P38567 (HYALP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hyaluronidase PH-20
Short name=Hyal-PH20
EC=3.2.1.35

Alternative name(s):
Hyaluronoglucosaminidase PH-20
Sperm adhesion molecule 1
Sperm surface protein PH-20

Gene names

Name:	SPAM1
Synonyms:	HYAL3, PH20

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	509 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	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. Ref.2
Catalytic activity	Random hydrolysis of (1->4)-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate.
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor.
Tissue specificity	Testis. Ref.1
Post-translational modification	N-glycosylated. Ref.5
Sequence similarities	Belongs to the glycosyl hydrolase 56 family.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Glycosidase Hydrolase
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	binding of sperm to zona pellucida Traceable author statement. Source: ProtInc carbohydrate metabolic process Traceable author statement. Source: ProtInc cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW fusion of sperm to egg plasma membrane Inferred from electronic annotation. Source: InterPro
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: ProtInc
Molecular function	hyalurononglucosaminidase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 35	35	By similarity
	Chain	36 – 490	455	Hyaluronidase PH-20		PRO_0000012089
	Propeptide	491 – 509	19	Removed in mature form Potential		PRO_0000012090
Sites
	Active site	148	1	Proton donor By similarity
Amino acid modifications
	Lipidation	490	1	GPI-anchor amidated serine Potential
	Glycosylation	82	1	N-linked (GlcNAc...) Potential
	Glycosylation	166	1	N-linked (GlcNAc...) Potential
	Glycosylation	235	1	N-linked (GlcNAc...) Potential
	Glycosylation	254	1	N-linked (GlcNAc...) Potential
	Glycosylation	368	1	N-linked (GlcNAc...) Potential
	Glycosylation	393	1	N-linked (GlcNAc...) Potential
	Disulfide bond	60 ↔ 351		By similarity
	Disulfide bond	224 ↔ 238		By similarity
	Disulfide bond	376 ↔ 387		By similarity
	Disulfide bond	381 ↔ 435		By similarity
	Disulfide bond	437 ↔ 464		By similarity
Natural variations
	Natural variant	5	1	K → Q Found in a renal cell carcinoma sample; somatic mutation. Ref.6		VAR_064756
	Natural variant	47	1	V → A. Corresponds to variant rs34633019 [ dbSNP | Ensembl ].		VAR_049213
Experimental info
	Mutagenesis	146	1	D → N: Reduces activity by 80%. Ref.5
	Mutagenesis	148	1	E → Q: Loss of activity. Ref.5
	Mutagenesis	211	1	R → G: Reduces activity by over 90%. Ref.5
	Mutagenesis	284	1	E → Q: Loss of activity. Ref.5
	Mutagenesis	287	1	R → T: Loss of activity. Ref.5
	Sequence conflict	48	1	P → A in AAC60607. Ref.2
	Sequence conflict	499	1	L → W in AAC60607. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P38567 [UniParc]. Last modified October 1, 1994. Version 1. Checksum: 5ADB4739747E32E8	FASTA	509	57,848
	10 20 30 40 50 60 MGVLKFKHIF FRSFVKSSGV SQIVFTFLLI PCCLTLNFRA PPVIPNVPFL WAWNAPSEFC 70 80 90 100 110 120 LGKFDEPLDM SLFSFIGSPR INATGQGVTI FYVDRLGYYP YIDSITGVTV NGGIPQKISL 130 140 150 160 170 180 QDHLDKAKKD ITFYMPVDNL GMAVIDWEEW RPTWARNWKP KDVYKNRSIE LVQQQNVQLS 190 200 210 220 230 240 LTEATEKAKQ EFEKAGKDFL VETIKLGKLL RPNHLWGYYL FPDCYNHHYK KPGYNGSCFN 250 260 270 280 290 300 VEIKRNDDLS WLWNESTALY PSIYLNTQQS PVAATLYVRN RVREAIRVSK IPDAKSPLPV 310 320 330 340 350 360 FAYTRIVFTD QVLKFLSQDE LVYTFGETVA LGASGIVIWG TLSIMRSMKS CLLLDNYMET 370 380 390 400 410 420 ILNPYIINVT LAAKMCSQVL CQEQGVCIRK NWNSSDYLHL NPDNFAIQLE KGGKFTVRGK 430 440 450 460 470 480 PTLEDLEQFS EKFYCSCYST LSCKEKADVK DTDAVDVCIA DGVCIDAFLK PPMETEEPQI 490 500 FYNASPSTLS ATMFIVSILF LIISSVASL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of the human and monkey sperm surface protein PH-20." Lin Y., Kimmel L.H., Myles D.G., Primakoff P. Proc. Natl. Acad. Sci. U.S.A. 90:10071-10075(1993) [PubMed: 8234258] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Testis.
[2]	"The human sperm protein PH-20 has hyaluronidase activity." Gmachl M., Sagan S., Ketter S., Kreil G. FEBS Lett. 336:545-548(1993) [PubMed: 8282124] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Testis.
[3]	"Expression analysis, genomic structure, and mapping to 7q31 of the human sperm adhesion molecule gene SPAM1." Jones M.H., Davey P.M., Aplin H., Affara N.A. Genomics 29:796-800(1995) [PubMed: 8575780] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[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: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"In vitro mutagenesis of PH-20 hyaluronidase from human sperm." Arming S., Strobl B., Wechselberger C., Kreil G. Eur. J. Biochem. 247:810-814(1997) [PubMed: 9288901] [Abstract] Cited for: MUTAGENESIS OF ASP-146; GLU-148; ARG-211; GLU-284 AND ARG-287, GLYCOSYLATION.
[6]	"Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma." Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M. , Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A. Nature 469:539-542(2011) [PubMed: 21248752] [Abstract] Cited for: VARIANT GLN-5.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L13781 mRNA. No translation available. S67798 mRNA. Translation: AAC60607.2. X84347 mRNA. Translation: CAA59086.1. AC004690 Genomic DNA. Translation: AAQ96882.1.
IPI	IPI00219717.
PIR	S40465.
RefSeq	NP_001167515.1. NM_001174044.1. NP_001167516.1. NM_001174045.1. NP_001167517.1. NM_001174046.1. NP_694859.1. NM_153189.2.
UniGene	Hs.121494.
3D structure databases
ProteinModelPortal	P38567.
SMR	P38567. Positions 37-446.
ModBase	Search...
Protein-protein interaction databases
STRING	P38567.
Protein family/group databases
CAZy	GH56. Glycoside Hydrolase Family 56.
Polymorphism databases
DMDM	585673.
Proteomic databases
PRIDE	P38567.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000223028; ENSP00000223028; ENSG00000106304. ENST00000439500; ENSP00000402123; ENSG00000106304. ENST00000460182; ENSP00000417934; ENSG00000106304.
GeneID	6677.
KEGG	hsa:6677.
UCSC	uc003vld.1. human.
Organism-specific databases
CTD	6677.
GeneCards	GC07P123565.
HGNC	HGNC:11217. SPAM1.
HPA	HPA017984.
MIM	600930. gene.
neXtProt	NX_P38567.
PharmGKB	PA36053.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG05950.
HOVERGEN	HBG052053.
Enzyme and pathway databases
BioCyc	MetaCyc:HS02884-MONOMER.
Gene expression databases
ArrayExpress	P38567.
Bgee	P38567.
CleanEx	HS_HYAL3. HS_SPAM1.
Genevestigator	P38567.
GermOnline	ENSG00000106304. Homo sapiens.
Family and domain databases
InterPro	IPR013785. Aldolase_TIM. IPR001439. Glyco_hydro_56_PH20. IPR017853. Glycoside_hydrolase_SF. IPR018155. Hyaluronidase. [Graphical view]
Gene3D	G3DSA:3.20.20.70. Aldolase_TIM. 1 hit.
KO	K01197.
PANTHER	PTHR11769. Glyco_hydro_56. 1 hit. PTHR11769:SF4. Glyco_hydro_56_PH20. 1 hit.
Pfam	PF01630. Glyco_hydro_56. 1 hit. [Graphical view]
PIRSF	PIRSF038193. Hyaluronidase. 1 hit.
PRINTS	PR00846. GLHYDRLASE56. PR00848. SPERMPH20.
SUPFAM	SSF51445. Glyco_hydro_cat. 1 hit.
ProtoNet	Search...
Other
DrugBank	DB00070. Hyaluronidase.
NextBio	26035.
SOURCE	Search...

Entry information

Entry name

HYALP_HUMAN

Accession

Primary (citable) accession number: P38567

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	October 1, 1994
Last modified:	January 25, 2012
This is version 112 of the entry and version 1 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.