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Protein Page:
P38A (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
P38A a proline-directed ser/thr MAP kinase, and one of four p38 kinases that play important roles in cellular responses to inflammatory cytokines, DNA damage, oxidative stress, and some GPCRs, leading to direct activation of transcription factors and of other downstream kinases including MSK1, MSK2, eEF2K, MK2, and PRAK. MSK1 and -2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli. MK2 and -3 control gene expression mostly at the post-transcriptional level. eEF2K is important for the elongation of mRNA during translation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17, which then cleaves the ectodomain of TGF-alpha family ligands, a process leading to the activation of EGFR signaling and cell proliferation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, CHOPO, p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. Interacts directly with HDAC3 interacts directly and selectively to repress ATF2 transcriptional activity, and regulate TNF gene expression in LPS-stimulated cells. Phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. May also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Regulates the endocytosis of membrane receptors that depend on RAB5A. Regulates the clathrin-mediated internalization of EGFR induced by inflammatory cytokines and UV irradiation by phosphorylating the EGFR and RAB5A effectors. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Interacts with casein kinase II subunits CSNK2A1 and CSNK2B. Activated by cell stresses such as DNA damage, heat shock, osmotic shock, anisomycin and sodium arsenite, as well as pro-inflammatory stimuli such as LPS and IL-1. Phosphorylated by ZAP70 in an alternative activation pathway in response to TCR signaling in T-cells, a pathway is inhibited by GADD45A. Four alternatively spliced isoforms of the human protein have been observed. Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis Note: This description may include information from UniProtKB.
Protein type: Protein kinase, Ser/Thr (non-receptor); Kinase, protein; Protein kinase, CMGC; EC 2.7.11.24; EC 2.7.1.37; CMGC group; MAPK family; MAPK/p38 subfamily; p38 subfamily
Cellular Component: nucleoplasm; spindle pole; mitochondrion; cytoplasm; nucleus; cytosol
Molecular Function: MAP kinase kinase activity; MAP kinase activity; protein serine/threonine kinase activity; protein binding; NFAT protein binding; ATP binding
Biological Process: nerve growth factor receptor signaling pathway; activation of MAPK activity; stress-activated MAPK cascade; osteoclast differentiation; toll-like receptor 3 signaling pathway; toll-like receptor 5 signaling pathway; cell surface receptor linked signal transduction; regulation of transcription factor activity; transmembrane receptor protein serine/threonine kinase signaling pathway; chondrocyte differentiation; toll-like receptor 4 signaling pathway; cartilage condensation; platelet activation; skeletal muscle development; transcription, DNA-dependent; positive regulation of blood vessel endothelial cell migration; glucose metabolic process; toll-like receptor 2 signaling pathway; mRNA metabolic process; regulation of transcription from RNA polymerase II promoter; muscle cell differentiation; response to muramyl dipeptide; DNA damage checkpoint; striated muscle cell differentiation; positive regulation of transcription from RNA polymerase II promoter; fatty acid oxidation; toll-like receptor 9 signaling pathway; apoptosis; cell morphogenesis; signal transduction; chemotaxis; toll-like receptor 10 signaling pathway; RNA metabolic process; lipopolysaccharide-mediated signaling pathway; angiogenesis; positive regulation of erythrocyte differentiation; MyD88-independent toll-like receptor signaling pathway; DNA damage response, signal transduction; positive regulation of myoblast differentiation; MyD88-dependent toll-like receptor signaling pathway; peptidyl-serine phosphorylation; positive regulation of protein import into nucleus; Ras protein signal transduction; toll-like receptor signaling pathway; innate immune response; positive regulation of muscle cell differentiation; gene expression; blood coagulation; cell motility; vascular endothelial growth factor receptor signaling pathway
Reference #:  Q16539 (UniProtKB)
Alt. Names/Synonyms: CSAID-binding protein; Csaids binding protein; CSBP; CSBP1; CSBP2; CSPB1; cytokine suppressive anti-inflammatory drug binding protein; Cytokine suppressive anti-inflammatory drug-binding protein; EXIP; MAP kinase 14; MAP kinase MXI2; MAP kinase p38 alpha; MAPK 14; MAPK14; MAX-interacting protein 2; Mitogen-activated protein kinase 14; Mitogen-activated protein kinase p38 alpha; MK14; MXI2; p38; p38 MAP kinase; p38 mitogen activated protein kinase; p38ALPHA; p38alpha Exip; PRKM14; PRKM15; RK; SAPK2A; stress-activated protein kinase 2A
Gene Symbols: MAPK14
Molecular weight: 41,293 Da
Basal Isoelectric point: 5.48  Predict pI for various phosphorylation states
CST Pathways:  Angiogenesis  |  B Cell Receptor Signaling  |  NF-kB Signaling  |  Phospholipase Signaling  |  Regulation of P38 MAPKs  |  T Cell Receptor Signaling  |  TGF-├č Signaling  |  Toll-Like Receptor Signaling  |  Translation: eIF4E and p70S6K
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

P38A

Protein Structure Not Found.

