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P50749

- RASF2_HUMAN

UniProt

P50749 - RASF2_HUMAN

Protein

Ras association domain-containing protein 2

Gene

RASSF2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      Previous versions | rss
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    Functioni

    Potential tumor suppressor. Acts as a KRAS-specific effector protein. May promote apoptosis and cell cycle arrest. Stabilizes STK3/MST2 by protecting it from proteasomal degradation.3 Publications

    GO - Molecular functioni

    1. protein binding Source: UniProtKB

    GO - Biological processi

    1. cell cycle Source: UniProtKB-KW
    2. signal transduction Source: InterPro

    Keywords - Biological processi

    Cell cycle

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ras association domain-containing protein 2
    Gene namesi
    Name:RASSF2
    Synonyms:KIAA0168
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 20

    Organism-specific databases

    HGNCiHGNC:9883. RASSF2.

    Subcellular locationi

    Nucleus. Cytoplasm
    Note: Translocates to the cytoplasm in the presence of STK3/MST2 AND STK4/MST1.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Keywords - Diseasei

    Tumor suppressor

    Organism-specific databases

    PharmGKBiPA34246.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 326326Ras association domain-containing protein 2PRO_0000097172Add
    BLAST

    Post-translational modificationi

    Phosphorylated by STK3/MST2 and STK4/MST1.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP50749.
    PaxDbiP50749.
    PRIDEiP50749.

    PTM databases

    PhosphoSiteiP50749.

    Expressioni

    Tissue specificityi

    Widely expressed with highest levels in brain, placenta, peripheral blood and lung. Frequently down-regulated in lung tumor cell lines.1 Publication

    Gene expression databases

    BgeeiP50749.
    CleanExiHS_RASSF2.
    GenevestigatoriP50749.

    Organism-specific databases

    HPAiHPA051200.

    Interactioni

    Subunit structurei

    Interacts directly with activated KRAS in a GTP-dependent manner. Interacts (via SARAH domain) with STK3/MST2 AND STK4/MST1.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    KDM1AO603412EBI-960081,EBI-710124
    KRASP011162EBI-960081,EBI-367415
    PRMT6Q96LA82EBI-960081,EBI-912440
    STK3Q1318810EBI-960081,EBI-992580
    STK4Q1304313EBI-960081,EBI-367376
    SUV39H1O434632EBI-960081,EBI-349968

    Protein-protein interaction databases

    BioGridi115115. 24 interactions.
    IntActiP50749. 27 interactions.
    MINTiMINT-6773106.
    STRINGi9606.ENSP00000368684.

    Structurei

    3D structure databases

    ProteinModelPortaliP50749.
    SMRiP50749. Positions 189-261.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini176 – 26489Ras-associatingPROSITE-ProRule annotationAdd
    BLAST
    Domaini272 – 31948SARAHPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 Ras-associating domain.PROSITE-ProRule annotation
    Contains 1 SARAH domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG264677.
    HOGENOMiHOG000231738.
    HOVERGENiHBG054302.
    InParanoidiP50749.
    KOiK09851.
    OMAiNTDYPLV.
    OrthoDBiEOG7DVDBF.
    PhylomeDBiP50749.
    TreeFamiTF319243.

    Family and domain databases

    InterProiIPR000159. Ras-assoc.
    IPR011524. SARAH_dom.
    IPR029071. Ubiquitin-rel_dom.
    [Graphical view]
    PfamiPF00788. RA. 1 hit.
    [Graphical view]
    SMARTiSM00314. RA. 1 hit.
    [Graphical view]
    SUPFAMiSSF54236. SSF54236. 1 hit.
    PROSITEiPS50200. RA. 1 hit.
    PS50951. SARAH. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P50749-1) [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

    MDYSHQTSLV PCGQDKYISK NELLLHLKTY NLYYEGQNLQ LRHREEEDEF    50
    IVEGLLNISW GLRRPIRLQM QDDNERIRPP PSSSSWHSGC NLGAQGTTLK 100
    PLTVPKVQIS EVDAPPEGDQ MPSSTDSRGL KPLQEDTPQL MRTRSDVGVR 150
    RRGNVRTPSD QRRIRRHRFS INGHFYNHKT SVFTPAYGSV TNVRINSTMT 200
    TPQVLKLLLN KFKIENSAEE FALYVVHTSG EKQKLKATDY PLIARILQGP 250
    CEQISKVFLM EKDQVEEVTY DVAQYIKFEM PVLKSFIQKL QEEEDREVKK 300
    LMRKYTVLRL MIRQRLEEIA ETPATI 326
    Length:326
    Mass (Da):37,790
    Last modified:October 1, 1996 - v1
    Checksum:iC29D16376904249E
    GO
    Isoform 2 (identifier: P50749-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-96: MDYSHQTSLV...HSGCNLGAQG → MSLNWNLTLQNEWPLLEFSK
         231-326: EKQKLKATDY...EEIAETPATI → GPM

    Note: No experimental confirmation available.

    Show »
    Length:157
    Mass (Da):17,879
    Checksum:i77E624A912E98685
    GO

    Sequence cautioni

    The sequence BAA11485.2 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti166 – 1661R → C in BAD96370. 1 PublicationCurated
    Sequence conflicti256 – 2561K → Q in BAD96370. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti144 – 1441R → H in a colorectal cancer sample; somatic mutation. 1 Publication
    VAR_035825

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 9696MDYSH…LGAQG → MSLNWNLTLQNEWPLLEFSK in isoform 2. 2 PublicationsVSP_055851Add
    BLAST
    Alternative sequencei231 – 32696EKQKL…TPATI → GPM in isoform 2. 2 PublicationsVSP_055852Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY154470 mRNA. Translation: AAN59975.1.
    AY154471 mRNA. Translation: AAN59976.1.
    AY154472 mRNA. Translation: AAN59977.1.
    D79990 mRNA. Translation: BAA11485.2. Different initiation.
    AK291458 mRNA. Translation: BAF84147.1.
    AK222650 mRNA. Translation: BAD96370.1.
    CR627436 mRNA. Translation: CAH10522.1.
    AL133354 Genomic DNA. Translation: CAC34362.1.
    CH471133 Genomic DNA. Translation: EAX10445.1.
    BC110385 mRNA. Translation: AAI10386.1.
    BC117118 mRNA. Translation: AAI17119.1.
    BC117120 mRNA. Translation: AAI17121.1.
    CCDSiCCDS13083.1.
    RefSeqiNP_055552.1. NM_014737.2.
    NP_739580.1. NM_170774.1.
    XP_005260952.1. XM_005260895.2.
    XP_006723731.1. XM_006723668.1.
    XP_006723732.1. XM_006723669.1.
    UniGeneiHs.631504.

    Genome annotation databases

    EnsembliENST00000379376; ENSP00000368684; ENSG00000101265. [P50749-1]
    ENST00000379400; ENSP00000368710; ENSG00000101265. [P50749-1]
    GeneIDi9770.
    KEGGihsa:9770.
    UCSCiuc002wld.3. human.

    Polymorphism databases

    DMDMi1723118.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY154470 mRNA. Translation: AAN59975.1 .
    AY154471 mRNA. Translation: AAN59976.1 .
    AY154472 mRNA. Translation: AAN59977.1 .
    D79990 mRNA. Translation: BAA11485.2 . Different initiation.
    AK291458 mRNA. Translation: BAF84147.1 .
    AK222650 mRNA. Translation: BAD96370.1 .
    CR627436 mRNA. Translation: CAH10522.1 .
    AL133354 Genomic DNA. Translation: CAC34362.1 .
    CH471133 Genomic DNA. Translation: EAX10445.1 .
    BC110385 mRNA. Translation: AAI10386.1 .
    BC117118 mRNA. Translation: AAI17119.1 .
    BC117120 mRNA. Translation: AAI17121.1 .
    CCDSi CCDS13083.1.
    RefSeqi NP_055552.1. NM_014737.2.
    NP_739580.1. NM_170774.1.
    XP_005260952.1. XM_005260895.2.
    XP_006723731.1. XM_006723668.1.
    XP_006723732.1. XM_006723669.1.
    UniGenei Hs.631504.

    3D structure databases

    ProteinModelPortali P50749.
    SMRi P50749. Positions 189-261.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 115115. 24 interactions.
    IntActi P50749. 27 interactions.
    MINTi MINT-6773106.
    STRINGi 9606.ENSP00000368684.

    PTM databases

    PhosphoSitei P50749.

    Polymorphism databases

    DMDMi 1723118.

    Proteomic databases

    MaxQBi P50749.
    PaxDbi P50749.
    PRIDEi P50749.

    Protocols and materials databases

    DNASUi 9770.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000379376 ; ENSP00000368684 ; ENSG00000101265 . [P50749-1 ]
    ENST00000379400 ; ENSP00000368710 ; ENSG00000101265 . [P50749-1 ]
    GeneIDi 9770.
    KEGGi hsa:9770.
    UCSCi uc002wld.3. human.

    Organism-specific databases

    CTDi 9770.
    GeneCardsi GC20M004760.
    HGNCi HGNC:9883. RASSF2.
    HPAi HPA051200.
    MIMi 609492. gene.
    neXtProti NX_P50749.
    PharmGKBi PA34246.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG264677.
    HOGENOMi HOG000231738.
    HOVERGENi HBG054302.
    InParanoidi P50749.
    KOi K09851.
    OMAi NTDYPLV.
    OrthoDBi EOG7DVDBF.
    PhylomeDBi P50749.
    TreeFami TF319243.

    Miscellaneous databases

    GeneWikii RASSF2.
    GenomeRNAii 9770.
    NextBioi 36774.
    PROi P50749.
    SOURCEi Search...

    Gene expression databases

    Bgeei P50749.
    CleanExi HS_RASSF2.
    Genevestigatori P50749.

    Family and domain databases

    InterProi IPR000159. Ras-assoc.
    IPR011524. SARAH_dom.
    IPR029071. Ubiquitin-rel_dom.
    [Graphical view ]
    Pfami PF00788. RA. 1 hit.
    [Graphical view ]
    SMARTi SM00314. RA. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54236. SSF54236. 1 hit.
    PROSITEi PS50200. RA. 1 hit.
    PS50951. SARAH. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "RASSF2 is inactivated by an epigenetic mechanism in ovarian cancers."
      Burbee D.G., White M.A., Miller D.S., Minna J.D., Muller C.Y.
      Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    2. "Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1."
      Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.
      DNA Res. 3:17-24(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Bone marrow.
    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: Brain.
    4. Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
      Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Cerebellum.
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Retina.
    6. "The DNA sequence and comparative analysis of human chromosome 20."
      Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
      , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
      Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "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] (ISOFORMS 1 AND 2).
      Tissue: Brain.
    9. "RASSF2 is a novel K-Ras-specific effector and potential tumor suppressor."
      Vos M.D., Ellis C.A., Elam C., Uelkue A.S., Taylor B.J., Clark G.J.
      J. Biol. Chem. 278:28045-28051(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH KRAS, TISSUE SPECIFICITY.
    10. "The Ras effector RASSF2 is a novel tumor-suppressor gene in human colorectal cancer."
      Akino K., Toyota M., Suzuki H., Mita H., Sasaki Y., Ohe-Toyota M., Issa J.P., Hinoda Y., Imai K., Tokino T.
      Gastroenterology 129:156-169(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    11. "Local activation of Rap1 contributes to directional vascular endothelial cell migration accompanied by extension of microtubules on which RAPL, a Rap1-associating molecule, localizes."
      Fujita H., Fukuhara S., Sakurai A., Yamagishi A., Kamioka Y., Nakaoka Y., Masuda M., Mochizuki N.
      J. Biol. Chem. 280:5022-5031(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    12. "RASSF2 associates with and stabilizes the proapoptotic kinase MST2."
      Cooper W.N., Hesson L.B., Matallanas D., Dallol A., von Kriegsheim A., Ward R., Kolch W., Latif F.
      Oncogene 28:2988-2998(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH STK3/MST2 AND STK4/MST1, SUBCELLULAR LOCATION, PHOSPHORYLATION.
    13. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    14. Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-144.

    Entry informationi

    Entry nameiRASF2_HUMAN
    AccessioniPrimary (citable) accession number: P50749
    Secondary accession number(s): A6NIX9
    , A8K5Z3, Q17S06, Q53HD0, Q6AHZ2, Q8IZA5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 121 of the entry and version 1 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 20
      Human chromosome 20: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3