Mitogen-activated protein kinase kinase kinase kinase 4

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase kinase kinase kinase 4
    EC=2.7.11.1
Alternative name(s):
    MAPK/ERK kinase kinase kinase 4
      Short name=MEK kinase kinase 4
      Short name=MEKKK 4
    HPK/GCK-like kinase HGK
    Nck-interacting kinase

Gene names

Name:	MAP4K4
Synonyms:	HGK, KIAA0687, NIK

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	1239 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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. Ref.1
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. Binds, via its CNH regulatory domain, to the N-terminal region of SPG3A. UniProtKB P97820
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
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12
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.

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Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Ref.1 Inferred from direct assay. Source: UniProtKB protein kinase cascade Ref.1 Inferred from direct assay. Source: UniProtKB response to stress Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Ref.1 Inferred from direct assay. Source: UniProtKB protein serine/threonine kinase activity Ref.1 Inferred from direct assay. Source: UniProtKB small GTPase regulator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Natural variant

682

1

D → V

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

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1239

1239

Mitogen-activated protein kinase kinase kinase kinase 4

PRO_0000086280

Regions

Domain

25 – 289

265

Protein kinase

Domain

844 – 1143

300

CNH

Nucleotide binding

31 – 39

9

ATP By similarity UniProtKB O00506

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

181

1

Phosphothreonine Ref.8

Modified residue

324

1

Phosphoserine Ref.11

Modified residue

326

1

Phosphoserine Ref.11

Modified residue

602

1

Phosphoserine Ref.8

Modified residue

629

1

Phosphoserine Ref.7 Ref.8 Ref.11 Ref.12

Modified residue

631

1

Phosphoserine Ref.7 Ref.8 Ref.11 Ref.12

Modified residue

639

1

Phosphoserine Ref.8 Ref.10 Ref.11 Ref.12

Modified residue

644

1

Phosphoserine Ref.11

Modified residue

656

1

Phosphoserine Ref.11 Ref.12

Modified residue

658

1

Phosphoserine Ref.12

Modified residue

692

1

Phosphoserine Ref.9

Modified residue

696

1

Phosphoserine Ref.9

Modified residue

712

1

Phosphoserine Ref.11

Modified residue

715

1

Phosphoserine Ref.11

Modified residue

801

1

Phosphoserine Ref.8

Modified residue

805

1

Phosphoserine Ref.7 Ref.8 Ref.11 Ref.12

Modified residue

828

1

Phosphothreonine Ref.11

Modified residue

842

1

Phosphoserine Ref.11

Modified residue

855

1

Phosphoserine Ref.11

Modified residue

857

1

Phosphothreonine Ref.11

Modified residue

900

1

Phosphoserine Ref.8

Modified residue

913

1

Phosphoserine Ref.11

Modified residue

915

1

Phosphothreonine 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.13

VAR_040746

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

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 (Tumor-associated) [UniParc]. Last modified March 28, 2003. Version 2. Checksum: 8FBBE2F9ABEEC757 Show »	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 « Hide
Isoform 2. Checksum: FD4A41765D9719F7 Show »	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 « Hide
Isoform 3. Checksum: 6DCBFA9AB27A8AD9 Show »	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 « Hide
Isoform 4 (HGK-S). Checksum: 03D9E1A3D7F9415D Show »	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 « Hide
Isoform 5 (HGK-L). Checksum: AF0219B2CA816B5B Show »	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 « Hide

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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: 9890973] [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: 12612079] [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: 9734811] [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., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [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: 12387898] [Abstract] Cited for: INTERACTION WITH SPG3A.
[7]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-629; SER-631 AND SER-805, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"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-181; SER-602; SER-629; SER-631; SER-639; SER-801; SER-805 AND SER-900, MASS SPECTROMETRY.
[9]	"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 SER-692 AND SER-696, MASS SPECTROMETRY.
[10]	"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: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-639, MASS SPECTROMETRY.
[11]	"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-324; SER-326; SER-629; SER-631; SER-639; SER-644; SER-656; SER-712; SER-715; SER-805; THR-828; SER-842; SER-855; THR-857; SER-913 AND THR-915, MASS SPECTROMETRY.
[12]	"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 SER-629; SER-631; SER-639; SER-656; SER-658 AND SER-805, MASS SPECTROMETRY.
[13]	"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. Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-712, VARIANT [LARGE SCALE ANALYSIS] VAL-682 (ISOFORM 3).
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	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_004825.2. NP_663719.1. NP_663720.1.
UniGene	Hs.431550
3D structure databases
HSSP	HSSP built from PDB template 1F3M based on UniProtKB Q13153.
ModBase	Search...
PTM databases
PhosphoSite	O95819.
Proteomic databases
PRIDE	O95819.
Genome annotation databases
Ensembl	ENSG00000071054. Homo sapiens. [Contig view]
GeneID	9448.
KEGG	hsa:9448.
Organism-specific databases
GeneCards	GC02P101773.
H-InvDB	HIX0002328.
HGNC	HGNC:6866. MAP4K4.
HPA	HPA008476.
MIM	604666. gene.
PharmGKB	PA30612.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	O95819.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
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.
GermOnline	ENSG00000071054. Homo sapiens.
Family and domain databases
InterPro	IPR001180. Citron. 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	PF00780. CNH. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00036. CNH. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	35392.
SOURCE	Search...

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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 5, 2009
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents