Seroatlas · Human Serome Atlas

PRG4

Proteoglycan 4

Also known as: bG174L6.2, CACP, FLJ32635, HAPO, JCAP, MSF, PRG4_HUMAN, SZP

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q92954
Gene: PRG4
Ensembl: ENSG00000116690
Chromosome: 1
Canonical length: 1404 aa
Protein class: Disease related genes, Human disease related genes, Plasma proteins, Predicted secreted proteins
Secretome location: Secreted to extracellular matrix
Quaternary structure: Homodimer

OverviewNCBI Gene

The protein encoded by this gene is a large proteoglycan that is synthesized by chondrocytes located at the surface of articular cartilage and by some synovial lining cells. This protein contains both chondroitin sulfate and keratan sulfate glycosaminoglycans. It functions as a boundary lubricant at the cartilage surface and contributes to the elastic absorption and energy dissipation of synovial fluid. Mutations in this gene result in camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

Canonical amino-acid sequenceUniProt

1404 residues, UniProt reviewed canonical sequence.

>Q92954|PRG4
     1  MAWKTLPIYL LLLLSVFVIQ QVSSQDLSSC AGRCGEGYSR DATCNCDYNC QHYMECCPDF
    61  KRVCTAELSC KGRCFESFER GRECDCDAQC KKYDKCCPDY ESFCAEVHNP TSPPSSKKAP
   121  PPSGASQTIK STTKRSPKPP NKKKTKKVIE SEEITEEHSV SENQESSSSS SSSSSSSTIR
   181  KIKSSKNSAA NRELQKKLKV KDNKKNRTKK KPTPKPPVVD EAGSGLDNGD FKVTTPDTST
   241  TQHNKVSTSP KITTAKPINP RPSLPPNSDT SKETSLTVNK ETTVETKETT TTNKQTSTDG
   301  KEKTTSAKET QSIEKTSAKD LAPTSKVLAK PTPKAETTTK GPALTTPKEP TPTTPKEPAS
   361  TTPKEPTPTT IKSAPTTPKE PAPTTTKSAP TTPKEPAPTT TKEPAPTTPK EPAPTTTKEP
   421  APTTTKSAPT TPKEPAPTTP KKPAPTTPKE PAPTTPKEPT PTTPKEPAPT TKEPAPTTPK
   481  EPAPTAPKKP APTTPKEPAP TTPKEPAPTT TKEPSPTTPK EPAPTTTKSA PTTTKEPAPT
   541  TTKSAPTTPK EPSPTTTKEP APTTPKEPAP TTPKKPAPTT PKEPAPTTPK EPAPTTTKKP
   601  APTTPKEPAP TTPKETAPTT PKKLTPTTPE KLAPTTPEKP APTTPEELAP TTPEEPTPTT
   661  PEEPAPTTPK AAAPNTPKEP APTTPKEPAP TTPKEPAPTT PKETAPTTPK GTAPTTLKEP
   721  APTTPKKPAP KELAPTTTKE PTSTTSDKPA PTTPKGTAPT TPKEPAPTTP KEPAPTTPKG
   781  TAPTTLKEPA PTTPKKPAPK ELAPTTTKGP TSTTSDKPAP TTPKETAPTT PKEPAPTTPK
   841  KPAPTTPETP PPTTSEVSTP TTTKEPTTIH KSPDESTPEL SAEPTPKALE NSPKEPGVPT
   901  TKTPAATKPE MTTTAKDKTT ERDLRTTPET TTAAPKMTKE TATTTEKTTE SKITATTTQV
   961  TSTTTQDTTP FKITTLKTTT LAPKVTTTKK TITTTEIMNK PEETAKPKDR ATNSKATTPK
  1021  PQKPTKAPKK PTSTKKPKTM PRVRKPKTTP TPRKMTSTMP ELNPTSRIAE AMLQTTTRPN
  1081  QTPNSKLVEV NPKSEDAGGA EGETPHMLLR PHVFMPEVTP DMDYLPRVPN QGIIINPMLS
  1141  DETNICNGKP VDGLTTLRNG TLVAFRGHYF WMLSPFSPPS PARRITEVWG IPSPIDTVFT
  1201  RCNCEGKTFF FKDSQYWRFT NDIKDAGYPK PIFKGFGGLT GQIVAALSTA KYKNWPESVY
  1261  FFKRGGSIQQ YIYKQEPVQK CPGRRPALNY PVYGETTQVR RRRFERAIGP SQTHTIRIQY
  1321  SPARLAYQDK GVLHNEVKVS ILWRGLPNVV TSAISLPNIR KPDGYDYYAF SKDQYYNIDV
  1381  PSRTARAITT RSGQTLSKVW YNCP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PRG4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Secreted
Secreted: Yes
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.6
Highest tissue expression: 174 nTPM

Expression across tissuesHPA

Tissue

liver: 174 nTPM
adipose tissue: 87 nTPM
blood vessel: 33 nTPM
heart muscle: 29 nTPM
lung: 24 nTPM
breast: 15 nTPM

Single-cell type

mesothelial cells: 1,833 nCPM
epicardial cells: 1,071 nCPM
hepatocytes: 374 nCPM
fibroblasts: 113 nCPM
fibro-adipogenic progenitors: 86 nCPM
pancreatic islet cells: 83 nCPM

Immune cell

T-reg: 1.2 nTPM
memory CD4 T-cell: 0.2 nTPM
naive CD4 T-cell: 0.1 nTPM
basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM

Brain region

hypothalamus: 66 nTPM
choroid plexus: 8.4 nTPM
cerebellum: 1 nTPM
cerebral cortex: 1 nTPM
spinal cord: 0.5 nTPM
pons: 0.4 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PRG4.

Disease | AllUniProt

Conditions PRG4 is implicated in, by any mechanism.

Camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) MIM:208250

Disease | GeneticClinVar

48 pathogenic / likely-pathogenic of 337 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Camptodactyly-arthropathy-coxa vara-pericarditis syndrome
Inborn genetic diseases
Abnormality of the skeletal system

Disease | ImmuneIEDB

Conditions an epitope on PRG4 was assayed in.

rheumatoid arthritis B and T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.74
gnomAD pLI: 0
gnomAD missense Z: -0.3
DepMap mean gene effect: -0.2
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

immune response

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads PRG4 as an antibody target. Whether an autoantibody or antibody against PRG4 could matter depends on whether native PRG4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

PRG4 is annotated as secreted, so native PRG4 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label PRG4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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