Full text data of RPSA
RPSA
(LAMBR, LAMR1)
[Confidence: low (only semi-automatic identification from reviews)]
40S ribosomal protein SA (37 kDa laminin receptor precursor; 37LRP; 37/67 kDa laminin receptor; LRP/LR; 67 kDa laminin receptor; 67LR; Colon carcinoma laminin-binding protein; Laminin receptor 1; LamR; Laminin-binding protein precursor p40; LBP/p40; Multidrug resistance-associated protein MGr1-Ag; NEM/1CHD4)
40S ribosomal protein SA (37 kDa laminin receptor precursor; 37LRP; 37/67 kDa laminin receptor; LRP/LR; 67 kDa laminin receptor; 67LR; Colon carcinoma laminin-binding protein; Laminin receptor 1; LamR; Laminin-binding protein precursor p40; LBP/p40; Multidrug resistance-associated protein MGr1-Ag; NEM/1CHD4)
UniProt
P08865
ID RSSA_HUMAN Reviewed; 295 AA.
AC P08865; P11085; P12030; Q16471; Q6IPD1; Q6IPD2; Q6NSD1; Q6NXQ8;
read moreAC Q86VC0;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 163.
DE RecName: Full=40S ribosomal protein SA;
DE AltName: Full=37 kDa laminin receptor precursor;
DE Short=37LRP;
DE AltName: Full=37/67 kDa laminin receptor;
DE Short=LRP/LR;
DE AltName: Full=67 kDa laminin receptor;
DE Short=67LR;
DE AltName: Full=Colon carcinoma laminin-binding protein;
DE AltName: Full=Laminin receptor 1;
DE Short=LamR;
DE AltName: Full=Laminin-binding protein precursor p40;
DE Short=LBP/p40;
DE AltName: Full=Multidrug resistance-associated protein MGr1-Ag;
DE AltName: Full=NEM/1CHD4;
GN Name=RPSA; Synonyms=LAMBR, LAMR1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2970639; DOI=10.1073/pnas.85.17.6394;
RA Yow H., Wong J.M., Chen H.S., Lee C., Steele G.D. Jr., Chen L.B.;
RT "Increased mRNA expression of a laminin-binding protein in human colon
RT carcinoma: complete sequence of a full-length cDNA encoding the
RT protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:6394-6398(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2543954; DOI=10.1093/nar/17.10.3829;
RA van den Ouweland A.M.W., van Duijnhoven H.L.P., Deichmann K.A.,
RA van Groningen J.J.M., de Leij L., van de Ven W.J.M.;
RT "Characteristics of a multicopy gene family predominantly consisting
RT of processed pseudogenes.";
RL Nucleic Acids Res. 17:3829-3843(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=1534510; DOI=10.1016/0304-3835(92)90096-E;
RA Satoh K., Narumi K., Sakai T., Abe T., Kikuchi T., Matsushima K.,
RA Sindoh S., Motomiya M.;
RT "Cloning of 67-kDa laminin receptor cDNA and gene expression in normal
RT and malignant cell lines of the human lung.";
RL Cancer Lett. 62:199-203(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8760291;
RA Jackers P., Minoletti F., Belotti D., Clausse N., Sozzi G.,
RA Sobel M.E., Castronovo V.;
RT "Isolation from a multigene family of the active human gene of the
RT metastasis-associated multifunctional protein 37LRP/p40 at chromosome
RT 3p21.3.";
RL Oncogene 13:495-503(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Shi Y., Zhai H., Wang X., Wu H., Ning X., Han Y., Zhang D., Xiao B.,
RA Wu K., Fan D.;
RT "Multidrug resistance associated protein MGr1-Ag is identical to human
RT 67-KDa laminin receptor precursor.";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TRP-117.
RC TISSUE=Bone marrow, Brain, Cervix, Hippocampus, Liver, Lung, Lymph,
RC Placenta, Prostate, Skin, and Urinary bladder;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-17, ACETYLATION AT SER-2, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V., Potts A., Barblan J., Quadroni M.;
RL Submitted (JUL-2004) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-295.
RA Siyanova E.Y., Lukashev V.A., Blinov V.M., Troyanovskii S.M.;
RT "Determination and analysis of the primary sequence of human laminin-
RT binding protein.";
RL Dokl. Biochem. 313:227-231(1990).
RN [10]
RP PROTEIN SEQUENCE OF 16-26 AND 90-99.
RX PubMed=8706699; DOI=10.1111/j.1432-1033.1996.0144u.x;
RA Vladimirov S.N., Ivanov A.V., Karpova G.G., Musolyamov A.K.,
RA Egorov T.A., Thiede B., Wittmann-Liebold B., Otto A.;
RT "Characterization of the human small-ribosomal-subunit proteins by N-
RT terminal and internal sequencing, and mass spectrometry.";
RL Eur. J. Biochem. 239:144-149(1996).
RN [11]
RP PROTEIN SEQUENCE OF 43-52; 64-80; 103-117; 129-155 AND 192-205, AND
RP MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 85-209.
RC TISSUE=Blood;
RX PubMed=8586453;
RA Selvamurugan N., Eliceiri G.L.;
RT "The gene for human E2 small nucleolar RNA resides in an intron of a
RT laminin-binding protein gene.";
RL Genomics 30:400-401(1995).
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 161-295, AND PROTEIN SEQUENCE OF
RP 177-184.
RX PubMed=2429301; DOI=10.1073/pnas.83.19.7137;
RA Wewer U.M., Liotta L.A., Jaye M., Ricca G.A., Drohan W.N.,
RA Claysmith A.P., Rao C.N., Wirth P., Coligan J.E., Albrechtsen R.,
RA Mudryj M., Sobel M.E.;
RT "Altered levels of laminin receptor mRNA in various human carcinoma
RT cells that have different abilities to bind laminin.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:7137-7141(1986).
RN [14]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 225-295.
RX PubMed=9582194;
RA Kenmochi N., Kawaguchi T., Rozen S., Davis E., Goodman N.,
RA Hudson T.J., Tanaka T., Page D.C.;
RT "A map of 75 human ribosomal protein genes.";
RL Genome Res. 8:509-523(1998).
RN [15]
RP FUNCTION, AND INTERACTION WITH LAMININ-1.
RX PubMed=6300843; DOI=10.1073/pnas.80.2.444;
RA Terranova V.P., Rao C.N., Kalebic T., Margulies I.M., Liotta L.A.;
RT "Laminin receptor on human breast carcinoma cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:444-448(1983).
RN [16]
RP DOMAINS, AND INTERACTION WITH LAMININ-1.
RX PubMed=1834645;
RA Castronovo V., Taraboletti G., Sobel M.E.;
RT "Functional domains of the 67-kDa laminin receptor precursor.";
RL J. Biol. Chem. 266:20440-20446(1991).
RN [17]
RP INTERACTION WITH LAMININ-1.
RX PubMed=8433567; DOI=10.1038/ki.1993.7;
RA Cioce V., Margulies I.M.K., Sobel M.E., Castronovo V.;
RT "Interaction between the 67 kilodalton metastasis-associated laminin
RT receptor and laminin.";
RL Kidney Int. 43:30-37(1993).
RN [18]
RP INTERACTION WITH PRNP.
RX PubMed=9396609; DOI=10.1038/nm1297-1383;
RA Rieger R., Edenhofer F., Lasmezas C.I., Weiss S.;
RT "The human 37-kDa laminin receptor precursor interacts with the prion
RT protein in eukaryotic cells.";
RL Nat. Med. 3:1383-1388(1997).
RN [19]
RP ACYLATION.
RX PubMed=9581863;
RX DOI=10.1002/(SICI)1097-4644(19980601)69:3<244::AID-JCB2>3.0.CO;2-R;
RA Buto S., Tagliabue E., Ardini E., Magnifico A., Ghirelli C.,
RA van den Brule F., Castronovo V., Colnaghi M.I., Sobel M.E., Menard S.;
RT "Formation of the 67-kDa laminin receptor by acylation of the
RT precursor.";
RL J. Cell. Biochem. 69:244-251(1998).
RN [20]
RP INTERACTION WITH LAMININ-5.
RX PubMed=9718729;
RA Ardini E., Pesole G., Tagliabue E., Magnifico A., Castronovo V.,
RA Sobel M.E., Colnaghi M.I., Menard S.;
RT "The 67-kDa laminin receptor originated from a ribosomal protein that
RT acquired a dual function during evolution.";
RL Mol. Biol. Evol. 15:1017-1025(1998).
RN [21]
RP INTERACTION WITH RPS21.
RX PubMed=10079194; DOI=10.1006/bbrc.1999.0343;
RA Sato M., Saeki Y., Tanaka K., Kaneda Y.;
RT "Ribosome-associated protein LBP/p40 binds to S21 protein of 40S
RT ribosome: analysis using a yeast two-hybrid system.";
RL Biochem. Biophys. Res. Commun. 256:385-390(1999).
RN [22]
RP INTERACTION WITH LAMB1.
RX PubMed=10772861; DOI=10.1006/jmbi.2000.3680;
RA Kazmin D.A., Hoyt T.R., Taubner L., Teintze M., Starkey J.R.;
RT "Phage display mapping for peptide 11 sensitive sequences binding to
RT laminin-1.";
RL J. Mol. Biol. 298:431-445(2000).
RN [23]
RP PRION-BINDING, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=11689427; DOI=10.1093/emboj/20.21.5863;
RA Gauczynski S., Peyrin J.-M., Haik S., Leucht C., Hundt C., Rieger R.,
RA Krasemann S., Deslys J.-P., Dormont D., Lasmezas C.I., Weiss S.;
RT "The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor
RT for the cellular prion protein.";
RL EMBO J. 20:5863-5875(2001).
RN [24]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND INTERACTION WITH
RP PPP1R16B AND PPP1CA.
RX PubMed=16263087; DOI=10.1016/j.bbrc.2005.10.089;
RA Kim K., Li L., Kozlowski K., Suh H.S., Cao W., Ballermann B.J.;
RT "The protein phosphatase-1 targeting subunit TIMAP regulates LAMR1
RT phosphorylation.";
RL Biochem. Biophys. Res. Commun. 338:1327-1334(2005).
RN [25]
RP FUNCTION AS A RECEPTOR FOR BACTERIA.
