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    SYN3 synapsin III [ Homo sapiens (human) ]

    Gene ID: 8224, updated on 10-Dec-2024

    Summary

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    Official Symbol
    SYN3provided by HGNC
    Official Full Name
    synapsin IIIprovided by HGNC
    Primary source
    HGNC:HGNC:11496
    See related
    Ensembl:ENSG00000185666 MIM:602705; AllianceGenome:HGNC:11496
    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
    Summary
    This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. The protein encoded by this gene shares the synapsin family domain model, with domains A, C, and E exhibiting the highest degree of conservation. The protein contains a unique domain J, located between domains C and E. Based on this gene's localization to 22q12.3, a possible schizophrenia susceptibility locus, and the established neurobiological roles of the synapsins, this family member may represent a candidate gene for schizophrenia. The TIMP3 gene is located within an intron of this gene and is transcribed in the opposite direction. Alternative splicing of this gene results in multiple splice variants that encode different isoforms. [provided by RefSeq, Oct 2008]
    Expression
    Biased expression in brain (RPKM 2.3), testis (RPKM 0.7) and 6 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SYN3 in Genome Data Viewer
    Location:
    22q12.3
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (32507820..33058381, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (32971715..33522831, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (32903807..33454367, complement)

    Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18877 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:32870558-32871058 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:32871059-32871559 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_63238 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_63240 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_63244 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr22:32898207-32898893 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:32897520-32898206 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:32924873-32925374 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:32925375-32925874 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:32927678-32928315 Neighboring gene uncharacterized LOC124905103 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:32928316-32928952 Neighboring gene BPI fold containing family C Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:33012121-33012620 Neighboring gene uncharacterized LOC107985545 Neighboring gene F-box protein 7 Neighboring gene uncharacterized LOC105373002 Neighboring gene SYN3 antisense RNA 1 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr22:33056914-33058113 Neighboring gene RNA, 5S ribosomal pseudogene 497 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:33148296-33149080 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:33153563-33153744 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:33159884-33160394 Neighboring gene uncharacterized LOC124905104 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:33216313-33216812 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:33271816-33272028 Neighboring gene Sharpr-MPRA regulatory region 12398 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:33283107-33283317 Neighboring gene TIMP metallopeptidase inhibitor 3 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:33347343-33347844 Neighboring gene Sharpr-MPRA regulatory region 592 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:33382939-33383840 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:33448207-33448890 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr22:33450113-33450805 Neighboring gene ETFRF1 pseudogene 1 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr22:33506225-33507424 Neighboring gene uncharacterized LOC124905107 Neighboring gene long intergenic non-protein coding RNA 1640 Neighboring gene LARGE xylosyl- and glucuronyltransferase 1

    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. Molecular and in silico analyses of SYN III gene variants in autism spectrum disorder. Baris RO, et al. Ir J Med Sci, 2023 Dec. PMID 37166614
    2. Characterization of transcripts from the synapsin III gene locus. Porton B, et al. J Neurochem, 1999 Dec. PMID 10582583
    3. Mutation analysis of synapsin III gene in schizophrenia. Tsai MT, et al. Am J Med Genet, 2002 Jan 8. PMID 11840510
    4. A rare polymorphism affects a mitogen-activated protein kinase site in synapsin III: possible relationship to schizophrenia. Porton B, et al. Biol Psychiatry, 2004 Jan 15. PMID 14732590
    5. Synapsin III is a key component of α-synuclein fibrils in Lewy bodies of PD brains. Longhena F, et al. Brain Pathol, 2018 Nov. PMID 29330884, Free PMC Article

