KinaseNET

Nomenclature

Short Name:

p38a

Full Name:

Mitogen-activated protein kinase 14

Alias:

CRK1
CSAID binding protein
Cytokine suppressive anti-inflammatory drug binding protein
EC 2.7.11.24
MAPK14
Kinase p38-alpha; PRKM15; p38a MAPK; SAPK2A
CSBP
CSBP1
CSBP2
CSPB1

Classification

Type:

Protein-serine/threonine kinase

Group:

CMGC

Family:

MAPK

SubFamily:

p38

Specific Links

Entrez-Gene Entry:	1432
Entrez-Protein Entry:	NP_001306
GeneCards Entry:	CSBP1
KinBASE Entry:	P38A
OMIM Entry:	600289
Pfam Entry:	Q16539
PhosphoNET Entry:	Q16539
Phosphosite Plus Entry:	626
Protein Data Bank Entry:	1A9U
ScanSite Entry:	Q16539
Source Entry:	MAPK14
UCSD-Nature Entry:	A001717
UniProt Entry:	Q16539
Kinexus Products:	p38a Mitogen-activated protein-serine kinase p38 alpha; Mitogen-activated protein kinase 14 pan-specific antibody AB-NK120-10 Mitogen-activated protein kinase 14 pan-specific antibody AB-NK120-4 Mitogen-activated protein kinase 14 pan-specific antibody AB-NK120-5 Mitogen-activated protein-serine kinase p38 alpha; Mitogen-activated protein kinase 14 pan-specific antibody AB-NK120-8 Mitogen-activated protein-serine kinase p38 alpha; Mitogen-activated protein kinase 14 T180+Y182 phosphosite-specific antibody AB-PK739 Mitogen-activated protein-serine kinase p38 alpha; Mitogen-activated protein kinase 14 T180+Y182 phosphosite-specific antibody AB-PK740 p38 MAPK KinSub - p38 MAPK peptide substrate - Powder PE-01ADG95 Mitogen-activated protein-serine kinase p38 alpha / Mitogen-activated protein kinase 14 (D324-K338, human) peptide - Powder PE-01AYB90 Mitogen-activated protein-serine kinase p38 alpha / Mitogen-activated protein kinase 14 (I346-S360, human) peptide - Powder PE-01AYC99 p38Subtide - p38a MAPK (MAPK14) protein kinase substrate peptide - Powder PE-01BIK99 Mitogen-activated protein-serine kinase p38 alpha / Mitogen-activated protein kinase 14 (M179-T185, human) pT180+pY182 phosphopeptide - Powder PE-04ADE99 Mitogen-activated protein-serine kinase p38 alpha / Mitogen-activated protein kinase 14 (D177-Y182, human) pT180+pY182 phosphopeptide - Powder PE-04ADS75 Mitogen-activated protein-serine kinase p38 alpha / Mitogen-activated protein kinase 14 (D177-V183, human) pT180+pY182 phosphopeptide - Powder PE-04BAM00 Mitogen-activated protein-serine kinase p38 alpha / Mitogen-activated protein kinase 14 (A172-E178, human) pT175 phosphopeptide - Powder PE-04BAN00 Mitogen-activated protein kinase 11 (M179-T185, human) pT182 phosphopeptide - Powder PE-04BAO00 p38SelectideA - p38a MAPK (MAPK14) protein kinase substrate peptide - Powder PE-14CAC90

General Links

Structure

Mol. Mass (Da):

41293

# Amino Acids:

360

# mRNA Isoforms:

mRNA Isoforms:

41,493 Da (360 AA; Q16539-2); 41,293 Da (360 AA; Q16539); 35,453 Da (307 AA; Q16539-4); 34,092 Da (297 AA; Q16539-3); 29,388 Da (256 AA; Q16539-5)

4D Structure:

Binds to a kinase interaction motif within the protein tyrosine phosphatase, PTPRR. This interaction retains MAPK14 in the cytoplasm and prevents nuclear accumulation. Interacts with SPAG9 By similarity. Interacts with NP60 and FAM48A.

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

1R39

Subfamily Alignment

Domain Distribution:

Start	End	Domain
24	308	Pkinase

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.

hiddentext

○	Mitogen-activated protein-serine kinase p38 alpha; Mitogen-activated protein kinase 14 pan-specific antibody AB-NK120-10
○	Mitogen-activated protein kinase 14 pan-specific antibody AB-NK120-4
○	Mitogen-activated protein kinase 14 pan-specific antibody AB-NK120-5
○	Mitogen-activated protein-serine kinase p38 alpha; Mitogen-activated protein kinase 14 pan-specific antibody AB-NK120-8
○	Mitogen-activated protein-serine kinase p38 alpha; Mitogen-activated protein kinase 14 T180+Y182 phosphosite-specific antibody AB-PK739
○	Mitogen-activated protein-serine kinase p38 alpha; Mitogen-activated protein kinase 14 T180+Y182 phosphosite-specific antibody AB-PK740
○	p38 MAPK KinSub - p38 MAPK peptide substrate - Powder PE-01ADG95
○	Mitogen-activated protein-serine kinase p38 alpha / Mitogen-activated protein kinase 14 (D324-K338, human) peptide - Powder PE-01AYB90
○	Mitogen-activated protein-serine kinase p38 alpha / Mitogen-activated protein kinase 14 (I346-S360, human) peptide - Powder PE-01AYC99
○	p38Subtide - p38a MAPK (MAPK14) protein kinase substrate peptide - Powder PE-01BIK99
○	Mitogen-activated protein-serine kinase p38 alpha / Mitogen-activated protein kinase 14 (M179-T185, human) pT180+pY182 phosphopeptide - Powder PE-04ADE99
○	Mitogen-activated protein-serine kinase p38 alpha / Mitogen-activated protein kinase 14 (D177-Y182, human) pT180+pY182 phosphopeptide - Powder PE-04ADS75
○	Mitogen-activated protein-serine kinase p38 alpha / Mitogen-activated protein kinase 14 (D177-V183, human) pT180+pY182 phosphopeptide - Powder PE-04BAM00
○	Mitogen-activated protein-serine kinase p38 alpha / Mitogen-activated protein kinase 14 (A172-E178, human) pT175 phosphopeptide - Powder PE-04BAN00
○	Mitogen-activated protein kinase 11 (M179-T185, human) pT182 phosphopeptide - Powder PE-04BAO00
○	p38SelectideA - p38a MAPK (MAPK14) protein kinase substrate peptide - Powder PE-14CAC90

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Acetylated:

K53, K152.

Serine phosphorylated:

S2, S28, S56, S326.

Threonine phosphorylated:

T7, T16, T123-, T175+, T180+, T185-, T241, T263.

Tyrosine phosphorylated:

Y182+, Y323+.

Ubiquitinated:

K15, K118, K139, K165.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

86

1732

55

2934
4

72

32

56
6

115

15

77
14

284

175

430
34

693

48

595
3

62

150

66
15

304

66

507
23

455

72

565
27

554

34

449
5

104

172

117
5

97

59

85
32

640

341

642
4

72

59

47
3

54

26

49
4

78

46

67
3

68

31

46
3

70

319

51
4

77

34

59
6

114

183

82
30

597

218

629
3

69

43

71
6

117

51

112
3

68

35

41
3

56

35

48
7

141

43

126
27

551

103

631
4

85

65

55
3

63

35

54
5

102

35

77
10

203

56

155
24

492

48

350
100

2022

66

4832
11

218

106

250
44

888

114

757
4

78

79

87

Evolution

Species Conservation

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:

100

100

100
96.1

97.8

100
89.4

90.8

100
-

-

100
-

-

99
-

-

96
-

-

-
99.4

99.4

99
98.6

99.2

99
-

-

-
-

-

-
96.4

98.6

92.5
88.4

94.7

87
85.9

92.2

89
-

-

-
68.5

80.3

70
75

85

-
62.9

76.7

64
-

-

-
-

-

-
-

-

-
-

-

48
-

-

46.5
43

57.9

54
50.6

69.4

53

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	MAP2K6 - P52564
2	MAPKAPK2 - P49137
3	ATF2 - P15336
4	DUSP10 - Q9Y6W6
5	MAP2K3 - P46734
6	MAPK1 - P28482
7	MEF2A - Q02078
8	DUSP16 - Q9BY84
9	DUSP1 - P28562
10	CDC25C - P30307
11	RPS6KA4 - O75676
12	STK39 - Q9UEW8
13	CDC25B - P30305
14	KRT8 - P05787
15	MKNK1 - Q9BUB5

Regulation

Activation:

Phosphorylation at Thr-180 and Tyr-182 increases phosphotransferase activity. These phospho-sites are targeted by MAP2K3, MAP2K6, and potentially also MAP2K4. Phosphorylation at Tyr-323 increases phosphotransferase activity.

