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P21754 (ZP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Zona pellucida sperm-binding protein 3
Alternative name(s):
Sperm receptor
ZP3A/ZP3B
Zona pellucida glycoprotein 3
Short name=Zp-3
Zona pellucida protein C

Cleaved into the following chain:

  1. Processed zona pellucida sperm-binding protein 3
Gene names
Name:ZP3
Synonyms:ZP3A, ZP3B, ZPC
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length424 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

The mammalian zona pellucida, which mediates species-specific sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy, is composed of three to four glycoproteins, ZP1, ZP2, ZP3, and ZP4. ZP3 is essential for sperm binding and zona matrix formation.

Subunit structure

Polymers of ZP2 and ZP3 organized into long filaments cross-linked by ZP1 homodimers By similarity.

Subcellular location

Processed zona pellucida sperm-binding protein 3: Secretedextracellular spaceextracellular matrix. Note: The glycoproteinaceous translucent extracellular matrix that surrounds the mammalian oocyte is called zona pellucida.

Cell membrane; Single-pass type I membrane protein.

Tissue specificity

Oocytes.

Domain

The ZP domain is involved in the polymerization of the ZP proteins to form the zona pellucida.

Post-translational modification

Proteolytically cleaved before the transmembrane segment to yield the secreted ectodomain incorporated in the zona pellucida. Ref.6

N-glycosylated By similarity. Ref.6

O-glycosylated; removal of O-linked glycans may play an important role in the post-fertilization block to polyspermy By similarity. Ref.6

Sequence similarities

Belongs to the ZP domain family. ZPC subfamily.

Contains 1 ZP domain.

Ontologies

Keywords
   Biological processFertilization
   Cellular componentCell membrane
Extracellular matrix
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionReceptor
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Pyrrolidone carboxylic acid
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbinding of sperm to zona pellucida

Inferred from direct assay PubMed 19246320PubMed 19700799. Source: UniProtKB

blastocyst formation

Inferred from sequence or structural similarity. Source: UniProtKB

calcium ion transmembrane transport

Inferred from direct assay PubMed 20394732. Source: GOC

egg coat formation

Inferred from sequence or structural similarity. Source: UniProtKB

humoral immune response mediated by circulating immunoglobulin

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular protein transport

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular signal transduction

Inferred from mutant phenotype PubMed 18667750. Source: UniProtKB

manganese ion transmembrane transport

Inferred from sequence or structural similarity. Source: GOC

manganese ion transport

Inferred from sequence or structural similarity. Source: UniProtKB

multicellular organism reproduction

Traceable author statement. Source: Reactome

negative regulation of binding of sperm to zona pellucida

Inferred from direct assay PubMed 18667750. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

oocyte development

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol-mediated signaling

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of T cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of acrosomal vesicle exocytosis

Inferred from direct assay PubMed 19246320. Source: UniProtKB

positive regulation of acrosome reaction

Inferred from direct assay PubMed 11751269PubMed 18667750PubMed 20394732. Source: UniProtKB

positive regulation of antral ovarian follicle growth

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of calcium ion import

Inferred from direct assay PubMed 11751269. Source: UniProtKB

positive regulation of humoral immune response

Inferred from direct assay PubMed 19004505. Source: UniProtKB

positive regulation of inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interferon-gamma production

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-4 production

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of leukocyte migration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of ovarian follicle development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of phosphatidylinositol biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein kinase B signaling

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein kinase activity

Inferred from direct assay PubMed 18667750. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of type IV hypersensitivity

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase C signaling

Inferred from mutant phenotype PubMed 18667750. Source: UniProtKB

single fertilization

Traceable author statement. Source: Reactome

   Cellular_componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 9609824. Source: UniProtKB

endoplasmic reticulum

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular matrix

Inferred from direct assay PubMed 19246320. Source: UniProtKB

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from mutant phenotype PubMed 19246320. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

multivesicular body

Inferred from sequence or structural similarity. Source: UniProtKB

outer acrosomal membrane

Inferred from sequence or structural similarity. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

proteinaceous extracellular matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

secretory granule

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionacrosin binding

Inferred from physical interaction PubMed 15950651. Source: UniProtKB

carbohydrate binding

Inferred from direct assay PubMed 19246320. Source: UniProtKB

manganese ion transmembrane transporter activity

Inferred from sequence or structural similarity. Source: UniProtKB

signal transducer activity

Inferred from mutant phenotype PubMed 18667750. Source: UniProtKB

store-operated calcium channel activity

Inferred from direct assay PubMed 20394732. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform ZP3A (identifier: P21754-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform ZP3B (identifier: P21754-2)