    See all (42) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Molecular and in silico analyses of SYN III gene variants in autism spectrum disorder.
      Title: Molecular and in silico analyses of SYN III gene variants in autism spectrum disorder.
    2. Investigation of possible associations of the BDNF, SNAP-25 and SYN III genes with the neurocognitive measures: BDNF and SNAP-25 genes might be involved in attention domain, SYN III gene in executive function.
      Title: Investigation of possible associations of the BDNF, SNAP-25 and SYN III genes with the neurocognitive measures: BDNF and SNAP-25 genes might be involved in attention domain, SYN III gene in executive function.
    3. Synapsin III is a crucial alpha-synuclein interactant and a key component of Lewy bodies fibrils in the brain of patients affected by Parkinson's disease.
      Title: Synapsin III is a key component of α-synuclein fibrils in Lewy bodies of PD brains.
    4. These findings contribute to previous work showing dysregulation of Synapsins, particularly SYN2, in mood disorders and improve our understanding of the regulatory mechanisms that precipitate these changes likely leading to the BD or MDD phenotype.
      Title: DNA hypomethylation of Synapsin II CpG islands associates with increased gene expression in bipolar disorder and major depression.
    5. Syn-3 may mimic Syn-1A in the ability to bind and modulate Cavs, but preferring Cav2.3 to perhaps participate in triggering fusion of newcomer insulin SGs during second-phase GSIS.
      Title: Syntaxin-3 Binds and Regulates Both R- and L-Type Calcium Channels in Insulin-Secreting INS-1 832/13 Cells.
    6. These findings support a reciprocal modulatory interaction of alpha-syn and synapsin III in the regulation of dopamine neuron synaptic function.
      Title: α-synuclein and synapsin III cooperatively regulate synaptic function in dopamine neurons.
    7. The variations of MnSOD (rs4880) and SYN III (rs3788470, rs3827336, rs5998557) were not major risk factors for PD among Chinese, at least in our study populations
      Title: No association of four candidate genetic variants in MnSOD and SYNIII with Parkinson's disease in two Chinese populations.
    8. A significant difference was determined between attention deficit hyperactivity disorder and synapsin III gene -631 C>G polymorphism compared to the control group.
      Title: Association of synapsin III gene with adult attention deficit hyperactivity disorder.
    9. A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration.
      Title: Proteomic analysis identifies dysfunction in cellular transport, energy, and protein metabolism in different brain regions of atypical frontotemporal lobar degeneration.
    10. This protein has been found differentially expressed in thalami from patients with schizophrenia.
      Title: Proteome analysis of the thalamus and cerebrospinal fluid reveals glycolysis dysfunction and potential biomarkers candidates for schizophrenia.
    Submit: New GeneRIF Correction See all GeneRIFs (21)

    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

    EBI GWAS Catalog

    Description
    Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration.
    EBI GWAS Catalog
    Hundreds of variants clustered in genomic loci and biological pathways affect human height.
    EBI GWAS Catalog
    Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
    EBI GWAS Catalog

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in neurotransmitter secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of synaptic transmission, GABAergic TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in synapse organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in synaptic vesicle clustering IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in extrinsic component of synaptic vesicle membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in postsynaptic density IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in synaptic vesicle TAS
    Traceable Author Statement
    more info
    		 PubMed 
    is_active_in synaptic vesicle membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    synapsin-3
    Names
    cN28H9.2 (synapsin III)

    NCBI Reference Sequences (RefSeq)

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    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.

    Genomic

    1. NG_029545.2 RefSeqGene

      Range
      5000..555561
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001135774.2 → NP_001129246.1  synapsin-3 isoform IIIg

      See identical proteins and their annotated locations for NP_001129246.1

      Status: REVIEWED

      Source sequence(s)
      Z71183, Z80902, Z82181, Z82246, Z83846, Z98256
      UniProtKB/TrEMBL
      Q17R54, Q59EX7
      Conserved Domains (4) summary
      PRK07764
      Location:393 → 535
      PRK07764; DNA polymerase III subunits gamma and tau; Validated
      pfam02078
      Location:93 → 189
      Synapsin; N-terminal domain
      pfam10581
      Location:1 → 29
      Synapsin_N; Synapsin N-terminal
      cl17255
      Location:192 → 394
      CPSase_L_D2; Carbamoyl-phosphate synthase L chain, ATP binding domain

    2. NM_001369907.1 → NP_001356836.1  synapsin-3 isoform IIIa

      Status: REVIEWED

      Source sequence(s)
      Z71183, Z80902, Z82181, Z82246, Z83846, Z98256
      Consensus CDS
      CCDS13908.1
      UniProtKB/Swiss-Prot
      B1B1F9, O14994
      UniProtKB/TrEMBL
      Q59EX7
      Conserved Domains (4) summary
      PRK07764
      Location:394 → 536
      PRK07764; DNA polymerase III subunits gamma and tau; Validated
      pfam02078
      Location:93 → 190
      Synapsin; N-terminal domain
      pfam10581
      Location:1 → 29
      Synapsin_N; Synapsin N-terminal
      cl17255
      Location:193 → 395
      CPSase_L_D2; Carbamoyl-phosphate synthase L chain, ATP binding domain

    3. NM_001369908.1 → NP_001356837.1  synapsin-3 isoform IIIa

      Status: REVIEWED

      Source sequence(s)
      Z71183, Z80902, Z82181, Z82246, Z83846, Z98256
      Consensus CDS
      CCDS13908.1
      UniProtKB/Swiss-Prot
      B1B1F9, O14994
      UniProtKB/TrEMBL
      Q59EX7
      Conserved Domains (4) summary
      PRK07764
      Location:394 → 536
      PRK07764; DNA polymerase III subunits gamma and tau; Validated
      pfam02078
      Location:93 → 190
      Synapsin; N-terminal domain
      pfam10581
      Location:1 → 29
      Synapsin_N; Synapsin N-terminal
      cl17255
      Location:193 → 395
      CPSase_L_D2; Carbamoyl-phosphate synthase L chain, ATP binding domain

