ZHX2_MOUSE
ID ZHX2_MOUSE Reviewed; 836 AA.
AC Q8C0C0;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Zinc fingers and homeoboxes protein 2;
DE AltName: Full=Alpha-fetoprotein regulator 1;
DE Short=AFP regulator 1;
DE AltName: Full=Regulator of AFP;
DE AltName: Full=Zinc finger and homeodomain protein 2;
GN Name=Zhx2; Synonyms=Afr1, Raf;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:BAC27546.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=129 {ECO:0000269|PubMed:14659886};
RX PubMed=14659886; DOI=10.1016/j.gene.2003.09.013;
RA Kawata H., Yamada K., Shou Z., Mizutani T., Miyamoto K.;
RT "The mouse zinc-fingers and homeoboxes (ZHX) family: ZHX2 forms a
RT heterodimer with ZHX3.";
RL Gene 323:133-140(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH59178.1};
RC TISSUE=Brain {ECO:0000312|EMBL:AAH59178.1};
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 SUBCELLULAR LOCATION.
RC TISSUE=Kidney;
RX PubMed=17056598; DOI=10.1074/jbc.m606664200;
RA Liu G., Clement L.C., Kanwar Y.S., Avila-Casado C., Chugh S.S.;
RT "ZHX proteins regulate podocyte gene expression during the development of
RT nephrotic syndrome.";
RL J. Biol. Chem. 281:39681-39692(2006).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH EFNB1.
RX PubMed=19515908; DOI=10.1523/jneurosci.5841-08.2009;
RA Wu C., Qiu R., Wang J., Zhang H., Murai K., Lu Q.;
RT "ZHX2 Interacts with Ephrin-B and regulates neural progenitor maintenance
RT in the developing cerebral cortex.";
RL J. Neurosci. 29:7404-7412(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-824 AND SER-826, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=30146259; DOI=10.1016/j.bbrc.2018.08.088;
RA Kawamura Y., Yamanaka K., Poh B., Kuribayashi H., Koso H., Watanabe S.;
RT "The role of Zhx2 transcription factor in bipolar cell differentiation
RT during mouse retinal development.";
RL Biochem. Biophys. Res. Commun. 503:3023-3030(2018).
CC -!- FUNCTION: Acts as a transcriptional repressor (PubMed:19515908).
CC Represses the promoter activity of the CDC25C gene stimulated by NFYA
CC (By similarity). May play a role in retinal development where it
CC regulates the composition of bipolar cell populations, by promoting
CC differentiation of bipolar OFF-type cells (PubMed:30146259). In the
CC brain, may promote maintenance and suppress differentiation of neural
CC progenitor cells in the developing cortex (PubMed:19515908).
CC {ECO:0000250|UniProtKB:Q9Y6X8, ECO:0000269|PubMed:19515908,
CC ECO:0000269|PubMed:30146259}.
CC -!- SUBUNIT: Homodimer (via homeobox domain 1) (By similarity). Heterodimer
CC with ZHX1 (via homeobox domain 1) (By similarity). Heterodimer with
CC ZHX3 (via homeobox domain 1) (By similarity). Heterodimerization with
CC ZHX1 is not necessary for repressor activity (By similarity). Interacts
CC (via homeobox domain) with NFYA (via N-terminus) (By similarity).
CC Interacts with EFNB1 intracellular domain peptide; the interaction
CC enhances ZHX2 transcriptional repression activity (PubMed:19515908).
CC {ECO:0000250|UniProtKB:Q9Y6X8, ECO:0000269|PubMed:19515908}.
CC -!- INTERACTION:
CC Q8C0C0; Q8BUR4: Dock1; NbExp=3; IntAct=EBI-646042, EBI-646023;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000269|PubMed:17056598, ECO:0000269|PubMed:19515908,
CC ECO:0000269|PubMed:30146259}. Note=Colocalizes with EFNB1 intracellular
CC domain in the nucleus. {ECO:0000269|PubMed:19515908}.
CC -!- TISSUE SPECIFICITY: Expressed in retina where it localizes to Muller
CC glial cells of the inner nuclear layer (at protein level)
CC (PubMed:30146259). Detected in heart, brain, spleen, lung, liver,
CC skeletal muscle, kidney and testis (PubMed:14659886).