Substrate Sequence Logo
Sequence Logo

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Sites Implicated In
apoptosis, altered: T180‑p, Y182‑p
cell adhesion, altered: T180‑p, Y182‑p
cell cycle regulation: T180‑p, Y182‑p
cell differentiation, altered: T123‑p
cell motility, altered: T180‑p, Y182‑p
cytoskeletal reorganization: T180‑p, Y182‑p
activity, induced: T180‑p, Y182‑p
enzymatic activity, induced: T180‑p, Y182‑p, Y323‑p
enzymatic activity, inhibited: T123‑p
molecular association, regulation: T123‑p, T180‑p
phosphorylation: T123‑p, T180‑p, Y182‑p, Y323‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

► Hide Isoforms
 
0 8 S2-p ______MsQERPTFY
0 1 T7 _MsQERPTFYRQELN
0 2 K15-ub FYRQELNktIWEVPE
0 1 T16-p YRQELNktIWEVPER
0 1 S28-p PERYQNLsPVGSGAY
1 0 K53-ac TGLRVAVkKLsRPFQ
0 1 S56-p RVAVkKLsRPFQSII
0 1 K118-ub ADLNNIVkCQKLtDD
1 0 T123-p IVkCQKLtDDHVQFL
0 4 K139-ub YQILRGLkYIHSADI
1 0 K152-ac DIIHRDLkPSNLAVN
0 2 K165-ub VNEDCELkILDFGLA
0 103 T175-p DFGLARHtDDEMtGy
313 1551 T180-p RHtDDEMtGyVAtRW
319 3687 Y182-p tDDEMtGyVAtRWYR
1 15 T185-p EMtGyVAtRWYRAPE
0 1 T241-p LILRLVGtPGAELLK
0 2 - gap
0 1 K248 tPGAELLKKISSESA
0 1 T263-p RNYIQSLtQMPKMNF
5 0 Y323-p DEPVADPyDQSFESR
4092 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (Biotinylated)
4511 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb
4551 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 488 Conjugate)
4552 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 647 Conjugate)
4631 : Phospho-p38 MAPK (Thr180/Tyr182) (12F8) Rabbit mAb
6908 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (PE Conjugate)
8632 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 594 Conjugate)
9211 : Phospho-p38 MAPK (Thr180/Tyr182) Antibody
9215 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb
9216 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb
9219 : Phospho-p38 MAPK (Thr180/Tyr182) Mouse mAb (Sepharose Bead Conjugate)
9836 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 555 Conjugate)
4092 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (Biotinylated)
4511 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb
4551 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 488 Conjugate)
4552 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 647 Conjugate)
4631 : Phospho-p38 MAPK (Thr180/Tyr182) (12F8) Rabbit mAb
6908 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (PE Conjugate)
8632 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 594 Conjugate)
9211 : Phospho-p38 MAPK (Thr180/Tyr182) Antibody
9215 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb
9216 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb
9219 : Phospho-p38 MAPK (Thr180/Tyr182) Mouse mAb (Sepharose Bead Conjugate)
9836 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 555 Conjugate)
  P38A iso2  
S2 ______MSQERPTFY
T7 _MSQERPTFYRQELN
K15 FYRQELNKTIWEVPE
T16 YRQELNKTIWEVPER
S28 PERYQNLSPVGSGAY
K53 TGLRVAVKKLSRPFQ
S56 RVAVKKLSRPFQSII
K118 ADLNNIVKCQKLTDD
T123 IVKCQKLTDDHVQFL
K139 YQILRGLKYIHSADI
K152 DIIHRDLKPSNLAVN
K165 VNEDCELKILDFGLA
T175 DFGLARHTDDEMTGy
T180 RHTDDEMTGyVATRW
Y182-p TDDEMTGyVATRWYR
T185 EMTGyVATRWYRAPE
- gap
T241-p QIMRLTGtPPAYLIN
- gap
T263 RNYIQSLTQMPKMNF
Y323 DEPVADPYDQSFESR
4092 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (Biotinylated)
4511 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb
4551 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 488 Conjugate)
4552 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 647 Conjugate)
4631 : Phospho-p38 MAPK (Thr180/Tyr182) (12F8) Rabbit mAb
6908 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (PE Conjugate)
8632 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 594 Conjugate)
9211 : Phospho-p38 MAPK (Thr180/Tyr182) Antibody
9215 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb
9216 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb
9219 : Phospho-p38 MAPK (Thr180/Tyr182) Mouse mAb (Sepharose Bead Conjugate)
9836 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 555 Conjugate)
4092 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (Biotinylated)
4511 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb
4551 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 488 Conjugate)
4552 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 647 Conjugate)
4631 : Phospho-p38 MAPK (Thr180/Tyr182) (12F8) Rabbit mAb
6908 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (PE Conjugate)
8632 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 594 Conjugate)
9211 : Phospho-p38 MAPK (Thr180/Tyr182) Antibody
9215 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb
9216 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb
9219 : Phospho-p38 MAPK (Thr180/Tyr182) Mouse mAb (Sepharose Bead Conjugate)
9836 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 555 Conjugate)
  mouse

