PCDHA4
Protocadherin alpha-4
Also known as: CNR1, CNRN1, CRNR1, PCDA4_HUMAN, PCDH-ALPHA4
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9UN74
- Gene
- PCDHA4
- Ensembl
- ENSG00000204967
- Chromosome
- 5
- Canonical length
- 947 aa
- Protein class
- Predicted membrane proteins
- Subcellular location
- Nucleoplasm,Plasma membrane,Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
947 residues, UniProt reviewed canonical sequence.
>Q9UN74|PCDHA4
1 MEFSWGSGQE SRRLLLLLLL LAAWEAGNGQ LHYSVSEEAK HGTFVGRIAQ DLGLELAELV
61 PRLFRVASKG RGGLLEVNLQ NGILFVNSRI DREELCRRSA ECSIHLEVIV DRPLQVFHVD
121 VEVRDINDNP PVFPATQKNL SIAESRPLDS RFPLEGASDA DIGENALLTY RLSPNEYFSL
181 EKPPDDELVK GLGLILRKSL DREEAPEIFL VLTATDGGKP ELTGTVQLLI TVLDANDNAP
241 AFDRTIYKVR LLENVPNGTL VIKLNASDLD EGLNGDIVYS FSNDISPNVK SKFHIDPITG
301 QIIVKGYIDF EESKSYEIIV EGIDKGQLPL SGHCRVIVEV EDNNDNVPDL EFKSLSLPIR
361 EDAPLGTVIA LISVSDKDMG VNGLVTCSLT SHVPFKLVST FKNYYSLVLD SALDRESVSA
421 YELVVTARDG GSPSLWATAS VSVEVADVND NAPAFAQPEY TVFVKENNPP GCHIFTVSAW
481 DADAQENALV SYSLVERRVG ERALSSYVSV HAESGKVYAL QPLDHEELEL LQFQVTARDA
541 GVPPLGSNVT LQVFVLDEND NAPALLAPRA GGTGGAVSEL VPWSVGVGHV VAKVRAVDAD
601 SGYNAWLSYE LQPGTGGARI PFRVGLYTGE ISTTRALDET DAPRHRLLVL VKDHGEPALT
661 ATATVLVSLV ESGQAPKASS RALVGAVGPD AALVDVNVYL IIAICAVSSL LVLTLLLYTA
721 LRCSALPTEG ACAPGKPTLV CSSAVGSWSY SQQRRPRVCS GEGPPKTDLM AFSPSLPDSR
781 DREDQLQTTE ESFAKPRQPN PDWRYSASLR AGMHSSVHLE EAGILRAGPG GPDQQWPTVS
841 SATPEPEAGE VSPPVGAGVN SNSWTFKYGP GNPKQSGPGE LPDKFIIPGS PAIISIRQEP
901 TNSQIDKSDF ITFGKKEETK KKKKKKKGNK TQEKKEKGNS TTDNSDQLocalizationUniProt · AlphaFold · HPA
Whether an antibody against PCDHA4 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
- Cell surface
- Secreted
- No
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.44
- Highest tissue expression
- 1.9 nTPM
Expression across tissuesHPA
Tissue
- cerebral cortex: 1.9 nTPM
- cerebellum: 1.4 nTPM
- gallbladder: 1.2 nTPM
- pancreas: 1.1 nTPM
- basal ganglia: 0.7 nTPM
- bone marrow: 0.7 nTPM
Single-cell type
- oligodendrocyte progenitor cells: 7.4 nCPM
- bergmann glia: 5.6 nCPM
- brain inhibitory neurons: 2.3 nCPM
- brain excitatory neurons: 2.1 nCPM
- ependymal cells: 1.8 nCPM
- oligodendrocytes: 1.4 nCPM
Immune cell
- basophil: 0.2 nTPM
- neutrophil: 0.2 nTPM
- eosinophil: 0.1 nTPM
- gdT-cell: 0.1 nTPM
- naive B-cell: 0.1 nTPM
- naive CD8 T-cell: 0.1 nTPM
Brain region
- cerebellum: 13 nTPM
- white matter: 9.2 nTPM
- basal ganglia: 9 nTPM
- cerebral cortex: 8.7 nTPM
- hippocampal formation: 8.5 nTPM
- amygdala: 7.9 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)
- 1.57
- gnomAD pLI
- 0
- gnomAD missense Z
- -0.77
- DepMap mean gene effect
- -0.06
- 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
- cell adhesion
- homophilic cell adhesion via plasma membrane adhesion molecules
- nervous system development
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of PCDHA4 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 PCDHA4 as an antibody target. Whether an autoantibody or antibody against PCDHA4 could matter depends on whether native PCDHA4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
PCDHA4 is annotated at the cell surface, where native PCDHA4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label PCDHA4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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