ALPK1_HUMAN
ID ALPK1_HUMAN Reviewed; 1244 AA.
AC Q96QP1; B4E3G1; F5H138; Q68CI9; Q6P9F9; Q6ZNK4; Q9P201;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Alpha-protein kinase 1 {ECO:0000303|PubMed:30111836};
DE EC=2.7.11.1 {ECO:0000269|PubMed:27169898, ECO:0000269|PubMed:30111836};
DE AltName: Full=Chromosome 4 kinase {ECO:0000303|PubMed:10021370};
DE AltName: Full=Lymphocyte alpha-protein kinase {ECO:0000312|HGNC:HGNC:20917};
GN Name=ALPK1 {ECO:0000303|PubMed:30111836, ECO:0000312|HGNC:HGNC:20917};
GN Synonyms=KIAA1527 {ECO:0000303|PubMed:10819331},
GN LAK {ECO:0000312|HGNC:HGNC:20917};
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), AND VARIANTS ASP-565; ARG-642;
RP ILE-732 AND THR-861.
RX PubMed=10021370; DOI=10.1016/s0960-9822(99)80006-2;
RA Ryazanov A.G., Pavur K.S., Dorovkov M.V.;
RT "Alpha-kinases: a new class of protein kinases with a novel catalytic
RT domain.";
RL Curr. Biol. 9:R43-R45(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS ASP-565;
RP ARG-642; ASP-681; ILE-732 AND THR-861.
RC TISSUE=Uterus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 77-1244 (ISOFORM 1), AND VARIANTS
RP ASP-565; ARG-642; ILE-732 AND THR-861.
RC TISSUE=Spleen;
RA Jikuya H., Takano J., Kikuno R., Nagase T., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 444-1244 (ISOFORM 1), VARIANTS
RP ASP-565; ARG-642; ILE-732 AND THR-861, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
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 [7]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1018-1244 (ISOFORM 1).
RX PubMed=15221005; DOI=10.1038/sj.onc.1207782;
RA Yamada S., Ohira M., Horie H., Ando K., Takayasu H., Suzuki Y., Sugano S.,
RA Hirata T., Goto T., Matsunaga T., Hiyama E., Hayashi Y., Ando H., Suita S.,
RA Kaneko M., Sasaki F., Hashizume K., Ohnuma N., Nakagawara A.;
RT "Expression profiling and differential screening between hepatoblastomas
RT and the corresponding normal livers: identification of high expression of
RT the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas.";
RL Oncogene 23:5901-5911(2004).
RN [9]
RP FUNCTION.
RX PubMed=15883161; DOI=10.1074/jbc.m502265200;
RA Heine M., Cramm-Behrens C.I., Ansari A., Chu H.P., Ryazanov A.G.,
RA Naim H.Y., Jacob R.;
RT "Alpha-kinase 1, a new component in apical protein transport.";
RL J. Biol. Chem. 280:25637-25643(2005).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=27169898; DOI=10.1038/srep25740;
RA Lee C.P., Chiang S.L., Ko A.M., Liu Y.F., Ma C., Lu C.Y., Huang C.M.,
RA Chang J.G., Kuo T.M., Chen C.L., Tsai E.M., Ko Y.C.;
RT "ALPK1 phosphorylates myosin IIA modulating TNF-alpha trafficking in gout
RT flares.";
RL Sci. Rep. 6:25740-25740(2016).
RN [11]
RP FUNCTION.
RX PubMed=28877472; DOI=10.1016/j.celrep.2017.08.039;
RA Zimmermann S., Pfannkuch L., Al-Zeer M.A., Bartfeld S., Koch M., Liu J.,
RA Rechner C., Soerensen M., Sokolova O., Zamyatina A., Kosma P.,
RA Maeurer A.P., Glowinski F., Pleissner K.P., Schmid M., Brinkmann V.,
RA Karlas A., Naumann M., Rother M., Machuy N., Meyer T.F.;
RT "ALPK1- and TIFA-dependent innate immune response triggered by the
RT Helicobacter pylori type IV secretion system.";
RL Cell Rep. 20:2384-2395(2017).
RN [12]
RP FUNCTION.
