RASF6_HUMAN
ID RASF6_HUMAN Reviewed; 369 AA.
AC Q6ZTQ3; Q68DT2; Q6PDA6; Q86WG9; Q86WH0;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Ras association domain-containing protein 6;
GN Name=RASSF6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
RA Burbee D.G., White M.A., Miller D.S., Minna J.D., Muller C.Y.;
RT "RASSF6, a member of the RASSF family of putative tumor suppressors, is
RT transcriptionally repressed in lung and breast cancers.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Small intestine;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANT PRO-163.
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND LACK OF INTERACTION WITH KRAS; MRAS; NRAS AND RRAS2.
RX PubMed=17367779; DOI=10.1016/j.yexcr.2007.02.013;
RA Ikeda M., Hirabayashi S., Fujiwara N., Mori H., Kawata A., Iida J., Bao Y.,
RA Sato Y., Iida T., Sugimura H., Hata Y.;
RT "Ras-association domain family protein 6 induces apoptosis via both
RT caspase-dependent and caspase-independent pathways.";
RL Exp. Cell Res. 313:1484-1495(2007).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=17404571; DOI=10.1038/sj.onc.1210440;
RA Allen N.P., Donninger H., Vos M.D., Eckfeld K., Hesson L., Gordon L.,
RA Birrer M.J., Latif F., Clark G.J.;
RT "RASSF6 is a novel member of the RASSF family of tumor suppressors.";
RL Oncogene 26:6203-6211(2007).
CC -!- FUNCTION: Involved in the induction of apoptosis, through both caspase-
CC dependent and caspase-independent pathways. May act as a Ras effector
CC protein. May suppress the serum-induced basal levels of NF-kappa-B (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:17367779}.
CC -!- SUBUNIT: Interacts with MOAP1 (By similarity). Interaction with
CC activated KRAS is still a matter of debate: interaction has been shown
CC in the mouse (PubMed:17404571), but not in human (PubMed:17367779).
CC Lack of interaction with MRAS, NRAS nor RRAS2 has also been reported
CC (PubMed:17367779). {ECO:0000250, ECO:0000269|PubMed:17367779,
CC ECO:0000269|PubMed:17404571}.
CC -!- INTERACTION:
CC Q6ZTQ3; Q13043: STK4; NbExp=4; IntAct=EBI-2933412, EBI-367376;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q6ZTQ3-1; Sequence=Displayed;
CC Name=2; Synonyms=A;
CC IsoId=Q6ZTQ3-2; Sequence=VSP_019370;
CC Name=3; Synonyms=B;
CC IsoId=Q6ZTQ3-3; Sequence=VSP_019371;
CC Name=4;
CC IsoId=Q6ZTQ3-4; Sequence=VSP_019370, VSP_019372;
CC -!- TISSUE SPECIFICITY: Highest expression in thymus, kidney and placenta.
CC Also detected in colon, small intestine and lung. Tends to be down-
CC regulated in 30-60% of tumors derived from breast, colon, kidney liver,
CC rectum, pancreas, stomach and the thyroid gland compared to the normal
CC counterpart. {ECO:0000269|PubMed:17404571}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH58835.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAH18138.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RASSF6ID43462ch4q13.html";
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DR EMBL; AY217665; AAO61690.1; -; mRNA.
DR EMBL; AY217664; AAO61689.1; -; mRNA.
DR EMBL; AK126346; BAC86530.1; -; mRNA.
DR EMBL; CR749283; CAH18138.1; ALT_SEQ; mRNA.
DR EMBL; BC058835; AAH58835.1; ALT_INIT; mRNA.
DR CCDS; CCDS3558.1; -. [Q6ZTQ3-1]
DR CCDS; CCDS3559.1; -. [Q6ZTQ3-2]
DR CCDS; CCDS58904.1; -. [Q6ZTQ3-4]
DR CCDS; CCDS58905.1; -. [Q6ZTQ3-3]
DR RefSeq; NP_001257320.1; NM_001270391.1. [Q6ZTQ3-4]
DR RefSeq; NP_001257321.1; NM_001270392.1. [Q6ZTQ3-3]
DR RefSeq; NP_803876.1; NM_177532.4. [Q6ZTQ3-2]
DR RefSeq; NP_958834.1; NM_201431.2. [Q6ZTQ3-1]
DR RefSeq; XP_011529990.1; XM_011531688.1. [Q6ZTQ3-2]
DR AlphaFoldDB; Q6ZTQ3; -.
DR BioGRID; 127936; 13.
DR IntAct; Q6ZTQ3; 5.
DR MINT; Q6ZTQ3; -.
DR STRING; 9606.ENSP00000340578; -.
DR iPTMnet; Q6ZTQ3; -.
DR PhosphoSitePlus; Q6ZTQ3; -.
DR BioMuta; RASSF6; -.
DR DMDM; 74749658; -.
DR EPD; Q6ZTQ3; -.
DR MassIVE; Q6ZTQ3; -.
DR PaxDb; Q6ZTQ3; -.
DR PeptideAtlas; Q6ZTQ3; -.
DR PRIDE; Q6ZTQ3; -.
DR ProteomicsDB; 68282; -. [Q6ZTQ3-1]
DR ProteomicsDB; 68283; -. [Q6ZTQ3-2]
DR ProteomicsDB; 68284; -. [Q6ZTQ3-3]
DR ProteomicsDB; 68285; -. [Q6ZTQ3-4]
DR Antibodypedia; 24560; 208 antibodies from 33 providers.
DR DNASU; 166824; -.
DR Ensembl; ENST00000307439.10; ENSP00000303877.5; ENSG00000169435.14. [Q6ZTQ3-2]
DR Ensembl; ENST00000335049.5; ENSP00000335582.5; ENSG00000169435.14. [Q6ZTQ3-3]
DR Ensembl; ENST00000342081.7; ENSP00000340578.3; ENSG00000169435.14. [Q6ZTQ3-1]
DR Ensembl; ENST00000395777.6; ENSP00000379123.2; ENSG00000169435.14. [Q6ZTQ3-4]
DR GeneID; 166824; -.
DR KEGG; hsa:166824; -.
DR MANE-Select; ENST00000307439.10; ENSP00000303877.5; NM_177532.5; NP_803876.1. [Q6ZTQ3-2]
DR UCSC; uc003hhc.3; human. [Q6ZTQ3-1]
DR CTD; 166824; -.
DR DisGeNET; 166824; -.
DR GeneCards; RASSF6; -.
DR HGNC; HGNC:20796; RASSF6.
DR HPA; ENSG00000169435; Tissue enhanced (lymphoid tissue, stomach).
DR MIM; 612620; gene.
DR neXtProt; NX_Q6ZTQ3; -.
DR OpenTargets; ENSG00000169435; -.
DR PharmGKB; PA134900075; -.
DR VEuPathDB; HostDB:ENSG00000169435; -.
DR eggNOG; KOG4239; Eukaryota.
DR GeneTree; ENSGT00940000159886; -.
DR HOGENOM; CLU_018893_0_0_1; -.
DR InParanoid; Q6ZTQ3; -.
DR OMA; WIFVNER; -.
DR OrthoDB; 1043350at2759; -.
DR PhylomeDB; Q6ZTQ3; -.
DR TreeFam; TF319243; -.
DR PathwayCommons; Q6ZTQ3; -.
DR SignaLink; Q6ZTQ3; -.
DR SIGNOR; Q6ZTQ3; -.
DR BioGRID-ORCS; 166824; 11 hits in 1069 CRISPR screens.
DR ChiTaRS; RASSF6; human.
DR GenomeRNAi; 166824; -.
DR Pharos; Q6ZTQ3; Tbio.
DR PRO; PR:Q6ZTQ3; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q6ZTQ3; protein.
DR Bgee; ENSG00000169435; Expressed in pancreatic ductal cell and 127 other tissues.
DR Genevisible; Q6ZTQ3; HS.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR InterPro; IPR000159; RA_dom.
DR InterPro; IPR033614; RASSF1-6.
DR InterPro; IPR033625; RASSF6.
DR InterPro; IPR011524; SARAH_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR22738; PTHR22738; 1.
DR PANTHER; PTHR22738:SF3; PTHR22738:SF3; 1.
DR Pfam; PF16517; Nore1-SARAH; 1.
DR Pfam; PF00788; RA; 1.
DR SMART; SM00314; RA; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50200; RA; 1.
DR PROSITE; PS50951; SARAH; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Phosphoprotein; Reference proteome.
FT CHAIN 1..369
FT /note="Ras association domain-containing protein 6"
FT /id="PRO_0000240404"
FT DOMAIN 218..306
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 313..360
FT /note="SARAH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00310"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80UQ2"
FT VAR_SEQ 1..32
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005, ECO:0000303|Ref.1"
FT /id="VSP_019370"
FT VAR_SEQ 23..80
FT /note="SSDHLKKEEKMTMMAHQYPSWIFINEKTFITREQLNSLLKTYNIFYENQKNL
FT HILYGE -> HFLSSGLILVTRQL (in isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_019371"
FT VAR_SEQ 222..255
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019372"
FT VARIANT 163
FT /note="S -> P (in dbSNP:rs12507775)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_026725"
FT VARIANT 306
FT /note="A -> G (in dbSNP:rs17804499)"
FT /id="VAR_034440"
SQ SEQUENCE 369 AA; 43384 MW; 19AF7D4B1ABA5ED6 CRC64;
MLWEETGAAP APARASDLPY RISSDHLKKE EKMTMMAHQY PSWIFINEKT FITREQLNSL
LKTYNIFYEN QKNLHILYGE TEDGKLIVEG MLDIFWGVKR PIQLKIQDEK PFSSFTSMKS
SDVFSSKGMT RWGEFDDLYR ISELDRTQIP MSEKRNSQED YLSYHSNTLK PHAKDEPDSP
VLYRTMSEAA LVRKRMKPLM MDRKERQKNR ASINGHFYNH ETSIFIPAFE SETKVRVNSN
MRTEEVIKQL LQKFKIENSP QDFALHIIFA TGEQRRLKKT DIPLLQRLLQ GPSEKNARIF
LMDKDAEEIS SDVAQYINFH FSLLESILQR LNEEEKREIQ RIVTKFNKEK AIILKCLQNK
LVIKTETTV