RX PubMed=15516338; DOI=10.1074/jbc.M410176200;
RA Kim K.J., Chung J.W., Kim K.S.;
RT "67-kDa laminin receptor promotes internalization of cytotoxic
RT necrotizing factor 1-expressing Escherichia coli K1 into human brain
RT microvascular endothelial cells.";
RL J. Biol. Chem. 280:1360-1368(2005).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 9-205.
RX PubMed=18063583; DOI=10.1074/jbc.C700206200;
RA Jamieson K.V., Wu J., Hubbard S.R., Meruelo D.;
RT "Crystal structure of the human laminin receptor precursor.";
RL J. Biol. Chem. 283:3002-3005(2008).
CC -!- FUNCTION: Required for the assembly and/or stability of the 40S
CC ribosomal subunit. Required for the processing of the 20S rRNA-
CC precursor to mature 18S rRNA in a late step of the maturation of
CC 40S ribosomal subunits. Also functions as a cell surface receptor
CC for laminin. Plays a role in cell adhesion to the basement
CC membrane and in the consequent activation of signaling
CC transduction pathways. May play a role in cell fate determination
CC and tissue morphogenesis. Acts as a PPP1R16B-dependent substrate
CC of PPP1CA. Also acts as a receptor for several other ligands,
CC including the pathogenic prion protein, viruses, and bacteria.
CC -!- SUBUNIT: Monomer (37LRP) and homodimer (67LR). Component of the
CC small ribosomal subunit. Mature ribosomes consist of a small (40S)
CC and a large (60S) subunit. The 40S subunit contains about 33
CC different proteins and 1 molecule of RNA (18S). The 60S subunit
CC contains about 49 different proteins and 3 molecules of RNA (28S,
CC 5.8S and 5S). Interacts with RPS21. Interacts with several
CC laminins including at least LAMB1. Interacts with MDK (By
CC similarity). Interacts with PRNP. The mature dimeric form
CC interacts with PPP1R16B (via its fourth ankyrin repeat). Interacts
CC with PPP1CA only in the presence of PPP1R16B.
CC -!- SUBCELLULAR LOCATION: Cell membrane. Cytoplasm. Nucleus (By
CC similarity). Note=67LR is found at the surface of the plasma
CC membrane, with its C-terminal laminin-binding domain accessible to
CC extracellular ligands. 37LRP is found at the cell surface, in the
CC cytoplasm and in the nucleus (By similarity). Colocalizes with
CC PPP1R16B in the cell membrane.
CC -!- PTM: Acylated. Acylation may be a prerequisite for conversion of
CC the monomeric 37 kDa laminin receptor precursor (37LRP) to the
CC mature dimeric 67 kDa laminin receptor (67LR), and may provide a
CC mechanism for membrane association.
CC -!- PTM: Cleaved by stromelysin-3 (ST3) at the cell surface. Cleavage
CC by stromelysin-3 may be a mechanism to alter cell-extracellular
CC matrix interactions (By similarity).
CC -!- MISCELLANEOUS: This protein appears to have acquired a second
CC function as a laminin receptor specifically in the vertebrate
CC lineage.
CC -!- MISCELLANEOUS: It is thought that in vertebrates 37/67 kDa laminin
CC receptor acquired a dual function during evolution. It developed
CC from the ribosomal protein SA, playing an essential role in the
CC protein biosynthesis lacking any laminin binding activity, to a
CC cell surface receptor with laminin binding activity.
CC -!- SIMILARITY: Belongs to the ribosomal protein S2P family.
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DR EMBL; J03799; AAA36161.1; -; mRNA.
DR EMBL; X15005; CAA33112.1; -; mRNA.
DR EMBL; S37431; AAB22299.1; -; mRNA.
DR EMBL; U43901; AAC50652.1; -; Genomic_DNA.
DR EMBL; AF503367; AAM33304.1; -; mRNA.
DR EMBL; BT007219; AAP35883.1; -; mRNA.
DR EMBL; BC005391; AAH05391.1; -; mRNA.
DR EMBL; BC008867; AAH08867.1; -; mRNA.
DR EMBL; BC010418; AAH10418.1; -; mRNA.
DR EMBL; BC013827; AAH13827.1; -; mRNA.
DR EMBL; BC034537; AAH34537.1; -; mRNA.
DR EMBL; BC050688; AAH50688.1; -; mRNA.
DR EMBL; BC053370; AAH53370.1; -; mRNA.
DR EMBL; BC062714; AAH62714.1; -; mRNA.
DR EMBL; BC066941; AAH66941.1; -; mRNA.
DR EMBL; BC068062; AAH68062.1; -; mRNA.
DR EMBL; BC070263; AAH70263.1; -; mRNA.
DR EMBL; BC071693; AAH71693.1; -; mRNA.
DR EMBL; BC071968; AAH71968.1; -; mRNA.
DR EMBL; BC071969; AAH71969.1; -; mRNA.
DR EMBL; BC071970; AAH71970.1; -; mRNA.
DR EMBL; BC073863; AAH73863.1; -; mRNA.
DR EMBL; BC107567; AAI07568.1; -; mRNA.
DR EMBL; X61156; CAA43469.1; -; mRNA.
DR EMBL; U36484; AAC50313.1; -; Genomic_DNA.
DR EMBL; M14199; AAA36165.1; -; mRNA.
DR EMBL; AB007146; BAA25812.1; -; Genomic_DNA.
DR PIR; A31233; A31233.
DR RefSeq; NP_001012321.1; NM_001012321.1.
DR RefSeq; NP_002286.2; NM_002295.4.
DR RefSeq; XP_005265185.1; XM_005265128.1.
DR RefSeq; XP_005265186.1; XM_005265129.1.
DR UniGene; Hs.449909; -.
DR PDB; 3BCH; X-ray; 2.15 A; A=2-220.
DR PDB; 3J3A; EM; 5.00 A; A=1-295.
DR PDBsum; 3BCH; -.
DR PDBsum; 3J3A; -.
DR ProteinModelPortal; P08865; -.
DR SMR; P08865; 9-205.
DR IntAct; P08865; 25.
DR MINT; MINT-1402850; -.
DR ChEMBL; CHEMBL6119; -.
DR PhosphoSite; P08865; -.
DR DMDM; 125969; -.
DR PaxDb; P08865; -.
DR PRIDE; P08865; -.
DR DNASU; 3921; -.
DR Ensembl; ENST00000301821; ENSP00000346067; ENSG00000168028.
DR Ensembl; ENST00000443003; ENSP00000389351; ENSG00000168028.
DR GeneID; 3921; -.
DR KEGG; hsa:3921; -.
DR UCSC; uc003cjp.3; human.
DR CTD; 3921; -.
DR GeneCards; GC03P039448; -.
DR HGNC; HGNC:6502; RPSA.
DR HPA; CAB009561; -.
DR MIM; 150370; gene.
DR neXtProt; NX_P08865; -.
DR Orphanet; 101351; Familial isolated congenital asplenia.
DR PharmGKB; PA30287; -.
DR eggNOG; COG0052; -.
DR HOVERGEN; HBG054466; -.
DR InParanoid; P08865; -.
DR KO; K02998; -.
DR OrthoDB; EOG73NG4F; -.
DR PhylomeDB; P08865; -.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_1762; 3' -UTR-mediated translational regulation.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; RPSA; human.
DR EvolutionaryTrace; P08865; -.
DR GeneWiki; Ribosomal_protein_SA; -.
DR GenomeRNAi; 3921; -.
DR NextBio; 15405; -.
DR PRO; PR:P08865; -.
DR ArrayExpress; P08865; -.
DR Bgee; P08865; -.
DR Genevestigator; P08865; -.
DR GO; GO:0030686; C:90S preribosome; IBA:RefGenome.
DR GO; GO:0022627; C:cytosolic small ribosomal subunit; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; TAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005055; F:laminin receptor activity; IEA:UniProtKB-HAMAP.
DR GO; GO:0043022; F:ribosome binding; IPI:UniProtKB.
DR GO; GO:0003735; F:structural constituent of ribosome; IBA:RefGenome.
DR GO; GO:0007155; P:cell adhesion; NAS:ProtInc.
DR GO; GO:0000447; P:endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); IBA:RefGenome.
DR GO; GO:0000461; P:endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA); IBA:RefGenome.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome.
DR GO; GO:0000028; P:ribosomal small subunit assembly; IBA:RefGenome.
DR GO; GO:0006407; P:rRNA export from nucleus; IBA:RefGenome.
DR GO; GO:0006614; P:SRP-dependent cotranslational protein targeting to membrane; TAS:Reactome.
DR GO; GO:0006414; P:translational elongation; TAS:Reactome.
DR GO; GO:0006413; P:translational initiation; TAS:Reactome.
DR GO; GO:0006415; P:translational termination; TAS:Reactome.
DR GO; GO:0019083; P:viral transcription; TAS:Reactome.
DR HAMAP; MF_03015; Ribosomal_S2_euk; 1; -.
DR HAMAP; MF_03016; Ribosomal_S2_laminin_receptor; 1; -.
DR InterPro; IPR027504; 40S_ribosomal_SA.
DR InterPro; IPR001865; Ribosomal_S2.
DR InterPro; IPR018130; Ribosomal_S2_CS.
DR InterPro; IPR027498; Ribosomal_S2_euk.
DR InterPro; IPR005707; Ribosomal_S2_euk/arc.
DR InterPro; IPR023591; Ribosomal_S2_flav_dom.
DR PANTHER; PTHR11489; PTHR11489; 1.
DR Pfam; PF00318; Ribosomal_S2; 1.
DR PRINTS; PR00395; RIBOSOMALS2.
DR SUPFAM; SSF52313; SSF52313; 1.
DR TIGRFAMs; TIGR01012; Sa_S2_E_A; 1.
DR PROSITE; PS00962; RIBOSOMAL_S2_1; 1.
DR PROSITE; PS00963; RIBOSOMAL_S2_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell membrane; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Membrane; Nucleus;
KW Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat;
KW Ribonucleoprotein; Ribosomal protein.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 295 40S ribosomal protein SA.
FT /FTId=PRO_0000134358.
FT REPEAT 230 232 [DE]-W-[ST] 1.
FT REPEAT 247 249 [DE]-W-[ST] 2.
FT REPEAT 266 268 [DE]-W-[ST] 3.
FT REPEAT 275 277 [DE]-W-[ST] 4.
FT REPEAT 293 295 [DE]-W-[ST] 5.
FT REGION 54 113 Interaction with PPP1R16B.
FT REGION 161 180 Laminin-binding.
FT REGION 205 229 Laminin-binding.
