HYALP_HUMAN
ID HYALP_HUMAN Reviewed; 509 AA.
AC P38567; Q8TC30;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Hyaluronidase PH-20;
DE Short=Hyal-PH20;
DE EC=3.2.1.35;
DE AltName: Full=Hyaluronoglucosaminidase PH-20;
DE AltName: Full=Sperm adhesion molecule 1;
DE AltName: Full=Sperm surface protein PH-20;
DE Flags: Precursor;
GN Name=SPAM1; Synonyms=HYAL3, PH20;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=8234258; DOI=10.1073/pnas.90.21.10071;
RA Lin Y., Kimmel L.H., Myles D.G., Primakoff P.;
RT "Molecular cloning of the human and monkey sperm surface protein PH-20.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:10071-10075(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC TISSUE=Testis;
RX PubMed=8282124; DOI=10.1016/0014-5793(93)80873-s;
RA Gmachl M., Sagan S., Ketter S., Kreil G.;
RT "The human sperm protein PH-20 has hyaluronidase activity.";
RL FEBS Lett. 336:545-548(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=8575780; DOI=10.1006/geno.1995.9931;
RA Jones M.H., Davey P.M., Aplin H., Affara N.A.;
RT "Expression analysis, genomic structure, and mapping to 7q31 of the human
RT sperm adhesion molecule gene SPAM1.";
RL Genomics 29:796-800(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP MUTAGENESIS OF ASP-146; GLU-148; ARG-211; GLU-284 AND ARG-287, AND
RP GLYCOSYLATION.
RX PubMed=9288901; DOI=10.1111/j.1432-1033.1997.t01-1-00810.x;
RA Arming S., Strobl B., Wechselberger C., Kreil G.;
RT "In vitro mutagenesis of PH-20 hyaluronidase from human sperm.";
RL Eur. J. Biochem. 247:810-814(1997).
RN [9]
RP VARIANT GLN-5.
RX PubMed=21248752; DOI=10.1038/nature09639;
RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT PBRM1 in renal carcinoma.";
RL Nature 469:539-542(2011).
CC -!- FUNCTION: Involved in sperm-egg adhesion. Upon fertilization sperm must
CC first penetrate a layer of cumulus cells that surrounds the egg before
CC reaching the zona pellucida. The cumulus cells are embedded in a matrix
CC containing hyaluronic acid which is formed prior to ovulation. This
CC protein aids in penetrating the layer of cumulus cells by digesting
CC hyaluronic acid. {ECO:0000269|PubMed:8282124}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Random hydrolysis of (1->4)-linkages between N-acetyl-beta-D-
CC glucosamine and D-glucuronate residues in hyaluronate.; EC=3.2.1.35;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P38567-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P38567-2; Sequence=VSP_042714;
CC -!- TISSUE SPECIFICITY: Testis. {ECO:0000269|PubMed:8234258}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:9288901}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 56 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SPAM1ID42361ch7q31.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L13781; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; S67798; AAC60607.2; -; mRNA.
DR EMBL; X84347; CAA59086.1; -; mRNA.
DR EMBL; AC004690; AAQ96882.1; -; Genomic_DNA.
DR EMBL; CH236947; EAL24329.1; -; Genomic_DNA.
DR EMBL; CH471070; EAW83606.1; -; Genomic_DNA.
DR EMBL; BC026163; AAH26163.1; -; mRNA.
DR CCDS; CCDS5790.1; -. [P38567-2]
DR CCDS; CCDS5791.1; -. [P38567-1]
DR PIR; S40465; S40465.
DR RefSeq; NP_001167515.1; NM_001174044.1. [P38567-1]
DR RefSeq; NP_001167516.1; NM_001174045.1. [P38567-1]
DR RefSeq; NP_001167517.1; NM_001174046.1. [P38567-1]
DR RefSeq; NP_003108.2; NM_003117.4. [P38567-2]
DR RefSeq; NP_694859.1; NM_153189.2. [P38567-1]
DR AlphaFoldDB; P38567; -.
