ANKK1_HUMAN
ID ANKK1_HUMAN Reviewed; 765 AA.
AC Q8NFD2;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Ankyrin repeat and protein kinase domain-containing protein 1;
DE EC=2.7.11.1;
DE AltName: Full=Protein kinase PKK2;
DE AltName: Full=Sugen kinase 288;
DE Short=SgK288;
DE AltName: Full=X-kinase;
GN Name=ANKK1; Synonyms=PKK2, SGK288;
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], AND TISSUE SPECIFICITY.
RX PubMed=15146457; DOI=10.1002/humu.20039;
RA Neville M.J., Johnstone E.C., Walton R.T.;
RT "Identification and characterization of ANKK1: a novel kinase gene closely
RT linked to DRD2 on chromosome band 11q23.1.";
RL Hum. Mutat. 23:540-545(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Inohara N.;
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, AND VARIANT LYS-713.
RX PubMed=14741327; DOI=10.1016/s0920-9964(03)00220-2;
RA Dubertret C., Gouya L., Hanoun N., Deybach J.-C., Ades J., Hamon M.,
RA Gorwood P.;
RT "The 3' region of the DRD2 gene is involved in genetic susceptibility to
RT schizophrenia.";
RL Schizophr. Res. 67:75-85(2004).
RN [4]
RP IDENTIFICATION.
RX PubMed=12471243; DOI=10.1126/science.1075762;
RA Manning G., Whyte D.B., Martinez R., Hunter T., Sudarsanam S.;
RT "The protein kinase complement of the human genome.";
RL Science 298:1912-1934(2002).
RN [5]
RP VARIANTS [LARGE SCALE ANALYSIS] TYR-4; HIS-122; THR-239; LEU-276; ARG-318;
RP THR-347; PHE-366; GLN-367; LYS-376; LYS-426; ARG-442; ARG-451; ARG-490;
RP ILE-595; LEU-596; SER-653; GLY-670; LYS-713; LEU-717; LEU-736 AND LYS-764.
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 -!- 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 -!- 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;
CC -!- INTERACTION:
CC Q8NFD2; Q99622: C12orf57; NbExp=3; IntAct=EBI-13280688, EBI-2808472;
CC Q8NFD2; Q53TS8: C2CD6; NbExp=3; IntAct=EBI-13280688, EBI-739879;
CC Q8NFD2; P15882: CHN1; NbExp=3; IntAct=EBI-13280688, EBI-718947;
CC Q8NFD2; P52757: CHN2; NbExp=3; IntAct=EBI-13280688, EBI-714925;
CC Q8NFD2; Q9NWT6: HIF1AN; NbExp=4; IntAct=EBI-13280688, EBI-745632;
CC Q8NFD2; O95619: YEATS4; NbExp=4; IntAct=EBI-13280688, EBI-399269;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and weakly expressed in
CC placenta and spinal cord. {ECO:0000269|PubMed:14741327,
CC ECO:0000269|PubMed:15146457}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; AJ541797; CAD62569.2; -; mRNA.
DR EMBL; AF487542; AAQ09005.1; -; mRNA.
DR EMBL; AF525298; AAM91924.1; -; Genomic_DNA.
DR CCDS; CCDS44734.1; -.
DR RefSeq; NP_848605.1; NM_178510.1.
DR AlphaFoldDB; Q8NFD2; -.
DR SMR; Q8NFD2; -.
DR BioGRID; 129088; 21.
DR IntAct; Q8NFD2; 18.
DR STRING; 9606.ENSP00000306678; -.
DR BindingDB; Q8NFD2; -.
DR ChEMBL; CHEMBL5547; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q8NFD2; -.
DR iPTMnet; Q8NFD2; -.
DR PhosphoSitePlus; Q8NFD2; -.
DR BioMuta; ANKK1; -.
DR DMDM; 74762569; -.
DR jPOST; Q8NFD2; -.
DR MassIVE; Q8NFD2; -.
DR MaxQB; Q8NFD2; -.
DR PaxDb; Q8NFD2; -.
DR PeptideAtlas; Q8NFD2; -.
DR PRIDE; Q8NFD2; -.
DR Antibodypedia; 2098; 115 antibodies from 29 providers.
DR DNASU; 255239; -.
DR Ensembl; ENST00000303941.4; ENSP00000306678.3; ENSG00000170209.5.
DR GeneID; 255239; -.
DR KEGG; hsa:255239; -.
DR MANE-Select; ENST00000303941.4; ENSP00000306678.3; NM_178510.2; NP_848605.1.
DR UCSC; uc001pny.3; human.
DR CTD; 255239; -.
DR DisGeNET; 255239; -.
DR GeneCards; ANKK1; -.
DR HGNC; HGNC:21027; ANKK1.
DR HPA; ENSG00000170209; Tissue enhanced (skin).
DR MIM; 608774; gene.
DR neXtProt; NX_Q8NFD2; -.
DR OpenTargets; ENSG00000170209; -.
DR PharmGKB; PA134872551; -.
DR VEuPathDB; HostDB:ENSG00000170209; -.
DR eggNOG; KOG0192; Eukaryota.
DR GeneTree; ENSGT00940000162060; -.
DR HOGENOM; CLU_015188_1_0_1; -.
DR InParanoid; Q8NFD2; -.
DR OMA; SIYGVCR; -.
DR OrthoDB; 1112022at2759; -.
DR PhylomeDB; Q8NFD2; -.
DR TreeFam; TF106506; -.
DR PathwayCommons; Q8NFD2; -.
DR SignaLink; Q8NFD2; -.
DR BioGRID-ORCS; 255239; 8 hits in 1101 CRISPR screens.
DR GeneWiki; ANKK1; -.
