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Q99418

- CYH2_HUMAN

UniProt

Q99418 - CYH2_HUMAN

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Protein
Cytohesin-2
Gene
CYTH2, ARNO, PSCD2, PSCD2L
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei280 – 2801Phosphatidylinositol 1,4,5-trisphosphate By similarity
Binding sitei291 – 2911Phosphatidylinositol 1,4,5-trisphosphate By similarity
Binding sitei301 – 3011Phosphatidylinositol 1,4,5-trisphosphate By similarity
Binding sitei339 – 3391Phosphatidylinositol 1,4,5-trisphosphate By similarity
Binding sitei350 – 3501Phosphatidylinositol 1,4,5-trisphosphate By similarity
Binding sitei351 – 3511Phosphatidylinositol 1,4,5-trisphosphate By similarity

GO - Molecular functioni

  1. ARF guanyl-nucleotide exchange factor activity Source: UniProtKB
  2. inositol 1,4,5 trisphosphate binding Source: UniProtKB
  3. lipid binding Source: UniProtKB-KW
  4. protein binding Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  1. actin cytoskeleton organization Source: ProtInc
  2. endocytosis Source: ProtInc
  3. regulation of ARF protein signal transduction Source: InterPro
  4. regulation of GTPase activity Source: GOC
  5. regulation of cell adhesion Source: RefGenome
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Ligandi

Lipid-binding

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:CYTH2
Synonyms:ARNO, PSCD2, PSCD2L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:9502. CYTH2.

Subcellular locationi

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.1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. membrane Source: ProtInc
  3. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi156 – 1561E → D: Inhibits GTP GDP exchange activity. Abolishes recruitment of ARF6 to the plasma membrane. 1 Publication
Mutagenesisi268 – 2681K → R: Does not reduces ARL4D GTP-dependent interaction but inhibits targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication
Mutagenesisi280 – 2801R → D: Does not reduces ARL4D GTP-dependent interaction but inhibits targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication
Mutagenesisi303 – 3031I → A: Reduces ARL4D GTP-dependent interaction and targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication
Mutagenesisi336 – 3361K → A: Reduces ARL4D GTP-dependent interaction and targeting to the plasma membrane mediated by ARL4C, ARL4C and ARL4D. 1 Publication

Organism-specific databases

PharmGKBiPA33849.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 400400Cytohesin-2
PRO_0000120197Add
BLAST

Proteomic databases

MaxQBiQ99418.
PaxDbiQ99418.
PRIDEiQ99418.

PTM databases

PhosphoSiteiQ99418.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

ArrayExpressiQ99418.
BgeeiQ99418.
CleanExiHS_CYTH2.
GenevestigatoriQ99418.

Organism-specific databases

HPAiCAB014872.

Interactioni

Subunit structurei

Heteromer. Composed of GRASP, CYTH2 and at least one GRM1 By similarity. Interacts with ARRB1. Interacts with ARL4D; the interaction is direct.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ADORA2AP292746EBI-448974,EBI-2902702
ARF1P840774EBI-448974,EBI-447171
ATP6V0A2Q9Y4872EBI-448974,EBI-988630
EGFRP005335EBI-448974,EBI-297353

Protein-protein interaction databases

BioGridi114687. 16 interactions.
DIPiDIP-31598N.
IntActiQ99418. 10 interactions.
MINTiMINT-3058896.
STRINGi9606.ENSP00000408236.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi63 – 7412
Helixi76 – 8510
Helixi93 – 10210
Helixi108 – 1158
Helixi120 – 13112
Helixi140 – 14910
Helixi157 – 17418
Beta strandi178 – 1803
Helixi182 – 20019
Helixi210 – 2167
Turni217 – 2204
Beta strandi221 – 2244
Helixi228 – 24013

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliQ99418.
SMRiQ99418. Positions 56-392.

Miscellaneous databases

EvolutionaryTraceiQ99418.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini72 – 201130SEC7
Add
BLAST
Domaini259 – 376118PH
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni268 – 2769Phosphatidylinositol 1,4,5-trisphosphate binding By similarity
Regioni387 – 3959C-terminal autoinhibitory region By similarity

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili10 – 6354 Reviewed prediction
Add
BLAST

Domaini

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 similaritiesi

Contains 1 PH domain.
Contains 1 SEC7 domain.

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiCOG5307.
HOGENOMiHOG000253023.
HOVERGENiHBG002647.
InParanoidiQ99418.
OrthoDBiEOG7RBZ9C.
PhylomeDBiQ99418.
TreeFamiTF352091.

Family and domain databases

Gene3Di1.10.1000.11. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR023394. Sec7_alpha_orthog.
IPR000904. Sec7_dom.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF01369. Sec7. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00222. Sec7. 1 hit.
[Graphical view]
SUPFAMiSSF48425. SSF48425. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50190. SEC7. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q99418-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MEDGVYEPPD LTPEERMELE NIRRRKQELL VEIQRLREEL SEAMSEVEGL    50
EANEGSKTLQ RNRKMAMGRK KFNMDPKKGI QFLVENELLQ NTPEEIARFL 100
YKGEGLNKTA IGDYLGEREE LNLAVLHAFV DLHEFTDLNL VQALRQFLWS 150
FRLPGEAQKI DRMMEAFAQR YCLCNPGVFQ STDTCYVLSF AVIMLNTSLH 200
NPNVRDKPGL ERFVAMNRGI NEGGDLPEEL LRNLYDSIRN EPFKIPEDDG 250
NDLTHTFFNP DREGWLLKLG GGRVKTWKRR WFILTDNCLY YFEYTTDKEP 300
RGIIPLENLS IREVDDPRKP NCFELYIPNN KGQLIKACKT EADGRVVEGN 350
HMVYRISAPT QEEKDEWIKS IQAAVSVDPF YEMLAARKKR ISVKKKQEQP 400
Length:400
Mass (Da):46,546
Last modified:February 21, 2001 - v2
Checksum:i70441A58483BD0E1
GO
Isoform 2 (identifier: Q99418-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:399
Mass (Da):46,489
Checksum:i436A1C1651C8894C
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei272 – 2721Missing in isoform 2.
VSP_006036

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti306 – 3061L → Q in AAH38713. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS12722.1. [Q99418-2]
RefSeqiNP_004219.3. NM_004228.6. [Q99418-2]
NP_059431.1. NM_017457.5. [Q99418-1]
UniGeneiHs.144011.

Genome annotation databases

EnsembliENST00000452733; ENSP00000408236; ENSG00000105443. [Q99418-2]
GeneIDi9266.
KEGGihsa:9266.
UCSCiuc002pjj.4. human. [Q99418-1]

Polymorphism databases

DMDMi13124707.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS12722.1. [Q99418-2 ]
RefSeqi NP_004219.3. NM_004228.6. [Q99418-2 ]
NP_059431.1. NM_017457.5. [Q99418-1 ]
UniGenei Hs.144011.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1PBV X-ray 2.00 A 52-246 [» ]
1R8M X-ray 1.70 E 50-252 [» ]
1R8Q X-ray 1.86 E/F 50-252 [» ]
1R8S X-ray 1.46 E 50-252 [» ]
1S9D X-ray 1.80 E 50-252 [» ]
4JMI X-ray 1.50 A 56-251 [» ]
4JMO X-ray 1.80 A 56-251 [» ]
4JWL X-ray 1.95 A 56-251 [» ]
4JXH X-ray 1.47 A 56-251 [» ]
4L5M X-ray 1.80 A 56-251 [» ]
ProteinModelPortali Q99418.
SMRi Q99418. Positions 56-392.
ModBasei Search...

Protein-protein interaction databases

BioGridi 114687. 16 interactions.
DIPi DIP-31598N.
IntActi Q99418. 10 interactions.
MINTi MINT-3058896.
STRINGi 9606.ENSP00000408236.

Chemistry

ChEMBLi CHEMBL5995.

PTM databases

PhosphoSitei Q99418.

Polymorphism databases

DMDMi 13124707.

Proteomic databases

MaxQBi Q99418.
PaxDbi Q99418.
PRIDEi Q99418.

Protocols and materials databases

DNASUi 9266.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000452733 ; ENSP00000408236 ; ENSG00000105443 . [Q99418-2 ]
GeneIDi 9266.
KEGGi hsa:9266.
UCSCi uc002pjj.4. human. [Q99418-1 ]

Organism-specific databases

CTDi 9266.
GeneCardsi GC19P048972.
HGNCi HGNC:9502. CYTH2.
HPAi CAB014872.
MIMi 602488. gene.
neXtProti NX_Q99418.
PharmGKBi PA33849.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5307.
HOGENOMi HOG000253023.
HOVERGENi HBG002647.
InParanoidi Q99418.
OrthoDBi EOG7RBZ9C.
PhylomeDBi Q99418.
TreeFami TF352091.

Miscellaneous databases

EvolutionaryTracei Q99418.
GeneWikii CYTH2.
GenomeRNAii 9266.
NextBioi 34733.
PROi Q99418.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q99418.
Bgeei Q99418.
CleanExi HS_CYTH2.
Genevestigatori Q99418.

Family and domain databases

Gene3Di 1.10.1000.11. 1 hit.
2.30.29.30. 1 hit.
InterProi IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR023394. Sec7_alpha_orthog.
IPR000904. Sec7_dom.
[Graphical view ]
Pfami PF00169. PH. 1 hit.
PF01369. Sec7. 1 hit.
[Graphical view ]
SMARTi SM00233. PH. 1 hit.
SM00222. Sec7. 1 hit.
[Graphical view ]
SUPFAMi SSF48425. SSF48425. 1 hit.
PROSITEi PS50003. PH_DOMAIN. 1 hit.
PS50190. SEC7. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.

Entry informationi

Entry nameiCYH2_HUMAN
AccessioniPrimary (citable) accession number: Q99418
Secondary accession number(s): A8K8P0, Q8IXY9, Q92958
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: February 21, 2001
Last modified: September 3, 2014
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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