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    SERPINB6 serpin family B member 6 [ Homo sapiens (human) ]

    Gene ID: 5269, updated on 10-Dec-2024

    Summary

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    Official Symbol
    SERPINB6provided by HGNC
    Official Full Name
    serpin family B member 6provided by HGNC
    Primary source
    HGNC:HGNC:8950
    See related
    Ensembl:ENSG00000124570 MIM:173321; AllianceGenome:HGNC:8950
    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
    CAP; PI6; PTI; PI-6; SPI3; DFNB91; MSTP057
    Summary
    The protein encoded by this gene is a member of the serpin (serine proteinase inhibitor) superfamily, and ovalbumin(ov)-serpin subfamily. It was originally discovered as a placental thrombin inhibitor. The mouse homolog was found to be expressed in the hair cells of the inner ear. Mutations in this gene are associated with nonsyndromic progressive hearing loss, suggesting that this serpin plays an important role in the inner ear in the protection against leakage of lysosomal content during stress, and that loss of this protection results in cell death and sensorineural hearing loss. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2010]
    Expression
    Ubiquitous expression in small intestine (RPKM 25.4), testis (RPKM 22.1) and 25 other tissues See more
    Orthologs
    all
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    Genomic context

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    See SERPINB6 in Genome Data Viewer
    Location:
    6p25.2
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (2948159..2971793, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (2817071..2840707, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (2948393..2972027, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23874 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23875 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23876 Neighboring gene serpin family B member 9 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23877 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23878 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23879 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:2869952-2870526 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:2875298-2876239 Neighboring gene SERPINB9 antisense RNA 1 Neighboring gene MPRA-validated peak5624 silencer Neighboring gene serpin family B member 9 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16834 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:2903007-2903508 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16836 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16837 Neighboring gene hESC enhancers GRCh37_chr6:2907997-2908830 and GRCh37_chr6:2908831-2909664 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr6:2916616-2917158 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:2921833-2922334 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:2928364-2929022 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:2929023-2929682 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:2960063-2960678 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:2971582-2972106 Neighboring gene SERPINB6-LINC01011 intergenic CAGE-defined mid-level expression enhancer Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:2988143-2988952 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:2988953-2989762 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:2989763-2990572 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:2990573-2991380 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:2994147-2994331 Neighboring gene long intergenic non-protein coding RNA 1011 Neighboring gene NQO2 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16839 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:3014049-3014548 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:3017263-3017764 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:3017765-3018264 Neighboring gene N-ribosyldihydronicotinamide:quinone dehydrogenase 2 Neighboring gene HIV-1 Tat specific factor 1 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. Chromosomal mapping of the human proteinase inhibitor 6 (PI6) gene to 6p25 by fluorescence in situ hybridization. Coughlin P, et al. Genomics, 1995 Mar 20. PMID 7601482
    2. Human cytoplasmic antiproteinase neutralizes rapidly and efficiently chymotrypsin and trypsin-like proteases utilizing distinct reactive site residues. Riewald M, et al. J Biol Chem, 1996 Jun 14. PMID 8662739
    3. Identification and characterization of the cytoplasmic antiproteinase (CAP) in human platelets. Evidence for the interaction of CAP with endogenous platelet proteins. Riewald M, et al. J Biol Chem, 1996 Mar 22. PMID 8636153
    4. Isolation and characterization of an intracellular serine proteinase inhibitor from a monkey kidney epithelial cell line. Morgenstern KA, et al. J Biol Chem, 1993 Oct 15. PMID 8408007
    5. Identification and purification of a novel serine proteinase inhibitor. Coughlin PB, et al. J Biol Chem, 1993 May 5. PMID 8486644

