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    PCSK4 proprotein convertase subtilisin/kexin type 4 [ Homo sapiens (human) ]

    Gene ID: 54760, updated on 10-Dec-2024

    Summary

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    Official Symbol
    PCSK4provided by HGNC
    Official Full Name
    proprotein convertase subtilisin/kexin type 4provided by HGNC
    Primary source
    HGNC:HGNC:8746
    See related
    Ensembl:ENSG00000115257 MIM:600487; AllianceGenome:HGNC:8746
    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
    PC4; SPC5
    Summary
    This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to subcellular compartments where a second autocatalytic even takes place and the catalytic activity is acquired. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. The protease is expressed only in the testis, placenta, and ovary. It plays a critical role in fertilization, fetoplacental growth, and embryonic development and processes multiple prohormones including pro-pituitary adenylate cyclase-activating protein and pro-insulin-like growth factor II. [provided by RefSeq, Jan 2014]
    Expression
    Biased expression in testis (RPKM 19.7) and kidney (RPKM 0.9) See more
    Orthologs
    mouse all
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    Genomic context

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    See PCSK4 in Genome Data Viewer
    Location:
    19p13.3
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (1481428..1490876, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (1451458..1460906, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (1481427..1490349, complement)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:1438140-1439010 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:1440750-1441618 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9711 Neighboring gene ribosomal protein S15 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9712 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9713 Neighboring gene Sharpr-MPRA regulatory region 2129 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9714 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:1452009-1452642 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:1452643-1453274 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:1453275-1453907 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:1453908-1454539 Neighboring gene APC regulator of WNT signaling pathway 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9715 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9716 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9717 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:1456369-1456885 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9718 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9719 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9720 Neighboring gene chromosome 19 open reading frame 25 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:1478399-1478899 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9721 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13614 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:1482223-1482834 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9722 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9723 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9724 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:1497018-1497572 Neighboring gene receptor accessory protein 6 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:1507743-1508592 Neighboring gene uncharacterized LOC124904609 Neighboring gene ADAMTS like 5

    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. Prohormone convertase PC4 processes the precursor of PACAP in the testis. Li M, et al. Ann N Y Acad Sci, 2000. PMID 11193847
    2. Proprotein convertase subtilisin/kexin type 4 in mammalian fertility: a review. Gyamera-Acheampong C, et al. Hum Reprod Update, 2009 Mar-Apr. PMID 19109312
    3. Single-nucleotide polymorphisms of the proprotein convertase subtilisin/ kexin type 5 (PCSK5) gene. Cao H, et al. J Hum Genet, 2001. PMID 11776387
    4. The testicular germ-cell protease PC4 is also expressed in macrophage-like cells of the ovary. Tadros H, et al. J Reprod Immunol, 2001 Feb. PMID 11164898
    5. Role of pro-IGF-II processing by proprotein convertase 4 in human placental development. Qiu Q, et al. Proc Natl Acad Sci U S A, 2005 Aug 2. PMID 16040806, Free PMC Article

    See all (27) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Maturation by propeptide removal occurs very inefficiently when rat or human proPCSK4 is overexpressed in HEK293 cells where it interacts with BiP.
      Title: The precursor to the germ cell-specific PCSK4 proteinase is inefficiently activated in transfected somatic cells: evidence of interaction with the BiP chaperone.
    2. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    3. Observational study of gene-disease association. (HuGE Navigator)
      Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
    4. abnormal processing of IGF-II by PC4 may represent a previously uncharacterized mechanism involved in the pathophysiology of fetoplacental growth restriction
      Title: Role of pro-IGF-II processing by proprotein convertase 4 in human placental development.
    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)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC34749, DKFZp434B217

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables serine-type endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in acrosome reaction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in binding of sperm to zona pellucida ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in fertilization ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in peptide hormone processing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in reproductive process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in sperm capacitation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    is_active_in Golgi membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in acrosomal membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in acrosomal vesicle ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in trans-Golgi network IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    proprotein convertase subtilisin/kexin type 4
    Names
    testicular tissue protein Li 135

    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_001395257.1 → NP_001382186.1  proprotein convertase subtilisin/kexin type 4 isoform 2 precursor

      Status: REVIEWED

      Source sequence(s)
      AC027307
      Related
      ENST00000441747.6
      Conserved Domains (1) summary
      cd04059
      Location:118 → 407
      Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases

    2. NM_017573.5 → NP_060043.2  proprotein convertase subtilisin/kexin type 4 isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_060043.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC027307
      Consensus CDS
      CCDS12069.2
      UniProtKB/Swiss-Prot
      Q6UW60, Q8IY88, Q9UF79
      UniProtKB/TrEMBL
      A0A140VJQ9
      Related
      ENSP00000300954.5, ENST00000300954.10
      Conserved Domains (5) summary
      cd04059
      Location:118 → 407
      Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
      smart00261
      Location:647 → 684
      FU; Furin-like repeats
      pfam00082
      Location:149 → 432
      Peptidase_S8; Subtilase family
      pfam01483
      Location:489 → 575
      P_proprotein; Proprotein convertase P-domain
      pfam16470
      Location:37 → 113
      S8_pro-domain; Peptidase S8 pro-domain

    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_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      1481428..1490876 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011528091.3 → XP_011526393.1  proprotein convertase subtilisin/kexin type 4 isoform X8

      Conserved Domains (5) summary
      cd04059
      Location:21 → 310
      Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
      smart00261
      Location:550 → 587
      FU; Furin-like repeats
      pfam00082
      Location:52 → 335
      Peptidase_S8; Subtilase family
      pfam01483
      Location:392 → 478
      P_proprotein; Proprotein convertase P-domain
      pfam16470
      Location:1 → 16
      S8_pro-domain; Peptidase S8 pro-domain

    2. XM_011528088.3 → XP_011526390.1  proprotein convertase subtilisin/kexin type 4 isoform X5

      Conserved Domains (5) summary
      cd04059
      Location:83 → 372
      Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
      smart00261
      Location:612 → 649
      FU; Furin-like repeats
      pfam00082
      Location:114 → 397
      Peptidase_S8; Subtilase family
      pfam01483
      Location:454 → 540
      P_proprotein; Proprotein convertase P-domain
      pfam16470
      Location:2 → 78
      S8_pro-domain; Peptidase S8 pro-domain

    3. XM_047438981.1 → XP_047294937.1  proprotein convertase subtilisin/kexin type 4 isoform X10

    4. XM_024451555.2 → XP_024307323.1  proprotein convertase subtilisin/kexin type 4 isoform X15

      Conserved Domains (4) summary
      cd04059
      Location:7 → 279
      Peptidases_S8_Protein_convertases_Kexins_Furin-lik; Peptidase S8 family domain in Protein convertases
      smart00261
      Location:519 → 556
      FU; Furin-like repeats
      pfam01483
      Location:361 → 447
      P_proprotein; Proprotein convertase P-domain
      cl28643
      Location:464 → 555
      VSP; Giardia variant-specific surface protein

    5. XM_011528090.3 → XP_011526392.1  proprotein convertase subtilisin/kexin type 4 isoform X7

      Conserved Domains (4) summary
      smart00261
      Location:553 → 590
      FU; Furin-like repeats
      pfam01483
      Location:395 → 481
      P_proprotein; Proprotein convertase P-domain
      pfam16470
      Location:37 → 113
      S8_pro-domain; Peptidase S8 pro-domain
      cl10459
      Location:118 → 193
      Peptidases_S8_S53; Peptidase domain in the S8 and S53 families

    6. XM_047438984.1 → XP_047294940.1  proprotein convertase subtilisin/kexin type 4 isoform X14

    7. XM_047438980.1 → XP_047294936.1  proprotein convertase subtilisin/kexin type 4 isoform X3

    8. XM_047438982.1 → XP_047294938.1  proprotein convertase subtilisin/kexin type 4 isoform X11

    9. XM_011528089.3 → XP_011526391.1  proprotein convertase subtilisin/kexin type 4 isoform X6

      Conserved Domains (4) summary
      smart00261
      Location:580 → 617
      FU; Furin-like repeats
      pfam01483
      Location:422 → 508
      P_proprotein; Proprotein convertase P-domain
      pfam16470
      Location:37 → 140
      S8_pro-domain; Peptidase S8 pro-domain
      cl10459
      Location:145 → 220
      Peptidases_S8_S53; Peptidase domain in the S8 and S53 families

    10. XM_011528095.3 → XP_011526397.1  proprotein convertase subtilisin/kexin type 4 isoform X16

      UniProtKB/TrEMBL
      B4DXQ5
      Conserved Domains (2) summary
      pfam16470
      Location:37 → 140
      S8_pro-domain; Peptidase S8 pro-domain
      cl10459
      Location:145 → 220
      Peptidases_S8_S53; Peptidase domain in the S8 and S53 families

    11. XM_011528086.3 → XP_011526388.1  proprotein convertase subtilisin/kexin type 4 isoform X2

      Conserved Domains (5) summary
      cd04059
      Location:145 → 434
      Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
      smart00261
      Location:665 → 702
      FU; Furin-like repeats
      pfam00082
      Location:176 → 459
      Peptidase_S8; Subtilase family
      pfam01483
      Location:507 → 593
      P_proprotein; Proprotein convertase P-domain
      pfam16470
      Location:37 → 140
      S8_pro-domain; Peptidase S8 pro-domain

    12. XM_011528087.3 → XP_011526389.1  proprotein convertase subtilisin/kexin type 4 isoform X4

      Conserved Domains (5) summary
      cd04059
      Location:145 → 434
      Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
      smart00261
      Location:616 → 653
      FU; Furin-like repeats
      pfam00082
      Location:176 → 459
      Peptidase_S8; Subtilase family
      pfam01483
      Location:516 → 551
      P_proprotein; Proprotein convertase P-domain
      pfam16470
      Location:37 → 140
      S8_pro-domain; Peptidase S8 pro-domain

    13. XM_011528093.3 → XP_011526395.1  proprotein convertase subtilisin/kexin type 4 isoform X12

      Conserved Domains (4) summary
      cd04059
      Location:145 → 434
      Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
      pfam00082
      Location:176 → 459
      Peptidase_S8; Subtilase family
      pfam01483
      Location:516 → 551
      P_proprotein; Proprotein convertase P-domain
      pfam16470
      Location:37 → 140
      S8_pro-domain; Peptidase S8 pro-domain

    14. XM_011528092.3 → XP_011526394.1  proprotein convertase subtilisin/kexin type 4 isoform X9

      Conserved Domains (4) summary
      cd04059
      Location:145 → 434
      Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
      pfam00082
      Location:176 → 459
      Peptidase_S8; Subtilase family
      pfam01483
      Location:516 → 602
      P_proprotein; Proprotein convertase P-domain
      pfam16470
      Location:37 → 140
      S8_pro-domain; Peptidase S8 pro-domain

    15. XM_011528085.3 → XP_011526387.1  proprotein convertase subtilisin/kexin type 4 isoform X1

      Conserved Domains (5) summary
      cd04059
      Location:145 → 434
      Peptidases_S8_Protein_convertases_Kexins_Furin-like; Peptidase S8 family domain in Protein convertases
      smart00261
      Location:674 → 711
      FU; Furin-like repeats
      pfam00082
      Location:176 → 459
      Peptidase_S8; Subtilase family
      pfam01483
      Location:516 → 602
      P_proprotein; Proprotein convertase P-domain
      pfam16470
      Location:37 → 140
      S8_pro-domain; Peptidase S8 pro-domain

