Q8IWW6 (RHG12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Rho GTPase-activating protein 12

Alternative name(s):
Rho-type GTPase-activating protein 12

Gene names

Name:

ARHGAP12

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

General annotation (Comments)

Function	GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state By similarity.
Sequence similarities	Contains 1 PH domain. Contains 1 Rho-GAP domain. Contains 1 SH3 domain. Contains 2 WW domains.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat SH3 domain
Molecular function	GTPase activation
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of GTPase activity Inferred from electronic annotation. Source: GOC regulation of small GTPase mediated signal transduction Traceable author statement. Source: Reactome small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	GTPase activator activity Inferred from electronic annotation. Source: UniProtKB-KW phospholipid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8IWW6-1)

Also known as: ARHGAP12b;

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: Q8IWW6-2)

Also known as: ARHGAP12a;

The sequence of this isoform differs from the canonical sequence as follows:
     433-462: Missing.

Isoform 3 (identifier: Q8IWW6-3)

The sequence of this isoform differs from the canonical sequence as follows:
     317-363: Missing.
     458-462: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 846	846	Rho GTPase-activating protein 12		PRO_0000056713
Regions
	Domain	12 – 74	63	SH3
	Domain	265 – 298	34	WW 1
	Domain	358 – 391	34	WW 2
	Domain	463 – 575	113	PH
	Domain	656 – 844	189	Rho-GAP
Amino acid modifications
	Modified residue	165	1	Phosphoserine Ref.9 Ref.10
	Modified residue	201	1	Phosphoserine Ref.7
	Modified residue	206	1	Phosphoserine By similarity
	Modified residue	213	1	Phosphoserine Ref.7 Ref.8
	Modified residue	215	1	Phosphoserine Ref.7 Ref.8
	Modified residue	231	1	Phosphothreonine By similarity
	Modified residue	240	1	Phosphoserine Ref.6 Ref.7 Ref.8
	Modified residue	243	1	Phosphotyrosine Ref.6 Ref.8
	Modified residue	521	1	Phosphothreonine By similarity
	Modified residue	592	1	Phosphoserine Ref.7
Natural variations
	Alternative sequence	317 – 363	47	Missing in isoform 3.		VSP_010326
	Alternative sequence	433 – 462	30	Missing in isoform 2.		VSP_010327
	Alternative sequence	458 – 462	5	Missing in isoform 3.		VSP_010328
	Natural variant	442	1	F → S. Corresponds to variant rs2808096 [ dbSNP | Ensembl ].		VAR_024454
Experimental info
	Sequence conflict	70	1	K → R in CAD38926. Ref.4
	Sequence conflict	760	1	Q → P in CAD38926. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ARHGAP12b) [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 274CF06B47F02DDC	FASTA	846	96,254
	10 20 30 40 50 60 MKMADRSGKI IPGQVYIEVE YDYEYEAKDR KIVIKQGERY ILVKKTNDDW WQVKPDENSK 70 80 90 100 110 120 AFYVPAQYVK EVTRKALMPP VKQVAGLPNN STKIMQSLHL QRSTENVNKL PELSSFGKPS 130 140 150 160 170 180 SSVQGTGLIR DANQNFGPSY NQGQTVNLSL DLTHNNGKFN NDSHSPKVSS QNRTRSFGHF 190 200 210 220 230 240 PGPEFLDVEK TSFSQEQSCD SAGEGSERIH QDSESGDELS SSSTEQIRAT TPPNQGRPDS 250 260 270 280 290 300 PVYANLQELK ISQSALPPLP GSPAIQINGE WETHKDSSGR CYYYNRGTQE RTWKPPRWTR 310 320 330 340 350 360 DASISKGDFQ NPGDQELLSS EENYYSTSYS QSDSQCGSPP RGWSEELDER GHTLYTSDYT 370 380 390 400 410 420 NEKWLKHVDD QGRQYYYSAD GSRSEWELPK YNASSQQQRE IIKSRSLDRR LQEPIVLTKW 430 440 450 460 470 480 RHSTIVLDTN DKESPTASKP CFPENESSPS SPKHQDTASS