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Reviewed, UniProtKB/Swiss-Prot Q9NS23 (RASF1_HUMAN)

Last modified July 7, 2009. Version 72. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Ras association domain-containing protein 1
Gene names
Name: RASSF1
Synonyms: RDA32
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length344 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Potential tumor suppressor. Required for death receptor-dependent apoptosis. Mediates activation of STK4 during Fas-induced apoptosis. When associated with MOAP1, promotes BAX conformational change and translocation to mitochondrial membranes in response to TNF and TNFSF10 stimulation. Isoform A interacts with CDC20, an activator of the anaphase-promoting complex, APC, resulting in the inhibition of APC activity and mitotic progression. Inhibits proliferation by negatively regulating cell cycle progression at the level of G1/S-phase transition by regulating accumulation of cyclin D1 protein. Isoform C has been shown not to perform these roles, no function has been identified for this isoform. Ref.1 Ref.2 Ref.4 Ref.9 Ref.10 Ref.12 Ref.13

Subunit structure

Interacts with MAP1S and XPA. Binds to the N-terminal of CDC20 during prometaphase. Binds to STK3 and STK4. Isoform A interacts with MOAP1 and E4F1. Recruited to the TNFRSF1A and TNFRSF10A complexes in response to their respective cognate ligand, after internalization. Can self-associate. Isoform A interacts with RSSF5 and probably associates with HRAS1 via a RSSF1 isoform A-RSSF5 heterodimer. Ref.1 Ref.9 Ref.10 Ref.12 Ref.13 Ref.5 Ref.7 Ref.8 Ref.11

Subcellular location

Isoform A: Cytoplasmcytoskeleton. Centrosome. Spindle. Note: Localizes to cytoplasmic microtubules during interphase, to bipolar centrosomes associated with microtubules during prophase, to spindle fibers and spindle poles at metaphase and anaphase, to the midzone during early telophase, and to the midbody in late telophase in cells. Ref.9

Isoform C: Nucleus. Note: Predominantly nuclear. Ref.9

Tissue specificity

Isoform A and isoform C are ubiquitously expressed in all tissues tested, however isoform A is absent in many corresponding cancer cell lines. Isoform B is mainly expressed in hematopoetic cells. Ref.1 Ref.2

Sequence similarities

Contains 1 phorbol-ester/DAG-type zinc finger.

Contains 1 Ras-associating domain.

Contains 1 SARAH domain.

Sequence caution

The sequence AAB67312.1 differs from that shown. Reason: Erroneous gene model prediction.

Alternative products

This entry describes 8 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]
Isoform D Ref.2 (identifier: Q9NS23-1)

Also known as: RASSF1D; Cardiac-specific;

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.
Note: Produced by alternative promoter usage.
Isoform A Ref.1 Ref.2 (identifier: Q9NS23-2)

Also known as: RASSF1A;

The sequence of this isoform differs from the canonical sequence as follows:
     84-88: RLSAD → H
Note: Localizes to cytoplasmic microtubules during interphase, to bipolar centrosomes associated with microtubules during prophase, to spindle fibers and spindle poles at metaphase and anaphase, to the midzone during early telophase, and to the midbody in late telophase in cells. Ref.9 Produced by alternative splicing of isoform D.
Isoform B Ref.1 (identifier: Q9NS23-3)

Also known as: RASSF1B;

The sequence of this isoform differs from the canonical sequence as follows:
     1-155: Missing.
Note: Produced by alternative splicing of isoform D.
Isoform C Ref.1 Ref.2 (identifier: Q9NS23-4)

Also known as: RASSF1C;

The sequence of this isoform differs from the canonical sequence as follows:
     1-74: Missing.
     75-123: VVRKGLQCAR...EPAVERDTNV → MGEAEAPSFE...SLARRPRRDQ
Note: Predominantly nuclear. Ref.9 Produced by alternative promoter usage.
Isoform E Ref.2 (identifier: Q9NS23-5)

Also known as: RASSF1E; Pancreas-specific;

The sequence of this isoform differs from the canonical sequence as follows:
     84-88: RLSAD → H
     123-123: V → VPILQ
Note: Produced by alternative splicing of isoform D.
Isoform F Ref.2 (identifier: Q9NS23-6)

Also known as: RASSF1F;

