DYR1A_RABIT
ID DYR1A_RABIT Reviewed; 200 AA.
AC P85051;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Dual specificity tyrosine-phosphorylation-regulated kinase 1A;
DE EC=2.7.12.1 {ECO:0000269|PubMed:11311120};
DE AltName: Full=Dual specificity YAK1-related kinase;
DE AltName: Full=Protein kinase minibrain homolog;
DE Short=MNBH;
DE AltName: Full=RP86;
DE Flags: Fragments;
GN Name=DYRK1A {ECO:0000303|PubMed:11311120};
GN Synonyms=DYRK {ECO:0000250|UniProtKB:Q13627};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1] {ECO:0000305}
RP PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, AND AUTOPHOSPHORYLATION.
RC STRAIN=New Zealand white {ECO:0000269|PubMed:11311120};
RC TISSUE=Skeletal muscle {ECO:0000269|PubMed:11311120};
RX PubMed=11311120; DOI=10.1042/bj3550597;
RA Woods Y.L., Rena G., Morrice N., Barthel A., Becker W., Guo S.,
RA Unterman T.G., Cohen P.;
RT "The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329
RT in vitro, a novel in vivo phosphorylation site.";
RL Biochem. J. 355:597-607(2001).
CC -!- FUNCTION: Dual-specificity kinase which possesses both serine/threonine
CC and tyrosine kinase activities. May play a role in a signaling pathway
CC regulating nuclear functions of cell proliferation. Modulates
CC alternative splicing by phosphorylating the splice factor SRSF6 (By
CC similarity). Exhibits a substrate preference for proline at position
CC P+1 and arginine at position P-3. Has pro-survival function and
CC negatively regulates the apoptotic process. Promotes cell survival upon
CC genotoxic stress through phosphorylation of SIRT1. This in turn
CC inhibits TP53 activity and apoptosis (By similarity). Phosphorylates
CC SEPTIN4, SEPTIN5 and SF3B1 (By similarity).
CC {ECO:0000250|UniProtKB:Q61214, ECO:0000250|UniProtKB:Q63470,
CC ECO:0000250|UniProtKB:Q9NR20, ECO:0000269|PubMed:11311120}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC Evidence={ECO:0000269|PubMed:11311120};
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=2.7.12.1;
CC Evidence={ECO:0000269|PubMed:11311120};
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=2.7.12.1; Evidence={ECO:0000269|PubMed:11311120};
CC -!- ACTIVITY REGULATION: Inhibited by RANBP9.
CC {ECO:0000250|UniProtKB:Q13627}.
CC -!- SUBUNIT: Interacts with RANBP9 (By similarity). Interacts with
CC RAD54L2/ARIP4 (By similarity). Interacts with CRY2 (By similarity).
CC Interacts with WDR68 (By similarity). Interacts with SIRT1 (By
CC similarity). Interacts with SEPTIN4 and SEPTIN5 (By similarity).
CC {ECO:0000250|UniProtKB:Q13627, ECO:0000250|UniProtKB:Q61214,
CC ECO:0000250|UniProtKB:Q63470}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11311120}.
CC -!- PTM: Can also autophosphorylate on serine and threonine residues (in
CC vitro) (By similarity). Autophosphorylated on numerous tyrosine
CC residues. {ECO:0000250|UniProtKB:Q13627, ECO:0000269|PubMed:11311120}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MNB/DYRK subfamily. {ECO:0000305}.
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DR AlphaFoldDB; P85051; -.
DR CORUM; P85051; -.
DR PRIDE; P85051; -.
DR eggNOG; KOG0667; Eukaryota.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR InterPro; IPR028318; DYRK1A/B_MNB.
DR PANTHER; PTHR24058:SF121; PTHR24058:SF121; 3.
PE 1: Evidence at protein level;
KW ATP-binding; Direct protein sequencing; Kinase; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
FT CHAIN <1..>200
FT /note="Dual specificity tyrosine-phosphorylation-regulated
FT kinase 1A"
FT /id="PRO_0000271242"
FT BINDING 58
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q63470,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 41
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT MOD_RES 76
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q63470"
FT MOD_RES 88
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT MOD_RES 122
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q13627"
FT NON_CONS 36..37
FT /evidence="ECO:0000303|PubMed:11311120"
FT NON_CONS 49..50
FT /evidence="ECO:0000303|PubMed:11311120"
FT NON_CONS 58..59
FT /evidence="ECO:0000303|PubMed:11311120"
FT NON_CONS 69..70
FT /evidence="ECO:0000303|PubMed:11311120"
FT NON_CONS 82..83
FT /evidence="ECO:0000303|PubMed:11311120"
FT NON_CONS 95..96
FT /evidence="ECO:0000303|PubMed:11311120"
FT NON_CONS 113..114
FT /evidence="ECO:0000303|PubMed:11311120"
FT NON_CONS 126..127
FT /evidence="ECO:0000303|PubMed:11311120"
FT NON_CONS 142..143
FT /evidence="ECO:0000303|PubMed:11311120"
FT NON_CONS 149..150
FT /evidence="ECO:0000303|PubMed:11311120"
FT NON_CONS 156..157
FT /evidence="ECO:0000303|PubMed:11311120"
FT NON_CONS 169..170
FT /evidence="ECO:0000303|PubMed:11311120"
FT NON_TER 1
FT /evidence="ECO:0000303|PubMed:11311120"
FT NON_TER 200
FT /evidence="ECO:0000303|PubMed:11311120"
SQ SEQUENCE 200 AA; 22896 MW; 9ACA2DC506146E90 CRC64;
QPSISDQQVS ALPYSDQIQQ PLTNQVMPDI VMLQRRWMDR YEIDSLIGKV EQEWVAIKAF
LNQAQIEVRH DTEMKYYIVH LKIVDFGSSC QLGQRIVEVL GIPPAHILDQ APKFFEKLPD
GTWSLKKLHN ILGVETGGPG GRFKDLILRM LDYDPKIQPY YALQHSFFKQ ETGIAGHPTY
QFSANTGPAH YMTEGHLAMR
