ID   Q59GL6_HUMAN            Unreviewed;      1455 AA.
AC   Q59GL6;
DT   26-APR-2005, integrated into UniProtKB/TrEMBL.
DT   26-APR-2005, sequence version 1.
DT   27-MAR-2024, entry version 109.
DE   RecName: Full=mitogen-activated protein kinase kinase kinase {ECO:0000256|ARBA:ARBA00012406};
DE            EC=2.7.11.25 {ECO:0000256|ARBA:ARBA00012406};
DE   Flags: Fragment;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606 {ECO:0000313|EMBL:BAD92330.1};
RN   [1] {ECO:0000313|EMBL:BAD92330.1}
RP   NUCLEOTIDE SEQUENCE.
RC   TISSUE=Brain {ECO:0000313|EMBL:BAD92330.1};
RA   Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA   Ohara O., Nagase T., Kikuno R.F.;
RT   "Homo sapiens protein coding cDNA.";
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.25;
CC         Evidence={ECO:0000256|ARBA:ARBA00000478};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC         Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.25; Evidence={ECO:0000256|ARBA:ARBA00000106};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000256|ARBA:ARBA00001946};
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC       protein kinase family. MAP kinase kinase kinase subfamily.
CC       {ECO:0000256|ARBA:ARBA00006529}.
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DR   EMBL; AB209093; BAD92330.1; -; mRNA.
DR   iPTMnet; Q59GL6; -.
DR   MaxQB; Q59GL6; -.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0004709; F:MAP kinase kinase kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   CDD; cd06624; STKc_ASK; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR046872; DRHyd-ASK.
DR   InterPro; IPR046873; HisK-N-like.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR043969; MAP3K_PH.
DR   InterPro; IPR025136; MAP3K_TRAF-bd.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR013761; SAM/pointed_sf.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR11584:SF332; MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 5; 1.
DR   PANTHER; PTHR11584; SERINE/THREONINE PROTEIN KINASE; 1.
DR   Pfam; PF19039; ASK_PH; 1.
DR   Pfam; PF20309; DRHyd-ASK; 1.
DR   Pfam; PF20302; HisK-N-like; 1.
DR   Pfam; PF13281; MAP3K_TRAF_bd; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   SUPFAM; SSF47769; SAM/Pointed domain; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE   2: Evidence at transcript level;
KW   ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PROSITE-
KW   ProRule:PRU10141};
KW   Coiled coil {ECO:0000256|ARBA:ARBA00023054, ECO:0000256|SAM:Coils};
KW   Kinase {ECO:0000313|EMBL:BAD92330.1};
KW   Magnesium {ECO:0000256|ARBA:ARBA00022842};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW   Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|PROSITE-
KW   ProRule:PRU10141};
KW   Serine/threonine-protein kinase {ECO:0000256|ARBA:ARBA00022527};
KW   Transferase {ECO:0000313|EMBL:BAD92330.1}.
FT   DOMAIN          760..1018
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000259|PROSITE:PS50011"
FT   REGION          1..53
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          148..167
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1263..1290
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          1326..1360
FT                   /evidence="ECO:0000256|SAM:Coils"
FT   COMPBIAS        28..42
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         789
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU10141"
FT   NON_TER         1
FT                   /evidence="ECO:0000313|EMBL:BAD92330.1"
SQ   SEQUENCE   1455 AA;  162958 MW;  A9C71935AB18A0E0 CRC64;
     TLQRASGAAT EAPRRSEPPP GSGVPSGERA PERRRRRGGE GAARDGSCLA RRARSSPELW
     LARRCGWAGD AAAVAARPGE MSTEADEGIT FSVPPFAPSG FCTIPEGGIC RRGGAAAVGE
     GEEHQLPPPP PGSFWNVESA AAPGIGCPAA TSSSSATRGR GSSVGGGSRR TTVAYVINEA
     SQGQLVVAES EALQSLREAC ETVGATLETL HFGKLDFGET TVLDRFYNAD IAVVEMSDAF
     RQPSLFYHLG VRESFSMANN IILYCDTNSD SLQSLKEIIC QKNTMCTGNY TFVPYMITPH
     NKVYCCDSSF MKGLTELMQP NFELLLGPIC LPLVDRFIQL LKVAQASSSQ YFRESILNDI
     RKARNLYTGK ELAAELARIR QRVDNIEVLT ADIVINLLLS YRDIQDYDSI VKLVETLEKL
     PTFDLASHHH VKFHYAFALN RRNLPGDRAK ALDIMIPMVQ SEGQVASDMY CLVGRIYKDM
     FLDSNFTDTE SRDHGASWFK KAFESEPTLQ SGINYAVLLL AAGHQFESSF ELRKVGVKLS
     SLLGKKGNLE KLQSYWEVGF FLGASVLAND HMRVIQASEK LFKLKTPAWY LKSIVETILI
     YKHFVKLTTE QPVAKQELVD FWMDFLVEAT KTDVTVVRFP VLILEPTKIY QPSYLSINNE
     VEEKTISIWH VLPDDKKGIH EWNFSASSVR GVSISKFEER CCFLYVLHNS DDFQIYFCTE
     PDCKKFFEMV NTITEEKGRS TEEGDCESDL LEYDYEYDEN GDRVVLGKGT YGIVYAGRDL
     SNQVRIAIKE IPERDSRYSQ PLHEEIALHK HLKHKNIVQY LGSFSENGFI KIFMEQVPGG
     SLSALLRSKW GPLKDNEQTI GFYTKQILEG LKYLHDNQIV HRDIKGDNVL INTYSGVLKI
     SDFGTSKRLA GINPCTETFT GTLQYMAPEI IDKGPRGYGK AADIWSLGCT IIEMATGKPP
     FYELGEPQAA MFKVGMFKVH PEIPESMSAE AKAFILKCFE PDPDKRACAN DLLVDEFLKV
     SSKKKKTQPK LSALSAGSNE YLRSISLPVP VLVEDTSSSS EYGSVSPDDT ELKVDPFSFK
     TRAKSCGERD VKGIRTLFLG IPDENFEDHS APPSPEEKDS GFFMLRKDSE RRATLHRILT
     EDQDKIVRNL MESLAQGAEE PKLKWEHITT LIASLREFVR STDRKIIATT LSKLKLELDF
     DSHGISQVQV VLFGFQDAVN KVLRNHNIKP HWMFALDSII RKAVQTAITI LVPELRPHFS
     LASESDTADQ EDLDVEDDHE EQPSNQTVRR PQAVIEDAVA TSGVSTLSST VSHDSQSAHR
     SLNVQLGRMK IETNRLLEEL VRKEKELQAL LHRAIEEKDQ EIKHLKLKSQ PIEIPELPVF
     HLNSSGTNTE DSELTDWLRV NGADEDTISR FLAEDYTLLD VLYYVTRDDL KCLRLRGGML
     CTLWKAIIDF RNKQT
//