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Protein

Hyaluronidase PH-20

Gene

SPAM1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in sperm-egg adhesion. Upon fertilization sperm must first penetrate a layer of cumulus cells that surrounds the egg before reaching the zona pellucida. The cumulus cells are embedded in a matrix containing hyaluronic acid which is formed prior to ovulation. This protein aids in penetrating the layer of cumulus cells by digesting hyaluronic acid.1 Publication

Catalytic activityi

Random hydrolysis of (1->4)-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei148Proton donorBy similarity1

GO - Molecular functioni

GO - Biological processi

  • binding of sperm to zona pellucida Source: ProtInc
  • carbohydrate metabolic process Source: ProtInc
  • cell adhesion Source: UniProtKB-KW
  • fusion of sperm to egg plasma membrane Source: InterPro
  • penetration of zona pellucida Source: Ensembl
  • sperm-egg recognition Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Keywords - Biological processi

Cell adhesion

Enzyme and pathway databases

BioCyciMetaCyc:HS02884-MONOMER.
ZFISH:HS02884-MONOMER.
ReactomeiR-HSA-2534343. Interaction With Cumulus Cells.

Protein family/group databases

CAZyiGH56. Glycoside Hydrolase Family 56.

Names & Taxonomyi

Protein namesi
Recommended name:
Hyaluronidase PH-20 (EC:3.2.1.35)
Short name:
Hyal-PH20
Alternative name(s):
Hyaluronoglucosaminidase PH-20
Sperm adhesion molecule 1
Sperm surface protein PH-20
Gene namesi
Name:SPAM1
Synonyms:HYAL3, PH20
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:11217. SPAM1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi146D → N: Reduces activity by 80%. 1 Publication1
Mutagenesisi148E → Q: Loss of activity. 1 Publication1
Mutagenesisi211R → G: Reduces activity by over 90%. 1 Publication1
Mutagenesisi284E → Q: Loss of activity. 1 Publication1
Mutagenesisi287R → T: Loss of activity. 1 Publication1

Organism-specific databases

DisGeNETi6677.
OpenTargetsiENSG00000106304.
PharmGKBiPA36053.

Polymorphism and mutation databases

BioMutaiSPAM1.
DMDMi585673.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 35By similarityAdd BLAST35
ChainiPRO_000001208936 – 490Hyaluronidase PH-20Add BLAST455
PropeptideiPRO_0000012090491 – 509Removed in mature formSequence analysisAdd BLAST19

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi60 ↔ 351By similarity
Glycosylationi82N-linked (GlcNAc...)Sequence analysis1
Glycosylationi166N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi224 ↔ 238By similarity
Glycosylationi235N-linked (GlcNAc...)Sequence analysis1
Glycosylationi254N-linked (GlcNAc...)Sequence analysis1
Glycosylationi368N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi376 ↔ 387By similarity
Disulfide bondi381 ↔ 435By similarity
Glycosylationi393N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi437 ↔ 464By similarity
Lipidationi490GPI-anchor amidated serineSequence analysis1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiP38567.
PeptideAtlasiP38567.
PRIDEiP38567.

PTM databases

iPTMnetiP38567.
PhosphoSitePlusiP38567.

Expressioni

Tissue specificityi

Testis.1 Publication

Gene expression databases

BgeeiENSG00000106304.
CleanExiHS_HYAL3.
HS_SPAM1.
ExpressionAtlasiP38567. baseline and differential.
GenevisibleiP38567. HS.

Organism-specific databases

HPAiHPA017984.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000345849.