FT REGION 242 295 Laminin-binding.
FT SITE 115 116 Cleavage; by ST3; site 1 (By similarity).
FT SITE 133 134 Cleavage; by ST3; site 2 (By similarity).
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 52 52 N6-acetyllysine.
FT MOD_RES 139 139 Phosphotyrosine.
FT MOD_RES 241 241 Phosphothreonine.
FT VARIANT 117 117 R -> W (in dbSNP:rs17856150).
FT /FTId=VAR_025522.
FT CONFLICT 60 60 L -> V (in Ref. 9; CAA43469).
FT CONFLICT 84 84 Q -> QVCGTV (in Ref. 2; CAA33112).
FT CONFLICT 115 115 A -> T (in Ref. 7; AAH50688).
FT CONFLICT 135 135 T -> S (in Ref. 7; AAH70263).
FT CONFLICT 211 211 E -> G (in Ref. 3; AAB22299).
FT CONFLICT 214 214 E -> G (in Ref. 7; AAH66941).
FT CONFLICT 228 228 Q -> L (in Ref. 3; AAB22299).
FT HELIX 12 21
FT TURN 22 24
FT HELIX 32 37
FT STRAND 38 41
FT STRAND 47 49
FT HELIX 51 66
FT HELIX 71 73
FT STRAND 74 78
FT HELIX 81 94
FT STRAND 97 101
FT TURN 105 109
FT STRAND 120 125
FT TURN 127 130
FT HELIX 131 139
FT STRAND 144 148
FT STRAND 158 163
FT HELIX 168 185
FT STRAND 191 193
FT HELIX 199 202
SQ SEQUENCE 295 AA; 32854 MW; C68DDB16B759E79E CRC64;
MSGALDVLQM KEEDVLKFLA AGTHLGGTNL DFQMEQYIYK RKSDGIYIIN LKRTWEKLLL
AARAIVAIEN PADVSVISSR NTGQRAVLKF AAATGATPIA GRFTPGTFTN QIQAAFREPR
LLVVTDPRAD HQPLTEASYV NLPTIALCNT DSPLRYVDIA IPCNNKGAHS VGLMWWMLAR
EVLRMRGTIS REHPWEVMPD LYFYRDPEEI EKEEQAAAEK AVTKEEFQGE WTAPAPEFTA
TQPEVADWSE GVQVPSVPIQ QFPTEDWSAQ PATEDWSAAP TAQATEWVGA TTDWS
//
ID RSSA_HUMAN Reviewed; 295 AA.
AC P08865; P11085; P12030; Q16471; Q6IPD1; Q6IPD2; Q6NSD1; Q6NXQ8;
read moreAC Q86VC0;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 163.
DE RecName: Full=40S ribosomal protein SA;
DE AltName: Full=37 kDa laminin receptor precursor;
DE Short=37LRP;
DE AltName: Full=37/67 kDa laminin receptor;
DE Short=LRP/LR;
DE AltName: Full=67 kDa laminin receptor;
DE Short=67LR;
DE AltName: Full=Colon carcinoma laminin-binding protein;
DE AltName: Full=Laminin receptor 1;
DE Short=LamR;
DE AltName: Full=Laminin-binding protein precursor p40;
DE Short=LBP/p40;
DE AltName: Full=Multidrug resistance-associated protein MGr1-Ag;
DE AltName: Full=NEM/1CHD4;
GN Name=RPSA; Synonyms=LAMBR, LAMR1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2970639; DOI=10.1073/pnas.85.17.6394;
RA Yow H., Wong J.M., Chen H.S., Lee C., Steele G.D. Jr., Chen L.B.;
RT "Increased mRNA expression of a laminin-binding protein in human colon
RT carcinoma: complete sequence of a full-length cDNA encoding the
RT protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:6394-6398(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2543954; DOI=10.1093/nar/17.10.3829;
RA van den Ouweland A.M.W., van Duijnhoven H.L.P., Deichmann K.A.,
RA van Groningen J.J.M., de Leij L., van de Ven W.J.M.;
RT "Characteristics of a multicopy gene family predominantly consisting
RT of processed pseudogenes.";
RL Nucleic Acids Res. 17:3829-3843(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=1534510; DOI=10.1016/0304-3835(92)90096-E;
RA Satoh K., Narumi K., Sakai T., Abe T., Kikuchi T., Matsushima K.,
RA Sindoh S., Motomiya M.;
RT "Cloning of 67-kDa laminin receptor cDNA and gene expression in normal
RT and malignant cell lines of the human lung.";
RL Cancer Lett. 62:199-203(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8760291;
RA Jackers P., Minoletti F., Belotti D., Clausse N., Sozzi G.,
RA Sobel M.E., Castronovo V.;
RT "Isolation from a multigene family of the active human gene of the
RT metastasis-associated multifunctional protein 37LRP/p40 at chromosome
RT 3p21.3.";
RL Oncogene 13:495-503(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Shi Y., Zhai H., Wang X., Wu H., Ning X., Han Y., Zhang D., Xiao B.,
RA Wu K., Fan D.;
RT "Multidrug resistance associated protein MGr1-Ag is identical to human
RT 67-KDa laminin receptor precursor.";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TRP-117.
RC TISSUE=Bone marrow, Brain, Cervix, Hippocampus, Liver, Lung, Lymph,
RC Placenta, Prostate, Skin, and Urinary bladder;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-17, ACETYLATION AT SER-2, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V., Potts A., Barblan J., Quadroni M.;
RL Submitted (JUL-2004) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-295.
RA Siyanova E.Y., Lukashev V.A., Blinov V.M., Troyanovskii S.M.;
RT "Determination and analysis of the primary sequence of human laminin-
RT binding protein.";
RL Dokl. Biochem. 313:227-231(1990).
RN [10]
RP PROTEIN SEQUENCE OF 16-26 AND 90-99.
RX PubMed=8706699; DOI=10.1111/j.1432-1033.1996.0144u.x;
RA Vladimirov S.N., Ivanov A.V., Karpova G.G., Musolyamov A.K.,
RA Egorov T.A., Thiede B., Wittmann-Liebold B., Otto A.;
RT "Characterization of the human small-ribosomal-subunit proteins by N-
RT terminal and internal sequencing, and mass spectrometry.";
RL Eur. J. Biochem. 239:144-149(1996).
RN [11]
RP PROTEIN SEQUENCE OF 43-52; 64-80; 103-117; 129-155 AND 192-205, AND
RP MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 85-209.
RC TISSUE=Blood;
RX PubMed=8586453;
RA Selvamurugan N., Eliceiri G.L.;
RT "The gene for human E2 small nucleolar RNA resides in an intron of a
RT laminin-binding protein gene.";
RL Genomics 30:400-401(1995).
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 161-295, AND PROTEIN SEQUENCE OF
RP 177-184.
RX PubMed=2429301; DOI=10.1073/pnas.83.19.7137;
RA Wewer U.M., Liotta L.A., Jaye M., Ricca G.A., Drohan W.N.,
RA Claysmith A.P., Rao C.N., Wirth P., Coligan J.E., Albrechtsen R.,
RA Mudryj M., Sobel M.E.;
RT "Altered levels of laminin receptor mRNA in various human carcinoma
RT cells that have different abilities to bind laminin.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:7137-7141(1986).
RN [14]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 225-295.
RX PubMed=9582194;
RA Kenmochi N., Kawaguchi T., Rozen S., Davis E., Goodman N.,
RA Hudson T.J., Tanaka T., Page D.C.;
RT "A map of 75 human ribosomal protein genes.";
RL Genome Res. 8:509-523(1998).
RN [15]
RP FUNCTION, AND INTERACTION WITH LAMININ-1.
RX PubMed=6300843; DOI=10.1073/pnas.80.2.444;
RA Terranova V.P., Rao C.N., Kalebic T., Margulies I.M., Liotta L.A.;
RT "Laminin receptor on human breast carcinoma cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:444-448(1983).
RN [16]
RP DOMAINS, AND INTERACTION WITH LAMININ-1.
RX PubMed=1834645;
RA Castronovo V., Taraboletti G., Sobel M.E.;
RT "Functional domains of the 67-kDa laminin receptor precursor.";
RL J. Biol. Chem. 266:20440-20446(1991).
RN [17]
RP INTERACTION WITH LAMININ-1.
RX PubMed=8433567; DOI=10.1038/ki.1993.7;
RA Cioce V., Margulies I.M.K., Sobel M.E., Castronovo V.;
RT "Interaction between the 67 kilodalton metastasis-associated laminin
RT receptor and laminin.";
RL Kidney Int. 43:30-37(1993).
RN [18]
RP INTERACTION WITH PRNP.
RX PubMed=9396609; DOI=10.1038/nm1297-1383;
RA Rieger R., Edenhofer F., Lasmezas C.I., Weiss S.;
RT "The human 37-kDa laminin receptor precursor interacts with the prion
RT protein in eukaryotic cells.";
RL Nat. Med. 3:1383-1388(1997).
RN [19]
RP ACYLATION.
RX PubMed=9581863;
RX DOI=10.1002/(SICI)1097-4644(19980601)69:3<244::AID-JCB2>3.0.CO;2-R;
RA Buto S., Tagliabue E., Ardini E., Magnifico A., Ghirelli C.,
RA van den Brule F., Castronovo V., Colnaghi M.I., Sobel M.E., Menard S.;
RT "Formation of the 67-kDa laminin receptor by acylation of the
RT precursor.";
RL J. Cell. Biochem. 69:244-251(1998).
RN [20]
RP INTERACTION WITH LAMININ-5.
RX PubMed=9718729;
RA Ardini E., Pesole G., Tagliabue E., Magnifico A., Castronovo V.,
RA Sobel M.E., Colnaghi M.I., Menard S.;
RT "The 67-kDa laminin receptor originated from a ribosomal protein that
RT acquired a dual function during evolution.";
RL Mol. Biol. Evol. 15:1017-1025(1998).
RN [21]
RP INTERACTION WITH RPS21.
RX PubMed=10079194; DOI=10.1006/bbrc.1999.0343;
RA Sato M., Saeki Y., Tanaka K., Kaneda Y.;
RT "Ribosome-associated protein LBP/p40 binds to S21 protein of 40S
RT ribosome: analysis using a yeast two-hybrid system.";
RL Biochem. Biophys. Res. Commun. 256:385-390(1999).
RN [22]
RP INTERACTION WITH LAMB1.
