P98171 (RHG04_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Rho GTPase-activating protein 4

Alternative name(s):
Rho-GAP hematopoietic protein C1
Rho-type GTPase-activating protein 4
p115

Gene names

Name:	ARHGAP4
Synonyms:	KIAA0131, RGC1, RHOGAP4

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

General annotation (Comments)

Function	Inhibitory effect on stress fiber organization. May down-regulate Rho-like GTPase in hematopoietic cells.
Subcellular location	Cytoplasm. Note: Just below the plasma membrane.
Tissue specificity	Predominantly in hematopoietic cells (spleen, thymus and leukocytes); low levels in placenta, lung and various fetal tissues.
Sequence similarities	Contains 1 FCH domain. Contains 1 Rho-GAP domain. Contains 1 SH3 domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil SH3 domain
Molecular function	GTPase activation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Rho protein signal transduction Traceable author statement Ref.1. Source: ProtInc apoptotic process Traceable author statement. Source: Reactome cytoskeleton organization Traceable author statement Ref.1. Source: ProtInc nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome focal adhesion Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular_function	Rho GTPase activator activity Traceable author statement Ref.1. Source: ProtInc SH3/SH2 adaptor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P98171-1)

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: P98171-2)

The sequence of this isoform differs from the canonical sequence as follows:
     227-227: K → KLWPPQRPVAASSCAPVCWLQAGFLVHPPWWGAMCAPSTHQ

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 946

946

Rho GTPase-activating protein 4

PRO_0000056701

Regions

Domain

15 – 88

74

FCH

Domain

507 – 695

189

Rho-GAP

Domain

746 – 805

60

SH3

Coiled coil

128 – 195

68

Potential

Natural variations

Alternative sequence

227

1

K → KLWPPQRPVAASSCAPVCWL QAGFLVHPPWWGAMCAPSTH Q in isoform 2.

VSP_042902

Natural variant

104

1

A → V.
Corresponds to variant rs5987182 [ dbSNP | Ensembl ].

VAR_028413

Experimental info

Sequence conflict

609

1

A → D in CAA55394. Ref.1

Sequence conflict

731

1

E → D in CAA55394. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

946

Helix Strand Turn

Details...

