ALPK1_MOUSE
ID ALPK1_MOUSE Reviewed; 1231 AA.
AC Q9CXB8; Q69ZH5; Q8BLT9;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 2.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Alpha-protein kinase 1 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q96QP1};
GN Name=Alpk1 {ECO:0000312|MGI:MGI:1918731};
GN Synonyms=Kiaa1527 {ECO:0000303|PubMed:15368895};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-209.
RC STRAIN=C57BL/6J; TISSUE=Aorta, Lung, and Vein;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 233-1231.
RC TISSUE=Brain;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=21208416; DOI=10.1186/1471-2202-12-1;
RA Chen M., Xu R.;
RT "Motor coordination deficits in Alpk1 mutant mice with the inserted
RT piggyBac transposon.";
RL BMC Neurosci. 12:1-1(2011).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30111836; DOI=10.1038/s41586-018-0433-3;
RA Zhou P., She Y., Dong N., Li P., He H., Borio A., Wu Q., Lu S., Ding X.,
RA Cao Y., Xu Y., Gao W., Dong M., Ding J., Wang D.C., Zamyatina A., Shao F.;
RT "Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-
RT heptose.";
RL Nature 561:122-126(2018).
RN [6]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=30967659; DOI=10.1038/s41436-019-0476-3;
RA Williams L.B., Javed A., Sabri A., Morgan D.J., Huff C.D., Grigg J.R.,
RA Heng X.T., Khng A.J., Hollink I.H.I.M., Morrison M.A., Owen L.A.,
RA Anderson K., Kinard K., Greenlees R., Novacic D., Nida Sen H., Zein W.M.,
RA Rodgers G.M., Vitale A.T., Haider N.B., Hillmer A.M., Ng P.C., Shankar A.,
RA Cheng A., Zheng L., Gillies M.C., van Slegtenhorst M., van Hagen P.M.,
RA Missotten T.O.A.R., Farley G.L., Polo M., Malatack J., Curtin J.,
RA Martin F., Arbuckle S., Alexander S.I., Chircop M., Davila S., Digre K.B.,
RA Jamieson R.V., DeAngelis M.M.;
RT "ALPK1 missense pathogenic variant in five families leads to ROSAH
RT syndrome, an ocular multisystem autosomal dominant disorder.";
RL Genet. Med. 21:2103-2115(2019).
CC -!- FUNCTION: Serine/threonine-protein kinase that detects bacterial
CC pathogen-associated molecular pattern metabolites (PAMPs) and initiates
CC an innate immune response, a critical step for pathogen elimination and
CC engagement of adaptive immunity (By similarity). Specifically
CC recognizes and binds ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose),
CC a potent PAMP present in all Gram-negative and some Gram-positive
CC bacteria (PubMed:30111836). ADP-Heptose-binding stimulates its kinase
CC activity to phosphorylate and activate TIFA, triggering pro-
CC inflammatory NF-kappa-B signaling (By similarity). May be involved in
CC monosodium urate monohydrate (MSU)-induced inflammation by mediating
CC phosphorylation of unconventional myosin MYO9A (By similarity). May
CC also play a role in apical protein transport by mediating
CC phosphorylation of unconventional myosin MYO1A (By similarity). May
CC play a role in ciliogenesis (By similarity).
CC {ECO:0000250|UniProtKB:Q96QP1, ECO:0000269|PubMed:30111836}.
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:0000250|UniProtKB:Q96QP1};
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:0000250|UniProtKB:Q96QP1};
CC -!- ACTIVITY REGULATION: Serine/threonine-protein kinase activity is
CC stimulated upon ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose)-
CC binding. {ECO:0000250|UniProtKB:Q96QP1}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q96QP1}. Cytoplasm, cytoskeleton, spindle pole
CC {ECO:0000250|UniProtKB:Q96QP1}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q96QP1}. Cell
CC projection, cilium {ECO:0000269|PubMed:30967659}. Note=Localized to the
CC basal body region of the photoreceptor cilium and the region of the
CC adjacent centriole. {ECO:0000269|PubMed:30967659}.
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:30967659). Expressed in
CC the retina and in sweat glands, especially in the myoepithelial cells
CC (PubMed:30967659). {ECO:0000269|PubMed:30967659}.