    See all (69) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A truncating mutation in SERPINB6 is associated with autosomal-recessive nonsyndromic sensorineural hearing loss.
      Title: A truncating mutation in SERPINB6 is associated with autosomal-recessive nonsyndromic sensorineural hearing loss.
    2. the discovery overexpression of GPD1 and RRBP1 proteins and lack of expression for HNRNPH1 and SERPINB6 proteins which are new candidate biomarkers of colon cancer.
      Title: [Colorectal cancer 2D-proteomics: identification of altered protein expression].
    3. Protects the intracellular compartment of keratinocytes from ectopic kallikrein-8.
      Title: SerpinB6 is an inhibitor of kallikrein-8 in keratinocytes.
    4. Expressed in developing gonads and in both somatic and germ cells of adult gonads.
      Title: Expression of serpinb6 serpins in germ and somatic cells of mouse gonads.
    5. In mast cells, SERPINB6 serves to regulate the activity of endogenous beta-tryptase in the cytoplasm.
      Title: Intracellular serpin SERPINB6 (PI6) is abundantly expressed by human mast cells and forms complexes with beta-tryptase monomers.
    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

    Associated conditions

    Description Tests
    Autosomal recessive nonsyndromic hearing loss 91
    MedGen: C3150704 OMIM: 613453 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)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of serpin peptidase inhibitor, clade B (ovalbumin), member 6 (SERPINB6) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Go to the HIV-1, Human Interaction Database

    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

    • MGC111370, DKFZp686I04222

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protease binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables serine-type endopeptidase inhibitor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables serine-type endopeptidase inhibitor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cellular response to osmotic stress IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in sensory perception of sound IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in collagen-containing extracellular matrix HDA PubMed 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region HDA PubMed 
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in ficolin-1-rich granule membrane TAS
    Traceable Author Statement
    more info
    		  
    NOT located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in secretory granule membrane TAS
    Traceable Author Statement
    more info
    		  
    part_of serine protease inhibitor complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in tertiary granule membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    serpin B6
    Names
    cytoplasmic antiproteinase
    protease inhibitor 6 (placental thrombin inhibitor)
    serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 6
    serpin peptidase inhibitor, clade B (ovalbumin), member 6

    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_027692.1 RefSeqGene

      Range
      5599..29007
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001195291.3 → NP_001182220.2  serpin B6 isoform b

      See identical proteins and their annotated locations for NP_001182220.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an additional exon in the 5' region, which includes an upstream in-frame AUG start codon, compared to variant 1. The resulting isoform (b) has a longer N-terminus, compared to isoform a. Variants 2 and 9 both encode the same isoform (b).
      Source sequence(s)
      AL133351
      Consensus CDS
      CCDS75386.1
      UniProtKB/TrEMBL
      A0A024QZX5
      Related
      ENSP00000481398.1, ENST00000616722.4
      Conserved Domains (1) summary
      cd19565
      Location:5 → 380
      serpinB6_CAP; serpin family B member 6, cytoplasmic antiproteinase

    2. NM_001271822.2 → NP_001258751.1  serpin B6 isoform c

      See identical proteins and their annotated locations for NP_001258751.1

      Status: REVIEWED

      Source sequence(s)
      AL133351, BC001394, CX782163, HY169891
      UniProtKB/Swiss-Prot
      P35237
      Conserved Domains (1) summary
      cd19565
      Location:15 → 390
      serpinB6_CAP; serpin family B member 6, cytoplasmic antiproteinase

    3. NM_001271823.2 → NP_001258752.1  serpin B6 isoform d

      See identical proteins and their annotated locations for NP_001258752.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains an alternate 5' exon, which includes an upstream in-frame AUG start codon, compared to variant 1. The resulting isoform (d) has a longer N-terminus, compared to isoform a.
      Source sequence(s)
      AL133351
      Consensus CDS
      CCDS75387.1
      UniProtKB/TrEMBL
      A0A087X1N8
      Related
      ENSP00000484343.1, ENST00000612421.3
      Conserved Domains (1) summary
      cl00137
      Location:23 → 395
      SERPIN; SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate ...

    4. NM_001271824.2 → NP_001258753.1  serpin B6 isoform a

      See identical proteins and their annotated locations for NP_001258753.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) contains an additional segment in the 5' UTR, compared to variant 1. Variants 1, 5-8, and 10 all encode the same isoform (a).
      Source sequence(s)
      AL133351
      Consensus CDS
      CCDS4479.1
      UniProtKB/Swiss-Prot
      B2RBA8, P35237, Q59F97, Q5TD06, Q7Z2Y7, Q96J44, Q9UDI7
      Related
      ENSP00000369919.3, ENST00000380546.7
      Conserved Domains (1) summary
      cd19565
      Location:1 → 376
      serpinB6_CAP; serpin family B member 6, cytoplasmic antiproteinase

