O95819 (M4K4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase kinase kinase kinase 4
EC=2.7.11.1

Alternative name(s):
HPK/GCK-like kinase HGK
MAPK/ERK kinase kinase kinase 4
Short name=MEK kinase kinase 4
Short name=MEKKK 4
Nck-interacting kinase

Gene names

Name:	MAP4K4
Synonyms:	HGK, KIAA0687, NIK

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	1239 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	Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322. Ref.1 Ref.15
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.1
Cofactor	Magnesium. Ref.1
Subunit structure	Interacts with the SH3 domain of the adapter proteins Nck By similarity. Interacts (via its CNH regulatory domain) with ATL1 (via the N-terminal region). Interacts with RAP2A (GTP-bound form preferentially). Ref.6 Ref.7 UniProtKB P97820
Subcellular location	Cytoplasm Ref.7.
Tissue specificity	Appears to be ubiquitous. Expressed in all tissue types examined. Isoform 5 appears to be more abundant in the brain. Isoform 4 is predominant in the liver, skeletal muscle and placenta. Ref.1
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. Contains 1 CNH domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intracellular protein kinase cascade Inferred from direct assay Ref.1. Source: UniProtKB regulation of JNK cascade Inferred from direct assay Ref.7. Source: UniProtKB response to stress Inferred from direct assay Ref.1. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	ATP binding Inferred from direct assay Ref.1. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.1. Source: UniProtKB small GTPase regulator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 Ref.1 (identifier: O95819-1)

Also known as: Tumor-associated;

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 Ref.1 (identifier: O95819-2)

The sequence of this isoform differs from the canonical sequence as follows:
     495-525: Missing.
     740-740: A → AGEV

Isoform 3 Ref.1 (identifier: O95819-3)

The sequence of this isoform differs from the canonical sequence as follows:
     623-623: V → VQWSHLASLK...SDSDEVPPRV
     740-740: A → AGEV

Isoform 4 Ref.1 (identifier: O95819-4)

Also known as: HGK-S;

The sequence of this isoform differs from the canonical sequence as follows:
     495-525: Missing.
     569-622: Missing.
     740-740: A → AGEV
     1112-1112: H → HVRKNPHSM

Isoform 5 Ref.1 (identifier: O95819-5)

Also known as: HGK-L;

The sequence of this isoform differs from the canonical sequence as follows:
     495-525: Missing.
     569-622: Missing.
     623-623: V → VQWSHLASLK...SDSDEVPPRV
     740-740: A → AGEV
     1112-1112: H → HVRKNPHSM