    4. NM_001369909.1 → NP_001356838.1  synapsin-3 isoform IIIg

      Status: REVIEWED

      Source sequence(s)
      Z71183, Z80902, Z82181, Z82246, Z83846, Z98256
      UniProtKB/TrEMBL
      Q17R54, Q59EX7
      Conserved Domains (4) summary
      PRK07764
      Location:393 → 535
      PRK07764; DNA polymerase III subunits gamma and tau; Validated
      pfam02078
      Location:93 → 189
      Synapsin; N-terminal domain
      pfam10581
      Location:1 → 29
      Synapsin_N; Synapsin N-terminal
      cl17255
      Location:192 → 394
      CPSase_L_D2; Carbamoyl-phosphate synthase L chain, ATP binding domain

    5. NM_001369910.1 → NP_001356839.1  synapsin-3 isoform IIIg

      Status: REVIEWED

      Source sequence(s)
      Z71183, Z80902, Z82181, Z82246, Z83846, Z98256
      UniProtKB/TrEMBL
      Q17R54, Q59EX7
      Conserved Domains (4) summary
      PRK07764
      Location:393 → 535
      PRK07764; DNA polymerase III subunits gamma and tau; Validated
      pfam02078
      Location:93 → 189
      Synapsin; N-terminal domain
      pfam10581
      Location:1 → 29
      Synapsin_N; Synapsin N-terminal
      cl17255
      Location:192 → 394
      CPSase_L_D2; Carbamoyl-phosphate synthase L chain, ATP binding domain

    6. NM_003490.4 → NP_003481.3  synapsin-3 isoform IIIa

      See identical proteins and their annotated locations for NP_003481.3

      Status: REVIEWED

      Source sequence(s)
      Z71183, Z80902, Z82181, Z82246, Z83846, Z98256
      Consensus CDS
      CCDS13908.1
      UniProtKB/Swiss-Prot
      B1B1F9, O14994
      UniProtKB/TrEMBL
      Q59EX7
      Related
      ENSP00000351614.2, ENST00000358763.7
      Conserved Domains (4) summary
      PRK07764
      Location:394 → 536
      PRK07764; DNA polymerase III subunits gamma and tau; Validated
      pfam02078
      Location:93 → 190
      Synapsin; N-terminal domain
      pfam10581
      Location:1 → 29
      Synapsin_N; Synapsin N-terminal
      cl17255
      Location:193 → 395
      CPSase_L_D2; Carbamoyl-phosphate synthase L chain, ATP binding domain

    7. NM_133633.3 → NP_598344.2  synapsin-3 isoform IIIc

      See identical proteins and their annotated locations for NP_598344.2

      Status: REVIEWED

      Source sequence(s)
      Z71183, Z80902, Z82181, Z82246, Z83846, Z98256
      UniProtKB/Swiss-Prot
      O14994
      Conserved Domains (3) summary
      pfam02078
      Location:93 → 190
      Synapsin; Synapsin, N-terminal domain
      pfam02750
      Location:193 → 395
      Synapsin_C; Synapsin, ATP binding domain
      pfam10581
      Location:1 → 29
      Synapsin_N; Synapsin N-terminal

    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_000022.11 Reference GRCh38.p14 Primary Assembly

      Range
      32507820..33058381 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047441527.1 → XP_047297483.1  synapsin-3 isoform X2

      UniProtKB/TrEMBL
      Q17R54, Q59EX7

    2. XM_017028961.3 → XP_016884450.1  synapsin-3 isoform X1

      UniProtKB/Swiss-Prot
      B1B1F9, O14994
      UniProtKB/TrEMBL
      Q59EX7
      Conserved Domains (4) summary
      PRK07764
      Location:394 → 536
      PRK07764; DNA polymerase III subunits gamma and tau; Validated
      pfam02078
      Location:93 → 190
      Synapsin; N-terminal domain
      pfam10581
      Location:1 → 29
      Synapsin_N; Synapsin N-terminal
      cl17255
      Location:193 → 395
      CPSase_L_D2; Carbamoyl-phosphate synthase L chain, ATP binding domain

    3. XM_017028962.3 → XP_016884451.1  synapsin-3 isoform X1

      UniProtKB/Swiss-Prot
      B1B1F9, O14994
      UniProtKB/TrEMBL
      Q59EX7
      Conserved Domains (4) summary
      PRK07764
      Location:394 → 536
      PRK07764; DNA polymerase III subunits gamma and tau; Validated
      pfam02078
      Location:93 → 190
      Synapsin; N-terminal domain
      pfam10581
      Location:1 → 29
      Synapsin_N; Synapsin N-terminal
      cl17255
      Location:193 → 395
      CPSase_L_D2; Carbamoyl-phosphate synthase L chain, ATP binding domain