CC -!- DISRUPTION PHENOTYPE: Mice show defects in motor coordination
CC (PubMed:21208416). The cerebellar architecture, Purkinje cell
CC morphology and electrophysiology of the Purkinje cells is apparently
CC not affected (PubMed:21208416). Mice display impaired ability to
CC initiate an innate immune response in response to ADP-D-glycero-beta-D-
CC manno-heptose (ADP-Heptose): mice injected with ADP-Heptose show no
CC increase in cytokine production (PubMed:30111836).
CC {ECO:0000269|PubMed:21208416, ECO:0000269|PubMed:30111836}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Alpha-type
CC protein kinase family. ALPK subfamily. {ECO:0000305}.
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DR EMBL; AC158308; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC163391; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK018401; BAB31195.1; -; mRNA.
DR EMBL; AK041315; BAC30902.1; -; mRNA.
DR EMBL; AK173191; BAD32469.1; -; mRNA.
DR CCDS; CCDS51067.1; -.
DR AlphaFoldDB; Q9CXB8; -.
DR SMR; Q9CXB8; -.
DR STRING; 10090.ENSMUSP00000029662; -.
DR iPTMnet; Q9CXB8; -.
DR PhosphoSitePlus; Q9CXB8; -.
DR MaxQB; Q9CXB8; -.
DR PaxDb; Q9CXB8; -.
DR PRIDE; Q9CXB8; -.
DR ProteomicsDB; 296176; -.
DR MGI; MGI:1918731; Alpk1.
DR eggNOG; ENOG502QX1X; Eukaryota.
DR InParanoid; Q9CXB8; -.
DR PhylomeDB; Q9CXB8; -.
DR Reactome; R-MMU-9645460; Alpha-protein kinase 1 signaling pathway.
DR ChiTaRS; Alpk1; mouse.
DR PRO; PR:Q9CXB8; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9CXB8; protein.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005929; C:cilium; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0032391; C:photoreceptor connecting cilium; IDA:UniProtKB.
DR GO; GO:0000922; C:spindle pole; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0048029; F:monosaccharide binding; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:0002753; P:cytoplasmic pattern recognition receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR InterPro; IPR043529; ALPK1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR004166; MHCK_EF2_kinase.
DR PANTHER; PTHR46747; PTHR46747; 1.
DR Pfam; PF02816; Alpha_kinase; 1.
DR SMART; SM00811; Alpha_kinase; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51158; ALPHA_KINASE; 1.
PE 2: Evidence at transcript level;
KW Cell projection; Cytoplasm; Cytoskeleton; Immunity; Innate immunity;
KW Kinase; Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..1231
FT /note="Alpha-protein kinase 1"
FT /id="PRO_0000260029"
FT DOMAIN 1003..1223
FT /note="Alpha-type protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00501"
FT REGION 508..540
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 609..637
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 692..739
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 767..791
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 811..843
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 859..888
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 520..540
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 609..634
