MARK4_HUMAN
ID MARK4_HUMAN Reviewed; 752 AA.
AC Q96L34; Q8NG37; Q96JG7; Q96SQ2; Q9BYD8;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=MAP/microtubule affinity-regulating kinase 4;
DE EC=2.7.11.1 {ECO:0000269|PubMed:14594945, ECO:0000269|PubMed:15009667, ECO:0000269|PubMed:23184942};
DE AltName: Full=MAP/microtubule affinity-regulating kinase-like 1;
GN Name=MARK4; Synonyms=KIAA1860, MARKL1;
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=11326310; DOI=10.1038/sj.neo.7900132;
RA Kato T., Satoh S., Okabe H., Kitahara O., Ono K., Kihara C., Tanaka T.,
RA Tsunoda T., Yamaoka Y., Nakamura Y., Furukawa Y.;
RT "Isolation of a novel human gene, MARKL1, homologous to MARK3 and its
RT involvement in hepatocellular carcinogenesis.";
RL Neoplasia 3:4-9(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, INTERACTION WITH GAMMA-TUBULIN, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=14594945; DOI=10.1074/jbc.m304528200;
RA Trinczek B., Brajenovic M., Ebneth A., Drewes G.;
RT "MARK4 is a novel microtubule-associated proteins/microtubule affinity-
RT regulating kinase that binds to the cellular microtubule network and to
RT centrosomes.";
RL J. Biol. Chem. 279:5915-5923(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=15009667; DOI=10.1046/j.1471-4159.2003.02228.x;
RA Schneider A., Laage R., von Ahsen O., Fischer A., Rossner M., Scheek S.,
RA Grunewald S., Kuner R., Weber D., Kruger C., Klaussner B., Gotz B.,
RA Hiemisch H., Newrzella D., Martin-Villalba A., Bach A., Schwaninger M.;
RT "Identification of regulated genes during permanent focal cerebral
RT ischaemia: characterization of the protein kinase 9b5/MARKL1/MARK4.";
RL J. Neurochem. 88:1114-1126(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Beghini A., Magnani I., Roversi G., Piepoli T., DiTerlizzi S., Pollo B.,
RA Conti A.M.F., Cowell J.K., Finocchiaro G., Larizza L.;
RT "Neural progenitor-restricted isoform of MARKL1 gene is upregulated by
RT 19q13 amplification in human glioblastoma.";
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Thyroid;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP ACTIVITY REGULATION, PHOSPHORYLATION AT THR-214, AND MUTAGENESIS OF
RP THR-214.
RX PubMed=14976552; DOI=10.1038/sj.emboj.7600110;
RA Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J.,
RA Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R.;
RT "LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily,
RT including MARK/PAR-1.";
RL EMBO J. 23:833-843(2004).
RN [8]
RP INTERACTION WITH YWHAQ.
RX PubMed=16959763; DOI=10.1074/mcp.m600147-mcp200;
RA Angrand P.O., Segura I., Voelkel P., Ghidelli S., Terry R., Brajenovic M.,
RA Vintersten K., Klein R., Superti-Furga G., Drewes G., Kuster B.,
RA Bouwmeester T., Acker-Palmer A.;
RT "Transgenic mouse proteomics identifies new 14-3-3-associated proteins
RT involved in cytoskeletal rearrangements and cell signaling.";
RL Mol. Cell. Proteomics 5:2211-2227(2006).
RN [9]
RP UBIQUITINATION, DEUBIQUITINATION BY USP9X, AND INTERACTION WITH USP9X.
RX PubMed=18254724; DOI=10.1042/bj20080067;
RA Al-Hakim A.K., Zagorska A., Chapman L., Deak M., Peggie M., Alessi D.R.;
RT "Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-
RT linked polyubiquitin chains.";
RL Biochem. J. 411:249-260(2008).
RN [10]
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 [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF THR-214.
