Reviewed, UniProtKB/Swiss-Prot Q9UNA1 (RHG26_HUMAN)

Names and origin

Protein names

Recommended name:
    Rho GTPase-activating protein 26
Alternative name(s):
    Rho-type GTPase-activating protein 26
    Oligophrenin-1-like protein
    GTPase regulator associated with focal adhesion kinase

Gene names

Name:	ARHGAP26
Synonyms:	GRAF, KIAA0621, OPHN1L

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

General annotation (Comments)

Function	GTPase-activating protein for RHOA and CDC42.
Subunit structure	Binds to the C-terminus of PTK2/FAK.
Subcellular location	Cell junction › focal adhesion By similarity. Cytoplasm › cytoskeleton By similarity. Note: Colocalizes with actin stress fibers and cortical actin structures By similarity.
Involvement in disease	Defects in ARHGAP26 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. Chromosomal translocation t(5;11)(q31;q23) with MLL has been found in a JMML patient. Ref.2
Sequence similarities	Contains 1 PH domain. Contains 1 Rho-GAP domain. Contains 1 SH3 domain.

Ontologies

Keywords
Cellular component	Cell junction Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Disease mutation Proto-oncogene
Domain	SH3 domain
Molecular function	GTPase activation
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	actin cytoskeleton organization Non-traceable author statement. Source: UniProtKB filopodium assembly Inferred from electronic annotation. Source: InterPro nervous system development Non-traceable author statement. Source: UniProtKB signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell focal adhesion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	Rho GTPase activator activity Ref.2 Non-traceable author statement. Source: UniProtKB SH3 domain binding Inferred from electronic annotation. Source: InterPro cytoskeletal adaptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PKN3	Q6P5Z2	2	EBI-1390913,EBI-1384335

Alternative products

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

Isoform 1 (identifier: Q9UNA1-1)

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: Q9UNA1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     700-754: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 814

814

Rho GTPase-activating protein 26

PRO_0000056718

Regions

Domain

265 – 369

105

PH

Domain

383 – 568

186

Rho-GAP

Domain

756 – 814

59

SH3

Compositional bias

584 – 701

118

Ser-rich

Amino acid modifications

Modified residue

402

1

Phosphothreonine Ref.7

Natural variations

Alternative sequence

700 – 754

55

Missing in isoform 2.

VSP_001659

Natural variant

417

1

N → S in JMML. Ref.2

VAR_013623

Experimental info

Sequence conflict

355

1

E → G in CAA71414. Ref.2

Sequence conflict

355

1

E → G in CAC29145. Ref.3

Sequence conflict

355

1

E → G in CAC29146. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

814

Helix Strand Turn

Details...

