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Q99418 (CYH2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytohesin-2
Alternative name(s):
ARF exchange factor
ARF nucleotide-binding site opener
Short name=Protein ARNO
PH, SEC7 and coiled-coil domain-containing protein 2
Gene names
Name:CYTH2
Synonyms:ARNO, PSCD2, PSCD2L
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length400 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts as a guanine-nucleotide exchange factor (GEF). Promotes guanine-nucleotide exchange on ARF1, ARF3 and ARF6. Promotes the activation of ARF factors through replacement of GDP with GTP. The cell membrane form, in association with ARL4 proteins, recruits ARF6 to the plasma membrane. Ref.6

Subunit structure

Heteromer. Composed of GRASP, CYTH2 and at least one GRM1 By similarity. Interacts with ARRB1. Interacts with ARL4D; the interaction is direct. Ref.5 Ref.6

Subcellular location

Cell membrane; Peripheral membrane protein. Cytoplasm. Note: Both isoform 1 and isoform 2 are recruited to the cell membrane through their association with ARL4A, ARL4C and ARL4D. They require also interaction with phosphoinositides for targeting to the plasma membrane. Ref.6

Tissue specificity

Ubiquitous.

Domain

Binds via its PH domain to the inositol head group of phosphatidylinositol 1,4,5-trisphosphate. The PH domain is necessary and sufficient for plasma membrane relocalization.

Autoinhibited by its C-terminal basic region By similarity.

Sequence similarities

Contains 1 PH domain.

Contains 1 SEC7 domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q99418-1)

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: Q99418-2)

The sequence of this isoform differs from the canonical sequence as follows:
     272-272: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 400400Cytohesin-2
PRO_0000120197

Regions

Domain72 – 201130SEC7
Domain259 – 376118PH
Region268 – 2769Phosphatidylinositol 1,4,5-trisphosphate binding By similarity
Region387 – 3959C-terminal autoinhibitory region By similarity
Coiled coil10 – 6354 Potential

Sites

Binding site2801Phosphatidylinositol 1,4,5-trisphosphate By similarity
Binding site2911Phosphatidylinositol 1,4,5-trisphosphate By similarity
Binding site3011Phosphatidylinositol 1,4,5-trisphosphate By similarity
Binding site3391Phosphatidylinositol 1,4,5-trisphosphate By similarity
Binding site3501Phosphatidylinositol 1,4,5-trisphosphate By similarity
Binding site3511Phosphatidylinositol 1,4,5-trisphosphate By similarity

Natural variations

Alternative sequence2721Missing in isoform 2.
VSP_006036

Experimental info

Mutagenesis1561E → D: Inhibits GTP GDP exchange activity. Abolishes recruitment of ARF6 to the plasma membrane. Ref.6
Mutagenesis2681K → R: Does not reduces ARL4D GTP-dependent interaction but inhibits targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. Ref.6
Mutagenesis2801R → D: Does not reduces ARL4D GTP-dependent interaction but inhibits targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. Ref.6
Mutagenesis3031I → A: Reduces ARL4D GTP-dependent interaction and targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. Ref.6
Mutagenesis3361K → A: Reduces ARL4D GTP-dependent interaction and targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. Ref.6
Sequence conflict3061L → Q in AAH38713. Ref.4

Secondary structure

......................... 400
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 21, 2001. Version 2.
Checksum: 70441A58483BD0E1

FASTA40046,546
        10         20         30         40         50         60 
MEDGVYEPPD LTPEERMELE NIRRRKQELL VEIQRLREEL SEAMSEVEGL EANEGSKTLQ 

        70         80         90        100        110        120 
RNRKMAMGRK KFNMDPKKGI QFLVENELLQ NTPEEIARFL YKGEGLNKTA IGDYLGEREE 

       130        140        150        160        170        180 
LNLAVLHAFV DLHEFTDLNL VQALRQFLWS FRLPGEAQKI DRMMEAFAQR YCLCNPGVFQ 

       190        200        210        220        230        240 
STDTCYVLSF AVIMLNTSLH NPNVRDKPGL ERFVAMNRGI NEGGDLPEEL LRNLYDSIRN 

       250        260        270        280        290        300 
EPFKIPEDDG NDLTHTFFNP DREGWLLKLG GGRVKTWKRR WFILTDNCLY YFEYTTDKEP 

       310        320        330        340        350        360 
RGIIPLENLS IREVDDPRKP NCFELYIPNN KGQLIKACKT EADGRVVEGN HMVYRISAPT 

       370        380        390        400 
QEEKDEWIKS IQAAVSVDPF YEMLAARKKR ISVKKKQEQP 

« Hide

Isoform 2 [UniParc].