RX PubMed=23184942; DOI=10.1074/jbc.c112.396903;
RA Li L., Guan K.L.;
RT "Microtubule-associated protein/microtubule affinity-regulating kinase 4
RT (MARK4) is a negative regulator of the mammalian target of rapamycin
RT complex 1 (mTORC1).";
RL J. Biol. Chem. 288:703-708(2013).
RN [12]
RP FUNCTION, INTERACTION WITH ODF2, AND SUBCELLULAR LOCATION.
RX PubMed=23400999; DOI=10.1083/jcb.201206013;
RA Kuhns S., Schmidt K.N., Reymann J., Gilbert D.F., Neuner A., Hub B.,
RA Carvalho R., Wiedemann P., Zentgraf H., Erfle H., Klingmuller U.,
RA Boutros M., Pereira G.;
RT "The microtubule affinity regulating kinase MARK4 promotes axoneme
RT extension during early ciliogenesis.";
RL J. Cell Biol. 200:505-522(2013).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-543, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
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 [14]
RP FUNCTION, INTERACTION WITH MAPT, AND SUBCELLULAR LOCATION.
RX PubMed=23666762; DOI=10.1007/s12017-013-8232-3;
RA Gu G.J., Lund H., Wu D., Blokzijl A., Classon C., von Euler G.,
RA Landegren U., Sunnemark D., Kamali-Moghaddam M.;
RT "Role of individual MARK isoforms in phosphorylation of tau at Ser262 in
RT Alzheimer's disease.";
RL NeuroMolecular Med. 15:458-469(2013).
RN [15]
RP FUNCTION, DEVELOPMENTAL STAGE, AND PHOSPHORYLATION.
RX PubMed=25123532; DOI=10.1016/j.ejcb.2014.07.004;
RA Rovina D., Fontana L., Monti L., Novielli C., Panini N., Sirchia S.M.,
RA Erba E., Magnani I., Larizza L.;
RT "Microtubule-associated protein/microtubule affinity-regulating kinase 4
RT (MARK4) plays a role in cell cycle progression and cytoskeletal dynamics.";
RL Eur. J. Cell Biol. 93:355-365(2014).
RN [16]
RP VARIANTS [LARGE SCALE ANALYSIS] GLN-377 AND CYS-418.
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: Serine/threonine-protein kinase (PubMed:15009667,
CC PubMed:14594945, PubMed:23666762, PubMed:23184942). Phosphorylates the
CC microtubule-associated protein MAPT/TAU (PubMed:14594945,
CC PubMed:23666762). Also phosphorylates the microtubule-associated
CC proteins MAP2 and MAP4 (PubMed:14594945). Involved in regulation of the
CC microtubule network, causing reorganization of microtubules into
CC bundles (PubMed:14594945, PubMed:25123532). Required for the initiation
CC of axoneme extension during cilium assembly (PubMed:23400999).
CC Regulates the centrosomal location of ODF2 and phosphorylates ODF2 in
CC vitro (PubMed:23400999). Plays a role in cell cycle progression,
CC specifically in the G1/S checkpoint (PubMed:25123532). Reduces neuronal
CC cell survival (PubMed:15009667). Plays a role in energy homeostasis by
CC regulating satiety and metabolic rate (By similarity). Promotes
CC adipogenesis by activating JNK1 and inhibiting the p38MAPK pathway, and
CC triggers apoptosis by activating the JNK1 pathway (By similarity).
CC Phosphorylates mTORC1 complex member RPTOR and acts as a negative
CC regulator of the mTORC1 complex, probably due to disruption of the
CC interaction between phosphorylated RPTOR and the RRAGA/RRAGC
CC heterodimer which is required for mTORC1 activation (PubMed:23184942).
CC {ECO:0000250|UniProtKB:Q8CIP4, ECO:0000269|PubMed:14594945,
CC ECO:0000269|PubMed:15009667, ECO:0000269|PubMed:23184942,
CC ECO:0000269|PubMed:23400999, ECO:0000269|PubMed:23666762,
CC ECO:0000269|PubMed:25123532}.