RX PubMed=10772861; DOI=10.1006/jmbi.2000.3680;
RA Kazmin D.A., Hoyt T.R., Taubner L., Teintze M., Starkey J.R.;
RT "Phage display mapping for peptide 11 sensitive sequences binding to
RT laminin-1.";
RL J. Mol. Biol. 298:431-445(2000).
RN [23]
RP PRION-BINDING, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=11689427; DOI=10.1093/emboj/20.21.5863;
RA Gauczynski S., Peyrin J.-M., Haik S., Leucht C., Hundt C., Rieger R.,
RA Krasemann S., Deslys J.-P., Dormont D., Lasmezas C.I., Weiss S.;
RT "The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor
RT for the cellular prion protein.";
RL EMBO J. 20:5863-5875(2001).
RN [24]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND INTERACTION WITH
RP PPP1R16B AND PPP1CA.
RX PubMed=16263087; DOI=10.1016/j.bbrc.2005.10.089;
RA Kim K., Li L., Kozlowski K., Suh H.S., Cao W., Ballermann B.J.;
RT "The protein phosphatase-1 targeting subunit TIMAP regulates LAMR1
RT phosphorylation.";
RL Biochem. Biophys. Res. Commun. 338:1327-1334(2005).
RN [25]
RP FUNCTION AS A RECEPTOR FOR BACTERIA.
RX PubMed=15516338; DOI=10.1074/jbc.M410176200;
RA Kim K.J., Chung J.W., Kim K.S.;
RT "67-kDa laminin receptor promotes internalization of cytotoxic
RT necrotizing factor 1-expressing Escherichia coli K1 into human brain
RT microvascular endothelial cells.";
RL J. Biol. Chem. 280:1360-1368(2005).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 9-205.
RX PubMed=18063583; DOI=10.1074/jbc.C700206200;
RA Jamieson K.V., Wu J., Hubbard S.R., Meruelo D.;
RT "Crystal structure of the human laminin receptor precursor.";
RL J. Biol. Chem. 283:3002-3005(2008).
CC -!- FUNCTION: Required for the assembly and/or stability of the 40S
CC ribosomal subunit. Required for the processing of the 20S rRNA-
CC precursor to mature 18S rRNA in a late step of the maturation of
CC 40S ribosomal subunits. Also functions as a cell surface receptor
CC for laminin. Plays a role in cell adhesion to the basement
CC membrane and in the consequent activation of signaling
CC transduction pathways. May play a role in cell fate determination
CC and tissue morphogenesis. Acts as a PPP1R16B-dependent substrate
CC of PPP1CA. Also acts as a receptor for several other ligands,
CC including the pathogenic prion protein, viruses, and bacteria.
CC -!- SUBUNIT: Monomer (37LRP) and homodimer (67LR). Component of the
CC small ribosomal subunit. Mature ribosomes consist of a small (40S)
CC and a large (60S) subunit. The 40S subunit contains about 33
CC different proteins and 1 molecule of RNA (18S). The 60S subunit
CC contains about 49 different proteins and 3 molecules of RNA (28S,
CC 5.8S and 5S). Interacts with RPS21. Interacts with several
CC laminins including at least LAMB1. Interacts with MDK (By
CC similarity). Interacts with PRNP. The mature dimeric form
CC interacts with PPP1R16B (via its fourth ankyrin repeat). Interacts
CC with PPP1CA only in the presence of PPP1R16B.
CC -!- SUBCELLULAR LOCATION: Cell membrane. Cytoplasm. Nucleus (By
CC similarity). Note=67LR is found at the surface of the plasma
CC membrane, with its C-terminal laminin-binding domain accessible to
CC extracellular ligands. 37LRP is found at the cell surface, in the
CC cytoplasm and in the nucleus (By similarity). Colocalizes with
CC PPP1R16B in the cell membrane.
CC -!- PTM: Acylated. Acylation may be a prerequisite for conversion of
CC the monomeric 37 kDa laminin receptor precursor (37LRP) to the
CC mature dimeric 67 kDa laminin receptor (67LR), and may provide a
CC mechanism for membrane association.
CC -!- PTM: Cleaved by stromelysin-3 (ST3) at the cell surface. Cleavage
CC by stromelysin-3 may be a mechanism to alter cell-extracellular
CC matrix interactions (By similarity).
CC -!- MISCELLANEOUS: This protein appears to have acquired a second
CC function as a laminin receptor specifically in the vertebrate
CC lineage.
CC -!- MISCELLANEOUS: It is thought that in vertebrates 37/67 kDa laminin
CC receptor acquired a dual function during evolution. It developed
CC from the ribosomal protein SA, playing an essential role in the
CC protein biosynthesis lacking any laminin binding activity, to a
CC cell surface receptor with laminin binding activity.
CC -!- SIMILARITY: Belongs to the ribosomal protein S2P family.
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DR EMBL; J03799; AAA36161.1; -; mRNA.
DR EMBL; X15005; CAA33112.1; -; mRNA.
DR EMBL; S37431; AAB22299.1; -; mRNA.
DR EMBL; U43901; AAC50652.1; -; Genomic_DNA.
DR EMBL; AF503367; AAM33304.1; -; mRNA.
DR EMBL; BT007219; AAP35883.1; -; mRNA.
DR EMBL; BC005391; AAH05391.1; -; mRNA.
DR EMBL; BC008867; AAH08867.1; -; mRNA.
DR EMBL; BC010418; AAH10418.1; -; mRNA.
DR EMBL; BC013827; AAH13827.1; -; mRNA.
DR EMBL; BC034537; AAH34537.1; -; mRNA.
DR EMBL; BC050688; AAH50688.1; -; mRNA.
DR EMBL; BC053370; AAH53370.1; -; mRNA.
DR EMBL; BC062714; AAH62714.1; -; mRNA.
DR EMBL; BC066941; AAH66941.1; -; mRNA.
DR EMBL; BC068062; AAH68062.1; -; mRNA.
DR EMBL; BC070263; AAH70263.1; -; mRNA.
DR EMBL; BC071693; AAH71693.1; -; mRNA.
DR EMBL; BC071968; AAH71968.1; -; mRNA.
DR EMBL; BC071969; AAH71969.1; -; mRNA.
DR EMBL; BC071970; AAH71970.1; -; mRNA.
DR EMBL; BC073863; AAH73863.1; -; mRNA.
DR EMBL; BC107567; AAI07568.1; -; mRNA.
DR EMBL; X61156; CAA43469.1; -; mRNA.
DR EMBL; U36484; AAC50313.1; -; Genomic_DNA.
DR EMBL; M14199; AAA36165.1; -; mRNA.
DR EMBL; AB007146; BAA25812.1; -; Genomic_DNA.
DR PIR; A31233; A31233.
DR RefSeq; NP_001012321.1; NM_001012321.1.
DR RefSeq; NP_002286.2; NM_002295.4.
DR RefSeq; XP_005265185.1; XM_005265128.1.
DR RefSeq; XP_005265186.1; XM_005265129.1.
DR UniGene; Hs.449909; -.
DR PDB; 3BCH; X-ray; 2.15 A; A=2-220.
DR PDB; 3J3A; EM; 5.00 A; A=1-295.
DR PDBsum; 3BCH; -.
DR PDBsum; 3J3A; -.
DR ProteinModelPortal; P08865; -.
DR SMR; P08865; 9-205.
DR IntAct; P08865; 25.
DR MINT; MINT-1402850; -.
DR ChEMBL; CHEMBL6119; -.
DR PhosphoSite; P08865; -.
DR DMDM; 125969; -.
DR PaxDb; P08865; -.
DR PRIDE; P08865; -.
DR DNASU; 3921; -.
DR Ensembl; ENST00000301821; ENSP00000346067; ENSG00000168028.
DR Ensembl; ENST00000443003; ENSP00000389351; ENSG00000168028.
DR GeneID; 3921; -.
DR KEGG; hsa:3921; -.
DR UCSC; uc003cjp.3; human.
DR CTD; 3921; -.
DR GeneCards; GC03P039448; -.
DR HGNC; HGNC:6502; RPSA.
DR HPA; CAB009561; -.
DR MIM; 150370; gene.
DR neXtProt; NX_P08865; -.
DR Orphanet; 101351; Familial isolated congenital asplenia.
DR PharmGKB; PA30287; -.
DR eggNOG; COG0052; -.
DR HOVERGEN; HBG054466; -.
DR InParanoid; P08865; -.
DR KO; K02998; -.
DR OrthoDB; EOG73NG4F; -.
DR PhylomeDB; P08865; -.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_1762; 3' -UTR-mediated translational regulation.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; RPSA; human.
DR EvolutionaryTrace; P08865; -.
DR GeneWiki; Ribosomal_protein_SA; -.
DR GenomeRNAi; 3921; -.
DR NextBio; 15405; -.
DR PRO; PR:P08865; -.
DR ArrayExpress; P08865; -.
DR Bgee; P08865; -.
DR Genevestigator; P08865; -.
DR GO; GO:0030686; C:90S preribosome; IBA:RefGenome.
DR GO; GO:0022627; C:cytosolic small ribosomal subunit; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; TAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005055; F:laminin receptor activity; IEA:UniProtKB-HAMAP.
DR GO; GO:0043022; F:ribosome binding; IPI:UniProtKB.
DR GO; GO:0003735; F:structural constituent of ribosome; IBA:RefGenome.
DR GO; GO:0007155; P:cell adhesion; NAS:ProtInc.
DR GO; GO:0000447; P:endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); IBA:RefGenome.
DR GO; GO:0000461; P:endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA); IBA:RefGenome.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome.
DR GO; GO:0000028; P:ribosomal small subunit assembly; IBA:RefGenome.
DR GO; GO:0006407; P:rRNA export from nucleus; IBA:RefGenome.
DR GO; GO:0006614; P:SRP-dependent cotranslational protein targeting to membrane; TAS:Reactome.
DR GO; GO:0006414; P:translational elongation; TAS:Reactome.
DR GO; GO:0006413; P:translational initiation; TAS:Reactome.
DR GO; GO:0006415; P:translational termination; TAS:Reactome.
DR GO; GO:0019083; P:viral transcription; TAS:Reactome.
DR HAMAP; MF_03015; Ribosomal_S2_euk; 1; -.
DR HAMAP; MF_03016; Ribosomal_S2_laminin_receptor; 1; -.
DR InterPro; IPR027504; 40S_ribosomal_SA.
