant rs12045447 [ dbSNP | Ensembl ].		VAR_021588
	Natural variant	1052	1	G → C in MARTS; may cause exon skipping. Ref.11		VAR_029881
	Natural variant	1092	1	S → T. Corresponds to variant rs2289189 [ dbSNP | Ensembl ].		VAR_021589
Experimental info
	Sequence conflict	289	1	G → R in AAC35881. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 4138F60B5199211E	FASTA	1,393	155,985
	10 20 30 40 50 60 MACSIVQFCY FQDLQAARDF LFPHLREEIL SGALRRDPSK STDWEDDGWG AWEENEPQEP 70 80 90 100 110 120 EEEGNTCKTQ KTSWLQDCVL SLSPTNDLMV IAREQKAVFL VPKWKYSDKG KEEMQFAVGW 130 140 150 160 170 180 SGSLNVEEGE CVTSALCIPL ASQKRSSTGR PDWTCIVVGF TSGYVRFYTE NGVLLLAQLL 190 200 210 220 230 240 NEDPVLQLKC RTYEIPRHPG VTEQNEELSI LYPAAIVTID GFSLFQSLRA CRNQVAKAAA 250 260 270 280 290 300 SGNENIQPPP LAYKKWGLQD IDTIIDHASV GIMTLSPFDQ MKTASNIGGF NAAIKNSPPA 310 320 330 340 350 360 MSQYITVGSN PFTGFFYALE GSTQPLLSHV ALAVASKLTS ALFNAASGWL GWKSKHEEEA 370 380 390 400 410 420 VQKQKPKVEP ATPLAVRFGL PDSRRHGESI CLSPCNTLAA VTDDFGRVIL LDVARGIAIR 430 440 450 460 470 480 MWKGYRDAQI GWIQTVEDLH ERVPEKADFS PFGNSQGPSR VAQFLVIYAP RRGILEVWST 490 500 510 520 530 540 QQGPRVGAFN VGKHCRLLYP GYKIMGLNNV TSQSWQPQTY QICLVDPVSG SVKTVNVPFH 550 560 570 580 590 600 LALSDKKSER AKDMHLVKKL AALLKTKSPN LDLVETEIKE LILDIKYPAT KKQALESILA 610 620 630 640 650 660 SERLPFSCLR NITQTLMDTL KSQELESVDE GLLQFCANKL KLLQLYESVS QLNSLDFHLD 670 680 690 700 710 720 TPFSDNDLAL LLRLDEKELL KLQALLEKYK QENTRTNVRF SDDKDGVLPV KTFLEYLEYE 730 740 750 760 770 780 KDVLNIKKIS EEEYVALGSF FFWKCLHGES STEDMCHTLE SAGLSPQLLL SLLLSVWLSK 790 800 810 820 830 840 EKDILDKPQS ICCLHTMLSL LSKMKVAIDE TWDSQSVSPW WQQMRTACIQ SENNGAALLS 850 860 870 880 890 900 AHVGHSVAAQ ISNNMTEKKF SQTVLGADSE ALTDSWEALS LDTEYWKLLL KQLEDCLILQ 910 920 930 940 950 960 TLLHSKGNTQ TSKVSSLQAE PLPRLSVKKL LEGGKGGIAD SVAKWIFKQD FSPEVLKLAN 970 980 990 1000 1010 1020 EERDAENPDE PKEGVNRSFL EVSEMEMDLG AIPDLLHLAY EQFPCSLELD VLHAHCCWEY 1030 1040 1050 1060 1070 1080 VVQWNKDPEE ARFFVRSIEH LKQIFNAHVQ NGIALMMWNT FLVKRFSAAT YLMDKVGKSP 1090 1100 1110 1120 1130 1140 KDRLCRRDVG MSDTAMTSFL GSCLDLLQIL MEADVSRDEI QVPVLDTEDA WLSVEGPISI 1150 1160 1170 1180 1190 1200 VELALEQKHI HYPLVEHHSI LCSILYAVMR FSLKTVKPLS LFDSKGKNAF FKDLTSIQLL 1210 1220 1230 1240 1250 1260 PSGEMDPNFI SVRQQFLLKV VSAAVQAQHS ATKVKDPTEE ATPTPFGKDQ DWPALAVDLA 1270 1280 1290 1300 1310 1320 HHLQVSEDVV RRHYVGELYN YGVDHLGEEA ILQVHDKEVL ASQLLVLTGQ RLAHALLHTQ 1330 1340 1350 1360 1370 1380 TKEGMELLAR LPPTLCTWLK AMDPQDLQNT EVPIATTAKL VNKVIELLPE KHGQYGLALH 1390 LIEAVEAISL PSL
	Isoform 2 [UniParc]. Checksum: F2E1A380FC809649	FASTA	206	23,361
	10 20 30 40 50 60 MACSIVQFCY FQDLQAARDF LFPHLREEIL SGALRRDPSK STDWEDDGWG AWEENEPQEP 70 80 90 100 110 120 EEEGNTCKTQ KTSWLQDCVL SLSPTNDLMV IAREQKAVFL VPKWKYSDKG KEEMQFAVGW 130 140 150 160 170 180 SGSLNVEEGE CVTSALCIPL ASQKRSSTGR PDWTCIVVGF TSGYVRFYTE NGVLLLAQLL 190 200 NEDPVLQLKC RTYEIPRHPG VTEQVV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of the noncatalytic subunit of the Rab3 subfamily-specific GTPase-activating protein." Nagano F., Sasaki T., Fukui K., Asakura T., Imazumi K., Takai Y. J. Biol. Chem. 273:24781-24785(1998) [PubMed: 9733780] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY. Tissue: Brain.
[2]	Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z. Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Dendritic cell.
