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 27-MAR-2024, entry version 205. DE RecName: Full=MAP/microtubule affinity-regulating kinase 4 {ECO:0000305}; 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 {ECO:0000303|PubMed:11326310}; GN Name=MARK4 {ECO:0000303|PubMed:14594945, ECO:0000312|HGNC:HGNC:13538}; GN Synonyms=KIAA1860 {ECO:0000303|PubMed:11347906}, MARKL1 GN {ECO:0000303|PubMed:11326310}; 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 FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NLRP3. RX PubMed=28656979; DOI=10.1038/ncomms15986; RA Li X., Thome S., Ma X., Amrute-Nayak M., Finigan A., Kitt L., Masters L., RA James J.R., Shi Y., Meng G., Mallat Z.; RT "MARK4 regulates NLRP3 positioning and inflammasome activation through a RT microtubule-dependent mechanism."; RL Nat. Commun. 8:15986-15986(2017). RN [17] 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 Involved in NLRP3 positioning along microtubules by mediating NLRP3 CC recruitment to microtubule organizing center (MTOC) upon inflammasome CC activation (PubMed:28656979). {ECO:0000250|UniProtKB:Q8CIP4, CC ECO:0000269|PubMed:14594945, ECO:0000269|PubMed:15009667, CC ECO:0000269|PubMed:23184942, ECO:0000269|PubMed:23400999, CC ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:25123532, CC ECO:0000269|PubMed:28656979}. 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). Interacts with NLRP3; promoting NLRP3 recruitment to CC microtubule organizing center (MTOC) (PubMed:28656979). CC {ECO:0000269|PubMed:14594945, ECO:0000269|PubMed:16959763, CC ECO:0000269|PubMed:18254724, ECO:0000269|PubMed:23400999, CC ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:28656979}. 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=7; 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, ECO:0000269|PubMed:28656979}. Cytoplasm, CC cytoskeleton, cilium basal body {ECO:0000269|PubMed:23400999}. CC Cytoplasm, cytoskeleton, cilium axoneme {ECO:0000269|PubMed:23400999}. CC Cytoplasm {ECO:0000269|PubMed:23400999, ECO:0000269|PubMed:23666762}. CC Cell projection, dendrite {ECO:0000269|PubMed:23666762}. Note=Localized CC at the tips of neurite-like processes in differentiated neuroblast CC cells. 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="https://atlasgeneticsoncology.org/gene/419/MARK4"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 74. DR IntAct; Q96L34; 41. 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 CPTAC; non-CPTAC-5644; -. DR EPD; Q96L34; -. DR jPOST; Q96L34; -. DR MassIVE; Q96L34; -. DR MaxQB; Q96L34; -. DR PaxDb; 9606-ENSP00000262891; -. DR PeptideAtlas; Q96L34; -. DR ProteomicsDB; 77145; -. [Q96L34-1] DR ProteomicsDB; 77146; -. [Q96L34-2] DR Pumba; Q96L34; -. DR Antibodypedia; 31285; 423 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 AGR; HGNC:13538; -. 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; LLRFTWN; -. DR OrthoDB; 5475340at2759; -. 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; 12 hits in 1188 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 200 other cell types or tissues. DR ExpressionAtlas; Q96L34; baseline and differential. 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:0008093; F:cytoskeletal anchor activity; IDA: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:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; IDA:UniProtKB. 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 CDD; cd12197; MARK4_C; 1. DR CDD; cd14072; STKc_MARK; 1. DR CDD; cd14407; UBA_MARK3_4; 1. DR Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1. DR Gene3D; 3.30.310.80; Kinase associated domain 1, KA1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR028375; KA1/Ssp2_C. DR InterPro; IPR001772; KA1_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR049508; MARK1-4_cat. 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 PANTHER; PTHR24346; MAP/MICROTUBULE AFFINITY-REGULATING KINASE; 1. DR PANTHER; PTHR24346:SF28; MAP_MICROTUBULE AFFINITY-REGULATING KINASE 4; 1. 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; KA1-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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. DR Genevisible; Q96L34; HS. 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 //