IKZF5_HUMAN
ID IKZF5_HUMAN Reviewed; 419 AA.
AC Q9H5V7; B3KVH7; D3DRE7; Q9H2T0;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Zinc finger protein Pegasus;
DE AltName: Full=Ikaros family zinc finger protein 5;
GN Name=IKZF5; Synonyms=ZNFN1A5;
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], FUNCTION, TISSUE SPECIFICITY, AND INTERACTION
RP WITH IKZF1; IKZF2; IKZF3 AND IKZF4.
RX PubMed=10978333; DOI=10.1074/jbc.m005457200;
RA Perdomo J., Holmes M., Chong B., Crossley M.;
RT "Eos and pegasus, two members of the Ikaros family of proteins with
RT distinct DNA binding activities.";
RL J. Biol. Chem. 275:38347-38354(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Synovial cell;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Endometrial adenocarcinoma, and Testis carcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [7]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-5, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [8]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-5, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [9]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-5, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [10]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-5 AND LYS-185, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN THC7, AND MUTAGENESIS OF
RP TYR-89; ARG-96; ILE-98; GLY-134; CYS-140; HIS-155 AND SER-200.
RX PubMed=31217188; DOI=10.1182/blood.2019000782;
RG NIHR BioResource;
RA Lentaigne C., Greene D., Sivapalaratnam S., Favier R., Seyres D., Thys C.,
RA Grassi L., Mangles S., Sibson K., Stubbs M., Burden F., Bordet J.C.,
RA Armari-Alla C., Erber W., Farrow S., Gleadall N., Gomez K., Megy K.,
RA Papadia S., Penkett C.J., Sims M.C., Stefanucci L., Stephens J.C.,
RA Read R.J., Stirrups K.E., Ouwehand W.H., Laffan M.A., Frontini M.,
RA Freson K., Turro E.;
RT "Germline mutations in the transcription factor IKZF5 cause
RT thrombocytopenia.";
RL Blood 134:2070-2081(2019).
RN [12]
RP VARIANTS THC7 VARIANT HIS-16 AND PRO-119.
RX PubMed=32419556; DOI=10.1080/09537104.2020.1764921;
RA Leinoe E., Kjaersgaard M., Zetterberg E., Ostrowski S., Greinacher A.,
RA Rossing M.;
RT "Highly impaired platelet ultrastructure in two families with novel IKZF5
RT variants.";
RL Platelets 32:492-497(2021).
CC -!- FUNCTION: Transcriptional repressor that binds the core 5'GNNTGTNG-3'
CC DNA consensus sequence (PubMed:10978333, PubMed:31217188). Involved in
CC megakaryocyte differentiation. {ECO:0000269|PubMed:10978333,
CC ECO:0000269|PubMed:31217188}.
CC -!- SUBUNIT: Self-associates. Interacts with other family members; IKZF1,
CC IKZF2, IKZF3 AND IKZF4. {ECO:0000269|PubMed:10978333}.
CC -!- INTERACTION:
CC Q9H5V7; Q9UKT9: IKZF3; NbExp=2; IntAct=EBI-2685636, EBI-747204;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:31217188}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, skeletal muscle, kidney,
CC and liver. Expressed in the hematopoietic cell lines MOLT-4, NALM-6 and
CC K-562. Highly expressed in THP-1 and M-07e cell lines, which have
CC characteristics of myeloid and early megakaryocytic cells respectively.
CC {ECO:0000269|PubMed:10978333}.
CC -!- DOMAIN: The N-terminal zinc fingers are involved in sequence-specific
CC DNA binding and heterotypic associations with other family members.
CC -!- DOMAIN: C-terminal zinc fingers mediate homodimerization.
CC -!- DISEASE: Thrombocytopenia 7 (THC7) [MIM:619130]: A form of
CC thrombocytopenia, a hematologic disorder defined by a decrease in the
CC number of platelets in circulating blood, resulting in the potential
CC for increased bleeding and decreased ability for clotting. THC7 is an
CC autosomal dominant form with highly variable severity, ranging from
CC absence of bleeding symptoms to epistaxis or more severe bleeding
CC episodes. {ECO:0000269|PubMed:31217188, ECO:0000269|PubMed:32419556}.
CC Note=The disease may be caused by variants affecting the gene
CC represented in this entry.
CC -!- MISCELLANEOUS: 'Pegasus' was the winged horse in Greek mythology.
CC -!- SIMILARITY: Belongs to the Ikaros C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
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DR EMBL; AF230808; AAG39220.1; -; mRNA.
DR EMBL; AK026626; BAB15512.1; -; mRNA.
DR EMBL; AK122899; BAG53789.1; -; mRNA.
DR EMBL; CR749800; CAH18660.1; -; mRNA.
DR EMBL; BX647958; CAH56199.1; -; mRNA.
DR EMBL; CH471066; EAW49292.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49293.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49294.1; -; Genomic_DNA.
DR CCDS; CCDS41574.1; -.
DR RefSeq; NP_001258769.1; NM_001271840.1.
DR RefSeq; XP_006718010.1; XM_006717947.3.
DR RefSeq; XP_016872039.1; XM_017016550.1.
DR RefSeq; XP_016872040.1; XM_017016551.1.
DR RefSeq; XP_016872041.1; XM_017016552.1.
DR AlphaFoldDB; Q9H5V7; -.
DR SMR; Q9H5V7; -.
DR BioGRID; 122147; 64.
DR IntAct; Q9H5V7; 56.
DR STRING; 9606.ENSP00000357881; -.
DR iPTMnet; Q9H5V7; -.
DR PhosphoSitePlus; Q9H5V7; -.
DR BioMuta; IKZF5; -.
DR DMDM; 74761459; -.
DR EPD; Q9H5V7; -.
DR jPOST; Q9H5V7; -.
DR MassIVE; Q9H5V7; -.
DR MaxQB; Q9H5V7; -.
DR PaxDb; Q9H5V7; -.
DR PeptideAtlas; Q9H5V7; -.
DR PRIDE; Q9H5V7; -.
DR ProteomicsDB; 80932; -.
DR Antibodypedia; 9078; 57 antibodies from 18 providers.
DR DNASU; 64376; -.
DR Ensembl; ENST00000368886.10; ENSP00000357881.5; ENSG00000095574.12.
DR Ensembl; ENST00000617859.4; ENSP00000478056.1; ENSG00000095574.12.
DR GeneID; 64376; -.
DR KEGG; hsa:64376; -.
DR MANE-Select; ENST00000368886.10; ENSP00000357881.5; NM_001372123.1; NP_001359052.1.
DR UCSC; uc001lha.4; human.
DR CTD; 64376; -.
DR DisGeNET; 64376; -.
DR GeneCards; IKZF5; -.
DR HGNC; HGNC:14283; IKZF5.
DR HPA; ENSG00000095574; Low tissue specificity.
DR MalaCards; IKZF5; -.
DR MIM; 606238; gene.
DR MIM; 619130; phenotype.
DR neXtProt; NX_Q9H5V7; -.
DR OpenTargets; ENSG00000095574; -.
DR Orphanet; 168629; Autosomal thrombocytopenia with normal platelets.
DR PharmGKB; PA162391969; -.
DR VEuPathDB; HostDB:ENSG00000095574; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000155035; -.
DR HOGENOM; CLU_734778_0_0_1; -.
DR InParanoid; Q9H5V7; -.
DR OMA; THNQRNY; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q9H5V7; -.
DR TreeFam; TF331860; -.
DR PathwayCommons; Q9H5V7; -.
DR SignaLink; Q9H5V7; -.
DR SIGNOR; Q9H5V7; -.
DR BioGRID-ORCS; 64376; 11 hits in 1104 CRISPR screens.
DR ChiTaRS; IKZF5; human.
DR GenomeRNAi; 64376; -.
DR Pharos; Q9H5V7; Tbio.
DR PRO; PR:Q9H5V7; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9H5V7; protein.