The sequence of this isoform differs from the canonical sequence as follows:
     364-372: PLIFLDRRG → ATDLPGQEW
     373-424: Missing.
Note: Found in a second polymorphic locus which, due to an extra G residue in exon 8, has the potential to encode a truncated protein of 372 amino acids.
Isoform 3 (identifier: P21754-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-51: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222
Chain23 – 350328Zona pellucida sperm-binding protein 3
PRO_0000041709
Chain23 – ?Processed zona pellucida sperm-binding protein 3PRO_0000304569
Propeptide351 – 42474Removed in mature form By similarity
PRO_0000041710

Regions

Topological domain23 – 387365Extracellular Potential
Transmembrane388 – 40821Helical; Potential
Topological domain409 – 42416Cytoplasmic Potential
Domain45 – 307263ZP

Amino acid modifications

Modified residue231Pyrrolidone carboxylic acid
Glycosylation1251N-linked (GlcNAc...) Ref.6
Glycosylation1471N-linked (GlcNAc...) Ref.6
Glycosylation1561O-linked (GalNAc...) By similarity
Glycosylation1621O-linked (GalNAc...) By similarity
Glycosylation1631O-linked (GalNAc...) By similarity
Glycosylation2261N-linked (GlcNAc...) Potential
Glycosylation2721N-linked (GlcNAc...) Ref.6
Disulfide bond46 ↔ 140 Ref.6
Disulfide bond78 ↔ 99 Ref.6
Disulfide bond217 ↔ 282 Ref.6
Disulfide bond239 ↔ 300 Ref.6

Natural variations

Alternative sequence1 – 5151Missing in isoform 3.
VSP_037556
Alternative sequence364 – 3729PLIFLDRRG → ATDLPGQEW in isoform ZP3B.
VSP_006949
Alternative sequence373 – 42452Missing in isoform ZP3B.
VSP_006950
Natural variant311G → R.
Corresponds to variant rs2286428 [ dbSNP | Ensembl ].
VAR_058011
Natural variant3151S → P. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs2906999 [ dbSNP | Ensembl ].
VAR_058012
Natural variant3401M → V.
Corresponds to variant rs2906997 [ dbSNP | Ensembl ].
VAR_058013

Experimental info

Sequence conflict3451R → T in CAA40095. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform ZP3A [UniParc].

Last modified July 7, 2009. Version 2.
Checksum: 0F3CCDA2427C0E3A

FASTA42447,018
        10         20         30         40         50         60 
MELSYRLFIC LLLWGSTELC YPQPLWLLQG GASHPETSVQ PVLVECQEAT LMVMVSKDLF 

        70         80         90        100        110        120 
GTGKLIRAAD LTLGPEACEP LVSMDTEDVV RFEVGLHECG NSMQVTDDAL VYSTFLLHDP 

       130        140        150        160        170        180 
RPVGNLSIVR TNRAEIPIEC RYPRQGNVSS QAILPTWLPF RTTVFSEEKL TFSLRLMEEN 

       190        200        210        220        230        240 
WNAEKRSPTF HLGDAAHLQA EIHTGSHVPL RLFVDHCVAT PTPDQNASPY HTIVDFHGCL 

       250        260        270        280        290        300 
VDGLTDASSA FKVPRPGPDT LQFTVDVFHF ANDSRNMIYI TCHLKVTLAE QDPDELNKAC 

       310        320        330        340        350        360 
SFSKPSNSWF PVEGSADICQ CCNKGDCGTP SHSRRQPHVM SQWSRSASRN RRHVTEEADV 

       370        380        390        400        410        420 
TVGPLIFLDR RGDHEVEQWA LPSDTSVVLL GVGLAVVVSL TLTAVILVLT RRCRTASHPV 


SASE 

« Hide

Isoform ZP3B [UniParc].