Inhibition:

Inhibited by dual specificity phosphatases, such as DUSP1. Phosphorylation at Thr-123 inhibits phosphotransferase activity and interaction with MKK6 and MAPKAPK2.

Synthesis:

Degradation:

Known Upstream Kinases

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.

Based on in vitro and/or in vivo phosphorylation data

Kinase Short Name	UniProt ID (Human)	Phosphosite Location	Phosphosite Sequence	Effect of Phosphorylation

BARK1	P25098	T123	IVKCQKLTDDHVQFL	-
PBK	Q96KB5	T180	RHTDDEMTGYVATRW	+
MEK6	P52564	T180	RHTDDEMTGYVATRW	+
MEK3	P46734	T180	RHTDDEMTGYVATRW	+
MEK4	P45985	T180	RHTDDEMTGYVATRW	+
p38a	Q16539	T180	RHTDDEMTGYVATRW	+
PBK	Q96KB5	Y182	TDDEMTGYVATRWYR	+
MEK6	P52564	Y182	TDDEMTGYVATRWYR	+
MEK3	P46734	Y182	TDDEMTGYVATRWYR	+
MEK4	P45985	Y182	TDDEMTGYVATRWYR	+
p38a	Q16539	Y182	TDDEMTGYVATRWYR	+
LCK	P06239	Y323	DEPVADPYDQSFESR	+
FYN	P06241	Y323	DEPVADPYDQSFESR	+
ZAP70	P43403	Y323	DEPVADPYDQSFESR	+

Known Downstream Substrates

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.

Based on in vitro and/or in vivo phosphorylation data

Substrate Short Name	UniProt ID (Human)	Phosphosite Location	Phosphosite Sequence	Effect of Phosphorylation