► Hide Isoforms
 
S2-p ______MsQERPtFY
T7-p _MsQERPtFYRQELN
K15-ub FYRQELNkTIWEVPE
T16 YRQELNkTIWEVPER
S28 PERYQNLSPVGSGAY
K53 TGHRVAVKKLSRPFQ
S56 RVAVKKLSRPFQSII
K118 ADLNNIVKCQKLTDD
T123 IVKCQKLTDDHVQFL
K139-ub YQILRGLkYIHSADI
K152 DIIHRDLKPSNLAVN
K165-ub VNEDCELkILDFGLA
T175-p DFGLARHtDDEMtGy
T180-p RHtDDEMtGyVAtRW
Y182-p tDDEMtGyVAtRWYR
T185-p EMtGyVAtRWYRAPE
T241 LILRLVGTPGAELLk
- gap
K248-ub TPGAELLkKISSESA
A263 RNYIQSLAQMPKMNF
Y323-p DEPVADPyDQSFESR
4092 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (Biotinylated)
4511 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb
4551 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 488 Conjugate)
4552 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 647 Conjugate)
4631 : Phospho-p38 MAPK (Thr180/Tyr182) (12F8) Rabbit mAb
6908 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (PE Conjugate)
8632 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 594 Conjugate)
9211 : Phospho-p38 MAPK (Thr180/Tyr182) Antibody
9215 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb
9216 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb
9219 : Phospho-p38 MAPK (Thr180/Tyr182) Mouse mAb (Sepharose Bead Conjugate)
9836 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 555 Conjugate)
4092 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (Biotinylated)
4511 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb
4551 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 488 Conjugate)
4552 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 647 Conjugate)
4631 : Phospho-p38 MAPK (Thr180/Tyr182) (12F8) Rabbit mAb
6908 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (PE Conjugate)
8632 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 594 Conjugate)
9211 : Phospho-p38 MAPK (Thr180/Tyr182) Antibody
9215 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb
9216 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb
9219 : Phospho-p38 MAPK (Thr180/Tyr182) Mouse mAb (Sepharose Bead Conjugate)
9836 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 555 Conjugate)
  P38A iso3  
S2 ______MSQERPTFY
T7 _MSQERPTFYRQELN
K15 FYRQELNKTIWEVPE
T16 YRQELNKTIWEVPER
S28 PERYQNLSPVGSGAY
K53 TGHRVAVKKLSRPFQ
S56 RVAVKKLSRPFQSII
K118 ADLNNIVKCQKLTDD
T123 IVKCQKLTDDHVQFL
K139 YQILRGLKYIHSADI
K152 DIIHRDLKPSNLAVN
K165 VNEDCELKILDFGLA
T175 DFGLARHTDDEMTGY
T180 RHTDDEMTGYVATRW
Y182 TDDEMTGYVATRWYR
T185 EMTGYVATRWYRAPE
- gap
T241-p QIMRLTGtPPAYLIN
- gap
A263 RNYIQSLAQMPKMNF
Y323 DEPVADPYDQSFESR
  rat

 
S2 ______MSQERPTFY
T7 _MSQERPTFYRQELN
K15 FYRQELNKTVWEVPE
T16 YRQELNKTVWEVPER
S28 PERYQNLSPVGSGAY
K53 TGHRVAVKKLSRPFQ
S56 RVAVKKLSRPFQSII
K118 ADLNNIVKCQKLTDD
T123 IVKCQKLTDDHVQFL
K139 YQILRGLKYIHSADI
K152 DIIHRDLKPSNLAVN
K165 VNEDCELKILDFGLA
T175 DFGLARHTDDEMtGy
T180-p RHTDDEMtGyVATRW
Y182-p TDDEMtGyVATRWYR
T185 EMtGyVATRWYRAPE
T241 LILRLVGTPGAELLK
- gap
K248 TPGAELLKKISSESA
A263 RNYIQSLAQMPKMNF
Y323 DEPVAEPYDQSFESR
4092 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (Biotinylated)
4511 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb
4551 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 488 Conjugate)
4552 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 647 Conjugate)
4631 : Phospho-p38 MAPK (Thr180/Tyr182) (12F8) Rabbit mAb
6908 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (PE Conjugate)
8632 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 594 Conjugate)
9215 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb
9219 : Phospho-p38 MAPK (Thr180/Tyr182) Mouse mAb (Sepharose Bead Conjugate)
9836 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 555 Conjugate)
4092 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (Biotinylated)
4511 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb
4551 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 488 Conjugate)
4552 : Phospho-p38 MAPK (Thr180/Tyr182) (28B10) Mouse mAb (Alexa Fluor(R) 647 Conjugate)
4631 : Phospho-p38 MAPK (Thr180/Tyr182) (12F8) Rabbit mAb
6908 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb (PE Conjugate)
8632 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 594 Conjugate)
9215 : Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb
9219 : Phospho-p38 MAPK (Thr180/Tyr182) Mouse mAb (Sepharose Bead Conjugate)
9836 : Phospho-p38 MAPK (Thr180/Tyr182) (D3F9) XP(R) Rabbit mAb (Alexa Fluor(R) 555 Conjugate)
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