Reviewed, UniProtKB/Swiss-Prot Q16539 (MK14_HUMAN)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase 14
    EC=2.7.11.24
Alternative name(s):
    Mitogen-activated protein kinase p38 alpha
      Short name=MAP kinase p38 alpha
    Cytokine suppressive anti-inflammatory drug-binding protein
      Short name=CSAID-binding protein
      Short name=CSBP
    MAX-interacting protein 2
    MAP kinase MXI2
    SAPK2A

Gene names

Name:	MAPK14
Synonyms:	CSBP, CSBP1, CSBP2, CSPB1, MXI2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	360 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Responds to activation by environmental stress, pro-inflammatory cytokines and lipopolysaccharide (LPS) by phosphorylating a number of transcription factors, such as ELK1 and ATF2 and several downstream kinases, such as MAPKAPK2 and MAPKAPK5. Plays a critical role in the production of some cytokines, for example IL-6. May play a role in stabilization of EPO mRNA during hypoxic stress. 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. Ref.16 Ref.17
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium. Ref.17
Enzyme regulation	Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K3 or MAP2K6, and potentially also MAP2K4. Inhibited by dual specificity phosphatases, such as DUSP1. Specifically inhibited by the binding of pyridinyl-imidazole compounds, which are cytokine-suppressive anti-inflammatory drugs (CSAID). Isoform Mxi2 is 100-fold less sensitive to these agents than the other isoforms and is not inhibited by DUSP1. Isoform Exip is not activated by MAP2K6. Ref.17 Ref.5
Subunit 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.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity.
Tissue specificity	Brain, heart, placenta, pancreas and skeletal muscle. Expressed to a lesser extent in lung, liver and kidney.
Domain	The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Post-translational modification	Dually phosphorylated on Thr-180 and Tyr-182, which activates the enzyme. Ref.19 Ref.20 Ref.21 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.19 Ref.20 Ref.21 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	Ras protein signal transduction Inferred from Experiment. Source: Reactome cell motion Traceable author statement. Source: ProtInc chemotaxis Traceable author statement. Source: ProtInc protein kinase cascade Ref.17 Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Inferred from Experiment. Source: Reactome nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase activity Traceable author statement. Source: ProtInc MP kinase activity Ref.1 Inferred from direct assay. Source: UniProtKB protein binding Ref.22 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FAM48A	Q8NEM7	2	EBI-73946,EBI-946984
GSTP1	P09211	1	EBI-73946,EBI-353467
MAPKAPK2	P49137	1	EBI-73946,EBI-993299
PKN1	Q16512	1	EBI-73946,EBI-602382
RPS6KA4	O75676	1	EBI-73946,EBI-73933
ZFP36L1	Q07352	1	EBI-73946,EBI-721823

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform CSBP2 (identifier: Q16539-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform CSBP1 (identifier: Q16539-2)

The sequence of this isoform differs from the canonical sequence as follows:
     230-254: DQLKLILRLVGTPGAELLKKISSES → NQLQQIMRLTGTPPAYLINRMPSHE

Isoform Mxi2 (identifier: Q16539-3)

The sequence of this isoform differs from the canonical sequence as follows:
     281-360: AVDLLEKMLV...PPLDQEEMES → GKLTIYPHLMDIELVMI

Isoform Exip (identifier: Q16539-4)

Also known as: Exon skip;

The sequence of this isoform differs from the canonical sequence as follows:
     255-307: ARNYIQSLTQ...TAAQALAHAY → LSTCWRRCLY...ISPLKAGTSL
     308-360: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.13

Chain

2 – 360

359

Mitogen-activated protein kinase 14

PRO_0000186291

Regions

Domain

24 – 308

285

Protein kinase

Nucleotide binding

30 – 38

9

ATP

Motif

180 – 182

3

TXY

Sites

Active site

168

1

Proton acceptor

Binding site

53

1

ATP

Amino acid modifications

Modified residue

2

1

Phosphoserine Ref.28

Modified residue

16

1

Phosphothreonine Ref.28

Modified residue

180

1

Phosphothreonine Ref.19 Ref.21 Ref.25 Ref.28 Ref.29

Modified residue

182

1

Phosphotyrosine Ref.19 Ref.20 Ref.21 Ref.24 Ref.25 Ref.27 Ref.28 Ref.29

Modified residue

263

1

Phosphothreonine Ref.26

Natural variations

Alternative sequence

230 – 254

25

DQLKL…ISSES → NQLQQIMRLTGTPPAYLINR MPSHE in isoform CSBP1.