[3]	"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:355-364(1998) [PubMed: 10048485] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[4]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed: 12168954] [Abstract] Cited for: SEQUENCE REVISION.
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Embryo.
[6]	"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].
[7]	"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: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 930-1393. Tissue: Testis.
[8]	"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-901, MASS SPECTROMETRY. Tissue: Platelet.
[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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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].
[11]	"Mutation in Rab3 GTPase-activating protein (RAB3GAP) noncatalytic subunit in a kindred with Martsolf syndrome." Aligianis I.A., Morgan N.V., Mione M., Johnson C.A., Rosser E., Hennekam R.C.M., Adams G., Trembath R.C., Pilz D.T., Stoodley N., Moore A.T., Wilson S., Maher E.R. Am. J. Hum. Genet. 78:702-707(2006) [PubMed: 16532399] [Abstract] Cited for: VARIANT MARTS CYS-1052.
[12]	"A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome." Borck G., Wunram H., Steiert A., Volk A.E., Korber F., Roters S., Herkenrath P., Wollnik B., Morris-Rosendahl D.J., Kubisch C. Hum. Genet. 129:45-50(2011) [PubMed: 20967465] [Abstract] Cited for: VARIANT WARBM2 167-PHE--THR-169 DEL.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF004828 mRNA. Translation: AAC35881.1. AF255648 mRNA. Translation: AAG44636.1. AB020646 mRNA. Translation: BAA74862.2. AK021928 mRNA. Translation: BAB13939.1. AL445435, AC103590 Genomic DNA. Translation: CAI15808.1. AL117631 mRNA. Translation: CAB56022.1.
IPI	IPI00477068. IPI00554590.
PIR	T17332.
RefSeq	NP_036546.2. NM_012414.3.
UniGene	Hs.654849. Hs.708165.
3D structure databases
ProteinModelPortal	Q9H2M9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H2M9. 2 interactions.
STRING	Q9H2M9.
PTM databases
PhosphoSite	Q9H2M9.
Polymorphism databases
DMDM	62511132.
Proteomic databases
PRIDE	Q9H2M9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000358951; ENSP00000351832; ENSG00000118873.
GeneID	25782.
KEGG	hsa:25782.
UCSC	uc001hme.1. human.
Organism-specific databases
CTD	25782.
GeneCards	GC01M220322.
H-InvDB	HIX0001603.
HGNC	HGNC:17168. RAB3GAP2.
HPA	HPA026273. HPA027299.
MIM	212720. phenotype. 609275. gene. 614225. phenotype.
neXtProt	NX_Q9H2M9.
Orphanet	1387. Cataract - intellectual deficit - hypogonadism.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG08273.
GeneTree	ENSGT00390000005794.
HOGENOM	HBG282729.
HOVERGEN	HBG067039.
InParanoid	Q9H2M9.
OMA	AQFLVIY.
OrthoDB	EOG470TGK.
PhylomeDB	Q9H2M9.
Enzyme and pathway databases
Pathway_Interaction_DB	botulinumtoxinpathway. Effects of Botulinum toxin.
Gene expression databases
ArrayExpress	Q9H2M9.
Bgee	Q9H2M9.
CleanEx	HS_RAB3GAP2.
Genevestigator	Q9H2M9.
GermOnline	ENSG00000118873. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other
NextBio	46935.
SOURCE	Search...

Entry information

Entry name

RBGPR_HUMAN

Accession

Primary (citable) accession number: Q9H2M9
Secondary accession number(s): O75872 , Q9HAB0, Q9UFJ7, Q9UQ15

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	March 1, 2001
Last modified:	January 25, 2012
This is version 80 of the entry and version 1 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.