MAP3K20
Mitogen-activated protein kinase kinase kinase 20
Also known as: M3K20_HUMAN, MLK7, MLTK, MLTKalpha, MLTKbeta, MRK, ZAK
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9NYL2
- Gene
- MAP3K20
- Ensembl
- ENSG00000091436
- Chromosome
- 2
- Canonical length
- 800 aa
- Protein class
- Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins
- Subcellular location
- Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
This gene is a member of the MAPKKK family of signal transduction molecules and encodes a protein with an N-terminal kinase catalytic domain, followed by a leucine zipper motif and a sterile-alpha motif (SAM). This magnesium-binding protein forms homodimers and is located in the cytoplasm. The protein mediates gamma radiation signaling leading to cell cycle arrest and activity of this protein plays a role in cell cycle checkpoint regulation in cells. The protein also has pro-apoptotic activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
800 residues, UniProt reviewed canonical sequence.
>Q9NYL2|MAP3K20
1 MSSLGASFVQ IKFDDLQFFE NCGGGSFGSV YRAKWISQDK EVAVKKLLKI EKEAEILSVL
61 SHRNIIQFYG VILEPPNYGI VTEYASLGSL YDYINSNRSE EMDMDHIMTW ATDVAKGMHY
121 LHMEAPVKVI HRDLKSRNVV IAADGVLKIC DFGASRFHNH TTHMSLVGTF PWMAPEVIQS
181 LPVSETCDTY SYGVVLWEML TREVPFKGLE GLQVAWLVVE KNERLTIPSS CPRSFAELLH
241 QCWEADAKKR PSFKQIISIL ESMSNDTSLP DKCNSFLHNK AEWRCEIEAT LERLKKLERD
301 LSFKEQELKE RERRLKMWEQ KLTEQSNTPL LPSFEIGAWT EDDVYCWVQQ LVRKGDSSAE
361 MSVYASLFKE NNITGKRLLL LEEEDLKDMG IVSKGHIIHF KSAIEKLTHD YINLFHFPPL
421 IKDSGGEPEE NEEKIVNLEL VFGFHLKPGT GPQDCKWKMY MEMDGDEIAI TYIKDVTFNT
481 NLPDAEILKM TKPPFVMEKW IVGIAKSQTV ECTVTYESDV RTPKSTKHVH SIQWSRTKPQ
541 DEVKAVQLAI QTLFTNSDGN PGSRSDSSAD CQWLDTLRMR QIASNTSLQR SQSNPILGSP
601 FFSHFDGQDS YAAAVRRPQV PIKYQQITPV NQSRSSSPTQ YGLTKNFSSL HLNSRDSGFS
661 SGNTDTSSER GRYSDRSRNK YGRGSISLNS SPRGRYSGKS QHSTPSRGRY PGKFYRVSQS
721 ALNPHQSPDF KRSPRDLHQP NTIPGMPLHP ETDSRASEED SKVSEGGWTK VEYRKKPHRP
781 SPAKTNKERA RGDHRGWRNFLocalizationUniProt · AlphaFold · HPA
Whether an antibody against MAP3K20 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)
- 0.43
- Highest tissue expression
- 261 nTPM
Expression across tissuesHPA
Tissue
- tongue: 261 nTPM
- skeletal muscle: 245 nTPM
- heart muscle: 183 nTPM
- endometrium: 72 nTPM
- smooth muscle: 70 nTPM
- adipose tissue: 67 nTPM
Single-cell type
- myonuclei: 1,067 nCPM
- thymic myoid cells: 684 nCPM
- smooth muscle cells: 507 nCPM
- vascular smooth muscle cells: 465 nCPM
- cardiomyocytes: 464 nCPM
- neutrophils: 339 nCPM
Immune cell
- myeloid DC: 16 nTPM
- classical monocyte: 9.4 nTPM
- intermediate monocyte: 8.3 nTPM
- non-classical monocyte: 8.3 nTPM
- total PBMC: 3.4 nTPM
- neutrophil: 2.6 nTPM
Brain region
- choroid plexus: 28 nTPM
- midbrain: 27 nTPM
- medulla oblongata: 25 nTPM
- thalamus: 22 nTPM
- hypothalamus: 21 nTPM
- spinal cord: 19 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about MAP3K20.
Disease | AllUniProt
Conditions MAP3K20 is implicated in, by any mechanism.
- Split-foot malformation with mesoaxial polydactyly (SFMMP) MIM:616890
- Myopathy, centronuclear, 6, with fiber-type disproportion (CNM6) MIM:617760
Disease | GeneticClinVar
14 pathogenic / likely-pathogenic of 454 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Split-foot malformation-mesoaxial polydactyly syndrome
- Myopathy, centronuclear, 6, with fiber-type disproportion
- Split hand-foot malformation 1
- Centronuclear myopathy
- MAP3K20-related disorder
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)
- 0.68
- gnomAD pLI
- 0
- 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 death
- cell differentiation
- cellular response to gamma radiation
- cellular response to UV-B
- chromosome segregation
- cytoskeleton organization
- DNA damage checkpoint signaling
- embryonic digit morphogenesis
- GCN2-mediated signaling
- inflammatory response
- JNK cascade
- limb development
- MAPK cascade
- negative regulation of translation in response to endoplasmic reticulum stress
- p38MAPK cascade
- positive regulation of apoptotic process
- positive regulation of programmed cell death
- protein autophosphorylation
- protein phosphorylation
- pyroptotic inflammatory response
- regulation of mitotic metaphase/anaphase transition
- stress-activated MAPK cascade
- stress-activated protein kinase signaling cascade
- negative regulation of stress-activated protein kinase signaling cascade
- positive regulation of mitotic DNA damage checkpoint
Molecular functions
- ATP binding
- JUN kinase kinase kinase activity
- magnesium ion binding
- MAP kinase kinase kinase activity
- protein kinase activator activity
- protein serine kinase activity
- protein serine/threonine kinase activity
- ribosome binding
- RNA binding
- small ribosomal subunit rRNA binding
- stalled ribosome sensor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Protein kinase domain
- Serine-threonine/tyrosine-protein kinase, catalytic domain
- Sterile alpha motif domain
- Serine/threonine-protein kinase, active site
- Protein kinase-like domain superfamily
- Sterile alpha motif/pointed domain superfamily
- Serine/Threonine Kinases and Pseudokinases
- SAM domain (Sterile alpha motif)
- Protein tyrosine and serine/threonine kinase
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of MAP3K20 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 MAP3K20 as an antibody target. Whether an autoantibody or antibody against MAP3K20 could matter depends on whether native MAP3K20 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
MAP3K20 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.
Annotation status
The present source text does not explicitly label MAP3K20 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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