Q9NRY4 (RHG35_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Rho GTPase-activating protein 35

Alternative name(s):
Glucocorticoid receptor DNA-binding factor 1
Glucocorticoid receptor repression factor 1
Short name=GRF-1
Rho GAP p190A
Short name=p190-A

Gene names

Name:	ARHGAP35
Synonyms:	GRF1, GRLF1, KIAA1722

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	1499 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Represses transcription of the glucocorticoid receptor by binding to the cis-acting regulatory sequence 5'-GAGAAAAGAAACTGGAGAAACTC-3'. May participate in the regulation of retinal development and degeneration. May transduce signals from p21-ras to the nucleus, acting via the ras GTPase-activating protein (GAP). May also act as a tumor suppressor. Ref.5 Ref.6
Subunit structure	Interacts with RASA1.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity.
Post-translational modification	Phosphorylation of Tyr-1105 by PTK6 promotes the association with RASA1, inactivating RHOA while activating RAS.
Sequence similarities	Contains 4 FF domains. Contains 1 Rho-GAP domain.
Sequence caution	The sequence AAA58618.1 differs from that shown. Reason: Frameshift at positions 389, 533, 540, 607, 614, 1167, 1241, 1292, 1334 and 1446. The sequence AAF80386.1 differs from that shown. Reason: Frameshift at positions 533, 540, 607 and 614. The sequence AAF80386.1 differs from that shown. Reason: Unlikely isoform. Aberrant splice sites.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Disease	Tumor suppressor
Domain	Repeat
Ligand	DNA-binding
Molecular function	GTPase activation Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon guidance Traceable author statement. Source: Reactome camera-type eye development Inferred from electronic annotation. Source: Compara forebrain development Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from direct assay Ref.6. Source: UniProtKB negative regulation of vascular permeability Inferred from electronic annotation. Source: Compara neural tube closure Inferred from electronic annotation. Source: Compara regulation of cell shape Inferred from electronic annotation. Source: Compara small GTPase mediated signal transduction Traceable author statement. Source: Reactome transcription, DNA-dependent Traceable author statement Ref.6. Source: ProtInc
Cellular_component	actin cytoskeleton Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome nucleus Inferred by curator Ref.6. Source: UniProtKB
Molecular_function	DNA binding Traceable author statement Ref.6. Source: ProtInc GTP binding Inferred from electronic annotation. Source: InterPro Rho GTPase activator activity Traceable author statement. Source: Reactome transcription corepressor activity Traceable author statement Ref.6. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1499

1499

Rho GTPase-activating protein 35

PRO_0000056730

Regions

Domain

270 – 327

58

FF 1

Domain

369 – 422

54

FF 2

Domain

429 – 483

55

FF 3

Domain

485 – 539

55

FF 4

Domain

1249 – 1436

188

Rho-GAP

Compositional bias

1440 – 1490

51

Pro-rich

Amino acid modifications

Modified residue

589

1

Phosphoserine Ref.12 Ref.13 Ref.14 Ref.16

Modified residue

773

1

Phosphoserine Ref.13

Modified residue

970

1

Phosphoserine Ref.10 Ref.12

Modified residue

975

1

Phosphoserine Ref.12 Ref.13

Modified residue

980

1

Phosphoserine By similarity

Modified residue

1072

1

Phosphoserine Ref.13

Modified residue

1087

1

Phosphotyrosine Ref.13

Modified residue

1105

1

Phosphotyrosine; by ABL2 and PTK6 Ref.9 Ref.13

Modified residue

1134

1

Phosphoserine Ref.13 Ref.16

Modified residue

1150

1

Phosphoserine Ref.12 Ref.16

Modified residue

1179

1

Phosphoserine Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16

Experimental info

Sequence conflict

251

1

R → P in AAF80386. Ref.5

Sequence conflict

309

1

V → D in AAF80386. Ref.5

Sequence conflict

362

1

S → G in AAF80386. Ref.5

Sequence conflict

414

1

Q → A in AAF80386. Ref.5

Sequence conflict

414

1

Q → A in AAA58618. Ref.6

Sequence conflict

474

1

M → T in AAF80386. Ref.5

Sequence conflict

474

1

M → T in AAA58618. Ref.6

Sequence conflict

978

1

C → S in AAF80386. Ref.5

Sequence conflict

1292

1

M → I in AAF80386. Ref.5

Sequence conflict

1452 – 1453

2

PS → RN in AAA58618. Ref.6

Secondary structure

1

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1499

Helix Strand Turn

Details...

