ID ZNHI1_BOVIN Reviewed; 154 AA.
AC Q24JY4;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-APR-2006, sequence version 1.
DT 24-JAN-2024, entry version 93.
DE RecName: Full=Zinc finger HIT domain-containing protein 1;
DE AltName: Full=p18 Hamlet {ECO:0000250|UniProtKB:O43257};
GN Name=ZNHIT1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Plays a role in chromatin remodeling by promoting the
CC incorporation of histone variant H2AZ1/H2A.Z into the genome to
CC regulate gene expression (By similarity). Promotes SRCAP complex-
CC mediated deposition of histone variant H2AZ1 to lymphoid fate regulator
CC genes, enhancing lymphoid lineage commitment (By similarity). Recruited
CC to the promoter of the transcriptional activator MYOG at the early
CC stages of muscle differentiation where it mediates binding of histone
CC H2AZ1 to chromatin and induces muscle-specific gene expression (By
CC similarity). Maintains hematopoietic stem cell (HSC) quiescence by
CC determining the chromatin accessibility at distal enhancers of HSC
CC quiescence genes such as PTEN, FSTL1 and KLF4, enhancing deposition of
CC H2AZ1 to promote their sustained transcription and restricting PI3K-AKT
CC signaling inhibition (By similarity). Plays a role in intestinal stem
CC cell maintenance by promoting H2AZ1 deposition at the transcription
CC start sites of genes involved in intestinal stem cell fate
CC determination including LGR5, TGFB1 and TGFBR2, thereby contributing to
CC gene transcription (By similarity). Promotes phosphorylation of the
CC H2AZ1 chaperone VPS72/YL1 which enhances the interaction between HZAZ1
CC and VPS72 (By similarity). Regulates the entry of male germ cells into
CC meiosis by controlling histone H2AZ1 deposition which facilitates the
CC expression of meiotic genes such as MEIOSIN, leading to the initiation
CC of meiosis (By similarity). Required for postnatal heart function
CC through its role in maintenance of cardiac Ca(2+) homeostasis by
CC modulating the expression of Ca(2+)-regulating proteins CASQ1 and
CC ATP2A2/SERCA2A via deposition of histone H2AZ1 at their promoters (By
CC similarity). During embryonic heart development, required for
CC mitochondrial maturation and oxidative metabolism by functioning
CC through H2AZ1 deposition to activate transcription of metabolic genes
CC and is also required to maintain the stability of the respiratory
CC complex (By similarity). In neural cells, increases deposition of the
CC H2AZ1 histone variant and promotes neurite growth (By similarity).
CC Plays a role in TP53/p53-mediated apoptosis induction by stimulating
CC the transcriptional activation of several proapoptotic p53 target genes
CC such as PMAIP1/NOXA and BBC3/PUMA (By similarity). Mediates cell cycle
CC arrest induced in response to gamma-irradiation by enhancing
CC recruitment of TP53/p53 to the promoter of the cell cycle inhibitor
CC CDKN1A, leading to its transcriptional activation (By similarity).
CC Recruited to the promoter of cyclin-dependent kinase CDK6 and inhibits
CC its transcription, possibly by decreasing the acetylation level of
CC histone H4, leading to cell cycle arrest at the G1 phase (By
CC similarity). Plays a role in lens fiber cell differentiation by
CC regulating the expression of cell cycle regulator CDKN1A/p21Cip1 (By
CC similarity). Binds to transcriptional repressor NR1D2 and relieves it
CC of its inhibitory effect on the transcription of apolipoprotein APOC3
CC without affecting its DNA-binding activity (By similarity).
CC {ECO:0000250|UniProtKB:O43257, ECO:0000250|UniProtKB:Q8R331}.
CC -!- SUBUNIT: Component of the chromatin-remodeling SRCAP complex composed
CC of at least SRCAP, DMAP1, RUVBL1, RUVBL2, ACTL6A, YEATS4, ACTR6 and
CC ZNHIT1 (By similarity). Interacts with MAPK11 and MAPK14 (By
CC similarity). Interacts with NR1D1 and NR2D2 (By similarity). Interacts
CC (via HIT-type zinc finger) with the RUVBL1/RUVBL2 complex in the
CC presence of ADP (By similarity). Interacts with histone deacetylase
CC HDAC1 (By similarity). Interacts with histone H2AZ1; the interaction
CC results in recruitment of H2AZ1 to the MYOG promoter region (By
CC similarity). Interacts with PCID2; the interaction results in
CC inhibition of SRCAP complex activity, preventing the deposition of
CC histone variant H2Az1 to lymphoid fate regulator genes and restricting
CC lymphoid lineage commitment (By similarity).