VSP_004842

Alternative sequence

255 – 307

53

ARNYI…LAHAY → LSTCWRRCLYWTQIRELQRP KPLHMPTLLSTTILMMNQWP ILMISPLKAGTSL in isoform Exip.

VSP_004843

Alternative sequence

281 – 360

80

AVDLL…EEMES → GKLTIYPHLMDIELVMI in isoform Mxi2.

VSP_004844

Alternative sequence

308 – 360

53

Missing in isoform Exip.

VSP_004845

Natural variant

51

1

A → V in a gastric adenocarcinoma sample; somatic mutation. Ref.34

VAR_042270

Natural variant

322

1

P → R in a lung adenocarcinoma sample; somatic mutation. Ref.34

VAR_042271

Natural variant

343

1

D → G Ref.34

VAR_042272

Experimental info

Mutagenesis

34

1

A → V: Lowered kinase activity. Ref.15

Mutagenesis

53

1

K → R: Loss of kinase activity. Ref.15

Mutagenesis

69

1

Y → H: Lowered kinase activity. Ref.18

Mutagenesis

168

1

D → A: Loss of kinase activity. Ref.15

Mutagenesis

175

1

T → A: Loss of kinase activity. Ref.15

Mutagenesis

176

1

D → A: Emulation of the active state. Increase in activity; when associated with S-327 or L-327. Ref.18

Mutagenesis

177

1

D → A: Loss of kinase activity. Ref.18

Mutagenesis

180

1

T → E: Loss of kinase activity. Ref.15

Mutagenesis

182

1

Y → F: Loss of kinase activity. Ref.15

Mutagenesis

320

1

A → T: Lowered kinase activity. Ref.18

Mutagenesis

327

1

F → L: Emulation of the active state. Increase in activity; when associated with A-176. Ref.18

Mutagenesis

327

1

F → S: Emulation of the active state. Increase in activity; when associated with A-176. Ref.18

Mutagenesis

337

1

W → R: Loss of kinase activity. Ref.18

Sequence conflict

67

1

R → G in BAF84398. Ref.6

Secondary structure

1

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360

Helix Strand Turn

Details...