CC {ECO:0000269|PubMed:14659886, ECO:0000269|PubMed:30146259}.
CC -!- DEVELOPMENTAL STAGE: Strongly expressed in retina from embryonic stages
CC 14.5 dpc to 17.5 dpc, where it is widely detected in retinal progenitor
CC cells (at protein level) (PubMed:30146259). Expression then gradually
CC declines and stabilizes at a low level by postnatal day 10 (P10) (at
CC protein level) (PubMed:30146259). At P0, expression refines to the
CC inner half of the neuroblastic layer (at protein level)
CC (PubMed:30146259). Expression further refines to the retinal inner
CC nuclear layer from stage P3 onwards (at protein level)
CC (PubMed:30146259). Detected in bipolar OFF-type cells at stage P7 (at
CC protein level) (PubMed:30146259). By stage P10, has only weak
CC expression in bipolar OFF-type cells but strong expression in Muller
CC glial cells (at protein level) (PubMed:30146259). Detected in brain at
CC embryonic stages 12.5 dpc to 15.5 dpc, specifically in the ventricular
CC zone and subventricular zone of the cortex (at protein level)
CC (PubMed:19515908). Probably localizes to neural progenitor cells in the
CC developing cortex (at protein level) (PubMed:19515908).
CC {ECO:0000269|PubMed:19515908, ECO:0000269|PubMed:30146259}.
CC -!- SIMILARITY: Belongs to the ZHX family. {ECO:0000305}.
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DR EMBL; AB099526; BAC87710.1; -; mRNA.
DR EMBL; AB099704; BAC87712.1; -; Genomic_DNA.
DR EMBL; AK031782; BAC27546.1; -; mRNA.
DR EMBL; BC059178; AAH59178.1; -; mRNA.
DR CCDS; CCDS27483.1; -.
DR RefSeq; NP_955520.1; NM_199449.2.
DR RefSeq; XP_011243990.1; XM_011245688.2.
DR RefSeq; XP_011243991.1; XM_011245689.2.
DR AlphaFoldDB; Q8C0C0; -.
DR SMR; Q8C0C0; -.
DR BioGRID; 239920; 2.
DR IntAct; Q8C0C0; 2.
DR MINT; Q8C0C0; -.
DR STRING; 10090.ENSMUSP00000094164; -.
DR iPTMnet; Q8C0C0; -.
DR PhosphoSitePlus; Q8C0C0; -.
DR EPD; Q8C0C0; -.
DR MaxQB; Q8C0C0; -.
DR PaxDb; Q8C0C0; -.
DR PRIDE; Q8C0C0; -.
DR ProteomicsDB; 302130; -.
DR Antibodypedia; 13770; 386 antibodies from 35 providers.
DR DNASU; 387609; -.
DR Ensembl; ENSMUST00000096430; ENSMUSP00000094164; ENSMUSG00000071757.
DR GeneID; 387609; -.
DR KEGG; mmu:387609; -.
DR UCSC; uc007vsp.1; mouse.
DR CTD; 22882; -.
DR MGI; MGI:2683087; Zhx2.
DR VEuPathDB; HostDB:ENSMUSG00000071757; -.
DR eggNOG; ENOG502RHIC; Eukaryota.
DR GeneTree; ENSGT00950000182893; -.
DR HOGENOM; CLU_009147_1_0_1; -.
DR InParanoid; Q8C0C0; -.
DR OMA; AKDQMAI; -.
DR OrthoDB; 518562at2759; -.
DR PhylomeDB; Q8C0C0; -.
DR TreeFam; TF333363; -.
DR BioGRID-ORCS; 387609; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Zhx2; mouse.
DR PRO; PR:Q8C0C0; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8C0C0; protein.
DR Bgee; ENSMUSG00000071757; Expressed in knee joint and 176 other tissues.
DR Genevisible; Q8C0C0; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0006402; P:mRNA catabolic process; IDA:MGI.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IDA:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0060040; P:retinal bipolar neuron differentiation; IMP:UniProtKB.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IDA:MGI.
DR CDD; cd00086; homeodomain; 4.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR041057; ZHX_Znf_C2H2.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00046; Homeodomain; 3.