The sequence of this isoform differs from the canonical sequence as follows:
     85-91: LSADCKF → RACGVGD
     93-344: Missing.
Note: Produced by alternative splicing of isoform D.
Isoform G Ref.2 (identifier: Q9NS23-7)

Also known as: RASSF1G;

The sequence of this isoform differs from the canonical sequence as follows:
     84-149: RLSADCKFTC...EQKIKEYNAQ → QQGRFLHRLH...PACAVTHKGT
     150-344: Missing.
Note: Produced by alternative splicing of isoform D.
Isoform H (identifier: Q9NS23-9)

The sequence of this isoform differs from the canonical sequence as follows:
     1-74: Missing.
     75-123: VVRKGLQCAR...EPAVERDTNV → MGEAEAPSFE...SLARRPRRDQ
     150-344: Missing.
Note: Produced by alternative splicing of isoform C.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 344344Ras association domain-containing protein 1
PRO_0000068891

Regions

Domain198 – 29295Ras-associating
Domain294 – 34148SARAH
Zinc finger51 – 10555Phorbol-ester/DAG-type
Region1 – 119119Mediates interaction with E4F1
Region315 – 3184MOAP1-binding

Amino acid modifications

Modified residue2061Phosphothreonine Ref.14

Natural variations

Alternative sequence1 – 155155Missing in isoform B. Ref.1
VSP_050770
Alternative sequence1 – 7474Missing in isoform C and isoform H. Ref.1 Ref.2
VSP_050773
Alternative sequence75 – 12349VVRKG…RDTNV → MGEAEAPSFEMTWSSTTSSG YCSQEDSDSELEQYFTARTS LARRPRRDQ in isoform C and isoform H. Ref.1 Ref.2
VSP_050774
Alternative sequence84 – 14966RLSAD…EYNAQ → QQGRFLHRLHQGSAEAGAPC LCALQQEATLLAGCPAGPRT GHKCQAPHFLLPAQGCCQAP ACAVTHKGT in isoform G. Ref.2
VSP_050775
Alternative sequence84 – 885RLSAD → H in isoform A and isoform E. Ref.1 Ref.2
VSP_050771
Alternative sequence85 – 917LSADCKF → RACGVGD in isoform F. Ref.2
VSP_050776
Alternative sequence93 – 344252Missing in isoform F. Ref.2
VSP_050777
Alternative sequence1231V → VPILQ in isoform E. Ref.2
VSP_050772
Alternative sequence150 – 344195Missing in isoform G and isoform H. Ref.2
VSP_050778
Natural variant211K → Q: dbSNP rs4688725. Ref.1 Ref.2
VAR_019542
Natural variant531R → C Ref.2
VAR_019543
Natural variant1331D → E Ref.2
VAR_019544
Natural variant1351S → F Prevents G1 cell cycle arrest; reduced protein phosphorylation. Ref.4
VAR_019545
Natural variant1371A → S Prevents G1 cell cycle arrest; reduced protein phosphorylation. dbSNP rs2073498. Ref.2 Ref.4
VAR_019546
Natural variant3291Y → C Ref.2
VAR_019547

Sequences

Sequence LengthMass (Da)Tools
Isoform D (RASSF1D) (Cardiac-specific) [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 4071B8D044C1DB2D

FASTA34439,219
        10         20         30         40         50         60 
MSGEPELIEL RELAPAGRAG KGRTRLERAN ALRIARGTAC NPTRQLVPGR GHRFQPAGPA 

        70         80         90        100        110        120 
THTWCDLCGD FIWGVVRKGL QCARLSADCK FTCHYRCRAL VCLDCCGPRD LGWEPAVERD 

       130        140        150        160        170        180 
TNVDEPVEWE TPDLSQAEIE QKIKEYNAQI NSNLFMSLNK DGSYTGFIKV QLKLVRPVSV 

       190        200        210        220        230        240 
PSSKKPPSLQ DARRGPGRGT SVRRRTSFYL PKDAVKHLHV LSRTRAREVI EALLRKFLVV 

       250        260        270        280        290        300 
DDPRKFALFE RAERHGQVYL RKLLDDEQPL RLRLLAGPSD KALSFVLKEN DSGEVNWDAF 

       310        320        330        340 
SMPELHNFLR ILQREEEEHL RQILQKYSYC RQKIQEALHA CPLG 

« Hide

Isoform A (RASSF1A).

