M3K21_HUMAN
ID M3K21_HUMAN Reviewed; 1036 AA.
AC Q5TCX8; A0A1W2PKR9; B2RN34; Q5TCX7; Q5TCX9; Q8WWN1; Q8WWN2; Q96JM1; X6R610;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 3.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase 21;
DE EC=2.7.11.25;
DE AltName: Full=Mitogen-activated protein kinase kinase kinase MLK4;
DE AltName: Full=Mixed lineage kinase 4;
GN Name=MAP3K21 {ECO:0000312|HGNC:HGNC:29798};
GN Synonyms=KIAA1804 {ECO:0000312|EMBL:BAB47433.1}, MLK4 {ECO:0000303|Ref.1};
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;
RN [1] {ECO:0000305, ECO:0000312|EMBL:CAC84640.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Heart {ECO:0000312|EMBL:CAC84639.1};
RA Kvasha S., Protopopov A., Rynditch A., Zabarovsky E., Kashuba V.;
RT "MLK4, a new member of mixed lineage kinases.";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000305, ECO:0000312|EMBL:BAB47433.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain {ECO:0000312|EMBL:BAB47433.1};
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4] {ECO:0000305, ECO:0000312|EMBL:CAC84640.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-528, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-614, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-528; THR-592 AND SER-614, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-528, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP FUNCTION, AND INTERACTION WITH TLR4.
RX PubMed=21602844; DOI=10.1038/cmi.2011.15;
RA Seit-Nebi A., Cheng W., Xu H., Han J.;
RT "MLK4 has negative effect on TLR4 signaling.";
RL Cell. Mol. Immunol. 9:27-33(2012).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-528 AND SER-614, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP VARIANTS [LARGE SCALE ANALYSIS] ASN-420; ASP-563; PHE-597; ILE-728;
RP ASP-741; GLY-784; TRP-892; ILE-900; CYS-977 AND LEU-982.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Negative regulator of TLR4 signaling. Does not activate
CC JNK1/MAPK8 pathway, p38/MAPK14, nor ERK2/MAPK1 pathways.
CC {ECO:0000269|PubMed:21602844}.
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:0000305};
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:0000305};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P80192};
CC -!- ACTIVITY REGULATION: Homodimerization via the leucine zipper domains is
CC required for autophosphorylation and subsequent activation.
CC {ECO:0000250|UniProtKB:Q16584}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with TLR4. {ECO:0000250,
CC ECO:0000269|PubMed:21602844}.
CC -!- INTERACTION:
CC Q5TCX8; O15111: CHUK; NbExp=2; IntAct=EBI-1057380, EBI-81249;
CC Q5TCX8; Q02779: MAP3K10; NbExp=3; IntAct=EBI-1057380, EBI-3392815;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1 {ECO:0000269|Ref.1}; Synonyms=MLK4beta;
CC IsoId=Q5TCX8-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|Ref.1}; Synonyms=MLK4alpha;
CC IsoId=Q5TCX8-2; Sequence=VSP_051733, VSP_051734;
CC Name=3;
CC IsoId=Q5TCX8-3; Sequence=VSP_051731, VSP_051732;
CC -!- PTM: Autophosphorylation on serine and threonine residues within the
CC activation loop plays a role in enzyme activation.
CC {ECO:0000250|UniProtKB:Q16584}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase kinase subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB47433.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ311797; CAC84639.1; -; mRNA.
DR EMBL; AJ311798; CAC84640.1; -; mRNA.
DR EMBL; AB058707; BAB47433.1; ALT_INIT; mRNA.
DR EMBL; AL133380; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471098; EAW69988.1; -; Genomic_DNA.
DR EMBL; BC136648; AAI36649.1; -; mRNA.
DR EMBL; BC136649; AAI36650.1; -; mRNA.
DR CCDS; CCDS1598.1; -. [Q5TCX8-1]
DR RefSeq; NP_115811.2; NM_032435.2. [Q5TCX8-1]
DR PDB; 4UYA; X-ray; 2.80 A; A=115-451.
DR PDBsum; 4UYA; -.
DR AlphaFoldDB; Q5TCX8; -.
DR SMR; Q5TCX8; -.
DR BioGRID; 124089; 99.
DR IntAct; Q5TCX8; 32.
DR STRING; 9606.ENSP00000355583; -.
DR BindingDB; Q5TCX8; -.
DR ChEMBL; CHEMBL3627584; -.
DR iPTMnet; Q5TCX8; -.
DR PhosphoSitePlus; Q5TCX8; -.
DR BioMuta; MAP3K21; -.
DR DMDM; 71153820; -.
DR EPD; Q5TCX8; -.
DR jPOST; Q5TCX8; -.
DR MassIVE; Q5TCX8; -.
DR MaxQB; Q5TCX8; -.
DR PaxDb; Q5TCX8; -.
DR PeptideAtlas; Q5TCX8; -.
DR PRIDE; Q5TCX8; -.