DR SMR; P38567; -.
DR BioGRID; 112559; 1.
DR STRING; 9606.ENSP00000345849; -.
DR DrugBank; DB08818; Hyaluronic acid.
DR CAZy; GH56; Glycoside Hydrolase Family 56.
DR GlyGen; P38567; 6 sites.
DR iPTMnet; P38567; -.
DR PhosphoSitePlus; P38567; -.
DR BioMuta; SPAM1; -.
DR DMDM; 585673; -.
DR MassIVE; P38567; -.
DR PaxDb; P38567; -.
DR PeptideAtlas; P38567; -.
DR PRIDE; P38567; -.
DR ProteomicsDB; 55298; -. [P38567-1]
DR ProteomicsDB; 55299; -. [P38567-2]
DR Antibodypedia; 2991; 190 antibodies from 24 providers.
DR DNASU; 6677; -.
DR Ensembl; ENST00000223028.11; ENSP00000223028.7; ENSG00000106304.16. [P38567-1]
DR Ensembl; ENST00000340011.9; ENSP00000345849.5; ENSG00000106304.16. [P38567-2]
DR Ensembl; ENST00000402183.3; ENSP00000386028.3; ENSG00000106304.16. [P38567-2]
DR Ensembl; ENST00000439500.5; ENSP00000402123.1; ENSG00000106304.16. [P38567-1]
DR Ensembl; ENST00000460182.5; ENSP00000417934.1; ENSG00000106304.16. [P38567-1]
DR Ensembl; ENST00000682466.1; ENSP00000508393.1; ENSG00000106304.16. [P38567-1]
DR GeneID; 6677; -.
DR KEGG; hsa:6677; -.
DR MANE-Select; ENST00000682466.1; ENSP00000508393.1; NM_153189.3; NP_694859.1.
DR UCSC; uc003vle.4; human. [P38567-1]
DR CTD; 6677; -.
DR DisGeNET; 6677; -.
DR GeneCards; SPAM1; -.
DR HGNC; HGNC:11217; SPAM1.
DR HPA; ENSG00000106304; Tissue enriched (testis).
DR MIM; 600930; gene.
DR neXtProt; NX_P38567; -.
DR OpenTargets; ENSG00000106304; -.
DR PharmGKB; PA36053; -.
DR VEuPathDB; HostDB:ENSG00000106304; -.
DR eggNOG; ENOG502R6HD; Eukaryota.
DR GeneTree; ENSGT01020000230364; -.
DR HOGENOM; CLU_036366_0_1_1; -.
DR InParanoid; P38567; -.
DR OMA; RAKIVFE; -.
DR PhylomeDB; P38567; -.
DR TreeFam; TF321598; -.
DR BioCyc; MetaCyc:HS02884-MON; -.
DR BRENDA; 3.2.1.35; 2681.
DR PathwayCommons; P38567; -.
DR Reactome; R-HSA-2534343; Interaction With Cumulus Cells And The Zona Pellucida.
DR BioGRID-ORCS; 6677; 7 hits in 1056 CRISPR screens.
DR GeneWiki; SPAM1; -.
DR GenomeRNAi; 6677; -.
DR Pharos; P38567; Tbio.
DR PRO; PR:P38567; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P38567; protein.
DR Bgee; ENSG00000106304; Expressed in sperm and 23 other tissues.
DR ExpressionAtlas; P38567; baseline and differential.
DR Genevisible; P38567; HS.
DR GO; GO:0001669; C:acrosomal vesicle; IBA:GO_Central.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004415; F:hyalurononglucosaminidase activity; IBA:GO_Central.
DR GO; GO:0007339; P:binding of sperm to zona pellucida; TAS:ProtInc.
DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:ProtInc.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0007342; P:fusion of sperm to egg plasma membrane involved in single fertilization; IEA:InterPro.
DR GO; GO:0030214; P:hyaluronan catabolic process; IBA:GO_Central.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR InterPro; IPR018155; Hyaluronidase.