Beta strand

761 – 765

5

Beta strand

771 – 774

4

Beta strand

782 – 785

4

Beta strand

794 – 801

8

Beta strand

803 – 807

5

Helix

808 – 810

3

Beta strand

811 – 813

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 5C81DBDECB32B18A	FASTA	814	92,235
	10 20 30 40 50 60 MGLPALEFSD CCLDSPHFRE TLKSHEAELD KTNKFIKELI KDGKSLISAL KNLSSAKRKF 70 80 90 100 110 120 ADSLNEFKFQ CIGDAETDDE MCIARSLQEF ATVLRNLEDE RIRMIENASE VLITPLEKFR 130 140 150 160 170 180 KEQIGAAKEA KKKYDKETEK YCGILEKHLN LSSKKKESQL QEADSQVDLV RQHFYEVSLE 190 200 210 220 230 240 YVFKVQEVQE RKMFEFVEPL LAFLQGLFTF YHHGYELAKD FGDFKTQLTI SIQNTRNRFE 250 260 270 280 290 300 GTRSEVESLM KKMKENPLEH KTISPYTMEG YLYVQEKRHF GTSWVKHYCT YQRDSKQITM 310 320 330 340 350 360 VPFDQKSGGK GGEDESVILK SCTRRKTDSI EKRFCFDVEA VDRPGVITMQ ALSEEDRRLW 370 380 390 400 410 420 MEAMDGREPV YNSNKDSQSE GTAQLDSIGF SIIRKCIHAV ETRGINEQGL YRIVGVNSRV 430 440 450 460 470 480 QKLLSVLMDP KTASETETDI CAEWEIKTIT SALKTYLRML PGPLMMYQFQ RSFIKAAKLE 490 500 510 520 530 540 NQESRVSEIH SLVHRLPEKN RQMLQLLMNH LANVANNHKQ NLMTVANLGV VFGPTLLRPQ 550 560 570 580 590 600 EETVAAIMDI KFQNIVIEIL IENHEKIFNT VPDMPLTNAQ LHLSRKKSSD SKPPSCSERP 610 620 630 640 650 660 LTLFHTVQST EKQEQRNSII NSSLESVSSN PNSILNSSSS LQPNMNSSDP DLAVVKPTRP 670 680 690 700 710 720 NSLPPNPSPT SPLSPSWPMF SAPSSPMPTS STSSDSSPVR SVAGFVWFSV AAVVLSLARS 730 740 750 760 770 780 SLHAVFSLLV NFVPCHPNLH LLFDRPEEAV HEDSSTPFRK AKALYACKAE HDSELSFTAG 790 800 810 TVFDNVHPSQ EPGWLEGTLN GKTGLIPENY VEFL
	Isoform 2. Checksum: 8FA48FDF1DCAFB7F	FASTA	759	86,165
	10 20 30 40 50 60 MGLPALEFSD CCLDSPHFRE TLKSHEAELD KTNKFIKELI KDGKSLISAL KNLSSAKRKF 70 80 90 100 110 120 ADSLNEFKFQ CIGDAETDDE MCIARSLQEF ATVLRNLEDE RIRMIENASE VLITPLEKFR 130 140 150 160 170 180 KEQIGAAKEA KKKYDKETEK YCGILEKHLN LSSKKKESQL QEADSQVDLV RQHFYEVSLE 190 200 210 220 230 240 YVFKVQEVQE RKMFEFVEPL LAFLQGLFTF YHHGYELAKD FGDFKTQLTI SIQNTRNRFE 250 260 270 280 290 300 GTRSEVESLM KKMKENPLEH KTISPYTMEG YLYVQEKRHF GTSWVKHYCT YQRDSKQITM 310 320 330 340 350 360 VPFDQKSGGK GGEDESVILK SCTRRKTDSI EKRFCFDVEA VDRPGVITMQ ALSEEDRRLW 370 380 390 400 410 420 MEAMDGREPV YNSNKDSQSE GTAQLDSIGF SIIRKCIHAV ETRGINEQGL YRIVGVNSRV 430 440 450 460 470 480 QKLLSVLMDP KTASETETDI CAEWEIKTIT SALKTYLRML PGPLMMYQFQ RSFIKAAKLE 490 500 510 520 530 540 NQESRVSEIH SLVHRLPEKN RQMLQLLMNH LANVANNHKQ NLMTVANLGV VFGPTLLRPQ 550 560 570 580 590 600 EETVAAIMDI KFQNIVIEIL IENHEKIFNT VPDMPLTNAQ LHLSRKKSSD SKPPSCSERP 610 620 630 640 650 660 LTLFHTVQST EKQEQRNSII NSSLESVSSN PNSILNSSSS LQPNMNSSDP DLAVVKPTRP 670 680 690 700 710 720 NSLPPNPSPT SPLSPSWPMF SAPSSPMPTS STSSDSSPVS TPFRKAKALY ACKAEHDSEL 730 740 750 SFTAGTVFDN VHPSQEPGWL EGTLNGKTGL IPENYVEFL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of human oligophrenin-1 like (OPHN1L) gene, complete CDS." Xia J.H., Tang X.X., Yu K.P., Pan Q., Dai H.P. Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Heart, Liver and Placenta.
[2]	"The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q." Borkhardt A., Bojesen S., Haas O.A., Fuchs U., Bartelheimer D., Loncarevic I.F., Bohle R.M., Harbott J., Repp R., Jaeger U., Viehmann S., Henn T., Korth P., Scharr D., Lampert F. Proc. Natl. Acad. Sci. U.S.A. 97:9168-9173(2000) [PubMed: 10908648] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), DISEASE, VARIANT LEUKEMIA SER-417.
[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 (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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Placenta.
[5]	"Genomic structure of the human GRAF gene." Bojesen S.E., Link C., Borkhardt A. Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 53-785.
[6]	"Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:169-176(1998) [PubMed: 9734811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 62-814 (ISOFORM 1). Tissue: Brain.
[7]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-402, MASS SPECTROMETRY. Tissue: T-cell.
[8]	"Solution structure of the SH3 domain of human oligophrenin-1-like protein (KIAA0621)." RIKEN structural genomics initiative (RSGI) Submitted (DEC-2003) to the PDB data bank Cited for: STRUCTURE BY NMR OF 754-814.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Wikipedia

