ID KLK8_HUMAN Reviewed; 260 AA. AC O60259; Q5V9X1; Q5V9X2; Q8IW69; Q9HCB3; Q9NR68; Q9NR69; Q9UIL9; Q9UQ47; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 28-JAN-2026, entry version 204. DE RecName: Full=Kallikrein-8; DE Short=hK8; DE EC=3.4.21.118; DE AltName: Full=Neuropsin; DE Short=NP; DE AltName: Full=Ovasin; DE AltName: Full=Serine protease 19; DE AltName: Full=Serine protease TADG-14; DE AltName: Full=Tumor-associated differentially expressed gene 14 protein; DE Flags: Precursor; GN Name=KLK8; Synonyms=NRPN, PRSS19, TADG14; ORFNames=UNQ283/PRO322; 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 [GENOMIC DNA / MRNA] (ISOFORM 1). RC TISSUE=Hippocampus; RX PubMed=9714609; DOI=10.1016/s0378-1119(98)00232-7; RA Yoshida S., Taniguchi M., Hirata A., Shiosaka S.; RT "Sequence analysis and expression of human neuropsin cDNA and gene."; RL Gene 213:9-16(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Ovary; RX PubMed=10485494; RA Underwood L.J., Tanimoto H., Wang Y., Shigemasa K., Parmley T.H., RA O'Brien T.J.; RT "Cloning of tumor-associated differentially expressed gene-14, a novel RT serine protease overexpressed by ovarian carcinoma."; RL Cancer Res. 59:4435-4439(1999). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain; RX PubMed=10102990; DOI=10.1046/j.1432-1327.1999.00213.x; RA Mitsui S., Tsuruoka N., Yamashiro K., Nakazato H., Yamaguchi N.; RT "A novel form of human neuropsin, a brain-related serine protease, is RT generated by alternative splicing and is expressed preferentially in human RT adult brain."; RL Eur. J. Biochem. 260:627-634(1999). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11054574; DOI=10.1016/s0378-1119(00)00382-6; RA Gan L., Lee I., Smith R., Argonza-Barrett R., Lei H., McCuaig J., Moss P., RA Paeper B., Wang K.; RT "Sequencing and expression analysis of the serine protease gene cluster RT located in chromosome 19q13 region."; RL Gene 257:119-130(2000). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 3 AND 4), AND TISSUE RP SPECIFICITY. RX PubMed=11309326; RA Magklara A., Scorilas A., Katsaros D., Massobrio M., Yousef G.M., RA Fracchioli S., Danese S., Diamandis E.P.; RT "The human KLK8 (neuropsin/ovasin) gene: identification of two novel splice RT variants and its prognostic value in ovarian cancer."; RL Clin. Cancer Res. 7:806-811(2001). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). RA Gan L., Gelinas R., Gown A.M., Moss P., Smith R., Wang K.; RT "Molecular cloning and characterization of a novel serine protease, ovasin, RT a potential molecular marker for ovarian carcinomas."; RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RA Michael I.P., Diamandis E.P.; RT "Human kallikrein 8 and human kallikrein 9 are organized as a bicistronic RT operon."; RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [10] 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 [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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 [12] RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2). RX PubMed=15282331; DOI=10.1093/molbev/msh220; RA Li Y., Qian Y.-P., Yu X.-J., Wang Y.-Q., Dong D.-G., Sun W., Ma R.-M., RA Su B.; RT "Recent origin of a hominoid-specific splice form of neuropsin, a gene RT involved in learning and memory."; RL Mol. Biol. Evol. 21:2111-2115(2004). RN [13] RP TISSUE SPECIFICITY. RX PubMed=11522960; DOI=10.1097/00001756-200108280-00031; RA Shimizu-Okabe C., Yousef G.M., Diamandis E.P., Yoshida S., Shiosaka S., RA Fahnestock M.; RT "Expression of the kallikrein gene family in normal and Alzheimer's disease RT brain."; RL NeuroReport 12:2747-2751(2001). RN [14] RP TISSUE SPECIFICITY. RX PubMed=12147714; DOI=10.1136/mp.55.4.235; RA Kuwae K., Matsumoto-Miyai K., Yoshida S., Sadayama T., Yoshikawa K., RA Hosokawa K., Shiosaka S.; RT "Epidermal expression of serine protease, neuropsin (KLK8) in normal and RT pathological skin samples."; RL Mol. Pathol. 55:235-241(2002). RN [15] RP USE AS A MARKER FOR OVARIAN CANCER. RX PubMed=12782581; RA Kishi T., Grass L., Soosaipillai A., Scorilas A., Harbeck N., RA Schmalfeldt B., Dorn J., Mysliwiec M., Schmitt M., Diamandis E.P.; RT "Human kallikrein 8, a novel biomarker for ovarian carcinoma."; RL Cancer Res. 63:2771-2774(2003). RN [16] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=16337200; DOI=10.1016/j.febslet.2005.11.039; RA Rajapakse S., Ogiwara K., Takano N., Moriyama A., Takahashi T.; RT "Biochemical characterization of human kallikrein 8 and its possible RT involvement in the degradation of extracellular matrix proteins."; RL FEBS Lett. 579:6879-6884(2005). RN [17] RP ALTERNATIVE SPLICING (ISOFORM 2). RX PubMed=17487847; DOI=10.1002/humu.20547; RA Lu Z.-X., Peng J., Su B.; RT "A human-specific mutation leads to the origin of a novel splice form of RT neuropsin (KLK8), a gene involved in learning and memory."; RL Hum. Mutat. 28:978-984(2007). RN [18] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=17761692; DOI=10.1093/jb/mvm156; RA Scott F.L., Sun J., Whisstock J.C., Kato K., Bird P.I.; RT "SerpinB6 is an inhibitor of kallikrein-8 in keratinocytes."; RL J. Biochem. 142:435-442(2007). RN [19] RP INTERACTION WITH SPINK9. RX PubMed=19194479; DOI=10.1038/jid.2008.448; RA Brattsand M., Stefansson K., Hubiche T., Nilsson S.K., Egelrud T.; RT "SPINK9: a selective, skin-specific Kazal-type serine protease inhibitor."; RL J. Invest. Dermatol. 129:1656-1665(2009). CC -!