Beta strand

8 – 13

6

Beta strand

16 – 21

6

Beta strand

24 – 29

6

Beta strand

38 – 43

6

Turn

44 – 47

4

Beta strand

48 – 54

7

Helix

62 – 77

16

Beta strand

87 – 90

4

Helix

96 – 98

3

Beta strand

103 – 107

5

Helix

124 – 143

20

Helix

153 – 155

3

Beta strand

156 – 158

3

Beta strand

164 – 166

3

Helix

191 – 194

4

Helix

204 – 218

15

Helix

228 – 239

12

Helix

244 – 247

4

Helix

253 – 260

8

Helix

270 – 273

4

Turn

274 – 276

3

Helix

279 – 288

10

Helix

293 – 295

3

Helix

299 – 303

5

Helix

306 – 308

3

Turn

309 – 311

3

Helix

314 – 316

3

Helix

325 – 327

3

Helix

334 – 347

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform CSBP2 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 286C81D0487618B3	FASTA	360	41,293
	10 20 30 40 50 60 MSQERPTFYR QELNKTIWEV PERYQNLSPV GSGAYGSVCA AFDTKTGLRV AVKKLSRPFQ 70 80 90 100 110 120 SIIHAKRTYR ELRLLKHMKH ENVIGLLDVF TPARSLEEFN DVYLVTHLMG ADLNNIVKCQ 130 140 150 160 170 180 KLTDDHVQFL IYQILRGLKY IHSADIIHRD LKPSNLAVNE DCELKILDFG LARHTDDEMT 190 200 210 220 230 240 GYVATRWYRA PEIMLNWMHY NQTVDIWSVG CIMAELLTGR TLFPGTDHID QLKLILRLVG 250 260 270 280 290 300 TPGAELLKKI SSESARNYIQ SLTQMPKMNF ANVFIGANPL AVDLLEKMLV LDSDKRITAA 310 320 330 340 350 360 QALAHAYFAQ YHDPDDEPVA DPYDQSFESR DLLIDEWKSL TYDEVISFVP PPLDQEEMES
	Isoform CSBP1. Checksum: 062EBC3E56683D14	FASTA	360	41,493
	10 20 30 40 50 60 MSQERPTFYR QELNKTIWEV PERYQNLSPV GSGAYGSVCA AFDTKTGLRV AVKKLSRPFQ 70 80 90 100 110 120 SIIHAKRTYR ELRLLKHMKH ENVIGLLDVF TPARSLEEFN DVYLVTHLMG ADLNNIVKCQ 130 140 150 160 170 180 KLTDDHVQFL IYQILRGLKY IHSADIIHRD LKPSNLAVNE DCELKILDFG LARHTDDEMT 190 200 210 220 230 240 GYVATRWYRA PEIMLNWMHY NQTVDIWSVG CIMAELLTGR TLFPGTDHIN QLQQIMRLTG 250 260 270 280 290 300 TPPAYLINRM PSHEARNYIQ SLTQMPKMNF ANVFIGANPL AVDLLEKMLV LDSDKRITAA 310 320 330 340 350 360 QALAHAYFAQ YHDPDDEPVA DPYDQSFESR DLLIDEWKSL TYDEVISFVP PPLDQEEMES
	Isoform Mxi2. Checksum: C17A753943B49F56	FASTA	297	34,092
	10 20 30 40 50 60 MSQERPTFYR QELNKTIWEV PERYQNLSPV GSGAYGSVCA AFDTKTGLRV AVKKLSRPFQ 70 80 90 100 110 120 SIIHAKRTYR ELRLLKHMKH ENVIGLLDVF TPARSLEEFN DVYLVTHLMG ADLNNIVKCQ 130 140 150 160 170 180 KLTDDHVQFL IYQILRGLKY IHSADIIHRD LKPSNLAVNE DCELKILDFG LARHTDDEMT 190 200 210 220 230 240 GYVATRWYRA PEIMLNWMHY NQTVDIWSVG CIMAELLTGR TLFPGTDHID QLKLILRLVG 250 260 270 280 290 TPGAELLKKI SSESARNYIQ SLTQMPKMNF ANVFIGANPL GKLTIYPHLM DIELVMI
	Isoform Exip (Exon skip). Checksum: 9297934FF4AC6F94	FASTA	307	35,453
	10 20 30 40 50 60 MSQERPTFYR QELNKTIWEV PERYQNLSPV GSGAYGSVCA AFDTKTGLRV AVKKLSRPFQ 70 80 90 100 110 120 SIIHAKRTYR ELRLLKHMKH ENVIGLLDVF TPARSLEEFN DVYLVTHLMG ADLNNIVKCQ 130 140 150 160 170 180 KLTDDHVQFL IYQILRGLKY IHSADIIHRD LKPSNLAVNE DCELKILDFG LARHTDDEMT 190 200 210 220 230 240 GYVATRWYRA PEIMLNWMHY NQTVDIWSVG CIMAELLTGR TLFPGTDHID QLKLILRLVG 250 260 270 280 290 300 TPGAELLKKI SSESLSTCWR RCLYWTQIRE LQRPKPLHMP TLLSTTILMM NQWPILMISP LKAGTSL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A protein kinase involved in the regulation of inflammatory cytokine biosynthesis." Lee J.C., Laydon J.T., McDonnell P.C., Gallagher T.F., Kumar S., Green D., McNulty D., Blumenthal M.J., Heys R.J., Landvatter S.W., Strickler J.E., McLaughlin M.M., Siemens I.R., Fisher S.M., Livi G.P., White J.R., Adams J.L., Young P.R. Nature 372:739-746(1994) [PubMed: 7997261] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS CSBP1 AND CSBP2), PARTIAL PROTEIN SEQUENCE. Tissue: Peripheral blood.
[2]	"Molecular cloning of human p38 MAP kinase." Han J., Richter B., Li Z., Kravchenko V.V., Ulevitch R.J. Biochim. Biophys. Acta 1265:224-227(1995) [PubMed: 7696354] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CSBP2). Tissue: Liver.
[3]	"Mxi2, a mitogen-activated protein kinase that recognizes and phosphorylates Max protein." Zervos A.S., Faccio L., Gatto J.P., Kyriakis J.M., Brent R. Proc. Natl. Acad. Sci. U.S.A. 92:10531-10534(1995) [PubMed: 7479834] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] (ISOFORM MXI2).
[4]	"Structure and polymorphism of two stress-activated protein kinase genes centromeric of the MHC: SAPK2a and SAPK4." Herbison C.E., Sayer D.C., Bellgard M., Allcock R.J.N., Christiansen F.T., Price P. DNA Seq. 10:229-243(1999) [PubMed: 10727080] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CSBP2). Tissue: B-cell.
