Seroatlas · Human Serome Atlas

P3H4

Endoplasmic reticulum protein SC65

Also known as: LEPREL4, NO55, SC65, SC65_HUMAN

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

Protein identityUniProt · HPA

UniProt accession: Q92791
Gene: P3H4
Ensembl: ENSG00000141696
Chromosome: 17
Canonical length: 437 aa
Protein class: Predicted intracellular proteins
Subcellular location: Endoplasmic reticulum,Vesicles
Secretome location: Intracellular and membrane

OverviewNCBI Gene

This nucleolar protein was first characterized because it was an autoantigen in cases on interstitial cystitis. The protein, with a predicted molecular weight of 50 kDa, appears to be localized in the particulate compartment of the interphase nucleolus, with a distribution distinct from that of nucleolar protein B23. During mitosis it is associated with chromosomes. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

437 residues, UniProt reviewed canonical sequence.

>Q92791|P3H4
     1  MARVAWGLLW LLLGSAGAQY EKYSFRGFPP EDLMPLAAAY GHALEQYEGE SWRESARYLE
    61  AALRLHRLLR DSEAFCHANC SGPAPAAKPD PDGGRADEWA CELRLFGRVL ERAACLRRCK
   121  RTLPAFQVPY PPRQLLRDFQ SRLPYQYLHY ALFKANRLEK AVAAAYTFLQ RNPKHELTAK
   181  YLNYYQGMLD VADESLTDLE AQPYEAVFLR AVKLYNSGDF RSSTEDMERA LSEYLAVFAR
   241  CLAGCEGAHE QVDFKDFYPA IADLFAESLQ CKVDCEANLT PNVGGYFVDK FVATMYHYLQ
   301  FAYYKLNDVR QAARSAASYM LFDPKDSVMQ QNLVYYRFHR ARWGLEEEDF QPREEAMLYH
   361  NQTAELRELL EFTHMYLQSD DEMELEETEP PLEPEDALSD AEFEGEGDYE EGMYADWWQE
   421  PDAKGDEAEA EPEPELA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against P3H4 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: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.37
Highest tissue expression: 15 nTPM

Expression across tissuesHPA

Tissue

pancreas: 15 nTPM
blood vessel: 15 nTPM
adrenal gland: 13 nTPM
pituitary gland: 12 nTPM
cervix: 12 nTPM
thyroid gland: 12 nTPM

Single-cell type

hepatic stellate cells: 58 nCPM
granulosa cells: 45 nCPM
extravillous trophoblasts: 35 nCPM
retinal horizontal cells: 32 nCPM
pancreatic islet cells: 31 nCPM
goblet cells: 30 nCPM

Immune cell

NK-cell: 8.5 nTPM
MAIT T-cell: 5 nTPM
gdT-cell: 3.9 nTPM
naive CD8 T-cell: 3.9 nTPM
naive CD4 T-cell: 2.9 nTPM
memory CD8 T-cell: 2.6 nTPM

Brain region

choroid plexus: 15 nTPM
cerebellum: 14 nTPM
hypothalamus: 13 nTPM
basal ganglia: 10 nTPM
cerebral cortex: 10 nTPM
amygdala: 9.8 nTPM

ReferencesPubMed · IEDB

Publications for P3H4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

2 publications

cDNA cloning and characterization of a novel nucleolar protein.
1996 · Mol Biol Cell · RCR 1.1 · 52 citations
Identification of nucleolar protein No55 as a tumour-associated autoantigen in patients with prostate cancer.
2000 · Br J Cancer · RCR 0.5 · 25 citations

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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): 1.26
gnomAD pLI: 0
DepMap mean gene effect: -0.19
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of P3H4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads P3H4 as an antibody target. Whether an autoantibody or antibody against P3H4 could matter depends on whether native P3H4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

P3H4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Source-annotated serology context

The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.

This nucleolar protein was first characterized because it was an autoantigen in cases on interstitial cystitis.

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