- FUNCTION: Serine protease which is capable of degrading a number of CC proteins such as casein, fibrinogen, kininogen, fibronectin and CC collagen type IV. Also cleaves L1CAM in response to increased neural CC activity. Induces neurite outgrowth and fasciculation of cultured CC hippocampal neurons. Plays a role in the formation and maturation of CC orphan and small synaptic boutons in the Schaffer-collateral pathway, CC regulates Schaffer-collateral long-term potentiation in the hippocampus CC and is required for memory acquisition and synaptic plasticity. CC Involved in skin desquamation and keratinocyte proliferation. Plays a CC role in the secondary phase of pathogenesis following spinal cord CC injury. {ECO:0000269|PubMed:16337200}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Cleavage of amide substrates following the basic amino acids CC Arg or Lys at the P1 position, with a preference for Arg over Lys.; CC EC=3.4.21.118; Evidence={ECO:0000269|PubMed:16337200}; CC -!- ACTIVITY REGULATION: Inhibited by a range of serine protease inhibitors CC including antipain, aprotinin, leupeptin, benzamidine and soybean CC trypsin inhibitor. {ECO:0000269|PubMed:16337200}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.07 mM for Pro-Phe-Arg-MCA {ECO:0000269|PubMed:16337200}; CC KM=0.07 mM for Z-Val-Val-Arg-MCA {ECO:0000269|PubMed:16337200}; CC KM=0.07 mM for Boc-Val-Pro-Arg-MCA {ECO:0000269|PubMed:16337200}; CC KM=0.10 mM for Boc-Leu-Lys-Arg-MCA {ECO:0000269|PubMed:16337200}; CC KM=0.10 mM for Boc-Val-Leu-Lys-MCA {ECO:0000269|PubMed:16337200}; CC KM=0.07 mM for Boc-Phe-Ser-Arg-MCA {ECO:0000269|PubMed:16337200}; CC Vmax=7.1 umol/min/mg enzyme toward Pro-Phe-Arg-MCA CC {ECO:0000269|PubMed:16337200}; CC Vmax=5.4 umol/min/mg enzyme toward Z-Val-Val-Arg-MCA CC {ECO:0000269|PubMed:16337200}; CC Vmax=3.9 umol/min/mg enzyme toward Boc-Val-Pro-Arg-MCA CC {ECO:0000269|PubMed:16337200}; CC Vmax=2.6 umol/min/mg enzyme toward Boc-Leu-Lys-Arg-MCA CC {ECO:0000269|PubMed:16337200}; CC Vmax=1.9 umol/min/mg enzyme toward Boc-Val-Leu-Lys-MCA CC {ECO:0000269|PubMed:16337200}; CC Vmax=1.6 umol/min/mg enzyme toward Boc-Phe-Ser-Arg-MCA CC {ECO:0000269|PubMed:16337200}; CC pH dependence: CC Optimum pH is 8.5. Active from pH 7-10. CC {ECO:0000269|PubMed:16337200}; CC -!- SUBUNIT: Interacts with SPINK9. {ECO:0000269|PubMed:19194479}. CC -!- INTERACTION: CC O60259; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-3915857, EBI-3867333; CC O60259; P42858: HTT; NbExp=3; IntAct=EBI-3915857, EBI-466029; CC O60259; Q92876: KLK6; NbExp=3; IntAct=EBI-3915857, EBI-2432309; CC O60259; Q15323: KRT31; NbExp=3; IntAct=EBI-3915857, EBI-948001; CC O60259; O76011: KRT34; NbExp=3; IntAct=EBI-3915857, EBI-1047093; CC O60259; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-3915857, EBI-11959885; CC O60259; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-3915857, EBI-10171774; CC O60259; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-3915857, EBI-3958099; CC O60259; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-3915857, EBI-945833; CC O60259; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-3915857, EBI-22310682; CC O60259; P50454: SERPINH1; NbExp=3; IntAct=EBI-3915857, EBI-350723; CC O60259; P37173: TGFBR2; NbExp=3; IntAct=EBI-3915857, EBI-296151; CC O60259; Q8IUH5: ZDHHC17; NbExp=3; IntAct=EBI-3915857, EBI-524753; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17761692}. Cytoplasm CC {ECO:0000269|PubMed:17761692}. Note=Shows a cytoplasmic distribution in CC the keratinocytes. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=O60259-1; Sequence=Displayed; CC Name=2; CC IsoId=O60259-2; Sequence=VSP_005401; CC Name=3; CC IsoId=O60259-3; Sequence=VSP_030350; CC Name=4; CC IsoId=O60259-4; Sequence=VSP_030351, VSP_030352; CC -!- TISSUE SPECIFICITY: Isoform 1 is predominantly expressed in the CC pancreas. Isoform 2 is expressed in adult brain and hippocampus. CC Isoform 1 and isoform 2 are found in fetal brain and placenta. Detected CC in salivary gland, uterus, thymus, breast, testis and kidney but not in CC spleen, liver, lung or normal ovarian tissue. Displays an 11.5-fold CC increase in Alzheimer disease hippocampus compared to controls and is CC overexpressed in some ovarian carcinomas. Expressed at low levels in CC normal skin while high levels are found in psoriasis vulgaris, CC seborrheic keratosis, lichen planus and squamous cell carcinoma skin CC samples. Expressed in the keratinocytes. {ECO:0000269|PubMed:11309326, CC ECO:0000269|PubMed:11522960, ECO:0000269|PubMed:12147714, CC ECO:0000269|PubMed:17761692}. CC -!- MISCELLANEOUS: Expressed at high levels in serum, ascites fluid and CC tumor cytosol of advanced stage ovarian cancer patients and may serve CC as a marker of ovarian cancer. CC -!- MISCELLANEOUS: [Isoform 2]: Produced as a result of a human-specific CC mutation which is not found in other primates. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the peptidase S1 family. Kallikrein subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00274}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41088/KLK8"; 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; AB009849; BAA28673.1; -; mRNA. DR EMBL; AB012761; BAA28676.1; -; Genomic_DNA. DR EMBL; AF055982; AAD56050.1; -; mRNA. DR EMBL; AB008390; BAA82665.1; -; mRNA. DR EMBL; AB008927; BAA82666.1; -; mRNA. DR EMBL; AB010780; BAA88684.1; -; Genomic_DNA. DR EMBL; AF243527; AAG33361.1; -; Genomic_DNA. DR EMBL; AF251125; AAF79144.1; -; Genomic_DNA. DR EMBL; AF251125; AAF79145.1; -; Genomic_DNA. DR EMBL; AF095742; AAD25979.1; -; mRNA. DR EMBL; AF095743; AAD29574.1; -; Genomic_DNA. DR EMBL; DQ267420; ABB83339.1; -; mRNA. DR EMBL; AY359036; AAQ89395.1; -; mRNA. DR EMBL; AC011473; AAG23254.1; -; Genomic_DNA. DR EMBL; AC011483; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471135; EAW71962.1; -; Genomic_DNA. DR EMBL; BC040887; AAH40887.1; -; mRNA. DR EMBL; AY563055; AAT76913.1; -; Genomic_DNA. DR EMBL; AY563055; AAT76914.1; -; Genomic_DNA. DR EMBL; AY563056; AAT76915.1; -; Genomic_DNA. DR EMBL; AY563056; AAT76916.1; -; Genomic_DNA. DR EMBL; AY563057; AAT76917.1; -; Genomic_DNA. DR EMBL; AY563057; AAT76918.1; -; Genomic_DNA. DR EMBL; AY563058; AAT76919.1; -; Genomic_DNA. DR EMBL; AY563058; AAT76920.1; -; Genomic_DNA. DR EMBL; AY563059; AAT76921.1; -; Genomic_DNA. DR EMBL; AY563059; AAT76922.1; -; Genomic_DNA. DR EMBL; AY563060; AAT76923.1; -; Genomic_DNA. DR EMBL; AY563060; AAT76924.1; -; Genomic_DNA. DR EMBL; AY563061; AAT76925.1; -; Genomic_DNA. DR EMBL; AY563061; AAT76926.1; -; Genomic_DNA. DR EMBL; AY563062; AAT76927.1; -; Genomic_DNA. DR EMBL; AY563062; AAT76928.1; -; Genomic_DNA. DR EMBL; AY563063; AAT76929.1; -; Genomic_DNA. DR EMBL; AY563063; AAT76930.1; -; Genomic_DNA. DR EMBL; AY563064; AAT76931.1; -; Genomic_DNA. DR EMBL; AY563064; AAT76932.1; -; Genomic_DNA. DR EMBL; AY563065; AAT76933.1; -; Genomic_DNA. DR EMBL; AY563065; AAT76934.1; -; Genomic_DNA. DR EMBL; AY563066; AAT76935.1; -; Genomic_DNA. DR EMBL; AY563066; AAT76936.1; -; Genomic_DNA. DR EMBL; AY563067; AAT76937.1; -; Genomic_DNA. DR EMBL; AY563067; AAT76938.1; -; Genomic_DNA. DR CCDS; CCDS12813.1; -. [O60259-1] DR CCDS; CCDS12814.1; -. [O60259-3] DR CCDS; CCDS12815.1; -. [O60259-4] DR CCDS; CCDS42600.1; -. [O60259-2] DR RefSeq; NP_001268360.1; NM_001281431.1. DR RefSeq; NP_009127.1; NM_007196.4. [O60259-1] DR RefSeq; NP_653088.1; NM_144505.3. [O60259-2] DR RefSeq; NP_653089.1; NM_144506.3. [O60259-3] DR RefSeq; NP_653090.1; NM_144507.3. [O60259-4] DR PDB; 5MS3; X-ray; 2.30 A; A=33-260. DR PDB; 5MS4; X-ray; 2.10 A; A/B/C/D=33-260. DR PDBsum; 5MS3; -. DR PDBsum; 5MS4; -. DR AlphaFoldDB; O60259; -. DR SMR; O60259; -. DR BioGRID; 116371; 46. DR FunCoup; O60259; 73. DR IntAct; O60259; 33. DR STRING; 9606.ENSP00000375682; -. DR BindingDB; O60259; -. DR ChEMBL; CHEMBL4812; -. DR GuidetoPHARMACOLOGY; 2378; -. DR MEROPS; S01.244; -. DR GlyCosmos; O60259; 1 site, No reported glycans. DR GlyGen; O60259; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; O60259; -. DR PhosphoSitePlus; O60259; -. DR BioMuta; KLK8; -. DR jPOST; O60259; -. DR MassIVE; O60259; -. DR PeptideAtlas; O60259; -. DR ProteomicsDB; 49286; -. [O60259-1] DR ProteomicsDB; 49287; -. [O60259-2] DR ProteomicsDB; 49288; -. [O60259-3] DR Pumba; O60259; -. DR Antibodypedia; 32417; 1348 antibodies from 32 providers. DR DNASU; 11202; -. DR Ensembl; ENST00000320838.9; ENSP00000325072.5; ENSG00000129455.17. [O60259-4] DR Ensembl; ENST00000347619.8; ENSP00000341555.3; ENSG00000129455.17. [O60259-3] DR Ensembl; ENST00000391806.6; ENSP00000375682.1; ENSG00000129455.17. [O60259-2] DR Ensembl; ENST00000593490.1; ENSP00000469278.1; ENSG00000129455.17. [O60259-4] DR Ensembl; ENST00000600767.5; ENSP00000472016.1; ENSG00000129455.17. [O60259-1] DR Ensembl; ENST00000695909.1; ENSP00000512260.1; ENSG00000129455.17. [O60259-1] DR GeneID; 11202; -. DR KEGG; hsa:11202; -. DR MANE-Select; ENST00000695909.1; ENSP00000512260.1; NM_007196.4; NP_009127.1. DR UCSC; uc002puq.2; human. [O60259-1] DR AGR; HGNC:6369; -. DR ClinPGx; PA30158; -. DR CTD; 11202; -. DR DisGeNET; 11202; -. DR GeneCards; KLK8; -. DR HGNC; HGNC:6369; KLK8. DR HPA; ENSG00000129455; Tissue enhanced (esophagus, skin, vagina). DR MIM; 605644; gene. DR OpenTargets; ENSG00000129455; -. DR VEuPathDB; HostDB:ENSG00000129455; -. DR GeneTree; ENSGT01020000230389; -. DR HOGENOM; CLU_006842_1_1_1; -. DR InParanoid; O60259; -. DR OMA; GMTCYSG; -. DR OrthoDB; 546450at2759; -. DR PAN-GO; O60259; 3 GO annotations based on evolutionary models. DR PhylomeDB; O60259; -. DR BRENDA; 3.4.21.118; 2681. DR PathwayCommons; O60259; -. DR Reactome; R-HSA-6809371; Formation of the cornified envelope. DR SignaLink; O60259; -. DR Agora; ENSG00000129455; -. DR BioGRID-ORCS; 11202; 10 hits in 1144 CRISPR screens. DR GeneWiki; KLK8; -. DR GenomeRNAi; 11202; -. DR Pharos; O60259; Tchem. DR PRO; PR:O60259; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; O60259; protein. DR Bgee; ENSG00000129455; Expressed in lower esophagus mucosa and 104 other cell types or tissues. DR ExpressionAtlas; O60259; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB. DR GO; GO:0030141; C:secretory granule; IBA:GO_Central. DR GO; GO:0097180; C:serine protease inhibitor complex; IDA:BHF-UCL. DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0038130; P:ERBB4 signaling pathway; IEA:Ensembl. DR GO; GO:0043616; P:keratinocyte proliferation; ISS:UniProtKB. DR GO; GO:0007613; P:memory; ISS:UniProtKB. DR GO; GO:0048812; P:neuron projection morphogenesis; ISS:UniProtKB. DR GO; GO:0051604; P:protein maturation; IBA:GO_Central. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0050807; P:regulation of synapse organization; ISS:UniProtKB. DR GO; GO:0009611; P:response to wounding; ISS:UniProtKB. DR GO; GO:0050808; P:synapse organization; IEA:Ensembl. DR CDD; cd00190; Tryp_SPc; 1. DR FunFam; 2.40.10.10:FF:000087; Kallikrein 8 (Neuropsin/ovasin); 1. DR FunFam; 2.40.10.10:FF:000041; kallikrein-6 isoform X2; 1. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR24271:SF62; KALLIKREIN-8; 1. DR PANTHER; PTHR24271; KALLIKREIN-RELATED; 1. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00134; TRYPSIN_HIS; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Disulfide bond; KW Glycoprotein; Hydrolase; Protease; Proteomics identification; KW Reference proteome; Secreted; Serine protease; Signal; Zymogen. FT SIGNAL 1..28 FT /evidence="ECO:0000255" FT PROPEP 29..32 FT /evidence="ECO:0000250" FT /id="PRO_0000027946" FT CHAIN 33..260 FT /note="Kallikrein-8" FT /id="PRO_0000027947" FT DOMAIN 33..257 FT /note="Peptidase S1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 73 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT ACT_SITE 120 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT ACT_SITE 212 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT CARBOHYD 110 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 39..173 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 58..74 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 145..246 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 152..218 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 184..198 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 208..233 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT VAR_SEQ 23 FT /note="A -> AACGSLDLLTKLYAENLPCVHLNPQWPSQPSHCPRGWRSNPLPPAA FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10102990" FT /id="VSP_005401" FT VAR_SEQ 24..164 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.7" FT /id="VSP_030350" FT VAR_SEQ 25..32 FT /note="HSRAQEDK -> RFWRPPGV (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_030351" FT VAR_SEQ 33..260 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_030352" FT VARIANT 154 FT /note="V -> I (in dbSNP:rs16988799)" FT /id="VAR_051855" FT CONFLICT 195 FT /note="G -> V (in Ref. 11; AAH40887)" FT /evidence="ECO:0000305" FT STRAND 47..54 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 56..64 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 67..70 FT /evidence="ECO:0007829|PDB:5MS4" FT HELIX 72..74 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 80..84 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 86..90 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 96..105 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 111..113 FT /evidence="ECO:0007829|PDB:5MS3" FT STRAND 122..128 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 133..136 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 151..158 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 160..164 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 172..178 FT /evidence="ECO:0007829|PDB:5MS4" FT HELIX 181..187 FT /evidence="ECO:0007829|PDB:5MS4" FT TURN 189..191 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 196..200 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 215..228 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 231..234 FT /evidence="ECO:0007829|PDB:5MS3" FT STRAND 236..238 FT /evidence="ECO:0007829|PDB:5MS4" FT STRAND 240..244 FT /evidence="ECO:0007829|PDB:5MS4" FT HELIX 245..247 FT /evidence="ECO:0007829|PDB:5MS4" FT HELIX 249..257 FT /evidence="ECO:0007829|PDB:5MS4" SQ SEQUENCE 260 AA; 28048 MW; EF439E5B8C83E660 CRC64; MGRPRPRAAK TWMFLLLLGG AWAGHSRAQE DKVLGGHECQ PHSQPWQAAL FQGQQLLCGG VLVGGNWVLT AAHCKKPKYT VRLGDHSLQN KDGPEQEIPV VQSIPHPCYN SSDVEDHNHD LMLLQLRDQA SLGSKVKPIS LADHCTQPGQ KCTVSGWGTV TSPRENFPDT LNCAEVKIFP QKKCEDAYPG QITDGMVCAG SSKGADTCQG DSGGPLVCDG ALQGITSWGS DPCGRSDKPG VYTNICRYLD WIKKIIGSKG // ID MARK1_HUMAN Reviewed; 795 AA. AC Q9P0L2; D3DTB0; D3DTB1; Q2HIY1; Q5VTF9; Q5VTG0; Q96SW9; Q9P251; DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 28-JAN-2026, entry version 205. DE RecName: Full=Serine/threonine-protein kinase MARK1; DE EC=2.7.11.1; DE EC=2.7.11.26; DE AltName: Full=MAP/microtubule affinity-regulating kinase 1; DE AltName: Full=PAR1 homolog c; DE Short=Par-1c; DE Short=Par1c; GN Name=MARK1 {ECO:0000312|HGNC:HGNC:6896}; GN Synonyms=KIAA1477 {ECO:0000312|EMBL:BAA96001.1}, GN MARK {ECO:0000312|EMBL:AAF72103.1}; 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} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ACTIVITY REGULATION, RP PHOSPHORYLATION AT THR-215, AND MUTAGENESIS OF THR-215. 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 [2] {ECO:0000305, ECO:0000312|EMBL:AAF72103.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Zhou H.J., Huang X.W., Zhou Y., Hu S.L., Yuan J.G., Qiang B.Q.; RT "Cloning and isolating human MARK."; RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases. RN [3] {ECO:0000305, ECO:0000312|EMBL:BAA96001.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain {ECO:0000269|PubMed:10819331}; RX PubMed=10819331; DOI=10.1093/dnares/7.2.143; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:143-150(2000). RN [4] {ECO:0000305, ECO:0000312|EMBL:BAB55152.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 [5] 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 [6] {ECO:0000305, ECO:0000312|EMBL:AAF72103.1} 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] 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 [8] {ECO:0000305} RP TISSUE SPECIFICITY. RX PubMed=9108484; DOI=10.1016/s0092-8674(00)80208-1; RA Drewes G., Ebneth A., Preuss U., Mandelkow E.