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.11
	Chain	2 – 1239	1238	Mitogen-activated protein kinase kinase kinase kinase 4		PRO_0000086280
Regions
	Domain	25 – 289	265	Protein kinase
	Domain	926 – 1213	288	CNH
	Nucleotide binding	31 – 39	9	ATP By similarity UniProtKB O00506
	Region	858 – 1212	355	Mediates interaction with RAP2A
Sites
	Active site	153	1	Proton acceptor By similarity UniProtKB O00506
	Binding site	54	1	ATP By similarity UniProtKB O00506
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.11
	Modified residue	5	1	Phosphoserine Ref.11
	Modified residue	629	1	Phosphoserine Ref.10 Ref.16
	Modified residue	631	1	Phosphoserine Ref.10 Ref.16
	Modified residue	639	1	Phosphoserine Ref.8 Ref.9 Ref.10 Ref.11 Ref.16
	Modified residue	644	1	Phosphoserine Ref.9 Ref.11
	Modified residue	712	1	Phosphoserine Ref.9
	Modified residue	800	1	Phosphoserine Ref.12
	Modified residue	801	1	Phosphoserine By similarity
	Modified residue	805	1	Phosphoserine Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
	Modified residue	900	1	Phosphoserine Ref.11
Natural variations
	Alternative sequence	495 – 525	31	Missing in isoform 2, isoform 4 and isoform 5. Ref.1		VSP_007054
	Alternative sequence	569 – 622	54	Missing in isoform 4 and isoform 5. Ref.1		VSP_007055
	Alternative sequence	623	1	V → VQWSHLASLKNNVSPVSRSH SFSDPSPKFAHHHLRSQDPC PPSRSEVLSQSSDSKSEAPD PTQKAWSRSDSDEVPPRV in isoform 3 and isoform 5. Ref.1		VSP_007056
	Alternative sequence	740	1	A → AGEV in isoform 2, isoform 3, isoform 4 and isoform 5. Ref.1		VSP_007057
	Alternative sequence	1112	1	H → HVRKNPHSM in isoform 4 and isoform 5. Ref.1		VSP_007058
	Natural variant	712	1	S → T. Ref.17		VAR_040746
Isoform 3:
	Natural variant	682	1	D → V.
Experimental info
	Sequence conflict	658	1	S → SS Ref.3
	Sequence conflict	658	1	S → SS Ref.4
	Sequence conflict	839	1	Q → R in AAO32626. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Tumor-associated) [UniParc]. Last modified March 28, 2003. Version 2. Checksum: 8FBBE2F9ABEEC757	FASTA	1,239	142,101
	10 20 30 40 50 60 MANDSPAKSL VDIDLSSLRD PAGIFELVEV VGNGTYGQVY KGRHVKTGQL AAIKVMDVTE 70 80 90 100 110 120 DEEEEIKLEI NMLKKYSHHR NIATYYGAFI KKSPPGHDDQ LWLVMEFCGA GSITDLVKNT 130 140 150 160 170 180 KGNTLKEDWI AYISREILRG LAHLHIHHVI HRDIKGQNVL LTENAEVKLV DFGVSAQLDR 190 200 210 220 230 240 TVGRRNTFIG TPYWMAPEVI ACDENPDATY DYRSDLWSCG ITAIEMAEGA PPLCDMHPMR 250 260 270 280 290 300 ALFLIPRNPP PRLKSKKWSK KFFSFIEGCL VKNYMQRPST EQLLKHPFIR DQPNERQVRI 310 320 330 340 350 360 QLKDHIDRTR KKRGEKDETE YEYSGSEEEE EEVPEQEGEP SSIVNVPGES TLRRDFLRLQ 370 380 390 400 410 420 QENKERSEAL RRQQLLQEQQ LREQEEYKRQ LLAERQKRIE QQKEQRRRLE EQQRREREAR 430 440 450 460 470 480 RQQEREQRRR EQEEKRRLEE LERRRKEEEE RRRAEEEKRR VEREQEYIRR QLEEEQRHLE 490 500 510 520 530 540 VLQQQLLQEQ AMLLECRWRE