DR Bgee; ENSG00000095574; Expressed in endothelial cell and 181 other tissues.
DR Genevisible; Q9H5V7; HS.
DR GO; GO:0005634; C:nucleus; IMP:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IMP:CAFA.
DR GO; GO:0003682; F:chromatin binding; IMP:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:CAFA.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0008270; F:zinc ion binding; IMP:CAFA.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR SMART; SM00355; ZnF_C2H2; 5.
DR SUPFAM; SSF57667; SSF57667; 3.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
PE 1: Evidence at protein level;
KW Disease variant; DNA-binding; Isopeptide bond; Metal-binding; Nucleus;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..419
FT /note="Zinc finger protein Pegasus"
FT /id="PRO_0000299471"
FT ZN_FING 82..104
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 110..132
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 138..161
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 364..386
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 392..416
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 223..247
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 262..356
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 287..352
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 5
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 185
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 16
FT /note="Q -> H (in THC7; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:32419556"
FT /id="VAR_085558"
FT VARIANT 119
FT /note="S -> P (in THC7; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:32419556"
FT /id="VAR_085559"
FT MUTAGEN 89
FT /note="Y->C: Decreased protein abundance. Decreased
FT chromatin binding. Decreased localization to the nucleus.
FT Tends to remain in the cytosol."
FT /evidence="ECO:0000269|PubMed:31217188"
FT MUTAGEN 96
FT /note="R->W: Decreased protein abundance. Decreased
FT chromatin binding. Decreased localization to the nucleus.
FT Tends to remain in the cytosol."
FT /evidence="ECO:0000269|PubMed:31217188"
FT MUTAGEN 98
FT /note="I->V: No effect on protein abundance. No effect on
FT chromatin binding. No effect on localization to the
FT nucleus."
FT /evidence="ECO:0000269|PubMed:31217188"
FT MUTAGEN 134
FT /note="G->E: Decreased protein abundance. Decreased
FT chromatin binding. Decreased localization to the nucleus.
FT Tends to remain in the cytosol."
FT /evidence="ECO:0000269|PubMed:31217188"
FT MUTAGEN 140
FT /note="C->R: Decreased protein abundance. Decreased
FT chromatin binding. Decreased localization to the nucleus.
FT Tends to remain in the cytosol."
FT /evidence="ECO:0000269|PubMed:31217188"
FT MUTAGEN 155
FT /note="H->Y: Decreased protein abundance. Decreased
FT chromatin binding. Decreased localization to the nucleus.
FT Tends to remain in the cytosol."
FT /evidence="ECO:0000269|PubMed:31217188"
FT MUTAGEN 200
FT /note="S->G: No effect on protein abundance. No effect on
FT chromatin binding. No effect on localization to the
FT nucleus."
FT /evidence="ECO:0000269|PubMed:31217188"
FT CONFLICT 209
FT /note="P -> L (in Ref. 1; AAG39220)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 419 AA; 46510 MW; 71845E9DE10BB2E8 CRC64;
MGEKKPEPLD FVKDFQEYLT QQTHHVNMIS GSVSGDKEAE ALQGAGTDGD QNGLDHPSVE
VSLDENSGML VDGFERTFDG KLKCRYCNYA SKGTARLIEH IRIHTGEKPH RCHLCPFASA
YERHLEAHMR SHTGEKPYKC ELCSFRCSDR SNLSHHRRRK HKMVPIKGTR SSLSSKKMWG
VLQKKTSNLG YSRRALINLS PPSMVVQKPD YLNDFTHEIP NIQTDSYESM AKTTPTGGLP
RDPQELMVDN PLNQLSTLAG QLSSLPPENQ NPASPDVVPC PDEKPFMIQQ PSTQAVVSAV
SASIPQSSSP TSPEPRPSHS QRNYSPVAGP SSEPSAHTST PSIGNSQPST PAPALPVQDP
QLLHHCQHCD MYFADNILYT IHMGCHGYEN PFQCNICGCK CKNKYDFACH FARGQHNQH
