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MGP006763

UniProt Annotations

Entry Information

Gene Name	homeodomain interacting protein kinase 1
Protein Entry	HIPK1_HUMAN
UniProt ID	Q86Z02
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=4; Name=1; Synonyms=HIPK1-alpha; IsoId=Q86Z02-1; Sequence=Displayed; Name=2; Synonyms=HIPK1-beta; IsoId=Q86Z02-2; Sequence=VSP_013130, VSP_013131; Name=3; IsoId=Q86Z02-3; Sequence=VSP_013128; Name=4; IsoId=Q86Z02-4; Sequence=VSP_013127, VSP_013129;
Catalytic Activity	ATP + a protein = ADP + a phosphoprotein.
Function	Serine/threonine-protein kinase involved in transcription regulation and TNF-mediated cellular apoptosis. Plays a role as a corepressor for homeodomain transcription factors. Phosphorylates DAXX and MYB. Phosphorylates DAXX in response to stress, and mediates its translocation from the nucleus to the cytoplasm. Inactivates MYB transcription factor activity by phosphorylation. Prevents MAP3K5-JNK activation in the absence of TNF. TNF triggers its translocation to the cytoplasm in response to stress stimuli, thus activating nuclear MAP3K5-JNK by derepression and promoting apoptosis. May be involved in anti- oxidative stress responses. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. Promotes angiogenesis and to be involved in erythroid differentiation. May be involved in malignant squamous cell tumor formation. {ECO:0000269\|PubMed:12702766, ECO:0000269\|PubMed:12968034, ECO:0000269\|PubMed:15701637, ECO:0000269\|PubMed:16390825, ECO:0000269\|PubMed:19646965}.
Interaction	P04637:TP53; NbExp=2; IntAct=EBI-692891, EBI-366083;
Ptm	Autophosphorylated. Phosphorylated and activated by JNK1. {ECO:0000269\|PubMed:12968034, ECO:0000269\|PubMed:19690332}.
Ptm	Degraded by PARK7 at the protein level.
Ptm	Sumoylated. When conjugated it is directed to nuclear speckles. SENP1-mediated desumoylation is mediated by TNF in response to stress stimuli, triggering transient translocation from nucleus to cytoplasm. {ECO:0000269\|PubMed:15701637, ECO:0000269\|PubMed:18219322}.
Similarity	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily. {ECO:0000305}.
Similarity	Contains 1 protein kinase domain. {ECO:0000255\|PROSITE-ProRule:PRU00159}.
Subcellular Location	Nucleus. Cytoplasm. Note=Predominantly nuclear. Translocates from nucleus to cytoplasm in response to stress stimuli via SENP1-mediated desumoylation.
Subunit	Interacts with Nkx1-2, Nkx2-5, MYB, PARK7, DAXX and p53/TP53. Part of a cytoplasmic complex made of HIPK1, DAB2IP and MAP3K5 in response to TNF. This complex formation promotes MAP3K5- JNK activation and subsequent apoptosis. {ECO:0000269\|PubMed:12529400, ECO:0000269\|PubMed:12702766, ECO:0000269\|PubMed:15701637, ECO:0000269\|PubMed:16390825, ECO:0000269\|PubMed:19646965}.
Tissue Specificity	Ubiquitously expressed with highest levels in skeletal muscle and heart. Overexpressed in breast cancer cell lines. Isoform 2 is highly expressed in testis. {ECO:0000269\|PubMed:12529400, ECO:0000269\|PubMed:12702766}.