Reviewed, UniProtKB/Swiss-Prot Q8N264 (RHG24_HUMAN)

Names and origin

Protein names

Recommended name:
    Rho GTPase-activating protein 24
Alternative name(s):
    Rho-type GTPase-activating protein 24
    Filamin-A-associated RhoGAP
      Short name=FilGAP
    RhoGAP of 73 kDa
    p73RhoGAP
    RAC1- and CDC42-specific GTPase-activating protein of 72 kDa
      Short name=RC-GAP72
    Sarcoma antigen NY-SAR-88

Gene names

Name:	ARHGAP24
Synonyms:	FILGAP

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	748 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Rho GTPase-activating protein involved in cell polarity, cell morphology and cytoskeletal organization. Acts as a GTPase activator for the Rac-type GTPase by converting it to an inactive GDP-bound state. Controls actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity. Able to suppress RAC1 and CDC42 activity in vitro. Overexpression induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Isoform 2 is a vascular cell-specific GAP involved in modulation of angiogenesis.
Subunit structure	Interacts with FLNA.
Subcellular location	Cytoplasm › cytoskeleton. Cell junction › adherens junction. Cell junction › focal adhesion. Cell projection. Note= Localizes to actin stress fibers. In migrating cells, localizes to membrane lamellae and protusions.
Tissue specificity	Isoform 1 is widely expressed with a higher level in kidney. Isoform 2 is mainly expressed in endothelial cells.
Induction	Isoform 2 is up-regulated during capillary tube formation in umbilical vein endothelial cells.
Domain	The coiled coil domain mediates the interaction with FLNA leading to its recruitment to lamellae.
Post-translational modification	Phosphorylated by ROCK, leading to activate the RacGAP activity.
Sequence similarities	Contains 1 PH domain. Contains 1 Rho-GAP domain.
Sequence caution	The sequence AAO65178.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
Biological process	Angiogenesis Differentiation
Cellular component	Cell junction Cell projection Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing
Domain	Coiled coil
Molecular function	Developmental protein GTPase activation
PTM	Phosphoprotein
Gene Ontology (GO)
Molecular function	protein binding Ref.8 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FLNA	P21333	3	EBI-988764,EBI-350432
Rock1	P70335	1	EBI-988764,EBI-989293	From a different organism.

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8N264-1)

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: Q8N264-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-93: Missing.
     94-130: DRMTANHESYLLMASTQNDMEDWVKSIRRVIWGPFGG → MPEDRNSGGCPAGALASTPFIPKTTYRRIKRCFSFRK

Isoform 3 (identifier: Q8N264-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-95: Missing.

Isoform 4 (identifier: Q8N264-4)

The sequence of this isoform differs from the canonical sequence as follows:
     245-246: GV → VS
     247-748: Missing.

Notes: No experimental confirmation available.

