HIPK1_RAT
ID HIPK1_RAT Reviewed; 1211 AA.
AC A4L9P5; A4L9P6;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Homeodomain-interacting protein kinase 1;
DE EC=2.7.11.1;
GN Name=Hipk1 {ECO:0000312|EMBL:ABO47653.1};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000305, ECO:0000312|EMBL:ABO47653.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RA Hagemann C., Stojic J., Weigelin B., Kessler A., Roosen K., Vince G.H.;
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Serine/threonine-protein kinase involved in transcription
CC regulation and TNF-mediated cellular apoptosis. Plays a role as a
CC corepressor for homeodomain transcription factors. Phosphorylates DAXX
CC and MYB. Phosphorylates DAXX in response to stress, and mediates its
CC translocation from the nucleus to the cytoplasm. Inactivates MYB
CC transcription factor activity by phosphorylation. Prevents MAP3K5-JNK
CC activation in the absence of TNF. TNF triggers its translocation to the
CC cytoplasm in response to stress stimuli, thus activating nuclear
CC MAP3K5-JNK by derepression and promoting apoptosis. May be involved in
CC anti-oxidative stress responses. Involved in the regulation of eye
CC size, lens formation and retinal lamination during late embryogenesis.
CC Promotes angiogenesis and to be involved in erythroid differentiation.
CC May be involved in malignant squamous cell tumor formation (By
CC similarity). Phosphorylates PAGE4 at 'Thr-51' which is critical for the
CC ability of PAGE4 to potentiate the transcriptional activator activity
CC of JUN (By similarity). {ECO:0000250|UniProtKB:Q86Z02}.
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:O88904};
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:O88904};
CC -!- SUBUNIT: Interacts with Nkx1-2, Nkx2-5, MYB, PARK7, DAXX and p53/TP53.
CC Part of a cytoplasmic complex made of HIPK1, DAB2IP and MAP3K5 in
CC response to TNF. This complex formation promotes MAP3K5-JNK activation
CC and subsequent apoptosis (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O88904}. Cytoplasm
CC {ECO:0000250|UniProtKB:O88904}. Nucleus speckle
CC {ECO:0000250|UniProtKB:O88904}. Note=Predominantly nuclear.
CC Translocates from nucleus to cytoplasm in response to stress stimuli
CC via SENP1-mediated desumoylation (By similarity).
CC {ECO:0000250|UniProtKB:O88904}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A4L9P5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A4L9P5-2; Sequence=VSP_052489;
CC -!- PTM: Phosphorylated and activated by JNK1. Autophosphorylated (By
CC similarity). {ECO:0000250|UniProtKB:Q86Z02}.
CC -!- PTM: Sumoylated. When conjugated it is directed to nuclear speckles.
CC SENP1-mediated desumoylation is mediated by TNF in response to stress
CC stimuli, triggering transient translocation from nucleus to cytoplasm
CC (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. HIPK subfamily. {ECO:0000305}.
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DR EMBL; EF460311; ABO47653.1; -; mRNA.
DR EMBL; EF460312; ABO47654.1; -; mRNA.
DR AlphaFoldDB; A4L9P5; -.
DR SMR; A4L9P5; -.
DR IntAct; A4L9P5; 1.
DR MINT; A4L9P5; -.
DR STRING; 10116.ENSRNOP00000061079; -.
DR CarbonylDB; A4L9P5; -.
DR iPTMnet; A4L9P5; -.
DR PhosphoSitePlus; A4L9P5; -.
DR PaxDb; A4L9P5; -.
DR PeptideAtlas; A4L9P5; -.
DR UCSC; RGD:1304941; rat. [A4L9P5-1]
DR RGD; 1304941; Hipk1.
DR eggNOG; KOG0667; Eukaryota.
DR InParanoid; A4L9P5; -.
DR PhylomeDB; A4L9P5; -.
DR Reactome; R-RNO-6804756; Regulation of TP53 Activity through Phosphorylation.
DR PRO; PR:A4L9P5; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0016607; C:nuclear speck; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0016605; C:PML body; ISO:RGD.
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; IBA:GO_Central.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0034333; P:adherens junction assembly; ISO:RGD.
DR GO; GO:0009952; P:anterior/posterior pattern specification; ISO:RGD.
DR GO; GO:0048596; P:embryonic camera-type eye morphogenesis; ISO:RGD.
DR GO; GO:0060059; P:embryonic retina morphogenesis in camera-type eye; ISO:RGD.
DR GO; GO:0072577; P:endothelial cell apoptotic process; ISO:RGD.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISO:RGD.
DR GO; GO:0061072; P:iris morphogenesis; ISO:RGD.
DR GO; GO:0060235; P:lens induction in camera-type eye; ISO:RGD.
