Q9Y6R4 (M3K4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase kinase kinase 4
EC=2.7.11.25

Alternative name(s):
MAP three kinase 1
MAPK/ERK kinase kinase 4
Short name=MEK kinase 4
Short name=MEKK 4

Gene names

Name:	MAP3K4
Synonyms:	KIAA0213, MAPKKK4, MEKK4, MTK1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1608 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6. Ref.1 Ref.7
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	N-terminal autoinhibitory domain interacts with the C-terminal kinase domain, inhibiting kinase activity, and preventing interaction with its substrate, MAP2K6. The GADD45 proteins activate the kinase by binding to the N-terminal domain. Activated by phosphorylation on Thr-1505. Ref.7
Subunit structure	Monomer and homodimer. Homodimerization enhances kinase activity. Interacts with TRAF4; this promotes homodimerization By similarity. Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with AXIN1 and DIXDC1; interaction with DIXDC1 prevents interaction with AXIN1. Ref.7 Ref.8 Ref.9
Subcellular location	Cytoplasm › perinuclear region By similarity. Note: Localized in perinuclear vesicular-like structures, probably Golgi-associated vesicles By similarity.
Tissue specificity	Expressed at high levels in heart, placenta, skeletal muscle and pancreas, and at lower levels in other tissues. Ref.1
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence BAA13204.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAC12766.2 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAH70639.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAH70640.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI20815.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI20816.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI21477.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI41309.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI41310.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	JNK cascade Traceable author statement Ref.1. Source: ProtInc chorionic trophoblast cell differentiation Inferred from electronic annotation. Source: Compara male germ-line sex determination Inferred from electronic annotation. Source: Compara placenta development Inferred from electronic annotation. Source: Compara positive regulation of JUN kinase activity Inferred from sequence or structural similarity. Source: UniProtKB regulation of gene expression Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase kinase activity Traceable author statement Ref.1. Source: ProtInc metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y6R4-1)

Also known as: A;

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 2 (identifier: Q9Y6R4-2)

Also known as: B;