-M., Mandelkow E.; RT "MARK - a novel family of protein kinases that phosphorylate microtubule- RT associated proteins and trigger microtubule disruption."; RL Cell 89:297-308(1997). RN [9] RP NEUROFIBRILLARY TANGLES IN ALZHEIMER BRAIN. RX PubMed=11089574; DOI=10.1093/jnen/59.11.966; RA Chin J.Y., Knowles R.B., Schneider A., Drewes G., Mandelkow E.M., RA Hyman B.T.; RT "Microtubule-affinity regulating kinase (MARK) is tightly associated with RT neurofibrillary tangles in Alzheimer brain: a fluorescence resonance energy RT transfer study."; RL J. Neuropathol. Exp. Neurol. 59:966-971(2000). RN [10] RP FUNCTION. RX PubMed=11433294; DOI=10.1038/35083016; RA Sun T.-Q., Lu B., Feng J.-J., Reinhard C., Jan Y.N., Fantl W.J., RA Williams L.T.; RT "PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt RT signalling."; RL Nat. Cell Biol. 3:628-636(2001). RN [11] RP PHOSPHORYLATION AT THR-208, ACTIVITY REGULATION, AND FUNCTION. RX PubMed=17573348; DOI=10.1074/jbc.m700590200; RA Kojima Y., Miyoshi H., Clevers H.C., Oshima M., Aoki M., Taketo M.M.; RT "Suppression of tubulin polymerization by the LKB1-microtubule-associated RT protein/microtubule affinity-regulating kinase signaling."; RL J. Biol. Chem. 282:23532-23540(2007). RN [12] RP POSSIBLE INVOLVEMENT IN AUTISM. RX PubMed=18492799; DOI=10.1093/hmg/ddn154; RA Maussion G., Carayol J., Lepagnol-Bestel A.M., Tores F., Loe-Mie Y., RA Milbreta U., Rousseau F., Fontaine K., Renaud J., Moalic J.M., Philippi A., RA Chedotal A., Gorwood P., Ramoz N., Hager J., Simonneau M.; RT "Convergent evidence identifying MAP/microtubule affinity-regulating kinase RT 1 (MARK1) as a susceptibility gene for autism."; RL Hum. Mol. Genet. 17:2541-2551(2008). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-5 AND SER-403, AND RP IDENTIFICATION BY 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588, 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 [16] 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 [17] RP REVIEW. RX PubMed=19559622; DOI=10.1016/j.tibs.2009.03.008; RA Matenia D., Mandelkow E.M.; RT "The tau of MARK: a polarized view of the cytoskeleton."; RL Trends Biochem. Sci. 34:332-342(2009). RN [18] RP REVIEW. RX PubMed=20071654; DOI=10.1096/fj.09-148064; RA Marx A., Nugoor C., Panneerselvam S., Mandelkow E.; RT "Structure and function of polarity-inducing kinase family MARK/Par-1 RT within the branch of AMPK/Snf1-related kinases."; RL FASEB J. 24:1637-1648(2010). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [21] 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 [22] 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 [23] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 45-371. RX PubMed=16803889; DOI=10.1074/jbc.m604865200; RA Marx A., Nugoor C., Muller J., Panneerselvam S., Timm T., Bilang M., RA Mylonas E., Svergun D.I., Mandelkow E.M., Mandelkow E.; RT "Structural variations in the catalytic and ubiquitin-associated domains of RT microtubule-associated protein/microtubule affinity regulating kinase RT (MARK) 1 and MARK2."; RL J. Biol. Chem. 281:27586-27599(2006). RN [24] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 683-795, DOMAIN KA1, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF ARG-698; ARG-701; 771-ARG--LYS-773 AND RP 773-LYS-ARG-774. RX PubMed=21145462; DOI=10.1016/j.cell.2010.11.028; RA Moravcevic K., Mendrola J.M., Schmitz K.R., Wang Y.H., Slochower D., RA Janmey P.A., Lemmon M.A.; RT "Kinase associated-1 domains drive MARK/PAR1 kinases to membrane targets by RT binding acidic phospholipids."; RL Cell 143:966-977(2010). RN [25] RP VARIANTS [LARGE SCALE ANALYSIS] CYS-233; THR-355; MET-530; LEU-578 AND RP GLY-691. 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:23666762). Involved CC in cell polarity and microtubule dynamics regulation. Phosphorylates CC DCX, MAP2 and MAP4. Phosphorylates the microtubule-associated protein CC MAPT/TAU (PubMed:23666762). Involved in cell polarity by CC phosphorylating the microtubule-associated proteins MAP2, MAP4 and CC MAPT/TAU at KXGS motifs, causing detachment from microtubules, and CC their disassembly. Involved in the regulation of neuronal migration CC through its dual activities in regulating cellular polarity and CC microtubule dynamics, possibly by phosphorylating and regulating DCX. CC Also acts as a positive regulator of the Wnt signaling pathway, CC probably by mediating phosphorylation of dishevelled proteins (DVL1, CC DVL2 and/or DVL3). {ECO:0000269|PubMed:11433294, CC ECO:0000269|PubMed:17573348, ECO:0000269|PubMed:23666762}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); 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:14976552}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000269|PubMed:14976552}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[tau protein] + ATP = O-phospho-L-seryl-[tau protein] CC + ADP + H(+); Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA- CC COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonyl-[tau protein] + ATP = O-phospho-L-threonyl-[tau CC protein] + ADP + H(+); Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703, CC Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.26; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Inhibited by phosphorylation at Ser-219 (By CC similarity). Activated by phosphorylation on Thr-215. {ECO:0000250, CC ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:17573348}. CC -!- SUBUNIT: Interacts with MAPT/TAU. {ECO:0000269|PubMed:23666762}. CC -!