MEEHRQAERL QRQLQQEQAY LLSLQHDHRR PHPQHSQQPP 550 560 570 580 590 600 PPQQERSKPS FHAPEPKAHY EPADRAREVE DRFRKTNHSS PEAQSKQTGR VLEPPVPSRS 610 620 630 640 650 660 ESFSNGNSES VHPALQRPAE PQVPVRTTSR SPVLSRRDSP LQGSGQQNSQ AGQRNSTSIE 670 680 690 700 710 720 PRLLWERVEK LVPRPGSGSS SGSSNSGSQP GSHPGSQSGS GERFRVRSSS KSEGSPSQRL 730 740 750 760 770 780 ENAVKKPEDK KEVFRPLKPA DLTALAKELR AVEDVRPPHK VTDYSSSSEE SGTTDEEDDD 790 800 810 820 830 840 VEQEGADEST SGPEDTRAAS SLNLSNGETE SVKTMIVHDD VESEPAMTPS KEGTLIVRQT 850 860 870 880 890 900 QSASSTLQKH KSSSSFTPFI DPRLLQISPS SGTTVTSVVG FSCDGMRPEA IRQDPTRKGS 910 920 930 940 950 960 VVNVNPTNTR PQSDTPEIRK YKKRFNSEIL CAALWGVNLL VGTESGLMLL DRSGQGKVYP 970 980 990 1000 1010 1020 LINRRRFQQM DVLEGLNVLV TISGKKDKLR VYYLSWLRNK ILHNDPEVEK KQGWTTVGDL 1030 1040 1050 1060 1070 1080 EGCVHYKVVK YERIKFLVIA LKSSVEVYAW APKPYHKFMA FKSFGELVHK PLLVDLTVEE 1090 1100 1110 1120 1130 1140 GQRLKVIYGS CAGFHAVDVD SGSVYDIYLP THIQCSIKPH AIIILPNTDG MELLVCYEDE 1150 1160 1170 1180 1190 1200 GVYVNTYGRI TKDVVLQWGE MPTSVAYIRS NQTMGWGEKA IEIRSVETGH LDGVFMHKRA 1210 1220 1230 QRLKFLCERN DKVFFASVRS GGSSQVYFMT LGRTSLLSW
	Isoform 2 [UniParc]. Checksum: FD4A41765D9719F7	FASTA	1,211	138,418
	10 20 30 40 50 60 MANDSPAKSL VDIDLSSLRD PAGIFELVEV VGNGTYGQVY KGRHVKTGQL AAIKVMDVTE 70 80 90 100 110 120 DEEEEIKLEI NMLKKYSHHR NIATYYGAFI KKSPPGHDDQ LWLVMEFCGA GSITDLVKNT 130 140 150 160 170 180 KGNTLKEDWI AYISREILRG LAHLHIHHVI HRDIKGQNVL LTENAEVKLV DFGVSAQLDR 190 200 210 220 230 240 TVGRRNTFIG TPYWMAPEVI ACDENPDATY DYRSDLWSCG ITAIEMAEGA PPLCDMHPMR 250 260 270 280 290 300 ALFLIPRNPP PRLKSKKWSK KFFSFIEGCL VKNYMQRPST EQLLKHPFIR DQPNERQVRI 310 320 330 340 350 360 QLKDHIDRTR KKRGEKDETE YEYSGSEEEE EEVPEQEGEP SSIVNVPGES TLRRDFLRLQ 370 380 390 400 410 420 QENKERSEAL RRQQLLQEQQ LREQEEYKRQ LLAERQKRIE QQKEQRRRLE EQQRREREAR 430 440 450 460 470 480 RQQEREQRRR EQEEKRRLEE LERRRKEEEE RRRAEEEKRR VEREQEYIRR QLEEEQRHLE 490 500 510 520 530 540 VLQQQLLQEQ AMLLHDHRRP HPQHSQQPPP PQQERSKPSF HAPEPKAHYE PADRAREVED 550 560 570 580 590 600 RFRKTNHSSP EAQSKQTGRV LEPPVPSRSE SFSNGNSESV HPALQRPAEP QVPVRTTSRS 610 620 630 640 650 660 PVLSRRDSPL QGSGQQNSQA GQRNSTSIEP RLLWERVEKL VPRPGSGSSS GSSNSGSQPG 670 680 690 700 710 720 SHPGSQSGSG ERFRVRSSSK SEGSPSQRLE NAVKKPEDKK EVFRPLKPAG EVDLTALAKE 730 740 750 760 770 780 LRAVEDVRPP HKVTDYSSSS EESGTTDEED DDVEQEGADE STSGPEDTRA ASSLNLSNGE 790 800 810 820 830 840 TESVKTMIVH DDVESEPAMT PSKEGTLIVR QTQSASSTLQ KHKSSSSFTP FIDPRLLQIS 850 860 870 880 890 900 PSSGTTVTSV VGFSCDGMRP EAIRQDPTRK GSVVNVNPTN TRPQSDTPEI RKYKKRFNSE 910 920 930 940 950 960 ILCAALWGVN LLVGTESGLM LLDRSGQGKV YPLINRRRFQ QMDVLEGLNV LVTISGKKDK 970 980 990 1000 1010 1020 LRVYYLSWLR NKILHNDPEV EKKQGWTTVG DLEGCVHYKV VKYERIKFLV IALKSSVEVY 1030 1040 1050 1060 1070 1080 AWAPKPYHKF MAFKSFGELV HKPLLVDLTV EEGQRLKVIY GSCAGFHAVD VDSGSVYDIY 1090 1100 1110 1120 1130 1140 LPTHIQCSIK PHAIIILPNT DGMELLVCYE DEGVYVNTYG RITKDVVLQW GEMPTSVAYI 1150 1160 1170 1180 1190 1200 RSNQTMGWGE KAIEIRSVET GHLDGVFMHK RAQRLKFLCE RNDKVFFASV RSGGSSQVYF 1210 MTLGRTSLLS W
