PDIA4
Protein disulfide-isomerase A4
Also known as: ERP70, ERP72, PDIA4_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P13667
- Gene
- PDIA4
- Ensembl
- ENSG00000155660
- Chromosome
- 7
- Canonical length
- 645 aa
- Protein class
- Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Endoplasmic reticulum
- Secretome location
- Intracellular and membrane
OverviewNCBI Gene
This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal ER-signal sequence, three catalytically active thioredoxin (TRX) domains, two TRX-like domains and a C-terminal ER-retention sequence. This protein, when bound to cyclophilin B, enhances the rate of immunoglobulin G intermolecular disulfide bonding and antibody assembly. [provided by RefSeq, Dec 2016]
Canonical amino-acid sequenceUniProt
645 residues, UniProt reviewed canonical sequence.
>P13667|PDIA4
1 MRPRKAFLLL LLLGLVQLLA VAGAEGPDED SSNRENAIED EEEEEEEDDD EEEDDLEVKE
61 ENGVLVLNDA NFDNFVADKD TVLLEFYAPW CGHCKQFAPE YEKIANILKD KDPPIPVAKI
121 DATSASVLAS RFDVSGYPTI KILKKGQAVD YEGSRTQEEI VAKVREVSQP DWTPPPEVTL
181 VLTKENFDEV VNDADIILVE FYAPWCGHCK KLAPEYEKAA KELSKRSPPI PLAKVDATAE
241 TDLAKRFDVS GYPTLKIFRK GRPYDYNGPR EKYGIVDYMI EQSGPPSKEI LTLKQVQEFL
301 KDGDDVIIIG VFKGESDPAY QQYQDAANNL REDYKFHHTF STEIAKFLKV SQGQLVVMQP
361 EKFQSKYEPR SHMMDVQGST QDSAIKDFVL KYALPLVGHR KVSNDAKRYT RRPLVVVYYS
421 VDFSFDYRAA TQFWRSKVLE VAKDFPEYTF AIADEEDYAG EVKDLGLSES GEDVNAAILD
481 ESGKKFAMEP EEFDSDTLRE FVTAFKKGKL KPVIKSQPVP KNNKGPVKVV VGKTFDSIVM
541 DPKKDVLIEF YAPWCGHCKQ LEPVYNSLAK KYKGQKGLVI AKMDATANDV PSDRYKVEGF
601 PTIYFAPSGD KKNPVKFEGG DRDLEHLSKF IEEHATKLSR TKEELLocalizationUniProt · AlphaFold · HPA
Whether an antibody against PDIA4 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)
- 0.31
- Highest tissue expression
- 235 nTPM
Expression across tissuesHPA
Tissue
- liver: 235 nTPM
- thyroid gland: 221 nTPM
- epididymis: 155 nTPM
- pancreas: 116 nTPM
- stomach: 90 nTPM
- cervix: 88 nTPM
Single-cell type
- epididymal principal cells: 781 nCPM
- hepatocytes: 653 nCPM
- extravillous trophoblasts: 538 nCPM
- plasma cells: 448 nCPM
- syncytiotrophoblasts: 268 nCPM
- prostatic glandular cells: 254 nCPM
Immune cell
- plasmacytoid DC: 252 nTPM
- total PBMC: 161 nTPM
- MAIT T-cell: 136 nTPM
- gdT-cell: 131 nTPM
- memory CD8 T-cell: 100 nTPM
- memory B-cell: 100 nTPM
Brain region
- white matter: 82 nTPM
- medulla oblongata: 59 nTPM
- thalamus: 56 nTPM
- choroid plexus: 54 nTPM
- hypothalamus: 49 nTPM
- cerebellum: 49 nTPM
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)
- 0.51
- gnomAD pLI
- 0.08
- gnomAD missense Z
- -0.13
- DepMap mean gene effect
- -0.03
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Protein disulfide-isomerase, thioredoxin-like domain
- Protein disulphide isomerase
- Thioredoxin domain
- Thioredoxin, conserved site
- Thioredoxin-like superfamily
- Thioredoxin
- Thioredoxin-like domain
- Protein disulphide-isomerase A4
- Protein disulfide-isomerase A4, TRX-like domain b
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of PDIA4 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 PDIA4 as an antibody target. Whether an autoantibody or antibody against PDIA4 could matter depends on whether native PDIA4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
PDIA4 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 protein, when bound to cyclophilin B, enhances the rate of immunoglobulin G intermolecular disulfide bonding and antibody assembly.
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