Isoform 5 (identifier: Q8N264-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MWLRKKDWQI...QQGKSISLIM
     91-94: GDRD → KIFS
     95-748: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 748	748	Rho GTPase-activating protein 24
Regions
	Domain	19 – 125	107	PH
	Domain	135 – 329	195	Rho-GAP
	Coiled coil	649 – 729	81	Potential
Amino acid modifications
	Modified residue	391	1	Phosphoserine
	Modified residue	402	1	Phosphoserine
	Modified residue	413	1	Phosphoserine
	Modified residue	415	1	Phosphoserine
	Modified residue	437	1	Phosphoserine
	Modified residue	452	1	Phosphothreonine
Natural variations
	Alternative sequence	1 – 95	95	Missing in isoform 3.
	Alternative sequence	1 – 93	93	Missing in isoform 2.
	Alternative sequence	1	1	M → MWLRKKDWQIFNEQFLKKEH AVGFCFSKCVLVEFSLKCFK KIKSSYWNNDALAFLGKKFL REKNKMTKKQTRNRQNKFPP KPALRSSPVHRVQHFPLLWK VKEPHYHLFFFAFSYCWSWE PFPSEQQPCPASVLSSQQGK SISLIM in isoform 5.
	Alternative sequence	91 – 94	4	GDRD → KIFS in isoform 5.
	Alternative sequence	94 – 130	37	DRMTA…GPFGG → MPEDRNSGGCPAGALASTPF IPKTTYRRIKRCFSFRK in isoform 2.
	Alternative sequence	95 – 748	654	Missing in isoform 5.
	Alternative sequence	245 – 246	2	GV → VS in isoform 4.
	Alternative sequence	247 – 748	502	Missing in isoform 4.
Experimental info
	Mutagenesis	175	1	R → A: Loss of function
	Mutagenesis	175	1	R → K: Does not abolish the effect on actin stress fibers but moderates its capability to induce membrane protrusions
	Sequence conflict	140	1	T → A in BAC03606. Ref.2
	Sequence conflict	357	1	Q → L in CAB66581. Ref.1
	Sequence conflict	722	1	M → V in BAC03606. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 20, 2007. Version 2. Checksum: 87A8E6DCA6869229	FASTA	748	84,258
	10 20 30 40 50 60 MEENNDSTEN PQQGQGRQNA IKCGWLRKQG GFVKTWHTRW FVLKGDQLYY FKDEDETKPL 70 80 90 100 110 120 GTIFLPGNKV SEHPCNEENP GKFLFEVVPG GDRDRMTANH ESYLLMASTQ NDMEDWVKSI 130 140 150 160 170 180 RRVIWGPFGG GIFGQKLEDT VRYEKRYGNR LAPMLVEQCV DFIRQRGLKE EGLFRLPGQA 190 200 210 220 230 240 NLVKELQDAF DCGEKPSFDS NTDVHTVASL LKLYLRELPE PVIPYAKYED FLSCAKLLSK 250 260 270 280 290 300 EEEAGVKELA KQVKSLPVVN YNLLKYICRF LDEVQSYSGV NKMSVQNLAT VFGPNILRPK 310 320 330 340 350 360 VEDPLTIMEG TVVVQQLMSV MISKHDCLFP KDAELQSKPQ DGVSNNNEIQ KKATMGQLQN 370 380 390 400 410 420 KENNNTKDSP SRQCSWDKSE SPQRSSMNNG SPTALSGSKT NSPKNSVHKL DVSRSPPLMV 430 440 450 460 470 480 KKNPAFNKGS GIVTNGSFSS SNAEGLEKTQ TTPNGSLQAR RSSSLKVSGT KMGTHSVQNG 490 500 510 520 530 540 TVRMGILNSD TLGNPTNVRN MSWLPNGYVT LRDNKQKEQA GELGQHNRLS TYDNVHQQFS 550 560 570 580 590 600 MMNLDDKQSI DSATWSTSSC EISLPENSNS CRSSTTTCPE QDFFGGNFED PVLDGPPQDD 610 620 630 640 650 660 LSHPRDYESK SDHRSVGGRS SRATSSSDNS ETFVGNSSSN HSALHSLVSS LKQEMTKQKI 670 680 690 700 710 720 EYESRIKSLE QRNLTLETEM MSLHDELDQE RKKFTMIEIK MRNAERAKED AEKRNDMLQK 730 740 EMEQFFSTFG ELTVEPRRTE RGNTIWIQ
	Isoform 2 [UniParc]. Checksum: 1497D420E9DD3FE5		655	73,409