Graf1 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF141884 mRNA. Translation: AAD39482.1.
Y10388 Genomic DNA. Translation: CAA71414.2.
CH471062 Genomic DNA. Translation: EAW61876.1.
BC068555 mRNA. Translation: AAH68555.1.
AJ309466 , AJ309467, AJ309468, AJ309469, AJ309470, AJ309471, AJ309472, AJ309473, AJ309474, AJ309475, AJ309476, AJ309477, AJ309478, AJ309479, AJ309480, AJ309481, AJ309482, AJ309483, AJ309484, AJ309485, AJ309486, AJ309487 Genomic DNA. Translation: CAC29145.2.
AJ309466 , AJ309467, AJ309468, AJ309469, AJ309470, AJ309471, AJ309472, AJ309473, AJ309474, AJ309475, AJ309476, AJ309477, AJ309478, AJ309479, AJ309480, AJ309481, AJ309482, AJ309483, AJ309484, AJ309485, AJ309487 Genomic DNA. Translation: CAC29146.2.
AB014521 mRNA. Translation: BAA31596.1.

IPI

IPI00007913.
IPI00216360.

PIR

F59430.

RefSeq

NP_001129080.1.
NP_055886.1.

UniGene

Hs.654668

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1UGV	NMR	-	A	756-814	[»]

SMR

Q9UNA1. Positions 6-366, 383-573.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UNA1. 1 interaction.

STRING

Q9UNA1.

PTM databases

PhosphoSite

Q9UNA1.

Proteomic databases

PRIDE

Q9UNA1.

Genome annotation databases

Ensembl

ENST00000274498; ENSP00000274498; ENSG00000145819; Homo sapiens. [Genome view]

GeneID

23092.

KEGG

hsa:23092.

UCSC

uc003lmt.1. human.
uc003lmu.1. human.

Organism-specific databases

CTD

23092.

GeneCards

GC05P142130.

H-InvDB

HIX0005269.

HGNC

HGNC:17073. ARHGAP26.

MIM

605370. gene.
607785. phenotype.

PharmGKB

PA134946198.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG09589.

HOGENOM

HBG444804.

HOVERGEN

Q9UNA1.

InParanoid

Q9UNA1.

OMA

KDFGDFK.

OrthoDB

EOG9RJJM8.

PhylomeDB

Q9UNA1.

Enzyme and pathway databases

Reactome

REACT_11044. Signaling by Rho GTPases.

Gene expression databases

ArrayExpress

Q9UNA1.

Bgee

Q9UNA1.

CleanEx

HS_ARHGAP26.

Genevestigator

Q9UNA1.

GermOnline

ENSG00000145819. Homo sapiens.

Family and domain databases

InterPro

IPR013606. IRSp53/MIM_homology_IMD.
IPR001849. Pleckstrin_homology.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF08397. IMD. 1 hit.
PF00620. RhoGAP. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

SMART

SM00233. PH. 1 hit.
SM00324. RhoGAP. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]

PROSITE

PS50003. PH_DOMAIN. 1 hit.
PS50238. RHOGAP. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

44247.

SOURCE

Search...

Entry information

Entry name

RHG26_HUMAN

Accession

Primary (citable) accession number: Q9UNA1
Secondary accession number(s): O75117 , Q5D035, Q9BYS6, Q9BYS7, Q9UJ00

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2002
Last sequence update:	May 1, 2000
Last modified:	January 19, 2010
This is version 100 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.