DR ProteomicsDB; 64992; -. [Q5TCX8-1]
DR ProteomicsDB; 64993; -. [Q5TCX8-2]
DR ProteomicsDB; 64994; -. [Q5TCX8-3]
DR Antibodypedia; 2080; 230 antibodies from 30 providers.
DR DNASU; 84451; -.
DR Ensembl; ENST00000366622.1; ENSP00000355581.1; ENSG00000143674.11. [Q5TCX8-3]
DR Ensembl; ENST00000366623.7; ENSP00000355582.3; ENSG00000143674.11. [Q5TCX8-2]
DR Ensembl; ENST00000366624.8; ENSP00000355583.3; ENSG00000143674.11. [Q5TCX8-1]
DR GeneID; 84451; -.
DR KEGG; hsa:84451; -.
DR MANE-Select; ENST00000366624.8; ENSP00000355583.3; NM_032435.3; NP_115811.2.
DR UCSC; uc001hvt.4; human. [Q5TCX8-1]
DR CTD; 84451; -.
DR DisGeNET; 84451; -.
DR GeneCards; MAP3K21; -.
DR HGNC; HGNC:29798; MAP3K21.
DR HPA; ENSG00000143674; Tissue enhanced (pancreas).
DR MIM; 614793; gene.
DR neXtProt; NX_Q5TCX8; -.
DR OpenTargets; ENSG00000143674; -.
DR VEuPathDB; HostDB:ENSG00000143674; -.
DR eggNOG; KOG0192; Eukaryota.
DR GeneTree; ENSGT00940000159629; -.
DR InParanoid; Q5TCX8; -.
DR OMA; DPEMPTP; -.
DR OrthoDB; 115270at2759; -.
DR PhylomeDB; Q5TCX8; -.
DR BRENDA; 2.7.11.25; 2681.
DR PathwayCommons; Q5TCX8; -.
DR SignaLink; Q5TCX8; -.
DR SIGNOR; Q5TCX8; -.
DR BioGRID-ORCS; 84451; 13 hits in 1060 CRISPR screens.
DR ChiTaRS; MAP3K21; human.
DR GenomeRNAi; 84451; -.
DR Pharos; Q5TCX8; Tbio.
DR PRO; PR:Q5TCX8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5TCX8; protein.
DR Bgee; ENSG00000143674; Expressed in kidney epithelium and 128 other tissues.
DR Genevisible; Q5TCX8; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004706; F:JUN kinase kinase kinase activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR016231; MLK1-4.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF14604; SH3_9; 1.
DR PIRSF; PIRSF000556; MAPKKK9_11; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Kinase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; SH3 domain; Transferase.
FT CHAIN 1..1036
FT /note="Mitogen-activated protein kinase kinase kinase 21"
FT /id="PRO_0000086268"
FT DOMAIN 38..102
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 124..401
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 425..446
FT /note="Leucine-zipper 1"
FT REGION 460..481
FT /note="Leucine-zipper 2"
FT REGION 517..551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 748..791
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 923..954
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..36
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 519..549
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 748..767
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 768..791
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 263
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q02779,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 130..138
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q02779,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 151
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q02779,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 299
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 303
FT /note="Phosphoserine; by autocatalysis and MAP4K1"
FT /evidence="ECO:0000250"
FT MOD_RES 528
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 543
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDG6"
FT MOD_RES 547
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDG6"
FT MOD_RES 592
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 614
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..554
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11347906"
FT /id="VSP_051731"
FT VAR_SEQ 555..559
FT /note="RAIQL -> MFFLV (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11347906"
FT /id="VSP_051732"
FT VAR_SEQ 559..570
FT /note="LTSDESNKTWGR -> CELSALPRGLLC (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_051733"
FT VAR_SEQ 571..1036
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_051734"
FT VARIANT 420
FT /note="D -> N (in dbSNP:rs35465006)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040729"
FT VARIANT 563
FT /note="E -> D (in dbSNP:rs35758282)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040730"
FT VARIANT 597
FT /note="S -> F (in dbSNP:rs34984140)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040731"
FT VARIANT 728
FT /note="V -> I (in dbSNP:rs3795375)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040732"
FT VARIANT 741
FT /note="E -> D (in dbSNP:rs3795374)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040733"
FT VARIANT 784
FT /note="C -> G (in dbSNP:rs963981)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040734"
FT VARIANT 892
FT /note="R -> W (in dbSNP:rs55681416)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040735"
FT VARIANT 900
FT /note="T -> I (in dbSNP:rs34499091)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040736"
FT VARIANT 977
FT /note="R -> C (in dbSNP:rs56065162)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040737"
FT VARIANT 982
FT /note="P -> L (in dbSNP:rs34794284)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040738"
FT CONFLICT 274
FT /note="K -> E (in Ref. 1; CAC84639/CAC84640)"
FT /evidence="ECO:0000305"
FT CONFLICT 330
FT /note="Y -> C (in Ref. 1; CAC84639/CAC84640)"
FT /evidence="ECO:0000305"
FT CONFLICT 687
FT /note="E -> G (in Ref. 1; CAC84640)"
FT /evidence="ECO:0000305"
FT CONFLICT 701
FT /note="S -> T (in Ref. 1; CAC84640)"
FT /evidence="ECO:0000305"
FT CONFLICT 705
FT /note="T -> A (in Ref. 1; CAC84640)"
FT /evidence="ECO:0000305"
FT CONFLICT 781
FT /note="P -> S (in Ref. 1; CAC84640)"
FT /evidence="ECO:0000305"
FT CONFLICT 872
FT /note="Q -> R (in Ref. 1; CAC84640)"
FT /evidence="ECO:0000305"
FT CONFLICT 1002
FT /note="A -> V (in Ref. 1; CAC84640)"
FT /evidence="ECO:0000305"
FT CONFLICT 1016
FT /note="C -> G (in Ref. 1; CAC84640)"
FT /evidence="ECO:0000305"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:4UYA"
FT STRAND 125..129
FT /evidence="ECO:0007829|PDB:4UYA"
FT STRAND 138..143
FT /evidence="ECO:0007829|PDB:4UYA"
FT STRAND 146..152
FT /evidence="ECO:0007829|PDB:4UYA"
FT HELIX 165..175
FT /evidence="ECO:0007829|PDB:4UYA"
FT STRAND 186..190
FT /evidence="ECO:0007829|PDB:4UYA"
FT STRAND 197..201
FT /evidence="ECO:0007829|PDB:4UYA"
FT HELIX 208..212
FT /evidence="ECO:0007829|PDB:4UYA"
FT HELIX 234..252
FT /evidence="ECO:0007829|PDB:4UYA"
FT STRAND 255..257
FT /evidence="ECO:0007829|PDB:4UYA"
FT HELIX 266..268
FT /evidence="ECO:0007829|PDB:4UYA"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:4UYA"
FT STRAND 285..287
FT /evidence="ECO:0007829|PDB:4UYA"
FT HELIX 313..316
FT /evidence="ECO:0007829|PDB:4UYA"
FT HELIX 323..339
FT /evidence="ECO:0007829|PDB:4UYA"
FT TURN 343..346
FT /evidence="ECO:0007829|PDB:4UYA"
FT HELIX 349..357
FT /evidence="ECO:0007829|PDB:4UYA"
FT HELIX 373..380
FT /evidence="ECO:0007829|PDB:4UYA"
FT HELIX 391..399
FT /evidence="ECO:0007829|PDB:4UYA"
FT HELIX 411..436
FT /evidence="ECO:0007829|PDB:4UYA"
FT CONFLICT Q5TCX8-2:566
FT /note="R -> P (in Ref. 1; CAC84639)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1036 AA; 113957 MW; 2520984802143069 CRC64;
MALRGAAGAT DTPVSSAGGA PGGSASSSST SSGGSASAGA GLWAALYDYE ARGEDELSLR
RGQLVEVLSQ DAAVSGDEGW WAGQVQRRLG IFPANYVAPC RPAASPAPPP SRPSSPVHVA
FERLELKELI GAGGFGQVYR ATWQGQEVAV KAARQDPEQD AAAAAESVRR EARLFAMLRH
PNIIELRGVC LQQPHLCLVL EFARGGALNR ALAAANAAPD PRAPGPRRAR RIPPHVLVNW
AVQIARGMLY LHEEAFVPIL HRDLKSSNIL LLEKIEHDDI CNKTLKITDF GLAREWHRTT
KMSTAGTYAW MAPEVIKSSL FSKGSDIWSY GVLLWELLTG EVPYRGIDGL AVAYGVAVNK
LTLPIPSTCP EPFAKLMKEC WQQDPHIRPS FALILEQLTA IEGAVMTEMP QESFHSMQDD
WKLEIQQMFD ELRTKEKELR SREEELTRAA LQQKSQEELL KRREQQLAER EIDVLERELN
ILIFQLNQEK PKVKKRKGKF KRSRLKLKDG HRISLPSDFQ HKITVQASPN LDKRRSLNSS
SSSPPSSPTM MPRLRAIQLT SDESNKTWGR NTVFRQEEFE DVKRNFKKKG CTWGPNSIQM
KDRTDCKERI RPLSDGNSPW STILIKNQKT MPLASLFVDQ PGSCEEPKLS PDGLEHRKPK
QIKLPSQAYI DLPLGKDAQR ENPAEAESWE EAASANAATV SIEMTPTNSL SRSPQRKKTE
SALYGCTVLL ASVALGLDLR ELHKAQAAEE PLPKEEKKKR EGIFQRASKS RRSASPPTSL
PSTCGEASSP PSLPLSSALG ILSTPSFSTK CLLQMDSEDP LVDSAPVTCD SEMLTPDFCP
TAPGSGREPA LMPRLDTDCS VSRNLPSSFL QQTCGNVPYC ASSKHRPSHH RRTMSDGNPT
PTGATIISAT GASALPLCPS PAPHSHLPRE VSPKKHSTVH IVPQRRPASL RSRSDLPQAY
PQTAVSQLAQ TACVVGRPGP HPTQFLAAKE RTKSHVPSLL DADVEGQSRD YTVPLCRMRS
KTSRPSIYEL EKEFLS
