Reviewed, UniProtKB/Swiss-Prot O15085 (ARHGB_HUMAN)

Names and origin

Protein names

Recommended name:
    Rho guanine nucleotide exchange factor 11
Alternative name(s):
    PDZ-RhoGEF

Gene names

Name:	ARHGEF11
Synonyms:	KIAA0380

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1522 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13.
Subunit structure	Interacts with GNA12 and GNA13 through the RGS domain. Interacts with RHOA, PLXNB1 and PLXNB2. Interacts with SLC1A6 By similarity.
Subcellular location	Cytoplasm. Membrane. Note: Translocated to the membrane upon stimulation. Ref.7
Tissue specificity	Ubiquitously expressed. Ref.4
Domain	The poly-Pro region is essential for plasma membrane localization upon stimulation.
Sequence similarities	Contains 1 DH (DBL-homology) domain. Contains 1 PDZ (DHR) domain. Contains 1 PH domain. Contains 1 RGSL (RGS-like) domain.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Domain	Coiled coil
Molecular function	GTPase activation Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Ref.4 Traceable author statement. Source: UniProtKB Rho protein signal transduction Ref.4 Inferred from direct assay. Source: UniProtKB actin cytoskeleton organization Ref.4 Non-traceable author statement. Source: UniProtKB cell motion Ref.4 Non-traceable author statement. Source: UniProtKB cytokinesis Ref.4 Non-traceable author statement. Source: UniProtKB establishment of cell polarity Ref.4 Non-traceable author statement. Source: UniProtKB positive regulation of transcription, DNA-dependent Ref.4 Inferred from direct assay. Source: UniProtKB regulation of Rho protein signal transduction Inferred from electronic annotation. Source: InterPro regulation of cell growth Ref.4 Non-traceable author statement. Source: UniProtKB striated muscle contraction Ref.4 Non-traceable author statement. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular function	G-protein-coupled receptor binding Inferred from direct assay. Source: MGI GTPase activator activity Inferred from electronic annotation. Source: UniProtKB-KW Rho guanyl-nucleotide exchange factor activity Ref.4 Traceable author statement. Source: UniProtKB signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABCA1	O95477	1	EBI-311099,EBI-784112
ABL1	P00519	1	EBI-311099,EBI-375543
CRK	P46108	1	EBI-311099,EBI-886
FYN	P06241	1	EBI-311099,EBI-515315
GRB2	P62993	1	EBI-311099,EBI-401755
NCK1	P16333	1	EBI-311099,EBI-389883
PIK3R1	P27986	1	EBI-311099,EBI-79464
PLCG1	P19174	1	EBI-311099,EBI-79387

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1522

1522

Rho guanine nucleotide exchange factor 11

PRO_0000080928

Regions

Domain

47 – 126

80

PDZ

Domain

306 – 486

181

RGSL

Domain

734 – 923

190

DH

Domain

965 – 1079

115

PH

Coiled coil

444 – 470

27

Potential

Compositional bias

1094 – 1099

6

Poly-Pro

Amino acid modifications

Modified residue

245

1

Phosphoserine Ref.10

Modified residue

251

1

Phosphoserine Ref.10

Modified residue

254

1

Phosphothreonine Ref.10

Modified residue

255

1

Phosphoserine Ref.10

Modified residue

663

1

Phosphoserine Ref.8 Ref.9

Modified residue

668

1

Phosphothreonine Ref.10 Ref.8 Ref.9

Modified residue

672

1

Phosphothreonine Ref.10 Ref.9

Modified residue

1155

1

Phosphoserine Ref.10 Ref.8

Modified residue

1295

1

Phosphoserine Ref.10

Modified residue

1300

1

Phosphoserine Ref.10

Modified residue

1457

1

Phosphoserine Ref.10

Modified residue

1458

1

Phosphoserine Ref.10

Modified residue

1462

1

Phosphothreonine Ref.10

Modified residue

1475

1

Phosphothreonine Ref.10

Modified residue

1480

1

Phosphoserine Ref.10

Modified residue

1489

1

Phosphoserine Ref.10

Modified residue

1491

1

Phosphoserine Ref.10

Natural variations

Natural variant

1427

1

H → R: dbSNP rs945508.

VAR_024285

Secondary structure

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1522

Helix Strand Turn

Details...

Beta strand

45 – 51

7

Beta strand

53 – 56

4

Beta strand

59 – 62

4

Beta strand

64 – 66

3

Beta strand

68 – 72

5

Beta strand

74 – 76

3

Turn

77 – 82

6

Beta strand

88 – 92

5

Beta strand

98 – 100

3

Helix

102 – 109

8

Beta strand

111 – 120

10

Helix

307 – 312

6

Helix

314 – 319

6

Helix

321 – 334

14

Helix

338 – 349

12

Helix

356 – 368

13

Helix

381 – 392

12

Helix

398 – 424

27

Helix

428 – 431

4

Turn

432 – 434

3

Helix

435 – 438

4

Helix

443 – 462

20

Helix

466 – 482

17

Turn

716 – 718

3

Beta strand

719 – 724

6

Helix

725 – 727

3

Helix

730 – 759

30

Helix

761 – 766

6

Helix

772 – 778

7

Beta strand

779 – 781

3

Helix

782 – 801

20

Helix

810 – 817

8

Helix

819 – 833

15

Helix

836 – 849

14

Helix

851 – 861

11

Helix

864 – 866

3

Helix

871 – 874

4

Helix

877 – 894

18

Helix

901 – 939

39

Turn

943 – 945

3

Turn

951 – 953

3

Helix

954 – 958

5

Helix

961 – 963

3

Beta strand

966 – 974

9

Beta strand

977 – 979

3

Beta strand

983 – 998

16

Beta strand

1024 – 1027

4

Helix

1028 – 1030

3

Beta strand

1031 – 1035

5

Beta strand

1040 – 1047

8

Beta strand

1050 – 1052

3

Beta strand

1056 – 1060

5

Helix

1064 – 1080

17

Sequences

	Sequence		Length	Mass (Da)
	O15085-1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: CA16E125B9F8A4AA	FASTA	1,522	167,704
	10 20 30 40 50 60 MSVRLPQSID RLSSLSSLGD SAPERKSPSH HRQPSDASET TGLVQRCVII QKDQHGFGFT 70 80 90 100 110 120 VSGDRIVLVQ SVRPGGAAMK AGVKEGDRII KVNGTMVTNS SHLEVVKLIK SGAYVALTLL 130 140 150 160 170 180 GSSPSSMGIS GLQQDPSPAG APRITSVIPS PPPPPPLPPP QRITGPKPLQ DPEVQKHATQ 190 200 210 220 230 240 ILRNMLRQEE KELQDILPLY GDTSQRPSEG RLSLDSQEGD SGLDSGTERF PSLSESLMNR 250 260 270 280 290 300 NSVLSDPGLD SPRTSPVIMA RVAQHHRRQG SDAAVPSTGD QGVDQSPKPL IIGPEEDYDP 310 320 330 340 350 360 GYFNNESDII FQDLEKLKSR PAHLGVFLRY IFSQADPSPL LFYLCAEVYQ QASPKDSRSL 370 380 390 400 410 420 GKDIWNIFLE KNAPLRVKIP EMLQAEIDSR LRNSEDARGV LCEAQEAAMP EIQEQIHDYR 430 440 450 460 470 480 TKRTLGLGSL YGENDLLDLD GDPLRERQVA EKQLAALGDI LSKYEEDRSA PMDFALNTYM 490 500 510 520 530 540 SHAGIRLREA RPSNTAEKAQ SAPDKDKWLP FFPKTKKSSN SKKEKDALED KKRNPILKYI 550 560 570 580 590 600 GKPKSSSQST FHIPLSPVEV KPGNVRNIIQ HFENNQQYDA PEPGTQRLST GSFPEDLLES 610 620 630 640 650 660 DSSRSEIRLG RSESLKGREE MKRSRKAENV PRSRSDVDMD AAAEATRLHQ SASSSTSSLS 670 680 690 700 710 720 TRSLENPTPP FTPKMGRRSI ESPSLGFCTD TLLPHLLEDD LGQLSDLEPE PDAQNWQHTV 730 740 750 760 770 780 GKDVVAGLTQ REIDRQEVIN ELFVTEASHL RTLRVLDLIF YQRMKKENLM PREELARLFP 790 800 810 820 830 840 NLPELIEIHN SWCEAMKKLR EEGPIIKEIS DLMLARFDGP AREELQQVAA QFCSYQSIAL 850 860 870 880 890 900 ELIKTKQRKE SRFQLFMQEA ESHPQCRRLQ LRDLIISEMQ RLTKYPLLLE SIIKHTEGGT 910 920 930 940 950 960 SEHEKLCRAR DQCREILKYV NEAVKQTENR HRLEGYQKRL DATALERASN PLAAEFKSLD 970 980 990 1000 1010 1020 LTTRKMIHEG PLTWRISKDK TLDLHVLLLE DLLVLLQKQD EKLLLKCHSK TAVGSSDSKQ 1030 1040 1050 1060 1070 1080 TFSPVLKLNA VLIRSVATDK RAFFIICTSK LGPPQIYELV ALTSSDKNTW MELLEEAVRN 1090 1100 1110 1120 1130 1140 ATRHPGAAPM PVHPPPPGPR