Checksum: 436A1C1651C8894C
Show »

FASTA39946,489

References

« Hide 'large scale' references
[1]"A human exchange factor for ARF contains Sec7- and pleckstrin-homology domains."
Chardin P., Paris S., Antonny B., Robineau S., Bernaud-Dufour S., Jackson C.L., Chabre M.
Nature 384:481-484(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"ARNO is a guanine nucleotide exchange factor for ADP-ribosylation factor 6."
Frank S.F., Upender S.K., Hansen S.H., Casanova J.E.
J. Biol. Chem. 273:23-27(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), CHARACTERIZATION.
Tissue: 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. expand/collapse author list , 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 1).
Tissue: Testis.
[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 1).
Tissue: Lung and Testis.
[5]"The calcium-sensing receptor changes cell shape via a beta-arrestin-1 ARNO ARF6 ELMO protein network."
Bouschet T., Martin S., Kanamarlapudi V., Mundell S., Henley J.M.
J. Cell Sci. 120:2489-2497(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARRB1.
[6]"The Arl4 family of small G proteins can recruit the cytohesin Arf6 exchange factors to the plasma membrane."
Hofmann I., Thompson A., Sanderson C.M., Munro S.
Curr. Biol. 17:711-716(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ARL4D AND ARRB1, MUTAGENESIS OF GLU-156; LYS-268; ARG-280; ILE-303 AND LYS-336, SUBCELLULAR LOCATION.
[7]"Structure of the guanine nucleotide exchange factor Sec7 domain of human ARNO and analysis of the interaction with ARF GTPase."
Mossessova E., Gulbis J.M., Goldberg J.
Cell 92:415-423(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 51-252.
[8]"Structure of the Sec7 domain of the Arf exchange factor ARNO."
Cherfils J., Menetrey J., Mathieu M., le Bras G., Robineau S., Beraud-Dufour S., Antonny B., Chardin P.
Nature 392:101-105(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 51-252.
[9]"Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor."
Renault L., Guibert B., Cherfils J.
Nature 426:525-530(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 50-252 IN COMPLEX WITH ARF1; GDP AND BREFELDIN A.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X99753 mRNA. Translation: CAA68084.1.
U70728 mRNA. Translation: AAB09591.1.
AK292405 mRNA. Translation: BAF85094.1.
BC004361 mRNA. Translation: AAH04361.1.
BC038713 mRNA. Translation: AAH38713.1.
CCDSCCDS12722.1. [Q99418-2]
RefSeqNP_004219.3. NM_004228.6. [Q99418-2]
NP_059431.1. NM_017457.5. [Q99418-1]
UniGeneHs.144011.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1PBVX-ray2.00A52-246[»]
1R8MX-ray1.70E50-252[»]
1R8QX-ray1.86E/F50-252[»]
1R8SX-ray1.46E50-252[»]
1S9DX-ray1.80E50-252[»]
4JMIX-ray1.50A56-251[»]
4JMOX-ray1.80A56-251[»]
4JWLX-ray1.95A56-251[»]
4JXHX-ray1.47A56-251[»]
4L5MX-ray1.80A56-251[»]
ProteinModelPortalQ99418.
SMRQ99418. Positions 56-392.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114687. 16 interactions.
DIPDIP-31598N.
IntActQ99418. 10 interactions.
MINTMINT-3058896.
STRING9606.ENSP00000408236.

Chemistry

ChEMBLCHEMBL5995.

PTM databases

PhosphoSiteQ99418.

Polymorphism databases

DMDM13124707.

Proteomic databases

MaxQBQ99418.
PaxDbQ99418.
PRIDEQ99418.

Protocols and materials databases

DNASU9266.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000452733; ENSP00000408236; ENSG00000105443. [Q99418-2]
GeneID9266.
KEGGhsa:9266.
UCSCuc002pjj.4. human. [Q99418-1]

Organism-specific databases

CTD9266.
GeneCardsGC19P048972.
HGNCHGNC:9502. CYTH2.
HPACAB014872.
MIM602488. gene.
neXtProtNX_Q99418.
PharmGKBPA33849.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5307.
HOGENOMHOG000253023.
HOVERGENHBG002647.
InParanoidQ99418.
OrthoDBEOG7RBZ9C.
PhylomeDBQ99418.
TreeFamTF352091.

Gene expression databases

ArrayExpressQ99418.
BgeeQ99418.
CleanExHS_CYTH2.
GenevestigatorQ99418.

Family and domain databases

Gene3D1.10.1000.11. 1 hit.
2.30.29.30. 1 hit.
InterProIPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR023394. Sec7_alpha_orthog.
IPR000904. Sec7_dom.
[Graphical view]
PfamPF00169. PH. 1 hit.
PF01369. Sec7. 1 hit.
[Graphical view]
SMARTSM00233. PH. 1 hit.
SM00222. Sec7. 1 hit.
[Graphical view]
SUPFAMSSF48425. SSF48425. 1 hit.
PROSITEPS50003. PH_DOMAIN. 1 hit.
PS50190. SEC7. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ99418.
GeneWikiCYTH2.
GenomeRNAi9266.
NextBio34733.
PROQ99418.
SOURCESearch...

Entry information

Entry nameCYH2_HUMAN
AccessionPrimary (citable) accession number: Q99418
Secondary accession number(s): A8K8P0, Q8IXY9, Q92958
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: February 21, 2001
Last modified: July 9, 2014
This is version 141 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM