Q7Z5H3 (RHG22_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Rho GTPase-activating protein 22

Alternative name(s):
Rho-type GTPase-activating protein 22

Gene names

Name:	ARHGAP22
Synonyms:	RHOGAP2

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

General annotation (Comments)

Function	Rho GTPase-activating protein involved in the signal transduction pathway that regulates endothelial cell capillary tube formation during angiogenesis. Acts as a GTPase activator for the RAC1 by converting it to an inactive GDP-bound state. Inhibits RAC1-dependent lamellipodia formation. May also play a role in transcription regulation via its interaction with VEZF1, by regulating activity of the endothelin-1 (EDN1) promoter By similarity.
Subunit structure	Interacts with VEZF1 By similarity.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: Mainly cytoplasmic. Some fraction is nuclear By similarity.
Sequence similarities	Contains 1 PH domain. Contains 1 Rho-GAP domain.

Ontologies

Keywords
Biological process	Angiogenesis Differentiation Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil
Molecular function	Developmental protein GTPase activation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of GTPase activity Inferred from electronic annotation. Source: GOC regulation of small GTPase mediated signal transduction Traceable author statement. Source: Reactome regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW small GTPase mediated signal transduction Traceable author statement. Source: Reactome transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	GTPase activator activity Inferred from electronic annotation. Source: UniProtKB-KW phospholipid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CACNA1A	O00555	2	EBI-3866859,EBI-766279

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q7Z5H3-1)

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: Q7Z5H3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     150-150: G → GGTARRSHAHPLEPLPP

Note: No experimental confirmation available.

Isoform 3 (identifier: Q7Z5H3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-107: MLSPKIRQAR...PGKHLFEISP → MPFWPIRCLKRSRRMPR

Note: No experimental confirmation available.

Isoform 4 (identifier: Q7Z5H3-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-329: MLSPKIRQAR...QVEDPVTIME → MGQPREFWHL...QGPSPPLFPA

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 698	698	Rho GTPase-activating protein 22		PRO_0000280469
Regions
	Domain	37 – 145	109	PH
	Domain	155 – 349	195	Rho-GAP
	Coiled coil	590 – 687	98	Potential
	Compositional bias	427 – 587	161	Ser-rich
Natural variations
	Alternative sequence	1 – 329	329	MLSPK…VTIME → MGQPREFWHLRSQVPVPTCH LLTVQPWCLLPHPTPAGGRE RRHSASSLLAALCLRKAVLR PHPAVLPGVGGCVVLSSGRM KAPLRGGLALGTGPAPTKLQ LLHDWQSEPGPSGWQQGPSP PLFPA in isoform 4.		VSP_023703
	Alternative sequence	1 – 107	107	MLSPK…FEISP → MPFWPIRCLKRSRRMPR in isoform 3.		VSP_023704
	Alternative sequence	150	1	G → GGTARRSHAHPLEPLPP in isoform 2.		VSP_023705
	Natural variant	410	1	T → K. Corresponds to variant rs1867586 [ dbSNP | Ensembl ].		VAR_031153
	Natural variant	612	1	R → C. Corresponds to variant rs3747853 [ dbSNP | Ensembl ].		VAR_031154