	Isoform 3 [UniParc]. Checksum: 6DCBFA9AB27A8AD9	FASTA	1,319	150,913
	10 20 30 40 50 60 MANDSPAKSL VDIDLSSLRD PAGIFELVEV VGNGTYGQVY KGRHVKTGQL AAIKVMDVTE 70 80 90 100 110 120 DEEEEIKLEI NMLKKYSHHR NIATYYGAFI KKSPPGHDDQ LWLVMEFCGA GSITDLVKNT 130 140 150 160 170 180 KGNTLKEDWI AYISREILRG LAHLHIHHVI HRDIKGQNVL LTENAEVKLV DFGVSAQLDR 190 200 210 220 230 240 TVGRRNTFIG TPYWMAPEVI ACDENPDATY DYRSDLWSCG ITAIEMAEGA PPLCDMHPMR 250 260 270 280 290 300 ALFLIPRNPP PRLKSKKWSK KFFSFIEGCL VKNYMQRPST EQLLKHPFIR DQPNERQVRI 310 320 330 340 350 360 QLKDHIDRTR KKRGEKDETE YEYSGSEEEE EEVPEQEGEP SSIVNVPGES TLRRDFLRLQ 370 380 390 400 410 420 QENKERSEAL RRQQLLQEQQ LREQEEYKRQ LLAERQKRIE QQKEQRRRLE EQQRREREAR 430 440 450 460 470 480 RQQEREQRRR EQEEKRRLEE LERRRKEEEE RRRAEEEKRR VEREQEYIRR QLEEEQRHLE 490 500 510 520 530 540 VLQQQLLQEQ AMLLECRWRE MEEHRQAERL QRQLQQEQAY LLSLQHDHRR PHPQHSQQPP 550 560 570 580 590 600 PPQQERSKPS FHAPEPKAHY EPADRAREVE DRFRKTNHSS PEAQSKQTGR VLEPPVPSRS 610 620 630 640 650 660 ESFSNGNSES VHPALQRPAE PQVQWSHLAS LKNNVSPVSR SHSFSDPSPK FAHHHLRSQD 670 680 690 700 710 720 PCPPSRSEVL SQSSDSKSEA PDPTQKAWSR SDSDEVPPRV PVRTTSRSPV LSRRDSPLQG 730 740 750 760 770 780 SGQQNSQAGQ RNSTSIEPRL LWERVEKLVP RPGSGSSSGS SNSGSQPGSH PGSQSGSGER 790 800 810 820 830 840 FRVRSSSKSE GSPSQRLENA VKKPEDKKEV FRPLKPAGEV DLTALAKELR AVEDVRPPHK 850 860 870 880 890 900 VTDYSSSSEE SGTTDEEDDD VEQEGADEST SGPEDTRAAS SLNLSNGETE SVKTMIVHDD 910 920 930 940 950 960 VESEPAMTPS KEGTLIVRQT QSASSTLQKH KSSSSFTPFI DPRLLQISPS SGTTVTSVVG 970 980 990 1000 1010 1020 FSCDGMRPEA IRQDPTRKGS VVNVNPTNTR PQSDTPEIRK YKKRFNSEIL CAALWGVNLL 1030 1040 1050 1060 1070 1080 VGTESGLMLL DRSGQGKVYP LINRRRFQQM DVLEGLNVLV TISGKKDKLR VYYLSWLRNK 1090 1100 1110 1120 1130 1140 ILHNDPEVEK KQGWTTVGDL EGCVHYKVVK YERIKFLVIA LKSSVEVYAW APKPYHKFMA 1150 1160 1170 1180 1190 1200 FKSFGELVHK PLLVDLTVEE GQRLKVIYGS CAGFHAVDVD SGSVYDIYLP THIQCSIKPH 1210 1220 1230 1240 1250 1260 AIIILPNTDG MELLVCYEDE GVYVNTYGRI TKDVVLQWGE MPTSVAYIRS NQTMGWGEKA 1270 1280 1290 1300 1310 IEIRSVETGH LDGVFMHKRA QRLKFLCERN DKVFFASVRS GGSSQVYFMT LGRTSLLSW
	Isoform 4 (HGK-S) [UniParc]. Checksum: 03D9E1A3D7F9415D	FASTA	1,165	133,401