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=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:14594945, ECO:0000269|PubMed:15009667,
CC ECO:0000269|PubMed:23184942};
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=2.7.11.1; Evidence={ECO:0000269|PubMed:14594945,
CC ECO:0000269|PubMed:15009667, ECO:0000269|PubMed:23184942};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:14594945};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-214.
CC {ECO:0000269|PubMed:14976552}.
CC -!- SUBUNIT: Interacts with MAPT/TAU (PubMed:23666762). Interacts with
CC gamma-tubulin (PubMed:14594945). Interacts with ODF2 (PubMed:23400999).
CC Interacts with USP9X (PubMed:18254724). Interacts with YWHAQ
CC (PubMed:16959763). {ECO:0000269|PubMed:14594945,
CC ECO:0000269|PubMed:16959763, ECO:0000269|PubMed:18254724,
CC ECO:0000269|PubMed:23400999, ECO:0000269|PubMed:23666762}.
CC -!- INTERACTION:
CC Q96L34; Q06481-5: APLP2; NbExp=3; IntAct=EBI-302319, EBI-25646567;
CC Q96L34; P05067: APP; NbExp=3; IntAct=EBI-302319, EBI-77613;
CC Q96L34; P60953: CDC42; NbExp=2; IntAct=EBI-302319, EBI-81752;
CC Q96L34; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-302319, EBI-9087876;
CC Q96L34; Q15323: KRT31; NbExp=3; IntAct=EBI-302319, EBI-948001;
CC Q96L34; P07948: LYN; NbExp=3; IntAct=EBI-302319, EBI-79452;
CC Q96L34; Q9BYG4: PARD6G; NbExp=2; IntAct=EBI-302319, EBI-295417;
CC Q96L34; Q8ND90: PNMA1; NbExp=2; IntAct=EBI-302319, EBI-302345;
CC Q96L34; P41743: PRKCI; NbExp=2; IntAct=EBI-302319, EBI-286199;
CC Q96L34; Q15831: STK11; NbExp=2; IntAct=EBI-302319, EBI-306838;
CC Q96L34; P23258: TUBG1; NbExp=4; IntAct=EBI-302319, EBI-302589;
CC Q96L34; Q04917: YWHAH; NbExp=6; IntAct=EBI-302319, EBI-306940;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000269|PubMed:14594945}. Cytoplasm,
CC cytoskeleton, microtubule organizing center
CC {ECO:0000269|PubMed:14594945}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000269|PubMed:23400999}. Cytoplasm, cytoskeleton, cilium
CC axoneme {ECO:0000269|PubMed:23400999}. Cytoplasm
CC {ECO:0000269|PubMed:23400999, ECO:0000269|PubMed:23666762}. Cell
CC projection, dendrite {ECO:0000269|PubMed:23666762}. Note=Localized at
CC the tips of neurite-like processes in differentiated neuroblast cells.
CC Detected in the cytoplasm and neuropil of the hippocampus.
CC {ECO:0000269|PubMed:14594945, ECO:0000269|PubMed:23666762}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=MARK4L;
CC IsoId=Q96L34-1; Sequence=Displayed;
CC Name=2; Synonyms=MARKL1S, MARK4S;
CC IsoId=Q96L34-2; Sequence=VSP_004946;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Isoform 2 is brain-specific
CC (PubMed:11326310). Expressed at highest levels in brain and testis.
CC Also expressed in heart, lung, liver, muscle, kidney and spleen
CC (PubMed:14594945). {ECO:0000269|PubMed:11326310,
CC ECO:0000269|PubMed:14594945}.
CC -!- DEVELOPMENTAL STAGE: Expressed at all stages of the mitotic cell cycle.
CC {ECO:0000269|PubMed:25123532}.
CC -!- PTM: Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins
CC which appear to impede LKB1-mediated phosphorylation. Deubiquitinated
CC by USP9X. {ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:18254724}.
CC -!- PTM: Phosphorylated at Thr-214 by STK11/LKB1 in complex with STE20-
CC related adapter-alpha (STRADA) pseudo kinase and CAB39
CC (PubMed:14976552). Phosphorylated throughout the cell cycle
CC (PubMed:25123532). {ECO:0000269|PubMed:14976552,
CC ECO:0000269|PubMed:25123532}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB47489.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB55238.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MARK4ID419.html";
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DR EMBL; AB049127; BAB39380.1; -; mRNA.
DR EMBL; AB088047; BAC03375.1; -; mRNA.
DR EMBL; AY057448; AAL23683.1; -; mRNA.
DR EMBL; AX305105; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AX305106; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY120867; AAM55491.1; -; mRNA.
DR EMBL; AB058763; BAB47489.1; ALT_INIT; mRNA.
DR EMBL; AK027619; BAB55238.1; ALT_INIT; mRNA.
DR EMBL; AK075272; BAC11510.1; -; mRNA.
DR CCDS; CCDS12658.1; -. [Q96L34-2]
DR CCDS; CCDS56097.1; -. [Q96L34-1]
DR RefSeq; NP_001186796.1; NM_001199867.1. [Q96L34-1]
DR RefSeq; NP_113605.2; NM_031417.3. [Q96L34-2]
DR PDB; 5ES1; X-ray; 2.80 A; A=44-370.
DR PDBsum; 5ES1; -.
DR AlphaFoldDB; Q96L34; -.
DR SMR; Q96L34; -.
DR BioGRID; 121760; 61.
DR IntAct; Q96L34; 40.
DR MINT; Q96L34; -.
DR STRING; 9606.ENSP00000262891; -.
DR BindingDB; Q96L34; -.
DR ChEMBL; CHEMBL5754; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q96L34; -.
DR GuidetoPHARMACOLOGY; 2100; -.
DR GlyGen; Q96L34; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96L34; -.
DR PhosphoSitePlus; Q96L34; -.
DR BioMuta; MARK4; -.
DR DMDM; 29840797; -.
DR EPD; Q96L34; -.
DR jPOST; Q96L34; -.
DR MassIVE; Q96L34; -.
DR MaxQB; Q96L34; -.
DR PaxDb; Q96L34; -.
DR PeptideAtlas; Q96L34; -.
DR PRIDE; Q96L34; -.
DR ProteomicsDB; 77145; -. [Q96L34-1]
DR ProteomicsDB; 77146; -. [Q96L34-2]
DR Antibodypedia; 31285; 387 antibodies from 37 providers.
DR DNASU; 57787; -.
DR Ensembl; ENST00000262891.9; ENSP00000262891.3; ENSG00000007047.16. [Q96L34-1]
DR Ensembl; ENST00000300843.8; ENSP00000300843.3; ENSG00000007047.16. [Q96L34-2]
DR GeneID; 57787; -.
DR KEGG; hsa:57787; -.
DR MANE-Select; ENST00000262891.9; ENSP00000262891.3; NM_001199867.2; NP_001186796.1.
DR UCSC; uc002pba.3; human. [Q96L34-1]
DR CTD; 57787; -.
DR DisGeNET; 57787; -.
DR GeneCards; MARK4; -.
DR HGNC; HGNC:13538; MARK4.
DR HPA; ENSG00000007047; Low tissue specificity.
DR MIM; 606495; gene.
DR neXtProt; NX_Q96L34; -.
DR OpenTargets; ENSG00000007047; -.
DR PharmGKB; PA30641; -.
DR VEuPathDB; HostDB:ENSG00000007047; -.
DR eggNOG; KOG0586; Eukaryota.
DR GeneTree; ENSGT00940000159555; -.
DR HOGENOM; CLU_000288_157_5_1; -.
DR InParanoid; Q96L34; -.
DR OMA; CHLPWDK; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; Q96L34; -.
DR TreeFam; TF315213; -.
DR PathwayCommons; Q96L34; -.
DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane.
DR SignaLink; Q96L34; -.
DR SIGNOR; Q96L34; -.
DR BioGRID-ORCS; 57787; 11 hits in 1108 CRISPR screens.
DR ChiTaRS; MARK4; human.
DR GeneWiki; MARK4; -.
DR GenomeRNAi; 57787; -.
DR Pharos; Q96L34; Tchem.
DR PRO; PR:Q96L34; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q96L34; protein.
DR Bgee; ENSG00000007047; Expressed in cortical plate and 198 other tissues.
DR ExpressionAtlas; Q96L34; baseline and differential.
DR Genevisible; Q96L34; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IMP:CACAO.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0000930; C:gamma-tubulin complex; IDA:ARUK-UCL.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005815; C:microtubule organizing center; IDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:ARUK-UCL.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; NAS:UniProtKB.
DR GO; GO:0043015; F:gamma-tubulin binding; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0048156; F:tau protein binding; NAS:ARUK-UCL.
DR GO; GO:0050321; F:tau-protein kinase activity; IDA:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; NAS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0044782; P:cilium organization; IGI:ARUK-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0001578; P:microtubule bundle formation; IEP:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IDA:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; IDA:ARUK-UCL.
DR GO; GO:0045724; P:positive regulation of cilium assembly; IMP:ARUK-UCL.
DR GO; GO:0043068; P:positive regulation of programmed cell death; NAS:UniProtKB.
DR GO; GO:1904781; P:positive regulation of protein localization to centrosome; IMP:ARUK-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0046605; P:regulation of centrosome cycle; IMP:ARUK-UCL.
DR InterPro; IPR028375; KA1/Ssp2_C.
DR InterPro; IPR001772; KA1_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR015940; UBA.
DR Pfam; PF02149; KA1; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00627; UBA; 1.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00165; UBA; 1.
DR SUPFAM; SSF103243; SSF103243; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50032; KA1; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50030; UBA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell cycle; Cell division;
KW Cell projection; Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton;
KW Kinase; Mitosis; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..752
FT /note="MAP/microtubule affinity-regulating kinase 4"
FT /id="PRO_0000086307"
FT DOMAIN 59..310
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 324..368
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 703..752
FT /note="KA1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00565"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 385..614
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 390..413
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 441..455
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 459..480
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 494..511
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 527..552
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 181
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 65..73
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 88
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 214
FT /note="Phosphothreonine; by LKB1"
FT /evidence="ECO:0000269|PubMed:14976552"
FT MOD_RES 423
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CIP4"
FT MOD_RES 543
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 628..752
FT /note="ADEPERIGGPEVTSCHLPWDQTETAPRLLRFPWSVKLTSSRPPEALMAALRQ
FT ATAAARCRCRQPQPFLLACLHGGAGGPEPLSHFEVEVCQLPRPGLRGVLFRRVAGTALA
FT FRTLVTRISNDLEL -> TLDPSKRQNSNRCVSGASLPQGSKIRSQTNLRESGDLRSQV
FT AIYLGIKRKPPPGCSDSPGV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11326310,
FT ECO:0000303|PubMed:11347906"
FT /id="VSP_004946"
FT VARIANT 377
FT /note="R -> Q (in dbSNP:rs35070611)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040766"
FT VARIANT 418
FT /note="R -> C (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs780763668)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040767"
FT MUTAGEN 214
FT /note="T->A: Prevents phosphorylation and activation by
FT STK11/LKB1 complex."
FT /evidence="ECO:0000269|PubMed:14976552"
FT MUTAGEN 214
FT /note="T->E: Mimicks phosphorylation state, leading to
FT increased activity. Decreases mTORC1 activity."