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2003. Version 1. Checksum: 3CE8CEB0A9E5D0F8	FASTA	698	76,779
	10 20 30 40 50 60 MLSPKIRQAR RARSKSLVMG EQSRSPGRMP CPHRLGPVLK AGWLKKQRSI MKNWQQRWFV 70 80 90 100 110 120 LRGDQLFYYK DKDEIKPQGF ISLQGTQVTE LPPGPEDPGK HLFEISPGGA GEREKVPANP 130 140 150 160 170 180 EALLLMASSQ RDMEDWVQAI RRVIWAPLGG GIFGQRLEET VHHERKYGPR LAPLLVEQCV 190 200 210 220 230 240 DFIRERGLTE EGLFRMPGQA NLVRDLQDSF DCGEKPLFDS TTDVHTVASL LKLYLRELPE 250 260 270 280 290 300 PVVPFARYED FLSCAQLLTK DEGEGTLELA KQVSNLPQAN YNLLRYICKF LDEVQAYSNV 310 320 330 340 350 360 NKMSVQNLAT VFGPNILRPQ VEDPVTIMEG TSLVQHLMTV LIRKHSQLFT APVPEGPTSP 370 380 390 400 410 420 RGGLQCAVGW GSEEVTRDSQ GEPGGPGLPA HRTSSLDGAA VAVLSRTAPT GPGSRCSPGK 430 440 450 460 470 480 KVQTLPSWKS SFRQPRSLSG SPKGGGSSLE VPIISSGGNW LMNGLSSLRG HRRASSGDRL 490 500 510 520 530 540 KDSGSVQRLS TYDNVPAPGL VPGIPSVASM AWSGASSSES SVGGSLSSCT ACRASDSSAR 550 560 570 580 590 600 SSLHTDWALE PSPLPSSSED PKSLDLDHSM DEAGAGASNS EPSEPDSPTR EHARRSEALQ 610 620 630 640 650 660 GLVTELRAEL CRQRTEYERS VKRIEEGSAD LRKRMSRLEE ELDQEKKKYI MLEIKLRNSE 670 680 690 RAREDAERRN QLLQREMEEF FSTLGSLTVG AKGARAPK
	Isoform 2 [UniParc]. Checksum: 74AB4A00D66DE416	FASTA	714	78,497
	10 20 30 40 50 60 MLSPKIRQAR RARSKSLVMG EQSRSPGRMP CPHRLGPVLK AGWLKKQRSI MKNWQQRWFV 70 80 90 100 110 120 LRGDQLFYYK DKDEIKPQGF ISLQGTQVTE LPPGPEDPGK HLFEISPGGA GEREKVPANP 130 140 150 160 170 180 EALLLMASSQ RDMEDWVQAI RRVIWAPLGG GTARRSHAHP LEPLPPGIFG QRLEETVHHE 190 200 210 220 230 240 RKYGPRLAPL LVEQCVDFIR ERGLTEEGLF RMPGQANLVR DLQDSFDCGE KPLFDSTTDV 250 260 270 280 290 300 HTVASLLKLY LRELPEPVVP FARYEDFLSC AQLLTKDEGE GTLELAKQVS NLPQANYNLL 310 320 330 340 350 360 RYICKFLDEV QAYSNVNKMS VQNLATVFGP NILRPQVEDP VTIMEGTSLV QHLMTVLIRK 370 380 390 400 410 420 HSQLFTAPVP EGPTSPRGGL QCAVGWGSEE VTRDSQGEPG GPGLPAHRTS SLDGAAVAVL 430 440 450 460 470 480 SRTAPTGPGS RCSPGKKVQT LPSWKSSFRQ PRSLSGSPKG GGSSLEVPII SSGGNWLMNG 490 500 510 520 530 540 LSSLRGHRRA SSGDRLKDSG SVQRLSTYDN VPAPGLVPGI PSVASMAWSG ASSSESSVGG 550 560 570 580 590 600 SLSSCTACRA SDSSARSSLH TDWALEPSPL PSSSEDPKSL DLDHSMDEAG AGASNSEPSE 610 620 630 640 650 660 PDSPTREHAR RSEALQGLVT ELRAELCRQR TEYERSVKRI EEGSADLRKR MSRLEEELDQ 670 680 690 700 710 EKKKYIMLEI KLRNSERARE DAERRNQLLQ REMEEFFSTL GSLTVGAKGA RAPK
	Isoform 3 [UniParc]. Checksum: 2D7543609C576A5D	FASTA	608	66,611
	10 20 30 40 50 60 MPFWPIRCLK RSRRMPRGGA GEREKVPANP EALLLMASSQ RDMEDWVQAI RRVIWAPLGG 70 80 90 100 110 120 GIFGQRLEET VHHERKYGPR LAPLLVEQCV DFIRERGLTE EGLFRMPGQA NLVRDLQDSF 130 140 150 160 170 180 DCGEKPLFDS TTDVHTVASL LKLYLRELPE PVVPFARYED FLSCAQLLTK DEGEGTLELA 190 200 210 220 230 240 KQVSNLPQAN YNLLRYICKF LDEVQAYSNV NKMSVQNLAT VFGPNILRPQ VEDPVTIMEG 250 260 270 280 290 300 TSLVQHLMTV LIRKHSQLFT APVPEGPTSP RGGLQCAVGW GSEEVTRDSQ GEPGGPGLPA 310 320 330 340 350 360 HRTSSLDGAA VAVLSRTAPT GPGSRCSPGK KVQTLPSWKS SFRQPRSLSG SPKGGGSSLE 370 380 390 400 410 420 VPIISSGGNW LMNGLSSLRG HRRASSGDRL KDSGSVQRLS TYDNVPAPGL VPGIPSVASM 430 440 450 460 470 480 AWSGASSSES SVGGSLSSCT ACRASDSSAR SSLHTDWALE PSPLPSSSED PKSLDLDHSM 490 500 510 520 530 540 DEAGAGASNS EPSEPDSPTR EHARRSEALQ GLVTELRAEL CRQRTEYERS VKRIEEGSAD 550 560 570 580 590 600 LRKRMSRLEE ELDQEKKKYI MLEIKLRNSE RAREDAERRN QLLQREMEEF FSTLGSLTVG AKGARAPK
	Isoform 4 [UniParc]. Checksum: 2E77D20B3241012D	FASTA	494	52,697