PKDQEKYGLL NVTKIAENGK 490 500 510 520 530 540 KVRKNWLSSW AVLQGSSLLF TKTQGSSTSW FGSNQSKPEF TVDLKGATIE MASKDKSSKK 550 560 570 580 590 600 NVFELKTRQG TELLIQSDND TVINDWFKVL SSTINNQAVE TDEGIEEEIP DSPGIEKHDK 610 620 630 640 650 660 EKEQKDPKKL RSFKVSSIDS SEQKKTKKNL KKFLTRRPTL QAVREKGYIK DQVFGSNLAN 670 680 690 700 710 720 LCQRENGTVP KFVKLCIEHV EEHGLDIDGI YRVSGNLAVI QKLRFAVNHD EKLDLNDSKW 730 740 750 760 770 780 EDIHVITGAL KMFFRELPEP LFTFNHFNDF VNAIKQEPRQ RVAAVKDLIR QLPKPNQDTM 790 800 810 820 830 840 QILFRHLRRV IENGEKNRMT YQSIAIVFGP TLLKPEKETG NIAVHTVYQN QIVELILLEL SSIFGR
	Isoform 2 (ARHGAP12a) [UniParc]. Checksum: A948E9F7904B8DC7	FASTA	816	93,114
	10 20 30 40 50 60 MKMADRSGKI IPGQVYIEVE YDYEYEAKDR KIVIKQGERY ILVKKTNDDW WQVKPDENSK 70 80 90 100 110 120 AFYVPAQYVK EVTRKALMPP VKQVAGLPNN STKIMQSLHL QRSTENVNKL PELSSFGKPS 130 140 150 160 170 180 SSVQGTGLIR DANQNFGPSY NQGQTVNLSL DLTHNNGKFN NDSHSPKVSS QNRTRSFGHF 190 200 210 220 230 240 PGPEFLDVEK TSFSQEQSCD SAGEGSERIH QDSESGDELS SSSTEQIRAT TPPNQGRPDS 250 260 270 280 290 300 PVYANLQELK ISQSALPPLP GSPAIQINGE WETHKDSSGR CYYYNRGTQE RTWKPPRWTR 310 320 330 340 350 360 DASISKGDFQ NPGDQELLSS EENYYSTSYS QSDSQCGSPP RGWSEELDER GHTLYTSDYT 370 380 390 400 410 420 NEKWLKHVDD QGRQYYYSAD GSRSEWELPK YNASSQQQRE IIKSRSLDRR LQEPIVLTKW 430 440 450 460 470 480 RHSTIVLDTN DKDQEKYGLL NVTKIAENGK KVRKNWLSSW AVLQGSSLLF TKTQGSSTSW 490 500 510 520 530 540 FGSNQSKPEF TVDLKGATIE MASKDKSSKK NVFELKTRQG TELLIQSDND TVINDWFKVL 550 560 570 580 590 600 SSTINNQAVE TDEGIEEEIP DSPGIEKHDK EKEQKDPKKL RSFKVSSIDS SEQKKTKKNL 610 620 630 640 650 660 KKFLTRRPTL QAVREKGYIK DQVFGSNLAN LCQRENGTVP KFVKLCIEHV EEHGLDIDGI 670 680 690 700 710 720 YRVSGNLAVI QKLRFAVNHD EKLDLNDSKW EDIHVITGAL KMFFRELPEP LFTFNHFNDF 730 740 750 760 770 780 VNAIKQEPRQ RVAAVKDLIR QLPKPNQDTM QILFRHLRRV IENGEKNRMT YQSIAIVFGP 790 800 810 TLLKPEKETG NIAVHTVYQN QIVELILLEL SSIFGR
	Isoform 3 [UniParc]. Checksum: 330029A7C1C294B3	FASTA	794	90,403
	10 20 30 40 50 60 MKMADRSGKI IPGQVYIEVE YDYEYEAKDR KIVIKQGERY ILVKKTNDDW WQVKPDENSK 70 80 90 100 110 120 AFYVPAQYVK EVTRKALMPP VKQVAGLPNN STKIMQSLHL QRSTENVNKL PELSSFGKPS 130 140 150 160 170 180 SSVQGTGLIR DANQNFGPSY NQGQTVNLSL DLTHNNGKFN NDSHSPKVSS QNRTRSFGHF 190 200 210 220 230 240 PGPEFLDVEK TSFSQEQSCD SAGEGSERIH QDSESGDELS SSSTEQIRAT TPPNQGRPDS 250 260 270 280 290 300 PVYANLQELK ISQSALPPLP GSPAIQINGE WETHKDSSGR CYYYNRGTQE RTWKPPRWTR 310 320 330 340 350 360 DASISKGDFQ NPGDQEWLKH VDDQGRQYYY SADGSRSEWE LPKYNASSQQ QREIIKSRSL 370 380 390 400 410 420 DRRLQEPIVL TKWRHSTIVL DTNDKESPTA SKPCFPENES SPSSPKHQDT DQEKYGLLNV 430 440 450 460 470 480 TKIAENGKKV RKNWLSSWAV LQGSSLLFTK TQGSSTSWFG SNQSKPEFTV DLKGATIEMA 490 500 510 520 530 540 SKDKSSKKNV FELKTRQGTE LLIQSDNDTV INDWFKVLSS TINNQAVETD EGIEEEIPDS 550 560 570 580 590 600 PGIEKHDKEK EQKDPKKLRS FKVSSIDSSE QKKTKKNLKK FLTRRPTLQA VREKGYIKDQ 610 620 630 640 650 660 VFGSNLANLC QRENGTVPKF VKLCIEHVEE HGLDIDGIYR VSGNLAVIQK LRFAVNHDEK 670 680 690 700 710 720 LDLNDSKWED IHVITGALKM FFRELPEPLF TFNHFNDFVN AIKQEPRQRV AAVKDLIRQL 730 740 750 760 770 780 PKPNQDTMQI LFRHLRRVIE NGEKNRMTYQ SIAIVFGPTL LKPEKETGNI AVHTVYQNQI 790 VELILLELSS IFGR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a novel human gene." Mao Y., Xie Y., Zhang Z. Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[2]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] OF 3-846 (ISOFORM 3). Tissue: Testis.
[5]	"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 559-846. Tissue: Uterus.
[6]	"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-240 AND TYR-243, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[7]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-201; SER-213; SER-215; SER-240 AND SER-592, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-213; SER-215; SER-240 AND TYR-243, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY033594 mRNA. Translation: AAK52311.1. AY033595 mRNA. Translation: AAK52312.1. AL390715 Genomic DNA. Translation: CAI12371.1. AL390715 Genomic DNA. Translation: CAI12372.1. AL390715 Genomic DNA. Translation: CAI12373.1. AL834250 mRNA. Translation: CAD38926.2. AL137485 mRNA. Translation: CAB70766.1. CH471072 Genomic DNA. Translation: EAW85980.1. CH471072 Genomic DNA. Translation: EAW85983.1. CH471072 Genomic DNA. Translation: EAW85985.1. BC051811 mRNA. Translation: AAH51811.1.
IPI	IPI00217418. IPI00328279. IPI00410501.
PIR	T46471.
RefSeq	NP_001257624.1. NM_001270695.1. NP_001257625.1. NM_001270696.1. NP_001257626.1. NM_001270697.1. NP_001257627.1. NM_001270698.1. NP_001257628.1. NM_001270699.1. NP_060757.4. NM_018287.6.
UniGene	Hs.499264. Hs.741991.
3D structure databases
ProteinModelPortal	Q8IWW6.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-3037739.
STRING	9606.ENSP00000345808.
PTM databases
PhosphoSite	Q8IWW6.
Polymorphism databases
DMDM	47117238.
Proteomic databases
PaxDb	Q8IWW6.
PRIDE	Q8IWW6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000311380; ENSP00000310984; ENSG00000165322. ENST00000344936; ENSP00000345808; ENSG00000165322. ENST00000375245; ENSP00000364394; ENSG00000165322. ENST00000375250; ENSP00000364399; ENSG00000165322.
GeneID	94134.
KEGG	hsa:94134.
UCSC	uc001ivy.1. human. uc001ivz.1. human. uc001iwc.1. human.
Organism-specific databases
CTD	94134.
GeneCards	GC10M032134.
HGNC	HGNC:16348. ARHGAP12.
HPA	HPA000412.
MIM	610577. gene.
neXtProt	NX_Q8IWW6.
PharmGKB	PA24957.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG279563.
HOVERGEN	HBG005328.
InParanoid	Q8IWW6.
OMA	GQVYIEV.
PhylomeDB	Q8IWW6.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
SignaLink	Q8IWW6.
Gene expression databases
ArrayExpress	Q8IWW6.
Bgee	Q8IWW6.
CleanEx	HS_ARHGAP12.
Genevestigator	Q8IWW6.
GermOnline	ENSG00000165322. Homo sapiens.
Family and domain databases
Gene3D	1.10.555.10. 1 hit. 2.30.29.30. 1 hit.
InterPro	IPR011993. PH_like_dom. IPR001849. Pleckstrin_homology. IPR015767. Rho_GTPase_activating. IPR008936. Rho_GTPase_activation_prot. IPR000198. RhoGAP_dom. IPR001452. SH3_domain. IPR001202. WW_dom. [Graphical view]
PANTHER	PTHR23181. PTHR23181. 1 hit.
Pfam	PF00169. PH. 1 hit. PF00620. RhoGAP. 1 hit. PF00397. WW. 1 hit. [Graphical view]
SMART	SM00233. PH. 1 hit. SM00324. RhoGAP. 1 hit. SM00326. SH3. 1 hit. SM00456. WW. 2 hits. [Graphical view]
SUPFAM	SSF48350. Rho_GAP. 1 hit. SSF50044. SH3. 1 hit. SSF51045. WW_Rsp5_WWP. 2 hits.
PROSITE	PS50003. PH_DOMAIN. 1 hit. PS50238. RHOGAP. 1 hit. PS50002. SH3. 1 hit. PS01159. WW_DOMAIN_1. False negative. PS50020. WW_DOMAIN_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ARHGAP12. human.
GenomeRNAi	94134.
NextBio	78410.
SOURCE	Search...

Entry information

Entry name

RHG12_HUMAN

Accession

Primary (citable) accession number: Q8IWW6
Secondary accession number(s): B1ANY0 , B1ANY1, B1ANY2, Q86UB3, Q8IWW7, Q8N3L1, Q9NT76

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	March 1, 2003
Last modified:	May 29, 2013
This is version 98 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.