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

Gene ID: 54760, updated on 11-Apr-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_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (1481428..1490876, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (1451458..1460906, complement)
105.20220307 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. Proprotein convertase subtilisin/kexin type 4 in mammalian fertility: a review. Gyamera-Acheampong C, et al. Hum Reprod Update, 2009 Mar-Apr. PMID 19109312
  2. Prohormone convertase PC4 processes the precursor of PACAP in the testis. Li M, et al. Ann N Y Acad Sci, 2000. PMID 11193847
  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. 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
  5. 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

See all (24) 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)

Genotypes

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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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_2023_10

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

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

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

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

  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

    Related
    ENST00000588195.5

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

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

  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

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

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

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

  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

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

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

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