	10 20 30 40 50 60 MGQPREFWHL RSQVPVPTCH LLTVQPWCLL PHPTPAGGRE RRHSASSLLA ALCLRKAVLR 70 80 90 100 110 120 PHPAVLPGVG GCVVLSSGRM KAPLRGGLAL GTGPAPTKLQ LLHDWQSEPG PSGWQQGPSP 130 140 150 160 170 180 PLFPAGTSLV QHLMTVLIRK HSQLFTAPVP EGPTSPRGGL QCAVGWGSEE VTRDSQGEPG 190 200 210 220 230 240 GPGLPAHRTS SLDGAAVAVL SRTAPTGPGS RCSPGKKVQT LPSWKSSFRQ PRSLSGSPKG 250 260 270 280 290 300 GGSSLEVPII SSGGNWLMNG LSSLRGHRRA SSGDRLKDSG SVQRLSTYDN VPAPGLVPGI 310 320 330 340 350 360 PSVASMAWSG ASSSESSVGG SLSSCTACRA SDSSARSSLH TDWALEPSPL PSSSEDPKSL 370 380 390 400 410 420 DLDHSMDEAG AGASNSEPSE PDSPTREHAR RSEALQGLVT ELRAELCRQR TEYERSVKRI 430 440 450 460 470 480 EEGSADLRKR MSRLEEELDQ EKKKYIMLEI KLRNSERARE DAERRNQLLQ REMEEFFSTL 490 GSLTVGAKGA RAPK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Huang C.Q., Shan Y.X., Liu S. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Erythroleukemia.
[3]	Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W., Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A. Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). Tissue: Brain.
[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] (ISOFORM 1).
[5]	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].
[6]	"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] (ISOFORM 2). Tissue: Lung and Testis.
[7]	"Identification and characterization of ARHGAP24 and ARHGAP25 genes in silico." Katoh M., Katoh M. Int. J. Mol. Med. 14:333-338(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY324801 mRNA. Translation: AAP85632.1. AK127586 mRNA. Translation: BAC87044.1. U90908 mRNA. Translation: AAB51057.1. EF560749 mRNA. Translation: ABQ59059.1. CH471187 Genomic DNA. Translation: EAW93127.1. BC126444 mRNA. Translation: AAI26445.1. BC136319 mRNA. Translation: AAI36320.1.
IPI	IPI00009685. IPI00644736. IPI00829760. IPI00941482.
RefSeq	NP_001242953.1. NM_001256024.1. NP_001242954.1. NM_001256025.2. NP_001242955.1. NM_001256026.1. NP_067049.2. NM_021226.3.
UniGene	Hs.655672.
3D structure databases
HSSP	HSSP built from PDB template 1V89 based on UniProtKB P42331.
ProteinModelPortal	Q7Z5H3.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q7Z5H3. 1 interaction.
STRING	9606.ENSP00000249601.
PTM databases
PhosphoSite	Q7Z5H3.
Polymorphism databases
DMDM	74750129.
Proteomic databases
PaxDb	Q7Z5H3.
PRIDE	Q7Z5H3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000249601; ENSP00000249601; ENSG00000128805. ENST00000417247; ENSP00000410054; ENSG00000128805. ENST00000417912; ENSP00000412461; ENSG00000128805.
GeneID	58504.
KEGG	hsa:58504.
UCSC	uc001jgr.3. human. uc001jgs.3. human. uc001jgt.3. human. uc001jgu.3. human.
Organism-specific databases
CTD	58504.
GeneCards	GC10M049654.
HGNC	HGNC:30320. ARHGAP22.
HPA	CAB020696.
MIM	610585. gene.
neXtProt	NX_Q7Z5H3.
PharmGKB	PA134979724.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG246008.
HOGENOM	HOG000232151.
HOVERGEN	HBG058875.
InParanoid	Q7Z5H3.
OMA	WKYSFRQ.
OrthoDB	EOG4PRSQG.
PhylomeDB	Q7Z5H3.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q7Z5H3.
Bgee	Q7Z5H3.
CleanEx	HS_ARHGAP22.
Genevestigator	Q7Z5H3.
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. IPR008936. Rho_GTPase_activation_prot. IPR000198. RhoGAP_dom. [Graphical view]
Pfam	PF00169. PH. 1 hit. PF00620. RhoGAP. 1 hit. [Graphical view]
SMART	SM00233. PH. 1 hit. SM00324. RhoGAP. 1 hit. [Graphical view]
SUPFAM	SSF48350. Rho_GAP. 1 hit.
PROSITE	PS50003. PH_DOMAIN. 1 hit. PS50238. RHOGAP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	58504.
NextBio	65012.
SOURCE	Search...

Entry information

Entry name

RHG22_HUMAN

Accession

Primary (citable) accession number: Q7Z5H3
Secondary accession number(s): A0AVP7 , A5YM75, B9EGA0, O00152, Q6ZSB0

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 2007
Last sequence update:	October 1, 2003
Last modified:	May 1, 2013
This is version 77 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.