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Protein

Ras association domain-containing protein 2

Gene

RASSF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 - Biological processi

  1. bone remodeling Source: Ensembl
  2. cell cycle Source: UniProtKB-KW
  3. epidermal growth factor receptor signaling pathway via I-kappaB kinase/NF-kappaB cascade Source: Ensembl
  4. homeostasis of number of cells Source: Ensembl
  5. negative regulation of NIK/NF-kappaB signaling Source: Ensembl
  6. ossification Source: Ensembl
  7. regulation of osteoblast differentiation Source: Ensembl
  8. regulation of osteoclast differentiation Source: Ensembl
  9. skeletal system development Source: Ensembl
Complete GO annotation...

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
Complete GO annotation...

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. 27 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.
GeneTreeiENSGT00510000046426.
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

        10         20         30         40         50
MDYSHQTSLV PCGQDKYISK NELLLHLKTY NLYYEGQNLQ LRHREEEDEF
60 70 80 90 100
IVEGLLNISW GLRRPIRLQM QDDNERIRPP PSSSSWHSGC NLGAQGTTLK
110 120 130 140 150
PLTVPKVQIS EVDAPPEGDQ MPSSTDSRGL KPLQEDTPQL MRTRSDVGVR
160 170 180 190 200
RRGNVRTPSD QRRIRRHRFS INGHFYNHKT SVFTPAYGSV TNVRINSTMT
210 220 230 240 250
TPQVLKLLLN KFKIENSAEE FALYVVHTSG EKQKLKATDY PLIARILQGP
260 270 280 290 300
CEQISKVFLM EKDQVEEVTY DVAQYIKFEM PVLKSFIQKL QEEEDREVKK
310 320
LMRKYTVLRL MIRQRLEEIA ETPATI
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. Curated

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:
EMBLi
GenBanki
DDBJi
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. [P50749-1]
RefSeqiNP_055552.1. NM_014737.2. [P50749-1]
NP_739580.1. NM_170774.1. [P50749-1]
XP_005260952.1. XM_005260895.2. [P50749-1]
XP_006723731.1. XM_006723668.1. [P50749-1]
XP_006723732.1. XM_006723669.1. [P50749-1]
UniGeneiHs.631504.

Genome annotation databases

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

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:
EMBLi
GenBanki
DDBJi
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. [P50749-1]
RefSeqiNP_055552.1. NM_014737.2. [P50749-1]
NP_739580.1. NM_170774.1. [P50749-1]
XP_005260952.1. XM_005260895.2. [P50749-1]
XP_006723731.1. XM_006723668.1. [P50749-1]
XP_006723732.1. XM_006723669.1. [P50749-1]
UniGeneiHs.631504.

3D structure databases

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

Protein-protein interaction databases

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

PTM databases

PhosphoSiteiP50749.

Polymorphism databases

DMDMi1723118.

Proteomic databases

MaxQBiP50749.
PaxDbiP50749.
PRIDEiP50749.

Protocols and materials databases

DNASUi9770.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9770.
GeneCardsiGC20M004760.
HGNCiHGNC:9883. RASSF2.
HPAiHPA051200.
MIMi609492. gene.
neXtProtiNX_P50749.
PharmGKBiPA34246.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG264677.
GeneTreeiENSGT00510000046426.
HOGENOMiHOG000231738.
HOVERGENiHBG054302.
InParanoidiP50749.
KOiK09851.
OMAiNTDYPLV.
OrthoDBiEOG7DVDBF.
PhylomeDBiP50749.
TreeFamiTF319243.

Miscellaneous databases

ChiTaRSiRASSF2. human.
GeneWikiiRASSF2.
GenomeRNAii9770.
NextBioi36774.
PROiP50749.
SOURCEiSearch...

Gene expression databases

BgeeiP50749.
CleanExiHS_RASSF2.
GenevestigatoriP50749.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: January 7, 2015
This is version 124 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.