Beta strand

14 – 21

8

Turn

25 – 30

6

Helix

35 – 43

9

Turn

47 – 49

3

Helix

60 – 63

4

Turn

66 – 70

5

Beta strand

72 – 79

8

Beta strand

91 – 96

6

Turn

102 – 104

3

Helix

110 – 112

3

Helix

116 – 120

5

Beta strand

123 – 126

4

Helix

136 – 138

3

Helix

142 – 144

3

Helix

151 – 153

3

Beta strand

154 – 156

3

Beta strand

159 – 165

7

Helix

174 – 190

17

Beta strand

195 – 200

6

Helix

202 – 204

3

Helix

207 – 218

12

Beta strand

220 – 222

3

Beta strand

225 – 227

3

Turn

230 – 233

4

Helix

236 – 248

13

Turn

268 – 271

4

Helix

272 – 284

13

Beta strand

286 – 288

3

Helix

292 – 299

8

Helix

303 – 311

9

Helix

314 – 330

17

Helix

1251 – 1254

4

Beta strand

1257 – 1259

3

Helix

1263 – 1275

13

Turn

1280 – 1284

5

Helix

1289 – 1301

13

Helix

1308 – 1310

3

Helix

1314 – 1327

14

Beta strand

1328 – 1330

3

Helix

1335 – 1344

10

Helix

1350 – 1362

13

Helix

1366 – 1383

18

Helix

1386 – 1389

4

Helix

1393 – 1405

13

Beta strand

1409 – 1412

4

Helix

1414 – 1430

17

Helix

1432 – 1436

5

Sequences

	Sequence		Length	Mass (Da)
	Q9NRY4 [UniParc]. Last modified October 3, 2012. Version 3. Checksum: 8CCB493414A7E3E6	FASTA	1,499	170,514
	10 20 30 40 50 60 MMMARKQDVR IPTYNISVVG LSGTEKEKGQ CGIGKSCLCN RFVRPSADEF HLDHTSVLST 70 80 90 100 110 120 SDFGGRVVNN DHFLYWGEVS RSLEDCVECK MHIVEQTEFI DDQTFQPHRS TALQPYIKRA 130 140 150 160 170 180 AATKLASAEK LMYFCTDQLG LEQDFEQKQM PDGKLLVDGF LLGIDVSRGM NRNFDDQLKF 190 200 210 220 230 240 VSNLYNQLAK TKKPIVVVLT KCDEGVERYI RDAHTFALSK KNLQVVETSA RSNVNVDLAF 250 260 270 280 290 300 STLVQLIDKS RGKTKIIPYF EALKQQSQQI ATAKDKYEWL VSRIVKNHNE NWLSVSRKMQ 310 320 330 340 350 360 ASPEYQDYVY LEGTQKAKKL FLQHIHRLKH EHIERRRKLY LAALPLAFEA LIPNLDEIDH 370 380 390 400 410 420 LSCIKAKKLL ETKPEFLKWF VVLEETPWDA TSHIDNMENE RIPFDLMDTV PAEQLYEAHL 430 440 450 460 470 480 EKLRNERKRV EMRRAFKENL ETSPFITPGK PWEEARSFIM NEDFYQWLEE SVYMDIYGKH 490 500 510 520 530 540 QKQIIDKAKE EFQELLLEYS ELFYELELDA KPSKEKMGVI QDVLGEEQRF KALQKLQAER 550 560 570 580 590 600 DALILKHIHF VYHPTKETCP SCPACVDAKI EHLISSRFIR PSDRNQKNSL SDPNIDRINL 610 620 630 640 650 660 VILGKDGLAR ELANEIRALC TNDDKYVIDG KMYELSLRPI EGNVRLPVNS FQTPTFQPHG 670 680 690 700 710 720 CLCLYNSKES LSYVVESIEK SRESTLGRRD NHLVHLPLTL ILVNKRGDTS GETLHSLIQQ 730 740 750 760 770 780 GQQIASKLQC VFLDPASAGI GYGRNINEKQ ISQVLKGLLD SKRNLNLVSS TASIKDLADV 790 800 810 820 830 840 DLRIVMCLMC GDPFSADDIL FPVLQSQTCK SSHCGSNNSV LLELPIGLHK KRIELSVLSY 850 860 870 880 890 900 HSSFSIRKSR LVHGYIVFYS AKRKASLAML RAFLCEVQDI IPIQLVALTD GAVDVLDNDL 910 920 930 940 950 960 SREQLTEGEE IAQEIDGRFT SIPCSQPQHK LEIFHPFFKD VVEKKNIIEA THMYDNAAEA 970 980 990 1000 1010 1020 CSTTEEVFNS PRAGSPLCNS NLQDSEEDIE PSYSLFREDT SLPSLSKDHS KLSMELEGND 1030 1040 1050 1060 1070 1080 GLSFIMSNFE SKLNNKVPPP VKPKPPVHFE ITKGDLSYLD QGHRDGQRKS VSSSPWLPQD 1090 1100 1110 1120 1130 1140 GFDPSDYAEP MDAVVKPRNE EENIYSVPHD STQGKIITIR NINKAQSNGS GNGSDSEMDT 1150 1160 1170 1180 1190 1200 SSLERGRKVS IVSKPVLYRT RCTRLGRFAS YRTSFSVGSD DELGPIRKKE EDQASQGYKG 1210 1220 1230 1240 1250 1260 DNAVIPYETD EDPRRRNILR SLRRNTKKPK PKPRPSITKA TWESNYFGVP LTTVVTPEKP 1270 1280 1290 1300 1310 1320 IPIFIERCIE YIEATGLSTE GIYRVSGNKS EMESLQRQFD QDHNLDLAEK DFTVNTVAGA 1330 1340 1350 1360 1370 1380 MKSFFSELPD PLVPYNMQID LVEAHKINDR EQKLHALKEV LKKFPKENHE VFKYVISHLN 1390 1400 1410 1420 1430 1440 KVSHNNKVNL MTSENLSICF WPTLMRPDFS TMDALTATRT YQTIIELFIQ QCPFFFYNRP 1450 1460 1470 1480 1490 ITEPPGARPS SPSAVASTVP FLTSTPVTSQ PSPPQSPPPT PQSPMQPLLP SQLQAEHTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O. DNA Res. 7:347-355(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[2]	"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] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[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 (JUL-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].
[5]	"p190-A, a human tumor suppressor gene, maps to the chromosomal region 19q13.3 that is reportedly deleted in some gliomas." Tikoo A., Czekay S., Viars C., White S., Heath J.K., Arden K., Maruta H. Gene 257:23-31(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-1491. Tissue: Mammary cancer.
[6]	"Molecular cloning and characterization of a factor that binds the human glucocorticoid receptor gene and represses its expression." LeClerc S., Palaniswami R., Xie B.X., Govindan M.V. J. Biol. Chem. 266:17333-17340(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 377-1453, FUNCTION. Tissue: Mammary cancer.
[7]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
[9]	"Breast tumor kinase phosphorylates p190RhoGAP to regulate rho and ras and promote breast carcinoma growth, migration, and invasion." Shen C.H., Chen H.Y., Lin M.S., Li F.Y., Chang C.C., Kuo M.L., Settleman J., Chen R.H. Cancer Res. 68:7779-7787(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-1105.
[10]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-970 AND SER-1179, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1179, MASS SPECTROMETRY. Tissue: Platelet.
[12]	"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-589; SER-970; SER-975; SER-1150 AND SER-1179, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"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-589; SER-773; SER-975; SER-1072; TYR-1087; TYR-1105; SER-1134 AND SER-1179, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[14]	"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-589 AND SER-1179, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]	"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-589; SER-1134; SER-1150 AND SER-1179, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB051509 mRNA. Translation: BAB21813.2.
CH471126 Genomic DNA. Translation: EAW57450.1.
BC150257 mRNA. Translation: AAI50258.1.
AF159851 mRNA. Translation: AAF80386.1. Sequence problems.
M73077 mRNA. Translation: AAA58618.1. Frameshift.

IPI

IPI00334715.
IPI00718985.

RefSeq

NP_004482.4. NM_004491.4.

UniGene

Hs.509447.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2K85	NMR	-	A	267-331	[»]
3C5H	X-ray	1.80	A	13-249	[»]
3FK2	X-ray	2.80	A/B/C/D	1212-1439	[»]

ProteinModelPortal

Q9NRY4.

SMR

Q9NRY4. Positions 13-249, 267-331, 1242-1437.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NRY4. 1 interaction.

STRING

9606.ENSP00000385720.

PTM databases

PhosphoSite

Q9NRY4.

Polymorphism databases

DMDM

29611783.

Proteomic databases

PaxDb

Q9NRY4.

PRIDE

Q9NRY4.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000404338; ENSP00000385720; ENSG00000160007.

GeneID

2909.

KEGG

hsa:2909.

UCSC

uc010ekv.3. human.

Organism-specific databases

CTD

2909.

GeneCards

GC19P047422.

H-InvDB

HIX0015264.

HGNC

HGNC:4591. ARHGAP35.

HPA

CAB037311.

MIM

605277. gene.

neXtProt

NX_Q9NRY4.

PharmGKB

PA28988.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG241832.

HOVERGEN

HBG051844.

InParanoid

Q9NRY4.

KO

K05732.

OrthoDB

EOG4DZ1TC.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.

Gene expression databases

Bgee

Q9NRY4.

CleanEx

HS_GRLF1.

Genevestigator

Q9NRY4.

GermOnline

ENSG00000160007. Homo sapiens.

Family and domain databases

Gene3D

1.10.555.10. 1 hit.

InterPro

IPR002713. FF_domain.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR001806. Small_GTPase.
[Graphical view]

Pfam

PF01846. FF. 1 hit.
PF00071. Ras. 1 hit.
PF00620. RhoGAP. 1 hit.
[Graphical view]

SMART

SM00441. FF. 4 hits.
SM00324. RhoGAP. 1 hit.
[Graphical view]

SUPFAM

SSF48350. Rho_GAP. 1 hit.

PROSITE

PS50238. RHOGAP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

ARHGAP35. human.

EvolutionaryTrace

Q9NRY4.

GenomeRNAi

2909.

NextBio

11533.

SOURCE

Search...

Entry information

Entry name

RHG35_HUMAN

Accession

Primary (citable) accession number: Q9NRY4
Secondary accession number(s): A7E2A4, Q14452, Q9C0E1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 4, 2003
Last sequence update:	October 3, 2012
Last modified:	May 1, 2013
This is version 129 of the entry and version 3 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.