ELAVL1	Q15717	T118	SGLPRTMTQKDVEDM	+
4E-BP1	Q13541	T36	PPGDYSTTPGGTLFS
4E-BP1	Q13541	T45	GGTLFSTTPGGTRII	-
Akt1 (PKBa)	P31749	S473	RPHFPQFSYSASGTA	+
Akt1 (PKBa)	P31749	T308	KDGATMKTFCGTPEY	+
AR	P10275	S650	GEASSTTSPTEETTQ	-
ATF2	P15336	T69	SVIVADQTPTPTRFL	+
ATF2	P15336	T71	IVADQTPTPTRFLKN	+
Bcl-2	P10415	S70	RDPVARTSPLQTPAA
Bcl-2	P10415	S87	AAAGPALSPVPPVVH	+
Bcl-2	P10415	T56	FSSQPGHTPHPAASR	+
Bim	O43521	S69	GPLAPPASPGPFATR
BTG2	P78543	S149	LLGRSSPSKNYVMAV
C-EBPa	P49715	S21	PMSSHLQSPPHAPSS
Caldesmon	Q05682	S789	QSVDKVTSPTKV___
Caspase 3	P42574	S150	FRGDRCRSLTGKPKL	-
Caspase 8	Q14790	S347	FTGLKCPSLAGKPKV	-
CDX2	Q99626	S283	RSVPEPLSPVSSLQA
CHOP	P35638	S79	EVTSTSQSPHSPDSS	-
CHOP	P35638	S82	STSQSPHSPDSSQSS	-
Cip1 (p21, CDKN1A)	P38936	S129	SGEQAEGSPGGPGDS	-
Cip1 (p21, CDKN1A)	P38936	T56	NFDFVTETPLEGDFA
cPLA2	P47712	S505	LNTSYPLSPLSDFAT	+
CRYAB	P02511	S59	PSFLRAPSWFDTGLS	?
Cx43	P17302	S278	SSPTAPLSPMSPPGY
Cx43	P17302	S281	TAPLSPMSPPGYKLV
Cyclin D1 (CCND1)	P24385	T286	EEVDLACTPTDVRDV
Cyclin D2 (CCND2)	P30279	T280	DELDQASTPTDVRDI
Cyclin D3 (CCND3)	P30281	T283	QGPSQTSTPTDVTAI
DLX5	P56178	S217	SDPMACNSPQSPAVW
DLX5	P56178	S34	MHHPSQESPTLPESS
E2A	P15923	S139	LNSPGPLSPSGMKGT
EEA1	Q15075	T1392	CSAKNALTPSSKKPV
EGFR	P00533	T693	RELVEPLTPSGEAPN	-
eIF2A	P05198	S52	MILLSELSRRRIRSI	-
Elk-1	P19419	S383	IHFWSTLSPIAPRSP	+
ELK4	P28324	S381	IHFWSTLSPVAPLSP	+
ELK4	P28324	S387	LSPVAPLSPARLQGA	+
ERa (ESR1)	P03372	S118	LHPPPQLSPFLQPHG	+
ERa (ESR1)	P03372	T311	NSLALSLTADQMVSA	+
ETV6	P41212	S22	ISYTPPESPVPSYAS	-
ETV6	P41212	S257	ESHPKPSSPRQESTR	-
EWS	Q01844	T79	QPPTGYTTPTAPQAY
FGFR1	P11362	S777	SMPLDQYSPSFPDTR	?
FOXO1A	Q12778	S287	GQEGAGDSPGSQFSK	-
FOXO1A	Q12778	S295	QFSKWPASPGSHSND
FOXO1A	Q12778	S329	STISGRLSPIMTEQD	-
FOXO1A	Q12778	S416	PPNTSLNSPSPNYQK	+
FOXO1A	Q12778	S432	TYGQSSMSPLPQMPI	+
FOXO1A	Q12778	S470	KELLTSDSPPHNDIM	+
FOXO1A	Q12778	T478	PPHNDIMTPVDPGVA
FOXO1A	Q12778	T560	NRLTQVKTPVQVPLP
GR	P04150	S211	PGKETNESPWRSDLL	?
H3.1	P68431	S10	TKQTARKSTGGKAPR
H3.2	P84228	S29	ATKAARKSAPATGGV
HBP1	O14790	S402	GFSKNCGSPESSQLS
HePTP	P35236	S93	ALQRQPPSPKQLEEE	-
HePTP	P35236	T66	EPICSVNTPREVTLH	-