DR GenomeRNAi; 255239; -.
DR Pharos; Q8NFD2; Tbio.
DR PRO; PR:Q8NFD2; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8NFD2; protein.
DR Bgee; ENSG00000170209; Expressed in right uterine tube and 86 other tissues.
DR ExpressionAtlas; Q8NFD2; baseline and differential.
DR GO; GO:0042995; C:cell projection; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0010564; P:regulation of cell cycle process; IDA:MGI.
DR Gene3D; 1.25.40.20; -; 5.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00023; Ank; 1.
DR Pfam; PF12796; Ank_2; 3.
DR Pfam; PF13637; Ank_4; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 11.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 11.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ANK repeat; ATP-binding; Kinase; Nucleotide-binding; Reference proteome;
KW Repeat; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..765
FT /note="Ankyrin repeat and protein kinase domain-containing
FT protein 1"
FT /id="PRO_0000085620"
FT DOMAIN 22..289
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 361..390
FT /note="ANK 1"
FT REPEAT 394..423
FT /note="ANK 2"
FT REPEAT 427..456
FT /note="ANK 3"
FT REPEAT 460..489
FT /note="ANK 4"
FT REPEAT 493..522
FT /note="ANK 5"
FT REPEAT 526..555
FT /note="ANK 6"
FT REPEAT 559..588
FT /note="ANK 7"
FT REPEAT 592..621
FT /note="ANK 8"
FT REPEAT 625..654
FT /note="ANK 9"
FT REPEAT 658..687
FT /note="ANK 10"
FT REPEAT 691..720
FT /note="ANK 11"
FT REPEAT 724..753
FT /note="ANK 12"
FT ACT_SITE 145
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 28..36
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 51
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VARIANT 4
FT /note="D -> Y (in dbSNP:rs35657708)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040359"
FT VARIANT 122
FT /note="R -> H (in dbSNP:rs35877321)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040360"
FT VARIANT 239
FT /note="A -> T (in dbSNP:rs7118900)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_036784"
FT VARIANT 276
FT /note="P -> L (in dbSNP:rs35488601)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040361"
FT VARIANT 318
FT /note="G -> R (in dbSNP:rs11604671)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_036785"
FT VARIANT 347
FT /note="K -> T (in a breast infiltrating ductal carcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040362"
FT VARIANT 366
FT /note="L -> F (in dbSNP:rs56339158)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040363"
FT VARIANT 367
FT /note="H -> Q (in dbSNP:rs34298987)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040364"
FT VARIANT 376
FT /note="E -> K (in dbSNP:rs56299709)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040365"
FT VARIANT 426
FT /note="E -> K (in dbSNP:rs55699907)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040366"
FT VARIANT 442
FT /note="G -> R (in dbSNP:rs4938016)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_036786"
FT VARIANT 451
FT /note="G -> R (in dbSNP:rs34983219)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040367"
FT VARIANT 490
FT /note="H -> R (in dbSNP:rs2734849)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_036787"
FT VARIANT 595
FT /note="T -> I (in dbSNP:rs55787008)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040368"
FT VARIANT 596
FT /note="P -> L (in dbSNP:rs7104979)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040369"
FT VARIANT 653
FT /note="N -> S (in dbSNP:rs55849504)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040370"
FT VARIANT 670
FT /note="S -> G (in dbSNP:rs56006094)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040371"
FT VARIANT 713
FT /note="E -> K (in dbSNP:rs1800497)"
FT /evidence="ECO:0000269|PubMed:14741327,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_025010"
FT VARIANT 717
FT /note="Q -> L (in a lung large cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040372"
FT VARIANT 736
FT /note="R -> L (in a lung squamous cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040373"
FT VARIANT 764
FT /note="E -> K (in a lung neuroendocrine carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040374"
SQ SEQUENCE 765 AA; 84632 MW; 549F6161B2976BF5 CRC64;
MAADPTELRL GSLPVFTRDD FEGDWRLVAS GGFSQVFQAR HRRWRTEYAI KCAPCLPPDA
ASSDVNYLIE EAAKMKKIKF QHIVSIYGVC KQPLGIVMEF MANGSLEKVL STHSLCWKLR
FRIIHETSLA MNFLHSIKPP LLHLDLKPGN ILLDSNMHVK ISDFGLSKWM EQSTRMQYIE
RSALRGMLSY IPPEMFLESN KAPGPKYDVY SFAIVIWELL TQKKPYSGFN MMMIIIRVAA
GMRPSLQPVS DQWPSEAQQM VDLMKRCWDQ DPKKRPCFLD ITIETDILLS LLQSRVAVPE
SKALARKVSC KLSLRQPGEV NEDISQELMD SDSGNYLKRA LQLSDRKNLV PRDEELCIYE
NKVTPLHFLV AQGSVEQVRL LLAHEVDVDC QTASGYTPLL IAAQDQQPDL CALLLAHGAD
ANRVDEDGWA PLHFAAQNGD DGTARLLLDH GACVDAQERE GWTPLHLAAQ NNFENVARLL
VSRQADPNLH EAEGKTPLHV AAYFGHVSLV KLLTSQGAEL DAQQRNLRTP LHLAVERGKV
RAIQHLLKSG AVPDALDQSG YGPLHTAAAR GKYLICKMLL RYGASLELPT HQGWTPLHLA
AYKGHLEIIH LLAESHANMG ALGAVNWTPL HLAARHGEEA VVSALLQCGA DPNAAEQSGW
TPLHLAVQRS TFLSVINLLE HHANVHARNK VGWTPAHLAA LKGNTAILKV LVEAGAQLDV
QDGVSCTPLQ LALRSRKQGI MSFLEGKEPS VATLGGSKPG AEMEI
