P13727 (PRG2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bone marrow proteoglycan
Short name=BMPG

Alternative name(s):
Proteoglycan 2

Cleaved into the following chain:

1. Eosinophil granule major basic protein
   Short name=EMBP
   Short name=MBP
   Alternative name(s):
   Pregnancy-associated major basic protein

Gene names

Name:	PRG2
Synonyms:	MBP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	222 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cytotoxin and helminthotoxin. Also induces non-cytolytic histamine release from human basophils. Involved in antiparasitic defense mechanisms and immune hypersensitivity reactions. The proform acts as a proteinase inhibitor, reducing the activity of PAPPA. Ref.22
Subunit structure	In pregnancy serum, the proform exists as a disulfide-linked 2:2 heterotetramer with PAPPA, as a disulfide-linked 2:2 heterotetramer with AGT, and as a complex (probably a 2:2:2 heterohexamer) with AGT and C3dg. Ref.11 Ref.12 Ref.16 Ref.19 Ref.22 Ref.23
Subcellular location	Bone marrow proteoglycan: Secreted. Note: The proform is secreted. Eosinophil granule major basic protein: Cytoplasmic vesicle › secretory vesicle. Note: The proform is secreted. The mature protein is found in the matrix of the eosinophil's large specific granule (crystalloid core).
Tissue specificity	High levels of the proform in placenta and pregnancy serum; in placenta, localized to X cells of septa and anchoring villi. Lower levels in a variety of other tissues including kidney, myometrium, endometrium, ovaries, breast, prostate, bone marrow and colon. Ref.20 Ref.21
Developmental stage	Levels of the proform increase in serum and placenta during pregnancy. Ref.12 Ref.21
Post-translational modification	Nitrated.
Miscellaneous	Binds heparin. Does not bind calcium.
Sequence similarities	Contains 1 C-type lectin domain.

Ontologies

Keywords
Biological process	Immunity
Cellular component	Cytoplasmic vesicle Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Heparin-binding Lectin
Molecular function	Antibiotic Antimicrobial
PTM	Disulfide bond Glycoprotein Nitration Proteoglycan
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	defense response to bacterium Inferred from electronic annotation. Source: UniProtKB-KW immune response Inferred from electronic annotation. Source: InterPro
Cellular_component	extracellular region Traceable author statement PubMed 8547309. Source: ProtInc transport vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	carbohydrate binding Traceable author statement Ref.5. Source: ProtInc heparin binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 16

16

Ref.10 Ref.11 Ref.12

Chain

17 – 222

206

Bone marrow proteoglycan

PRO_0000259923

Propeptide

17 – 105

89

Acidic

PRO_0000017385

Chain

106 – 222

117

Eosinophil granule major basic protein

PRO_0000017386

Regions

Domain

104 – 222

119

C-type lectin

Amino acid modifications

Glycosylation

23

1

O-linked (GalNAc...); partial Ref.18

Glycosylation

24

1

O-linked (GalNAc...) Ref.10 Ref.18

Glycosylation

25

1

O-linked (GalNAc...) Ref.10 Ref.18

Glycosylation

34

1

O-linked (GalNAc...); partial Ref.18

Glycosylation

62

1

O-linked (Xyl...) (chondroitin sulfate) Ref.10 Ref.18

Glycosylation

86

1

N-linked (GlcNAc...) Ref.10 Ref.18

Disulfide bond

51

Interchain (with C-461 in PAPPA) Ref.11 Ref.19 Ref.23

Disulfide bond

125 ↔ 220

Ref.11 Ref.19 Ref.23

Disulfide bond

169

Interchain (with C-732 in PAPPA) Ref.11 Ref.19 Ref.23

Disulfide bond

197 ↔ 212

Ref.11 Ref.19 Ref.23

Natural variations

Natural variant

179

1

R → C in a colorectal cancer sample; somatic mutation. Ref.26

VAR_036401

Natural variant

206

1

H → Y. Ref.1 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.9
Corresponds to variant rs536455 [ dbSNP | Ensembl ].

VAR_060729

Experimental info

Sequence conflict

84

1

D → H in AAA36203. Ref.1

Sequence conflict

192

1

S → T in CAA81207. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

222

Helix Strand Turn

Details...

Beta strand

109 – 116

8

Helix

118 – 129

12

Beta strand

130 – 133

4

Helix

139 – 149

11

Beta strand

153 – 164

12

Beta strand

166 – 168

3

Beta strand

171 – 174

4

Beta strand

187 – 189

3

Beta strand

196 – 201

6

Turn

202 – 205

4

Beta strand

207 – 210

4

Beta strand

216 – 221

6

Sequences

	Sequence		Length	Mass (Da)
	P13727 [UniParc]. Last modified December 15, 2009. Version 2. Checksum: CDD545642555E2D0	FASTA	222	25,206
	10 20 30 40 50 60 MKLPLLLALL FGAVSALHLR SETSTFETPL GAKTLPEDEE TPEQEMEETP CRELEEEEEW 70 80 90 100 110 120 GSGSEDASKK DGAVESISVP DMVDKNLTCP EEEDTVKVVG IPGCQTCRYL LVRSLQTFSQ 130 140 150 160 170 180 AWFTCRRCYR GNLVSIHNFN INYRIQCSVS ALNQGQVWIG GRITGSGRCR RFQWVDGSRW 190 200 210 220 NFAYWAAHQP WSRGGHCVAL CTRGGHWRRA HCLRRLPFIC SY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Acidic precursor revealed in human eosinophil granule major basic protein cDNA." Barker R.L., Gleich G.J., Pease L.R. J. Exp. Med. 168:1493-1498(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT TYR-206. Tissue: Promyelocyte.
[2]	Barker R.L. Submitted (OCT-1989) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 84.
[3]	"Cloning and sequence analysis of the human gene encoding eosinophil major basic protein." Barker R.L., Loegering D.A., Arakawa K.C., Pease L.R., Gleich G.J. Gene 86:285-289(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT TYR-206.
[4]	"Isolation of a complementary DNA clone encoding a precursor to human eosinophil major basic protein." McGrogan M., Simonsen C., Scott R., Giffith J., Ellis N., Kennedy J., Campanelli D., Nathan C., Gabay J. J. Exp. Med. 168:2295-2308(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT TYR-206.
[5]	"Purification and cDNA cloning of a novel factor produced by a human T-cell hybridoma: sequence homology with animal lectins." Yoshimatsu K., Ohya Y., Shikata Y., Seto T., Hasegawa Y., Tanaka I., Kawamura T., Kitoh K., Toyoshima S., Osawa T. Mol. Immunol. 29:537-546(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANT TYR-206.
[6]	"Human eosinophil major basic protein, a mediator of allergic inflammation, is expressed by alternative splicing from two promoters." Li M.S., Sun L., Satoh T., Fisher L.M., Spry C.J. Biochem. J. 305:921-927(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT TYR-206. Tissue: Bone marrow.
[7]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT TYR-206.
[8]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT TYR-206. Tissue: Placenta.
[10]	"Pro-major basic protein has three types of sugar chains at the pro-portion." Shikata Y., Hayashi Y., Yoshimatsu K., Ohya Y., Seto T., Fukushima K., Yoshida Y. Biochim. Biophys. Acta 1163:243-249(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 17-222, GLYCOSYLATION AT SER-24; THR-25; SER-62 AND ASN-86. Tissue: Liver.
[11]	"Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein." Oxvig C., Sand O., Kristensen T., Gleich G.J., Sottrup-Jensen L. J. Biol. Chem. 268:12243-12246(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 17-26; 47-52; 98-108; 172-179 AND 210-222, SUBUNIT, INTERCHAIN DISULFIDE BOND. Tissue: Serum.
[12]	"Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma." Oxvig C., Haaning J., Kristensen L., Wagner J.M., Rubin I., Stigbrand T., Gleich G.J., Sottrup-Jensen L. J. Biol. Chem. 270:13645-13651(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 17-29, SUBUNIT, DEVELOPMENTAL STAGE. Tissue: Serum.
