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    SPRTN SprT-like N-terminal domain [ Homo sapiens (human) ]

    Gene ID: 83932, updated on 13-Apr-2024

    Summary

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    Official Symbol
    SPRTNprovided by HGNC
    Official Full Name
    SprT-like N-terminal domainprovided by HGNC
    Primary source
    HGNC:HGNC:25356
    See related
    Ensembl:ENSG00000010072 MIM:616086; AllianceGenome:HGNC:25356
    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
    DVC1; PRO4323; spartan; C1orf124
    Summary
    The protein encoded by this gene may play a role in DNA repair during replication of damaged DNA. This protein recruits valosin containing protein (p97) to stalled DNA replication forks where it may prevent excessive translesional DNA synthesis and limit the number of DNA-damage induced mutations. It may also be involved in replication-related G2/M-checkpoint regulation. Deficiency of a similar protein in mouse causes chromosomal instability and progeroid phenotypes. Mutations in this gene have been associated with Ruijs-Aalfs syndrome (RJALS). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]
    Expression
    Broad expression in testis (RPKM 6.8), bone marrow (RPKM 3.1) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    1q42.2
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (231338293..231355023)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (230721543..230738274)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (231474039..231490769)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr1:231420145-231420646 Neighboring gene RNA, 5S ribosomal pseudogene 80 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:231472900-231473775 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:231473776-231474650 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:231474651-231475525 Neighboring gene exocyst complex component 8 Neighboring gene uncharacterized LOC107985360 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2729 Neighboring gene egl-9 family hypoxia inducible factor 1 Neighboring gene Sharpr-MPRA regulatory region 11665 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:231538414-231538617 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2730 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:231558174-231558498 Neighboring gene small nuclear ribonucleoprotein D2 pseudogene 2

    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. SPRTN patient variants cause global-genome DNA-protein crosslink repair defects. Weickert P, et al. Nat Commun, 2023 Jan 21. PMID 36681662, Free PMC Article
    2. The protease SPRTN and SUMOylation coordinate DNA-protein crosslink repair to prevent genome instability. Ruggiano A, et al. Cell Rep, 2021 Dec 7. PMID 34879279, Free PMC Article
    3. A ubiquitin switch controls autocatalytic inactivation of the DNA-protein crosslink repair protease SPRTN. Zhao S, et al. Nucleic Acids Res, 2021 Jan 25. PMID 33348378, Free PMC Article
    4. DNA Structure-Specific Cleavage of DNA-Protein Crosslinks by the SPRTN Protease. Reinking HK, et al. Mol Cell, 2020 Oct 1. PMID 32853547, Free PMC Article
    5. Structural Insight into DNA-Dependent Activation of Human Metalloprotease Spartan. Li F, et al. Cell Rep, 2019 Mar 19. PMID 30893605

    See all (45) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. SPRTN is involved in hepatocellular carcinoma development through the ER stress response.
      Title: SPRTN is involved in hepatocellular carcinoma development through the ER stress response.
    2. SPRTN patient variants cause global-genome DNA-protein crosslink repair defects.
      Title: SPRTN patient variants cause global-genome DNA-protein crosslink repair defects.
    3. Ubiquitin-directed AAA+ ATPase p97/VCP unfolds stable proteins crosslinked to DNA for proteolysis by SPRTN.
      Title: Ubiquitin-directed AAA+ ATPase p97/VCP unfolds stable proteins crosslinked to DNA for proteolysis by SPRTN.
    4. The protease SPRTN and SUMOylation coordinate DNA-protein crosslink repair to prevent genome instability.
      Title: The protease SPRTN and SUMOylation coordinate DNA-protein crosslink repair to prevent genome instability.
    5. Replication-dependent cytotoxicity and Spartan-mediated repair of trapped PARP1-DNA complexes.
      Title: Replication-dependent cytotoxicity and Spartan-mediated repair of trapped PARP1-DNA complexes.
    6. SPRTN protease-cleaved MRE11 decreases DNA repair and radiosensitises cancer cells.
      Title: SPRTN protease-cleaved MRE11 decreases DNA repair and radiosensitises cancer cells.
    7. USP11 mediates repair of DNA-protein cross-links by deubiquitinating SPRTN metalloprotease.
      Title: USP11 mediates repair of DNA-protein cross-links by deubiquitinating SPRTN metalloprotease.
    8. A ubiquitin switch controls autocatalytic inactivation of the DNA-protein crosslink repair protease SPRTN.
      Title: A ubiquitin switch controls autocatalytic inactivation of the DNA-protein crosslink repair protease SPRTN.
    9. DNA Structure-Specific Cleavage of DNA-Protein Crosslinks by the SPRTN Protease.
      Title: DNA Structure-Specific Cleavage of DNA-Protein Crosslinks by the SPRTN Protease.
    10. TEX264 recognises both unmodified and SUMO1-modifed TOP1 and initiates TOP1cc repair by recruiting p97 and SPRTN.
      Title: TEX264 coordinates p97- and SPRTN-mediated resolution of topoisomerase 1-DNA adducts.
    Submit: New GeneRIF Correction See all GeneRIFs (26)