- INTERACTION: CC Q9P0L2; P05067: APP; NbExp=3; IntAct=EBI-968587, EBI-77613; CC Q9P0L2; P63172: DYNLT1; NbExp=3; IntAct=EBI-968587, EBI-1176455; CC Q9P0L2; Q0VD86: INCA1; NbExp=3; IntAct=EBI-968587, EBI-6509505; CC Q9P0L2; O95988: TCL1B; NbExp=5; IntAct=EBI-968587, EBI-727338; CC Q9P0L2; Q8IY57-5: YAF2; NbExp=3; IntAct=EBI-968587, EBI-12111538; CC Q9P0L2; P61981: YWHAG; NbExp=4; IntAct=EBI-968587, EBI-359832; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21145462}; CC Peripheral membrane protein {ECO:0000269|PubMed:21145462}. Cytoplasm, CC cytoskeleton {ECO:0000250}. Cytoplasm {ECO:0000269|PubMed:23666762}. CC Cell projection, dendrite {ECO:0000269|PubMed:23666762}. Note=Appears CC to localize to an intracellular network. {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9P0L2-1; Sequence=Displayed; CC Name=2 {ECO:0000305}; CC IsoId=Q9P0L2-2; Sequence=VSP_051702, VSP_051704; CC Name=3 {ECO:0000305}; CC IsoId=Q9P0L2-3; Sequence=VSP_051703, VSP_051704; CC -!- TISSUE SPECIFICITY: Highly expressed in heart, skeletal muscle, brain, CC fetal brain and fetal kidney. {ECO:0000269|PubMed:9108484}. CC -!- DOMAIN: The UBA domain does not seem to bind ubiquitin and ubiquitin- CC like and might play a role in regulating the enzyme conformation and CC localization. Activation of the kinase activity following CC phosphorylation at Thr-208 is accompanied by a conformational change CC that alters the orientation of the UBA domain with respect to the CC catalytic domain (By similarity). {ECO:0000250}. CC -!- DOMAIN: The KA1 domain mediates binding to phospholipids and targeting CC to membranes. Binds phosphatidic acid (PA), phosphatidylserine (PtdSer) CC and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). CC {ECO:0000269|PubMed:21145462}. CC -!- PTM: Phosphorylation at Thr-613 by PRKCZ/aPKC in polarized epithelial CC cells inhibits the kinase activity (By similarity). Phosphorylated at CC Thr-215 by STK11/LKB1 in complex with STE20-related adapter-alpha CC (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-215 by TAOK1 CC activates the kinase activity, leading to phosphorylation and CC detachment of MAPT/TAU from microtubules. Phosphorylation at Ser-219 by CC GSK3-beta (GSK3B) inhibits the kinase activity. {ECO:0000250, CC ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:17573348}. CC -!- DISEASE: Note=Genetic variations in MARK1 may be associated with CC susceptibility to autism. MARK1 is overexpressed in the prefrontal CC cortex of patients with autism and causes changes in the function of CC cortical dendrites. CC -!- MISCELLANEOUS: Phosphorylation of MAPT/tau by MARK1 could play a role CC in early steps of Alzheimer disease. Pathological aggregation of CC MAPT/tau to neurofibrillary tangles, filamentous structures consisting CC of paired helical filaments (PHFs), is one of the hallmarks of CC Alzheimer disease. Hyperphosphorylation by MARK1 could be the initial CC step for this abnormal aggregation of tau in Alzheimer disease and CC animal models of tauopathy (PubMed:11089574). CC {ECO:0000305|PubMed:11089574}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr CC protein kinase family. SNF1 subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA96001.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAB55152.1; Type=Frameshift; Evidence={ECO:0000305}; 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; AF154845; AAF72103.1; -; mRNA. DR EMBL; AB040910; BAA96001.1; ALT_INIT; mRNA. DR EMBL; AK027493; BAB55152.1; ALT_FRAME; mRNA. DR EMBL; AC096640; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL592406; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471100; EAW93299.1; -; Genomic_DNA. DR EMBL; CH471100; EAW93300.1; -; Genomic_DNA. DR EMBL; CH471100; EAW93302.1; -; Genomic_DNA. DR EMBL; BC113869; AAI13870.1; -; mRNA. DR EMBL; BC114478; AAI14479.1; -; mRNA. DR CCDS; CCDS31029.2; -. [Q9P0L2-1] DR CCDS; CCDS65789.1; -. [Q9P0L2-3] DR RefSeq; NP_001273057.1; NM_001286128.2. [Q9P0L2-3] DR RefSeq; NP_061120.3; NM_018650.4. [Q9P0L2-1] DR PDB; 2HAK; X-ray; 2.60 A; A/B/C/D/E/F/G/H=45-371. DR PDB; 3OSE; X-ray; 1.70 A; A=683-795. DR PDB; 6C9D; X-ray; 2.50 A; A/B=45-795. DR PDBsum; 2HAK; -. DR PDBsum; 3OSE; -. DR PDBsum; 6C9D; -. DR AlphaFoldDB; Q9P0L2; -. DR SASBDB; Q9P0L2; -. DR SMR; Q9P0L2; -. DR BioGRID; 110309; 84. DR DIP; DIP-39777N; -. DR FunCoup; Q9P0L2; 1289. DR IntAct; Q9P0L2; 53. DR MINT; Q9P0L2; -. DR STRING; 9606.ENSP00000483424; -. DR BindingDB; Q9P0L2; -. DR ChEMBL; CHEMBL5940; -. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; Q9P0L2; -. DR GuidetoPHARMACOLOGY; 2097; -. DR CarbonylDB; Q9P0L2; -. DR iPTMnet; Q9P0L2; -. DR PhosphoSitePlus; Q9P0L2; -. DR BioMuta; MARK1; -. DR DMDM; 124056494; -. DR jPOST; Q9P0L2; -. DR MassIVE; Q9P0L2; -. DR PaxDb; 9606-ENSP00000483424; -. DR PeptideAtlas; Q9P0L2; -. DR ProteomicsDB; 83571; -. [Q9P0L2-1] DR ProteomicsDB; 83572; -. [Q9P0L2-2] DR ProteomicsDB; 83573; -. [Q9P0L2-3] DR Pumba; Q9P0L2; -. DR Antibodypedia; 2072; 432 antibodies from 33 providers. DR DNASU; 4139; -. DR Ensembl; ENST00000366917.6; ENSP00000355884.5; ENSG00000116141.18. [Q9P0L2-1] DR Ensembl; ENST00000366918.8; ENSP00000355885.4; ENSG00000116141.18. [Q9P0L2-3] DR GeneID; 4139; -. DR KEGG; hsa:4139; -. DR MANE-Select; ENST00000366917.6; ENSP00000355884.5; NM_018650.5; NP_061120.3. DR UCSC; uc001hmm.6; human. [Q9P0L2-1] DR AGR; HGNC:6896; -. DR ClinPGx; PA30639; -. DR CTD; 4139; -. DR DisGeNET; 4139; -. DR GeneCards; MARK1; -. DR HGNC; HGNC:6896; MARK1. DR