P52757 (CHIO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta-chimaerin

Alternative name(s):
Beta-chimerin
Rho GTPase-activating protein 3

Gene names

Name:	CHN2
Synonyms:	ARHGAP3, BCH

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

General annotation (Comments)

Function	GTPase-activating protein for p21-rac. Insufficient expression of beta-2 chimaerin is expected to lead to higher Rac activity and could therefore play a role in the progression from low-grade to high-grade tumors.
Enzyme regulation	In the inactive state, the N terminus protrudes into the active site of the Rho-GAP domain, sterically blocking Rac binding. Phospholipid binding to the Phorbol-ester/DAG-type zinc-finger/C1 domain triggers the cooperative dissociation of these interactions, allowing the N-terminus to move out of the active site and thereby activating the enzyme. Ref.6
Subcellular location	Membrane; Peripheral membrane protein Potential.
Tissue specificity	Highest levels in the brain and pancreas. Also expressed in the heart, placenta, and weakly in the kidney and liver. Expression is much reduced in the malignant gliomas, compared to normal brain or low-grade astrocytomas.
Sequence similarities	Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 Rho-GAP domain. Contains 1 SH2 domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH2 domain Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	GTPase activation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of small GTPase mediated signal transduction Traceable author statement. Source: Reactome small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	GTPase activator activity Traceable author statement Ref.2. Source: ProtInc SH3/SH2 adaptor activity Traceable author statement Ref.1. Source: ProtInc metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform Beta-2 (identifier: P52757-1)

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 Beta-1 (identifier: P52757-2)

The sequence of this isoform is not available.

Isoform 3 (identifier: P52757-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-56: MAASSNSSLS...REVENRPKYY → MFSEELWLEN...PPLKLFACSQ
     57-192: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 468

468

Beta-chimaerin

PRO_0000056697

Regions

Domain

59 – 127

69

SH2

Domain

277 – 468

192

Rho-GAP

Zinc finger

214 – 264

51

Phorbol-ester/DAG-type

Natural variations

Alternative sequence

1 – 56

56

MAASS…RPKYY → MFSEELWLENEKKCAVVRKS KQGRKRQELLAVAFGVKVGV KGGFLWPPLKLFACSQ in isoform 3.

VSP_046271

Alternative sequence

57 – 192

136

Missing in isoform 3.

VSP_046272

Natural variant

204

1

H → R. Ref.3
Corresponds to variant rs3750103 [ dbSNP | Ensembl ].

VAR_022118

Natural variant

438

1

P → S.
Corresponds to variant rs34971642 [ dbSNP | Ensembl ].

VAR_049136

Experimental info

Sequence conflict

1 – 6

6

MAASSN → MRLL in AAA16836. Ref.1

Sequence conflict

1 – 6

6

MAASSN → MRLL in AAA19191. Ref.1

Secondary structure

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468

Helix Strand Turn

Details...

Helix

29 – 36

8

Beta strand

58 – 63

6

Helix

66 – 73

8

Beta strand

79 – 84

6

Beta strand

86 – 88

3

Beta strand

92 – 98

7

Beta strand

101 – 104

4

Beta strand

108 – 114

7

Beta strand

116 – 118

3

Helix

125 – 138

14

Helix

141 – 146

6

Helix

153 – 155

3

Beta strand

156 – 161

6

Turn

229 – 231

3

Turn

237 – 240

4

Beta strand

246 – 248

3

Helix

255 – 257

3

Turn

266 – 269

4

Helix

279 – 286

8

Helix

292 – 303

12

Beta strand

306 – 308

3

Turn

309 – 313

5

Helix

318 – 328

11

Turn

331 – 334

4

Beta strand

339 – 342

4

Helix

346 – 358

13

Helix

369 – 373

5

Turn

374 – 377

4

Helix

381 – 392

12

Helix

397 – 405

9

Turn

406 – 410

5

Helix

411 – 414

4

Turn

415 – 419

5

Helix

424 – 431

8

Turn

432 – 434

3

Helix

445 – 448

4

Helix

450 – 462

13

Sequences

	Sequence		Length	Mass (Da)
	Isoform Beta-2 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 63254958E0B5804C	FASTA	468	53,924
	10 20 30 40 50 60 MAASSNSSLS GSSVSSDAEE YQPPIWKSYL YQLQQEAPRP KRIICPREVE NRPKYYGREF 70 80 90 100 110 120 HGIISREQAD ELLGGVEGAY ILRESQRQPG CYTLALRFGN QTLNYRLFHD GKHFVGEKRF 130 140 150 160 170 180 ESIHDLVTDG LITLYIETKA AEYISKMTTN PIYEHIGYAT LLREKVSRRL SRSKNEPRKT 190 200 210 220 230 240 NVTHEEHTAV EKISSLVRRA ALTHNDNHFN YEKTHNFKVH TFRGPHWCEY CANFMWGLIA 250 260 270 280 290 300 QGVRCSDCGL NVHKQCSKHV PNDCQPDLKR IKKVYCCDLT TLVKAHNTQR PMVVDICIRE 310 320 330 340 350 360 IEARGLKSEG LYRVSGFTEH IEDVKMAFDR DGEKADISAN VYPDINIITG ALKLYFRDLP 370 380 390 400 410 420 IPVITYDTYS KFIDAAKISN ADERLEAVHE VLMLLPPAHY ETLRYLMIHL KKVTMNEKDN 430 440 450 460 FMNAENLGIV FGPTLMRPPE DSTLTTLHDM RYQKLIVQIL IENEDVLF
	Isoform Beta-1 (Sequence not available).		–	–
	Isoform 3 [UniParc]. Checksum: 7A2B5C42F1769425	FASTA	332	38,178
	10 20 30 40 50 60 MFSEELWLEN EKKCAVVRKS KQGRKRQELL AVAFGVKVGV KGGFLWPPLK LFACSQISSL 70 80 90 100 110 120 VRRAALTHND NHFNYEKTHN FKVHTFRGPH WCEYCANFMW GLIAQGVRCS DCGLNVHKQC 130 140 150 160 170 180 SKHVPNDCQP DLKRIKKVYC CDLTTLVKAH NTQRPMVVDI CIREIEARGL KSEGLYRVSG 190 200 210 220 230 240 FTEHIEDVKM AFDRDGEKAD ISANVYPDIN IITGALKLYF RDLPIPVITY DTYSKFIDAA 250 260 270 280 290 300 KISNADERLE AVHEVLMLLP PAHYETLRYL MIHLKKVTMN EKDNFMNAEN LGIVFGPTLM 310 320 330 RPPEDSTLTT LHDMRYQKLI VQILIENEDV LF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cerebellar beta 2-chimaerin, a GTPase-activating protein for p21 ras-related rac is specifically expressed in granule cells and has a unique N-terminal SH2 domain." Leung T., How B.-E., Manser E., Lim L. J. Biol. Chem. 269:12888-12892(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-2). Tissue: Cerebellum.
[2]	"Identification and characterization of human beta 2-chimaerin: association with malignant transformation in astrocytoma." Yuan S., Miller D.W., Barnett G.H., Hahn J.F., Williams B.R.G. Cancer Res. 55:3456-3461(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-2). Tissue: Fetal brain.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT ARG-204. Tissue: Ileal mucosa.
[4]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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 BETA-2). Tissue: Brain.
[6]	"Structural mechanism for lipid activation of the Rac-specific GAP, beta2-chimaerin." Canagarajah B., Leskow F.C., Ho J.Y., Mischak H., Saidi L.F., Kazanietz M.G., Hurley J.H. Cell 119:407-418(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 7-466 IN COMPLEX WITH PHORBOL-ESTER, ENZYME REGULATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L29126 mRNA. Translation: AAA19191.1.
U07223 mRNA. Translation: AAA16836.1.
U28926 mRNA. Translation: AAA86528.1.
AK026415 mRNA. No translation available.
AC004417 Genomic DNA. Translation: AAC06177.1.
AC004593 Genomic DNA. No translation available.
AC005232 Genomic DNA. No translation available.
AC007096 Genomic DNA. No translation available.
AC007255 Genomic DNA. Translation: AAS07498.1.
BC112155 mRNA. Translation: AAI12156.1.

IPI

IPI00745327.
IPI01012038.

PIR

A53764.

RefSeq

NP_001035025.1. NM_001039936.1.
NP_004058.1. NM_004067.2.

UniGene

Hs.654611.
Hs.654753.
Hs.663145.
Hs.710429.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XA6	X-ray	3.20	A	7-466	[»]

ProteinModelPortal

P52757.

ModBase

Search...

Protein-protein interaction databases

IntAct

P52757. 2 interactions.

MINT

MINT-1420866.

STRING

9606.ENSP00000222792.

PTM databases

PhosphoSite

P52757.

Polymorphism databases

DMDM

2506455.

Proteomic databases

PaxDb

P52757.

PRIDE

P52757.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000222792; ENSP00000222792; ENSG00000106069.
ENST00000409041; ENSP00000386849; ENSG00000106069.

GeneID

1124.

KEGG

hsa:1124.

UCSC

uc003szz.3. human.

Organism-specific databases

CTD

1124.

GeneCards

GC07P029186.

HGNC

HGNC:1944. CHN2.

HPA

HPA018989.

MIM

602857. gene.

neXtProt

NX_P52757.

PharmGKB

PA26474.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG295484.

HOVERGEN

HBG080489.

InParanoid

P52757.

OrthoDB

EOG4W9J3S.

PhylomeDB

P52757.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P52757.

Bgee

P52757.

CleanEx

HS_CHN2.

Genevestigator

P52757.

GermOnline

ENSG00000106069. Homo sapiens.

Family and domain databases

Gene3D

1.10.555.10. 1 hit.
3.30.505.10. 1 hit.

InterPro

IPR020454. DAG/PE-bd.
IPR017356. N-chimaerin.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR000980. SH2.
[Graphical view]

Pfam

PF00130. C1_1. 1 hit.
PF00620. RhoGAP. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]

PIRSF

PIRSF038015. N-chimaerin. 1 hit.

PRINTS

PR00008. DAGPEDOMAIN.

SMART

SM00109. C1. 1 hit.
SM00324. RhoGAP. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]

SUPFAM

SSF48350. Rho_GAP. 1 hit.

PROSITE

PS50238. RHOGAP. 1 hit.
PS50001. SH2. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P52757.

ChEMBL

CHEMBL4504.

EvolutionaryTrace

P52757.

GenomeRNAi

1124.

NextBio

4668.

SOURCE

Search...

Entry information

Entry name

CHIO_HUMAN

Accession

Primary (citable) accession number: P52757
Secondary accession number(s): E9PGE0, Q2M203, Q75MM2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 136 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.