The sequence of this isoform differs from the canonical sequence as follows:
     1175-1224: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1608	1608	Mitogen-activated protein kinase kinase kinase 4		PRO_0000086247
Regions
	Domain	1343 – 1601	259	Protein kinase
	Nucleotide binding	1349 – 1357	9	ATP By similarity
	Compositional bias	4 – 7	4	Poly-Ala
	Compositional bias	25 – 38	14	Poly-Pro
	Compositional bias	1190 – 1202	13	Poly-Ala
Sites
	Active site	1463	1	Proton acceptor By similarity
	Binding site	1372	1	ATP By similarity
Amino acid modifications
	Modified residue	456	1	Phosphoserine Ref.13
	Modified residue	457	1	Phosphoserine Ref.13
	Modified residue	458	1	Phosphothreonine Ref.13
	Modified residue	461	1	Phosphoserine Ref.13
	Modified residue	499	1	Phosphoserine Ref.10
Natural variations
	Alternative sequence	1175 – 1224	50	Missing in isoform 2.		VSP_004884
	Natural variant	157	1	R → H. Ref.6 Corresponds to variant rs4559074 [ dbSNP | Ensembl ].		VAR_059767
	Natural variant	294	1	I → T. Ref.14 Corresponds to variant rs35842248 [ dbSNP | Ensembl ].		VAR_040686
	Natural variant	335	1	V → I. Ref.14 Corresponds to variant rs35730939 [ dbSNP | Ensembl ].		VAR_040687
	Natural variant	566	1	R → H. Ref.14 Corresponds to variant rs55765351 [ dbSNP | Ensembl ].		VAR_040688
	Natural variant	584	1	Q → H. Ref.14 Corresponds to variant rs34018542 [ dbSNP | Ensembl ].		VAR_040689
	Natural variant	906	1	H → P. Ref.14 Corresponds to variant rs35533223 [ dbSNP | Ensembl ].		VAR_040690
	Natural variant	1413	1	E → Q in an ovarian serous carcinoma sample; somatic mutation. Ref.14		VAR_040691
	Natural variant	1492	1	A → V. Ref.14		VAR_040692
Experimental info
	Mutagenesis	1372	1	K → R: Loss of activity. Ref.1 Ref.7
	Sequence conflict	35	1	P → PP in AAI36277. Ref.6
	Sequence conflict	500	1	E → D in AAI46771. Ref.6
	Sequence conflict	791	1	R → I in AAB68804. Ref.1
	Sequence conflict	1190	1	Missing in EAW47587. Ref.5
	Sequence conflict	1190	1	Missing in AAI43736. Ref.6
	Sequence conflict	1190	1	Missing in AAI36277. Ref.6
	Sequence conflict	1199	1	Missing in AAB68804. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (A) [UniParc]. Last modified May 18, 2010. Version 2. Checksum: C22294914945EA91	FASTA	1,608	181,685
	10 20 30 40 50 60 MREAAAALVP PPAFAVTPAA AMEEPPPPPP PPPPPPEPET ESEPECCLAA RQEGTLGDSA 70 80 90 100 110 120 CKSPESDLED FSDETNTENL YGTSPPSTPR QMKRMSTKHQ RNNVGRPASR SNLKEKMNAP 130 140 150 160 170 180 NQPPHKDTGK TVENVEEYSY KQEKKIRAAL RTTERDRKKN VQCSFMLDSV GGSLPKKSIP 190 200 210 220 230 240 DVDLNKPYLS LGCSNAKLPV SVPMPIARPA RQTSRTDCPA DRLKFFETLR LLLKLTSVSK 250 260 270 280 290 300 KKDREQRGQE NTSGFWLNRS NELIWLELQA WHAGRTINDQ DFFLYTARQA IPDIINEILT 310 320 330 340 350 360 FKVDYGSFAF VRDRAGFNGT SVEGQCKATP GTKIVGYSTH HEHLQRQRVS FEQVKRIMEL 370 380 390 400 410 420 LEYIEALYPS LQALQKDYEK YAAKDFQDRV QALCLWLNIT KDLNQKLRIM GTVLGIKNLS 430 440 450 460 470 480 DIGWPVFEIP SPRPSKGNEP EYEGDDTEGE