Beta strand

749 – 755

7

Beta strand

772 – 780

9

Beta strand

783 – 788

6

Beta strand

791 – 801

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: ED3D48C5DAA24969	FASTA	946	105,026
	10 20 30 40 50 60 MAAHGKLRRE RGLQAEYETQ VKEMRWQLSE QLRCLELQGE LRRELLQELA EFMRRRAEVE 70 80 90 100 110 120 LEYSRGLEKL AERFSSRGGR LGSSREHQSF RKEPSLLSPL HCWAVLLQHT RQQSRESAAL 130 140 150 160 170 180 SEVLAGPLAQ RLSHIAEDVG RLVKKSRDLE QQLQDELLEV VSELQTAKKT YQAYHMESVN 190 200 210 220 230 240 AEAKLREAER QEEKRAGRSV PTTTAGATEA GPLRKSSLKK GGRLVEKRQA KFMEHKLKCT 250 260 270 280 290 300 KARNEYLLSL ASVNAAVSNY YLHDVLDLMD CCDTGFHLAL GQVLRSYTAA ESRTQASQVQ 310 320 330 340 350 360 GLGSLEEAVE ALDPPGDKAK VLEVHATVFC PPLRFDYHPH DGDEVAEICV EMELRDEILP 370 380 390 400 410 420 RAQNIQSRLD RQTIETEEVN KTLKATLQAL LEVVASDDGD VLDSFQTSPS TESLKSTSSD 430 440 450 460 470 480 PGSRQAGRRR GQQQETETFY LTKLQEYLSG RSILAKLQAK HEKLQEALQR GDKEEQEVSW 490 500 510 520 530 540 TQYTQRKFQK SRQPRPSSQY NQRLFGGDME KFIQSSGQPV PLVVESCIRF INLNGLQHEG 550 560 570 580 590 600 IFRVSGAQLR VSEIRDAFER GEDPLVEGCT AHDLDSVAGV LKLYFRSLEP PLFPPDLFGE 610 620 630 640 650 660 LLASSELEAT AERVEHVSRL LWRLPAPVLV VLRYLFTFLN HLAQYSDENM MDPYNLAVCF 670 680 690 700 710 720 GPTLLPVPAG QDPVALQGRV NQLVQTLIVQ PDRVFPPLTS LPGPVYEKCM APPSASCLGD 730 740 750 760 770 780 AQLESLGADN EPELEAEMPA QEDDLEGVVE AVACFAYTGR TAQELSFRRG DVLRLHERAS 790 800 810 820 830 840 SDWWRGEHNG MRGLIPHKYI TLPAGTEKQV VGAGLQTAGE SGSSPEGLLA SELVHRPEPC 850 860 870 880 890 900 TSPEAMGPSG HRRRCLVPAS PEQHVEVDKA VAQNMDSVFK ELLGKTSVRQ GLGPASTTSP 910 920 930 940 SPGPRSPKAP PSSRLGRNKG FSRGPGAPAS PSASHPQGLD TTPKPH
	Isoform 2 [UniParc]. Checksum: 7098B225673075FB	FASTA	986	109,393
	10 20 30 40 50 60 MAAHGKLRRE RGLQAEYETQ VKEMRWQLSE QLRCLELQGE LRRELLQELA EFMRRRAEVE 70 80 90 100 110 120 LEYSRGLEKL AERFSSRGGR LGSSREHQSF RKEPSLLSPL HCWAVLLQHT RQQSRESAAL 130 140 150 160 170 180 SEVLAGPLAQ RLSHIAEDVG RLVKKSRDLE QQLQDELLEV VSELQTAKKT YQAYHMESVN 190 200 210 220 230 240 AEAKLREAER QEEKRAGRSV PTTTAGATEA GPLRKSSLKK GGRLVEKLWP PQRPVAASSC 250 260 270 280 290 300 APVCWLQAGF LVHPPWWGAM CAPSTHQRQA KFMEHKLKCT KARNEYLLSL ASVNAAVSNY 310 320 330 340 350 360 YLHDVLDLMD CCDTGFHLAL GQVLRSYTAA ESRTQASQVQ GLGSLEEAVE ALDPPGDKAK 370 380 390 400 410 420 VLEVHATVFC PPLRFDYHPH DGDEVAEICV EMELRDEILP RAQNIQSRLD RQTIETEEVN 430 440 450 460 470 480 KTLKATLQAL LEVVASDDGD VLDSFQTSPS TESLKSTSSD PGSRQAGRRR GQQQETETFY 490 500 510 520 530 540 LTKLQEYLSG RSILAKLQAK HEKLQEALQR GDKEEQEVSW TQYTQRKFQK SRQPRPSSQY 550 560 570 580 590 600 NQRLFGGDME KFIQSSGQPV PLVVESCIRF INLNGLQHEG IFRVSGAQLR VSEIRDAFER 610 620 630 640 650 660 GEDPLVEGCT AHDLDSVAGV LKLYFRSLEP PLFPPDLFGE LLASSELEAT AERVEHVSRL 670 680 690 700 710 720 LWRLPAPVLV VLRYLFTFLN HLAQYSDENM MDPYNLAVCF GPTLLPVPAG QDPVALQGRV 730 740 750 760 770 780 NQLVQTLIVQ PDRVFPPLTS LPGPVYEKCM APPSASCLGD AQLESLGADN EPELEAEMPA 790 800 810 820 830 840 QEDDLEGVVE AVACFAYTGR TAQELSFRRG DVLRLHERAS SDWWRGEHNG MRGLIPHKYI 850 860 870 880 890 900 TLPAGTEKQV VGAGLQTAGE SGSSPEGLLA SELVHRPEPC TSPEAMGPSG HRRRCLVPAS 910 920 930 940 950 960 PEQHVEVDKA VAQNMDSVFK ELLGKTSVRQ GLGPASTTSP SPGPRSPKAP PSSRLGRNKG 970 980 FSRGPGAPAS PSASHPQGLD TTPKPH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"An X chromosome-linked gene encoding a protein with characteristics of a rhoGAP predominantly expressed in hematopoietic cells." Tribioli C., Droetto S., Bione S., Cesareni G., Torrisi M.R., Lotti L.V., Lanfrancone L., Toniolo D., Pelicci P.-G. Proc. Natl. Acad. Sci. U.S.A. 93:695-699(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Embryo.
[2]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton 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 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: Pancreas.
[5]	"Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1." Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N. DNA Res. 2:167-174(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-946 (ISOFORM 1). Tissue: Bone marrow.
[6]	"Isolation of new genes in distal Xq28: transcriptional map and identification of a human homologue of the ARD1 N-acetyl transferase of Saccharomyces cerevisiae." Tribioli C., Mancini M., Plassart E., Bione S., Rivella S., Sala C., Torri G., Toniolo D. Hum. Mol. Genet. 3:1061-1068(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-103 (ISOFORM 1). Tissue: Embryo.
[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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. 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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[9]	"Solution structure of SH3 domain in Rho-GTPase-activating protein 4." RIKEN structural genomics initiative (RSGI) Submitted (OCT-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 746-814.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X78817 mRNA. Translation: CAA55394.1.
U52112 Genomic DNA. No translation available.
CH471172 Genomic DNA. Translation: EAW72778.1.
BC052303 mRNA. Translation: AAH52303.1.
D50921 mRNA. Translation: BAA09480.1.