Checksum: 73FB7C7D87507D9F
Show »

FASTA34038,814
Isoform B (RASSF1B).

Checksum: 2D7C1F632EA7A23B
Show »

FASTA18921,899
Isoform C (RASSF1C).

Checksum: 2E7006EA16A38D25
Show »

FASTA27031,226
Isoform E (RASSF1E) (Pancreas-specific).

Checksum: DB422771EB2AB7B2
Show »

FASTA34439,265
Isoform F (RASSF1F).

Checksum: C8FEFAAD37425A01
Show »

FASTA929,937
Isoform G (RASSF1G).

Checksum: 18403EEC734C2695
Show »

FASTA15216,120
Isoform H.

Checksum: 5B7A6F7C7409E740
Show »

FASTA758,656

References

« Hide 'large scale' references
[1]"Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3."
Dammann R., Li C., Yoon J.-H., Chin P.L., Bates S., Pfeifer G.P.
Nat. Genet. 25:315-319(2000) [PubMed: 10888881] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C), FUNCTION, TISSUE SPECIFICITY, VARIANT GLN-21, INTERACTION WITH XPA.
[2]"Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression."
Burbee D.G., Forgacs E., Zochbauer-Muller S., Shivakumar L., Fong K., Gao B., Randle D., Kondo M., Virmani A., Bader S., Sekido Y., Latif F., Milchgrub S., Toyooka S., Gazdar A.F., Lerman M.I., Zabarovsky E., White M., Minna J.D.
J. Natl. Cancer Inst. 93:691-699(2001) [PubMed: 11333291] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; C; D; E; F AND G), FUNCTION, TISSUE SPECIFICITY, VARIANTS GLN-21; CYS-53; GLU-133; SER-137 AND CYS-329.
Tissue: Heart, Lung and Pancreas.
[3]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed: 16641997] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The RASSF1A tumor suppressor blocks cell cycle progression and inhibits cyclin D1 accumulation."
Shivakumar L., Minna J., Sakamaki T., Pestell R., White M.A.
Mol. Cell. Biol. 22:4309-4318(2002) [PubMed: 12024041] [Abstract]
Cited for: FUNCTION, VARIANT PHE-135, CHARACTERIZATION OF VARIANTS PHE-135 AND SER-137.
[5]"The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1."
Ortiz-Vega S., Khokhlatchev A., Nedwidek M., Zhang X.F., Dammann R., Pfeifer G.P., Avruch J.
Oncogene 21:1381-1390(2002) [PubMed: 11857081] [Abstract]
Cited for: SELF-ASSOCIATION, INTERACTION WITH RSSF5 AND HRAS1.
[6]Erratum
Ortiz-Vega S., Khokhlatchev A., Nedwidek M., Zhang X.F., Dammann R., Pfeifer G.P., Avruch J.
Oncogene 21:1943-1943(2002)
[7]"Identification of the E1A-regulated transcription factor p120 E4F as an interacting partner of the RASSF1A candidate tumor suppressor gene."
Fenton S.L., Dallol A., Agathanggelou A., Hesson L., Ahmed-Choudhury J., Baksh S., Sardet C., Dammann R., Minna J.D., Downward J., Maher E.R., Latif F.
Cancer Res. 64:102-107(2004) [PubMed: 14729613] [Abstract]
Cited for: INTERACTION WITH E4F1.
[8]"RASSF1A interacts with microtubule-associated proteins and modulates microtubule dynamics."
Dallol A., Agathanggelou A., Fenton S.L., Ahmed-Choudhury J., Hesson L., Vos M.D., Clark G.J., Downward J., Maher E.R., Latif F.
Cancer Res. 64:4112-4116(2004) [PubMed: 15205320] [Abstract]
Cited for: INTERACTION WITH MAP1S.
[9]"The tumour suppressor RASSF1A regulates mitosis by inhibiting the APC-Cdc20 complex."
Song M.S., Song S.J., Ayad N.G., Chang J.S., Lee J.H., Hong H.K., Lee H., Choi N., Kim J., Kim H., Kim J.W., Choi E.-J., Kirschner M.W., Lim D.-S.
Nat. Cell Biol. 6:129-137(2004) [PubMed: 14743218] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CDC20.
[10]"Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras."
Praskova M., Khoklatchev A., Ortiz-Vega S., Avruch J.
Biochem. J. 381:453-462(2004) [PubMed: 15109305] [Abstract]
Cited for: FUNCTION, INTERACTION WITH STK3 AND STK4.
[11]"Specificity of the methylation-suppressed A isoform of candidate tumor suppressor RASSF1 for microtubule hyperstabilization is determined by cell death inducer C19ORF5."
Liu L., Vo A., McKeehan W.L.
Cancer Res. 65:1830-1838(2005) [PubMed: 15753381] [Abstract]
Cited for: INTERACTION WITH MAP1S.
[12]"The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax conformational change and cell death."
Baksh S., Tommasi S., Fenton S., Yu V.C., Martins L.M., Pfeifer G.P., Latif F., Downward J., Neel B.G.
Mol. Cell 18:637-650(2005) [PubMed: 15949439] [Abstract]
Cited for: INTERACTION WITH MOAP1, FUNCTION.
[13]"Role of the tumor suppressor RASSF1A in Mst1-mediated apoptosis."
Oh H.J., Lee K.-K., Song S.J., Jin M.S., Song M.S., Lee J.H., Im C.R., Lee J.-O., Yonehara S., Lim D.-S.
Cancer Res. 66:2562-2569(2006) [PubMed: 16510573] [Abstract]
Cited for: FUNCTION, INTERACTION WITH STK3 AND STK4.
[14]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-206, MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