DR InterPro; IPR001865; Ribosomal_S2.
DR InterPro; IPR018130; Ribosomal_S2_CS.
DR InterPro; IPR027498; Ribosomal_S2_euk.
DR InterPro; IPR005707; Ribosomal_S2_euk/arc.
DR InterPro; IPR023591; Ribosomal_S2_flav_dom.
DR PANTHER; PTHR11489; PTHR11489; 1.
DR Pfam; PF00318; Ribosomal_S2; 1.
DR PRINTS; PR00395; RIBOSOMALS2.
DR SUPFAM; SSF52313; SSF52313; 1.
DR TIGRFAMs; TIGR01012; Sa_S2_E_A; 1.
DR PROSITE; PS00962; RIBOSOMAL_S2_1; 1.
DR PROSITE; PS00963; RIBOSOMAL_S2_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell membrane; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Membrane; Nucleus;
KW Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat;
KW Ribonucleoprotein; Ribosomal protein.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 295 40S ribosomal protein SA.
FT /FTId=PRO_0000134358.
FT REPEAT 230 232 [DE]-W-[ST] 1.
FT REPEAT 247 249 [DE]-W-[ST] 2.
FT REPEAT 266 268 [DE]-W-[ST] 3.
FT REPEAT 275 277 [DE]-W-[ST] 4.
FT REPEAT 293 295 [DE]-W-[ST] 5.
FT REGION 54 113 Interaction with PPP1R16B.
FT REGION 161 180 Laminin-binding.
FT REGION 205 229 Laminin-binding.
FT REGION 242 295 Laminin-binding.
FT SITE 115 116 Cleavage; by ST3; site 1 (By similarity).
FT SITE 133 134 Cleavage; by ST3; site 2 (By similarity).
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 52 52 N6-acetyllysine.
FT MOD_RES 139 139 Phosphotyrosine.
FT MOD_RES 241 241 Phosphothreonine.
FT VARIANT 117 117 R -> W (in dbSNP:rs17856150).
FT /FTId=VAR_025522.
FT CONFLICT 60 60 L -> V (in Ref. 9; CAA43469).
FT CONFLICT 84 84 Q -> QVCGTV (in Ref. 2; CAA33112).
FT CONFLICT 115 115 A -> T (in Ref. 7; AAH50688).
FT CONFLICT 135 135 T -> S (in Ref. 7; AAH70263).
FT CONFLICT 211 211 E -> G (in Ref. 3; AAB22299).
FT CONFLICT 214 214 E -> G (in Ref. 7; AAH66941).
FT CONFLICT 228 228 Q -> L (in Ref. 3; AAB22299).
FT HELIX 12 21
FT TURN 22 24
FT HELIX 32 37
FT STRAND 38 41
FT STRAND 47 49
FT HELIX 51 66
FT HELIX 71 73
FT STRAND 74 78
FT HELIX 81 94
FT STRAND 97 101
FT TURN 105 109
FT STRAND 120 125
FT TURN 127 130
FT HELIX 131 139
FT STRAND 144 148
FT STRAND 158 163
FT HELIX 168 185
FT STRAND 191 193
FT HELIX 199 202
SQ SEQUENCE 295 AA; 32854 MW; C68DDB16B759E79E CRC64;
MSGALDVLQM KEEDVLKFLA AGTHLGGTNL DFQMEQYIYK RKSDGIYIIN LKRTWEKLLL
AARAIVAIEN PADVSVISSR NTGQRAVLKF AAATGATPIA GRFTPGTFTN QIQAAFREPR
LLVVTDPRAD HQPLTEASYV NLPTIALCNT DSPLRYVDIA IPCNNKGAHS VGLMWWMLAR
EVLRMRGTIS REHPWEVMPD LYFYRDPEEI EKEEQAAAEK AVTKEEFQGE WTAPAPEFTA
TQPEVADWSE GVQVPSVPIQ QFPTEDWSAQ PATEDWSAAP TAQATEWVGA TTDWS
//
MIM
150370
*RECORD*
*FIELD* NO
150370
*FIELD* TI
*150370 RIBOSOMAL PROTEIN SA; RPSA
;;LAMININ RECEPTOR 1; LAMR1;;
LAMBR;;
LAMININ RECEPTOR, 67-KD; 67LR
read more*FIELD* TX
CLONING
Gehlsen et al. (1988) isolated a receptor for the adhesive basement
membrane protein laminin (150290, 150310, 150320) from human
glioblastoma cells by affinity chromatography on laminin. These RuGli
glioblastoma cells were later shown to be rat cells (Gehlsen et al.,
1988). This receptor has a heterodimeric structure similar to that of
receptors for other extracellular matrix proteins such as the
fibronectin (135620) and vitronectin (193210) receptors. Incorporation
of the laminin receptor into lysosomal membranes made it possible for
lysosomes to attach to surfaces coated with laminin.
Bignon et al. (1991) cloned 2 cDNAs for the human 67-kD laminin
receptor. They found that these clones hybridize to many restriction
fragments in Southern blot analyses in the human. The particular
patterns were accounted for by the presence of up to 16 and 21 copies of
the laminin receptor gene per haploid genome in human and mouse,
respectively. In contrast, a single gene copy was found in the chicken.
Yow et al. (1988) cloned a human colon carcinoma cDNA encoding a
laminin-binding protein. The cDNA hybridized to a 1.2-kb transcript, the
level of which was approximately 9-fold higher in colon carcinoma than
in adjacent normal colonic epithelium. The deduced 295-amino acid
protein has a highly negatively charged C-terminal segment and lacks
consensus sequences for an N-terminal signal sequence, amphipathic
alpha-helices, and N-glycosylation sites.
Satoh et al. (1992) cloned cDNAs encoding the 67-kD laminin receptor
from both a human lung cell line and a human lung cancer cell line. They
demonstrated that the level of the laminin receptor transcript was
higher in the lung cancer cell line than in the lung cell line.
Tohgo et al. (1994) found that the amino acid sequence of the rat 40S
ribosomal subunit is 99% identical to that of the human 68-kD
laminin-binding protein, indicating that the 40S ribosomal subunit is
identical to the 68-kD laminin-binding protein.
MAPPING
By fluorescence in situ hybridization, Jackers et al. (1996) localized
the LAMR1 gene to 3p21.3. Kenmochi et al. (1998) mapped the LAMR1 gene,
which they called RPSA, to 3p using somatic cell hybrid and radiation
hybrid mapping panels.
Bignon et al. (1991) identified laminin receptor pseudogenes on
chromosomes 3, 12, 14, and X. The features suggested that the laminin
receptor gene belongs to a retroposon family in mammals.
Lafreniere et al. (1993) demonstrated that a laminin receptor
pseudogene, which they symbolized LAMRP4, is located at Xq13 in a 2.6-Mb
segment that also contains the XIST gene (314670).
GENE STRUCTURE
The 37-kD precursor of the 67-kD laminin receptor (37LRP) is a
polypeptide whose expression is consistently upregulated in aggressive
carcinoma. It appears to be a multifunctional protein involved in the
translational machinery; it has also been identified as p40
ribosome-associated protein. Jackers et al. (1996) isolated the active
37LRP/p40 human gene. They found that it contains 7 exons and 6 introns.
Ribonuclease protection experiments suggested multiple transcription
start sites. The promoter area does not bear a TATA box but contains 4
Sp1 sites. The first intron is also GC-rich, containing 5 Sp1 sites.
Intron 4 contains a full sequence of the small nucleolar E2 RNA (RNE2;
180646) between nucleotides 4365 and 4516, and intron 3 contains 2 Alu
sequences.
GENE FUNCTION
Montuori et al. (1999) investigated the expression of integrin laminin
receptors in normal thyroid primary cultures; immortalized normal
thyroid cells (TAD-2); papillary (NPA), follicular (WRO), and anaplastic
(ARO) thyroid tumor cell lines; 7 thyroid tumors (4 papillary and 3
follicular carcinomas); and normal thyroid glands. Despite the presence
of several integrin laminin receptors, adhesion of TAD-2, NPA, and ARO
cells to immobilized laminin-1 was poor, whereas WRO cells and
follicular carcinoma-derived cells displayed a strong adhesion. Indeed,
WRO and follicular carcinoma-derived cells showed expression of a
nonintegrin laminin receptor, the 67-kD high-affinity laminin receptor
(67LR). TAD-2, NPA, and ARO cells as well as nodular goiter, toxic
adenoma, follicular adenoma, and papillary carcinoma-derived cells did
not express the 67LR. The expression in follicular carcinoma cells of a
functional, high-affinity 67LR, together with nonfunctional integrin
laminin receptors, could be responsible for the tendency of follicular
carcinoma cells to metastasize by mediating stable contacts with basal
membranes.
Chen et al. (2002) found that human normal and leukemic T cells produce
GNRH2 (602352) and GNRH1 (152760). Exposure of normal or cancerous human
or mouse T cells to GNRH2 or GNRH1 triggered de novo gene transcription
and cell-surface expression of the laminin receptor, which is involved
in cellular adhesion and migration and in tumor invasion and metastasis.
GNRH2 or GNRH1 also induced adhesion to laminin and chemotaxis toward
SDF1A (600835), and augmented entry in vivo of metastatic T-lymphoma
into the spleen and bone marrow. Homing of normal T cells into specific
organs was reduced in mice lacking GNRH1. A specific GNRH1 receptor
antagonist blocked GNRH1 but not GNRH2-induced effects, which was
suggestive of signaling through distinct receptors. Chen et al. (2002)
suggested that GNRH2 and GNRH1, secreted from nerves or autocrine or
paracrine sources, interact directly with T cells and trigger gene
transcription, adhesion, chemotaxis, and homing to specific organs.
MOLECULAR GENETICS
Bolze et al. (2013) demonstrated that heterozygous mutations in the RPSA
gene cause autosomal dominant isolated congenital asplenia (271400) by
haploinsufficiency, revealing an essential role for RPSA in human spleen
development. Bolze et al. (2013) identified a nonsense mutation, a
frameshift duplication, and 5 different missense mutations. These 7
mutations were not identified in more than 10,000 alleles reported in
the 1,000 Genomes Project or the NHLBI Exome Sequencing Project. The
missense mutations affected residues strictly conserved in mammals,
vertebrates, and yeast.