    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

    Associated conditions

    Description Tests
    Progeroid features-hepatocellular carcinoma predisposition syndrome
    MedGen: C4015461 OMIM: 616200 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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

    • dJ876B10.3, DKFZp547N043

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables K63-linked polyubiquitin modification-dependent protein binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metalloendopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables polyubiquitin modification-dependent protein binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables single-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ubiquitin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA damage response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in DNA damage response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein autoprocessing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein-DNA covalent cross-linking repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in proteolysis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to UV IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in translesion synthesis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in translesion synthesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nuclear speck IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    DNA-dependent metalloprotease SPRTN
    Names
    DNA damage protein targeting VCP
    DNA damage-targeting VCP (p97) adaptor
    zinc finger RAD18 domain-containing protein
    NP_001010984.1
    NP_001248391.1
    NP_114407.3
    XP_006711881.1
    XP_054194986.1

    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_042052.1 RefSeqGene

      Range
      5358..22088
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001010984.4 → NP_001010984.1  DNA-dependent metalloprotease SPRTN isoform b

      See identical proteins and their annotated locations for NP_001010984.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has an alternate segment in the 3' end which results in the introduction of an early stop codon, compared to variant 1. This variant encodes a protein (isoform B) with a shorter C-terminus which lacks a Rad18-like CCHC zinc finger domain, compared to isoform A.
      Source sequence(s)
      AL117352, AY358611, BC068478, BU630543
      Consensus CDS
      CCDS31054.1
      UniProtKB/Swiss-Prot
      Q9H040
      Related
      ENSP00000375731.4, ENST00000391858.8
      Conserved Domains (1) summary
      pfam10263
      Location:45 → 213
      SprT-like; SprT-like family

    2. NM_001261462.3 → NP_001248391.1  DNA-dependent metalloprotease SPRTN isoform c

      See identical proteins and their annotated locations for NP_001248391.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks a coding exon and has an alternate segment in the 3' end which results in the introduction of an early stop codon, compared to variant 1. This variant encodes a protein (isoform C) with a shorter C-terminus which lacks a Rad18-like CCHC zinc finger domain, compared to isoform A.
      Source sequence(s)
      AL117352, AY358611, BC068478, BU630543
      Consensus CDS
      CCDS58066.1
      UniProtKB/Swiss-Prot
      Q9H040
      Related
      ENSP00000008440.9, ENST00000008440.9
      Conserved Domains (1) summary
      pfam10263
      Location:45 → 170
      SprT-like; SprT-like family

    3. NM_032018.7 → NP_114407.3  DNA-dependent metalloprotease SPRTN isoform a

      See identical proteins and their annotated locations for NP_114407.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (A).
      Source sequence(s)
      AL117352, BC068478, BU630543
      Consensus CDS
      CCDS1594.1
      UniProtKB/Swiss-Prot
      B1AKT0, B5MEF7, Q5TE78, Q6UWW6, Q96BC5, Q96KA0, Q9H040
      Related
      ENSP00000295050.7, ENST00000295050.12
      Conserved Domains (2) summary
      smart00734
      Location:453 → 476
      ZnF_Rad18; Rad18-like CCHC zinc finger
      pfam10263
      Location:45 → 213
      SprT-like; SprT-like family

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      231338293..231355023
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006711818.4 → XP_006711881.1  DNA-dependent metalloprotease SPRTN isoform X1

      Conserved Domains (2) summary
      smart00734
      Location:410 → 433
      ZnF_Rad18; Rad18-like CCHC zinc finger
      smart00731
      Location:43 → 169
      SprT; SprT homologues

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      230721543..230738274
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054339011.1 → XP_054194986.1  DNA-dependent metalloprotease SPRTN isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9H040.2 GenPept UniProtKB/Swiss-Prot:Q9H040

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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