FT /evidence="ECO:0000269|PubMed:14976552,
FT ECO:0000269|PubMed:23184942"
FT CONFLICT 70
FT /note="F -> S (in Ref. 1; BAB39380/BAC03375)"
FT /evidence="ECO:0000305"
FT CONFLICT 518
FT /note="P -> L (in Ref. 6; BAB55238)"
FT /evidence="ECO:0000305"
FT STRAND 59..67
FT /evidence="ECO:0007829|PDB:5ES1"
FT STRAND 69..78
FT /evidence="ECO:0007829|PDB:5ES1"
FT TURN 79..81
FT /evidence="ECO:0007829|PDB:5ES1"
FT STRAND 84..91
FT /evidence="ECO:0007829|PDB:5ES1"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:5ES1"
FT HELIX 97..111
FT /evidence="ECO:0007829|PDB:5ES1"
FT STRAND 121..126
FT /evidence="ECO:0007829|PDB:5ES1"
FT STRAND 128..135
FT /evidence="ECO:0007829|PDB:5ES1"
FT HELIX 143..150
FT /evidence="ECO:0007829|PDB:5ES1"
FT HELIX 155..174
FT /evidence="ECO:0007829|PDB:5ES1"
FT STRAND 186..189
FT /evidence="ECO:0007829|PDB:5ES1"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:5ES1"
FT TURN 219..221
FT /evidence="ECO:0007829|PDB:5ES1"
FT HELIX 224..228
FT /evidence="ECO:0007829|PDB:5ES1"
FT HELIX 235..251
FT /evidence="ECO:0007829|PDB:5ES1"
FT HELIX 261..270
FT /evidence="ECO:0007829|PDB:5ES1"
FT HELIX 281..290
FT /evidence="ECO:0007829|PDB:5ES1"
FT TURN 295..297
FT /evidence="ECO:0007829|PDB:5ES1"
FT HELIX 301..304
FT /evidence="ECO:0007829|PDB:5ES1"
FT HELIX 308..311
FT /evidence="ECO:0007829|PDB:5ES1"
FT HELIX 332..339
FT /evidence="ECO:0007829|PDB:5ES1"
FT TURN 340..342
FT /evidence="ECO:0007829|PDB:5ES1"
FT HELIX 345..352
FT /evidence="ECO:0007829|PDB:5ES1"
FT TURN 353..355
FT /evidence="ECO:0007829|PDB:5ES1"
FT HELIX 359..366
FT /evidence="ECO:0007829|PDB:5ES1"
FT TURN 367..369
FT /evidence="ECO:0007829|PDB:5ES1"
SQ SEQUENCE 752 AA; 82520 MW; 4B430FFD2B150E7A CRC64;
MSSRTVLAPG NDRNSDTHGT LGSGRSSDKG PSWSSRSLGA RCRNSIASCP EEQPHVGNYR
LLRTIGKGNF AKVKLARHIL TGREVAIKII DKTQLNPSSL QKLFREVRIM KGLNHPNIVK
LFEVIETEKT LYLVMEYASA GEVFDYLVSH GRMKEKEARA KFRQIVSAVH YCHQKNIVHR
DLKAENLLLD AEANIKIADF GFSNEFTLGS KLDTFCGSPP YAAPELFQGK KYDGPEVDIW
SLGVILYTLV SGSLPFDGHN LKELRERVLR GKYRVPFYMS TDCESILRRF LVLNPAKRCT
LEQIMKDKWI NIGYEGEELK PYTEPEEDFG DTKRIEVMVG MGYTREEIKE SLTSQKYNEV
TATYLLLGRK TEEGGDRGAP GLALARVRAP SDTTNGTSSS KGTSHSKGQR SSSSTYHRQR
RHSDFCGPSP APLHPKRSPT STGEAELKEE RLPGRKASCS TAGSGSRGLP PSSPMVSSAH
NPNKAEIPER RKDSTSTPNN LPPSMMTRRN TYVCTERPGA ERPSLLPNGK ENSSGTPRVP
PASPSSHSLA PPSGERSRLA RGSTIRSTFH GGQVRDRRAG GGGGGGVQNG PPASPTLAHE
AAPLPAGRPR PTTNLFTKLT SKLTRRVADE PERIGGPEVT SCHLPWDQTE TAPRLLRFPW
SVKLTSSRPP EALMAALRQA TAAARCRCRQ PQPFLLACLH GGAGGPEPLS HFEVEVCQLP
RPGLRGVLFR RVAGTALAFR TLVTRISNDL EL