ANIMAL MODEL
Arrhythmogenic right ventricular dysplasia (ARVD; 107970) is a
hereditary cardiomyopathy that causes sudden death in the young. Asano
et al. (2004) found a line of mice with inherited right ventricular
dysplasia (RVD) caused by mutation of the gene laminin receptor-1
(Lamr1). This locus contained an intron-processing retroposon that was
transcribed in the mice with RVD. Introduction of a mutated Lamr1 gene
into normal mice by breeding or by direct injection caused
susceptibility to RVD, which was similar to that seen in the RVD mice.
An in vitro study of cardiomyocytes expressing the product of mutated
Lamr1 showed early cell death accompanied by alteration of the chromatin
architecture. They found that heterochromatin protein-1 (HP1; 604478)
bound specifically to mutant Lamr1. HP1 is a dynamic regulator of
heterochromatin sites, suggesting that mutant LAMR1 impairs a crucial
process of transcriptional regulation. Indeed, mutant Lamr1 caused
specific changes to gene expression in cardiomyocytes, as detected by
gene chip analysis. Asano et al. (2004) concluded that products of the
Lamr1 transposon interact with HP1 to cause degeneration of
cardiomyocytes. This mechanism may also contribute to the etiology of
human ARVD. They noted that the human LAMR1 gene maps to 3p21 and that a
form of ARVD, ARVD5 (604400), maps to 3p23.
*FIELD* AV
.0001
ASPLENIA, ISOLATED CONGENITAL
RPSA, GLN9TER
In affected members of a Caucasian family from the United States
(kindred E) with isolated congenital asplenia (271400), Bolze et al.
(2013) identified heterozygosity for a c.25C-T transition in the RPSA
gene that resulted in a nonsense mutation, gln9 to ter (Q9X). The
mutation segregated in the mother and son and was presumably present in
2 other sibs who had died of overwhelming infection.
.0002
ASPLENIA, ISOLATED CONGENITAL
RPSA, 5-BP DUP, 590TCATG
In a mother and 2 sons (kindred C) with isolated congenital asplenia
(271400), Bolze et al. (2013) identified heterozygosity for a 5-bp
duplication in exon 5 of the RPSA gene (c.590_594dup) that resulted in
frameshift and premature termination (Pro199SerfsTer25). Cloning and
analysis of protein generated from activated T cells from patients
showed that less than 10% of the transcripts carried the mutation, which
suggested that mutant mRNAs were subject to nonsense-mediated decay. The
mother was Caucasian and the father was of Tamil descent from Reunion
Island. This family had been reported by Mahlaoui et al. (2011) as
family D.
.0003
ASPLENIA, ISOLATED CONGENITAL
RPSA, ARG180GLY
In affected members of 2 families (kindreds D and A) with isolated
congenital asplenia (271400), Bolze et al. (2013) detected
heterozygosity for a c.538C-G transversion in the RPSA gene that
resulted in an arg180-to-gly substitution (R180G). Haplotype analysis
indicated that the mutation arose independently in each kindred. In
kindred A, affected individuals occurred in 3 generations.
.0004
ASPLENIA, ISOLATED CONGENITAL
RPSA, ARG180TRP
In a Caucasian individual from Sweden (kindred T) with isolated
congenital asplenia (271400), Bolze et al. (2013) identified
heterozygosity for a 538C-T transition in the RPSA gene that resulted in
an arg180-to-trp substitution (R180W). Since neither parent carried the
mutation and the patient had 3 unaffected sibs, the mutation was
presumed to have arisen de novo.
.0005
ASPLENIA, ISOLATED CONGENITAL
RPSA, ARG186CYS
In a family of Congolese origin (kindred B) with 3 affected members with
isolated congenital asplenia (271400), Bolze et al. (2013) identified a
heterozygous c.556C-T transition in the RPSA gene that resulted in an
arg186-to-cys substitution (R186C). This family had been reported by
Mahlaoui et al. (2011) as family E and had been reported by Koss et al.
(2012) as having a causative mutation in the NKX2-5 gene (600584.0024).
The RPSA mutation segregated with the disease in a father and 2 sons,
one deceased; 3 other deceased sibs were probably affected. Koss et al.
(2012) presented a case report of this family. Three children died of
fulminant infection within the first year of life; they were not further
studied. A fourth child died of sepsis at age 23 months. Postmortem
examination of this child showed asplenia with normal heart and visceral
placement, and mutation analysis identified the P236H mutation. The
fifth child and the father, who both carried the mutation, were found to
have ICAS; the child was placed on prophylaxis, whereas the father did
not have a history of infections, suggesting incomplete penetrance.
Studies in mouse embryos and cellular studies of splenic mesenchymal
cells demonstrated a pivotal role for the NKX2-5 gene in spleen
development.
.0006
ASPLENIA, ISOLATED CONGENITAL
RPSA, THR54ASN
In 2 affected children with isolated congenital asplenia (271400) from a
Caucasian French family (kindred F), Bolze et al. (2013) identified
heterozygosity for a c.161C-A transversion in the RPSA gene that
resulted in a thr54-to-asn substitution (T54N). Since neither parent was
found to carry the mutation, inheritance was attributed to germline
mosaicism. This family had been reported by Mahlaoui et al. (2011) as
family B, and by Ferlicot et al. (1997).
.0007
ASPLENIA, ISOLATED CONGENITAL
RPSA, LEU58PHE
In an individual of French descent (kindred O) with isolated congenital
asplenia (271400), Bolze et al. (2013) identified heterozygosity for a
c.172C-T transition in the RPSA gene that resulted in a leu58-to-phe
substitution (L58F). The mutation apparently arose de novo.
*FIELD* RF
1. Asano, Y.; Takashima, S.; Asakura, M.; Shintani, Y.; Liao, Y.;
Minamino, T.; Asanuma, H.; Sanada, S.; Kim, J.; Ogai, A.; Fukushima,
T.; Oikawa, Y.; Okazaki, Y.; Kaneda, Y.; Sato, M.; Miyazaki, J.; Kitamura,
S.; Tomoike, H.; Kitakaze, M.; Hori, M.: Lamr1 functional retroposon
causes right ventricular dysplasia in mice. Nature Genet. 36: 123-130,
2004.
2. Bignon, C.; Roux-Dosseto, M.; Zeigler, M. E.; Mattei, M.-G.; Lissitzky,
J.-C.; Wicha, M. S.; Martin, P.-M.: Genomic analysis of the 67-kDa
laminin receptor in normal and pathological tissues: circumstantial
evidence for retroposon features. Genomics 10: 481-485, 1991.
3. Bolze, A.; Mahlaoui, N.; Byun, M.; Turner, B.; Trede, N.; Ellis,
S. R.; Abhyankar, A.; Itan, Y.; Patin, E.; Brebner, S.; Sackstein,
P.; Puel, A.; and 20 others: Ribosomal protein SA haploinsufficiency
in humans with isolated congenital asplenia. Science 340: 976-978,
2013.
4. Chen, A.; Ganor, Y.; Rahimipour, S.; Ben-Aroya, N.; Koch, Y.; Levite,
M.: The neuropeptides GnRH-II and GnRH-I are produced by human T
cells and trigger laminin receptor gene expression, adhesion, chemotaxis
and homing to specific organs. Nature Med. 8: 1421-1426, 2002.
5. Ferlicot, S.; Emile, J.-F.; Le Bris, J.-L.; Cheron, G.; Brousse,
N.: L'asplenie congenitale: un deficit immunitaire de l'enfant de
decouverte souvent trop tardive. Ann. Path. 17: 44-46, 1997.
6. Gehlsen, K. R.; Dillner, L.; Engvall, E.; Ruoslahti, E.: The human
laminin receptor is a member of the integrin family of cell adhesion
receptors. Science 241: 1228-1229, 1988. Note: Erratum: Science
245:342-343, 1989.
7. Jackers, P.; Minoletti, F.; Belotti, D.; Clausse, N.; Sozzi, G.;
Sobel, M. E.; Castronovo, V.: Isolation from a multigene family of
the active human gene of the metastasis-associated multifunctional
protein 37LRP/p40 at chromosome 3p21.3. Oncogene 13: 495-503, 1996.
Note: Erratum: Oncogene 14: 627 only, 1997.
8. Kenmochi, N.; Kawaguchi, T.; Rozen, S.; Davis, E.; Goodman, N.;
Hudson, T. J.; Tanaka, T.; Page, D. C.: A map of 75 human ribosomal
protein genes. Genome Res. 8: 509-523, 1998.
9. Koss, M.; Bolze, A.; Brendolan, A.; Saggese, M.; Capellini, T.
D.; Bojilova, E.; Boisson, B.; Prall, O. W. J.; Elliott, D. A.; Solloway,
M.; Lenti, E.; Hidaka, C.; Chang, C.-P.; Mahlaoui, N.; Harvey, R.
P.; Casanova, J.-L.; Selleri, L.: Congenital asplenia in mice and
humans with mutations in a Pbx/Nkx2-5/p15 module. Dev. Cell 22:
913-926, 2012.
10. Lafreniere, R. G.; Brown, C. J.; Rider, S.; Chelly, J.; Taillon-Miller,
P.; Chinault, A. C.; Monaco, A. P.; Willard, H. F.: 2.6 Mb YAC contig
of the human X inactivation center region in Xq13: physical linkage
of the RPS4X, PHKA1, XIST and DXS128E genes. Hum. Molec. Genet. 2:
1105-1115, 1993.
11. Mahlaoui, N.; Minard-Colin, V.; Picard, C.; Bolze, A.; Ku, C.-L.;
Tournilhac, O.; Gilbert-Dussardier, B.; Pautard, B.; Durand, P.; Devictor,
D.; Lachassinne, E.; Guillois, B.; Morin, M.; Gouraud, F.; Valensi,
F.; Fischer, A.; Puel, A.; Abel, L.; Bonnet, D.; Casanova, J.-L.:
Isolated congenital asplenia: a French nationwide retrospective survey
of 20 cases. J. Pediat. 158: 142-148, 2011.
12. Montuori, N.; Muller, F.; De Riu, S.; Fenzi, G.; Sobel, M. E.;
Rossi, G.; Vitale, M.: Laminin receptors in differentiated thyroid
tumors: restricted expression of the 67-kilodalton laminin receptor
in follicular carcinoma cells. J. Clin. Endocr. Metab. 84: 2086-2092,
1999.
13. Satoh, K.; Narumi, K.; Sakai, T.; Abe, T.; Kikuchi, T.; Matsushima,
K.; Sindoh, S.; Motomiya, M.: Cloning of 67-kDa laminin receptor
cDNA and gene expression in normal and malignant cell lines of the
human lung. Cancer Lett. 62: 199-203, 1992.
14. Tohgo, A.; Takasawa, S.; Munakata, H.; Yonekura, H.; Hayashi,
N.; Okamoto, H.: Structural determination and characterization of
a 40 kDa protein isolated from rat 40 S ribosomal subunit. FEBS Lett. 340:
133-138, 1994.
15. Yow, H. K.; Wong, J. M.; Chen, H. S.; Lee, C. G.; Davis, S.; Steele,
G. D., Jr.; Chen, L. B.: Increased mRNA expression of a laminin-binding
protein in human colon carcinoma: complete sequence of a full-length
cDNA encoding the protein. Proc. Nat. Acad. Sci. 85: 6394-6398,
1988. Note: Erratum: Proc. Nat. Acad. Sci. 86: 7032 only, 1989.
*FIELD* CN
Ada Hamosh - updated: 9/11/2013
Victor A. McKusick - updated: 1/23/2004
Ada Hamosh - updated: 2/13/2003
Alan F. Scott - updated: 4/30/2002
John A. Phillips, III - updated: 3/20/2000
Patti M. Sherman - updated: 3/10/1999
Victor A. McKusick - updated: 3/27/1998
*FIELD* CD
Victor A. McKusick: 9/14/1988
*FIELD* ED
alopez: 10/08/2013
alopez: 9/11/2013
terry: 11/13/2012
wwang: 7/23/2008
alopez: 2/17/2004
alopez: 1/23/2004
terry: 1/23/2004
alopez: 2/19/2003
terry: 2/13/2003
joanna: 4/30/2002
mgross: 4/4/2000
terry: 3/20/2000
carol: 3/23/1999
psherman: 3/27/1998
dholmes: 3/6/1998
mark: 6/13/1995
carol: 9/20/1993
supermim: 3/16/1992
carol: 6/24/1991
supermim: 3/20/1990
ddp: 10/27/1989
*RECORD*
*FIELD* NO
150370
*FIELD* TI
*150370 RIBOSOMAL PROTEIN SA; RPSA
;;LAMININ RECEPTOR 1; LAMR1;;
LAMBR;;
LAMININ RECEPTOR, 67-KD; 67LR
read more*FIELD* TX
CLONING
Gehlsen et al. (1988) isolated a receptor for the adhesive basement
membrane protein laminin (150290, 150310, 150320) from human
glioblastoma cells by affinity chromatography on laminin. These RuGli
glioblastoma cells were later shown to be rat cells (Gehlsen et al.,
1988). This receptor has a heterodimeric structure similar to that of
receptors for other extracellular matrix proteins such as the
fibronectin (135620) and vitronectin (193210) receptors. Incorporation
of the laminin receptor into lysosomal membranes made it possible for
lysosomes to attach to surfaces coated with laminin.
Bignon et al. (1991) cloned 2 cDNAs for the human 67-kD laminin
receptor. They found that these clones hybridize to many restriction
fragments in Southern blot analyses in the human. The particular
patterns were accounted for by the presence of up to 16 and 21 copies of
the laminin receptor gene per haploid genome in human and mouse,
respectively. In contrast, a single gene copy was found in the chicken.
Yow et al. (1988) cloned a human colon carcinoma cDNA encoding a
laminin-binding protein. The cDNA hybridized to a 1.2-kb transcript, the
level of which was approximately 9-fold higher in colon carcinoma than
in adjacent normal colonic epithelium. The deduced 295-amino acid
protein has a highly negatively charged C-terminal segment and lacks
consensus sequences for an N-terminal signal sequence, amphipathic
alpha-helices, and N-glycosylation sites.
Satoh et al. (1992) cloned cDNAs encoding the 67-kD laminin receptor
from both a human lung cell line and a human lung cancer cell line. They
demonstrated that the level of the laminin receptor transcript was
higher in the lung cancer cell line than in the lung cell line.
Tohgo et al. (1994) found that the amino acid sequence of the rat 40S
ribosomal subunit is 99% identical to that of the human 68-kD
laminin-binding protein, indicating that the 40S ribosomal subunit is
identical to the 68-kD laminin-binding protein.
MAPPING
By fluorescence in situ hybridization, Jackers et al. (1996) localized
the LAMR1 gene to 3p21.3. Kenmochi et al. (1998) mapped the LAMR1 gene,
which they called RPSA, to 3p using somatic cell hybrid and radiation
hybrid mapping panels.
Bignon et al. (1991) identified laminin receptor pseudogenes on
chromosomes 3, 12, 14, and X. The features suggested that the laminin
receptor gene belongs to a retroposon family in mammals.
Lafreniere et al. (1993) demonstrated that a laminin receptor
pseudogene, which they symbolized LAMRP4, is located at Xq13 in a 2.6-Mb
segment that also contains the XIST gene (314670).
GENE STRUCTURE
The 37-kD precursor of the 67-kD laminin receptor (37LRP) is a
polypeptide whose expression is consistently upregulated in aggressive
carcinoma. It appears to be a multifunctional protein involved in the
translational machinery; it has also been identified as p40
ribosome-associated protein. Jackers et al. (1996) isolated the active
37LRP/p40 human gene. They found that it contains 7 exons and 6 introns.
Ribonuclease protection experiments suggested multiple transcription
start sites. The promoter area does not bear a TATA box but contains 4
Sp1 sites. The first intron is also GC-rich, containing 5 Sp1 sites.
Intron 4 contains a full sequence of the small nucleolar E2 RNA (RNE2;
180646) between nucleotides 4365 and 4516, and intron 3 contains 2 Alu
sequences.
GENE FUNCTION
Montuori et al. (1999) investigated the expression of integrin laminin
receptors in normal thyroid primary cultures; immortalized normal
thyroid cells (TAD-2); papillary (NPA), follicular (WRO), and anaplastic
(ARO) thyroid tumor cell lines; 7 thyroid tumors (4 papillary and 3
follicular carcinomas); and normal thyroid glands. Despite the presence
of several integrin laminin receptors, adhesion of TAD-2, NPA, and ARO
cells to immobilized laminin-1 was poor, whereas WRO cells and
follicular carcinoma-derived cells displayed a strong adhesion. Indeed,
WRO and follicular carcinoma-derived cells showed expression of a
nonintegrin laminin receptor, the 67-kD high-affinity laminin receptor
(67LR). TAD-2, NPA, and ARO cells as well as nodular goiter, toxic
adenoma, follicular adenoma, and papillary carcinoma-derived cells did
not express the 67LR. The expression in follicular carcinoma cells of a
functional, high-affinity 67LR, together with nonfunctional integrin
laminin receptors, could be responsible for the tendency of follicular
carcinoma cells to metastasize by mediating stable contacts with basal
membranes.
Chen et al. (2002) found that human normal and leukemic T cells produce
GNRH2 (602352) and GNRH1 (152760). Exposure of normal or cancerous human
or mouse T cells to GNRH2 or GNRH1 triggered de novo gene transcription
and cell-surface expression of the laminin receptor, which is involved
in cellular adhesion and migration and in tumor invasion and metastasis.
GNRH2 or GNRH1 also induced adhesion to laminin and chemotaxis toward
SDF1A (600835), and augmented entry in vivo of metastatic T-lymphoma
into the spleen and bone marrow. Homing of normal T cells into specific
organs was reduced in mice lacking GNRH1. A specific GNRH1 receptor
antagonist blocked GNRH1 but not GNRH2-induced effects, which was
suggestive of signaling through distinct receptors. Chen et al. (2002)
suggested that GNRH2 and GNRH1, secreted from nerves or autocrine or
paracrine sources, interact directly with T cells and trigger gene
transcription, adhesion, chemotaxis, and homing to specific organs.
MOLECULAR GENETICS
Bolze et al. (2013) demonstrated that heterozygous mutations in the RPSA
gene cause autosomal dominant isolated congenital asplenia (271400) by
haploinsufficiency, revealing an essential role for RPSA in human spleen
development. Bolze et al. (2013) identified a nonsense mutation, a
frameshift duplication, and 5 different missense mutations. These 7
mutations were not identified in more than 10,000 alleles reported in
the 1,000 Genomes Project or the NHLBI Exome Sequencing Project. The
missense mutations affected residues strictly conserved in mammals,
vertebrates, and yeast.
ANIMAL MODEL
Arrhythmogenic right ventricular dysplasia (ARVD; 107970) is a
hereditary cardiomyopathy that causes sudden death in the young. Asano
et al. (2004) found a line of mice with inherited right ventricular
dysplasia (RVD) caused by mutation of the gene laminin receptor-1
(Lamr1). This locus contained an intron-processing retroposon that was
transcribed in the mice with RVD. Introduction of a mutated Lamr1 gene
into normal mice by breeding or by direct injection caused
susceptibility to RVD, which was similar to that seen in the RVD mice.
An in vitro study of cardiomyocytes expressing the product of mutated
Lamr1 showed early cell death accompanied by alteration of the chromatin
architecture. They found that heterochromatin protein-1 (HP1; 604478)
bound specifically to mutant Lamr1. HP1 is a dynamic regulator of
heterochromatin sites, suggesting that mutant LAMR1 impairs a crucial
process of transcriptional regulation. Indeed, mutant Lamr1 caused
specific changes to gene expression in cardiomyocytes, as detected by
gene chip analysis. Asano et al. (2004) concluded that products of the
Lamr1 transposon interact with HP1 to cause degeneration of
cardiomyocytes. This mechanism may also contribute to the etiology of
human ARVD. They noted that the human LAMR1 gene maps to 3p21 and that a
form of ARVD, ARVD5 (604400), maps to 3p23.
*FIELD* AV
.0001
ASPLENIA, ISOLATED CONGENITAL
RPSA, GLN9TER
In affected members of a Caucasian family from the United States
(kindred E) with isolated congenital asplenia (271400), Bolze et al.
(2013) identified heterozygosity for a c.25C-T transition in the RPSA
gene that resulted in a nonsense mutation, gln9 to ter (Q9X). The
mutation segregated in the mother and son and was presumably present in
2 other sibs who had died of overwhelming infection.