LKELESSTDE SEEEQISDPR VPEIRQPIDN 490 500 510 520 530 540 SFDIQSRDCI SKKLERLESE DDSLGWGAPD WSTEAGFSRH CLTSIYRPFV DKALKQMGLR 550 560 570 580 590 600 KLILRLHKLM DGSLQRARIA LVKNDRPVEF SEFPDPMWGS DYVQLSRTPP SSEEKCSAVS 610 620 630 640 650 660 WEELKAMDLP SFEPAFLVLC RVLLNVIHEC LKLRLEQRPA GEPSLLSIKQ LVRECKEVLK 670 680 690 700 710 720 GGLLMKQYYQ FMLQEVLEDL EKPDCNIDAF EEDLHKMLMV YFDYMRSWIQ MLQQLPQASH 730 740 750 760 770 780 SLKNLLEEEW NFTKEITHYI RGGEAQAGKL FCDIAGMLLK STGSFLEFGL QESCAEFWTS 790 800 810 820 830 840 ADDSSASDEI RRSVIEISRA LKELFHEARE RASKALGFAK MLRKDLEIAA EFRLSAPVRD 850 860 870 880 890 900 LLDVLKSKQY VKVQIPGLEN LQMFVPDTLA EEKSIILQLL NAAAGKDCSK DSDDVLIDAY 910 920 930 940 950 960 LLLTKHGDRA RDSEDSWGTW EAQPVKVVPQ VETVDTLRSM QVDNLLLVVM QSAHLTIQRK 970 980 990 1000 1010 1020 AFQQSIEGLM TLCQEQTSSQ PVIAKALQQL KNDALELCNR ISNAIDRVDH MFTSEFDAEV 1030 1040 1050 1060 1070 1080 DESESVTLQQ YYREAMIQGY NFGFEYHKEV VRLMSGEFRQ KIGDKYISFA RKWMNYVLTK 1090 1100 1110 1120 1130 1140 CESGRGTRPR WATQGFDFLQ AIEPAFISAL PEDDFLSLQA LMNECIGHVI GKPHSPVTGL 1150 1160 1170 1180 1190 1200 YLAIHRNSPR PMKVPRCHSD PPNPHLIIPT PEGFSTRSMP SDARSHGSPA AAAAAAAAAV 1210 1220 1230 1240 1250 1260 AASRPSPSGG DSVLPKSISS AHDTRGSSVP ENDRLASIAA ELQFRSLSRH SSPTEERDEP 1270 1280 1290 1300 1310 1320 AYPRGDSSGS TRRSWELRTL ISQSKDTASK LGPIEAIQKS VRLFEEKRYR EMRRKNIIGQ 1330 1340 1350 1360 1370 1380 VCDTPKSYDN VMHVGLRKVT FKWQRGNKIG EGQYGKVYTC ISVDTGELMA MKEIRFQPND 1390 1400 1410 1420 1430 1440 HKTIKETADE LKIFEGIKHP NLVRYFGVEL HREEMYIFME YCDEGTLEEV SRLGLQEHVI 1450 1460 1470 1480 1490 1500 RLYSKQITIA INVLHEHGIV HRDIKGANIF LTSSGLIKLG DFGCSVKLKN NAQTMPGEVN 1510 1520 1530 1540 1550 1560 STLGTAAYMA PEVITRAKGE GHGRAADIWS LGCVVIEMVT GKRPWHEYEH NFQIMYKVGM 1570 1580 1590 1600 GHKPPIPERL SPEGKDFLSH CLESDPKMRW TASQLLDHSF VKVCTDEE
	Isoform 2 (B) [UniParc]. Checksum: 4F94E9CF82E88354	FASTA	1,558	177,014
	10 20 30 40 50 60 MREAAAALVP PPAFAVTPAA AMEEPPPPPP PPPPPPEPET ESEPECCLAA RQEGTLGDSA 70 80 90 100 110 120 CKSPESDLED FSDETNTENL YGTSPPSTPR QMKRMSTKHQ RNNVGRPASR SNLKEKMNAP 130 140 150 160 170 180 NQPPHKDTGK TVENVEEYSY KQEKKIRAAL RTTERDRKKN VQCSFMLDSV GGSLPKKSIP 190 200 210 220 230 240 DVDLNKPYLS LGCSNAKLPV SVPMPIARPA RQTSRTDCPA DRLKFFETLR LLLKLTSVSK 250 260 270 280 290 300 KKDREQRGQE NTSGFWLNRS NELIWLELQA WHAGRTINDQ DFFLYTARQA IPDIINEILT 310 320 330 340 350 360 FKVDYGSFAF VRDRAGFNGT SVEGQCKATP GTKIVGYSTH HEHLQRQRVS FEQVKRIMEL 370 380 390 400 410 420 LEYIEALYPS LQALQKDYEK YAAKDFQDRV QALCLWLNIT KDLNQKLRIM GTVLGIKNLS 430 440 450 460 470 480 DIGWPVFEIP SPRPSKGNEP EYEGDDTEGE LKELESSTDE SEEEQISDPR VPEIRQPIDN 490 500 510 520 530 540 SFDIQSRDCI SKKLERLESE DDSLGWGAPD WSTEAGFSRH CLTSIYRPFV DKALKQMGLR 550 560 570 580 590 600 KLILRLHKLM DGSLQRARIA LVKNDRPVEF SEFPDPMWGS DYVQLSRTPP SSEEKCSAVS 610 620 630 640 650 660 WEELKAMDLP SFEPAFLVLC RVLLNVIHEC LKLRLEQRPA GEPSLLSIKQ LVRECKEVLK 670 680 690 700 710 720 GGLLMKQYYQ FMLQEVLEDL EKPDCNIDAF EEDLHKMLMV YFDYMRSWIQ MLQQLPQASH 