[5]	"Exip, a new alternative splicing variant of p38 alpha, can induce an earlier onset of apoptosis in HeLa cells." Sudo T., Yagasaki Y., Hama H., Watanabe N., Osada H. Biochem. Biophys. Res. Commun. 291:838-843(2002) [PubMed: 11866441] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM EXIP), ENZYME REGULATION. Tissue: Renal cell carcinoma.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CSBP2).
[8]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CSBP2).
[9]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[10]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CSBP2). Tissue: Placenta.
[13]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-10. Tissue: Platelet.
[14]	"Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27." Freshney N.W., Rawlinson L., Guesdon F., Jones E., Cowley S., Hsuan J., Saklatvala J. Cell 78:1039-1049(1994) [PubMed: 7923354] [Abstract] Cited for: PROTEIN SEQUENCE OF 174-186.
[15]	"Human mitogen-activated protein kinase CSBP1, but not CSBP2, complements a hog1 deletion in yeast." Kumar S., McLaughlin M.M., McDonnell P.C., Lee J.C., Livi G.P., Young P.R. J. Biol. Chem. 270:29043-29046(1995) [PubMed: 7493921] [Abstract] Cited for: MUTAGENESIS OF ALA-34; LYS-53; ASP-168; THR-175; THR-180 AND TYR-182.
[16]	"Requirement for p38alpha in erythropoietin expression: a role for stress kinases in erythropoiesis." Tamura K., Sudo T., Senftleben U., Dadak A.M., Johnson R., Karin M. Cell 102:221-231(2000) [PubMed: 10943842] [Abstract] Cited for: FUNCTION. Tissue: Hepatoma.
[17]	"Distinct carboxy-termini confer divergent characteristics to the mitogen-activated protein kinase p38alpha and its splice isoform Mxi2." Sanz V., Arozarena I., Crespo P. FEBS Lett. 474:169-174(2000) [PubMed: 10838079] [Abstract] Cited for: FUNCTION (ISOFORM MXI2), COFACTOR, ENZYME REGULATION.
[18]	"Active mutants of the human p38alpha mitogen-activated protein kinase." Diskin R., Askari N., Capone R., Engelberg D., Livnah O. J. Biol. Chem. 279:47040-47049(2004) [PubMed: 15284239] [Abstract] Cited for: MUTAGENESIS OF TYR-69; ASP-176; ASP-177; ALA-320; PHE-327 AND TRP-337.
[19]	"Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, MASS SPECTROMETRY.
[20]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-182, MASS SPECTROMETRY.
[21]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, MASS SPECTROMETRY. Tissue: Epithelium.
[22]	"p38 and a p38-interacting protein are critical for downregulation of E-cadherin during mouse gastrulation." Zohn I.E., Li Y., Skolnik E.Y., Anderson K.V., Han J., Niswander L. Cell 125:957-969(2006) [PubMed: 16751104] [Abstract] Cited for: INTERACTION WITH FAM48A.
[23]	"Nuclear protein NP60 regulates p38 MAPK activity." Fu J., Yang Z., Wei J., Han J., Gu J. J. Cell Sci. 119:115-123(2006) [PubMed: 16352664] [Abstract] Cited for: INTERACTION WITH NP60.
[24]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-182, MASS SPECTROMETRY.
[25]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, MASS SPECTROMETRY.
[26]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-263, MASS SPECTROMETRY.
[27]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-182, MASS SPECTROMETRY. Tissue: Platelet.
[28]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; THR-16; THR-180 AND TYR-182, MASS SPECTROMETRY.
[29]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, MASS SPECTROMETRY.
[30]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[31]	"Crystal structure of p38 mitogen-activated protein kinase." Wilson K.P., Fitzgibbon M.J., Caron P.R., Griffith J.P., Chen W., McCaffrey P.G., Chambers S.P., Su M.S.-S. J. Biol. Chem. 271:27696-27700(1996) [PubMed: 8910361] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[32]	"A highly specific inhibitor of human p38 MAP kinase binds in the ATP pocket." Tong L., Pav S., White D.M., Rogers S., Crane K.M., Cywin C.L., Brown M.L., Pargellis C.A. Nat. Struct. Biol. 4:311-316(1997) [PubMed: 9095200] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[33]	"Structural basis of inhibitor selectivity in MAP kinases." Wang Z., Canagarajah B.J., Boehm J.C., Kassisa S., Cobb M.H., Young P.R., Abdel-Meguid S., Adams J.L., Goldsmith E.J. Structure 6:1117-1128(1998) [PubMed: 9753691] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[34]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-51; ARG-322 AND GLY-343.
+	Additional computationally mapped references.