.0002
ASPLENIA, ISOLATED CONGENITAL
RPSA, 5-BP DUP, 590TCATG
In a mother and 2 sons (kindred C) with isolated congenital asplenia
(271400), Bolze et al. (2013) identified heterozygosity for a 5-bp
duplication in exon 5 of the RPSA gene (c.590_594dup) that resulted in
frameshift and premature termination (Pro199SerfsTer25). Cloning and
analysis of protein generated from activated T cells from patients
showed that less than 10% of the transcripts carried the mutation, which
suggested that mutant mRNAs were subject to nonsense-mediated decay. The
mother was Caucasian and the father was of Tamil descent from Reunion
Island. This family had been reported by Mahlaoui et al. (2011) as
family D.
.0003
ASPLENIA, ISOLATED CONGENITAL
RPSA, ARG180GLY
In affected members of 2 families (kindreds D and A) with isolated
congenital asplenia (271400), Bolze et al. (2013) detected
heterozygosity for a c.538C-G transversion in the RPSA gene that
resulted in an arg180-to-gly substitution (R180G). Haplotype analysis
indicated that the mutation arose independently in each kindred. In
kindred A, affected individuals occurred in 3 generations.
.0004
ASPLENIA, ISOLATED CONGENITAL
RPSA, ARG180TRP
In a Caucasian individual from Sweden (kindred T) with isolated
congenital asplenia (271400), Bolze et al. (2013) identified
heterozygosity for a 538C-T transition in the RPSA gene that resulted in
an arg180-to-trp substitution (R180W). Since neither parent carried the
mutation and the patient had 3 unaffected sibs, the mutation was
presumed to have arisen de novo.
.0005
ASPLENIA, ISOLATED CONGENITAL
RPSA, ARG186CYS
In a family of Congolese origin (kindred B) with 3 affected members with
isolated congenital asplenia (271400), Bolze et al. (2013) identified a
heterozygous c.556C-T transition in the RPSA gene that resulted in an
arg186-to-cys substitution (R186C). This family had been reported by
Mahlaoui et al. (2011) as family E and had been reported by Koss et al.
(2012) as having a causative mutation in the NKX2-5 gene (600584.0024).
The RPSA mutation segregated with the disease in a father and 2 sons,
one deceased; 3 other deceased sibs were probably affected. Koss et al.
(2012) presented a case report of this family. Three children died of
fulminant infection within the first year of life; they were not further
studied. A fourth child died of sepsis at age 23 months. Postmortem
examination of this child showed asplenia with normal heart and visceral
placement, and mutation analysis identified the P236H mutation. The
fifth child and the father, who both carried the mutation, were found to
have ICAS; the child was placed on prophylaxis, whereas the father did
not have a history of infections, suggesting incomplete penetrance.
Studies in mouse embryos and cellular studies of splenic mesenchymal
cells demonstrated a pivotal role for the NKX2-5 gene in spleen
development.
.0006
ASPLENIA, ISOLATED CONGENITAL
RPSA, THR54ASN
In 2 affected children with isolated congenital asplenia (271400) from a
Caucasian French family (kindred F), Bolze et al. (2013) identified
heterozygosity for a c.161C-A transversion in the RPSA gene that
resulted in a thr54-to-asn substitution (T54N). Since neither parent was
found to carry the mutation, inheritance was attributed to germline
mosaicism. This family had been reported by Mahlaoui et al. (2011) as
family B, and by Ferlicot et al. (1997).
.0007
ASPLENIA, ISOLATED CONGENITAL
RPSA, LEU58PHE
In an individual of French descent (kindred O) with isolated congenital
asplenia (271400), Bolze et al. (2013) identified heterozygosity for a
c.172C-T transition in the RPSA gene that resulted in a leu58-to-phe
substitution (L58F). The mutation apparently arose de novo.
*FIELD* RF
1. Asano, Y.; Takashima, S.; Asakura, M.; Shintani, Y.; Liao, Y.;
Minamino, T.; Asanuma, H.; Sanada, S.; Kim, J.; Ogai, A.; Fukushima,
T.; Oikawa, Y.; Okazaki, Y.; Kaneda, Y.; Sato, M.; Miyazaki, J.; Kitamura,
S.; Tomoike, H.; Kitakaze, M.; Hori, M.: Lamr1 functional retroposon
causes right ventricular dysplasia in mice. Nature Genet. 36: 123-130,
2004.
2. Bignon, C.; Roux-Dosseto, M.; Zeigler, M. E.; Mattei, M.-G.; Lissitzky,
J.-C.; Wicha, M. S.; Martin, P.-M.: Genomic analysis of the 67-kDa
laminin receptor in normal and pathological tissues: circumstantial
evidence for retroposon features. Genomics 10: 481-485, 1991.
3. Bolze, A.; Mahlaoui, N.; Byun, M.; Turner, B.; Trede, N.; Ellis,
S. R.; Abhyankar, A.; Itan, Y.; Patin, E.; Brebner, S.; Sackstein,
P.; Puel, A.; and 20 others: Ribosomal protein SA haploinsufficiency
in humans with isolated congenital asplenia. Science 340: 976-978,
2013.
4. Chen, A.; Ganor, Y.; Rahimipour, S.; Ben-Aroya, N.; Koch, Y.; Levite,
M.: The neuropeptides GnRH-II and GnRH-I are produced by human T
cells and trigger laminin receptor gene expression, adhesion, chemotaxis
and homing to specific organs. Nature Med. 8: 1421-1426, 2002.
5. Ferlicot, S.; Emile, J.-F.; Le Bris, J.-L.; Cheron, G.; Brousse,
N.: L'asplenie congenitale: un deficit immunitaire de l'enfant de
decouverte souvent trop tardive. Ann. Path. 17: 44-46, 1997.
6. Gehlsen, K. R.; Dillner, L.; Engvall, E.; Ruoslahti, E.: The human
laminin receptor is a member of the integrin family of cell adhesion
receptors. Science 241: 1228-1229, 1988. Note: Erratum: Science
245:342-343, 1989.
7. Jackers, P.; Minoletti, F.; Belotti, D.; Clausse, N.; Sozzi, G.;
Sobel, M. E.; Castronovo, V.: Isolation from a multigene family of
the active human gene of the metastasis-associated multifunctional
protein 37LRP/p40 at chromosome 3p21.3. Oncogene 13: 495-503, 1996.
Note: Erratum: Oncogene 14: 627 only, 1997.
8. Kenmochi, N.; Kawaguchi, T.; Rozen, S.; Davis, E.; Goodman, N.;
Hudson, T. J.; Tanaka, T.; Page, D. C.: A map of 75 human ribosomal
protein genes. Genome Res. 8: 509-523, 1998.
9. Koss, M.; Bolze, A.; Brendolan, A.; Saggese, M.; Capellini, T.
D.; Bojilova, E.; Boisson, B.; Prall, O. W. J.; Elliott, D. A.; Solloway,
M.; Lenti, E.; Hidaka, C.; Chang, C.-P.; Mahlaoui, N.; Harvey, R.
P.; Casanova, J.-L.; Selleri, L.: Congenital asplenia in mice and
humans with mutations in a Pbx/Nkx2-5/p15 module. Dev. Cell 22:
913-926, 2012.
10. Lafreniere, R. G.; Brown, C. J.; Rider, S.; Chelly, J.; Taillon-Miller,
P.; Chinault, A. C.; Monaco, A. P.; Willard, H. F.: 2.6 Mb YAC contig
of the human X inactivation center region in Xq13: physical linkage
of the RPS4X, PHKA1, XIST and DXS128E genes. Hum. Molec. Genet. 2:
1105-1115, 1993.
11. Mahlaoui, N.; Minard-Colin, V.; Picard, C.; Bolze, A.; Ku, C.-L.;
Tournilhac, O.; Gilbert-Dussardier, B.; Pautard, B.; Durand, P.; Devictor,
D.; Lachassinne, E.; Guillois, B.; Morin, M.; Gouraud, F.; Valensi,
F.; Fischer, A.; Puel, A.; Abel, L.; Bonnet, D.; Casanova, J.-L.:
Isolated congenital asplenia: a French nationwide retrospective survey
of 20 cases. J. Pediat. 158: 142-148, 2011.
12. Montuori, N.; Muller, F.; De Riu, S.; Fenzi, G.; Sobel, M. E.;
Rossi, G.; Vitale, M.: Laminin receptors in differentiated thyroid
tumors: restricted expression of the 67-kilodalton laminin receptor
in follicular carcinoma cells. J. Clin. Endocr. Metab. 84: 2086-2092,
1999.
13. Satoh, K.; Narumi, K.; Sakai, T.; Abe, T.; Kikuchi, T.; Matsushima,
K.; Sindoh, S.; Motomiya, M.: Cloning of 67-kDa laminin receptor
cDNA and gene expression in normal and malignant cell lines of the
human lung. Cancer Lett. 62: 199-203, 1992.
14. Tohgo, A.; Takasawa, S.; Munakata, H.; Yonekura, H.; Hayashi,
N.; Okamoto, H.: Structural determination and characterization of
a 40 kDa protein isolated from rat 40 S ribosomal subunit. FEBS Lett. 340:
133-138, 1994.
15. Yow, H. K.; Wong, J. M.; Chen, H. S.; Lee, C. G.; Davis, S.; Steele,
G. D., Jr.; Chen, L. B.: Increased mRNA expression of a laminin-binding
protein in human colon carcinoma: complete sequence of a full-length
cDNA encoding the protein. Proc. Nat. Acad. Sci. 85: 6394-6398,
1988. Note: Erratum: Proc. Nat. Acad. Sci. 86: 7032 only, 1989.
*FIELD* CN
Ada Hamosh - updated: 9/11/2013
Victor A. McKusick - updated: 1/23/2004
Ada Hamosh - updated: 2/13/2003
Alan F. Scott - updated: 4/30/2002
John A. Phillips, III - updated: 3/20/2000
Patti M. Sherman - updated: 3/10/1999
Victor A. McKusick - updated: 3/27/1998
*FIELD* CD
Victor A. McKusick: 9/14/1988
*FIELD* ED
alopez: 10/08/2013
alopez: 9/11/2013
terry: 11/13/2012
wwang: 7/23/2008
alopez: 2/17/2004
alopez: 1/23/2004
terry: 1/23/2004
alopez: 2/19/2003
terry: 2/13/2003
joanna: 4/30/2002
mgross: 4/4/2000
terry: 3/20/2000
carol: 3/23/1999
psherman: 3/27/1998
dholmes: 3/6/1998
mark: 6/13/1995
carol: 9/20/1993
supermim: 3/16/1992
carol: 6/24/1991
supermim: 3/20/1990
ddp: 10/27/1989