	10 20 30 40 50 60 MANDSPAKSL VDIDLSSLRD PAGIFELVEV VGNGTYGQVY KGRHVKTGQL AAIKVMDVTE 70 80 90 100 110 120 DEEEEIKLEI NMLKKYSHHR NIATYYGAFI KKSPPGHDDQ LWLVMEFCGA GSITDLVKNT 130 140 150 160 170 180 KGNTLKEDWI AYISREILRG LAHLHIHHVI HRDIKGQNVL LTENAEVKLV DFGVSAQLDR 190 200 210 220 230 240 TVGRRNTFIG TPYWMAPEVI ACDENPDATY DYRSDLWSCG ITAIEMAEGA PPLCDMHPMR 250 260 270 280 290 300 ALFLIPRNPP PRLKSKKWSK KFFSFIEGCL VKNYMQRPST EQLLKHPFIR DQPNERQVRI 310 320 330 340 350 360 QLKDHIDRTR KKRGEKDETE YEYSGSEEEE EEVPEQEGEP SSIVNVPGES TLRRDFLRLQ 370 380 390 400 410 420 QENKERSEAL RRQQLLQEQQ LREQEEYKRQ LLAERQKRIE QQKEQRRRLE EQQRREREAR 430 440 450 460 470 480 RQQEREQRRR EQEEKRRLEE LERRRKEEEE RRRAEEEKRR VEREQEYIRR QLEEEQRHLE 490 500 510 520 530 540 VLQQQLLQEQ AMLLHDHRRP HPQHSQQPPP PQQERSKPSF HAPEPKAHYE PADRAREVPV 550 560 570 580 590 600 RTTSRSPVLS RRDSPLQGSG QQNSQAGQRN STSIEPRLLW ERVEKLVPRP GSGSSSGSSN 610 620 630 640 650 660 SGSQPGSHPG SQSGSGERFR VRSSSKSEGS PSQRLENAVK KPEDKKEVFR PLKPAGEVDL 670 680 690 700 710 720 TALAKELRAV EDVRPPHKVT DYSSSSEESG TTDEEDDDVE QEGADESTSG PEDTRAASSL 730 740 750 760 770 780 NLSNGETESV KTMIVHDDVE SEPAMTPSKE GTLIVRQTQS ASSTLQKHKS SSSFTPFIDP 790 800 810 820 830 840 RLLQISPSSG TTVTSVVGFS CDGMRPEAIR QDPTRKGSVV NVNPTNTRPQ SDTPEIRKYK 850 860 870 880 890 900 KRFNSEILCA ALWGVNLLVG TESGLMLLDR SGQGKVYPLI NRRRFQQMDV LEGLNVLVTI 910 920 930 940 950 960 SGKKDKLRVY YLSWLRNKIL HNDPEVEKKQ GWTTVGDLEG CVHYKVVKYE RIKFLVIALK 970 980 990 1000 1010 1020 SSVEVYAWAP KPYHKFMAFK SFGELVHKPL LVDLTVEEGQ RLKVIYGSCA GFHAVDVDSG 1030 1040 1050 1060 1070 1080 SVYDIYLPTH VRKNPHSMIQ CSIKPHAIII LPNTDGMELL VCYEDEGVYV NTYGRITKDV 1090 1100 1110 1120 1130 1140 VLQWGEMPTS VAYIRSNQTM GWGEKAIEIR SVETGHLDGV FMHKRAQRLK FLCERNDKVF 1150 1160 FASVRSGGSS QVYFMTLGRT SLLSW
	Isoform 5 (HGK-L) [UniParc]. Checksum: AF0219B2CA816B5B	FASTA	1,242	141,929
	10 20 30 40 50 60 MANDSPAKSL VDIDLSSLRD PAGIFELVEV VGNGTYGQVY KGRHVKTGQL AAIKVMDVTE 70 80 90 100 110 120 DEEEEIKLEI NMLKKYSHHR NIATYYGAFI KKSPPGHDDQ LWLVMEFCGA GSITDLVKNT 130 140 150 160 170 180 KGNTLKEDWI AYISREILRG LAHLHIHHVI HRDIKGQNVL LTENAEVKLV DFGVSAQLDR 190 200 210 220 230 240 TVGRRNTFIG TPYWMAPEVI ACDENPDATY DYRSDLWSCG ITAIEMAEGA PPLCDMHPMR 250 260 270 280 290 300 ALFLIPRNPP PRLKSKKWSK KFFSFIEGCL VKNYMQRPST EQLLKHPFIR DQPNERQVRI 310 320 330 340 350 360 QLKDHIDRTR KKRGEKDETE YEYSGSEEEE EEVPEQEGEP SSIVNVPGES TLRRDFLRLQ 370 380 390 400 410 420 QENKERSEAL RRQQLLQEQQ LREQEEYKRQ LLAERQKRIE QQKEQRRRLE EQQRREREAR 430 440 450 460 470 480 RQQEREQRRR EQEEKRRLEE LERRRKEEEE RRRAEEEKRR VEREQEYIRR QLEEEQRHLE 490 500 510 520 530 540 VLQQQLLQEQ AMLLHDHRRP HPQHSQQPPP PQQERSKPSF HAPEPKAHYE PADRAREVQW 550 560 570 580 590 600 SHLASLKNNV SPVSRSHSFS DPSPKFAHHH LRSQDPCPPS RSEVLSQSSD SKSEAPDPTQ 610 620 630 640 650 660 KAWSRSDSDE VPPRVPVRTT SRSPVLSRRD SPLQGSGQQN SQAGQRNSTS IEPRLLWERV 670 680 690 700 710 720 EKLVPRPGSG SSSGSSNSGS QPGSHPGSQS GSGERFRVRS SSKSEGSPSQ RLENAVKKPE 730 740 750 760 770 780 DKKEVFRPLK PAGEVDLTAL AKELRAVEDV RPPHKVTDYS SSSEESGTTD EEDDDVEQEG 790 800 810 820 830 840 ADESTSGPED TRAASSLNLS NGETESVKTM IVHDDVESEP AMTPSKEGTL IVRQTQSASS 850 860 870 880 890 900 TLQKHKSSSS FTPFIDPRLL QISPSSGTTV TSVVGFSCDG MRPEAIRQDP TRKGSVVNVN 910 920 930 940 950 960 PTNTRPQSDT PEIRKYKKRF NSEILCAALW GVNLLVGTES GLMLLDRSGQ GKVYPLINRR 970 980 990 1000 1010 1020 RFQQMDVLEG LNVLVTISGK KDKLRVYYLS WLRNKILHND PEVEKKQGWT TVGDLEGCVH 1030 1040 1050 1060 1070 1080 YKVVKYERIK FLVIALKSSV EVYAWAPKPY HKFMAFKSFG ELVHKPLLVD LTVEEGQRLK 1090 1100 1110 1120 1130 1140 VIYGSCAGFH AVDVDSGSVY DIYLPTHVRK NPHSMIQCSI KPHAIIILPN TDGMELLVCY 1150 1160 1170 1180 1190 1200 EDEGVYVNTY GRITKDVVLQ WGEMPTSVAY IRSNQTMGWG EKAIEIRSVE TGHLDGVFMH 1210 1220 1230 1240 KRAQRLKFLC ERNDKVFFAS VRSGGSSQVY FMTLGRTSLL SW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway." Yao Z., Zhou G., Wang X.S., Brown A., Diener K., Gan H., Tan T.-H. J. Biol. Chem. 274:2118-2125(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 5), FUNCTION, TISSUE SPECIFICITY. Tissue: Macrophage.
[2]	"The STE20 kinase HGK is broadly expressed in human tumor cells and can modulate cellular transformation, invasion, and adhesion." Wright J.H., Wang X., Manning G., LaMere B.J., Le P., Zhu S., Khatry D., Flanagan P.M., Buckley S.D., Whyte D.B., Howlett A.R., Bischoff J.R., Lipson K.E., Jallal B. Mol. Cell. Biol. 23:2068-2082(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Glioblastoma.
[3]	"Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:169-176(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 38-1239 (ISOFORM 2). Tissue: Brain.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 262-1239 (ISOFORM 3). Tissue: Testis.
[5]	"Isolation, expression profile and chromosome assignment of a novel serine/threonine kinase gene." Saito T., Seki N., Hori T. Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 700-1239. Tissue: Brain.
[6]	"A novel GTP-binding protein hGBP3 interacts with NIK/HGK." Luan Z., Zhang Y., Liu A., Man Y., Cheng L., Hu G. FEBS Lett. 530:233-238(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ATL1.
[7]	"Mitogen-activated protein kinase kinase kinase kinase 4 as a putative effector of Rap2 to activate the c-Jun N-terminal kinase." Machida N., Umikawa M., Takei K., Sakima N., Myagmar B.E., Taira K., Uezato H., Ogawa Y., Kariya K. J. Biol. Chem. 279:15711-15714(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAP2A, SUBCELLULAR LOCATION.
[8]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-639, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-639; SER-644; SER-712 AND SER-805, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-629; SER-631; SER-639 AND SER-805, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5; SER-639; SER-644; SER-805 AND SER-900, MASS SPECTROMETRY, CLEAVAGE OF INITIATOR METHIONINE.
[12]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-800 AND SER-805, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[13]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-805, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"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].
[15]	"Smad inhibition by the Ste20 kinase Misshapen." Kaneko S., Chen X., Lu P., Yao X., Wright T.G., Rajurkar M., Kariya K., Mao J., Ip Y.T., Xu L. Proc. Natl. Acad. Sci. U.S.A. 108:11127-11132(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[16]	"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-629; SER-631 AND SER-639, MASS SPECTROMETRY.
[17]	"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: VARIANT [LARGE SCALE ANALYSIS] THR-712, VARIANT [LARGE SCALE ANALYSIS] VAL-682 (ISOFORM 3).
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF096300 mRNA. Translation: AAD16137.1. AY212247 mRNA. Translation: AAO32626.1. AB014587 mRNA. Translation: BAA31662.1. AL137755 mRNA. Translation: CAB70907.2. AB013385 mRNA. Translation: BAA33714.1.
IPI	IPI00006752. IPI00219799. IPI00219800. IPI00219802. IPI00639883.
PIR	T46481.
RefSeq	NP_001229488.1. NM_001242559.1. NP_004825.3. NM_004834.4. NP_663720.1. NM_145687.3.
UniGene	Hs.741154.
3D structure databases
ProteinModelPortal	O95819.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95819. 15 interactions.
STRING	9606.ENSP00000313644.
PTM databases
PhosphoSite	O95819.
Proteomic databases
PaxDb	O95819.
PRIDE	O95819.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000347699; ENSP00000314363; ENSG00000071054.
GeneID	9448.
KEGG	hsa:9448.
UCSC	uc002tbc.3. human. uc002tbd.3. human. uc002tbg.3. human. uc002tbh.3. human.
Organism-specific databases
CTD	9448.
GeneCards	GC02P102313.
HGNC	HGNC:6866. MAP4K4.
HPA	HPA008476.
MIM	604666. gene.
neXtProt	NX_O95819.
PharmGKB	PA30612.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000290708.
HOVERGEN	HBG036506.
KO	K04407.
Enzyme and pathway databases
Pathway_Interaction_DB	ceramidepathway. Ceramide signaling pathway. ephbfwdpathway. EPHB forward signaling. tnfpathway. TNF receptor signaling pathway.
Gene expression databases
ArrayExpress	O95819.
Bgee	O95819.
CleanEx	HS_MAP4K4.
Genevestigator	O95819.
GermOnline	ENSG00000071054. Homo sapiens.
Family and domain databases
InterPro	IPR001180. Citron. 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	PF00780. CNH. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00036. CNH. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS50219. CNH. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O95819.
ChEMBL	CHEMBL6166.
ChiTaRS	MAP4K4. human.
GenomeRNAi	9448.
NextBio	35392.
SOURCE	Search...

Entry information

Entry name

M4K4_HUMAN

Accession

Primary (citable) accession number: O95819
Secondary accession number(s): O75172, Q9NST7

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 28, 2003
Last sequence update:	March 28, 2003
Last modified:	May 1, 2013
This is version 130 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.