HPA; ENSG00000116141; Low tissue specificity. DR MIM; 606511; gene. DR OpenTargets; ENSG00000116141; -. DR VEuPathDB; HostDB:ENSG00000116141; -. DR eggNOG; KOG0586; Eukaryota. DR GeneTree; ENSGT00940000157560; -. DR InParanoid; Q9P0L2; -. DR OrthoDB; 193931at2759; -. DR PAN-GO; Q9P0L2; 5 GO annotations based on evolutionary models. DR PhylomeDB; Q9P0L2; -. DR PathwayCommons; Q9P0L2; -. DR SignaLink; Q9P0L2; -. DR SIGNOR; Q9P0L2; -. DR Agora; ENSG00000116141; -. DR BioGRID-ORCS; 4139; 14 hits in 1190 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; MARK1; human. DR EvolutionaryTrace; Q9P0L2; -. DR GeneWiki; MARK1; -. DR GenomeRNAi; 4139; -. DR Pharos; Q9P0L2; Tchem. DR PRO; PR:Q9P0L2; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9P0L2; protein. DR Bgee; ENSG00000116141; Expressed in cortical plate and 178 other cell types or tissues. DR ExpressionAtlas; Q9P0L2; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB. DR GO; GO:0030425; C:dendrite; IDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0015630; C:microtubule cytoskeleton; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0098794; C:postsynapse; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0070300; F:phosphatidic acid binding; IDA:UniProtKB. DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB. DR GO; GO:0001786; F:phosphatidylserine 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; IMP:UniProtKB. DR GO; GO:0007010; P:cytoskeleton organization; ISS:UniProtKB. DR GO; GO:0051654; P:establishment of mitochondrion localization; ISS:ARUK-UCL. DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB. DR GO; GO:0000226; P:microtubule cytoskeleton organization; ISS:ARUK-UCL. DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IDA:ARUK-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:ARUK-UCL. DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:ARUK-UCL. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0050773; P:regulation of dendrite development; ISS:ARUK-UCL. DR GO; GO:0010975; P:regulation of neuron projection development; ISS:ARUK-UCL. DR GO; GO:0150052; P:regulation of postsynapse assembly; IEA:Ensembl. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. DR CDD; cd12196; MARK1-3_C; 1. DR CDD; cd14072; STKc_MARK; 1. DR CDD; cd14405; UBA_MARK1; 1. DR FunFam; 1.10.510.10:FF:001032; KP78b, isoform A; 1. DR FunFam; 1.10.8.10:FF:000011; Non-specific serine/threonine protein kinase; 1. DR FunFam; 3.30.200.20:FF:000003; Non-specific serine/threonine protein kinase; 1. DR FunFam; 3.30.310.80:FF:000001; Non-specific serine/threonine protein kinase; 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; 3.30.200.20; Phosphorylase Kinase, domain 1; 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:SF21; SERINE_THREONINE-PROTEIN KINASE MARK1; 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. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Autism; KW Autism spectrum disorder; Cell membrane; Cell projection; Cytoplasm; KW Cytoskeleton; Kinase; Lipid-binding; Magnesium; Membrane; Metal-binding; KW Nucleotide-binding; Phosphoprotein; Proteomics identification; KW Reference proteome; Serine/threonine-protein kinase; Transferase; KW Wnt signaling pathway. FT CHAIN 1..795 FT /note="Serine/threonine-protein kinase MARK1" FT /id="PRO_0000086298" FT DOMAIN 60..311 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 325..370 FT /note="UBA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212" FT DOMAIN 746..795 FT /note="KA1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00565" FT REGION 1..40 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 377..495 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 539..700 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 31..40 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 380..403 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 447..459 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 462..473 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 486..495 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 590..599 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 647..657 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 661..676 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 683..697 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 182 FT /note="Proton acceptor" FT /evidence="ECO:0000250|UniProtKB:Q9H0K1, FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10027" FT BINDING 66..74 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9H0K1, FT ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 89 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:O08678, FT ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 5 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 208 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:17573348" FT MOD_RES 215 FT /note="Phosphothreonine; by LKB1 and TAOK1" FT /evidence="ECO:0000269|PubMed:14976552" FT MOD_RES 219 FT /note="Phosphoserine; by GSK3-beta" FT /evidence="ECO:0000250|UniProtKB:O08678" FT MOD_RES 382 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5" FT MOD_RES 390 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5" FT MOD_RES 393 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5" FT MOD_RES 403 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 423 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5" FT MOD_RES 444 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O08678" FT MOD_RES 475 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5" FT MOD_RES 588 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 613 FT /note="Phosphothreonine; by PKC/PRKCZ" FT /evidence="ECO:0000250" FT MOD_RES 666 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5" FT VAR_SEQ 1..135 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_051702" FT VAR_SEQ 120..141 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10819331" FT /id="VSP_051703" FT VAR_SEQ 663..677 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:10819331, FT ECO:0000303|PubMed:14702039" FT /id="VSP_051704" FT VARIANT 233 FT /note="Y -> C (in a gastric adenocarcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040760" FT VARIANT 355 FT /note="N -> T (in an ovarian serous carcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040761" FT VARIANT 530 FT /note="V -> M (in dbSNP:rs56212551)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040762" FT VARIANT 578 FT /note="P -> L (in dbSNP:rs55691439)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040763" FT VARIANT 645 FT /note="R -> G (in dbSNP:rs12123778)" FT /id="VAR_030018" FT VARIANT 691 FT /note="E -> G (in dbSNP:rs55688276)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040764" FT MUTAGEN 215 FT /note="T->A: Prevents phosphorylation and activation by FT STK11/LKB1 complex." FT /evidence="ECO:0000269|PubMed:14976552" FT MUTAGEN 215 FT /note="T->E: Constitutively active." FT /evidence="ECO:0000269|PubMed:14976552" FT MUTAGEN 698 FT /note="R->S: Impairs phospholipid-binding, targeting to FT membrane and vesicle-binding; when associated with S-701." FT /evidence="ECO:0000269|PubMed:21145462" FT MUTAGEN 701 FT /note="R->S: Impairs phospholipid-binding, targeting to FT membrane and vesicle-binding; when associated with S-698." FT /evidence="ECO:0000269|PubMed:21145462" FT MUTAGEN 771..773 FT /note="RFK->AFA: Impairs phospholipid-binding." FT /evidence="ECO:0000269|PubMed:21145462" FT CONFLICT 16 FT /note="E -> V (in Ref. 2; AAF72103)" FT /evidence="ECO:0000305" FT CONFLICT 20 FT /note="S -> T (in Ref. 2; AAF72103)" FT /evidence="ECO:0000305" FT CONFLICT 522 FT /note="D -> N (in Ref. 4; BAB55152)" FT /evidence="ECO:0000305" FT CONFLICT 544 FT /note="V -> A (in Ref. 4; BAB55152)" FT /evidence="ECO:0000305" FT CONFLICT 763 FT /note="P -> A (in Ref. 4; BAB55152)" FT /evidence="ECO:0000305" FT CONFLICT 794 FT /note="K -> M (in Ref. 3; BAA96001)" FT /evidence="ECO:0000305" FT STRAND 55..57 FT /evidence="ECO:0007829|PDB:6C9D" FT STRAND 60..68 FT /evidence="ECO:0007829|PDB:6C9D" FT STRAND 70..79 FT /evidence="ECO:0007829|PDB:6C9D" FT TURN 80..82 FT /evidence="ECO:0007829|PDB:6C9D" FT STRAND 85..92 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 93..95 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 98..111 FT /evidence="ECO:0007829|PDB:6C9D" FT STRAND 122..127 FT /evidence="ECO:0007829|PDB:6C9D" FT STRAND 129..136 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 146..151 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 156..175 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 185..187 FT /evidence="ECO:0007829|PDB:6C9D" FT STRAND 188..190 FT /evidence="ECO:0007829|PDB:6C9D" FT STRAND 196..198 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 201..203 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 220..222 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 225..228 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 236..252 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 262..271 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 282..291 FT /evidence="ECO:0007829|PDB:6C9D" FT TURN 296..298 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 302..305 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 309..312 FT /evidence="ECO:0007829|PDB:6C9D" FT STRAND 316..318 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 333..341 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 346..355 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 360..368 FT /evidence="ECO:0007829|PDB:6C9D" FT TURN 706..708 FT /evidence="ECO:0007829|PDB:6C9D" FT HELIX 714..727 FT /evidence="ECO:0007829|PDB:3OSE" FT STRAND 731..736 FT /evidence="ECO:0007829|PDB:3OSE" FT STRAND 739..745 FT /evidence="ECO:0007829|PDB:3OSE" FT TURN 747..750 FT /evidence="ECO:0007829|PDB:3OSE" FT STRAND 753..762 FT /evidence="ECO:0007829|PDB:3OSE" FT HELIX 763..765 FT /evidence="ECO:0007829|PDB:3OSE" FT STRAND 767..777 FT /evidence="ECO:0007829|PDB:3OSE" FT HELIX 779..792 FT /evidence="ECO:0007829|PDB:3OSE" SQ SEQUENCE 795 AA; 89003 MW; 71BF6EB76912631B CRC64; MSARTPLPTV NERDTENHTS VDGYTEPHIQ PTKSSSRQNI PRCRNSITSA TDEQPHIGNY RLQKTIGKGN FAKVKLARHV LTGREVAVKI IDKTQLNPTS LQKLFREVRI MKILNHPNIV KLFEVIETEK TLYLVMEYAS GGEVFDYLVA HGRMKEKEAR AKFRQIVSAV QYCHQKYIVH RDLKAENLLL DGDMNIKIAD FGFSNEFTVG NKLDTFCGSP PYAAPELFQG KKYDGPEVDV WSLGVILYTL VSGSLPFDGQ NLKELRERVL RGKYRIPFYM STDCENLLKK LLVLNPIKRG SLEQIMKDRW MNVGHEEEEL KPYTEPDPDF NDTKRIDIMV TMGFARDEIN DALINQKYDE VMATYILLGR KPPEFEGGES LSSGNLCQRS RPSSDLNNST LQSPAHLKVQ RSISANQKQR RFSDHAGPSI PPAVSYTKRP QANSVESEQK EEWDKDVARK LGSTTVGSKS EMTASPLVGP ERKKSSTIPS NNVYSGGSMA RRNTYVCERT TDRYVALQNG KDSSLTEMSV SSISSAGSSV ASAVPSARPR HQKSMSTSGH PIKVTLPTIK DGSEAYRPGT TQRVPAASPS AHSISTATPD RTRFPRGSSS RSTFHGEQLR ERRSVAYNGP PASPSHETGA FAHARRGTST GIISKITSKF VRRDPSEGEA SGRTDTSRST SGEPKERDKE EGKDSKPRSL RFTWSMKTTS SMDPNDMMRE IRKVLDANNC DYEQKERFLL FCVHGDARQD SLVQWEMEVC KLPRLSLNGV RFKRISGTSI AFKNIASKIA NELKL //