CC {ECO:0000250|UniProtKB:O43257, ECO:0000250|UniProtKB:Q8R331}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O43257}.
CC -!- PTM: Phosphorylated on Thr by MAPK11 or MAPK14 (By similarity).
CC Phosphorylation is required for MYOG induction, for deposition of
CC histone H2AZ1 at the MYOG promoter and for SRCAP complex integrity (By
CC similarity). {ECO:0000250|UniProtKB:O43257}.
CC -!- SIMILARITY: Belongs to the ZNHIT1 family. {ECO:0000305}.
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DR EMBL; BC114191; AAI14192.1; -; mRNA.
DR RefSeq; NP_001039650.1; NM_001046185.2.
DR AlphaFoldDB; Q24JY4; -.
DR STRING; 9913.ENSBTAP00000060443; -.
DR PaxDb; 9913-ENSBTAP00000000448; -.
DR Ensembl; ENSBTAT00000000448.4; ENSBTAP00000000448.3; ENSBTAG00000000343.4.
DR GeneID; 514997; -.
DR KEGG; bta:514997; -.
DR CTD; 10467; -.
DR VEuPathDB; HostDB:ENSBTAG00000000343; -.
DR VGNC; VGNC:37358; ZNHIT1.
DR eggNOG; KOG3362; Eukaryota.
DR GeneTree; ENSGT00390000018426; -.
DR HOGENOM; CLU_106918_2_1_1; -.
DR InParanoid; Q24JY4; -.
DR OMA; CIPCGAR; -.
DR OrthoDB; 2029831at2759; -.
DR TreeFam; TF314330; -.
DR Proteomes; UP000009136; Chromosome 25.
DR Bgee; ENSBTAG00000000343; Expressed in retina and 108 other cell types or tissues.
DR ExpressionAtlas; Q24JY4; baseline and differential.
DR GO; GO:0000812; C:Swr1 complex; IBA:GO_Central.
DR GO; GO:0042393; F:histone binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031491; F:nucleosome binding; IBA:GO_Central.
DR GO; GO:0055074; P:calcium ion homeostasis; ISS:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB.
DR GO; GO:0003015; P:heart process; ISS:UniProtKB.
DR GO; GO:0036335; P:intestinal stem cell homeostasis; ISS:UniProtKB.
DR GO; GO:0042692; P:muscle cell differentiation; IEA:Ensembl.
DR GO; GO:1902164; P:positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; ISS:UniProtKB.
DR GO; GO:1905458; P:positive regulation of lymphoid progenitor cell differentiation; ISS:UniProtKB.
DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; ISS:UniProtKB.
DR Gene3D; 3.30.60.190; -; 1.
DR InterPro; IPR039723; Vps71/ZNHIT1.
DR InterPro; IPR007529; Znf_HIT.
DR PANTHER; PTHR13093; ZINC FINGER HIT DOMAIN CONTAINING PROTEIN 1; 1.
DR PANTHER; PTHR13093:SF0; ZINC FINGER HIT DOMAIN-CONTAINING PROTEIN 1; 1.
DR Pfam; PF04438; zf-HIT; 1.
DR SUPFAM; SSF144232; HIT/MYND zinc finger-like; 1.
DR PROSITE; PS51083; ZF_HIT; 1.
PE 2: Evidence at transcript level;
KW Chromatin regulator; Coiled coil; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..154
FT /note="Zinc finger HIT domain-containing protein 1"
FT /id="PRO_0000239846"
FT ZN_FING 117..149
FT /note="HIT-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00453"
FT REGION 1..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 72..110
FT /note="Interaction with NR1D2"
FT /evidence="ECO:0000250|UniProtKB:O43257"
FT COILED 23..39
FT /evidence="ECO:0000255"
FT MOTIF 38..47
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:O43257"
FT COMPBIAS 1..40
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 117
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00453"
FT BINDING 120
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00453"
FT BINDING 128
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00453"
FT BINDING 131
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00453"
FT BINDING 136
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00453"
FT BINDING 140
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00453"
FT BINDING 144
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00453"
FT BINDING 149
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00453"
FT MOD_RES 103
FT /note="Phosphothreonine; by MAPK11 and MAPK14"
FT /evidence="ECO:0000250|UniProtKB:O43257"
SQ SEQUENCE 154 AA; 17536 MW; 6A45F05249DC07A6 CRC64;
MVEKKTSVRS QDPGQRRVLD RAARQRRINR QLEALENDNF QDDPHAGLPQ LGKRLPQFDD
DADTGKKKKK TRGDHFKLRF RKNFQALLEE QNLSVAEGPN YLTACAGPPS RPQRPFCAVC
GFPSPYTCVS CGARYCTVRC LGTHQETRCL KWTV
//
