CRYAB
Alpha-crystallin B chain
Also known as: CRYA2, CRYAB_HUMAN, HSPB5
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P02511
- Gene
- CRYAB
- Ensembl
- ENSG00000109846
- Chromosome
- 11
- Canonical length
- 175 aa
- Protein class
- Cancer-related genes, Disease related genes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters
- Subcellular location
- Plasma membrane,Cytosol
- Secretome location
- Intracellular and membrane
OverviewNCBI Gene
Mammalian lens crystallins are divided into alpha, beta, and gamma families. Alpha crystallins are composed of two gene products: alpha-A and alpha-B, for acidic and basic, respectively. Alpha crystallins can be induced by heat shock and are members of the small heat shock protein (HSP20) family. They act as molecular chaperones although they do not renature proteins and release them in the fashion of a true chaperone; instead they hold them in large soluble aggregates. These heterogeneous aggregates consist of 30-40 subunits; the alpha-A and alpha-B subunits have a 3:1 ratio, respectively. Two additional functions of alpha crystallins are an autokinase activity and participation in the intracellular architecture. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Alpha-A and alpha-B gene products are differentially expressed; alpha-A is preferentially restricted to the lens and alpha-B is expressed widely in many tissues and organs. Elevated expression of alpha-B crystallin occurs in many neurological diseases; a missense mutation cosegregated in a family with a desmin-related myopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2019]
Canonical amino-acid sequenceUniProt
175 residues, UniProt reviewed canonical sequence.
>P02511|CRYAB
1 MDIAIHHPWI RRPFFPFHSP SRLFDQFFGE HLLESDLFPT STSLSPFYLR PPSFLRAPSW
61 FDTGLSEMRL EKDRFSVNLD VKHFSPEELK VKVLGDVIEV HGKHEERQDE HGFISREFHR
121 KYRIPADVDP LTITSSLSSD GVLTVNGPRK QVSGPERTIP ITREEKPAVT AAPKKLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CRYAB 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)
- 0.44
- Highest tissue expression
- 10,538 nTPM
Expression across tissuesHPA
Tissue
- heart muscle: 10,538 nTPM
- tongue: 8,773 nTPM
- skeletal muscle: 7,430 nTPM
- spinal cord: 4,674 nTPM
- midbrain: 2,675 nTPM
- kidney: 2,165 nTPM
Single-cell type
- epididymal efferent duct absorptive cells: 3,659 nCPM
- thymic myoid cells: 3,391 nCPM
- schwann cells: 3,219 nCPM
- esophageal apical cells: 2,670 nCPM
- epididymal efferent duct ciliated cells: 2,186 nCPM
- pancreatic duct cells: 1,898 nCPM
Immune cell
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
- MAIT T-cell: 0 nTPM
Brain region
- white matter: 4,366 nTPM
- medulla oblongata: 2,791 nTPM
- basal ganglia: 2,511 nTPM
- pons: 2,405 nTPM
- cerebellum: 2,403 nTPM
- spinal cord: 2,070 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CRYAB.
Disease | AllUniProt
Conditions CRYAB is implicated in, by any mechanism.
- Myopathy, myofibrillar, 2A, adult-onset (MFM2A) MIM:608810
- Cataract 16, multiple types (CTRCT16) MIM:613763
- Myopathy, myofibrillar, 2B, infantile-onset (MFM2B) MIM:613869
- Cardiomyopathy, dilated, 1II (CMD1II) MIM:615184
Disease | GeneticClinVar
18 pathogenic / likely-pathogenic of 349 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Dilated cardiomyopathy 1II
- Cataract 16 multiple types
- Myofibrillar myopathy 2
- Cardiomyopathy, familial restrictive, 1
- Developmental cataract
Disease | ImmuneIEDB
Conditions an epitope on CRYAB was assayed in.
- multiple sclerosis B and T cell
- autoimmune uveitis B 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)
- 1.43
- gnomAD pLI
- 0.02
- gnomAD missense Z
- 0.48
- DepMap mean gene effect
- -0.05
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- apoptotic process involved in morphogenesis
- cellular response to gamma radiation
- glutathione metabolic process
- lens development in camera-type eye
- muscle contraction
- muscle organ development
- negative regulation of amyloid fibril formation
- negative regulation of apoptotic process
- negative regulation of cell growth
- negative regulation of DNA-templated transcription
- negative regulation of gene expression
- negative regulation of intracellular transport
- negative regulation of protein-containing complex assembly
- negative regulation of reactive oxygen species metabolic process
- protein folding
- protein refolding
- protein stabilization
- regulation of programmed cell death
- response to estradiol
- response to heat
- response to hydrogen peroxide
- response to hypoxia
- stress-activated MAPK cascade
- tubulin complex assembly
- microtubule polymerization or depolymerization
Molecular functions
- amyloid-beta binding
- identical protein binding
- metal ion binding
- microtubule binding
- protein homodimerization activity
- protein-containing complex binding
- structural constituent of eye lens
- structural molecule activity
- unfolded protein binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CRYAB 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 CRYAB as an antibody target. Whether an autoantibody or antibody against CRYAB could matter depends on whether native CRYAB is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CRYAB is annotated as secreted, so native CRYAB 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 CRYAB as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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