RX PubMed=28222186; DOI=10.1371/journal.ppat.1006224;
RA Milivojevic M., Dangeard A.S., Kasper C.A., Tschon T., Emmenlauer M.,
RA Pique C., Schnupf P., Guignot J., Arrieumerlou C.;
RT "ALPK1 controls TIFA/TRAF6-dependent innate immunity against heptose-1,7-
RT bisphosphate of gram-negative bacteria.";
RL PLoS Pathog. 13:E1006224-E1006224(2017).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 1-446 IN COMPLEX WITH
RP ADP-D-GLYCERO-BETA-D-MANNO-HEPTOSE, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLN-67; ARG-116;
RP ARG-150; ARG-153; ASP-231; LYS-233; THR-237; PHE-295 AND LYS-1067.
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 [14]
RP VARIANTS [LARGE SCALE ANALYSIS] ARG-67; ASP-175; MET-292; MET-320; GLU-339;
RP GLU-383; ASP-565; ARG-642; LEU-660; ASP-681; ILE-732; THR-861; SER-870;
RP ILE-873; ASP-910; ASP-916; LEU-935; GLN-1084; PRO-1117 AND GLY-1160.
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).
RN [15]
RP VARIANT ROSAH MET-237, INVOLVEMENT IN ROSAH, TISSUE SPECIFICITY, FUNCTION,
RP 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).
RN [16]
RP VARIANT ROSAH MET-237, AND INVOLVEMENT IN ROSAH.
RX PubMed=31939038; DOI=10.1007/s10875-020-00741-6;
RA Zhong L., Wang J., Wang W., Wang L., Quan M., Tang X., Gou L., Wei M.,
RA Xiao J., Zhang T., Sui R., Zhou Q., Song H.;
RT "Juvenile Onset Splenomegaly and Oculopathy Due to Germline Mutation in
RT ALPK1.";
RL J. Clin. Immunol. 40:350-358(2020).
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 (PubMed:28877472, PubMed:28222186,
CC PubMed:30111836). Specifically recognizes and binds ADP-D-glycero-beta-
CC D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-
CC negative and some Gram-positive bacteria (PubMed:30111836). ADP-
CC Heptose-binding stimulates its kinase activity to phosphorylate and
CC activate TIFA, triggering pro-inflammatory NF-kappa-B signaling
CC (PubMed:30111836). May be involved in monosodium urate monohydrate
CC (MSU)-induced inflammation by mediating phosphorylation of
CC unconventional myosin MYO9A (PubMed:27169898). May also play a role in
CC apical protein transport by mediating phosphorylation of unconventional
CC myosin MYO1A (PubMed:15883161). May play a role in ciliogenesis
CC (PubMed:30967659). {ECO:0000269|PubMed:15883161,
CC ECO:0000269|PubMed:27169898, ECO:0000269|PubMed:28222186,
CC ECO:0000269|PubMed:28877472, ECO:0000269|PubMed:30111836,
CC ECO:0000269|PubMed:30967659}.
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:27169898, ECO:0000269|PubMed:30111836};
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:27169898,
CC ECO:0000269|PubMed:30111836};
CC -!- ACTIVITY REGULATION: Serine/threonine-protein kinase activity is
CC stimulated upon ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose)-
CC binding. {ECO:0000269|PubMed:30111836}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:30111836}.
CC Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:30967659}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:30967659}. Cell projection, cilium
CC {ECO:0000269|PubMed:30967659}. Note=Localized at the base of primary
CC cilia. {ECO:0000269|PubMed:30967659}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96QP1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96QP1-2; Sequence=VSP_044735;
CC -!- TISSUE SPECIFICITY: Highly expressed in liver. Expressed in the optic
CC nerve and retinal pigmented epithelium. Lower expression is observed in
CC the macula and extramacular retina (PubMed:30967659).
CC {ECO:0000269|PubMed:10819331, ECO:0000269|PubMed:30967659}.
CC -!- DISEASE: Retinal dystrophy, optic nerve edema, splenomegaly,
CC anhidrosis, and migraine headache syndrome (ROSAH) [MIM:614979]: An
CC autosomal dominant disorder characterized by decreased vision
CC associated with optic nerve edema, evident in childhood. Low-grade
CC ocular inflammation is common in affected individuals. Later in
CC childhood or the second decade of life, patients have increasing visual
CC impairment, abnormal cone function and loss of rod function. By the
CC third decade of life, visual acuity ranges from counting fingers to no
CC light perception. Patients also show anhidrosis, splenomegaly, mild
CC pancytopenia, and most experience headaches that may be migraine-like
CC in nature. {ECO:0000269|PubMed:30967659, ECO:0000269|PubMed:31939038}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Alpha-type
CC protein kinase family. ALPK subfamily. {ECO:0000305}.
CC -!- CAUTION: D-glycero-beta-D-manno-heptose 1,7-bisphosphate (HBP) was
CC initially thought to constitute the bacterial pathogen-associated
CC molecular pattern metabolite (PAMP) triggering the ALPK1-TIFA innate
CC immunune response (PubMed:28877472, PubMed:28222186). It was however
CC shown that ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose) constitutes
CC the main PAMP that activates the kinase activity of ALPK1
CC (PubMed:30111836). {ECO:0000269|PubMed:28222186,
CC ECO:0000269|PubMed:28877472, ECO:0000269|PubMed:30111836}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC85140.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC85140.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC85140.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=BC060780; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY044164; AAK94675.1; -; mRNA.
DR EMBL; AK304708; BAG65473.1; -; mRNA.
DR EMBL; AC004049; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC109347; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC060780; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK131090; BAC85140.1; ALT_SEQ; mRNA.
DR EMBL; AB040960; BAA96051.1; -; mRNA.
DR EMBL; AB075877; BAD38659.1; -; mRNA.
DR CCDS; CCDS3697.1; -. [Q96QP1-1]
DR CCDS; CCDS58923.1; -. [Q96QP1-2]
DR RefSeq; NP_001095876.1; NM_001102406.1. [Q96QP1-1]
DR RefSeq; NP_001240813.1; NM_001253884.1. [Q96QP1-2]
DR RefSeq; NP_079420.3; NM_025144.3. [Q96QP1-1]
DR PDB; 5Z2C; X-ray; 2.59 A; A/B/C/D/E/F/G/H/I=1-446.
DR PDBsum; 5Z2C; -.
DR AlphaFoldDB; Q96QP1; -.
DR SMR; Q96QP1; -.
DR BioGRID; 123183; 9.
DR IntAct; Q96QP1; 3.
DR STRING; 9606.ENSP00000398048; -.
DR iPTMnet; Q96QP1; -.
DR PhosphoSitePlus; Q96QP1; -.
DR BioMuta; ALPK1; -.
DR DMDM; 308153632; -.
DR EPD; Q96QP1; -.
DR MassIVE; Q96QP1; -.
DR MaxQB; Q96QP1; -.
DR PaxDb; Q96QP1; -.
DR PeptideAtlas; Q96QP1; -.
DR PRIDE; Q96QP1; -.
DR ProteomicsDB; 25531; -.
DR ProteomicsDB; 77886; -. [Q96QP1-1]
DR Antibodypedia; 26436; 102 antibodies from 24 providers.
DR DNASU; 80216; -.
DR Ensembl; ENST00000177648.13; ENSP00000177648.9; ENSG00000073331.18. [Q96QP1-1]
DR Ensembl; ENST00000458497.6; ENSP00000398048.1; ENSG00000073331.18. [Q96QP1-1]
DR Ensembl; ENST00000504176.6; ENSP00000426044.2; ENSG00000073331.18. [Q96QP1-2]
DR Ensembl; ENST00000650871.1; ENSP00000498374.1; ENSG00000073331.18. [Q96QP1-1]
DR GeneID; 80216; -.
DR KEGG; hsa:80216; -.
DR MANE-Select; ENST00000650871.1; ENSP00000498374.1; NM_025144.4; NP_079420.3.
DR UCSC; uc003ian.5; human. [Q96QP1-1]
DR CTD; 80216; -.
DR DisGeNET; 80216; -.
DR GeneCards; ALPK1; -.
DR HGNC; HGNC:20917; ALPK1.
DR HPA; ENSG00000073331; Low tissue specificity.
DR MalaCards; ALPK1; -.
DR MIM; 607347; gene.
DR MIM; 614979; phenotype.
DR neXtProt; NX_Q96QP1; -.
DR OpenTargets; ENSG00000073331; -.
DR Orphanet; 313800; Retinal dystrophy-optic nerve edema-splenomegaly-anhidrosis-migraine headache syndrome.
DR PharmGKB; PA134891785; -.
DR VEuPathDB; HostDB:ENSG00000073331; -.
DR eggNOG; ENOG502QX1X; Eukaryota.
DR GeneTree; ENSGT00940000159753; -.
DR HOGENOM; CLU_007421_0_0_1; -.
DR InParanoid; Q96QP1; -.
DR OMA; KCNEICH; -.
DR PhylomeDB; Q96QP1; -.
DR TreeFam; TF316085; -.
DR PathwayCommons; Q96QP1; -.
DR Reactome; R-HSA-9645460; Alpha-protein kinase 1 signaling pathway.
DR SignaLink; Q96QP1; -.
DR BioGRID-ORCS; 80216; 8 hits in 1076 CRISPR screens.
DR ChiTaRS; ALPK1; human.
DR GeneWiki; ALPK1; -.
DR GenomeRNAi; 80216; -.
DR Pharos; Q96QP1; Tbio.
DR PRO; PR:Q96QP1; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q96QP1; protein.
DR Bgee; ENSG00000073331; Expressed in buccal mucosa cell and 173 other tissues.
DR ExpressionAtlas; Q96QP1; baseline and differential.
DR Genevisible; Q96QP1; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0048029; F:monosaccharide binding; IPI: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:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0002753; P:cytoplasmic pattern recognition receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
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 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell projection;
KW Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton; Disease variant;
KW Immunity; Innate immunity; Kinase; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..1244
FT /note="Alpha-protein kinase 1"
FT /id="PRO_0000260028"
FT DOMAIN 1017..1237
FT /note="Alpha-type protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00501"
FT REGION 650..675
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 701..737
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 757..798
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 824..848
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 703..733
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:0000269|PubMed:30111836"
FT BINDING 67
FT /ligand="ADP-D-glycero-beta-D-manno-heptose"
FT /ligand_id="ChEBI:CHEBI:59967"
FT /evidence="ECO:0000269|PubMed:30111836"
FT BINDING 116
FT /ligand="ADP-D-glycero-beta-D-manno-heptose"
FT /ligand_id="ChEBI:CHEBI:59967"
FT /evidence="ECO:0000269|PubMed:30111836"
FT BINDING 150..153
FT /ligand="ADP-D-glycero-beta-D-manno-heptose"
FT /ligand_id="ChEBI:CHEBI:59967"
FT /evidence="ECO:0000269|PubMed:30111836"
FT BINDING 231
FT /ligand="ADP-D-glycero-beta-D-manno-heptose"
FT /ligand_id="ChEBI:CHEBI:59967"
FT /evidence="ECO:0000269|PubMed:30111836"
FT BINDING 233
FT /ligand="ADP-D-glycero-beta-D-manno-heptose"
FT /ligand_id="ChEBI:CHEBI:59967"
FT /evidence="ECO:0000269|PubMed:30111836"
FT BINDING 236..237
FT /ligand="ADP-D-glycero-beta-D-manno-heptose"
FT /ligand_id="ChEBI:CHEBI:59967"
FT /evidence="ECO:0000269|PubMed:30111836"
FT BINDING 295
FT /ligand="ADP-D-glycero-beta-D-manno-heptose"
FT /ligand_id="ChEBI:CHEBI:59967"
FT /evidence="ECO:0000269|PubMed:30111836"
FT VAR_SEQ 1..92
FT /note="MNNQKVVAVLLQECKQVLDQLLLEAPDVSEEDKSEDQRCRALLPSELRTLIQ
FT EAKEMKWPFVPEKWQYKQAVGPEDKTNLKDVIGAGLQQLL -> MCRKRTRARTSAAE
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044735"
FT VARIANT 67
FT /note="Q -> R (in dbSNP:rs33943680)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041511"
FT VARIANT 175
FT /note="N -> D (in dbSNP:rs6533616)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_028982"
FT VARIANT 237
FT /note="T -> M (in ROSAH)"
FT /evidence="ECO:0000269|PubMed:30967659,
FT ECO:0000269|PubMed:31939038"
FT /id="VAR_084993"
FT VARIANT 292
FT /note="T -> M (in dbSNP:rs34120296)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041512"
FT VARIANT 320
FT /note="L -> M (in dbSNP:rs757602009)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041513"
FT VARIANT 339
FT /note="K -> E (in an ovarian mucinous carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041514"
FT VARIANT 383
FT /note="K -> E (in dbSNP:rs147641444)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041515"
FT VARIANT 565
FT /note="G -> D (in dbSNP:rs2074388)"
FT /evidence="ECO:0000269|PubMed:10021370,
FT ECO:0000269|PubMed:10819331, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:17344846, ECO:0000269|Ref.5"
FT /id="VAR_028983"
FT VARIANT 642
FT /note="H -> R (in dbSNP:rs13148353)"
FT /evidence="ECO:0000269|PubMed:10021370,
FT ECO:0000269|PubMed:10819331, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:17344846, ECO:0000269|Ref.5"
FT /id="VAR_028984"
FT VARIANT 660
FT /note="P -> L (in dbSNP:rs35389530)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041516"
FT VARIANT 681
FT /note="G -> D (in dbSNP:rs35519493)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_041517"
FT VARIANT 732
FT /note="M -> I (in dbSNP:rs2074379)"
FT /evidence="ECO:0000269|PubMed:10021370,
FT ECO:0000269|PubMed:10819331, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:17344846, ECO:0000269|Ref.5"
FT /id="VAR_028985"
FT VARIANT 861
FT /note="M -> T (in dbSNP:rs11726117)"
FT /evidence="ECO:0000269|PubMed:10021370,
FT ECO:0000269|PubMed:10819331, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:17344846, ECO:0000269|Ref.5"
FT /id="VAR_028986"
FT VARIANT 870
FT /note="G -> S (in dbSNP:rs2074380)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_028987"
FT VARIANT 873
FT /note="R -> I (in dbSNP:rs34946272)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041518"
FT VARIANT 910
FT /note="E -> D (in dbSNP:rs35308602)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041519"
FT VARIANT 916
FT /note="N -> D (in dbSNP:rs2074381)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_028988"
FT VARIANT 935
FT /note="P -> L (in dbSNP:rs34780600)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041520"
FT VARIANT 1008
FT /note="H -> P (in dbSNP:rs34079946)"
FT /id="VAR_057741"
FT VARIANT 1084
FT /note="R -> Q (in dbSNP:rs34677416)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041521"
FT VARIANT 1117
FT /note="L -> P (in dbSNP:rs35756863)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041522"
FT VARIANT 1160
FT /note="A -> G (in dbSNP:rs55696324)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041523"
FT MUTAGEN 67
FT /note="Q->A: Impaired ADP-D-glycero-beta-D-manno-heptose-
FT binding and ability to activate the serine/threonine-
FT protein kinase activity; when associated with A-231."
FT /evidence="ECO:0000269|PubMed:30111836"
FT MUTAGEN 116
FT /note="R->A: Impaired ADP-D-glycero-beta-D-manno-heptose-
FT binding and ability to activate the serine/threonine-
FT protein kinase activity."
FT /evidence="ECO:0000269|PubMed:30111836"
FT MUTAGEN 150
FT /note="R->A: Impaired ADP-D-glycero-beta-D-manno-heptose-
FT binding and ability to activate the serine/threonine-
FT protein kinase activity."
FT /evidence="ECO:0000269|PubMed:30111836"
FT MUTAGEN 153
FT /note="R->A: Impaired ADP-D-glycero-beta-D-manno-heptose-
FT binding and ability to activate the serine/threonine-
FT protein kinase activity."
FT /evidence="ECO:0000269|PubMed:30111836"
FT MUTAGEN 231
FT /note="D->A: Impaired ADP-D-glycero-beta-D-manno-heptose-
FT binding and ability to activate the serine/threonine-
FT protein kinase activity; when associated with A-67."
FT /evidence="ECO:0000269|PubMed:30111836"
FT MUTAGEN 233
FT /note="K->A: Impaired ADP-D-glycero-beta-D-manno-heptose-
FT binding and ability to activate the serine/threonine-
FT protein kinase activity."
FT /evidence="ECO:0000269|PubMed:30111836"
FT MUTAGEN 237
FT /note="T->E: Impaired ADP-D-glycero-beta-D-manno-heptose-
FT binding and ability to activate the serine/threonine-
FT protein kinase activity; when associated with K-295."
FT /evidence="ECO:0000269|PubMed:30111836"
FT MUTAGEN 295
FT /note="F->K: Impaired ADP-D-glycero-beta-D-manno-heptose-
FT binding and ability to activate the serine/threonine-
FT protein kinase activity; when associated with E-237."
FT /evidence="ECO:0000269|PubMed:30111836"
FT MUTAGEN 1067
FT /note="K->M: Abolishes the serine/threonine-protein kinase
FT and ability to initiate the innate immune response."
FT /evidence="ECO:0000269|PubMed:30111836"
FT CONFLICT 83
FT /note="V -> L (in Ref. 5; BAC85140)"
FT /evidence="ECO:0000305"
FT CONFLICT 577
FT /note="S -> G (in Ref. 2; BAG65473)"
FT /evidence="ECO:0000305"
FT HELIX 4..23
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 30..41
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 45..55
FT /evidence="ECO:0007829|PDB:5Z2C"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 80..86
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 88..100
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 104..120
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 124..137
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 145..157
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 161..173
FT /evidence="ECO:0007829|PDB:5Z2C"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:5Z2C"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 187..206
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 210..225
FT /evidence="ECO:0007829|PDB:5Z2C"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 232..248
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 251..258
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 266..270
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 274..288
FT /evidence="ECO:0007829|PDB:5Z2C"
FT TURN 289..291
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 293..311
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 318..337
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 348..369
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 373..394
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 398..418
FT /evidence="ECO:0007829|PDB:5Z2C"
FT HELIX 442..444
FT /evidence="ECO:0007829|PDB:5Z2C"
SQ SEQUENCE 1244 AA; 138861 MW; 857D353D159A1630 CRC64;
MNNQKVVAVL LQECKQVLDQ LLLEAPDVSE EDKSEDQRCR ALLPSELRTL IQEAKEMKWP
FVPEKWQYKQ AVGPEDKTNL KDVIGAGLQQ LLASLRASIL ARDCAAAAAI VFLVDRFLYG
LDVSGKLLQV AKGLHKLQPA TPIAPQVVIR QARISVNSGK LLKAEYILSS LISNNGATGT
WLYRNESDKV LVQSVCIQIR GQILQKLGMW YEAAELIWAS IVGYLALPQP DKKGLSTSLG
ILADIFVSMS KNDYEKFKNN PQINLSLLKE FDHHLLSAAE ACKLAAAFSA YTPLFVLTAV
NIRGTCLLSY SSSNDCPPEL KNLHLCEAKE AFEIGLLTKR DDEPVTGKQE LHSFVKAAFG
LTTVHRRLHG ETGTVHAASQ LCKEAMGKLY NFSTSSRSQD REALSQEVMS VIAQVKEHLQ
VQSFSNVDDR SYVPESFECR LDKLILHGQG DFQKILDTYS QHHTSVCEVF ESDCGNNKNE
QKDAKTGVCI TALKTEIKNI DTVSTTQEKP HCQRDTGISS SLMGKNVQRE LRRGGRRNWT
HSDAFRVSLD QDVETETEPS DYSNGEGAVF NKSLSGSQTS SAWSNLSGFS SSASWEEVNY
HVDDRSARKE PGKEHLVDTQ CSTALSEELE NDREGRAMHS LHSQLHDLSL QEPNNDNLEP
SQNQPQQQMP LTPFSPHNTP GIFLAPGAGL LEGAPEGIQE VRNMGPRNTS AHSRPSYRSA
SWSSDSGRPK NMGTHPSVQK EEAFEIIVEF PETNCDVKDR QGKEQGEEIS ERGAGPTFKA
SPSWVDPEGE TAESTEDAPL DFHRVLHNSL GNISMLPCSS FTPNWPVQNP DSRKSGGPVA
EQGIDPDAST VDEEGQLLDS MDVPCTNGHG SHRLCILRQP PGQRAETPNS SVSGNILFPV
LSEDCTTTEE GNQPGNMLNC SQNSSSSSVW WLKSPAFSSG SSEGDSPWSY LNSSGSSWVS
LPGKMRKEIL EARTLQPDDF EKLLAGVRHD WLFQRLENTG VFKPSQLHRA HSALLLKYSK
KSELWTAQET IVYLGDYLTV KKKGRQRNAF WVHHLHQEEI LGRYVGKDYK EQKGLWHHFT
DVERQMTAQH YVTEFNKRLY EQNIPTQIFY IPSTILLILE DKTIKGCISV EPYILGEFVK
LSNNTKVVKT EYKATEYGLA YGHFSYEFSN HRDVVVDLQG WVTGNGKGLI YLTDPQIHSV
DQKVFTTNFG KRGIFYFFNN QHVECNEICH RLSLTRPSME KPCT