    16. XM_047438983.1 → XP_047294939.1  proprotein convertase subtilisin/kexin type 4 isoform X13

    17. XM_047438991.1 → XP_047294947.1  proprotein convertase subtilisin/kexin type 4 isoform X23

      UniProtKB/TrEMBL
      B3KQ28

    18. XM_024451556.2 → XP_024307324.2  proprotein convertase subtilisin/kexin type 4 isoform X22

      UniProtKB/TrEMBL
      B4DXQ5

    19. XM_047438988.1 → XP_047294944.1  proprotein convertase subtilisin/kexin type 4 isoform X19

      UniProtKB/TrEMBL
      B4DXQ5

    20. XM_047438985.1 → XP_047294941.1  proprotein convertase subtilisin/kexin type 4 isoform X16

      UniProtKB/TrEMBL
      B4DXQ5

    21. XM_047438986.1 → XP_047294942.1  proprotein convertase subtilisin/kexin type 4 isoform X17

    22. XM_047438987.1 → XP_047294943.1  proprotein convertase subtilisin/kexin type 4 isoform X18

    23. XM_047438990.1 → XP_047294946.1  proprotein convertase subtilisin/kexin type 4 isoform X21

      UniProtKB/TrEMBL
      B4DXQ5
      Related
      ENST00000588195.5

    24. XM_047438989.1 → XP_047294945.1  proprotein convertase subtilisin/kexin type 4 isoform X20

      UniProtKB/TrEMBL
      B4DXQ5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      1451458..1460906 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054321284.1 → XP_054177259.1  proprotein convertase subtilisin/kexin type 4 isoform X8

    2. XM_054321281.1 → XP_054177256.1  proprotein convertase subtilisin/kexin type 4 isoform X5

    3. XM_054321286.1 → XP_054177261.1  proprotein convertase subtilisin/kexin type 4 isoform X10

    4. XM_054321291.1 → XP_054177266.1  proprotein convertase subtilisin/kexin type 4 isoform X15

    5. XM_054321283.1 → XP_054177258.1  proprotein convertase subtilisin/kexin type 4 isoform X7

    6. XM_054321290.1 → XP_054177265.1  proprotein convertase subtilisin/kexin type 4 isoform X14

    7. XM_054321279.1 → XP_054177254.1  proprotein convertase subtilisin/kexin type 4 isoform X3

    8. XM_054321287.1 → XP_054177262.1  proprotein convertase subtilisin/kexin type 4 isoform X11

    9. XM_054321282.1 → XP_054177257.1  proprotein convertase subtilisin/kexin type 4 isoform X6

    10. XM_054321293.1 → XP_054177268.1  proprotein convertase subtilisin/kexin type 4 isoform X16

      UniProtKB/TrEMBL
      B4DXQ5

    11. XM_054321278.1 → XP_054177253.1  proprotein convertase subtilisin/kexin type 4 isoform X2

    12. XM_054321280.1 → XP_054177255.1  proprotein convertase subtilisin/kexin type 4 isoform X4

    13. XM_054321288.1 → XP_054177263.1  proprotein convertase subtilisin/kexin type 4 isoform X12

    14. XM_054321285.1 → XP_054177260.1  proprotein convertase subtilisin/kexin type 4 isoform X9

    15. XM_054321277.1 → XP_054177252.1  proprotein convertase subtilisin/kexin type 4 isoform X1

    16. XM_054321289.1 → XP_054177264.1  proprotein convertase subtilisin/kexin type 4 isoform X13

    17. XM_054321300.1 → XP_054177275.1  proprotein convertase subtilisin/kexin type 4 isoform X23

      UniProtKB/TrEMBL
      B3KQ28

    18. XM_054321299.1 → XP_054177274.1  proprotein convertase subtilisin/kexin type 4 isoform X22

      UniProtKB/TrEMBL
      B4DXQ5

    19. XM_054321296.1 → XP_054177271.1  proprotein convertase subtilisin/kexin type 4 isoform X19

      UniProtKB/TrEMBL
      B4DXQ5

    20. XM_054321292.1 → XP_054177267.1  proprotein convertase subtilisin/kexin type 4 isoform X16

      UniProtKB/TrEMBL
      B4DXQ5

    21. XM_054321294.1 → XP_054177269.1  proprotein convertase subtilisin/kexin type 4 isoform X17

    22. XM_054321295.1 → XP_054177270.1  proprotein convertase subtilisin/kexin type 4 isoform X18

    23. XM_054321298.1 → XP_054177273.1  proprotein convertase subtilisin/kexin type 4 isoform X21

      UniProtKB/TrEMBL
      B4DXQ5

    24. XM_054321297.1 → XP_054177272.1  proprotein convertase subtilisin/kexin type 4 isoform X20

      UniProtKB/TrEMBL
      B4DXQ5
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6UW60.2 GenPept UniProtKB/Swiss-Prot:Q6UW60

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