EPAQQGPTPS RVELDDSDVF HGEPEPEELP GGTGSQQRVQ 1150 1160 1170 1180 1190 1200 GKHQVLLEDP EQEGSAEEEE LGVLPCPSTS LDGENRGIRT RNPIHLAFPG PLFMEGLADS 1210 1220 1230 1240 1250 1260 ALEDVENLRH LILWSLLPGH TMETQAAQEP EDDLTPTPSV ISVTSHPWDP GSPGQAPPGG 1270 1280 1290 1300 1310 1320 EGDNTQLAGL EGERPEQEDM GLCSLEHLPP RTRNSGIWES PELDRNLAED ASSTEAAGGY 1330 1340 1350 1360 1370 1380 KVVRKAEVAG SKVVPALPES GQSEPGPPEV EGGTKATGNC FYVSMPSGPP DSSTDHSEAP 1390 1400 1410 1420 1430 1440 MSPPQPDSLP AGQTEPQPQL QGGNDDPRRP SRSPPSLALR DVGMIFHTIE QLTLKLNRLK 1450 1460 1470 1480 1490 1500 DMELAHRELL KSLGGESSGG TTPVGSFHTE AARWTDGSLS PPAKEPLASD SRNSHELGPC 1510 1520 PEDGSDAPLE DSTADAAASP GP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:141-150(1997) [PubMed: 9205841] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a dbl family member." Ruemenapp U., Blomquist A., Schwoerer G., Schablowski H., Psoma A., Jakobs K.H. FEBS Lett. 459:313-318(1999) [PubMed: 10526156] [Abstract] Cited for: INTERACTION WITH RHOA.
[4]	"A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho." Fukuhara S., Murga C., Zohar M., Igishi T., Gutkind J.S. J. Biol. Chem. 274:5868-5879(1999) [PubMed: 10026210] [Abstract] Cited for: INTERACTION WITH GNA12 AND GNA13, TISSUE SPECIFICITY. Tissue: Brain.
[5]	"B plexins activate Rho through PDZ-RhoGEF." Driessens M.H.E., Olivo C., Nagata K., Inagaki M., Collard J.G. FEBS Lett. 529:168-172(2002) [PubMed: 12372594] [Abstract] Cited for: INTERACTION WITH PLXNB1 AND PLXNB2.
[6]	"Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia-associated Rho GEF (LARG) and PDZ-RhoGEF." Perrot V., Vazquez-Prado J., Gutkind J.S. J. Biol. Chem. 277:43115-43120(2002) [PubMed: 12183458] [Abstract] Cited for: INTERACTION WITH PLXNB1 AND PLXNB2.
[7]	"Functions of a rho-specific guanine nucleotide exchange factor in neurite retraction. Possible role of a proline-rich motif of KIAA0380 in localization." Togashi H., Nagata K., Takagishi M., Saitoh N., Inagaki M. J. Biol. Chem. 275:29570-29578(2000) [PubMed: 10900204] [Abstract] Cited for: SUBCELLULAR LOCATION.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-663; THR-668 AND SER-1155, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-663; THR-668 AND THR-672, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245; SER-251; THR-254; SER-255; THR-668; THR-672; SER-1155; SER-1295; SER-1300; SER-1457; SER-1458; THR-1462; THR-1475; SER-1480; SER-1489 AND SER-1491, MASS SPECTROMETRY.
[11]	"Structure of the RGS-like domain from PDZ-RhoGEF: linking heterotrimeric g protein-coupled signaling to Rho GTPases." Longenecker K.L., Lewis M.E., Chikumi H., Gutkind J.S., Derewenda Z.S. Structure 9:559-569(2001) [PubMed: 11470431] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 281-490.
[12]	"Solution structure of the PDZ domain of human Rho guanine nucleotide exchange factor 11." RIKEN structural genomics initiative (RSGI) Submitted (OCT-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 44-123.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AB002378 mRNA. Translation: BAA20834.2. Different initiation.
AL356104, AL157713 Genomic DNA. Translation: CAH72940.1.
AL157713, AL356104 Genomic DNA. Translation: CAH70127.1.

IPI

IPI00157442.

RefSeq

NP_055599.1.

UniGene

Hs.516954

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HTJ	X-ray	2.20	F	281-490	[»]
1XCG	X-ray	2.50	A/E	714-1081	[»]
2DLS	NMR	-	A	44-123	[»]

SMR

O15085. Positions 37-120.

ModBase

Search...

Protein-protein interaction databases

IntAct

O15085. 11 interactions.

STRING

O15085.

PTM databases

PhosphoSite

O15085.

Proteomic databases

PRIDE

O15085.

Genome annotation databases

Ensembl

ENST00000315174; ENSP00000313470; ENSG00000132694; Homo sapiens. [Genome view]
ENST00000361409; ENSP00000354644; ENSG00000132694; Homo sapiens. [Genome view]
ENST00000368194; ENSP00000357177; ENSG00000132694; Homo sapiens. [Genome view]
ENST00000413909; ENSP00000414518; ENSG00000132694; Homo sapiens. [Genome view]

GeneID

9826.

KEGG

hsa:9826.

NMPDR

fig|9606.3.peg.2332.

UCSC

uc001fqo.1. human.

Organism-specific databases

CTD

9826.

GeneCards

GC01M155171.

HGNC

HGNC:14580. ARHGEF11.

HPA

HPA011026.
HPA012037.
HPA014658.

MIM

605708. gene.

PharmGKB

PA24968.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

O15085.

Enzyme and pathway databases

Reactome

REACT_11044. Signaling by Rho GTPases.
REACT_11061. Signalling by NGF.
REACT_14797. Signaling by GPCR.
REACT_18266. Axon guidance.

Gene expression databases

ArrayExpress

O15085.

Bgee

O15085.

CleanEx

HS_ARHGEF11.

Genevestigator

O15085.

GermOnline

ENSG00000132694. Homo sapiens.

Family and domain databases

InterPro

IPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR001478. PDZ/DHR/GLGF.
IPR011993. PH_type.
IPR001849. Pleckstrin_homology.
IPR000342. Regulat_G_prot_signal.
IPR015212. Regulat_G_prot_signal-like.
IPR015721. RhoGEF-like.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 1 hit.
G3DSA:1.20.900.10. RhoGEF. 1 hit.

PANTHER

PTHR22825. RhoGEF_like. 1 hit.

Pfam

PF00595. PDZ. 1 hit.
PF09128. RGS-like. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]

SMART

SM00228. PDZ. 1 hit.
SM00233. PH. 1 hit.
SM00315. RGS. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]

PROSITE

PS00741. DH_1. False negative.
PS50010. DH_2. 1 hit.
PS50106. PDZ. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50132. RGS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

37012.

SOURCE

Search...

Entry information

Entry name

ARHGB_HUMAN

Accession

Primary (citable) accession number: O15085
Secondary accession number(s): Q5VY40

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 29, 2003
Last sequence update:	January 1, 1998
Last modified:	November 3, 2009
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.