730 740 750 760 770 780 SLKNLLEEEW NFTKEITHYI RGGEAQAGKL FCDIAGMLLK STGSFLEFGL QESCAEFWTS 790 800 810 820 830 840 ADDSSASDEI RRSVIEISRA LKELFHEARE RASKALGFAK MLRKDLEIAA EFRLSAPVRD 850 860 870 880 890 900 LLDVLKSKQY VKVQIPGLEN LQMFVPDTLA EEKSIILQLL NAAAGKDCSK DSDDVLIDAY 910 920 930 940 950 960 LLLTKHGDRA RDSEDSWGTW EAQPVKVVPQ VETVDTLRSM QVDNLLLVVM QSAHLTIQRK 970 980 990 1000 1010 1020 AFQQSIEGLM TLCQEQTSSQ PVIAKALQQL KNDALELCNR ISNAIDRVDH MFTSEFDAEV 1030 1040 1050 1060 1070 1080 DESESVTLQQ YYREAMIQGY NFGFEYHKEV VRLMSGEFRQ KIGDKYISFA RKWMNYVLTK 1090 1100 1110 1120 1130 1140 CESGRGTRPR WATQGFDFLQ AIEPAFISAL PEDDFLSLQA LMNECIGHVI GKPHSPVTGL 1150 1160 1170 1180 1190 1200 YLAIHRNSPR PMKVPRCHSD PPNPHLIIPT PEGFRGSSVP ENDRLASIAA ELQFRSLSRH 1210 1220 1230 1240 1250 1260 SSPTEERDEP AYPRGDSSGS TRRSWELRTL ISQSKDTASK LGPIEAIQKS VRLFEEKRYR 1270 1280 1290 1300 1310 1320 EMRRKNIIGQ VCDTPKSYDN VMHVGLRKVT FKWQRGNKIG EGQYGKVYTC ISVDTGELMA 1330 1340 1350 1360 1370 1380 MKEIRFQPND HKTIKETADE LKIFEGIKHP NLVRYFGVEL HREEMYIFME YCDEGTLEEV 1390 1400 1410 1420 1430 1440 SRLGLQEHVI RLYSKQITIA INVLHEHGIV HRDIKGANIF LTSSGLIKLG DFGCSVKLKN 1450 1460 1470 1480 1490 1500 NAQTMPGEVN STLGTAAYMA PEVITRAKGE GHGRAADIWS LGCVVIEMVT GKRPWHEYEH 1510 1520 1530 1540 1550 NFQIMYKVGM GHKPPIPERL SPEGKDFLSH CLESDPKMRW TASQLLDHSF VKVCTDEE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A human homolog of the yeast Ssk2/Ssk22 MAP kinase kinase kinases, MTK1, mediates stress-induced activation of the p38 and JNK pathways." Takekawa M., Posas F., Saito H. EMBO J. 16:4973-4982(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, ALTERNATIVE SPLICING, MUTAGENESIS OF LYS-1372. Tissue: Fetal liver and Skeletal muscle.
[2]	"Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain." Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N. DNA Res. 3:321-329(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Bone marrow.
[3]	Ohara O., Nagase T., Kikuno R., Nomura N. Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT HIS-157. Tissue: Cerebellum.
[7]	"Regulation of MTK1/MEKK4 kinase activity by its N-terminal autoinhibitory domain and GADD45 binding." Mita H., Tsutsui J., Takekawa M., Witten E.A., Saito H. Mol. Cell. Biol. 22:4544-4555(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, INTERACTION WITH GADD45 AND MAP2K6, MUTAGENESIS OF LYS-1372.
[8]	"The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase activation by Axin and dishevelled through distinct mechanisms." Wong C.K., Luo W., Deng Y., Zou H., Ye Z., Lin S.-C. J. Biol. Chem. 279:39366-39373(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AXIN1 AND DIXDC1.
[9]	"MEKK4 is an effector of the embryonic TRAF4 for JNK activation." Abell A.N., Johnson G.L. J. Biol. Chem. 280:35793-35796(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TRAF4.
[10]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-499, MASS SPECTROMETRY.
