CRADD

Protein identityUniProt · HPA

UniProt accession

P78560

Gene

CRADD

Ensembl

ENSG00000169372

Chromosome

12

Canonical length

199 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Cytosol

OverviewNCBI Gene

This gene encodes a protein containing a death domain (DD) motif. This protein recruits caspase 2/ICH1 to the cell death signal transduction complex, which includes tumor necrosis factor receptor 1 (TNFR1A) and RIPK1/RIP kinase, and acts in promoting apoptosis. A mutation in this gene was associated with cognitive disability. A related pseudogene is found on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

Canonical amino-acid sequenceUniProt

199 residues, UniProt reviewed canonical sequence.

>P78560|CRADD
     1  MEARDKQVLR SLRLELGAEV LVEGLVLQYL YQEGILTENH IQEINAQTTG LRKTMLLLDI
    61  LPSRGPKAFD TFLDSLQEFP WVREKLKKAR EEAMTDLPAG DRLTGIPSHI LNSSPSDRQI
   121  NQLAQRLGPE WEPMVLSLGL SQTDIYRCKA NHPHNVQSQV VEAFIRWRQR FGKQATFQSL
   181  HNGLRAVEVD PSLLLHMLE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CRADD 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)

0.3

Highest tissue expression

39 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CRADD.

Disease | AllUniProt

Conditions CRADD is implicated in, by any mechanism.

• Intellectual developmental disorder, autosomal recessive 34, with variant lissencephaly (MRT34) MIM:614499

Disease | GeneticClinVar

8 pathogenic / likely-pathogenic of 88 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Intellectual disability, autosomal recessive 34
• Intellectual disability
• Moderate intellectual disability
• Familial isolated arrhythmogenic right ventricular dysplasia

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)

0.44

gnomAD pLI

0.88

gnomAD missense Z

0.1

DepMap mean gene effect

0.12

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• apoptotic signaling pathway
• cellular response to mechanical stimulus
• DNA damage response
• DNA damage response, signal transduction by p53 class mediator
• extrinsic apoptotic signaling pathway via death domain receptors
• positive regulation of apoptotic process
• positive regulation of apoptotic signaling pathway

Molecular functions

• death domain binding
• protease binding
• protein-macromolecule adaptor activity

Cellular components

• cytoplasm
• cytosol
• endopeptidase complex
• nucleolus
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Death domain
• CARD domain
• Death-like domain superfamily
• Death domain
• Caspase recruitment domain
• CRADD, Death domain
• Death domain-containing protein CRADD
• RAIDD, CARD domain

KeywordsUniProt

• Apoptosis
• Cytoplasm
• Intellectual disability
• Lissencephaly
• Nucleus

InteractionsUniProt · HPA

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

• TNFRSF1A
• TRADD
• CASP2
• PIDD1