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 692..729
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 811..833
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 61
FT /ligand="ADP-D-glycero-beta-D-manno-heptose"
FT /ligand_id="ChEBI:CHEBI:59967"
FT /evidence="ECO:0000250|UniProtKB:Q96QP1"
FT BINDING 67
FT /ligand="ADP-D-glycero-beta-D-manno-heptose"
FT /ligand_id="ChEBI:CHEBI:59967"
FT /evidence="ECO:0000250|UniProtKB:Q96QP1"
FT BINDING 116
FT /ligand="ADP-D-glycero-beta-D-manno-heptose"
FT /ligand_id="ChEBI:CHEBI:59967"
FT /evidence="ECO:0000250|UniProtKB:Q96QP1"
FT BINDING 150..153
FT /ligand="ADP-D-glycero-beta-D-manno-heptose"
FT /ligand_id="ChEBI:CHEBI:59967"
FT /evidence="ECO:0000250|UniProtKB:Q96QP1"
FT BINDING 231
FT /ligand="ADP-D-glycero-beta-D-manno-heptose"
FT /ligand_id="ChEBI:CHEBI:59967"
FT /evidence="ECO:0000250|UniProtKB:Q96QP1"
FT BINDING 233
FT /ligand="ADP-D-glycero-beta-D-manno-heptose"
FT /ligand_id="ChEBI:CHEBI:59967"
FT /evidence="ECO:0000250|UniProtKB:Q96QP1"
FT BINDING 236..237
FT /ligand="ADP-D-glycero-beta-D-manno-heptose"
FT /ligand_id="ChEBI:CHEBI:59967"
FT /evidence="ECO:0000250|UniProtKB:Q96QP1"
FT BINDING 295
FT /ligand="ADP-D-glycero-beta-D-manno-heptose"
FT /ligand_id="ChEBI:CHEBI:59967"
FT /evidence="ECO:0000250|UniProtKB:Q96QP1"
FT CONFLICT 93..110
FT /note="AALRASILVQDCAAASAI -> VGRILPPVPLTSPREAFR (in Ref. 2;
FT BAC30902)"
FT /evidence="ECO:0000305"
FT CONFLICT 209..210
FT /note="MW -> TD (in Ref. 2; BAB31195)"
FT /evidence="ECO:0000305"
FT CONFLICT 233
FT /note="K -> Q (in Ref. 3; BAD32469)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1231 AA; 136134 MW; 94C2C68F6C74241D CRC64;
MNNQDAVASI LHECKQVLDR LLLETPDVST EDKSEDQRCR ASLPSELRTL IQEAEEMKWP
FVPEKWQYKQ AMSPEDKTNL QDVIGAGLQQ LLAALRASIL VQDCAAASAI VFLMDRFLYG
LDVSGKLLQV AKGLHKLKPA TPIAPQVVIR QARVSVNSGK LLKAEYILSS LISNNGATGT
WLYRNESDKV LVQSVCIQIR GQILQKLGMW YEAAELIWAS VIGYLTLPQP DKKGISTSLG
ILADIFVSMS KTDYEKFKKS PKVNLALLKE FDHHLLSAAE ACKLAAAFSA YTPLFVLRAV
NIRGTCLLSY SCSADCPPGM KSVHLCEAKE AFEIGLLTKK DGELVSGKQE LHSFIKAAFG
LTTVHSRLHG ETDAVRAARQ LCSEAVGKLY TFSTSPTSQD REGLSQEIMS LISQVKGHLR
VQSFPNLDVC SYVPESFKCG LDRLILHGHV DFQQILETYS QHHTSVCEVF ESTCGNSKSN
QRDTKSEVCI TTLKTETNTA DTMVATLERV SSQDSRSTAS SKMSKKDQGK LQRERGRSWT
RSKAFRVSLD LDMETETEPP NHSNGGTDVF NKSLRDNSSS CSWGRLSGLS SSTSWEEVNC
AVQDVVRKGS GQEKHPVEAQ SSEAVSEEPK RNRSSRAVFL SSKLRGVSLQ TTGDDNLESS
PSQLHNHTSI LPFNAKDTCL ASGAGLVETA EGSNNTSLQS SHSCGSDSWS LSSSDRFTDV
TTNPSVQEEE PSGIMGDVPE SKYDFKDWHG EKNGGTLTEI CTGPELTFAP SSVDPEGETA
ESTDDGLSPS QVALGCLEGS HSMSTRRTFF PDGSVQNADS AKTGCSVRDQ TVDPDASTVD
EEGQMLDSTE VCSIGQDGAH RPRALRSGQS AEGPKSFVNG SRPSPIFDED FSTTEEGEEL
GSMLKSSQNS SSYSPWWLKS PAFSRSSSDG ESSWSLLNSS RSSFASLAGQ TSQEILEART
LQPDDLEKLL AGVRHDWLLQ RLENTGVLKS NQLQQAHSAL LLKYSKKSEL WTAQETVVYL
GDYLKVKKKG KQRNAFWVHY LHQEETLGRY VGKEYKERKG LRHHFTDVER QMTAQHYVTE
FNKRLYEQKI PTQIFYVPST ILLILEDRTI KGCISVEPYI LGEFVKLSNN TKVVKNEYKA
TEYGLAYGHF SYEFSNHRDV VVDLQGWVTG NGKGLIYLTD PQIHSVDQKD VTTNFGKRGI
FYFFNNQHAS CNEICHRLSL TRPSLEQTSK V