Web resources

Wikipedia

P38 mitogen-activated protein kinases entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

L35263 mRNA. Translation: AAA57455.1.
L35264 mRNA. Translation: AAA57456.1.
L35253 mRNA. Translation: AAA74301.1.
U19775 Genomic RNA. Translation: AAC50329.1.
AF100544 mRNA. Translation: AAF36770.1.
AB074150 mRNA. Translation: BAB85654.1.
AK291709 mRNA. Translation: BAF84398.1.
BT006933 mRNA. Translation: AAP35579.1.
CR536505 mRNA. Translation: CAG38743.1.
EU332860 Genomic DNA. Translation: ABY87549.1.
Z95152 Genomic DNA. No translation available.
CH471081 Genomic DNA. Translation: EAX03869.1.
BC000092 mRNA. Translation: AAH00092.1.
BC031574 mRNA. Translation: AAH31574.1.

IPI

IPI00002857.
IPI00221141.
IPI00221142.
IPI00221143.

PIR

S53536.

RefSeq

NP_001306.1.
NP_620581.1.
NP_620583.1.

UniGene

Hs.485233
Hs.588289

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A9U	X-ray	2.50	A	1-360	[»]
1BL6	X-ray	2.50	A	1-360	[»]
1BL7	X-ray	2.50	A	1-360	[»]
1BMK	X-ray	2.40	A	1-360	[»]
1DI9	X-ray	2.60	A	1-360	[»]
1IAN	X-ray	2.00	A	2-360	[»]
1KV1	X-ray	2.50	A	1-360	[»]
1KV2	X-ray	2.80	A	1-360	[»]
1M7Q	X-ray	2.40	A	1-360	[»]
1OUK	X-ray	2.50	A	1-360	[»]
1OUY	X-ray	2.50	A	1-360	[»]
1OVE	X-ray	2.10	A	1-360	[»]
1OZ1	X-ray	2.10	A	1-360	[»]
1R39	X-ray	2.30	A	1-360	[»]
1R3C	X-ray	2.00	A	1-360	[»]
1W7H	X-ray	2.21	A	2-359	[»]
1W82	X-ray	2.20	A	2-359	[»]
1W83	X-ray	2.50	A	2-359	[»]
1W84	X-ray	2.20	A	2-359	[»]
1WBN	X-ray	2.40	A	2-359	[»]
1WBO	X-ray	2.16	A	2-359	[»]
1WBS	X-ray	1.80	A	2-359	[»]
1WBT	X-ray	2.00	A	2-359	[»]
1WBV	X-ray	2.00	A	2-359	[»]
1WBW	X-ray	2.41	A	2-359	[»]
1WFC	X-ray	2.30	A	1-360	[»]
1YQJ	X-ray	2.00	A	2-359	[»]
1ZYJ	X-ray	2.00	A	1-360	[»]
1ZZ2	X-ray	2.00	A	1-360	[»]
1ZZL	X-ray	2.00	A	4-353	[»]
2BAJ	X-ray	2.25	A	2-359	[»]
2BAK	X-ray	2.20	A	2-359	[»]
2BAL	X-ray	2.10	A	2-359	[»]
2BAQ	X-ray	2.80	A	2-359	[»]
2FSL	X-ray	1.70	X	2-359	[»]
2FSM	X-ray	1.86	X	2-359	[»]
2FSO	X-ray	1.83	X	2-359	[»]
2FST	X-ray	1.45	X	2-359	[»]
2GFS	X-ray	1.75	A	2-359	[»]
2I0H	X-ray	2.00	A	1-360	[»]
2NPQ	X-ray	1.80	A	2-359	[»]
2OKR	X-ray	2.00	A/D	2-359	[»]
2ONL	X-ray	4.00	A/B	2-359	[»]
2P5A	X-ray	2.10	A	1-360	[»]
2PKJ	X-ray	2.00	A	5-352	[»]
2PTJ	X-ray	2.20	A	1-360	[»]
2PTO	X-ray	2.30	A	1-360	[»]
2PV5	X-ray	2.10	A	1-360	[»]
2PV8	X-ray	2.20	A	1-360	[»]
2QD9	X-ray	1.70	A	2-360	[»]
2RG5	X-ray	2.40	A	2-360	[»]
2RG6	X-ray	1.72	A	2-360	[»]
2ZAZ	X-ray	1.80	A	1-360	[»]
2ZB0	X-ray	2.10	A	1-360	[»]
2ZB1	X-ray	2.50	A	1-360	[»]
3BV2	X-ray	2.40	A	2-360	[»]
3BV3	X-ray	2.59	A	2-360	[»]
3BX5	X-ray	2.40	A	2-360	[»]
3C5U	X-ray	2.80	A	2-360	[»]
3CG2	X-ray	2.15	A	2-360	[»]
3CTQ	X-ray	1.95	A	5-352	[»]
3D7Z	X-ray	2.10	A	1-360	[»]
3D83	X-ray	1.90	A	1-360	[»]
3DS6	X-ray	2.90	A/B/C/D	1-360	[»]
3DT1	X-ray	2.80	A	1-360	[»]
3E92	X-ray	2.00	A	1-360	[»]
3E93	X-ray	2.00	A	1-360	[»]
3FC1	X-ray	2.40	X	1-360	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q16539. 26 interactions.