HNF4A	P41235	S167	VLSRQITSPVSGING
JDP-2	Q8WYK2	T148	VRTDSVKTPESEGNP
KHSRP	Q92945	T692	QAAYYGQTPVPGPQP
KRT8	P05787	S432	SAYGGLTSPGLSYSL
KRT8	P05787	S74	TVNQSLLSPLVLEVD
Kv2.1	Q14721	S805	ESSPLPTSPKFLRQN
LIMK1	P53667	S310	PGAGSLGSPASQRKD
MAPKAPK2	P49137	S272	SNHGLAISPGMKTRI	+
MAPKAPK2	P49137	T222	TSHNSLTTPCYTPYY	+
MAPKAPK2	P49137	T25	APPPQPPTPALPHPP
MAPKAPK2	P49137	T334	QSTKVPQTPLHTSRV	+
MAPKAPK3	Q16644	S251	SNTGQAISPGMKRRI
MAPKAPK3	Q16644	T201	TTQNALQTPCYTPYY	+
MAPKAPK3	Q16644	T313	QSMVVPQTPLHTARV
MAPKAPK5	Q8IW41	T182	IDQGDLMTPQFTPYY	+
MEF2A	Q02078	S192	TTLHRNVSPGAPQRP
MEF2A	Q02078	S223	VPNGAGSSPVGNGFV
MEF2A	Q02078	S408	SIKSEPISPPRDRMT	-
MEF2A	Q02078	S479	DPRGDFHSPIVLGRP
MEF2A	Q02078	S494	PNTEDRESPSVKRMR
MEF2A	Q02078	S98	KEHRGCDSPDPDTSY
MEF2A	Q02078	T108	PDTSYVLTPHTEEKY
MEF2A	Q02078	T312	QATQPLATPVVSVTT	+
MEF2A	Q02078	T319	TPVVSVTTPSLPPQG	+
MEF2C	Q06413	T293	QSAQSLATPVVSVAT	+
MEF2C	Q06413	T300	TPVVSVATPTLPGQG	+
MEF2C iso3	Q06413	S387	TRHEAGRSPVDSLSS	+
MITF	O75030	S414	IPSTGLCSPDLVNRI
MNK1 (MKNK1)	Q9BUB5	T250	NSCTPITTPELTTPC	+
MNK1 (MKNK1)	Q9BUB5	T255	ITTPELTTPCGSAEY	+
MNK2 (GPRK7)	Q9HBH9	T244	GDCSPISTPELLTPC	+
MNK2 (GPRK7)	Q9HBH9	T249	ISTPELLTPCGSAEY	+
MNK2 (GPRK7)	Q9HBH9	T379	APENTLPTPMVLQRN	+
MRP14	P06702	T113	KPGLGEGTP______
MSK1 (RPS6KA5)	O75582	S360	TEMDPTYSPAALPQS	+
MSK1 (RPS6KA5)	O75582	T581	PDNQPLKTPCFTLHY	+
MSK1 (RPS6KA5)	O75582	T700	LSSNPLMTPDILGSS	+
MSK2 (RPS6KA4)	O75676	S196	EEKERTFSFCGTIEY	+
MSK2 (RPS6KA4)	O75676	S343	TRLEPVYSPPGSPPP	+
MSK2 (RPS6KA4)	O75676	S347	PVYSPPGSPPPGDPR	+
MSK2 (RPS6KA4)	O75676	S360	PRIFQGYSFVAPSIL	+
MSK2 (RPS6KA4)	O75676	T568	SPGVPMQTPCFTLQY	+
MSK2 (RPS6KA4)	O75676	T687	RSSPPLRTPDVLESS	+
Myf-6	P23409	S31	PLEVAEGSPLYPGSD
Myf-6	P23409	S42	PGSDGTLSPCQDQMP
MZF-1	P28698	S256	EEAGGIFSPGFALQL
MZF-1	P28698	S294	GLSGQIQSPSREGGF
MZF-1 iso2	P28698	S257	EEVGGIFSPGFTLQM
MZF-1 iso2	P28698	S275	TAEPDMMSPHLHVPW
MZF-1 iso2	P28698	S295	SLSGQIQSPTTEGGF
NCoA2	Q15596	S736	TIKQEPVSPKKKENA
NCOA3 (SRC-3)	Q9Y6Q9	S505	SPVAGVHSPMASSGN	-
NCOA3 (SRC-3)	Q9Y6Q9	S543	SLLSTLSSPGPKLDN	-
NCOA3 (SRC-3)	Q9Y6Q9	S860	NRAVSLDSPVSVGSS	-
NCOA3 (SRC-3)	Q9Y6Q9	S867	SPVSVGSSPPVKNIS	-
NFAT2	O95644	S172	YRDPSCLSPASSLSS
NFAT3	Q14934	S168	QGGGAFFSPSPGSSS	-
NFAT3	Q14934	S170	GGAFFSPSPGSSSLS	-
p38a MAPK (MAPK14)	Q16539	T180	RHTDDEMTGYVATRW	+
p38a MAPK (MAPK14)	Q16539	Y182	TDDEMTGYVATRWYR	+
p47phox	P14598	S345	QARPGPQSPGSPLEE	+
p47phox	P14598	S348	PGPQSPGSPLEEERQ
p53	P04637	S15	PSVEPPLSQETFSDL	+
p53	P04637	S33	LPENNVLSPLPSQAM	+
p53	P04637	S46	AMDDLMLSPDDIEQW	+
PAK6	Q9NQU5	S165	MPWPEPQSPRVLPNG	+
PDX1	P52945	S61	LGALEQGSPPDISPY	+
PDX1	P52945	S66	QGSPPDISPYEVPPL	+
PGC-1	Q9UBK2	S266	SLPLTPESPNDPKGS
PGC-1	Q9UBK2	T263	TTLSLPLTPESPNDP
PGC-1	Q9UBK2	T299	AGLTPPTTPPHKANQ
PIP5K2B	P78356	S326	SYGTPPDSPGNLLSF	-
PKCe (PRKCE)	Q02156	S350	RSKSAPTSPCDQEIK
PKR (PRKR; EIF2AK2)	P19525	T451	KRTRSKGTLRYMSPE	-
PPARA	Q07869	S12	ESPLCPLSPLEAGDL	-
PPARA	Q07869	S211	LEAGDLESPLSEEFL
PPARA	Q07869	S6	__MVDTESPLCPLSP	-
PXN	P49023	S83	FIHQQPQSSSPVYGS
PXN iso2	P49023	S85	HQQPQSSSPVYGSSA
RARG2	P13631	S77	SEEMVPSSPSPPPPP	+
RARG2	P13631	S79	EMVPSSPSPPPPPRV	+
SCN10A	Q9Y5Y9	S552	QQGPLPRSPLPQPSN
SCN8A	Q9UQD0	S553	SLLSIPGSPFLSRHN
Shc1	P29353	S36	TPPEELPSPSASSLG	-
Shc1	P29353	S54	PPLPGDDSPTTLCSF	+
Shc1	P29353	T386	PTAPNAQTPSHLGAT	+
SIAH2	O43255	S28	PQPQHTPSPAAPPAA
SLC9A1 (NHE1)	P19634	S723	VITIDPASPQSPESV
SLC9A1 (NHE1)	P19634	S726	IDPASPQSPESVDLV	+
SLC9A1 (NHE1)	P19634	S729	ASPQSPESVDLVNEE	+
SLC9A1 (NHE1)	P19634	T718	KEDLPVITIDPASPQ
STAT1	P42224	S727	TDNLLPMSPEEFDEV	-
STAT3	P40763	S727	NTIDLPMSPRTLDSL	-
STAT4	Q14765	S721	PSDLLPMSPSVYAVL
STMN1	P16949	S25	QAFELILSPRSKESV
STMN1	P16949	S38	SVPEFPLSPPKKKDL
STMN2	Q93045	S62	ELILKPPSPISEAPR
STMN2	Q93045	S73	EAPRILASPKKKDLS
TAB1	Q15750	S423	QMVNGAHSASTLDEA
TAB1	Q15750	S438	TPTLTNQSPTLTLQS
TAB1	Q15750	T431	ASTLDEATPTLTNQS
TAB2	Q9NYJ8	S423	SAASRNMSGQVSMGP
TAB2	Q9NYJ8	T431	ASTLDEATPTLTNQS
Tau iso5 (Tau-C)	P10636-5	S185	APKTPPSSGEPPKSG
Tau iso5 (Tau-C)	P10636-5	S202	SGYSSPGSPGTPGSR
Tau iso5 (Tau-C)	P10636-5	T205	SSPGSPGTPGSRSRT
Tau iso5 (Tau-C)	P10636-5	T245	SAKSRLQTAPVPMPD
Tau iso9 (Tau-F)	P10636-9	S305	KHVPGGGSVQIVYKP
Tau iso9 (Tau-F)	P10636-9	S356	RVQSKIGSLDNITHV
Tau iso9 (Tau-F)	P10636-9	S404	PVVSGDTSPRHLSNV
USF1	P22415	T153	EALLGQATPPGTGQF
ZFYVE20	Q9H1K0	S215	ESLSTHTSPSQSPNS

Protein Kinase Specificity

Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites

Matrix Type:

Experimentally derived from alignment of 173 known protein substrate phosphosites and 55 peptides phosphorylated by recombinant p38a MAPK in vitro tested in-house by Kinexus. Note that additional binding sites on p38 substrates with D motifs (consensus= K/R-k-x-s-l/p-l-l-l-p-p or p-x-L/v/i-x-p-p-x-x-x-x-l-l-x-r/k-k/r-R/k-K/r) facilitate higher selectivity for phosphorylation by this protein kinase.

Domain #:

Inhibitors

For further details on these inhibitors click on the Compound Name and enter it into DrugKiNET or click on the ID's

Based on in vitro and/or in vivo phosphorylation data

Compound Name	KD, Ki or IC50 (nM)	PubChem ID	ChEMBL ID	PubMed ID

Doramapimod	Kd = 46 pM	156422	103667	14561086
SPDD01923	IC50 = 110 pM	447721	305178	10377223
Kinome_3519	Ki = 200 pM	16730109	259922	18359226
SCIO-469	Kd = 480 pM	9871074		19950901
VX745	IC50 = 800 pM	3038525	119385	16945533
CHEMBL420047	Kd = 1 nM	23646852	420047	12086485
CHEMBL383172	Ki = 1.6 nM	11235063	383172	16190753
SureCN4219451	IC50 = 1.8 nM	9999342	212968	16759861
SureCN5632345	Ki = 1.9 nM	44593646	515466	18602262
CHEMBL215652	IC50 = 2.5 nM	23647319	215652	16759861
PH797804	IC50 = 2.5 nM	22049997	1088751	21641211
AMG-47a	IC50 = 3 nM	16086114	215943	16970394
SureCN4762364	IC50 = 3.2 nM	10473563	213423	16759861
VX702	Kd = 3.7 nM	10341154	1090090	19950901
Aminopyrimidine amide, 13b	IC50 = 5 nM	16118737	272888	18321037
SureCN3936664	IC50 = 5 nM	11626920	475817	19097792
2ofv	IC50 = 6 nM	15991573		16970394
LY2228820	IC50 = 7 nM	11570805		18039577
CHEMBL213451	IC50 = 7.6 nM	23647330	213451	16759861
SureCN5495613	IC50 = 9 nM	24764449		16970394
SureCN6744546	Ki = 9 nM	24856363	478649	18602262
SureCN5774497	IC50 = 9.6 nM	9948405	379929	16759861
SB202190	Kd = 9.8 nM	5353940	278041	18183025
CHEMBL1964275	Kd < 10 nM	57394915	1964275	19035792
SB203580	IC50 = 10 nM	176155	10	15454232
SureCN6744546	Kd < 10 nM	24856363	478649	19035792
SB220025	IC50 = 19 nM	5164	274064	11597418
Dasatinib	Kd = 27 nM	11153014	1421	18183025
p38 MAP Kinase Inhibitor	IC50 = 35 nM	4665	91730	15837310
Sorafenib	IC50 = 38 nM	216239	1336	19962319
CHEMBL1092754	IC50 = 50 nM	44541014	1092754	20188552
PD169316	IC50 > 50 nM	4712	17331	22037377
AST-487	Kd = 73 nM	11409972	574738	18183025
7-hydroxystaurosporine	IC50 > 100 nM	72271	1236539
A-83-01	IC50 = 100 nM	16218924	1170377
AT9283	IC50 > 100 nM	24905142		19143567
Regorafenib	IC50 < 100 nM	11167602		21170960
SB681323	IC50 < 100 nM	10297982
SKF-86002	IC50 = 110 nM	5228	313417	19928858
Nilotinib	IC50 > 150 nM	644241	255863	22037377
ZM336372	IC50 = 180 nM	5730	186526	15454231
CHEMBL364623	IC50 = 202 nM	11153014	364623	17154512
FR180204	Ki = 310 nM	11493598	259551	18077363
Foretinib	Kd = 320 nM	42642645	1230609	22037378
ML3403	IC50 = 380 nM	6419739	111364	12852754
SureCN4875304	IC50 = 540 nM	46871765		20472445
AG1478	IC50 = 560 nM	2051	7917	15454232
HG-9-91-01	IC50 < 600 nM
LY364947	IC50 = 740 nM	447966	261454	12954047
Celocoxib	IC50 = 810 nM	2662		15990304
A 443654	IC50 > 900 nM	10172943	379300
BX517	IC50 > 900 nM	11161844	228654
Gö6976	IC50 > 900 nM	3501	302449
1-Naphthyl PP1	IC50 = 1 µM	4877
Baricitinib	IC50 > 1 µM	44205240		20363976
CHEMBL194721	IC50 > 1 µM	44401437	194721	15808450
CHEMBL195641	IC50 > 1 µM	44401410	195641	15808450
CK7	Ki > 1 µM	447961		15027857
CP673451	IC50 > 1 µM	10158940		15705896
MK5108	IC50 > 1 µM	24748204		20053775
PP1	IC50 = 1 µM	1400	306380
PP1 Analog II; 1NM-PP1	IC50 = 1 µM	5154691	573578
SB505124	IC50 = 1 µM	16079009	1835714
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
Staurosporine	IC50 = 1 µM	5279		12166950
SureCN10063060	Ki > 1 µM	52936621		21391610
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
Afatinib	Kd = 1.3 µM	10184653	1173655	22037378
BMS-777607	IC50 > 2 µM	24794418		19260711
Momelotinib	IC50 > 2 µM	25062766		19295546
BIX02188	IC50 = 3.7 µM	23507698		18834865
BIX02188	IC50 = 3.9 µM	23507698		18834865
CHEMBL493169	Ki > 4 µM	44219632	493169	19414255
CHEMBL494221	Ki > 4 µM	5328125	494221	19414255
GW5074 (Raf1 Kinase Inhibitor I)	IC50 < 4 µM	5924208
JNJ-28871063	IC50 > 4 µM	17747413		17975007
Pyrimidylpyrrole, 11e	Ki > 4 µM	11634725	583042	19827834
BMS-690514	Kd < 4.5 µM	11349170		21531814
Harmane	IC50 > 4.5 µM	5281404	12014
IRAK-4 kinase inhibitor b	IC50 > 4.5 µM
Rapamycin	IC50 > 4.5 µM	5284616	413
CHEMBL1788116	IC50 = 4.8 µM	11422034	1788116	15999997

Disease Linkage

General Disease Association:

Infectious disease, and neuronal disorders

Specific Diseases (Non-cancerous):

Influenza; Alexander disease

Comments:

p38a is implicated in the pathophysiology of inflammatory bowel disease. It may be a potential therapeutic target for spinal muscle atrophy, which is an autosomal recessive neurodegenerative disease characterized by progressive muscle atrophy. Spinal muscle atrophy results from deletion or mutation of SMN1 gene, which can be induced by p38a activitation.

Comments:

p38a may be also involved in drug resistance development of acute myeloid leukemias.

Gene Expression in Cancers:

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Brain glioblastomas (%CFC= +221, p<0.012); and Brain oligodendrogliomas (%CFC= +193, p<0.06). The COSMIC website notes an up-regulated expression score for p38a in diverse human cancers of 565, which is 1.2-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 152 for this protein kinase in human cancers was 2.5-fold of the average score of 60 for the human protein kinases.

Mutagenesis Experiments:

Insertional mutagenesis studies in mice support a role for this protein kinase in mouse cancer oncogenesis.

Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.08 % in 25411 diverse cancer specimens. This rate is very similar (+ 6% higher) to the average rate of 0.075 % calculated for human protein kinases in general.

Mutation Rate in Specific Cancers:

Highest percent mutation rates per 100 amino acids length in human cancers: 0.48 % in 805 skin cancers tested; 0.38 % in 1093 large intestine cancers tested.

Frequency of Mutated Sites:

None > 4 in 20,694 cancer specimens

Comments:

Only 2 deletions, 3 insertions, and no complex mutations are noted on the COSMIC website.

COSMIC Entry:

MAPK14

OMIM Entry:

600289

Nomenclature

Short Name:

Full Name:

Alias:

Classification

Type:

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Family:

SubFamily:

Specific Links

General Links

Structure

Mol. Mass (Da):

# Amino Acids:

# mRNA Isoforms:

mRNA Isoforms:

4D Structure:

1D Structure:

3D Image (rendered using PV Viewer):

PDB ID

Subfamily Alignment

Domain Distribution:

Kinexus Products

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Post-translation Modifications

Acetylated:

Serine phosphorylated:

Threonine phosphorylated:

Tyrosine phosphorylated:

Ubiquitinated:

Distribution

Human Tissue Distribution

% Max Expression: Mean Expression: Number of Samples: Standard Deviation:

% Max Expression: Mean Expression: Number of Samples: Standard Deviation:

Evolution

Species Conservation

PhosphoNET % Identity: PhosphoNET % Similarity: Homologene %Identity:

PhosphoNET % Identity: PhosphoNET % Similarity: Homologene %Identity:

Binding Proteins

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Regulation

Activation:

Inhibition:

Synthesis:

Degradation:

Known Upstream Kinases

Based on in vitro and/or in vivo phosphorylation data

Known Downstream Substrates

Based on in vitro and/or in vivo phosphorylation data

Protein Kinase Specificity

Matrix Type:

Domain #:

Inhibitors

Based on in vitro and/or in vivo phosphorylation data

Disease Linkage

General Disease Association:

Specific Diseases (Non-cancerous):

Comments:

Comments:

Gene Expression in Cancers:

Mutagenesis Experiments:

Mutation Rate in All Cancers:

Mutation Rate in Specific Cancers:

Frequency of Mutated Sites:

Comments:

COSMIC Entry:

OMIM Entry:

% Max Expression:

Mean Expression:

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% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity: