Full text data of PRG2
PRG2
(MBP)
[Confidence: high (present in two of the MS resources)]
Bone marrow proteoglycan; BMPG (Proteoglycan 2; Eosinophil granule major basic protein; EMBP; MBP; Pregnancy-associated major basic protein; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Bone marrow proteoglycan; BMPG (Proteoglycan 2; Eosinophil granule major basic protein; EMBP; MBP; Pregnancy-associated major basic protein; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00010341
IPI00010341 Eosinophil granule major basic protein precursor Eosinophil granule major basic protein precursor membrane n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 extracellular n/a expected molecular weight found in band ~ 14 kDa
IPI00010341 Eosinophil granule major basic protein precursor Eosinophil granule major basic protein precursor membrane n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 extracellular n/a expected molecular weight found in band ~ 14 kDa
UniProt
P13727
ID PRG2_HUMAN Reviewed; 222 AA.
AC P13727; P81448; Q14227; Q6ICT2;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-DEC-2009, sequence version 2.
DT 22-JAN-2014, entry version 152.
DE RecName: Full=Bone marrow proteoglycan;
DE Short=BMPG;
DE AltName: Full=Proteoglycan 2;
DE Contains:
DE RecName: Full=Eosinophil granule major basic protein;
DE Short=EMBP;
DE Short=MBP;
DE AltName: Full=Pregnancy-associated major basic protein;
DE Flags: Precursor;
GN Name=PRG2; Synonyms=MBP;
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], AND VARIANT TYR-206.
RC TISSUE=Promyelocyte;
RX PubMed=3171483; DOI=10.1084/jem.168.4.1493;
RA Barker R.L., Gleich G.J., Pease L.R.;
RT "Acidic precursor revealed in human eosinophil granule major basic
RT protein cDNA.";
RL J. Exp. Med. 168:1493-1498(1988).
RN [2]
RP SEQUENCE REVISION TO 84.
RA Barker R.L.;
RL Submitted (OCT-1989) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT TYR-206.
RX PubMed=2323577; DOI=10.1016/0378-1119(90)90292-Y;
RA Barker R.L., Loegering D.A., Arakawa K.C., Pease L.R., Gleich G.J.;
RT "Cloning and sequence analysis of the human gene encoding eosinophil
RT major basic protein.";
RL Gene 86:285-289(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT TYR-206.
RX PubMed=3199069; DOI=10.1084/jem.168.6.2295;
RA McGrogan M., Simonsen C., Scott R., Giffith J., Ellis N., Kennedy J.,
RA Campanelli D., Nathan C., Gabay J.;
RT "Isolation of a complementary DNA clone encoding a precursor to human
RT eosinophil major basic protein.";
RL J. Exp. Med. 168:2295-2308(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND VARIANT
RP TYR-206.
RX PubMed=1565101; DOI=10.1016/0161-5890(92)90012-M;
RA Yoshimatsu K., Ohya Y., Shikata Y., Seto T., Hasegawa Y., Tanaka I.,
RA Kawamura T., Kitoh K., Toyoshima S., Osawa T.;
RT "Purification and cDNA cloning of a novel factor produced by a human
RT T-cell hybridoma: sequence homology with animal lectins.";
RL Mol. Immunol. 29:537-546(1992).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT TYR-206.
RC TISSUE=Bone marrow;
RX PubMed=7531438;
RA Li M.S., Sun L., Satoh T., Fisher L.M., Spry C.J.;
RT "Human eosinophil major basic protein, a mediator of allergic
RT inflammation, is expressed by alternative splicing from two
RT promoters.";
RL Biochem. J. 305:921-927(1995).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TYR-206.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TYR-206.
RC TISSUE=Placenta;
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 [10]
RP PROTEIN SEQUENCE OF 17-222, AND GLYCOSYLATION AT SER-24; THR-25;
RP SER-62 AND ASN-86.
RC TISSUE=Liver;
RX PubMed=8507662; DOI=10.1016/0167-4838(93)90158-N;
RA Shikata Y., Hayashi Y., Yoshimatsu K., Ohya Y., Seto T., Fukushima K.,
RA Yoshida Y.;
RT "Pro-major basic protein has three types of sugar chains at the pro-
RT portion.";
RL Biochim. Biophys. Acta 1163:243-249(1993).
RN [11]
RP PROTEIN SEQUENCE OF 17-26; 47-52; 98-108; 172-179 AND 210-222,
RP SUBUNIT, AND INTERCHAIN DISULFIDE BOND.
RC TISSUE=Serum;
RX PubMed=7685339;
RA Oxvig C., Sand O., Kristensen T., Gleich G.J., Sottrup-Jensen L.;
RT "Circulating human pregnancy-associated plasma protein-A is disulfide-
RT bridged to the proform of eosinophil major basic protein.";
RL J. Biol. Chem. 268:12243-12246(1993).
RN [12]
RP PROTEIN SEQUENCE OF 17-29, SUBUNIT, AND DEVELOPMENTAL STAGE.
RC TISSUE=Serum;
RX PubMed=7539791; DOI=10.1074/jbc.270.23.13645;
RA Oxvig C., Haaning J., Kristensen L., Wagner J.M., Rubin I.,
RA Stigbrand T., Gleich G.J., Sottrup-Jensen L.;
RT "Identification of angiotensinogen and complement C3dg as novel
RT proteins binding the proform of eosinophil major basic protein in
RT human pregnancy serum and plasma.";
RL J. Biol. Chem. 270:13645-13651(1995).
RN [13]
RP PROTEIN SEQUENCE OF 106-222.
RX PubMed=3410852;
RA Wasmoen T.L., Bell M.P., Loegering D.A., Gleich G.J.,
RA Prendergast F.G., McKean D.J.;
RT "Biochemical and amino acid sequence analysis of human eosinophil
RT granule major basic protein.";
RL J. Biol. Chem. 263:12559-12563(1988).
RN [14]
RP PROTEIN SEQUENCE OF 106-125.
RX PubMed=2501794; DOI=10.1073/pnas.86.14.5610;
RA Gabay J.E., Scott R.W., Campanelli D., Griffith J., Wilde C.,
RA Marra M.N., Seeger M., Nathan C.F.;
RT "Antibiotic proteins of human polymorphonuclear leukocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:5610-5614(1989).
RN [15]
RP PROTEIN SEQUENCE OF 108-124.
RX PubMed=3422083;
RA Weller P.F., Ackerman S.J., Smith J.A.;
RT "Eosinophil granule cationic proteins: major basic protein is distinct
RT from the smaller subunit of eosinophil peroxidase.";
RL J. Leukoc. Biol. 43:1-4(1988).
RN [16]
RP PROTEIN SEQUENCE OF 172-179 AND 210-222, AND SUBUNIT.
RC TISSUE=Serum;
RX PubMed=7508748; DOI=10.1021/bi00172a040;
RA Kristensen T., Oxvig C., Sand O., Moller N.P.H., Sottrup-Jensen L.;
RT "Amino acid sequence of human pregnancy-associated plasma protein-A
RT derived from cloned cDNA.";
RL Biochemistry 33:1592-1598(1994).