    5. NM_001271825.2 → NP_001258754.1  serpin B6 isoform a

      See identical proteins and their annotated locations for NP_001258754.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) contains an alternate 5' UTR exon, compared to variant 1. Variants 1, 5-8, and 10 all encode the same isoform (a).
      Source sequence(s)
      BC001394, CX755337, DA847833
      Consensus CDS
      CCDS4479.1
      UniProtKB/Swiss-Prot
      B2RBA8, P35237, Q59F97, Q5TD06, Q7Z2Y7, Q96J44, Q9UDI7
      Related
      ENSP00000369896.1, ENST00000380524.5
      Conserved Domains (1) summary
      cd19565
      Location:1 → 376
      serpinB6_CAP; serpin family B member 6, cytoplasmic antiproteinase

    6. NM_001297699.2 → NP_001284628.1  serpin B6 isoform a

      See identical proteins and their annotated locations for NP_001284628.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) contains an additional segment in the 5' UTR, compared to variant 1. Variants 1, 5-8, and 10 all encode the same isoform (a).
      Source sequence(s)
      AL133351
      Consensus CDS
      CCDS4479.1
      UniProtKB/Swiss-Prot
      B2RBA8, P35237, Q59F97, Q5TD06, Q7Z2Y7, Q96J44, Q9UDI7
      Related
      ENSP00000493936.1, ENST00000643098.1
      Conserved Domains (1) summary
      cd19565
      Location:1 → 376
      serpinB6_CAP; serpin family B member 6, cytoplasmic antiproteinase

    7. NM_001297700.2 → NP_001284629.1  serpin B6 isoform a

      See identical proteins and their annotated locations for NP_001284629.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) contains an alternate 5' UTR exon, compared to variant 1. Variants 1, 5-8, and 10 all encode the same isoform (a).
      Source sequence(s)
      AL133351
      Consensus CDS
      CCDS4479.1
      UniProtKB/Swiss-Prot
      B2RBA8, P35237, Q59F97, Q5TD06, Q7Z2Y7, Q96J44, Q9UDI7
      Related
      ENSP00000369891.1, ENST00000380520.6
      Conserved Domains (1) summary
      cd19565
      Location:1 → 376
      serpinB6_CAP; serpin family B member 6, cytoplasmic antiproteinase

    8. NM_001374515.1 → NP_001361444.1  serpin B6 isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9), as well as variant 2, encodes isoform b.
      Source sequence(s)
      AL133351
      Consensus CDS
      CCDS75386.1
      UniProtKB/TrEMBL
      A0A024QZX5
      Conserved Domains (1) summary
      cd19565
      Location:5 → 380
      serpinB6_CAP; serpin family B member 6, cytoplasmic antiproteinase

    9. NM_001374516.1 → NP_001361445.1  serpin B6 isoform a

      Status: REVIEWED

      Description
      Transcript Variant: This variant (10), as well as variants 1 and 5-8, encodes isoform a.
      Source sequence(s)
      AL133351
      Consensus CDS
      CCDS4479.1
      UniProtKB/Swiss-Prot
      B2RBA8, P35237, Q59F97, Q5TD06, Q7Z2Y7, Q96J44, Q9UDI7
      Related
      ENSP00000369901.1, ENST00000380529.5
      Conserved Domains (1) summary
      cd19565
      Location:1 → 376
      serpinB6_CAP; serpin family B member 6, cytoplasmic antiproteinase

    10. NM_001374517.1 → NP_001361446.1  serpin B6 isoform e

      Status: REVIEWED

      Source sequence(s)
      AL133351
      Consensus CDS
      CCDS93850.1
      UniProtKB/TrEMBL
      A0A2R8YD12
      Related
      ENSP00000494161.1, ENST00000642543.1
      Conserved Domains (1) summary
      cl38926
      Location:11 → 332
      serpin; SERine Proteinase INhibitors (serpin) family

    11. NM_004568.6 → NP_004559.4  serpin B6 isoform a

      See identical proteins and their annotated locations for NP_004559.4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the predominant transcript. Variants 1, 5-8, and 10 all encode the same isoform (a).
      Source sequence(s)
      AL133351
      Consensus CDS
      CCDS4479.1
      UniProtKB/Swiss-Prot
      B2RBA8, P35237, Q59F97, Q5TD06, Q7Z2Y7, Q96J44, Q9UDI7
      Related
      ENSP00000369912.2, ENST00000380539.7
      Conserved Domains (1) summary
      cd19565
      Location:1 → 376
      serpinB6_CAP; serpin family B member 6, cytoplasmic antiproteinase

    RNA

    1. NR_164657.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL133351

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      2948159..2971793 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047418893.1 → XP_047274849.1  serpin B6 isoform X4

      UniProtKB/TrEMBL
      A0A2R8YD12

    2. XM_011514672.2 → XP_011512974.1  serpin B6 isoform X1

      Conserved Domains (1) summary
      cd02058
      Location:82 → 454
      PAI-2; Plasminogen Activator Inhibitor-2 (PAI-2). PAI-2 is a serine protease inhibitor that belongs to the ov-serpin branch of the serpin superfamily. It is is an effective inhibitor of urinary plasminogen activator (urokinase or uPA) and is involved in cell ...

    3. XM_047418885.1 → XP_047274841.1  serpin B6 isoform X1

    4. XM_047418887.1 → XP_047274843.1  serpin B6 isoform X1

    5. XM_047418884.1 → XP_047274840.1  serpin B6 isoform X1

    6. XM_024446465.2 → XP_024302233.1  serpin B6 isoform X4

      UniProtKB/TrEMBL
      A0A2R8YD12
      Conserved Domains (1) summary
      cl38926
      Location:11 → 332
      serpin; SERine Proteinase INhibitors (serpin) family

    7. XM_047418888.1 → XP_047274844.1  serpin B6 isoform X1

    8. XM_047418890.1 → XP_047274846.1  serpin B6 isoform X5

      UniProtKB/TrEMBL
      A0A024QZX5

    9. XM_017010941.2 → XP_016866430.1  serpin B6 isoform X4

      UniProtKB/TrEMBL
      A0A2R8YD12
      Conserved Domains (1) summary
      cl38926
      Location:11 → 332
      serpin; SERine Proteinase INhibitors (serpin) family

    10. XM_047418889.1 → XP_047274845.1  serpin B6 isoform X2

      UniProtKB/TrEMBL
      A0A024QZX5

    11. XM_047418883.1 → XP_047274839.1  serpin B6 isoform X1

    12. XM_047418892.1 → XP_047274848.1  serpin B6 isoform X3

      UniProtKB/Swiss-Prot
      B2RBA8, P35237, Q59F97, Q5TD06, Q7Z2Y7, Q96J44, Q9UDI7

    13. XM_047418891.1 → XP_047274847.1  serpin B6 isoform X3

      UniProtKB/Swiss-Prot
      B2RBA8, P35237, Q59F97, Q5TD06, Q7Z2Y7, Q96J44, Q9UDI7

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      2817071..2840707 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054355638.1 → XP_054211613.1  serpin B6 isoform X4

      UniProtKB/TrEMBL
      A0A2R8YD12

    2. XM_054355631.1 → XP_054211606.1  serpin B6 isoform X1

    3. XM_054355633.1 → XP_054211608.1  serpin B6 isoform X1

    4. XM_054355634.1 → XP_054211609.1  serpin B6 isoform X1

    5. XM_054355632.1 → XP_054211607.1  serpin B6 isoform X1

    6. XM_054355635.1 → XP_054211610.1  serpin B6 isoform X1

    7. XM_054355639.1 → XP_054211614.1  serpin B6 isoform X4

      UniProtKB/TrEMBL
      A0A2R8YD12

    8. XM_054355630.1 → XP_054211605.1  serpin B6 isoform X1

    9. XM_054355636.1 → XP_054211611.1  serpin B6 isoform X2

      UniProtKB/TrEMBL
      A0A024QZX5

    10. XM_054355637.1 → XP_054211612.1  serpin B6 isoform X3

      UniProtKB/Swiss-Prot
      B2RBA8, P35237, Q59F97, Q5TD06, Q7Z2Y7, Q96J44, Q9UDI7
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P35237.3 GenPept UniProtKB/Swiss-Prot:P35237

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