Checksum: AB7BD85572DB7B4A
Show »

FASTA37241,469
Isoform 3 [UniParc].

Checksum: 2CF838B25DC801C0
Show »

FASTA37341,272

References

« Hide 'large scale' references
[1]"Human homolog of the mouse sperm receptor."
Chamberlin M.E., Dean J.
Proc. Natl. Acad. Sci. U.S.A. 87:6014-6018(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ZP3A), VARIANT PRO-315.
[2]"Cloning and characterization of the human sperm receptor ligand ZP3: evidence for a second polymorphic allele with a different frequency in the Caucasian and Japanese populations."
van Duin M., Polman J.E., Verkoelen C.C., Bunschoten H., Meyerink J.H., Olijve W., Aitken R.J.
Genomics 14:1064-1070(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ZP3A AND ZP3B), VARIANT PRO-315.
Tissue: Ovary.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT PRO-315.
Tissue: Lung.
[4]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] (ISOFORM 3), VARIANT PRO-315.
Tissue: Brain.
[6]"Mass spectrometry analysis of recombinant human ZP3 expressed in glycosylation-deficient CHO cells."
Zhao M., Boja E.S., Hoodbhoy T., Nawrocki J., Kaufman J.B., Kresge N., Ghirlando R., Shiloach J., Pannell L., Levine R.L., Fales H.M., Dean J.
Biochemistry 43:12090-12104(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SIGNAL SEQUENCE CLEAVAGE SITE, PYROGLUTAMATE FORMATION AT GLU-23, PROTEOLYTIC PROCESSING, DISULFIDE BONDS, GLYCOSYLATION AT ASN-125; ASN-147 AND ASN-272.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Molecular chastity - Issue 93 of April 2008

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M60504 mRNA. Translation: AAA61336.1.
X56777 mRNA. Translation: CAA40095.1.
AK292763 mRNA. Translation: BAF85452.1.
AC005522 Genomic DNA. No translation available.
BC113949 mRNA. Translation: AAI13950.2.
PIRA36000.
RefSeqNP_001103824.1. NM_001110354.1.
NP_009086.4. NM_007155.5.
UniGeneHs.656137.

3D structure databases

ProteinModelPortalP21754.
SMRP21754. Positions 41-330.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113565. 9 interactions.
STRING9606.ENSP00000378326.

PTM databases

PhosphoSiteP21754.

Polymorphism databases

DMDM251757420.

Proteomic databases

PaxDbP21754.
PRIDEP21754.

Protocols and materials databases

DNASU7784.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000336517; ENSP00000337310; ENSG00000188372. [P21754-3]
ENST00000394857; ENSP00000378326; ENSG00000188372. [P21754-1]
GeneID7784.
KEGGhsa:7784.
UCSCuc003ufc.4. human. [P21754-1]

Organism-specific databases

CTD7784.
GeneCardsGC07P076026.
HGNCHGNC:13189. ZP3.
HPAHPA054061.
MIM182889. gene.
neXtProtNX_P21754.
PharmGKBPA37757.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG43042.
HOGENOMHOG000220813.
HOVERGENHBG007985.
OMALMEEDWG.
OrthoDBEOG773XG3.
PhylomeDBP21754.
TreeFamTF331369.

Enzyme and pathway databases

ReactomeREACT_163848. Reproduction.

Gene expression databases

ArrayExpressP21754.
BgeeP21754.
CleanExHS_ZP3.
GenevestigatorP21754.

Family and domain databases

InterProIPR001507. ZP_dom.
IPR017977. ZP_dom_CS.
[Graphical view]
PfamPF00100. Zona_pellucida. 1 hit.
[Graphical view]
PRINTSPR00023. ZPELLUCIDA.
SMARTSM00241. ZP. 1 hit.
[Graphical view]
PROSITEPS00682. ZP_1. 1 hit.
PS51034. ZP_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiZP3.
GenomeRNAi7784.
NextBio30137.
PROP21754.
SOURCESearch...

Entry information

Entry nameZP3_HUMAN
AccessionPrimary (citable) accession number: P21754
Secondary accession number(s): Q06633, Q29RW0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: July 7, 2009
Last modified: April 16, 2014
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM