MAK_HUMAN
ID MAK_HUMAN Reviewed; 623 AA.
AC P20794; F1T0K6; G1FL29; Q547D0; Q9NUH7;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 27-APR-2001, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Serine/threonine-protein kinase MAK;
DE EC=2.7.11.1 {ECO:0000269|PubMed:12084720, ECO:0000269|PubMed:21986944};
DE AltName: Full=Male germ cell-associated kinase;
GN Name=MAK;
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] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, INDUCTION, AUTOPHOSPHORYLATION, PHOSPHORYLATION, AND
RP MUTAGENESIS OF LYS-33.
RC TISSUE=Testis;
RX PubMed=12084720; DOI=10.1074/jbc.m203940200;
RA Xia L., Robinson D., Ma A.H., Chen H.C., Wu F., Qiu Y., Kung H.J.;
RT "Identification of human male germ cell-associated kinase, a kinase
RT transcriptionally activated by androgen in prostate cancer cells.";
RL J. Biol. Chem. 277:35422-35433(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING (ISOFORM 2),
RP VARIANTS RP62 SER-13; ARG-27; HIS-130; HIS-166 AND THR-181,
RP CHARACTERIZATION OF VARIANTS RP62 SER-13 AND HIS-130, AND VARIANT LEU-325.
RC TISSUE=Retina;
RX PubMed=21835304; DOI=10.1016/j.ajhg.2011.07.005;
RA Ozgul R.K., Siemiatkowska A.M., Yucel D., Myers C.A., Collin R.W.,
RA Zonneveld M.N., Beryozkin A., Banin E., Hoyng C.B., van den Born L.I.,
RA Bose R., Shen W., Sharon D., Cremers F.P., Klevering B.J.,
RA den Hollander A.I., Corbo J.C.;
RT "Exome sequencing and cis-regulatory mapping identify mutations in MAK, a
RT gene encoding a regulator of ciliary length, as a cause of retinitis
RT pigmentosa.";
RL Am. J. Hum. Genet. 89:253-264(2011).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING (ISOFORM 2),
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INVOLVEMENT IN RP62.
RC TISSUE=Retina;
RX PubMed=21825139; DOI=10.1073/pnas.1108918108;
RA Tucker B.A., Scheetz T.E., Mullins R.F., DeLuca A.P., Hoffmann J.M.,
RA Johnston R.M., Jacobson S.G., Sheffield V.C., Stone E.M.;
RT "Exome sequencing and analysis of induced pluripotent stem cells identify
RT the cilia-related gene male germ cell-associated kinase (MAK) as a cause of
RT retinitis pigmentosa.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:E569-E576(2011).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Retinoblastoma;
RX PubMed=21697133; DOI=10.1167/iovs.11-7479;
RA Oshikawa M., Tsutsui C., Ikegami T., Fuchida Y., Matsubara M., Toyama S.,
RA Usami R., Ohtoko K., Kato S.;
RT "Full-length transcriptome analysis of human retina-derived cell lines
RT ARPE-19 and Y79 using the vector-capping method.";
RL Invest. Ophthalmol. Vis. Sci. 52:6662-6670(2011).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 121-163.
RX PubMed=2183027; DOI=10.1128/mcb.10.5.2261-2268.1990;
RA Matsushime H., Jinno A., Takagi N., Shibuya M.;
RT "A novel mammalian protein kinase gene (mak) is highly expressed in
RT testicular germ cells at and after meiosis.";
RL Mol. Cell. Biol. 10:2261-2268(1990).
RN [8]
RP FUNCTION, INTERACTION WITH AR, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=16951154; DOI=10.1158/0008-5472.can-06-1636;
RA Ma A.H., Xia L., Desai S.J., Boucher D.L., Guan Y., Shih H.M., Shi X.B.,
RA deVere White R.W., Chen H.W., Tepper C.G., Kung H.J.;
RT "Male germ cell-associated kinase, a male-specific kinase regulated by
RT androgen, is a coactivator of androgen receptor in prostate cancer cells.";
RL Cancer Res. 66:8439-8447(2006).
RN [9]
RP FUNCTION, INTERACTION WITH CDK20 AND FZR1, CATALYTIC ACTIVITY, COFACTOR,
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-157 AND TYR-159, AND
RP MUTAGENESIS OF THR-157 AND TYR-159.
RX PubMed=21986944; DOI=10.1038/onc.2011.464;
RA Wang L.Y., Kung H.J.;
RT "Male germ cell-associated kinase is overexpressed in prostate cancer cells
RT and causes mitotic defects via deregulation of APC/C(CDH1).";
RL Oncogene 31:2907-2918(2012).
RN [10]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-189; PRO-272; SER-384; SER-520 AND
RP LEU-550.
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: Essential for the regulation of ciliary length and required
CC for the long-term survival of photoreceptors (By similarity).
CC Phosphorylates FZR1 in a cell cycle-dependent manner. Plays a role in
CC the transcriptional coactivation of AR. Could play an important
CC function in spermatogenesis. May play a role in chromosomal stability
CC in prostate cancer cells. {ECO:0000250, ECO:0000269|PubMed:12084720,
CC ECO:0000269|PubMed:16951154, ECO:0000269|PubMed:21986944}.
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:12084720, ECO:0000269|PubMed:21986944};
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:12084720,
CC ECO:0000269|PubMed:21986944};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:12084720, ECO:0000269|PubMed:21986944};
CC -!- SUBUNIT: Interacts with RP1 (By similarity). Interacts with AR and
CC CDK20. Found in a complex containing MAK, AR and NCOA3. Interacts with
CC FZR1 (via WD repeats). {ECO:0000250, ECO:0000269|PubMed:16951154,
CC ECO:0000269|PubMed:21986944}.
CC -!- INTERACTION:
CC P20794; P10275: AR; NbExp=5; IntAct=EBI-3911321, EBI-608057;
CC P20794; Q9UM11: FZR1; NbExp=7; IntAct=EBI-3911321, EBI-724997;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome. Cytoplasm, cytoskeleton, spindle.
CC Midbody. Cell projection, cilium, photoreceptor outer segment
CC {ECO:0000250}. Photoreceptor inner segment. Note=Localized in both the
CC connecting cilia and the outer segment axonemes (By similarity).
CC Localized uniformly in nuclei during interphase, to the mitotic spindle
CC and centrosomes during metaphase and anaphase, and also to midbody at
CC anaphase until telophase. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P20794-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P20794-2; Sequence=VSP_042470;
CC Name=3;
CC IsoId=P20794-3; Sequence=VSP_042471;
CC -!- TISSUE SPECIFICITY: Expressed in prostate cancer cell lines at
CC generally higher levels than in normal prostate epithelial cell lines.
CC Isoform 1 is expressed in kidney, testis, lung, trachea, and retina.
CC Isoform 2 is retina-specific where it is expressed in rod and cone
CC photoreceptors. {ECO:0000269|PubMed:12084720,
CC ECO:0000269|PubMed:21825139}.
CC -!- INDUCTION: Up-regulated by dihydrotestosterone (DHT) in androgen-
CC sensitive LNCaP prostate cancer cells in a dose-dependent manner. Up-
CC regulation by DHT is transient, reaching maximum levels after 24 hours
CC and decreases slightly after 48 hours. {ECO:0000269|PubMed:12084720}.
CC -!- PTM: Autophosphorylated. Phosphorylated on serine and threonine
CC residues. {ECO:0000269|PubMed:12084720, ECO:0000269|PubMed:21986944}.
CC -!- DISEASE: Retinitis pigmentosa 62 (RP62) [MIM:614181]: A retinal
CC dystrophy belonging to the group of pigmentary retinopathies. Retinitis
CC pigmentosa is characterized by retinal pigment deposits visible on
CC fundus examination and primary loss of rod photoreceptor cells followed
CC by secondary loss of cone photoreceptors. Patients typically have night
CC vision blindness and loss of midperipheral visual field. As their
CC condition progresses, they lose their far peripheral visual field and
CC eventually central vision as well. {ECO:0000269|PubMed:21825139,
CC ECO:0000269|PubMed:21835304}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
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DR EMBL; AF505623; AAN16405.1; -; mRNA.
DR EMBL; JN226411; AEL29206.1; -; mRNA.
DR EMBL; AB593146; BAJ84080.1; -; mRNA.
DR EMBL; AL024498; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471087; EAW55283.1; -; Genomic_DNA.
DR EMBL; M35863; AAA36195.1; -; Genomic_DNA.
DR CCDS; CCDS4516.1; -. [P20794-1]
DR CCDS; CCDS75398.1; -. [P20794-3]
DR CCDS; CCDS75399.1; -. [P20794-2]
DR PIR; B34711; B34711.
DR RefSeq; NP_001229314.1; NM_001242385.1. [P20794-3]
DR RefSeq; NP_001229886.1; NM_001242957.2. [P20794-2]
DR RefSeq; NP_005897.1; NM_005906.5. [P20794-1]
DR RefSeq; XP_011512921.1; XM_011514619.2. [P20794-2]
DR RefSeq; XP_011512922.1; XM_011514620.2. [P20794-2]
DR RefSeq; XP_011512924.1; XM_011514622.2. [P20794-3]
DR RefSeq; XP_016866352.1; XM_017010863.1.
DR RefSeq; XP_016866353.1; XM_017010864.1.
DR AlphaFoldDB; P20794; -.
DR SMR; P20794; -.
DR BioGRID; 110291; 40.
DR CORUM; P20794; -.
DR IntAct; P20794; 35.
DR STRING; 9606.ENSP00000346484; -.
DR BindingDB; P20794; -.
DR ChEMBL; CHEMBL1163106; -.
DR iPTMnet; P20794; -.
DR PhosphoSitePlus; P20794; -.
DR BioMuta; MAK; -.
DR DMDM; 13432166; -.
DR EPD; P20794; -.
DR jPOST; P20794; -.
DR MassIVE; P20794; -.
DR MaxQB; P20794; -.
DR PaxDb; P20794; -.
DR PeptideAtlas; P20794; -.
DR PRIDE; P20794; -.
DR ProteomicsDB; 53787; -. [P20794-1]
DR ProteomicsDB; 53788; -. [P20794-2]
DR ProteomicsDB; 53789; -. [P20794-3]
DR Antibodypedia; 24855; 448 antibodies from 30 providers.
DR DNASU; 4117; -.
DR Ensembl; ENST00000313243.6; ENSP00000313021.2; ENSG00000111837.12. [P20794-1]
DR Ensembl; ENST00000354489.7; ENSP00000346484.3; ENSG00000111837.12. [P20794-2]
DR Ensembl; ENST00000474039.5; ENSP00000476067.1; ENSG00000111837.12. [P20794-1]
DR Ensembl; ENST00000536370.6; ENSP00000442221.2; ENSG00000111837.12. [P20794-3]
DR GeneID; 4117; -.
DR KEGG; hsa:4117; -.
DR MANE-Select; ENST00000354489.7; ENSP00000346484.3; NM_001242957.3; NP_001229886.1. [P20794-2]
DR UCSC; uc003mzm.4; human. [P20794-1]
DR CTD; 4117; -.
DR DisGeNET; 4117; -.
DR GeneCards; MAK; -.
DR GeneReviews; MAK; -.
DR HGNC; HGNC:6816; MAK.
DR HPA; ENSG00000111837; Tissue enriched (retina).
DR MalaCards; MAK; -.
DR MIM; 154235; gene.
DR MIM; 614181; phenotype.
DR neXtProt; NX_P20794; -.
DR OpenTargets; ENSG00000111837; -.
DR Orphanet; 791; Retinitis pigmentosa.
DR PharmGKB; PA30564; -.
DR VEuPathDB; HostDB:ENSG00000111837; -.
DR eggNOG; KOG0661; Eukaryota.
DR GeneTree; ENSGT00940000156581; -.
DR InParanoid; P20794; -.
DR OMA; PMHQENI; -.
DR OrthoDB; 76933at2759; -.
DR PhylomeDB; P20794; -.
DR TreeFam; TF328769; -.
DR BRENDA; 2.7.11.22; 2681.
DR PathwayCommons; P20794; -.
DR SignaLink; P20794; -.
DR SIGNOR; P20794; -.
DR BioGRID-ORCS; 4117; 15 hits in 1105 CRISPR screens.
DR ChiTaRS; MAK; human.
DR GeneWiki; MAK_(gene); -.
DR GenomeRNAi; 4117; -.
DR Pharos; P20794; Tchem.
DR PRO; PR:P20794; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P20794; protein.
DR Bgee; ENSG00000111837; Expressed in sperm and 115 other tissues.
DR ExpressionAtlas; P20794; baseline and differential.
DR Genevisible; P20794; HS.
DR GO; GO:0005930; C:axoneme; IEA:Ensembl.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
DR GO; GO:0031514; C:motile cilium; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032391; C:photoreceptor connecting cilium; IEA:Ensembl.
DR GO; GO:0001917; C:photoreceptor inner segment; IDA:UniProtKB.
DR GO; GO:0001750; C:photoreceptor outer segment; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; NAS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0060271; P:cilium assembly; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0042073; P:intraciliary transport; IBA:GO_Central.
DR GO; GO:1902856; P:negative regulation of non-motile cilium assembly; IEA:Ensembl.
DR GO; GO:1905515; P:non-motile cilium assembly; IEA:Ensembl.
DR GO; GO:0045494; P:photoreceptor cell maintenance; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; NAS:UniProtKB.
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 Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell projection; Cilium; Cytoplasm;
KW Cytoskeleton; Developmental protein; Differentiation; Disease variant;
KW Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Retinitis pigmentosa;
KW Serine/threonine-protein kinase; Spermatogenesis; Transcription;
KW Transcription regulation; Transferase.
FT CHAIN 1..623
FT /note="Serine/threonine-protein kinase MAK"
FT /id="PRO_0000086284"
FT DOMAIN 4..284
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 328..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 416..469
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 333..393
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 416..439
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 445..469
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 125
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 10..18
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 33
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 157
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:21986944"
FT MOD_RES 159
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:21986944"
FT VAR_SEQ 532
FT /note="A -> AEESIIKPIEKLSCNETFPEKLEDPQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:21825139,
FT ECO:0000303|PubMed:21835304"
FT /id="VSP_042470"
FT VAR_SEQ 533..572
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:21697133"
FT /id="VSP_042471"
FT VARIANT 13
FT /note="G -> S (in RP62; results in a complete loss of
FT kinase activity compared to wild-type; dbSNP:rs387906647)"
FT /evidence="ECO:0000269|PubMed:21835304"
FT /id="VAR_066988"
FT VARIANT 27
FT /note="G -> R (in RP62; dbSNP:rs754916169)"
FT /evidence="ECO:0000269|PubMed:21835304"
FT /id="VAR_066989"
FT VARIANT 130
FT /note="N -> H (in RP62; results in a complete loss of
FT kinase activity compared to wild-type; dbSNP:rs387906646)"
FT /evidence="ECO:0000269|PubMed:21835304"
FT /id="VAR_066990"
FT VARIANT 166
FT /note="R -> H (in RP62; dbSNP:rs387906648)"
FT /evidence="ECO:0000269|PubMed:21835304"
FT /id="VAR_066991"
FT VARIANT 181
FT /note="I -> T (in RP62; dbSNP:rs750559316)"
FT /evidence="ECO:0000269|PubMed:21835304"
FT /id="VAR_066992"
FT VARIANT 189
FT /note="I -> V (in dbSNP:rs56215624)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042006"
FT VARIANT 272
FT /note="R -> P (in a breast infiltrating ductal carcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042007"
FT VARIANT 325
FT /note="P -> L (in dbSNP:rs371971492)"
FT /evidence="ECO:0000269|PubMed:21835304"
FT /id="VAR_066993"
FT VARIANT 329
FT /note="D -> E (in dbSNP:rs17579447)"
FT /id="VAR_053932"
FT VARIANT 384
FT /note="N -> S (in dbSNP:rs55773478)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042008"
FT VARIANT 520
FT /note="P -> S (in dbSNP:rs567083)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042009"
FT VARIANT 550
FT /note="F -> L (in dbSNP:rs56217305)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042010"
FT MUTAGEN 33
FT /note="K->R: Abolishes autophosphorylation."
FT /evidence="ECO:0000269|PubMed:12084720"
FT MUTAGEN 157
FT /note="T->A: Abolishes autophosphorylation and impairs
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:21986944"
FT MUTAGEN 159
FT /note="Y->F: Abolishes autophosphorylation and impairs
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:21986944"
SQ SEQUENCE 623 AA; 70581 MW; 67F540266F370285 CRC64;
MNRYTTMRQL GDGTYGSVLM GKSNESGELV AIKRMKRKFY SWDECMNLRE VKSLKKLNHA
NVIKLKEVIR ENDHLYFIFE YMKENLYQLM KDRNKLFPES VIRNIMYQIL QGLAFIHKHG
FFHRDMKPEN LLCMGPELVK IADFGLAREL RSQPPYTDYV STRWYRAPEV LLRSSVYSSP
IDVWAVGSIM AELYMLRPLF PGTSEVDEIF KICQVLGTPK KSDWPEGYQL ASSMNFRFPQ
CVPINLKTLI PNASNEAIQL MTEMLNWDPK KRPTASQALK HPYFQVGQVL GPSSNHLESK
QSLNKQLQPL ESKPSLVEVE PKPLPDIIDQ VVGQPQPKTS QQPLQPIQPP QNLSVQQPPK
QQSQEKPPQT LFPSIVKNMP TKPNGTLSHK SGRRRWGQTI FKSGDSWEEL EDYDFGASHS
KKPSMGVFKE KRKKDSPFRL PEPVPSGSNH STGENKSLPA VTSLKSDSEL STAPTSKQYY
LKQSRYLPGV NPKKVSLIAS GKEINPHTWS NQLFPKSLGP VGAELAFKRS NAGNLGSYAT
YNQSGYIPSF LKKEVQSAGQ RIHLAPLNAT ASEYTWNTKT GRGQFSGRTY NPTAKNLNIV
NRAQPIPSVH GRTDWVAKYG GHR
