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    SPAM1 sperm adhesion molecule 1 [ Homo sapiens (human) ]

    Gene ID: 6677, updated on 9-Dec-2024

    Summary

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    Official Symbol
    SPAM1provided by HGNC
    Official Full Name
    sperm adhesion molecule 1provided by HGNC
    Primary source
    HGNC:HGNC:11217
    See related
    Ensembl:ENSG00000106304 MIM:600930; AllianceGenome:HGNC:11217
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HYA1; PH20; HYAL1; HYAL3; HYAL5; PH-20; SPAG15; HEL-S-96n
    Summary
    Hyaluronidase degrades hyaluronic acid, a major structural proteoglycan found in extracellular matrices and basement membranes. Six members of the hyaluronidase family are clustered into two tightly linked groups on chromosome 3p21.3 and 7q31.3. This gene was previously referred to as HYAL1 and HYA1 and has since been assigned the official symbol SPAM1; another family member on chromosome 3p21.3 has been assigned HYAL1. This gene encodes a GPI-anchored enzyme located on the human sperm surface and inner acrosomal membrane. This multifunctional protein is a hyaluronidase that enables sperm to penetrate through the hyaluronic acid-rich cumulus cell layer surrounding the oocyte, a receptor that plays a role in hyaluronic acid induced cell signaling, and a receptor that is involved in sperm-zona pellucida adhesion. Abnormal expression of this gene in tumors has implicated this protein in degradation of basement membranes leading to tumor invasion and metastasis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]
    Expression
    Restricted expression toward testis (RPKM 5.9) See more
    Orthologs
    all
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    Genomic context

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    See SPAM1 in Genome Data Viewer
    Location:
    7q31.32
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (123925241..123971414)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (125241959..125288129)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (123565295..123611468)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene hyaluronidase 4 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr7:123438019-123438540 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:123438541-123439062 Neighboring gene RNA, U6 small nuclear 11, pseudogene Neighboring gene hyaluronidase 6, pseudogene Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr7:123534015-123535214 Neighboring gene COX6A1 pseudogene 6 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr7:123634231-123635109 Neighboring gene uncharacterized LOC105375483 Neighboring gene transmembrane protein 229A

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. N-Glycosylation and enzymatic activity of the rHuPH20 expressed in Chinese hamster ovary cells. Liu T, et al. Anal Biochem, 2021 Nov 1. PMID 34520755
    2. A hyaluronidase activity of the sperm plasma membrane protein PH-20 enables sperm to penetrate the cumulus cell layer surrounding the egg. Lin Y, et al. J Cell Biol, 1994 Jun. PMID 8195297, Free PMC Article
    3. The human sperm protein PH-20 has hyaluronidase activity. Gmachl M, et al. FEBS Lett, 1993 Dec 28. PMID 8282124
    4. Expression analysis, genomic structure, and mapping to 7q31 of the human sperm adhesion molecule gene SPAM1. Jones MH, et al. Genomics, 1995 Oct 10. PMID 8575780
    5. Sperm adhesion molecules: structure and function. Jansen S, et al. Cells Tissues Organs, 2001. PMID 11114590

    See all (26) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Low acrosin activity is associated with decreased Spam1/acrosin expression and GSH deficiency-caused premature acrosome release of human sperm cells.
      Title: Low acrosin activity is associated with decreased Spam1/acrosin expression and GSH deficiency-caused premature acrosome release of human sperm cells.
    2. N-Glycosylation and enzymatic activity of the rHuPH20 expressed in Chinese hamster ovary cells.
      Title: N-Glycosylation and enzymatic activity of the rHuPH20 expressed in Chinese hamster ovary cells.
    3. Human Hyaluronidase PH20 Potentiates the Antitumor Activities of Mesothelin-Specific CAR-T Cells Against Gastric Cancer.
      Title: Human Hyaluronidase PH20 Potentiates the Antitumor Activities of Mesothelin-Specific CAR-T Cells Against Gastric Cancer.
    4. Human posterior head 20 (hPH20) and homo sapiens sperm acrosome associated 1 (hSPACA1) immunocontraceptive epitopes reduced fertility in male/female mice.
      Title: Discovery of human posterior head 20 (hPH20) and homo sapiens sperm acrosome associated 1 (hSPACA1) immunocontraceptive epitopes and their effects on fertility in male and female mice.
    5. results indicate that neither rHuPH20 nor its directly generated HA catabolites have inflammatory properties in the air pouch model, and rHuPH20 can instead inhibit some aspects of inflammation, such as neutrophil infiltration into the air pouch.
      Title: Recombinant human hyaluronidase PH20 does not stimulate an acute inflammatory response and inhibits lipopolysaccharide-induced neutrophil recruitment in the air pouch model of inflammation.
    6. HSPA2 regulates the expression of sperm surface receptors involved in human sperm-oocyte recognition, such as arylsulfatase A and SPAM1.
      Title: Investigation of the mechanisms by which the molecular chaperone HSPA2 regulates the expression of sperm surface receptors involved in human sperm-oocyte recognition.
    7. The interaction between SPAM1, ARSA and HSPA2 in a multimeric complex mediating sperm-egg interaction.
      Title: The molecular chaperone HSPA2 plays a key role in regulating the expression of sperm surface receptors that mediate sperm-egg recognition.
    8. PH20 is elevated in demyelinating lesions and that increased PH20 expression is sufficient to inhibit oligodendrocyte precursor cell maturation and remyelination.
      Title: Digestion products of the PH20 hyaluronidase inhibit remyelination.
    9. Observational study of gene-disease association. (HuGE Navigator)
      Title: Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.
    10. SPAM1 mRNA & protein occur in all 3 regions of epididymis & vas deferens. It has hyaluronidase activity at pH 7.0. The proximal promoter has epididymal transcription factor sites including androgen receptor elements. Its role may be in sperm maturation.
      Title: SPAM1 (PH-20) protein and mRNA expression in the epididymides of humans and macaques: utilizing laser microdissection/RT-PCR.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC26532