PTM databases

PhosphoSite

Q16539.

2-D gel databases

OGP

Q16539.

Proteomic databases

PRIDE

Q16539.

Genome annotation databases

Ensembl

ENSG00000112062. Homo sapiens. [Contig view]

GeneID

1432.

KEGG

hsa:1432.

Organism-specific databases

GeneCards

GC06P036103.

H-InvDB

HIX0005815.

HGNC

HGNC:6876. MAPK14.

HPA

CAB010285.

MIM

600289. gene.

PharmGKB

PA30621.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q16539.

HOVERGEN

Q16539.

OMA

Q16539. SEILDFH.

Enzyme and pathway databases

BRENDA

2.7.11.24. 247.

Pathway_Interaction_DB

angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
nfkappabatypicalpathway. Atypical NF-kappaB pathway.
bcr_5pathway. BCR signaling pathway.
endothelinpathway. Endothelins.
epopathway. EPO signaling pathway.
il12_2pathway. IL12-mediated signaling events.
il2_1pathway. IL2-mediated signaling events.
il4_2pathway. IL4-mediated signaling events.
il6_7pathway. IL6-mediated signaling events.
p38_mkk3_6pathway. p38 MAPK signaling pathway.
p38_mk2pathway. p38 signaling mediated by MAPKAP kinases.
ar_tf_pathway. Regulation of Androgen receptor activity.
p38alphabetapathway. Regulation of p38-alpha and p38-beta.
retinoic_acid_pathway. Retinoic acid receptors-mediated signaling.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.
s1p_s1p2_pathway. S1P2 pathway.
p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta.
txa2pathway. Thromboxane A2 receptor signaling.
mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway.
lymphangiogenesis_pathway. VEGFR3 signaling in lymphatic endothelium.

Reactome

REACT_11061. Signalling by NGF.

Gene expression databases

ArrayExpress

Q16539.

Bgee

Q16539.

CleanEx

HS_MAPK14.

GermOnline

ENSG00000112062. Homo sapiens.

Family and domain databases

InterPro

IPR003527. MAP_kinase_CS.
IPR008352. MAPK_p38.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

PRINTS

PR01773. P38MAPKINASE.

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

PROSITE

PS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. False negative.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

5841.

SOURCE

Search...

Entry information

Entry name

MK14_HUMAN

Accession

Primary (citable) accession number: Q16539
Secondary accession number(s): A6ZJ92 , A8K6P4, B0LPH0, O60776, Q13083, Q14084, Q8TDX0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 117 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)