Structurei

3D structure databases

ProteinModelPortaliP38567.
SMRiP38567.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the glycosyl hydrolase 56 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IECJ. Eukaryota.
ENOG410XPZT. LUCA.
GeneTreeiENSGT00550000074476.
HOGENOMiHOG000015133.
HOVERGENiHBG052053.
InParanoidiP38567.
KOiK01197.
OMAiHLNPDNF.
OrthoDBiEOG091G064G.
PhylomeDBiP38567.
TreeFamiTF321598.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR017853. Glycoside_hydrolase_SF.
IPR018155. Hyaluronidase.
IPR001439. Hyaluronidase_PH20.
[Graphical view]
PANTHERiPTHR11769. PTHR11769. 1 hit.
PfamiPF01630. Glyco_hydro_56. 1 hit.
[Graphical view]
PIRSFiPIRSF038193. Hyaluronidase. 1 hit.
PIRSF500773. Hyaluronidase_PH20_Hyal5. 1 hit.
PRINTSiPR00846. GLHYDRLASE56.
SUPFAMiSSF51445. SSF51445. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P38567-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGVLKFKHIF FRSFVKSSGV SQIVFTFLLI PCCLTLNFRA PPVIPNVPFL
60 70 80 90 100
WAWNAPSEFC LGKFDEPLDM SLFSFIGSPR INATGQGVTI FYVDRLGYYP
110 120 130 140 150
YIDSITGVTV NGGIPQKISL QDHLDKAKKD ITFYMPVDNL GMAVIDWEEW
160 170 180 190 200
RPTWARNWKP KDVYKNRSIE LVQQQNVQLS LTEATEKAKQ EFEKAGKDFL
210 220 230 240 250
VETIKLGKLL RPNHLWGYYL FPDCYNHHYK KPGYNGSCFN VEIKRNDDLS
260 270 280 290 300
WLWNESTALY PSIYLNTQQS PVAATLYVRN RVREAIRVSK IPDAKSPLPV
310 320 330 340 350
FAYTRIVFTD QVLKFLSQDE LVYTFGETVA LGASGIVIWG TLSIMRSMKS
360 370 380 390 400
CLLLDNYMET ILNPYIINVT LAAKMCSQVL CQEQGVCIRK NWNSSDYLHL
410 420 430 440 450
NPDNFAIQLE KGGKFTVRGK PTLEDLEQFS EKFYCSCYST LSCKEKADVK
460 470 480 490 500
DTDAVDVCIA DGVCIDAFLK PPMETEEPQI FYNASPSTLS ATMFIVSILF

LIISSVASL
Length:509
Mass (Da):57,848
Last modified:October 1, 1994 - v1
Checksum:i5ADB4739747E32E8
GO
Isoform 2 (identifier: P38567-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     496-509: VSILFLIISSVASL → WRLEVWDQGISRIGFF

Note: No experimental confirmation available.
Show »
Length:511
Mass (Da):58,395
Checksum:i8620113DE58741C7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti48P → A in AAC60607 (PubMed:8282124).Curated1
Sequence conflicti499L → W in AAC60607 (PubMed:8282124).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0647565K → Q Found in a renal cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_04921347V → A.Corresponds to variant rs34633019dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_042714496 – 509VSILF…SVASL → WRLEVWDQGISRIGFF in isoform 2. 1 PublicationAdd BLAST14

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L13781 mRNA. No translation available.
S67798 mRNA. Translation: AAC60607.2.
X84347 mRNA. Translation: CAA59086.1.
AC004690 Genomic DNA. Translation: AAQ96882.1.
CH236947 Genomic DNA. Translation: EAL24329.1.
CH471070 Genomic DNA. Translation: EAW83606.1.
BC026163 mRNA. Translation: AAH26163.1.
CCDSiCCDS5790.1. [P38567-2]
CCDS5791.1. [P38567-1]
PIRiS40465.
RefSeqiNP_001167515.1. NM_001174044.1. [P38567-1]
NP_001167516.1. NM_001174045.1. [P38567-1]
NP_001167517.1. NM_001174046.1. [P38567-1]
NP_003108.2. NM_003117.4. [P38567-2]
NP_694859.1. NM_153189.2. [P38567-1]
UniGeneiHs.121494.

Genome annotation databases

EnsembliENST00000223028; ENSP00000223028; ENSG00000106304. [P38567-1]
ENST00000340011; ENSP00000345849; ENSG00000106304. [P38567-2]
ENST00000402183; ENSP00000386028; ENSG00000106304. [P38567-2]
ENST00000439500; ENSP00000402123; ENSG00000106304. [P38567-1]
ENST00000460182; ENSP00000417934; ENSG00000106304. [P38567-1]
GeneIDi6677.
KEGGihsa:6677.
UCSCiuc003vle.4. human. [P38567-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L13781 mRNA. No translation available.
S67798 mRNA. Translation: AAC60607.2.
X84347 mRNA. Translation: CAA59086.1.
AC004690 Genomic DNA. Translation: AAQ96882.1.
CH236947 Genomic DNA. Translation: EAL24329.1.
CH471070 Genomic DNA. Translation: EAW83606.1.
BC026163 mRNA. Translation: AAH26163.1.
CCDSiCCDS5790.1. [P38567-2]
CCDS5791.1. [P38567-1]
PIRiS40465.
RefSeqiNP_001167515.1. NM_001174044.1. [P38567-1]
NP_001167516.1. NM_001174045.1. [P38567-1]
NP_001167517.1. NM_001174046.1. [P38567-1]
NP_003108.2. NM_003117.4. [P38567-2]
NP_694859.1. NM_153189.2. [P38567-1]
UniGeneiHs.121494.

3D structure databases

ProteinModelPortaliP38567.
SMRiP38567.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000345849.

Protein family/group databases

CAZyiGH56. Glycoside Hydrolase Family 56.

PTM databases

iPTMnetiP38567.
PhosphoSitePlusiP38567.

Polymorphism and mutation databases

BioMutaiSPAM1.
DMDMi585673.

Proteomic databases

PaxDbiP38567.
PeptideAtlasiP38567.
PRIDEiP38567.

Protocols and materials databases

DNASUi6677.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000223028; ENSP00000223028; ENSG00000106304. [P38567-1]
ENST00000340011; ENSP00000345849; ENSG00000106304. [P38567-2]
ENST00000402183; ENSP00000386028; ENSG00000106304. [P38567-2]
ENST00000439500; ENSP00000402123; ENSG00000106304. [P38567-1]
ENST00000460182; ENSP00000417934; ENSG00000106304. [P38567-1]
GeneIDi6677.
KEGGihsa:6677.
UCSCiuc003vle.4. human. [P38567-1]

Organism-specific databases

CTDi6677.
DisGeNETi6677.
GeneCardsiSPAM1.
HGNCiHGNC:11217. SPAM1.
HPAiHPA017984.
MIMi600930. gene.
neXtProtiNX_P38567.
OpenTargetsiENSG00000106304.
PharmGKBiPA36053.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IECJ. Eukaryota.
ENOG410XPZT. LUCA.
GeneTreeiENSGT00550000074476.
HOGENOMiHOG000015133.
HOVERGENiHBG052053.
InParanoidiP38567.
KOiK01197.
OMAiHLNPDNF.
OrthoDBiEOG091G064G.
PhylomeDBiP38567.
TreeFamiTF321598.

Enzyme and pathway databases

BioCyciMetaCyc:HS02884-MONOMER.
ZFISH:HS02884-MONOMER.
ReactomeiR-HSA-2534343. Interaction With Cumulus Cells.

Miscellaneous databases

GeneWikiiSPAM1.
GenomeRNAii6677.
PROiP38567.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000106304.
CleanExiHS_HYAL3.
HS_SPAM1.
ExpressionAtlasiP38567. baseline and differential.
GenevisibleiP38567. HS.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR017853. Glycoside_hydrolase_SF.
IPR018155. Hyaluronidase.
IPR001439. Hyaluronidase_PH20.
[Graphical view]
PANTHERiPTHR11769. PTHR11769. 1 hit.
PfamiPF01630. Glyco_hydro_56. 1 hit.
[Graphical view]
PIRSFiPIRSF038193. Hyaluronidase. 1 hit.
PIRSF500773. Hyaluronidase_PH20_Hyal5. 1 hit.
PRINTSiPR00846. GLHYDRLASE56.
SUPFAMiSSF51445. SSF51445. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiHYALP_HUMAN
AccessioniPrimary (citable) accession number: P38567
Secondary accession number(s): Q8TC30
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1994
Last modified: November 30, 2016
This is version 154 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.