RN [17]
RP PROTEIN SEQUENCE OF 177-196.
RC TISSUE=Placenta;
RX PubMed=2584934; DOI=10.1084/jem.170.6.2051;
RA Wasmoen T.L., McKean D.J., Benirschke K., Coulam C.B., Gleich G.J.;
RT "Evidence of eosinophil granule major basic protein in human
RT placenta.";
RL J. Exp. Med. 170:2051-2063(1989).
RN [18]
RP GLYCOSYLATION AT THR-23; SER-24; THR-25; THR-34; SER-62 AND ASN-86.
RX PubMed=7524900;
RA Oxvig C., Haaning J., Hojrup P., Sottrup-Jensen L.;
RT "Location and nature of carbohydrate groups in proform of human major
RT basic protein isolated from pregnancy serum.";
RL Biochem. Mol. Biol. Int. 33:329-336(1994).
RN [19]
RP DISULFIDE BONDS.
RX PubMed=8137941; DOI=10.1016/0014-5793(94)80459-1;
RA Oxvig C., Gleich G.J., Sottrup-Jensen L.;
RT "Localization of disulfide bridges and free sulfhydryl groups in human
RT eosinophil granule major basic protein.";
RL FEBS Lett. 341:213-217(1994).
RN [20]
RP TISSUE SPECIFICITY.
RX PubMed=7526035;
RA Bonno M., Oxvig C., Kephart G.M., Wagner J.M., Kristensen T.,
RA Sottrup-Jensen L., Gleich G.J.;
RT "Localization of pregnancy-associated plasma protein-A and
RT colocalization of pregnancy-associated plasma protein-A messenger
RT ribonucleic acid and eosinophil granule major basic protein messenger
RT ribonucleic acid in placenta.";
RL Lab. Invest. 71:560-566(1994).
RN [21]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10491647;
RA Overgaard M.T., Oxvig C., Christiansen M., Lawrence J.B.,
RA Conover C.A., Gleich G.J., Sottrup-Jensen L., Haaning J.;
RT "Messenger ribonucleic acid levels of pregnancy-associated plasma
RT protein-A and the proform of eosinophil major basic protein:
RT expression in human reproductive and nonreproductive tissues.";
RL Biol. Reprod. 61:1083-1089(1999).
RN [22]
RP FUNCTION, AND SUBUNIT.
RX PubMed=10913121; DOI=10.1074/jbc.M001384200;
RA Overgaard M.T., Haaning J., Boldt H.B., Olsen I.M., Laursen L.S.,
RA Christiansen M., Gleich G.J., Sottrup-Jensen L., Conover C.A.,
RA Oxvig C.;
RT "Expression of recombinant human pregnancy-associated plasma protein-A
RT and identification of the proform of eosinophil major basic protein as
RT its physiological inhibitor.";
RL J. Biol. Chem. 275:31128-31133(2000).
RN [23]
RP INTERCHAIN DISULFIDE BONDS.
RX PubMed=12421832; DOI=10.1074/jbc.M208777200;
RA Overgaard M.T., Sorensen E.S., Stachowiak D., Boldt H.B.,
RA Kristensen L., Sottrup-Jensen L., Oxvig C.;
RT "Complex of pregnancy-associated plasma protein-A and the proform of
RT eosinophil major basic protein. Disulfide structure and carbohydrate
RT attachment sites.";
RL J. Biol. Chem. 278:2106-2117(2003).
RN [24]
RP NITRATION.
RX PubMed=18694936; DOI=10.1074/jbc.M801196200;
RA Ulrich M., Petre A., Youhnovski N., Proemm F., Schirle M., Schumm M.,
RA Pero R.S., Doyle A., Checkel J., Kita H., Thiyagarajan N.,
RA Acharya K.R., Schmid-Grendelmeier P., Simon H.-U., Schwarz H.,
RA Tsutsui M., Shimokawa H., Bellon G., Lee J.J., Przybylski M.,
RA Doering G.;
RT "Post-translational tyrosine nitration of eosinophil granule toxins
RT mediated by eosinophil peroxidase.";
RL J. Biol. Chem. 283:28629-28640(2008).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 107-222, AND HEPARIN-BINDING.
RX PubMed=11319227; DOI=10.1074/jbc.M100848200;
RA Swaminathan G.J., Weaver A.J., Loegering D.A., Checkel J.L.,
RA Leonidas D.D., Gleich G.J., Acharya K.R.;
RT "Crystal structure of the eosinophil major basic protein at 1.8-A. An
RT atypical lectin with a paradigm shift in specificity.";
RL J. Biol. Chem. 276:26197-26203(2001).
RN [26]
RP VARIANT [LARGE SCALE ANALYSIS] CYS-179.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Cytotoxin and helminthotoxin. Also induces non-cytolytic
CC histamine release from human basophils. Involved in antiparasitic
CC defense mechanisms and immune hypersensitivity reactions. The
CC proform acts as a proteinase inhibitor, reducing the activity of
CC PAPPA.
CC -!- SUBUNIT: In pregnancy serum, the proform exists as a disulfide-
CC linked 2:2 heterotetramer with PAPPA, as a disulfide-linked 2:2
CC heterotetramer with AGT, and as a complex (probably a 2:2:2
CC heterohexamer) with AGT and C3dg.
CC -!- SUBCELLULAR LOCATION: Bone marrow proteoglycan: Secreted. Note=The
CC proform is secreted.
CC -!- SUBCELLULAR LOCATION: Eosinophil granule major basic protein:
CC Cytoplasmic vesicle, secretory vesicle. Note=The proform is
CC secreted. The mature protein is found in the matrix of the
CC eosinophil's large specific granule (crystalloid core).
CC -!- TISSUE SPECIFICITY: High levels of the proform in placenta and
CC pregnancy serum; in placenta, localized to X cells of septa and
CC anchoring villi. Lower levels in a variety of other tissues
CC including kidney, myometrium, endometrium, ovaries, breast,
CC prostate, bone marrow and colon.
CC -!- DEVELOPMENTAL STAGE: Levels of the proform increase in serum and
CC placenta during pregnancy.
CC -!- PTM: Nitrated.
CC -!- MISCELLANEOUS: Binds heparin. Does not bind calcium.
CC -!- SIMILARITY: Contains 1 C-type lectin domain.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Major basic protein entry;
CC URL="http://en.wikipedia.org/wiki/Major_basic_protein";
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=Eosinophil major basic protein;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType;=view&cbpId;=cbp_hum_Ctlect_207";
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DR EMBL; Y00809; CAA68751.1; -; mRNA.
DR EMBL; M36805; AAA36203.1; -; mRNA.
DR EMBL; M34462; AAA35796.1; -; Genomic_DNA.
DR EMBL; M35670; AAA35965.1; -; mRNA.
DR EMBL; X14088; CAA32250.1; -; mRNA.
DR EMBL; X65787; CAA46670.1; -; mRNA.
DR EMBL; Z26248; CAA81207.1; -; mRNA.
DR EMBL; CR450311; CAG29307.1; -; mRNA.
DR EMBL; AP000781; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005929; AAH05929.1; -; mRNA.
