ZPR1_HUMAN
ID ZPR1_HUMAN Reviewed; 459 AA.
AC O75312; Q2TAA0;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Zinc finger protein ZPR1;
DE AltName: Full=Zinc finger protein 259;
GN Name=ZPR1; Synonyms=ZNF259;
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 INTERACTION WITH EEF1A1.
RX PubMed=9852145; DOI=10.1083/jcb.143.6.1471;
RA Gangwani L., Mikrut M., Galcheva-Gargova Z., Davis R.J.;
RT "Interaction of ZPR1 with translation elongation factor-1alpha in
RT proliferating cells.";
RL J. Cell Biol. 143:1471-1484(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Pancreas, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH EGFR, AND SUBCELLULAR LOCATION.
RX PubMed=8650580; DOI=10.1126/science.272.5269.1797;
RA Galcheva-Gargova Z., Konstantinov K.N., Wu I.-H., Klier F.G., Barrett T.,
RA Davis R.J.;
RT "Binding of zinc finger protein ZPR1 to the epidermal growth factor
RT receptor.";
RL Science 272:1797-1802(1996).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=9763455; DOI=10.1091/mbc.9.10.2963;
RA Galcheva-Gargova Z., Gangwani L., Konstantinov K.N., Mikrut M.,
RA Theroux S.J., Enoch T., Davis R.J.;
RT "The cytoplasmic zinc finger protein ZPR1 accumulates in the nucleolus of
RT proliferating cells.";
RL Mol. Biol. Cell 9:2963-2971(1998).
RN [6]
RP FUNCTION, INTERACTION WITH SMN1, AND SUBCELLULAR LOCATION.
RX PubMed=11283611; DOI=10.1038/35070059;
RA Gangwani L., Mikrut M., Theroux S., Sharma M., Davis R.J.;
RT "Spinal muscular atrophy disrupts the interaction of ZPR1 with the SMN
RT protein.";
RL Nat. Cell Biol. 3:376-383(2001).
RN [7]
RP IDENTIFICATION IN AN IMPORT SNRNP COMPLEX.
RX PubMed=12095920; DOI=10.1093/hmg/11.15.1785;
RA Narayanan U., Ospina J.K., Frey M.R., Hebert M.D., Matera A.G.;
RT "SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex
RT with snurportin1 and importin beta.";
RL Hum. Mol. Genet. 11:1785-1795(2002).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17068332; DOI=10.1074/jbc.m608165200;
RA Gangwani L.;
RT "Deficiency of the zinc finger protein ZPR1 causes defects in transcription
RT and cell cycle progression.";
RL J. Biol. Chem. 281:40330-40340(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22422766; DOI=10.1093/hmg/dds102;
RA Ahmad S., Wang Y., Shaik G.M., Burghes A.H., Gangwani L.;
RT "The zinc finger protein ZPR1 is a potential modifier of spinal muscular
RT atrophy.";
RL Hum. Mol. Genet. 21:2745-2758(2012).
RN [11]
RP FUNCTION, INVOLVEMENT IN GKAF, VARIANT GKAF THR-196, AND CHARACTERIZATION
RP OF VARIANT GKAF THR-196.
RX PubMed=29851065; DOI=10.1111/cge.13388;
RG Care4Rare Canada Consortium;
RA Ito Y.A., Smith A.C., Kernohan K.D., Pena I.A., Ahmed A., McDonell L.M.,
RA Beaulieu C., Bulman D.E., Smidt A., Sawyer S.L., Dyment D.A., Boycott K.M.,
RA Clericuzio C.L.;
RT "A ZPR1 mutation is associated with a novel syndrome of growth restriction,
RT distinct craniofacial features, alopecia, and hypoplastic kidneys.";
RL Clin. Genet. 94:303-312(2018).
CC -!- FUNCTION: Acts as a signaling molecule that communicates proliferative
CC growth signals from the cytoplasm to the nucleus. It is involved in the
CC positive regulation of cell cycle progression (PubMed:29851065). Plays
CC a role for the localization and accumulation of the survival motor
CC neuron protein SMN1 in sub-nuclear bodies, including gems and Cajal
CC bodies. Induces neuron differentiation and stimulates axonal growth and
CC formation of growth cone in spinal cord motor neurons. Plays a role in
CC the splicing of cellular pre-mRNAs. May be involved in H(2)O(2)-induced
CC neuronal cell death. {ECO:0000269|PubMed:11283611,
CC ECO:0000269|PubMed:17068332, ECO:0000269|PubMed:22422766,
CC ECO:0000269|PubMed:29851065}.
CC -!- SUBUNIT: Component of an import snRNP complex composed of KPNB1, SNUPN,
CC SMN1 and ZNF259. Interacts (via C-terminal region) with SMN1 (via C-
CC terminal region); the interaction occurs after treatment with serum.
CC Interacts with elongation factor 1-alpha EEF1A1; the interaction occurs
CC in a epidermal growth factor (EGF)-dependent manner. Interacts (via
CC zinc fingers) with EGFR (via C-terminal cytoplasmic kinase domain); the
CC interaction is negatively regulated in response to epidermal growth
CC factor (EGF) stimulation and the EGFR kinase activity. May also bind to
CC the PDGFR receptor. {ECO:0000269|PubMed:11283611,
CC ECO:0000269|PubMed:12095920, ECO:0000269|PubMed:8650580,
CC ECO:0000269|PubMed:9852145}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus, nucleolus. Nucleus, gem.
CC Nucleus, Cajal body. Cytoplasm, perinuclear region. Cytoplasm. Cell
CC projection, axon {ECO:0000250}. Cell projection, growth cone
CC {ECO:0000250}. Note=Colocalized with SMN1 in Gemini of coiled bodies
CC (gems), Cajal bodies, axon and growth cones of neurons (By similarity).
CC Localized predominantly in the cytoplasm in serum-starved cells growth
CC arrested in G0 of the mitotic cell cycle. Localized both in the nucleus
CC and cytoplasm at the G1 phase of the mitotic cell cycle. Accumulates in
CC the subnuclear bodies during progression into the S phase of the
CC mitotic cell cycle. Diffusely localized throughout the cell during
CC mitosis. Colocalized with NPAT and SMN1 in nuclear bodies including
CC gems (Gemini of coiled bodies) and Cajal bodies in a cell cycle-
CC dependent manner. Translocates together with EEF1A1 from the cytoplasm
CC to the nucleolus after treatment with mitogens. Colocalized with EGFR
CC in the cytoplasm of quiescent cells. Translocates from the cytoplasm to
CC the nucleus in a epidermal growth factor (EGF)-dependent manner.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in fibroblast; weakly expressed in
CC fibroblast of spinal muscular atrophy (SMA) patients.
CC {ECO:0000269|PubMed:22422766}.
CC -!- DISEASE: Growth restriction, hypoplastic kidneys, alopecia, and
CC distinctive facies (GKAF) [MIM:619321]: An autosomal recessive disorder
CC characterized by pre- and postnatal growth restriction with
CC microcephaly, distinctive craniofacial features, congenital alopecia,
CC hypoplastic kidneys with renal insufficiency, global developmental
CC delay, severe congenital sensorineural hearing loss, hydrocephalus,
CC genital hypoplasia, and early mortality. {ECO:0000269|PubMed:29851065}.
CC Note=The disease may be caused by variants affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the ZPR1 family. {ECO:0000305}.
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DR EMBL; AF019767; AAC33514.1; -; mRNA.
DR EMBL; BT006642; AAP35288.1; -; mRNA.
DR EMBL; BC004256; AAH04256.1; -; mRNA.
DR EMBL; BC012162; AAH12162.1; -; mRNA.
DR EMBL; BC017349; AAH17349.1; -; mRNA.
DR EMBL; BC017380; AAH17380.1; -; mRNA.
DR EMBL; BC111028; AAI11029.1; -; mRNA.
DR CCDS; CCDS8375.1; -.
DR RefSeq; NP_001304015.1; NM_001317086.1.
DR RefSeq; NP_003895.1; NM_003904.4.
DR AlphaFoldDB; O75312; -.
DR SMR; O75312; -.
DR BioGRID; 114401; 84.
DR IntAct; O75312; 10.
DR MINT; O75312; -.
DR STRING; 9606.ENSP00000227322; -.
DR iPTMnet; O75312; -.
DR MetOSite; O75312; -.
DR PhosphoSitePlus; O75312; -.
DR BioMuta; ZPR1; -.
DR EPD; O75312; -.
DR jPOST; O75312; -.
DR MassIVE; O75312; -.
DR MaxQB; O75312; -.
DR PaxDb; O75312; -.
DR PeptideAtlas; O75312; -.
DR PRIDE; O75312; -.
DR ProteomicsDB; 49889; -.
DR Antibodypedia; 18410; 273 antibodies from 28 providers.
DR DNASU; 8882; -.
DR Ensembl; ENST00000227322.8; ENSP00000227322.3; ENSG00000109917.11.
DR GeneID; 8882; -.
DR KEGG; hsa:8882; -.
DR MANE-Select; ENST00000227322.8; ENSP00000227322.3; NM_003904.5; NP_003895.1.
DR UCSC; uc001ppp.4; human.
DR CTD; 8882; -.
DR DisGeNET; 8882; -.
DR GeneCards; ZPR1; -.
DR HGNC; HGNC:13051; ZPR1.
DR HPA; ENSG00000109917; Low tissue specificity.
DR MIM; 603901; gene.
DR MIM; 619321; phenotype.
DR neXtProt; NX_O75312; -.
DR OpenTargets; ENSG00000109917; -.
DR PharmGKB; PA37629; -.
DR VEuPathDB; HostDB:ENSG00000109917; -.
DR eggNOG; KOG2703; Eukaryota.
DR GeneTree; ENSGT00390000005306; -.