IPI

IPI00328842.
IPI00398854.

PIR

I38100.

RefSeq

NP_001158213.1. NM_001164741.1.
NP_001657.3. NM_001666.4.

UniGene

Hs.701324.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EPD	NMR	-	A	746-814	[»]

ProteinModelPortal

P98171.

ModBase

Search...

Protein-protein interaction databases

IntAct

P98171. 2 interactions.

STRING

9606.ENSP00000203786.

PTM databases

PhosphoSite

P98171.

Polymorphism databases

DMDM

116242759.

Proteomic databases

PaxDb

P98171.

PRIDE

P98171.

Protocols and materials databases

DNASU

393.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000350060; ENSP00000203786; ENSG00000089820.
ENST00000370028; ENSP00000359045; ENSG00000089820.
ENST00000596481; ENSP00000469103; ENSG00000268876.
ENST00000602200; ENSP00000472759; ENSG00000268876.

GeneID

393.

KEGG

hsa:393.

UCSC

uc004fjk.2. human.

Organism-specific databases

CTD

393.

GeneCards

GC0XM153172.

HGNC

HGNC:674. ARHGAP4.

HPA

HPA001012.
HPA001083.

MIM

300023. gene.

neXtProt

NX_P98171.

PharmGKB

PA24958.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG264793.

HOGENOM

HOG000039980.

HOVERGEN

HBG051637.

OMA

GSSREHQ.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P98171.

Bgee

P98171.

CleanEx

HS_ARHGAP4.

Genevestigator

P98171.

GermOnline

ENSG00000089820. Homo sapiens.

Family and domain databases

Gene3D

1.10.555.10. 1 hit.

InterPro

IPR001060. FCH_dom.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF00611. FCH. 1 hit.
PF00620. RhoGAP. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

SMART

SM00055. FCH. 1 hit.
SM00324. RhoGAP. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF48350. Rho_GAP. 1 hit.
SSF50044. SH3. 1 hit.

PROSITE

PS50133. FCH. 1 hit.
PS50238. RHOGAP. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P98171.

GenomeRNAi

393.

NextBio

1639.

PMAP-CutDB

P98171.

SOURCE

Search...

Entry information

Entry name

RHG04_HUMAN

Accession

Primary (citable) accession number: P98171
Secondary accession number(s): Q14144, Q86UY3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 128 of the entry and version 2 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.