DR PIR; I54055; JL0085.
DR RefSeq; NP_001230174.1; NM_001243245.1.
DR RefSeq; NP_002719.3; NM_002728.4.
DR RefSeq; XP_005274151.1; XM_005274094.1.
DR RefSeq; XP_005274152.1; XM_005274095.1.
DR RefSeq; XP_005274153.1; XM_005274096.1.
DR UniGene; Hs.512633; -.
DR PDB; 1H8U; X-ray; 1.80 A; A/B=106-222.
DR PDB; 2BRS; X-ray; 2.20 A; A/B=106-222.
DR PDBsum; 1H8U; -.
DR PDBsum; 2BRS; -.
DR ProteinModelPortal; P13727; -.
DR SMR; P13727; 107-222.
DR IntAct; P13727; 2.
DR MINT; MINT-1375191; -.
DR STRING; 9606.ENSP00000312134; -.
DR DrugBank; DB00020; Sargramostim.
DR MEROPS; I63.001; -.
DR DMDM; 281185479; -.
DR PaxDb; P13727; -.
DR PRIDE; P13727; -.
DR DNASU; 5553; -.
DR Ensembl; ENST00000311862; ENSP00000312134; ENSG00000186652.
DR Ensembl; ENST00000525955; ENSP00000433016; ENSG00000186652.
DR GeneID; 5553; -.
DR KEGG; hsa:5553; -.
DR UCSC; uc001nkc.3; human.
DR CTD; 5553; -.
DR GeneCards; GC11M057154; -.
DR H-InvDB; HIX0009634; -.
DR HGNC; HGNC:9362; PRG2.
DR HPA; HPA038515; -.
DR MIM; 605601; gene.
DR neXtProt; NX_P13727; -.
DR PharmGKB; PA33734; -.
DR eggNOG; NOG266233; -.
DR HOGENOM; HOG000261603; -.
DR HOVERGEN; HBG005583; -.
DR InParanoid; P13727; -.
DR KO; K10786; -.
DR OMA; FTCRRCY; -.
DR OrthoDB; EOG779P0F; -.
DR PhylomeDB; P13727; -.
DR ChiTaRS; PRG2; human.
DR EvolutionaryTrace; P13727; -.
DR GeneWiki; Major_basic_protein; -.
DR GenomeRNAi; 5553; -.
DR NextBio; 21522; -.
DR PRO; PR:P13727; -.
DR ArrayExpress; P13727; -.
DR CleanEx; HS_MBP; -.
DR CleanEx; HS_PRG2; -.
DR Genevestigator; P13727; -.
DR GO; GO:0005576; C:extracellular region; TAS:ProtInc.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0030246; F:carbohydrate binding; TAS:ProtInc.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR Gene3D; 3.10.100.10; -; 1.
DR InterPro; IPR001304; C-type_lectin.
DR InterPro; IPR016186; C-type_lectin-like.
DR InterPro; IPR018378; C-type_lectin_CS.
DR InterPro; IPR016187; C-type_lectin_fold.
DR InterPro; IPR002352; Eosinophil_major_basic.
DR PANTHER; PTHR10068; PTHR10068; 1.
DR Pfam; PF00059; Lectin_C; 1.
DR PRINTS; PR00770; EMAJORBASICP.
DR SMART; SM00034; CLECT; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR PROSITE; PS00615; C_TYPE_LECTIN_1; 1.
DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Complete proteome;
KW Cytoplasmic vesicle; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Heparin-binding; Immunity; Lectin; Nitration;
KW Polymorphism; Proteoglycan; Reference proteome; Secreted; Signal.
FT SIGNAL 1 16
FT CHAIN 17 222 Bone marrow proteoglycan.
FT /FTId=PRO_0000259923.
FT PROPEP 17 105 Acidic.
FT /FTId=PRO_0000017385.
FT CHAIN 106 222 Eosinophil granule major basic protein.
FT /FTId=PRO_0000017386.
FT DOMAIN 104 222 C-type lectin.
FT CARBOHYD 23 23 O-linked (GalNAc...); partial.
FT CARBOHYD 24 24 O-linked (GalNAc...).
FT CARBOHYD 25 25 O-linked (GalNAc...).
FT CARBOHYD 34 34 O-linked (GalNAc...); partial.
FT CARBOHYD 62 62 O-linked (Xyl...) (chondroitin sulfate).
FT CARBOHYD 86 86 N-linked (GlcNAc...).
FT DISULFID 51 51 Interchain (with C-461 in PAPPA).
FT DISULFID 125 220
FT DISULFID 169 169 Interchain (with C-732 in PAPPA).
FT DISULFID 197 212
FT VARIANT 179 179 R -> C (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036401.
FT VARIANT 206 206 H -> Y (in dbSNP:rs536455).
FT /FTId=VAR_060729.
FT CONFLICT 84 84 D -> H (in Ref. 1; AAA36203).
FT CONFLICT 192 192 S -> T (in Ref. 6; CAA81207).
FT STRAND 109 116
FT HELIX 118 129
FT STRAND 130 133
FT HELIX 139 149
FT STRAND 153 164
FT STRAND 166 168
FT STRAND 171 174
FT STRAND 187 189
FT STRAND 196 201
FT TURN 202 205
FT STRAND 207 210
FT STRAND 216 221
SQ SEQUENCE 222 AA; 25206 MW; CDD545642555E2D0 CRC64;
MKLPLLLALL FGAVSALHLR SETSTFETPL GAKTLPEDEE TPEQEMEETP CRELEEEEEW
GSGSEDASKK DGAVESISVP DMVDKNLTCP EEEDTVKVVG IPGCQTCRYL LVRSLQTFSQ
AWFTCRRCYR GNLVSIHNFN INYRIQCSVS ALNQGQVWIG GRITGSGRCR RFQWVDGSRW
NFAYWAAHQP WSRGGHCVAL CTRGGHWRRA HCLRRLPFIC SY
//
ID PRG2_HUMAN Reviewed; 222 AA.
AC P13727; P81448; Q14227; Q6ICT2;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-DEC-2009, sequence version 2.
DT 22-JAN-2014, entry version 152.
DE RecName: Full=Bone marrow proteoglycan;
DE Short=BMPG;
DE AltName: Full=Proteoglycan 2;
DE Contains:
DE RecName: Full=Eosinophil granule major basic protein;
DE Short=EMBP;
DE Short=MBP;
DE AltName: Full=Pregnancy-associated major basic protein;
DE Flags: Precursor;
GN Name=PRG2; Synonyms=MBP;
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], AND VARIANT TYR-206.
RC TISSUE=Promyelocyte;
RX PubMed=3171483; DOI=10.1084/jem.168.4.1493;
RA Barker R.L., Gleich G.J., Pease L.R.;
RT "Acidic precursor revealed in human eosinophil granule major basic
RT protein cDNA.";
RL J. Exp. Med. 168:1493-1498(1988).
RN [2]
RP SEQUENCE REVISION TO 84.
RA Barker R.L.;
RL Submitted (OCT-1989) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT TYR-206.