[13]	"Biochemical and amino acid sequence analysis of human eosinophil granule major basic protein." Wasmoen T.L., Bell M.P., Loegering D.A., Gleich G.J., Prendergast F.G., McKean D.J. J. Biol. Chem. 263:12559-12563(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 106-222.
[14]	"Antibiotic proteins of human polymorphonuclear leukocytes." Gabay J.E., Scott R.W., Campanelli D., Griffith J., Wilde C., Marra M.N., Seeger M., Nathan C.F. Proc. Natl. Acad. Sci. U.S.A. 86:5610-5614(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 106-125.
[15]	"Eosinophil granule cationic proteins: major basic protein is distinct from the smaller subunit of eosinophil peroxidase." Weller P.F., Ackerman S.J., Smith J.A. J. Leukoc. Biol. 43:1-4(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 108-124.
[16]	"Amino acid sequence of human pregnancy-associated plasma protein-A derived from cloned cDNA." Kristensen T., Oxvig C., Sand O., Moller N.P.H., Sottrup-Jensen L. Biochemistry 33:1592-1598(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 172-179 AND 210-222, SUBUNIT. Tissue: Serum.
[17]	"Evidence of eosinophil granule major basic protein in human placenta." Wasmoen T.L., McKean D.J., Benirschke K., Coulam C.B., Gleich G.J. J. Exp. Med. 170:2051-2063(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 177-196. Tissue: Placenta.
[18]	"Location and nature of carbohydrate groups in proform of human major basic protein isolated from pregnancy serum." Oxvig C., Haaning J., Hojrup P., Sottrup-Jensen L. Biochem. Mol. Biol. Int. 33:329-336(1994) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-23; SER-24; THR-25; THR-34; SER-62 AND ASN-86.
[19]	"Localization of disulfide bridges and free sulfhydryl groups in human eosinophil granule major basic protein." Oxvig C., Gleich G.J., Sottrup-Jensen L. FEBS Lett. 341:213-217(1994) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS.
[20]	"Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta." Bonno M., Oxvig C., Kephart G.M., Wagner J.M., Kristensen T., Sottrup-Jensen L., Gleich G.J. Lab. Invest. 71:560-566(1994) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[21]	"Messenger ribonucleic acid levels of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein: expression in human reproductive and nonreproductive tissues." Overgaard M.T., Oxvig C., Christiansen M., Lawrence J.B., Conover C.A., Gleich G.J., Sottrup-Jensen L., Haaning J. Biol. Reprod. 61:1083-1089(1999) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[22]	"Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor." 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. J. Biol. Chem. 275:31128-31133(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT.
[23]	"Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment sites." Overgaard M.T., Sorensen E.S., Stachowiak D., Boldt H.B., Kristensen L., Sottrup-Jensen L., Oxvig C. J. Biol. Chem. 278:2106-2117(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERCHAIN DISULFIDE BONDS.
[24]	"Post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase." Ulrich M., Petre A., Youhnovski N., Proemm F., Schirle M., Schumm M., Pero R.S., Doyle A., Checkel J., Kita H., Thiyagarajan N., Acharya K.R., Schmid-Grendelmeier P., Simon H.-U., Schwarz H., Tsutsui M., Shimokawa H., Bellon G. , Lee J.J., Przybylski M., Doering G. J. Biol. Chem. 283:28629-28640(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NITRATION.
[25]	"Crystal structure of the eosinophil major basic protein at 1.8-A. An atypical lectin with a paradigm shift in specificity." Swaminathan G.J., Weaver A.J., Loegering D.A., Checkel J.L., Leonidas D.D., Gleich G.J., Acharya K.R. J. Biol. Chem. 276:26197-26203(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 107-222, HEPARIN-BINDING.
[26]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-179.
+	Additional computationally mapped references.

Web resources

Wikipedia

Major basic protein entry

Functional Glycomics Gateway - Glycan Binding

Eosinophil major basic protein

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y00809 mRNA. Translation: CAA68751.1.
M36805 mRNA. Translation: AAA36203.1.
M34462 Genomic DNA. Translation: AAA35796.1.
M35670 mRNA. Translation: AAA35965.1.
X14088 mRNA. Translation: CAA32250.1.
X65787 mRNA. Translation: CAA46670.1.
Z26248 mRNA. Translation: CAA81207.1.
CR450311 mRNA. Translation: CAG29307.1.
AP000781 Genomic DNA. No translation available.
BC005929 mRNA. Translation: AAH05929.1.

IPI

IPI00010341.

PIR

JL0085. I54055.

RefSeq

NP_001230174.1. NM_001243245.1.
NP_002719.3. NM_002728.4.

UniGene

Hs.512633.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H8U	X-ray	1.80	A/B	106-222	[»]
2BRS	X-ray	2.20	A/B	106-222	[»]

ProteinModelPortal

P13727.

SMR

P13727. Positions 107-222.

ModBase

Search...

Protein-protein interaction databases

IntAct

P13727. 2 interactions.

MINT

MINT-1375191.

STRING

9606.ENSP00000312134.

Protein family/group databases

MEROPS

I63.001.

Polymorphism databases

DMDM

281185479.

Proteomic databases

PaxDb

P13727.

PRIDE

P13727.

Protocols and materials databases

DNASU

5553.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000311862; ENSP00000312134; ENSG00000186652.
ENST00000525955; ENSP00000433016; ENSG00000186652.

GeneID

5553.

KEGG

hsa:5553.

UCSC

uc001nkc.3. human.

Organism-specific databases

CTD

5553.

GeneCards

GC11M057154.

H-InvDB

HIX0009634.

HGNC

HGNC:9362. PRG2.

HPA

HPA038515.

MIM

605601. gene.

neXtProt

NX_P13727.

PharmGKB

PA33734.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG266233.

HOGENOM

HOG000261603.

HOVERGEN

HBG005583.

InParanoid

P13727.

KO

K10786.

OMA

FTCRRCY.

OrthoDB

EOG49KFRG.

PhylomeDB

P13727.

Gene expression databases

ArrayExpress

P13727.

CleanEx

HS_MBP.
HS_PRG2.

Genevestigator

P13727.

GermOnline

ENSG00000186652. Homo sapiens.

Family and domain databases

Gene3D

3.10.100.10. 1 hit.

InterPro

IPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR018378. C-type_lectin_CS.
IPR016187. C-type_lectin_fold.
IPR002352. Eosinophil_major_basic.
[Graphical view]

PANTHER

PTHR10068. PTHR10068. 1 hit.

Pfam

PF00059. Lectin_C. 1 hit.
[Graphical view]

PRINTS

PR00770. EMAJORBASICP.

SMART

SM00034. CLECT. 1 hit.
[Graphical view]

SUPFAM

SSF56436. C-type_lectin_fold. 1 hit.

PROSITE

PS00615. C_TYPE_LECTIN_1. 1 hit.
PS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

PRG2. human.

DrugBank

DB00020. Sargramostim.

EvolutionaryTrace

P13727.

GenomeRNAi

5553.

NextBio

21522.

SOURCE

Search...

Entry information

Entry name

PRG2_HUMAN

Accession

Primary (citable) accession number: P13727
Secondary accession number(s): P81448, Q14227, Q6ICT2

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	December 15, 2009
Last modified:	April 3, 2013
This is version 147 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.