	10 20 30 40 50 60 MPEDRNSGGC PAGALASTPF IPKTTYRRIK RCFSFRKGIF GQKLEDTVRY EKRYGNRLAP 70 80 90 100 110 120 MLVEQCVDFI RQRGLKEEGL FRLPGQANLV KELQDAFDCG EKPSFDSNTD VHTVASLLKL 130 140 150 160 170 180 YLRELPEPVI PYAKYEDFLS CAKLLSKEEE AGVKELAKQV KSLPVVNYNL LKYICRFLDE 190 200 210 220 230 240 VQSYSGVNKM SVQNLATVFG PNILRPKVED PLTIMEGTVV VQQLMSVMIS KHDCLFPKDA 250 260 270 280 290 300 ELQSKPQDGV SNNNEIQKKA TMGQLQNKEN NNTKDSPSRQ CSWDKSESPQ RSSMNNGSPT 310 320 330 340 350 360 ALSGSKTNSP KNSVHKLDVS RSPPLMVKKN PAFNKGSGIV TNGSFSSSNA EGLEKTQTTP 370 380 390 400 410 420 NGSLQARRSS SLKVSGTKMG THSVQNGTVR MGILNSDTLG NPTNVRNMSW LPNGYVTLRD 430 440 450 460 470 480 NKQKEQAGEL GQHNRLSTYD NVHQQFSMMN LDDKQSIDSA TWSTSSCEIS LPENSNSCRS 490 500 510 520 530 540 STTTCPEQDF FGGNFEDPVL DGPPQDDLSH PRDYESKSDH RSVGGRSSRA TSSSDNSETF 550 560 570 580 590 600 VGNSSSNHSA LHSLVSSLKQ EMTKQKIEYE SRIKSLEQRN LTLETEMMSL HDELDQERKK 610 620 630 640 650 FTMIEIKMRN AERAKEDAEK RNDMLQKEME QFFSTFGELT VEPRRTERGN TIWIQ
	Isoform 3 [UniParc]. Checksum: F6A68FEF1E0A5564		653	73,290
	10 20 30 40 50 60 MTANHESYLL MASTQNDMED WVKSIRRVIW GPFGGGIFGQ KLEDTVRYEK RYGNRLAPML 70 80 90 100 110 120 VEQCVDFIRQ RGLKEEGLFR LPGQANLVKE LQDAFDCGEK PSFDSNTDVH TVASLLKLYL 130 140 150 160 170 180 RELPEPVIPY AKYEDFLSCA KLLSKEEEAG VKELAKQVKS LPVVNYNLLK YICRFLDEVQ 190 200 210 220 230 240 SYSGVNKMSV QNLATVFGPN ILRPKVEDPL TIMEGTVVVQ QLMSVMISKH DCLFPKDAEL 250 260 270 280 290 300 QSKPQDGVSN NNEIQKKATM GQLQNKENNN TKDSPSRQCS WDKSESPQRS SMNNGSPTAL 310 320 330 340 350 360 SGSKTNSPKN SVHKLDVSRS PPLMVKKNPA FNKGSGIVTN GSFSSSNAEG LEKTQTTPNG 370 380 390 400 410 420 SLQARRSSSL KVSGTKMGTH SVQNGTVRMG ILNSDTLGNP TNVRNMSWLP NGYVTLRDNK 430 440 450 460 470 480 QKEQAGELGQ HNRLSTYDNV HQQFSMMNLD DKQSIDSATW STSSCEISLP ENSNSCRSST 490 500 510 520 530 540 TTCPEQDFFG GNFEDPVLDG PPQDDLSHPR DYESKSDHRS VGGRSSRATS SSDNSETFVG 550 560 570 580 590 600 NSSSNHSALH SLVSSLKQEM TKQKIEYESR IKSLEQRNLT LETEMMSLHD ELDQERKKFT 610 620 630 640 650 MIEIKMRNAE RAKEDAEKRN DMLQKEMEQF FSTFGELTVE PRRTERGNTI WIQ
	Isoform 4 [UniParc]. Checksum: 9AC9E1CA3D589430		246	28,249
	10 20 30 40 50 60 MEENNDSTEN PQQGQGRQNA IKCGWLRKQG GFVKTWHTRW FVLKGDQLYY FKDEDETKPL 70 80 90 100 110 120 GTIFLPGNKV SEHPCNEENP GKFLFEVVPG GDRDRMTANH ESYLLMASTQ NDMEDWVKSI 130 140 150 160 170 180 RRVIWGPFGG GIFGQKLEDT VRYEKRYGNR LAPMLVEQCV DFIRQRGLKE EGLFRLPGQA 190 200 210 220 230 240 NLVKELQDAF DCGEKPSFDS NTDVHTVASL LKLYLRELPE PVIPYAKYED FLSCAKLLSK EEEAVS
	Isoform 5 [UniParc]. Checksum: 44E3F4574FA33D77		239	28,221
	10 20 30 40 50 60 MWLRKKDWQI FNEQFLKKEH AVGFCFSKCV LVEFSLKCFK KIKSSYWNND ALAFLGKKFL 70 80 90 100 110 120 REKNKMTKKQ TRNRQNKFPP KPALRSSPVH RVQHFPLLWK VKEPHYHLFF FAFSYCWSWE 130 140 150 160 170 180 PFPSEQQPCP ASVLSSQQGK SISLIMEENN DSTENPQQGQ GRQNAIKCGW LRKQGGFVKT 190 200 210 220 230 WHTRWFVLKG DQLYYFKDED ETKPLGTIFL PGNKVSEHPC NEENPGKFLF EVVPGKIFS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5). Tissue: Spleen and Tongue.
[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] (ISOFORMS 3 AND 4). Tissue: Chondrosarcoma.
[4]	"Immunomic analysis of human sarcoma." Lee S.-Y., Obata Y., Yoshida M., Stockert E., Williamson B., Jungbluth A.A., Chen Y.-T., Old L.J., Scanlan M.J. Proc. Natl. Acad. Sci. U.S.A. 100:2651-2656(2003) [PubMed: 12601173] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 233-510.