DR GO; GO:0030182; P:neuron differentiation; ISO:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; ISO:RGD.
DR GO; GO:0010842; P:retina layer formation; ISO:RGD.
DR GO; GO:0007224; P:smoothened signaling pathway; ISO:RGD.
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 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Cytoplasm; Isopeptide bond; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transcription; Transcription regulation;
KW Transferase; Ubl conjugation.
FT CHAIN 1..1211
FT /note="Homeodomain-interacting protein kinase 1"
FT /id="PRO_0000296298"
FT DOMAIN 190..518
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 835..856
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 885..1094
FT /note="Interaction with TP53"
FT /evidence="ECO:0000250|UniProtKB:O88904"
FT REGION 891..998
FT /note="Required for localization to nuclear speckles"
FT /evidence="ECO:0000250"
FT REGION 902..926
FT /note="SUMO interaction motifs (SIM); required for nuclear
FT localization and kinase activity"
FT /evidence="ECO:0000250"
FT REGION 1002..1023
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1047..1070
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1085..1105
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 844..847
FT /note="Nuclear localization signal 1 (NLS1)"
FT /evidence="ECO:0000250"
FT ACT_SITE 315
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 196..204
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 219
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 872
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86Z02"
FT MOD_RES 1201
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86Z02"
FT CROSSLNK 25
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 25
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q86Z02"
FT CROSSLNK 120
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q86Z02"
FT CROSSLNK 124
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q86Z02"
FT CROSSLNK 991
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q86Z02"
FT CROSSLNK 1204
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 552..585
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_052489"
SQ SEQUENCE 1211 AA; 130801 MW; EB1ABD970F71BDF4 CRC64;
MASQLQVFSP PSVSSSAFCS AKKLKIEPSG WDVSGQSSND KYYTHSKTLP ATQGQASSSH
QVANFNIPAY DQGLLLQAPA VEHIVVTAAD SSGSAATATF QSSQTLTHRS NVSLLEPYQK
CGLKRKSEEV DSNGSVQIIE EHPPLMLQNR TVVGAAATTT TVTTKSSSSS GEGDYQLVQH
EILCSMTNSY EVLEFLGRGT FGQVAKCWKR STKEIVAIKI LKNHPSYARQ GQIEVSILSR
LSSENADEYN FVRSYECFQH KNHTCLVFEM LEQNLYDFLK QNKFSPLPLK YIRPILQQVA
TALMKLKSLG LIHADLKPEN IMLVDPVRQP YRVKVIDFGS ASHVSKAVCS TYLQSRYYRA
PEIILGLPFC EAIDMWSLGC VIAELFLGWP LYPGASEYDQ IRYISQTQGL PAEYLLSAGT
KTTRFFNRDP NLGYPLWRLK TPEEHELETG IKSKEARKYI FNCLDDMAQV NMSTDLEGTD
MLAEKADRRE YIDLLKKMLT IDADKRVTPL KTLNHQFVTM THLLDFPHSN HVKSCFQNME
ICKRRVHMYD TVSQIKSPFT THVAPSTSTN LTMSFSNQLS TVHNQASVLA SSSTAAAATL
SLANSDVSLL NYQSALYPPS AAPVPGVAQQ GVSLQPGTTQ ICTQTDPFQQ TFIVCPPAFQ
TGLQATTKHS GFPVRMDNAV PLVPQAPAAQ PLQIQSGVLT QGSCTPLMVA TLHPQVATIT
PQYAVPFTLS CAAGRPALVE QTAAVQQAWP GGTQQILLPS AWQQLPGVAL HNSVQPTAVI
PEAMGSSQQL ADWRNAHSHG NQYSTIMQQP SLLTNHVTLA TAQPLNVGVA HVVRQQQSSS
LPSRKNKQSA PVSSTSSLEV LPSQVYSLVG SSPLRTTSSY NSLVPVQDQH QPIIIPDTPS
PPVSVITIRS DTDEEEDNKF KPSSSSLKAR SNVISYVTVN DSPDSDSSLS SPYPTDTLSA
LRGNSGTLLE GPGRTAADGI GTRTIIVPPL KTQLGDCTGA TQASGLLSSS KTKPVASVSG
QSSGCCITPT GYRAQRGGAS AVQPLNLSQN QQSSSASTSQ ERSSNPAPRR QQAFVAPLSQ
APYAFQHGSP LHSTGHPHLA PAPAHLPSQP HLYTYAAPTS AAALGSTSSI AHLFSPQGSS
RHAAAYTTHP STLVHQVPVS VGPSLLTSAS VAPAQYQHQF ATQSYIGSSR GSTIYTGYPL
SPTKISQYSY L