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables hyalurononglucosaminidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in binding of sperm to zona pellucida TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in carbohydrate metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell adhesion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in fusion of sperm to egg plasma membrane involved in single fertilization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in hyaluronan catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in acrosomal vesicle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in side of membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    hyaluronidase PH-20
    Names
    PH-20 hyaluronidase
    epididymis secretory sperm binding protein Li 96n
    hyal-PH20
    hyaluronoglucosaminidase PH-20
    sperm adhesion molecule 1 (PH-20 hyaluronidase, zona pellucida binding)
    sperm surface protein PH-20
    NP_001167515.1
    NP_001167516.1
    NP_001167517.1
    NP_003108.2
    NP_694859.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001174044.2 → NP_001167515.1  hyaluronidase PH-20 isoform 2

      See identical proteins and their annotated locations for NP_001167515.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and uses an alternate splice pattern in the 3' coding region and 3' UTR, compared to variant 1, resulting in a shorter and distinct C-terminus (isoform 2). Variants 2-5 all encode the same isoform.
      Source sequence(s)
      AY920278, X84347
      Consensus CDS
      CCDS5791.1
      UniProtKB/Swiss-Prot
      P38567, Q8TC30
      UniProtKB/TrEMBL
      Q5D1J4
      Related
      ENSP00000417934.1, ENST00000460182.5
      Conserved Domains (1) summary
      pfam01630
      Location:42 → 369
      Glyco_hydro_56; Hyaluronidase

    2. NM_001174045.2 → NP_001167516.1  hyaluronidase PH-20 isoform 2

      See identical proteins and their annotated locations for NP_001167516.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and uses an alternate splice pattern in the 3' coding region and 3' UTR, compared to variant 1, resulting in a shorter and distinct C-terminus (isoform 2). Variants 2-5 all encode the same isoform.
      Source sequence(s)
      AK292229, AY920280, X84347
      Consensus CDS
      CCDS5791.1
      UniProtKB/Swiss-Prot
      P38567, Q8TC30
      UniProtKB/TrEMBL
      Q5D1J4
      Related
      ENSP00000402123.1, ENST00000439500.5
      Conserved Domains (1) summary
      pfam01630
      Location:42 → 369
      Glyco_hydro_56; Hyaluronidase

    3. NM_001174046.2 → NP_001167517.1  hyaluronidase PH-20 isoform 2

      See identical proteins and their annotated locations for NP_001167517.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR and uses an alternate splice pattern in the 3' coding region and 3' UTR, compared to variant 1, resulting in a shorter and distinct C-terminus (isoform 2). Variants 2-5 all encode the same isoform.
      Source sequence(s)
      AK292229, AY920281, X84347
      Consensus CDS
      CCDS5791.1
      UniProtKB/Swiss-Prot
      P38567, Q8TC30
      UniProtKB/TrEMBL
      Q5D1J4
      Conserved Domains (1) summary
      pfam01630
      Location:42 → 369
      Glyco_hydro_56; Hyaluronidase

    4. NM_003117.5 → NP_003108.2  hyaluronidase PH-20 isoform 1

      See identical proteins and their annotated locations for NP_003108.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC004690, AK292229, AY920279, BC026163
      Consensus CDS
      CCDS5790.1
      UniProtKB/Swiss-Prot
      P38567
      UniProtKB/TrEMBL
      Q5D1J4
      Related
      ENSP00000345849.5, ENST00000340011.9
      Conserved Domains (1) summary
      pfam01630
      Location:42 → 369
      Glyco_hydro_56; Hyaluronidase

    5. NM_153189.3 → NP_694859.1  hyaluronidase PH-20 isoform 2

      See identical proteins and their annotated locations for NP_694859.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice pattern in the 3' coding region and 3' UTR, compared to variant 1, resulting in a shorter and distinct C-terminus (isoform 2). Variants 2-5 all encode the same isoform.
      Source sequence(s)
      AY920279, X84347
      Consensus CDS
      CCDS5791.1
      UniProtKB/Swiss-Prot
      P38567, Q8TC30
      UniProtKB/TrEMBL
      Q5D1J4
      Related
      ENSP00000508393.1, ENST00000682466.1
      Conserved Domains (1) summary
      pfam01630
      Location:42 → 369
      Glyco_hydro_56; Hyaluronidase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      123925241..123971414
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      125241959..125288129
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P38567.1 GenPept UniProtKB/Swiss-Prot:P38567

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