P21754 (ZP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	424 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	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: Secreted › extracellular space › extracellular matrix. 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 process	Fertilization
Cellular component	Cell membrane Extracellular matrix Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Pyrrolidone carboxylic acid
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	binding of sperm to zona pellucida Inferred from direct assay PubMed 19246320PubMed 19700799. Source: UniProtKB blastocyst formation Inferred from sequence or structural similarity. Source: UniProtKB 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 negative regulation of binding of sperm to zona pellucida Inferred from direct assay PubMed 18667750. Source: UniProtKB negative regulation of transcription, DNA-dependent 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 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 cascade 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-dependent 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 cascade Inferred from mutant phenotype PubMed 18667750. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from sequence or structural similarity. Source: UniProtKB endoplasmic reticulum Inferred from sequence or structural similarity. Source: UniProtKB extracellular matrix Inferred from direct assay PubMed 19246320. Source: UniProtKB extracellular space Inferred from mutant phenotype PubMed 19246320. Source: UniProtKB integral to 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
Molecular_function	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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22
	Chain	23 – 350	328	Zona pellucida sperm-binding protein 3		PRO_0000041709
	Chain	23 – ?		Processed zona pellucida sperm-binding protein 3		PRO_0000304569
	Propeptide	351 – 424	74	Removed in mature form By similarity		PRO_0000041710
Regions
	Topological domain	23 – 387	365	Extracellular Potential
	Transmembrane	388 – 408	21	Helical; Potential
	Topological domain	409 – 424	16	Cytoplasmic Potential
	Domain	45 – 307	263	ZP
Amino acid modifications
	Modified residue	23	1	Pyrrolidone carboxylic acid
	Glycosylation	125	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	147	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	156	1	O-linked (GalNAc...) By similarity
	Glycosylation	162	1	O-linked (GalNAc...) By similarity
	Glycosylation	163	1	O-linked (GalNAc...) By similarity
	Glycosylation	226	1	N-linked (GlcNAc...) Potential
	Glycosylation	272	1	N-linked (GlcNAc...) Ref.6
	Disulfide bond	46 ↔ 140		Ref.6
	Disulfide bond	78 ↔ 99		Ref.6
	Disulfide bond	217 ↔ 282		Ref.6
	Disulfide bond	239 ↔ 300		Ref.6
Natural variations
	Alternative sequence	1 – 51	51	Missing in isoform 3.		VSP_037556
	Alternative sequence	364 – 372	9	PLIFLDRRG → ATDLPGQEW in isoform ZP3B.		VSP_006949
	Alternative sequence	373 – 424	52	Missing in isoform ZP3B.		VSP_006950
	Natural variant	31	1	G → R. Corresponds to variant rs2286428 [ dbSNP | Ensembl ].		VAR_058011
	Natural variant	315	1	S → P. Ref.1 Ref.2 Ref.3 Ref.5 Corresponds to variant rs2906999 [ dbSNP | Ensembl ].		VAR_058012
	Natural variant	340	1	M → V. Corresponds to variant rs2906997 [ dbSNP | Ensembl ].		VAR_058013
Experimental info
	Sequence conflict	345	1	R → T in CAA40095. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform ZP3A [UniParc]. Last modified July 7, 2009. Version 2. Checksum: 0F3CCDA2427C0E3A	FASTA	424	47,018
	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
	Isoform ZP3B [UniParc]. Checksum: AB7BD85572DB7B4A	FASTA	372	41,469
	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 TVGATDLPGQ EW
	Isoform 3 [UniParc]. Checksum: 2CF838B25DC801C0	FASTA	373	41,272
	10 20 30 40 50 60 MVMVSKDLFG TGKLIRAADL TLGPEACEPL VSMDTEDVVR FEVGLHECGN SMQVTDDALV 70 80 90 100 110 120 YSTFLLHDPR PVGNLSIVRT NRAEIPIECR YPRQGNVSSQ AILPTWLPFR TTVFSEEKLT 130 140 150 160 170 180 FSLRLMEENW NAEKRSPTFH LGDAAHLQAE IHTGSHVPLR LFVDHCVATP TPDQNASPYH 190 200 210 220 230 240 TIVDFHGCLV DGLTDASSAF KVPRPGPDTL QFTVDVFHFA NDSRNMIYIT CHLKVTLAEQ 250 260 270 280 290 300 DPDELNKACS FSKPSNSWFP VEGSADICQC CNKGDCGTPS HSRRQPHVMS QWSRSASRNR 310 320 330 340 350 360 RHVTEEADVT VGPLIFLDRR GDHEVEQWAL PSDTSVVLLG VGLAVVVSLT LTAVILVLTR 370 RCRTASHPVS ASE

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00010350. IPI00218458. IPI00736368.
PIR	A36000.
RefSeq	NP_001103824.1. NM_001110354.1. NP_009086.4. NM_007155.5.
UniGene	Hs.656137.
3D structure databases
ProteinModelPortal	P21754.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000378326.
PTM databases
PhosphoSite	P21754.
Polymorphism databases
DMDM	251757420.
Proteomic databases
PaxDb	P21754.
PRIDE	P21754.
Protocols and materials databases
DNASU	7784.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000336517; ENSP00000337310; ENSG00000188372. ENST00000394857; ENSP00000378326; ENSG00000188372.
GeneID	7784.
KEGG	hsa:7784.
UCSC	uc003ufc.4. human.
Organism-specific databases
CTD	7784.
GeneCards	GC07P076026.
HGNC	HGNC:13189. ZP3.
HPA	HPA054061.
MIM	182889. gene.
neXtProt	NX_P21754.
PharmGKB	PA37757.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG43042.
HOGENOM	HOG000220813.
HOVERGEN	HBG007985.
OMA	TPDQNAS.
Gene expression databases
ArrayExpress	P21754.
Bgee	P21754.
CleanEx	HS_ZP3.
Genevestigator	P21754.
GermOnline	ENSG00000188372. Homo sapiens.
Family and domain databases
InterPro	IPR001507. ZP_dom. IPR017977. ZP_dom_CS. [Graphical view]
Pfam	PF00100. Zona_pellucida. 1 hit. [Graphical view]
PRINTS	PR00023. ZPELLUCIDA.
SMART	SM00241. ZP. 1 hit. [Graphical view]
PROSITE	PS00682. ZP_1. 1 hit. PS51034. ZP_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	7784.
NextBio	30137.
SOURCE	Search...

Entry information

Entry name

ZP3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 122 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.