    4. XM_047441525.1 → XP_047297481.1  synapsin-3 isoform X2

      UniProtKB/TrEMBL
      Q17R54, Q59EX7

    5. XM_017028963.3 → XP_016884452.1  synapsin-3 isoform X1

      UniProtKB/Swiss-Prot
      B1B1F9, O14994
      UniProtKB/TrEMBL
      Q59EX7
      Conserved Domains (4) summary
      PRK07764
      Location:394 → 536
      PRK07764; DNA polymerase III subunits gamma and tau; Validated
      pfam02078
      Location:93 → 190
      Synapsin; N-terminal domain
      pfam10581
      Location:1 → 29
      Synapsin_N; Synapsin N-terminal
      cl17255
      Location:193 → 395
      CPSase_L_D2; Carbamoyl-phosphate synthase L chain, ATP binding domain

    6. XM_047441526.1 → XP_047297482.1  synapsin-3 isoform X2

      UniProtKB/TrEMBL
      Q17R54, Q59EX7

    7. XM_011530405.4 → XP_011528707.1  synapsin-3 isoform X1

      See identical proteins and their annotated locations for XP_011528707.1

      UniProtKB/Swiss-Prot
      B1B1F9, O14994
      UniProtKB/TrEMBL
      Q59EX7
      Conserved Domains (4) summary
      PRK07764
      Location:394 → 536
      PRK07764; DNA polymerase III subunits gamma and tau; Validated
      pfam02078
      Location:93 → 190
      Synapsin; N-terminal domain
      pfam10581
      Location:1 → 29
      Synapsin_N; Synapsin N-terminal
      cl17255
      Location:193 → 395
      CPSase_L_D2; Carbamoyl-phosphate synthase L chain, ATP binding domain

    8. XM_011530410.4 → XP_011528712.1  synapsin-3 isoform X3

      Conserved Domains (3) summary
      pfam02078
      Location:5 → 72
      Synapsin; Synapsin, N-terminal domain
      pfam02750
      Location:75 → 277
      Synapsin_C; Synapsin, ATP binding domain
      pfam16620
      Location:330 → 441
      23ISL; Unstructured linker between I-set domains 2 and 3 on MYLCK

    9. XM_047441529.1 → XP_047297485.1  synapsin-3 isoform X4

    10. XM_047441528.1 → XP_047297484.1  synapsin-3 isoform X4

    11. XM_047441530.1 → XP_047297486.1  synapsin-3 isoform X5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060946.1 Alternate T2T-CHM13v2.0

      Range
      32971715..33522831 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054325984.1 → XP_054181959.1  synapsin-3 isoform X2

      UniProtKB/TrEMBL
      Q17R54, Q59EX7

    2. XM_054325981.1 → XP_054181956.1  synapsin-3 isoform X1

      UniProtKB/Swiss-Prot
      B1B1F9, O14994
      UniProtKB/TrEMBL
      Q59EX7

    3. XM_054325978.1 → XP_054181953.1  synapsin-3 isoform X1

      UniProtKB/Swiss-Prot
      B1B1F9, O14994
      UniProtKB/TrEMBL
      Q59EX7

    4. XM_054325982.1 → XP_054181957.1  synapsin-3 isoform X2

      UniProtKB/TrEMBL
      Q17R54, Q59EX7

    5. XM_054325979.1 → XP_054181954.1  synapsin-3 isoform X1

      UniProtKB/Swiss-Prot
      B1B1F9, O14994
      UniProtKB/TrEMBL
      Q59EX7

    6. XM_054325983.1 → XP_054181958.1  synapsin-3 isoform X2

      UniProtKB/TrEMBL
      Q17R54, Q59EX7

    7. XM_054325980.1 → XP_054181955.1  synapsin-3 isoform X1

      UniProtKB/Swiss-Prot
      B1B1F9, O14994
      UniProtKB/TrEMBL
      Q59EX7

    8. XM_054325985.1 → XP_054181960.1  synapsin-3 isoform X3

    9. XM_054325987.1 → XP_054181962.1  synapsin-3 isoform X4

    10. XM_054325988.1 → XP_054181963.1  synapsin-3 isoform X4

    11. XM_054325986.1 → XP_054181961.1  synapsin-3 isoform X4

    12. XM_054325989.1 → XP_054181964.1  synapsin-3 isoform X5

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_133632.1: Suppressed sequence

      Description
      NM_133632.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O14994.2 GenPept UniProtKB/Swiss-Prot:O14994

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