RX PubMed=2323577; DOI=10.1016/0378-1119(90)90292-Y;
RA Barker R.L., Loegering D.A., Arakawa K.C., Pease L.R., Gleich G.J.;
RT "Cloning and sequence analysis of the human gene encoding eosinophil
RT major basic protein.";
RL Gene 86:285-289(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT TYR-206.
RX PubMed=3199069; DOI=10.1084/jem.168.6.2295;
RA McGrogan M., Simonsen C., Scott R., Giffith J., Ellis N., Kennedy J.,
RA Campanelli D., Nathan C., Gabay J.;
RT "Isolation of a complementary DNA clone encoding a precursor to human
RT eosinophil major basic protein.";
RL J. Exp. Med. 168:2295-2308(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND VARIANT
RP TYR-206.
RX PubMed=1565101; DOI=10.1016/0161-5890(92)90012-M;
RA Yoshimatsu K., Ohya Y., Shikata Y., Seto T., Hasegawa Y., Tanaka I.,
RA Kawamura T., Kitoh K., Toyoshima S., Osawa T.;
RT "Purification and cDNA cloning of a novel factor produced by a human
RT T-cell hybridoma: sequence homology with animal lectins.";
RL Mol. Immunol. 29:537-546(1992).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT TYR-206.
RC TISSUE=Bone marrow;
RX PubMed=7531438;
RA Li M.S., Sun L., Satoh T., Fisher L.M., Spry C.J.;
RT "Human eosinophil major basic protein, a mediator of allergic
RT inflammation, is expressed by alternative splicing from two
RT promoters.";
RL Biochem. J. 305:921-927(1995).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TYR-206.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TYR-206.
RC TISSUE=Placenta;
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 [10]
RP PROTEIN SEQUENCE OF 17-222, AND GLYCOSYLATION AT SER-24; THR-25;
RP SER-62 AND ASN-86.
RC TISSUE=Liver;
RX PubMed=8507662; DOI=10.1016/0167-4838(93)90158-N;
RA Shikata Y., Hayashi Y., Yoshimatsu K., Ohya Y., Seto T., Fukushima K.,
RA Yoshida Y.;
RT "Pro-major basic protein has three types of sugar chains at the pro-
RT portion.";
RL Biochim. Biophys. Acta 1163:243-249(1993).
RN [11]
RP PROTEIN SEQUENCE OF 17-26; 47-52; 98-108; 172-179 AND 210-222,
RP SUBUNIT, AND INTERCHAIN DISULFIDE BOND.
RC TISSUE=Serum;
RX PubMed=7685339;
RA Oxvig C., Sand O., Kristensen T., Gleich G.J., Sottrup-Jensen L.;
RT "Circulating human pregnancy-associated plasma protein-A is disulfide-
RT bridged to the proform of eosinophil major basic protein.";
RL J. Biol. Chem. 268:12243-12246(1993).
RN [12]
RP PROTEIN SEQUENCE OF 17-29, SUBUNIT, AND DEVELOPMENTAL STAGE.
RC TISSUE=Serum;
RX PubMed=7539791; DOI=10.1074/jbc.270.23.13645;
RA Oxvig C., Haaning J., Kristensen L., Wagner J.M., Rubin I.,
RA Stigbrand T., Gleich G.J., Sottrup-Jensen L.;
RT "Identification of angiotensinogen and complement C3dg as novel
RT proteins binding the proform of eosinophil major basic protein in
RT human pregnancy serum and plasma.";
RL J. Biol. Chem. 270:13645-13651(1995).
RN [13]
RP PROTEIN SEQUENCE OF 106-222.
RX PubMed=3410852;
RA Wasmoen T.L., Bell M.P., Loegering D.A., Gleich G.J.,
RA Prendergast F.G., McKean D.J.;
RT "Biochemical and amino acid sequence analysis of human eosinophil
RT granule major basic protein.";
RL J. Biol. Chem. 263:12559-12563(1988).
RN [14]
RP PROTEIN SEQUENCE OF 106-125.
RX PubMed=2501794; DOI=10.1073/pnas.86.14.5610;
RA Gabay J.E., Scott R.W., Campanelli D., Griffith J., Wilde C.,
RA Marra M.N., Seeger M., Nathan C.F.;
RT "Antibiotic proteins of human polymorphonuclear leukocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:5610-5614(1989).
RN [15]
RP PROTEIN SEQUENCE OF 108-124.
RX PubMed=3422083;
RA Weller P.F., Ackerman S.J., Smith J.A.;
RT "Eosinophil granule cationic proteins: major basic protein is distinct
RT from the smaller subunit of eosinophil peroxidase.";
RL J. Leukoc. Biol. 43:1-4(1988).
RN [16]
RP PROTEIN SEQUENCE OF 172-179 AND 210-222, AND SUBUNIT.
RC TISSUE=Serum;
RX PubMed=7508748; DOI=10.1021/bi00172a040;
RA Kristensen T., Oxvig C., Sand O., Moller N.P.H., Sottrup-Jensen L.;
RT "Amino acid sequence of human pregnancy-associated plasma protein-A
RT derived from cloned cDNA.";
RL Biochemistry 33:1592-1598(1994).
RN [17]
RP PROTEIN SEQUENCE OF 177-196.
RC TISSUE=Placenta;
RX PubMed=2584934; DOI=10.1084/jem.170.6.2051;
RA Wasmoen T.L., McKean D.J., Benirschke K., Coulam C.B., Gleich G.J.;
RT "Evidence of eosinophil granule major basic protein in human
RT placenta.";
RL J. Exp. Med. 170:2051-2063(1989).
RN [18]
RP GLYCOSYLATION AT THR-23; SER-24; THR-25; THR-34; SER-62 AND ASN-86.
RX PubMed=7524900;
RA Oxvig C., Haaning J., Hojrup P., Sottrup-Jensen L.;
RT "Location and nature of carbohydrate groups in proform of human major
RT basic protein isolated from pregnancy serum.";
RL Biochem. Mol. Biol. Int. 33:329-336(1994).
RN [19]
RP DISULFIDE BONDS.
RX PubMed=8137941; DOI=10.1016/0014-5793(94)80459-1;
RA Oxvig C., Gleich G.J., Sottrup-Jensen L.;
RT "Localization of disulfide bridges and free sulfhydryl groups in human
RT eosinophil granule major basic protein.";
RL FEBS Lett. 341:213-217(1994).
RN [20]
RP TISSUE SPECIFICITY.
RX PubMed=7526035;
RA Bonno M., Oxvig C., Kephart G.M., Wagner J.M., Kristensen T.,
RA Sottrup-Jensen L., Gleich G.J.;
RT "Localization of pregnancy-associated plasma protein-A and
RT colocalization of pregnancy-associated plasma protein-A messenger
RT ribonucleic acid and eosinophil granule major basic protein messenger
RT ribonucleic acid in placenta.";
RL Lab. Invest. 71:560-566(1994).
RN [21]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10491647;
RA Overgaard M.T., Oxvig C., Christiansen M., Lawrence J.B.,
RA Conover C.A., Gleich G.J., Sottrup-Jensen L., Haaning J.;
RT "Messenger ribonucleic acid levels of pregnancy-associated plasma
RT protein-A and the proform of eosinophil major basic protein:
RT expression in human reproductive and nonreproductive tissues.";
RL Biol. Reprod. 61:1083-1089(1999).