DR HOGENOM; CLU_024138_5_0_1; -.
DR InParanoid; O75312; -.
DR OMA; PVQSQKG; -.
DR OrthoDB; 453044at2759; -.
DR PhylomeDB; O75312; -.
DR TreeFam; TF313084; -.
DR PathwayCommons; O75312; -.
DR SignaLink; O75312; -.
DR BioGRID-ORCS; 8882; 781 hits in 1113 CRISPR screens.
DR GeneWiki; ZNF259; -.
DR GenomeRNAi; 8882; -.
DR Pharos; O75312; Tbio.
DR PRO; PR:O75312; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O75312; protein.
DR Bgee; ENSG00000109917; Expressed in cortical plate and 191 other tissues.
DR ExpressionAtlas; O75312; baseline and differential.
DR Genevisible; O75312; HS.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0015030; C:Cajal body; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0097504; C:Gemini of coiled bodies; IDA:UniProtKB.
DR GO; GO:0030426; C:growth cone; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IEA:Ensembl.
DR GO; GO:0031369; F:translation initiation factor binding; IPI:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:Ensembl.
DR GO; GO:1902742; P:apoptotic process involved in development; ISS:UniProtKB.
DR GO; GO:0061564; P:axon development; IMP:UniProtKB.
DR GO; GO:0030576; P:Cajal body organization; IMP:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IBA:GO_Central.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0042023; P:DNA endoreduplication; ISS:UniProtKB.
DR GO; GO:0001833; P:inner cell mass cell proliferation; IEA:Ensembl.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:2000672; P:negative regulation of motor neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0045927; P:positive regulation of growth; ISS:UniProtKB.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IDA:UniProtKB.
DR GO; GO:0033120; P:positive regulation of RNA splicing; IMP:UniProtKB.
DR GO; GO:0071931; P:positive regulation of transcription involved in G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:1990261; P:pre-mRNA catabolic process; IMP:UniProtKB.
DR GO; GO:0031641; P:regulation of myelination; ISS:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0021510; P:spinal cord development; ISS:UniProtKB.
DR GO; GO:0001834; P:trophectodermal cell proliferation; ISS:UniProtKB.
DR Gene3D; 2.20.25.420; -; 2.
DR Gene3D; 2.60.120.1040; -; 2.
DR InterPro; IPR004457; Znf_ZPR1.
DR InterPro; IPR040141; ZPR1.
DR InterPro; IPR042451; ZPR1_A/B_dom.
DR InterPro; IPR042452; ZPR1_Znf1/2.
DR PANTHER; PTHR10876; PTHR10876; 1.
DR Pfam; PF03367; zf-ZPR1; 2.
DR SMART; SM00709; Zpr1; 2.
DR TIGRFAMs; TIGR00310; ZPR1_znf; 2.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasm; Deafness; Differentiation; Dwarfism;
KW Hypotrichosis; Metal-binding; mRNA processing; mRNA splicing; Nucleus;
KW Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1..459
FT /note="Zinc finger protein ZPR1"
FT /id="PRO_0000119036"
FT ZN_FING 51..83
FT /note="C4-type 1"
FT /evidence="ECO:0000269|PubMed:8650580"
FT ZN_FING 259..291
FT /note="C4-type 2"
FT /evidence="ECO:0000269|PubMed:8650580"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 439..459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 13..31
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 196
FT /note="I -> T (in GKAF; unknown pathological significance;
FT homozygous patient fibroblasts have impaired ability to
FT progress through the cell cycle; decreased protein
FT abundance in patient fibroblasts)"
FT /evidence="ECO:0000269|PubMed:29851065"
FT /id="VAR_085794"
FT VARIANT 264
FT /note="A -> V (in dbSNP:rs35120633)"
FT /id="VAR_052999"
SQ SEQUENCE 459 AA; 50925 MW; E3DB820F490F2835 CRC64;
MAASGAVEPG PPGAAVAPSP APAPPPAPDH LFRPISAEDE EQQPTEIESL CMNCYCNGMT
RLLLTKIPFF REIIVSSFSC EHCGWNNTEI QSAGRIQDQG VRYTLSVRAL EDMNREVVKT
DSAATRIPEL DFEIPAFSQK GALTTVEGLI TRAISGLEQD QPARRANKDA TAERIDEFIV
KLKELKQVAS PFTLIIDDPS GNSFVENPHA PQKDDALVIT HYNRTRQQEE MLGLQEEAPA
EKPEEEDLRN EVLQFSTNCP ECNAPAQTNM KLVQIPHFKE VIIMATNCEN CGHRTNEVKS
GGAVEPLGTR ITLHITDASD MTRDLLKSET CSVEIPELEF ELGMAVLGGK FTTLEGLLKD
IRELVTKNPF TLGDSSNPGQ TERLQEFSQK MDQIIEGNMK AHFIMDDPAG NSYLQNVYAP
EDDPEMKVER YKRTFDQNEE LGLNDMKTEG YEAGLAPQR