[11]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456; SER-457; THR-458 AND SER-461, MASS SPECTROMETRY.
[14]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-294; ILE-335; HIS-566; HIS-584; PRO-906; GLN-1413 AND VAL-1492.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF002715 mRNA. Translation: AAB68804.1. D86968 mRNA. Translation: BAA13204.2. Different initiation. AL109942 , AL139393, AL591045, AL596452 Genomic DNA. Translation: CAC12766.2. Sequence problems. AL109942 , AL139393, AL591045, AL596452 Genomic DNA. Translation: CAI21477.1. Sequence problems. AL139393 , AL109942, AL591045, AL596452 Genomic DNA. Translation: CAI20815.1. Sequence problems. AL139393 , AL109942, AL591045, AL596452 Genomic DNA. Translation: CAI20816.1. Sequence problems. AL591045 , AL109942, AL139393, AL596452 Genomic DNA. Translation: CAH70639.1. Sequence problems. AL591045 , AL109942, AL139393, AL596452 Genomic DNA. Translation: CAH70640.1. Sequence problems. AL596452 , AL109942, AL139393, AL591045 Genomic DNA. Translation: CAI41309.1. Sequence problems. AL596452 , AL109942, AL139393, AL591045 Genomic DNA. Translation: CAI41310.1. Sequence problems. CH471051 Genomic DNA. Translation: EAW47587.1. BC136276 mRNA. Translation: AAI36277.1. BC143735 mRNA. Translation: AAI43736.1. BC146770 mRNA. Translation: AAI46771.1.
IPI	IPI00186536. IPI00386260.
PIR	T03022.
RefSeq	NP_005913.2. NM_005922.2. NP_006715.2. NM_006724.2.
UniGene	Hs.390428.
3D structure databases
ProteinModelPortal	Q9Y6R4.
SMR	Q9Y6R4. Positions 1301-1603.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y6R4. 7 interactions.
MINT	MINT-1213156.
STRING	9606.ENSP00000375986.
PTM databases
PhosphoSite	Q9Y6R4.
Polymorphism databases
DMDM	296434576.
Proteomic databases
PaxDb	Q9Y6R4.
PRIDE	Q9Y6R4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000366919; ENSP00000355886; ENSG00000085511. ENST00000392142; ENSP00000375986; ENSG00000085511.
GeneID	4216.
KEGG	hsa:4216.
UCSC	uc003qtn.3. human. uc003qto.3. human.
Organism-specific databases
CTD	4216.
GeneCards	GC06P161412.
H-InvDB	HIX0151295.
HGNC	HGNC:6856. MAP3K4.
HPA	HPA007625.
MIM	602425. gene.
neXtProt	NX_Q9Y6R4.
PharmGKB	PA30600.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOVERGEN	HBG006304.
InParanoid	Q9Y6R4.
KO	K04428.
OMA	SDPPNPH.
PhylomeDB	Q9Y6R4.
Enzyme and pathway databases
BRENDA	2.7.12.2. 2681.
Pathway_Interaction_DB	p38_mkk3_6pathway. p38 MAPK signaling pathway.
Gene expression databases
ArrayExpress	Q9Y6R4.
Bgee	Q9Y6R4.
CleanEx	HS_MAP3K4.
Genevestigator	Q9Y6R4.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL4853.
ChiTaRS	MAP3K4. human.
GenomeRNAi	4216.
NextBio	16627.
SOURCE	Search...

Entry information

Entry name

M3K4_HUMAN

Accession

Primary (citable) accession number: Q9Y6R4
Secondary accession number(s): A6H8W0 , B7ZLD3, B9EG75, Q5VTT8, Q5VTT9, Q92612, Q9H408

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 126 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.