AF061836 mRNA. Translation: AAC16001.1.
AF132675 mRNA. Translation: AAD44174.1.
AF132676 mRNA. Translation: AAD44175.1.
AF132677 mRNA. Translation: AAD44176.1.
AF040703 mRNA. Translation: AAC70910.2.
AF102770 mRNA. Translation: AAF35127.2.
AF102771 mRNA. Translation: AAF35128.2.
AF102772 mRNA. Translation: AAF35129.2.
AF286217 mRNA. Translation: AAG10038.1.
AF291719 mRNA. Translation: AAG10064.1.
AC002455 Genomic DNA. No translation available.
AC002481 Genomic DNA. Translation: AAB67312.1. Sequence problems.
IPIIPI00172514.
IPI00172661.
IPI00221057.
IPI00395780.
IPI00426162.
IPI00426164.
IPI00426165.
IPI00455193.
RefSeqNP_009113.3.
NP_733831.1.
NP_733832.1.
UniGeneHs.476270

3D structure databases

HSSPHSSP built from PDB template 1PTQ based on UniProtKB P28867.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9NS23. 13 interactions.

PTM databases

PhosphoSiteQ9NS23.

Genome annotation databases

EnsemblENSG00000068028. Homo sapiens. [Contig view]
GeneID11186.
KEGGhsa:11186.
UCSCuc003daa.1. human.
uc003dad.1. human.

Organism-specific databases

GeneCardsGC03M050342.
H-InvDBHIX0030705.
HGNCHGNC:9882. RASSF1.
MIM605082. gene.
PharmGKBPA34245.
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ9NS23.
OMAQ9NS23. RDQDEAV.

Gene expression databases

ArrayExpressQ9NS23.
BgeeQ9NS23.
GermOnlineENSG00000068028. Homo sapiens.

Family and domain databases

InterProIPR002219. DAG_PE_bd.
IPR000159. Ras-assoc.
IPR011524. SARAH.
[Graphical view]
PfamPF00130. C1_1. 1 hit.
PF00788. RA. 1 hit.
[Graphical view]
SMARTSM00109. C1. 1 hit.
SM00314. RA. 1 hit.
[Graphical view]
PROSITEPS50200. RA. 1 hit.
PS50951. SARAH. 1 hit.
PS00479. ZF_DAG_PE_1. False negative.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio42571.
SOURCESearch...

Entry information

Entry nameRASF1_HUMAN
AccessionPrimary (citable) accession number: Q9NS23
Secondary accession number(s): O14571 expand/collapse secondary AC list , O60539, O60710, Q9HB04, Q9HB18, Q9NS22, Q9UND4, Q9UND5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: October 1, 2000
Last modified: July 7, 2009
This is version 72 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents