RASM_HUMAN
ID RASM_HUMAN Reviewed; 208 AA.
AC O14807; B4DIK0; Q86WX8;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 2.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Ras-related protein M-Ras;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P01116};
DE AltName: Full=Ras-related protein R-Ras3;
DE Flags: Precursor;
GN Name=MRAS; Synonyms=RRAS3;
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] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=9400994; DOI=10.1038/sj.onc.1201674;
RA Kimmelman A., Tolkacheva T., Lorenzi M.V., Osada M., Chan A.M.-L.;
RT "Identification and characterization of R-ras3: a novel member of the RAS
RT gene family with a non-ubiquitous pattern of tissue distribution.";
RL Oncogene 15:2675-2686(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=10477695;
RA Louahed J., Grasso L., De Smet C., van Roost E., Wildmann C.,
RA Nicolaides N.C., Levitt R.C., Renauld J.-C.;
RT "Interleukin-9-induced expression of M-Ras/R-Ras3 oncogene in T-helper
RT clones.";
RL Blood 94:1701-1710(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Hippocampus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Pancreas, and Spleen;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
RP FUNCTION, INTERACTION WITH MRAS AND RAF1, AND IDENTIFICATION IN A COMPLEX
RP WITH PP1CA; PPP1CB; PPP1CC; RAF1 AND SHOC2.
RX PubMed=16630891; DOI=10.1016/j.molcel.2006.03.027;
RA Rodriguez-Viciana P., Oses-Prieto J., Burlingame A., Fried M.,
RA McCormick F.;
RT "A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit
RT of PP1 functions as an M-Ras effector to modulate Raf activity.";
RL Mol. Cell 22:217-230(2006).
RN [9]
RP INVOLVEMENT IN NS11, VARIANTS NS11 VAL-23 AND ILE-68, CHARACTERIZATION OF
RP VARIANT NS11 VAL-23, AND FUNCTION.
RX PubMed=28289718; DOI=10.1172/jci.insight.91225;
RA Higgins E.M., Bos J.M., Mason-Suares H., Tester D.J., Ackerman J.P.,
RA MacRae C.A., Sol-Church K., Gripp K.W., Urrutia R., Ackerman M.J.;
RT "Elucidation of MRAS-mediated Noonan syndrome with cardiac hypertrophy.";
RL JCI Insight 2:E91225-E91225(2017).
RN [10]
RP VARIANT NS11 ARG-71.
RX PubMed=31173466; DOI=10.1002/ajmg.a.61261;
RA Suzuki H., Takenouchi T., Uehara T., Takasago S., Ihara S., Yoshihashi H.,
RA Kosaki K.;
RT "Severe Noonan syndrome phenotype associated with a germline Q71R MRAS
RT variant: a recurrent substitution in RAS homologs in various cancers.";
RL Am. J. Med. Genet. A 179:1628-1630(2019).
CC -!- FUNCTION: Serves as an important signal transducer for a novel upstream
CC stimuli in controlling cell proliferation. Activates the MAP kinase
CC pathway. {ECO:0000269|PubMed:16630891, ECO:0000269|PubMed:28289718}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2;
CC Evidence={ECO:0000250|UniProtKB:P01116};
CC -!- SUBUNIT: Interacts with RGL3. Interacts (active GTP-bound form
CC preferentially) with RGS14 (By similarity). Forms a multiprotein
CC complex with SHOC2, Raf (RAF1) and protein phosphatase 1 (PPP1CA,
CC PPP1CB and PPP1CC). {ECO:0000250|UniProtKB:P97538,
CC ECO:0000269|PubMed:16630891}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O14807-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O14807-2; Sequence=VSP_044792;
CC -!- TISSUE SPECIFICITY: Expression highly restricted to the brain and
CC heart.
CC -!- INDUCTION: By IL9/interleukin-9, but not by IL2/interleukin-2 or
CC IL4/interleukin-4.
CC -!- DISEASE: Noonan syndrome 11 (NS11) [MIM:618499]: A form of Noonan
CC syndrome, a disease characterized by short stature, facial dysmorphic
CC features such as hypertelorism, a downward eyeslant and low-set
CC posteriorly rotated ears, and a high incidence of congenital heart
CC defects and hypertrophic cardiomyopathy. Other features can include a
CC short neck with webbing or redundancy of skin, deafness, motor delay,
CC variable intellectual deficits, multiple skeletal defects,
CC cryptorchidism, and bleeding diathesis. Individuals with Noonan
CC syndrome are at risk of juvenile myelomonocytic leukemia, a
CC myeloproliferative disorder characterized by excessive production of
CC myelomonocytic cells. NS11 inheritance is autosomal dominant.
CC {ECO:0000269|PubMed:28289718, ECO:0000269|PubMed:31173466}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
CC {ECO:0000305}.
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DR EMBL; AF022080; AAC52085.1; -; mRNA.
DR EMBL; AF043938; AAD02287.1; -; mRNA.
DR EMBL; AF493918; AAM12632.1; -; mRNA.
DR EMBL; AK295640; BAG58512.1; -; mRNA.
DR EMBL; AK316071; BAH14442.1; -; mRNA.
DR EMBL; BT020057; AAV38860.1; -; mRNA.
DR EMBL; AC022337; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC047690; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS3100.1; -. [O14807-1]
DR CCDS; CCDS58855.1; -. [O14807-2]
DR RefSeq; NP_001078518.1; NM_001085049.2. [O14807-1]
DR RefSeq; NP_001239019.1; NM_001252090.1. [O14807-1]
DR RefSeq; NP_001239020.1; NM_001252091.1. [O14807-2]
DR RefSeq; NP_001239021.1; NM_001252092.1. [O14807-2]
DR RefSeq; NP_001239022.1; NM_001252093.1. [O14807-2]
DR RefSeq; NP_036351.3; NM_012219.4. [O14807-1]
DR RefSeq; XP_005247285.1; XM_005247228.1. [O14807-1]
DR RefSeq; XP_016861376.1; XM_017005887.1. [O14807-1]
DR AlphaFoldDB; O14807; -.
DR SASBDB; O14807; -.
DR SMR; O14807; -.
DR BioGRID; 116486; 14.
DR DIP; DIP-35406N; -.
DR IntAct; O14807; 5.
DR MINT; O14807; -.
DR STRING; 9606.ENSP00000289104; -.
DR iPTMnet; O14807; -.
DR PhosphoSitePlus; O14807; -.
DR BioMuta; MRAS; -.
DR EPD; O14807; -.
DR jPOST; O14807; -.
DR MassIVE; O14807; -.
DR PaxDb; O14807; -.
DR PeptideAtlas; O14807; -.
DR PRIDE; O14807; -.
DR ProteomicsDB; 4310; -.
DR ProteomicsDB; 48250; -. [O14807-1]
DR ABCD; O14807; 1 sequenced antibody.
DR Antibodypedia; 33434; 158 antibodies from 26 providers.
DR DNASU; 22808; -.
DR Ensembl; ENST00000289104.8; ENSP00000289104.4; ENSG00000158186.13. [O14807-1]
DR Ensembl; ENST00000423968.7; ENSP00000389682.2; ENSG00000158186.13. [O14807-1]
DR Ensembl; ENST00000464896.5; ENSP00000419582.1; ENSG00000158186.13. [O14807-2]
DR Ensembl; ENST00000474559.1; ENSP00000418356.1; ENSG00000158186.13. [O14807-1]
DR Ensembl; ENST00000614350.4; ENSP00000484586.1; ENSG00000158186.13. [O14807-2]
DR Ensembl; ENST00000621127.4; ENSP00000481637.1; ENSG00000158186.13. [O14807-2]
DR GeneID; 22808; -.
DR KEGG; hsa:22808; -.
DR MANE-Select; ENST00000423968.7; ENSP00000389682.2; NM_001085049.3; NP_001078518.1.
DR UCSC; uc011bmi.3; human. [O14807-1]
DR CTD; 22808; -.
DR DisGeNET; 22808; -.
DR GeneCards; MRAS; -.
DR GeneReviews; MRAS; -.
DR HGNC; HGNC:7227; MRAS.
DR HPA; ENSG00000158186; Tissue enhanced (brain, heart muscle).
DR MalaCards; MRAS; -.
DR MIM; 608435; gene.
DR MIM; 618499; phenotype.
DR neXtProt; NX_O14807; -.
DR OpenTargets; ENSG00000158186; -.
DR Orphanet; 648; Noonan syndrome.
DR PharmGKB; PA30932; -.
DR VEuPathDB; HostDB:ENSG00000158186; -.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000156353; -.
DR HOGENOM; CLU_041217_9_8_1; -.
DR InParanoid; O14807; -.
DR OMA; IVNFHTQ; -.
DR PhylomeDB; O14807; -.
DR TreeFam; TF312796; -.
DR PathwayCommons; O14807; -.
DR Reactome; R-HSA-5673000; RAF activation.
DR Reactome; R-HSA-9726840; SHOC2 M1731 mutant abolishes MRAS complex function.
DR Reactome; R-HSA-9726842; Gain-of-function MRAS complexes activate RAF signaling.
DR SignaLink; O14807; -.
DR SIGNOR; O14807; -.
DR BioGRID-ORCS; 22808; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; MRAS; human.
DR GeneWiki; MRAS; -.
DR GenomeRNAi; 22808; -.
DR Pharos; O14807; Tbio.
DR PRO; PR:O14807; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; O14807; protein.
DR Bgee; ENSG00000158186; Expressed in lateral globus pallidus and 180 other tissues.
DR ExpressionAtlas; O14807; baseline and differential.
DR Genevisible; O14807; HS.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0030742; F:GTP-dependent protein binding; IPI:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IMP:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; TAS:ProtInc.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0007265; P:Ras protein signal transduction; IMP:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR020849; Small_GTPase_Ras-type.
DR PANTHER; PTHR24070; PTHR24070; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51421; RAS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disease variant; GTP-binding;
KW Hydrolase; Lipoprotein; Membrane; Methylation; Nucleotide-binding;
KW Prenylation; Reference proteome.
FT CHAIN 1..205
FT /note="Ras-related protein M-Ras"
FT /id="PRO_0000082654"
FT PROPEP 206..208
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000281304"
FT MOTIF 42..50
FT /note="Effector region"
FT BINDING 20..27
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 67..71
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 126..129
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 205
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 205
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..76
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_044792"
FT VARIANT 23
FT /note="G -> V (in NS11; constitutively active form;
FT increased GTPase activity)"
FT /evidence="ECO:0000269|PubMed:28289718"
FT /id="VAR_083112"
FT VARIANT 68
FT /note="T -> I (in NS11)"
FT /evidence="ECO:0000269|PubMed:28289718"
FT /id="VAR_083113"
FT VARIANT 71
FT /note="Q -> R (in NS11)"
FT /evidence="ECO:0000269|PubMed:31173466"
FT /id="VAR_083114"
SQ SEQUENCE 208 AA; 23846 MW; 0B2B55AFA96B3EC4 CRC64;
MATSAVPSDN LPTYKLVVVG DGGVGKSALT IQFFQKIFVP DYDPTIEDSY LKHTEIDNQW
AILDVLDTAG QEEFSAMREQ YMRTGDGFLI VYSVTDKASF EHVDRFHQLI LRVKDRESFP
MILVANKVDL MHLRKITREQ GKEMATKHNI PYIETSAKDP PLNVDKAFHD LVRVIRQQIP
EKSQKKKKKT KWRGDRATGT HKLQCVIL