RN [22]
RP FUNCTION, AND SUBUNIT.
RX PubMed=10913121; DOI=10.1074/jbc.M001384200;
RA Overgaard M.T., Haaning J., Boldt H.B., Olsen I.M., Laursen L.S.,
RA Christiansen M., Gleich G.J., Sottrup-Jensen L., Conover C.A.,
RA Oxvig C.;
RT "Expression of recombinant human pregnancy-associated plasma protein-A
RT and identification of the proform of eosinophil major basic protein as
RT its physiological inhibitor.";
RL J. Biol. Chem. 275:31128-31133(2000).
RN [23]
RP INTERCHAIN DISULFIDE BONDS.
RX PubMed=12421832; DOI=10.1074/jbc.M208777200;
RA Overgaard M.T., Sorensen E.S., Stachowiak D., Boldt H.B.,
RA Kristensen L., Sottrup-Jensen L., Oxvig C.;
RT "Complex of pregnancy-associated plasma protein-A and the proform of
RT eosinophil major basic protein. Disulfide structure and carbohydrate
RT attachment sites.";
RL J. Biol. Chem. 278:2106-2117(2003).
RN [24]
RP NITRATION.
RX PubMed=18694936; DOI=10.1074/jbc.M801196200;
RA Ulrich M., Petre A., Youhnovski N., Proemm F., Schirle M., Schumm M.,
RA Pero R.S., Doyle A., Checkel J., Kita H., Thiyagarajan N.,
RA Acharya K.R., Schmid-Grendelmeier P., Simon H.-U., Schwarz H.,
RA Tsutsui M., Shimokawa H., Bellon G., Lee J.J., Przybylski M.,
RA Doering G.;
RT "Post-translational tyrosine nitration of eosinophil granule toxins
RT mediated by eosinophil peroxidase.";
RL J. Biol. Chem. 283:28629-28640(2008).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 107-222, AND HEPARIN-BINDING.
RX PubMed=11319227; DOI=10.1074/jbc.M100848200;
RA Swaminathan G.J., Weaver A.J., Loegering D.A., Checkel J.L.,
RA Leonidas D.D., Gleich G.J., Acharya K.R.;
RT "Crystal structure of the eosinophil major basic protein at 1.8-A. An
RT atypical lectin with a paradigm shift in specificity.";
RL J. Biol. Chem. 276:26197-26203(2001).
RN [26]
RP VARIANT [LARGE SCALE ANALYSIS] CYS-179.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Cytotoxin and helminthotoxin. Also induces non-cytolytic
CC histamine release from human basophils. Involved in antiparasitic
CC defense mechanisms and immune hypersensitivity reactions. The
CC proform acts as a proteinase inhibitor, reducing the activity of
CC PAPPA.
CC -!- SUBUNIT: In pregnancy serum, the proform exists as a disulfide-
CC linked 2:2 heterotetramer with PAPPA, as a disulfide-linked 2:2
CC heterotetramer with AGT, and as a complex (probably a 2:2:2
CC heterohexamer) with AGT and C3dg.
CC -!- SUBCELLULAR LOCATION: Bone marrow proteoglycan: Secreted. Note=The
CC proform is secreted.
CC -!- SUBCELLULAR LOCATION: Eosinophil granule major basic protein:
CC Cytoplasmic vesicle, secretory vesicle. Note=The proform is
CC secreted. The mature protein is found in the matrix of the
CC eosinophil's large specific granule (crystalloid core).
CC -!- TISSUE SPECIFICITY: High levels of the proform in placenta and
CC pregnancy serum; in placenta, localized to X cells of septa and
CC anchoring villi. Lower levels in a variety of other tissues
CC including kidney, myometrium, endometrium, ovaries, breast,
CC prostate, bone marrow and colon.
CC -!- DEVELOPMENTAL STAGE: Levels of the proform increase in serum and
CC placenta during pregnancy.
CC -!- PTM: Nitrated.
CC -!- MISCELLANEOUS: Binds heparin. Does not bind calcium.
CC -!- SIMILARITY: Contains 1 C-type lectin domain.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Major basic protein entry;
CC URL="http://en.wikipedia.org/wiki/Major_basic_protein";
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=Eosinophil major basic protein;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType;=view&cbpId;=cbp_hum_Ctlect_207";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
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DR EMBL; Y00809; CAA68751.1; -; mRNA.
DR EMBL; M36805; AAA36203.1; -; mRNA.
DR EMBL; M34462; AAA35796.1; -; Genomic_DNA.
DR EMBL; M35670; AAA35965.1; -; mRNA.
DR EMBL; X14088; CAA32250.1; -; mRNA.
DR EMBL; X65787; CAA46670.1; -; mRNA.
DR EMBL; Z26248; CAA81207.1; -; mRNA.
DR EMBL; CR450311; CAG29307.1; -; mRNA.
DR EMBL; AP000781; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005929; AAH05929.1; -; mRNA.
DR PIR; I54055; JL0085.
DR RefSeq; NP_001230174.1; NM_001243245.1.
DR RefSeq; NP_002719.3; NM_002728.4.
DR RefSeq; XP_005274151.1; XM_005274094.1.
DR RefSeq; XP_005274152.1; XM_005274095.1.
DR RefSeq; XP_005274153.1; XM_005274096.1.
DR UniGene; Hs.512633; -.
DR PDB; 1H8U; X-ray; 1.80 A; A/B=106-222.
DR PDB; 2BRS; X-ray; 2.20 A; A/B=106-222.
DR PDBsum; 1H8U; -.
DR PDBsum; 2BRS; -.
DR ProteinModelPortal; P13727; -.
DR SMR; P13727; 107-222.
DR IntAct; P13727; 2.
DR MINT; MINT-1375191; -.
DR STRING; 9606.ENSP00000312134; -.
DR DrugBank; DB00020; Sargramostim.
DR MEROPS; I63.001; -.
DR DMDM; 281185479; -.
DR PaxDb; P13727; -.
DR PRIDE; P13727; -.
DR DNASU; 5553; -.
DR Ensembl; ENST00000311862; ENSP00000312134; ENSG00000186652.
DR Ensembl; ENST00000525955; ENSP00000433016; ENSG00000186652.
DR GeneID; 5553; -.
DR KEGG; hsa:5553; -.
DR UCSC; uc001nkc.3; human.
DR CTD; 5553; -.
DR GeneCards; GC11M057154; -.
DR H-InvDB; HIX0009634; -.
DR HGNC; HGNC:9362; PRG2.
DR HPA; HPA038515; -.
DR MIM; 605601; gene.
DR neXtProt; NX_P13727; -.
DR PharmGKB; PA33734; -.
DR eggNOG; NOG266233; -.
DR HOGENOM; HOG000261603; -.
DR HOVERGEN; HBG005583; -.
DR InParanoid; P13727; -.
DR KO; K10786; -.
DR OMA; FTCRRCY; -.
DR OrthoDB; EOG779P0F; -.
DR PhylomeDB; P13727; -.
DR ChiTaRS; PRG2; human.
DR EvolutionaryTrace; P13727; -.
DR GeneWiki; Major_basic_protein; -.
DR GenomeRNAi; 5553; -.
DR NextBio; 21522; -.
DR PRO; PR:P13727; -.
DR ArrayExpress; P13727; -.
DR CleanEx; HS_MBP; -.
DR CleanEx; HS_PRG2; -.
DR Genevestigator; P13727; -.
DR GO; GO:0005576; C:extracellular region; TAS:ProtInc.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0030246; F:carbohydrate binding; TAS:ProtInc.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR Gene3D; 3.10.100.10; -; 1.
DR InterPro; IPR001304; C-type_lectin.
DR InterPro; IPR016186; C-type_lectin-like.
DR InterPro; IPR018378; C-type_lectin_CS.
DR InterPro; IPR016187; C-type_lectin_fold.
DR InterPro; IPR002352; Eosinophil_major_basic.
DR PANTHER; PTHR10068; PTHR10068; 1.
DR Pfam; PF00059; Lectin_C; 1.
DR PRINTS; PR00770; EMAJORBASICP.
DR SMART; SM00034; CLECT; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR PROSITE; PS00615; C_TYPE_LECTIN_1; 1.
DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Complete proteome;
KW Cytoplasmic vesicle; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Heparin-binding; Immunity; Lectin; Nitration;
KW Polymorphism; Proteoglycan; Reference proteome; Secreted; Signal.
FT SIGNAL 1 16
FT CHAIN 17 222 Bone marrow proteoglycan.
FT /FTId=PRO_0000259923.
FT PROPEP 17 105 Acidic.
FT /FTId=PRO_0000017385.
FT CHAIN 106 222 Eosinophil granule major basic protein.
FT /FTId=PRO_0000017386.
FT DOMAIN 104 222 C-type lectin.
FT CARBOHYD 23 23 O-linked (GalNAc...); partial.
FT CARBOHYD 24 24 O-linked (GalNAc...).
FT CARBOHYD 25 25 O-linked (GalNAc...).
FT CARBOHYD 34 34 O-linked (GalNAc...); partial.
FT CARBOHYD 62 62 O-linked (Xyl...) (chondroitin sulfate).
FT CARBOHYD 86 86 N-linked (GlcNAc...).
FT DISULFID 51 51 Interchain (with C-461 in PAPPA).
FT DISULFID 125 220
FT DISULFID 169 169 Interchain (with C-732 in PAPPA).
FT DISULFID 197 212
FT VARIANT 179 179 R -> C (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036401.
FT VARIANT 206 206 H -> Y (in dbSNP:rs536455).
FT /FTId=VAR_060729.
FT CONFLICT 84 84 D -> H (in Ref. 1; AAA36203).
FT CONFLICT 192 192 S -> T (in Ref. 6; CAA81207).
FT STRAND 109 116
FT HELIX 118 129
FT STRAND 130 133
FT HELIX 139 149
FT STRAND 153 164
FT STRAND 166 168
FT STRAND 171 174
FT STRAND 187 189
FT STRAND 196 201
FT TURN 202 205
FT STRAND 207 210
FT STRAND 216 221
SQ SEQUENCE 222 AA; 25206 MW; CDD545642555E2D0 CRC64;
MKLPLLLALL FGAVSALHLR SETSTFETPL GAKTLPEDEE TPEQEMEETP CRELEEEEEW
GSGSEDASKK DGAVESISVP DMVDKNLTCP EEEDTVKVVG IPGCQTCRYL LVRSLQTFSQ
AWFTCRRCYR GNLVSIHNFN INYRIQCSVS ALNQGQVWIG GRITGSGRCR RFQWVDGSRW
NFAYWAAHQP WSRGGHCVAL CTRGGHWRRA HCLRRLPFIC SY
//
MIM
605601
*RECORD*
*FIELD* NO
605601
*FIELD* TI
*605601 PROTEOGLYCAN 2; PRG2
;;EOSINOPHIL GRANULE MAJOR BASIC PROTEIN; MBP
*FIELD* TX
read more
CLONING
Eosinophil granule major basic protein (MBP) comprises the crystalloid
core of the eosinophil granule. Wasmoen et al. (1988) and Weller et al.
(1988) published a partial amino acid sequence for MBP, also designated
proteoglycan-2 (PRG2). Using this partial sequence, Barker et al. (1988)
isolated a full-length PRG2 cDNA from a human promyelocytic leukemia
cell line (HL60) cDNA library. McGrogan et al. (1988) independently
isolated a PRG2 cDNA from an HL60 cell line cDNA. Yoshimatsu et al.
(1992) also identified PRG2 in a search for a natural killer (NK)
cell-activating factor purified from the supernatant of a T-cell
hybridoma.
McGrogan et al. (1988) and Barker et al. (1988) determined that the PRG2
cDNA encodes a deduced 222-amino acid protein with a 15-amino acid
hydrophobic signal sequence. PRG2 is initially translated as a 25-kD
preproprotein that is posttranslationally modified to a proprotein.
Posttranslational modification results in the mature form of PRG2, which
is encoded by the carboxy 117 amino acids of the preproprotein and has a
molecular mass of 14 kD. The 90-amino acid N-terminal domain has 1
potential N-linked glycosylation site. Yoshimatsu et al. (1992) reported
that the C-terminal end of PRG2 shares homology with animal lectins.
McGrogan et al. (1988) determined that the putative PRG2 proprotein,
also known as proMBP, is a bipolar molecule. The amino-terminal half is
hydrophilic, whereas the mature PRG2 is hydrophobic. Barker et al.
(1988) hypothesized that the translation of PRG2 as a bipolar proprotein
may mask the toxic effects of the mature PRG2 and protect the eosinophil
from damage while the protein is processed through the endoplasmic
reticulum to its sequestered site in the eosinophil granule.
Using Northern blot analysis, McGrogan et al. (1988) detected a major
1-kb transcript and a minor 0.5-kb PRG2 transcript in HL60 cells. By the
same method, Li et al. (1995) detected a 1-kb transcript in immature
cells including bone-marrow and HL60 cells, but not in purified blood
eosinophils. Using RT-PCR, Li et al. (1995) detected an additional
1.6-kb transcript in bone marrow cells and HL60 cells at lower levels
than the 1-kb transcript. In differentiated blood eosinophils from
idiopathic hypereosinophilic syndrome patients, the 1.6-kb transcript
predominated.
GENE STRUCTURE
Li et al. (1995) isolated genomic clones of PRG2 and determined that
PRG2 is contains 14 exons spanning 35 kb, with 5 coding exons (exons
10-14). After comparing cDNA and genomic clones, Li et al. (1995)
hypothesized that the 2 PRG2 transcripts originate from alternatively
spliced variants that differ in the 5-prime untranslated region. The
1-kb transcript is derived from exons 9-14. The 1.6-kb transcript is
derived from exons 1-8 and 10-14. Li et al. (1995) hypothesized that
promoter switching may occur during eosinophil differentiation and may
be used to reduce protein synthesis. Once the mature PRG2 is stably
stored in granules, terminally differentiated eosinophils may reduce
their PRG2 expression by switching promoters.
GENE FUNCTION
Consistent with the hypothesized function of PRG2 as a cytotoxic
polypeptide, McGrogan et al. (1988) found that PRG2 has microbicidal
activity against gram-negative and gram-positive bacteria and fungi.
Yoshimatsu et al. (1992) demonstrated that PRG2 enhanced natural killer
cell activity. PRG2 also enhanced the activity of killer T cells induced
by the mixed lymphocyte tumor cell reaction.
Oxvig et al. (1993) analyzed tryptic peptides from circulating
pregnancy-associated plasma protein-A (PAPPA; 176385) and found
sequences that exactly matched 3 predicted tryptic peptides from proMBP,
suggesting that proMBP is a constituent of circulating PAPPA. Sequence
analysis and denaturing gel chromatography of PAPPA/proMBP confirmed the
finding. Oxvig et al. (1993) concluded that circulating PAPPA is a
disulfide-bridged complex with proMBP in which the subunits of the
constituents are present in a 1:1 molar ratio.
Overgaard et al. (2000) compared the proteolytic activity of recombinant
PAPPA and pregnancy serum PAPPA/proMBP complex and observed a greater
than 100-fold difference, showing that proMBP functions as a proteinase
inhibitor in vivo. Pregnancy serum and plasma were found to contain
traces (less than 1%) of uncomplexed PAPPA with a much higher specific
activity than the PAPPA/proMBP complex, suggesting that the measurable
activity of the PAPPA/proMBP complex probably results from the presence
of a minor subpopulation of partly inhibited PAPPA that exists in a 2:1
complex with proMBP. Overgaard et al. (2000) stated that inhibition of
PAPPA by proMBP represented a novel inhibitory mechanism with the enzyme
irreversibly bound to its inhibitor by disulfide bonds.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PRG2
gene to chromosome 11 (TMAP A005W41). By FISH, Plager et al. (2001)
mapped the PRG2 and PRG3 (606814) genes to chromosome 11cen-q12.
*FIELD* RF
1. Barker, R. L.; Gleich, G. J.; Pease, L. R.: Acidic precursor revealed
in human eosinophil granule major basic protein cDNA. J. Exp. Med. 168:
1493-1498, 1988. Note: Erratum: J. Exp. Med. 170: 1057 only, 1989.
2. Li, M.-S.; Sun, L.; Satoh, T.; Fisher, L. M.; Spry, C. J. F.:
Human eosinophil major basic protein, a mediator of allergic inflammation,
is expressed by alternative splicing from two promoters. Biochem.
J. 305: 921-927, 1995.
3. McGrogan, M.; Simonsen, C.; Scott, R.; Griffith, J.; Ellis, N.;
Kennedy, J.; Campanelli, D.; Nathan, C.; Gabay, J.: Isolation of
a complementary DNA clone encoding a precursor to human eosinophil
major basic protein. J. Exp. Med. 168: 2295-2308, 1988.
4. Overgaard, M. T.; Haaning, J.; Boldt, H. B.; Olsen, I. M.; Laursen,
L. S.; Christiansen, M.; Gleich, G. J.; Sottrup-Jensen, L.; Conover,
C. A.; Oxvig, C.: Expression of recombinant human pregnancy-associated
plasma protein-A and identification of the proform of eosinophil major
basic protein as its physiological inhibitor. J. Biol. Chem. 275:
31128-31133, 2000.
5. Oxvig, C.; Sand, O.; Kristensen, T.; Gleich, G. J.; Sottrup-Jensen,
L.: Circulating human pregnancy-associated plasma protein-A is disulfide-bridged
to the proform of eosinophil major basic protein. J. Biol. Chem. 268:
12243-12246, 1993.
6. Plager, D. A.; Weiler, D. A.; Loegering, D. A.; Johnson, W. B.;
Haley, L.; Eddy, R. L.; Shows, T. B.; Gleich, G. J.: Comparative
structure, proximal promoter elements, and chromosome location of
the human eosinophil major basic protein genes. Genomics 71: 271-281,
2001.
7. Wasmoen, T. L.; Bell, M. P.; Loegering, D. A.; Gleich, G. J.; Prendergast,
F. G.; McKean, D. J.: Biochemical and amino acid sequence analysis
of human eosinophil granule major basic protein. J. Biol. Chem. 263:
12559-12563, 1988.
8. Weller, P. F.; Ackerman, S. J.; Smith, J. A.: Eosinophil granule
proteins: major basic protein is distinct from the smaller subunit
of eosinophil peroxidase. J. Leukoc. Biol. 43: 1-4, 1988.
9. Yoshimatsu, K.; Ohya, Y.; Shikata, Y.; Seto, T.; Hasegawa, Y.;
Tanaka, I.; Kawamura, T.; Kitoh, K.; Toyoshima, S.; Osawa, T.: Purification
and cDNA cloning of a novel factor produced by a human T-cell hybridoma:
sequence homology with animal lectins. Molec. Immun. 29: 537-546,
1992.
*FIELD* CN
Marla J. F. O'Neill - updated: 4/4/2006
Patricia A. Hartz - updated: 4/2/2002
*FIELD* CD
Dawn Watkins-Chow: 1/29/2001
*FIELD* ED
terry: 09/24/2012
wwang: 4/18/2006
terry: 4/4/2006
carol: 4/2/2002
terry: 11/14/2001
carol: 1/30/2001
mcapotos: 1/30/2001
carol: 1/30/2001
*RECORD*
*FIELD* NO
605601
*FIELD* TI
*605601 PROTEOGLYCAN 2; PRG2
;;EOSINOPHIL GRANULE MAJOR BASIC PROTEIN; MBP
*FIELD* TX
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CLONING
Eosinophil granule major basic protein (MBP) comprises the crystalloid
core of the eosinophil granule. Wasmoen et al. (1988) and Weller et al.
(1988) published a partial amino acid sequence for MBP, also designated
proteoglycan-2 (PRG2). Using this partial sequence, Barker et al. (1988)
isolated a full-length PRG2 cDNA from a human promyelocytic leukemia
cell line (HL60) cDNA library. McGrogan et al. (1988) independently
isolated a PRG2 cDNA from an HL60 cell line cDNA. Yoshimatsu et al.
(1992) also identified PRG2 in a search for a natural killer (NK)
cell-activating factor purified from the supernatant of a T-cell
hybridoma.
McGrogan et al. (1988) and Barker et al. (1988) determined that the PRG2
cDNA encodes a deduced 222-amino acid protein with a 15-amino acid
hydrophobic signal sequence. PRG2 is initially translated as a 25-kD
preproprotein that is posttranslationally modified to a proprotein.
Posttranslational modification results in the mature form of PRG2, which
is encoded by the carboxy 117 amino acids of the preproprotein and has a
molecular mass of 14 kD. The 90-amino acid N-terminal domain has 1
potential N-linked glycosylation site. Yoshimatsu et al. (1992) reported
that the C-terminal end of PRG2 shares homology with animal lectins.
McGrogan et al. (1988) determined that the putative PRG2 proprotein,
also known as proMBP, is a bipolar molecule. The amino-terminal half is
hydrophilic, whereas the mature PRG2 is hydrophobic. Barker et al.
(1988) hypothesized that the translation of PRG2 as a bipolar proprotein
may mask the toxic effects of the mature PRG2 and protect the eosinophil
from damage while the protein is processed through the endoplasmic
reticulum to its sequestered site in the eosinophil granule.
Using Northern blot analysis, McGrogan et al. (1988) detected a major
1-kb transcript and a minor 0.5-kb PRG2 transcript in HL60 cells. By the
same method, Li et al. (1995) detected a 1-kb transcript in immature
cells including bone-marrow and HL60 cells, but not in purified blood
eosinophils. Using RT-PCR, Li et al. (1995) detected an additional
1.6-kb transcript in bone marrow cells and HL60 cells at lower levels
than the 1-kb transcript. In differentiated blood eosinophils from
idiopathic hypereosinophilic syndrome patients, the 1.6-kb transcript
predominated.
GENE STRUCTURE
Li et al. (1995) isolated genomic clones of PRG2 and determined that
PRG2 is contains 14 exons spanning 35 kb, with 5 coding exons (exons
10-14). After comparing cDNA and genomic clones, Li et al. (1995)
hypothesized that the 2 PRG2 transcripts originate from alternatively
spliced variants that differ in the 5-prime untranslated region. The
1-kb transcript is derived from exons 9-14. The 1.6-kb transcript is
derived from exons 1-8 and 10-14. Li et al. (1995) hypothesized that
promoter switching may occur during eosinophil differentiation and may
be used to reduce protein synthesis. Once the mature PRG2 is stably
stored in granules, terminally differentiated eosinophils may reduce
their PRG2 expression by switching promoters.
GENE FUNCTION
Consistent with the hypothesized function of PRG2 as a cytotoxic
polypeptide, McGrogan et al. (1988) found that PRG2 has microbicidal
activity against gram-negative and gram-positive bacteria and fungi.
Yoshimatsu et al. (1992) demonstrated that PRG2 enhanced natural killer
cell activity. PRG2 also enhanced the activity of killer T cells induced
by the mixed lymphocyte tumor cell reaction.
Oxvig et al. (1993) analyzed tryptic peptides from circulating
pregnancy-associated plasma protein-A (PAPPA; 176385) and found
sequences that exactly matched 3 predicted tryptic peptides from proMBP,
suggesting that proMBP is a constituent of circulating PAPPA. Sequence
analysis and denaturing gel chromatography of PAPPA/proMBP confirmed the
finding. Oxvig et al. (1993) concluded that circulating PAPPA is a
disulfide-bridged complex with proMBP in which the subunits of the
constituents are present in a 1:1 molar ratio.
Overgaard et al. (2000) compared the proteolytic activity of recombinant
PAPPA and pregnancy serum PAPPA/proMBP complex and observed a greater
than 100-fold difference, showing that proMBP functions as a proteinase
inhibitor in vivo. Pregnancy serum and plasma were found to contain
traces (less than 1%) of uncomplexed PAPPA with a much higher specific
activity than the PAPPA/proMBP complex, suggesting that the measurable
activity of the PAPPA/proMBP complex probably results from the presence
of a minor subpopulation of partly inhibited PAPPA that exists in a 2:1
complex with proMBP. Overgaard et al. (2000) stated that inhibition of
PAPPA by proMBP represented a novel inhibitory mechanism with the enzyme
irreversibly bound to its inhibitor by disulfide bonds.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PRG2
gene to chromosome 11 (TMAP A005W41). By FISH, Plager et al. (2001)
mapped the PRG2 and PRG3 (606814) genes to chromosome 11cen-q12.
*FIELD* RF
1. Barker, R. L.; Gleich, G. J.; Pease, L. R.: Acidic precursor revealed
in human eosinophil granule major basic protein cDNA. J. Exp. Med. 168:
1493-1498, 1988. Note: Erratum: J. Exp. Med. 170: 1057 only, 1989.
2. Li, M.-S.; Sun, L.; Satoh, T.; Fisher, L. M.; Spry, C. J. F.:
Human eosinophil major basic protein, a mediator of allergic inflammation,
is expressed by alternative splicing from two promoters. Biochem.
J. 305: 921-927, 1995.
3. McGrogan, M.; Simonsen, C.; Scott, R.; Griffith, J.; Ellis, N.;
Kennedy, J.; Campanelli, D.; Nathan, C.; Gabay, J.: Isolation of
a complementary DNA clone encoding a precursor to human eosinophil
major basic protein. J. Exp. Med. 168: 2295-2308, 1988.
4. Overgaard, M. T.; Haaning, J.; Boldt, H. B.; Olsen, I. M.; Laursen,
L. S.; Christiansen, M.; Gleich, G. J.; Sottrup-Jensen, L.; Conover,
C. A.; Oxvig, C.: Expression of recombinant human pregnancy-associated
plasma protein-A and identification of the proform of eosinophil major
basic protein as its physiological inhibitor. J. Biol. Chem. 275:
31128-31133, 2000.
5. Oxvig, C.; Sand, O.; Kristensen, T.; Gleich, G. J.; Sottrup-Jensen,
L.: Circulating human pregnancy-associated plasma protein-A is disulfide-bridged
to the proform of eosinophil major basic protein. J. Biol. Chem. 268:
12243-12246, 1993.
6. Plager, D. A.; Weiler, D. A.; Loegering, D. A.; Johnson, W. B.;
Haley, L.; Eddy, R. L.; Shows, T. B.; Gleich, G. J.: Comparative
structure, proximal promoter elements, and chromosome location of
the human eosinophil major basic protein genes. Genomics 71: 271-281,
2001.
7. Wasmoen, T. L.; Bell, M. P.; Loegering, D. A.; Gleich, G. J.; Prendergast,
F. G.; McKean, D. J.: Biochemical and amino acid sequence analysis
of human eosinophil granule major basic protein. J. Biol. Chem. 263:
12559-12563, 1988.
8. Weller, P. F.; Ackerman, S. J.; Smith, J. A.: Eosinophil granule
proteins: major basic protein is distinct from the smaller subunit
of eosinophil peroxidase. J. Leukoc. Biol. 43: 1-4, 1988.
9. Yoshimatsu, K.; Ohya, Y.; Shikata, Y.; Seto, T.; Hasegawa, Y.;
Tanaka, I.; Kawamura, T.; Kitoh, K.; Toyoshima, S.; Osawa, T.: Purification
and cDNA cloning of a novel factor produced by a human T-cell hybridoma:
sequence homology with animal lectins. Molec. Immun. 29: 537-546,
1992.
*FIELD* CN
Marla J. F. O'Neill - updated: 4/4/2006
Patricia A. Hartz - updated: 4/2/2002
*FIELD* CD
Dawn Watkins-Chow: 1/29/2001
*FIELD* ED
terry: 09/24/2012
wwang: 4/18/2006
terry: 4/4/2006
carol: 4/2/2002
terry: 11/14/2001
carol: 1/30/2001
mcapotos: 1/30/2001
carol: 1/30/2001