CRKL
Crk-like protein
Also known as: CRKL_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P46109
- Gene
- CRKL
- Ensembl
- ENSG00000099942
- Chromosome
- 22
- Canonical length
- 303 aa
- Protein class
- Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Cytosol
OverviewNCBI Gene
This gene encodes a protein kinase containing SH2 and SH3 (src homology) domains which has been shown to activate the RAS and JUN kinase signaling pathways and transform fibroblasts in a RAS-dependent fashion. It is a substrate of the BCR-ABL tyrosine kinase, plays a role in fibroblast transformation by BCR-ABL, and may be oncogenic.[provided by RefSeq, Jan 2009]
Canonical amino-acid sequenceUniProt
303 residues, UniProt reviewed canonical sequence.
>P46109|CRKL
1 MSSARFDSSD RSAWYMGPVS RQEAQTRLQG QRHGMFLVRD SSTCPGDYVL SVSENSRVSH
61 YIINSLPNRR FKIGDQEFDH LPALLEFYKI HYLDTTTLIE PAPRYPSPPM GSVSAPNLPT
121 AEDNLEYVRT LYDFPGNDAE DLPFKKGEIL VIIEKPEEQW WSARNKDGRV GMIPVPYVEK
181 LVRSSPHGKH GNRNSNSYGI PEPAHAYAQP QTTTPLPAVS GSPGAAITPL PSTQNGPVFA
241 KAIQKRVPCA YDKTALALEV GDIVKVTRMN INGQWEGEVN GRKGLFPFTH VKIFDPQNPD
301 ENELocalizationUniProt · AlphaFold · HPA
Whether an antibody against CRKL 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
- 0
- Mean surface accessibility (rSASA)
- 0.42
- Highest tissue expression
- 51 nTPM
Expression across tissuesHPA
Tissue
- skeletal muscle: 51 nTPM
- bone marrow: 51 nTPM
- tongue: 40 nTPM
- thymus: 31 nTPM
- cerebellum: 30 nTPM
- cerebral cortex: 30 nTPM
Single-cell type
- platelets: 89 nCPM
- late spermatids: 73 nCPM
- neutrophils: 70 nCPM
- extravillous trophoblasts: 68 nCPM
- esophageal apical cells: 64 nCPM
- megakaryocytes: 56 nCPM
Immune cell
- non-classical monocyte: 26 nTPM
- eosinophil: 22 nTPM
- total PBMC: 21 nTPM
- naive CD4 T-cell: 20 nTPM
- MAIT T-cell: 19 nTPM
- naive CD8 T-cell: 19 nTPM
Brain region
- thalamus: 71 nTPM
- spinal cord: 71 nTPM
- midbrain: 67 nTPM
- medulla oblongata: 66 nTPM
- white matter: 62 nTPM
- cerebral cortex: 62 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)
- 0.64
- gnomAD pLI
- 0.45
- gnomAD missense Z
- 1.94
- DepMap mean gene effect
- -0.93
- DepMap dependency class
- common
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- acetylcholine receptor signaling pathway
- anterior/posterior pattern specification
- B cell apoptotic process
- blood vessel development
- cell chemotaxis
- cell migration
- cellular response to interleukin-7
- cellular response to transforming growth factor beta stimulus
- cellular response to xenobiotic stimulus
- cerebellar neuron development
- cerebral cortex development
- chordate pharynx development
- cranial skeletal system development
- dendrite development
- endothelin receptor signaling pathway
- enzyme-linked receptor protein signaling pathway
- establishment of cell polarity
- fibroblast growth factor receptor signaling pathway
- helper T cell diapedesis
- hippocampus development
- intracellular signal transduction
- JNK cascade
- lipid metabolic process
- male gonad development
- negative regulation of gene expression
- negative regulation of SMAD protein signal transduction
- neuron migration
- outflow tract morphogenesis
- parathyroid gland development
- positive regulation of cell population proliferation
- positive regulation of ERK1 and ERK2 cascade
- positive regulation of Rac protein signal transduction
- positive regulation of skeletal muscle acetylcholine-gated channel clustering
- positive regulation of substrate adhesion-dependent cell spreading
- postsynaptic specialization assembly
- Ras protein signal transduction
- reelin-mediated signaling pathway
- regulation of cell adhesion mediated by integrin
- regulation of cell growth
- regulation of dendrite development
- regulation of T cell migration
- retinoic acid receptor signaling pathway
- single fertilization
- spermatogenesis
- T cell receptor signaling pathway
- thymus development
- urogenital system development
- positive regulation of glial cell migration
Molecular functions
- cadherin binding
- identical protein binding
- phosphotyrosine residue binding
- receptor tyrosine kinase binding
- RNA binding
- RNA polymerase II-specific DNA-binding transcription factor binding
- signaling adaptor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CRKL 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 CRKL as an antibody target. Whether an autoantibody or antibody against CRKL could matter depends on whether native CRKL is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CRKL is annotated at the cell surface, where native CRKL 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 CRKL as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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