[5]	"Identification and characterization of ARHGAP24 and ARHGAP25 genes in silico." Katoh M., Katoh M. Int. J. Mol. Med. 14:333-338(2004) [PubMed: 15254788] [Abstract] Cited for: IDENTIFICATION.
[6]	"A vascular cell-restricted RhoGAP, p73RhoGAP, is a key regulator of angiogenesis." Su Z.-J., Hahn C.N., Goodall G.J., Reck N.M., Leske A.F., Davy A., Kremmidiotis G., Vadas M.A., Gamble J.R. Proc. Natl. Acad. Sci. U.S.A. 101:12212-12217(2004) [PubMed: 15302923] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, INDUCTION, MUTAGENESIS OF ARG-175.
[7]	"Characterization of a novel GTPase-activating protein associated with focal adhesions and the actin cytoskeleton." Lavelin I., Geiger B. J. Biol. Chem. 280:7178-7185(2005) [PubMed: 15611138] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF ARG-175.
[8]	"FilGAP, a Rho- and ROCK-regulated GAP for Rac binds filamin A to control actin remodelling." Ohta Y., Hartwig J.H., Stossel T.P. Nat. Cell Biol. 8:803-814(2006) [PubMed: 16862148] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH FLNA, PHOSPHORYLATION AT SER-391; SER-402; SER-413; SER-415; SER-437 AND THR-452.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AL136646 mRNA. Translation: CAB66581.1. AK091196 mRNA. Translation: BAC03606.1. AK130576 mRNA. Translation: BAC85384.1. BC047918 mRNA. Translation: AAH47918.1. BC098580 mRNA. Translation: AAH98580.1. AY211925 mRNA. Translation: AAO65178.1. Frameshift.
PIR	A59430.
RefSeq	NP_001020787.2. NP_001036134.1. NP_112595.2.
UniGene	Hs.444229 Hs.667822
3D structure databases
HSSP	HSSP built from PDB template 1F7C based on UniProtKB Q98935.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8N264.
PTM databases
PhosphoSite	Q8N264.
Genome annotation databases
Ensembl	ENSG00000138639. Homo sapiens. [Contig view]
GeneID	83478.
KEGG	hsa:83478.
Organism-specific databases
HGNC	HGNC:25361. ARHGAP24.
HPA	HPA014288.
MIM	610586. gene.
PharmGKB	PA134934054.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	Q8N264.
Enzyme and pathway databases
Reactome	REACT_11044. Signaling by Rho GTPases.
Gene expression databases
ArrayExpress	Q8N264.
CleanEx	HS_ARHGAP24.
Family and domain databases
InterPro	IPR001849. PH. IPR011993. PH_type. IPR000198. RhoGAP. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 1 hit. G3DSA:1.10.555.10. RhoGAP. 1 hit.
Pfam	PF00169. PH. 1 hit. PF00620. RhoGAP. 1 hit. [Graphical view]
SMART	SM00233. PH. 1 hit. SM00324. RhoGAP. 1 hit. [Graphical view]
PROSITE	PS50003. PH_DOMAIN. 1 hit. PS50238. RHOGAP. 1 hit. [Graphical view]
ProDom	Q8N264. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

RHG24_HUMAN

Accession

Primary (citable) accession number: Q8N264
Secondary accession number(s): Q4KMG1 , Q6ZNV3, Q86TI5, Q86WE4, Q9H0T6

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 2007
Last sequence update:	March 20, 2007
Last modified:	July 22, 2008
This is version 47 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)