DR InterPro; IPR001439; Hyaluronidase_PH20/Hyal5.
DR PANTHER; PTHR11769; PTHR11769; 1.
DR Pfam; PF01630; Glyco_hydro_56; 1.
DR PIRSF; PIRSF038193; Hyaluronidase; 1.
DR PIRSF; PIRSF500773; Hyaluronidase_PH20_Hyal5; 1.
DR PRINTS; PR00846; GLHYDRLASE56.
DR SUPFAM; SSF51445; SSF51445; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell adhesion; Cell membrane; Disulfide bond;
KW Glycoprotein; Glycosidase; GPI-anchor; Hydrolase; Lipoprotein; Membrane;
KW Reference proteome; Signal.
FT SIGNAL 1..35
FT /evidence="ECO:0000250"
FT CHAIN 36..490
FT /note="Hyaluronidase PH-20"
FT /id="PRO_0000012089"
FT PROPEP 491..509
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000012090"
FT ACT_SITE 148
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT LIPID 490
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 82
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 254
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 368
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 393
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 60..351
FT /evidence="ECO:0000250"
FT DISULFID 224..238
FT /evidence="ECO:0000250"
FT DISULFID 376..387
FT /evidence="ECO:0000250"
FT DISULFID 381..435
FT /evidence="ECO:0000250"
FT DISULFID 437..464
FT /evidence="ECO:0000250"
FT VAR_SEQ 496..509
FT /note="VSILFLIISSVASL -> WRLEVWDQGISRIGFF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_042714"
FT VARIANT 5
FT /note="K -> Q (found in a renal cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064756"
FT VARIANT 47
FT /note="V -> A (in dbSNP:rs34633019)"
FT /id="VAR_049213"
FT MUTAGEN 146
FT /note="D->N: Reduces activity by 80%."
FT /evidence="ECO:0000269|PubMed:9288901"
FT MUTAGEN 148
FT /note="E->Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:9288901"
FT MUTAGEN 211
FT /note="R->G: Reduces activity by over 90%."
FT /evidence="ECO:0000269|PubMed:9288901"
FT MUTAGEN 284
FT /note="E->Q: Loss of activity."
FT /evidence="ECO:0000269|PubMed:9288901"
FT MUTAGEN 287
FT /note="R->T: Loss of activity."
FT /evidence="ECO:0000269|PubMed:9288901"
FT CONFLICT 48
FT /note="P -> A (in Ref. 2; AAC60607)"
FT /evidence="ECO:0000305"
FT CONFLICT 499
FT /note="L -> W (in Ref. 2; AAC60607)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 509 AA; 57848 MW; 5ADB4739747E32E8 CRC64;
MGVLKFKHIF FRSFVKSSGV SQIVFTFLLI PCCLTLNFRA PPVIPNVPFL WAWNAPSEFC
LGKFDEPLDM SLFSFIGSPR INATGQGVTI FYVDRLGYYP YIDSITGVTV NGGIPQKISL
QDHLDKAKKD ITFYMPVDNL GMAVIDWEEW RPTWARNWKP KDVYKNRSIE LVQQQNVQLS
LTEATEKAKQ EFEKAGKDFL VETIKLGKLL RPNHLWGYYL FPDCYNHHYK KPGYNGSCFN
VEIKRNDDLS WLWNESTALY PSIYLNTQQS PVAATLYVRN RVREAIRVSK IPDAKSPLPV
FAYTRIVFTD QVLKFLSQDE LVYTFGETVA LGASGIVIWG TLSIMRSMKS CLLLDNYMET
ILNPYIINVT LAAKMCSQVL CQEQGVCIRK NWNSSDYLHL NPDNFAIQLE KGGKFTVRGK
PTLEDLEQFS EKFYCSCYST LSCKEKADVK DTDAVDVCIA DGVCIDAFLK PPMETEEPQI
FYNASPSTLS ATMFIVSILF LIISSVASL