DR Pfam; PF18387; zf_C2H2_ZHX; 1.
DR SMART; SM00389; HOX; 4.
DR SMART; SM00355; ZnF_C2H2; 2.
DR SUPFAM; SSF46689; SSF46689; 4.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS50071; HOMEOBOX_2; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 1.
PE 1: Evidence at protein level;
KW Differentiation; DNA-binding; Homeobox; Isopeptide bond; Metal-binding;
KW Neurogenesis; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Repressor; Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..836
FT /note="Zinc fingers and homeoboxes protein 2"
FT /id="PRO_0000049392"
FT ZN_FING 78..101
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042,
FT ECO:0000305"
FT ZN_FING 110..133
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042,
FT ECO:0000305"
FT DNA_BIND 263..324
FT /note="Homeobox 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108,
FT ECO:0000305"
FT DNA_BIND 439..501
FT /note="Homeobox 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108,
FT ECO:0000305"
FT DNA_BIND 530..591
FT /note="Homeobox 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108,
FT ECO:0000305"
FT DNA_BIND 628..690
FT /note="Homeobox 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108,
FT ECO:0000305"
FT REGION 1..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 27..77
FT /note="Interaction with EFNB1"
FT /evidence="ECO:0000269|PubMed:19515908"
FT REGION 164..214
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 195..358
FT /note="Required for homodimerization"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X8"
FT REGION 263..497
FT /note="Required for interaction with NFYA"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X8"
FT REGION 263..446
FT /note="Required for repressor activity"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X8"
FT REGION 317..446
FT /note="Required for nuclear localization"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X8"
FT REGION 404..442
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 699..836
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..16
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 21..35
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 46..61
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 164..182
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 190..211
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 422..436
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 732..751
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 769..783
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 824
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 826
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CROSSLNK 64
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X8"
FT CROSSLNK 455
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X8"
FT CONFLICT 70
FT /note="L -> P (in Ref. 1; BAC87710/BAC87712)"
FT /evidence="ECO:0000305"
FT CONFLICT 699
FT /note="M -> L (in Ref. 1; BAC87710/BAC87712)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 836 AA; 92259 MW; C28AF20925D62054 CRC64;
MASKRKSTTP CMVRTSQVLE QDMLEEADRA KDKGAGMPQS DVTKDSWAAE PEHSSKETEV
VEVKSMGENL SKKLQGGYEC KYCPYSTQNL NEFTEHVDMQ HPNVILNPLY VCAECNFTTK
KYDSLSDHNS KFHPGETNFK LKLIKRNNQT VLEQSIEATN HVVPITASGP GSSDNDPGVS
VGKTPMTKTG KLKADAKKVP KKPDEAAPEN HMEGTARLVT DTAEILARLG SVELLQDSLG
HVMPSVQLPP NINLVPKVPV PLNTTKYNSA LDTNATMINS FNKFPYPTQA ELSWLTAASK
HPEEHIRIWF ATQRLKHGIS WSPEEVEEAR KKMFNGTIQS VPPTITVLPA QLTPTKVSQP
ILQTALPCQI LGQPSLVLTQ VTSGSTTVSC SPITLAVAGV TNHGQKRPLV TPQAAPEPKR
PHIAQVPEPP PKVANTPLTP ASDRKKTKLQ IAHLKASFLQ SQFPDDAEVY RLIEVTGLAR
SEIKKWFSDH RYRCQRGIVH ITSESLAKDQ MAITGTRHGR TYHVYPDFAP QKFKEKSQGQ
LKTLEDSFLK SSFPTQAEVE RLRVETKLSR REIDSWFSER RKLRDSMEQA VLDSMGSGKK
GSDAVAPNGA LSRLDQLSGA QLAGSLPSPS SAIVQNQEQV HLLRSTFART QWPTPQEYDQ
LAAKTGLVRT EIVRWFKENR CLLKTGTLSW LEQYQRHHMS DDRGRDAVSR KVAKQVAESP
KNGSEAAHQY AKDPKALSEE DSEKLVPRMK VGGDPTKDCL AGKPSEATSD RSEGSRDGQG
SEENEESGIV DFVEVTVGEE DAISEKWGSW SRRVAEGTVE RADSDSDSTP AEAGQA
