P50749 (RASF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ras association domain-containing protein 2

Gene names

Name:	RASSF2
Synonyms:	KIAA0168

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

General annotation (Comments)

Function	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. Ref.9 Ref.10 Ref.12
Subunit structure	Interacts directly with activated KRAS in a GTP-dependent manner. Interacts (via SARAH domain) with STK3/MST2 AND STK4/MST1. Ref.9 Ref.12
Subcellular location	Nucleus. Cytoplasm. Note: Translocates to the cytoplasm in the presence of STK3/MST2 AND STK4/MST1. Ref.11 Ref.12
Tissue specificity	Widely expressed with highest levels in brain, placenta, peripheral blood and lung. Frequently down-regulated in lung tumor cell lines. Ref.9
Post-translational modification	Phosphorylated by STK3/MST2 and STK4/MST1. Ref.12
Sequence similarities	Contains 1 Ras-associating domain. Contains 1 SARAH domain.
Sequence caution	The sequence BAA11485.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Tumor suppressor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
KRAS	P01116	2	EBI-960081,EBI-367415
STK4	Q13043	5	EBI-960081,EBI-367376

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 326	326	Ras association domain-containing protein 2		PRO_0000097172
Regions
	Domain	176 – 264	89	Ras-associating
	Domain	272 – 319	48	SARAH
Natural variations
	Natural variant	144	1	R → H in a colorectal cancer sample; somatic mutation. Ref.14		VAR_035825
Experimental info
	Sequence conflict	166	1	R → C in BAD96370. Ref.4
	Sequence conflict	256	1	K → Q in BAD96370. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P50749 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: C29D16376904249E	FASTA	326	37,790
	10 20 30 40 50 60 MDYSHQTSLV PCGQDKYISK NELLLHLKTY NLYYEGQNLQ LRHREEEDEF IVEGLLNISW 70 80 90 100 110 120 GLRRPIRLQM QDDNERIRPP PSSSSWHSGC NLGAQGTTLK PLTVPKVQIS EVDAPPEGDQ 130 140 150 160 170 180 MPSSTDSRGL KPLQEDTPQL MRTRSDVGVR RRGNVRTPSD QRRIRRHRFS INGHFYNHKT 190 200 210 220 230 240 SVFTPAYGSV TNVRINSTMT TPQVLKLLLN KFKIENSAEE FALYVVHTSG EKQKLKATDY 250 260 270 280 290 300 PLIARILQGP CEQISKVFLM EKDQVEEVTY DVAQYIKFEM PVLKSFIQKL QEEEDREVKK 310 320 LMRKYTVLRL MIRQRLEEIA ETPATI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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].
[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]. 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]. 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]. Tissue: Cerebellum.
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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]. 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]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-144.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY154470 mRNA. Translation: AAN59975.1. 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. BC117118 mRNA. Translation: AAI17119.1. BC117120 mRNA. Translation: AAI17121.1.
IPI	IPI00414179.
RefSeq	NP_055552.1. NM_014737.2. NP_739580.1. NM_170774.1.
UniGene	Hs.631504.
3D structure databases
ProteinModelPortal	P50749.
ModBase	Search...
Protein-protein interaction databases
IntAct	P50749. 6 interactions.
MINT	MINT-6773106.
STRING	9606.ENSP00000368684.
PTM databases
PhosphoSite	P50749.
Polymorphism databases
DMDM	1723118.
Proteomic databases
PaxDb	P50749.
PRIDE	P50749.
Protocols and materials databases
DNASU	9770.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000379376; ENSP00000368684; ENSG00000101265. ENST00000379400; ENSP00000368710; ENSG00000101265.
GeneID	9770.
KEGG	hsa:9770.
UCSC	uc002wld.3. human.
Organism-specific databases
CTD	9770.
GeneCards	GC20M004760.
HGNC	HGNC:9883. RASSF2.
HPA	HPA051200.
MIM	609492. gene.
neXtProt	NX_P50749.
PharmGKB	PA34246.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG264677.
HOGENOM	HOG000231738.
HOVERGEN	HBG054302.
InParanoid	P50749.
KO	K09851.
OMA	GCNLGAH.
OrthoDB	EOG41C6WR.
Gene expression databases
Bgee	P50749.
CleanEx	HS_RASSF2.
Genevestigator	P50749.
GermOnline	ENSG00000101265. Homo sapiens.
Family and domain databases
InterPro	IPR000159. Ras-assoc. IPR011524. SARAH_dom. [Graphical view]
Pfam	PF00788. RA. 1 hit. [Graphical view]
SMART	SM00314. RA. 1 hit. [Graphical view]
PROSITE	PS50200. RA. 1 hit. PS50951. SARAH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	9770.
NextBio	36774.
SOURCE	Search...

Entry information

Entry name

RASF2_HUMAN

Accession

Primary (citable) accession number: P50749
Secondary accession number(s): A6NIX9 , A8K5Z3, Q17S06, Q53HD0, Q6AHZ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 29, 2013
This is version 107 of the entry and version 1 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.