FEZF1_HUMAN
ID FEZF1_HUMAN Reviewed; 475 AA.
AC A0PJY2; A0PJY3; A4D0W3; B4DUP9; B7ZM98;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Fez family zinc finger protein 1;
DE AltName: Full=Zinc finger protein 312B;
GN Name=FEZF1; Synonyms=FEZ, ZNF312B;
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 [LARGE SCALE MRNA] (ISOFORM 1).
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Testis;
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 TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=19318583; DOI=10.1158/0008-5472.can-08-2240;
RA Song I.S., Oh N.S., Kim H.T., Ha G.H., Jeong S.Y., Kim J.M., Kim D.I.,
RA Yoo H.S., Kim C.H., Kim N.S.;
RT "Human ZNF312b promotes the progression of gastric cancer by
RT transcriptional activation of the K-ras gene.";
RL Cancer Res. 69:3131-3139(2009).
RN [5]
RP INVOLVEMENT IN HH22, VARIANT HH22 TYR-278, AND CHARACTERIZATION OF VARIANT
RP HH22 TYR-278.
RX PubMed=25192046; DOI=10.1016/j.ajhg.2014.08.006;
RA Kotan L.D., Hutchins B.I., Ozkan Y., Demirel F., Stoner H., Cheng P.J.,
RA Esen I., Gurbuz F., Bicakci Y.K., Mengen E., Yuksel B., Wray S.,
RA Topaloglu A.K.;
RT "Mutations in FEZF1 cause Kallmann syndrome.";
RL Am. J. Hum. Genet. 95:326-331(2014).
CC -!- FUNCTION: Transcription repressor. Involved in the axonal projection
CC and proper termination of olfactory sensory neurons (OSN). Plays a role
CC in rostro-caudal patterning of the diencephalon and in prethalamic
CC formation. Expression is required in OSN to cell-autonomously regulate
CC OSN axon projections. Regulates non-cell-autonomously the layer
CC formation of the olfactory bulb development and the interneurons. May
CC be required for correct rostral migration of the interneuron
CC progenitors (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC A0PJY2; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-11988727, EBI-3867333;
CC A0PJY2; Q5TD97: FHL5; NbExp=3; IntAct=EBI-11988727, EBI-750641;
CC A0PJY2; Q6A162: KRT40; NbExp=3; IntAct=EBI-11988727, EBI-10171697;
CC A0PJY2; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-11988727, EBI-11959885;
CC A0PJY2; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-11988727, EBI-10171774;
CC A0PJY2; Q99750: MDFI; NbExp=3; IntAct=EBI-11988727, EBI-724076;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19318583}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A0PJY2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A0PJY2-2; Sequence=VSP_026732;
CC Name=3;
CC IsoId=A0PJY2-3; Sequence=VSP_026733;
CC -!- TISSUE SPECIFICITY: Expressed in brain. Little or no expression in
CC other tissues. Overexpressed specifically in gastric cancers. A 2- to
CC 20-fold increase is found in over 50% of gastric cancer tissues.
CC {ECO:0000269|PubMed:19318583}.
CC -!- DISEASE: Hypogonadotropic hypogonadism 22 with or without anosmia
CC (HH22) [MIM:616030]: A disorder characterized by absent or incomplete
CC sexual maturation by the age of 18 years, in conjunction with low
CC levels of circulating gonadotropins and testosterone and no other
CC abnormalities of the hypothalamic-pituitary axis. In some cases, it is
CC associated with non-reproductive phenotypes, such as anosmia, cleft
CC palate, and sensorineural hearing loss. Anosmia or hyposmia is related
CC to the absence or hypoplasia of the olfactory bulbs and tracts.
CC Hypogonadism is due to deficiency in gonadotropin-releasing hormone and
CC probably results from a failure of embryonic migration of gonadotropin-
CC releasing hormone-synthesizing neurons. In the presence of anosmia,
CC idiopathic hypogonadotropic hypogonadism is referred to as Kallmann
CC syndrome, whereas in the presence of a normal sense of smell, it has
CC been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
CC {ECO:0000269|PubMed:25192046}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Triggers oncogenic activity specifically in gastric
CC tumors through activation of KRAS in the ERK signaling pathway.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
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DR EMBL; AK300742; BAG62411.1; -; mRNA.
DR EMBL; CH236947; EAL24342.1; -; Genomic_DNA.
DR EMBL; BC127714; AAI27715.1; -; mRNA.
DR EMBL; BC127715; AAI27716.1; -; mRNA.
DR EMBL; BC136684; AAI36685.1; -; mRNA.
DR EMBL; BC144367; AAI44368.1; -; mRNA.
DR CCDS; CCDS34741.2; -. [A0PJY2-1]
DR CCDS; CCDS55157.1; -. [A0PJY2-2]
DR RefSeq; NP_001019784.2; NM_001024613.3. [A0PJY2-1]
DR RefSeq; NP_001153736.1; NM_001160264.2. [A0PJY2-2]
DR RefSeq; XP_005250394.1; XM_005250337.3. [A0PJY2-1]
DR RefSeq; XP_011514504.1; XM_011516202.2. [A0PJY2-2]
DR AlphaFoldDB; A0PJY2; -.
DR SMR; A0PJY2; -.
DR BioGRID; 133180; 27.
DR IntAct; A0PJY2; 7.
DR STRING; 9606.ENSP00000411145; -.
DR iPTMnet; A0PJY2; -.
DR PhosphoSitePlus; A0PJY2; -.
DR BioMuta; FEZF1; -.
DR jPOST; A0PJY2; -.
DR MassIVE; A0PJY2; -.
DR PaxDb; A0PJY2; -.
DR PeptideAtlas; A0PJY2; -.
DR PRIDE; A0PJY2; -.
DR ProteomicsDB; 71; -. [A0PJY2-1]
DR ProteomicsDB; 72; -. [A0PJY2-2]
DR ProteomicsDB; 73; -. [A0PJY2-3]
DR Antibodypedia; 31725; 116 antibodies from 19 providers.
DR DNASU; 389549; -.
DR Ensembl; ENST00000427185.2; ENSP00000392727.2; ENSG00000128610.12. [A0PJY2-2]
DR Ensembl; ENST00000442488.7; ENSP00000411145.2; ENSG00000128610.12. [A0PJY2-1]
DR GeneID; 389549; -.
DR KEGG; hsa:389549; -.
DR MANE-Select; ENST00000442488.7; ENSP00000411145.2; NM_001024613.4; NP_001019784.2.
DR UCSC; uc003vkc.4; human. [A0PJY2-1]
DR CTD; 389549; -.
DR DisGeNET; 389549; -.
DR GeneCards; FEZF1; -.
DR GeneReviews; FEZF1; -.
DR HGNC; HGNC:22788; FEZF1.
DR HPA; ENSG00000128610; Tissue enriched (brain).
DR MalaCards; FEZF1; -.
DR MIM; 613301; gene.
DR MIM; 616030; phenotype.
DR neXtProt; NX_A0PJY2; -.
DR OpenTargets; ENSG00000128610; -.
DR Orphanet; 478; Kallmann syndrome.
DR PharmGKB; PA162388419; -.
DR VEuPathDB; HostDB:ENSG00000128610; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000159477; -.
DR HOGENOM; CLU_021813_2_1_1; -.
DR InParanoid; A0PJY2; -.
DR OMA; SQIQHYM; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; A0PJY2; -.
DR TreeFam; TF316780; -.
DR PathwayCommons; A0PJY2; -.
DR SignaLink; A0PJY2; -.
DR BioGRID-ORCS; 389549; 9 hits in 1086 CRISPR screens.
DR GenomeRNAi; 389549; -.
DR Pharos; A0PJY2; Tbio.
DR PRO; PR:A0PJY2; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; A0PJY2; protein.
DR Bgee; ENSG00000128610; Expressed in hypothalamus and 39 other tissues.
DR ExpressionAtlas; A0PJY2; baseline and differential.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IEA:Ensembl.
DR GO; GO:0043697; P:cell dedifferentiation; IEA:Ensembl.
DR GO; GO:0021797; P:forebrain anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:1904936; P:interneuron migration; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0021772; P:olfactory bulb development; IEA:Ensembl.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0050767; P:regulation of neurogenesis; IEA:Ensembl.
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 Pfam; PF00096; zf-C2H2; 5.
DR SMART; SM00355; ZnF_C2H2; 6.
DR SUPFAM; SSF57667; SSF57667; 3.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 6.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 6.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; Differentiation;
KW Disease variant; DNA-binding; Hypogonadotropic hypogonadism;
KW Kallmann syndrome; Metal-binding; Neurogenesis; Nucleus;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..475
FT /note="Fez family zinc finger protein 1"
FT /id="PRO_0000295114"
FT ZN_FING 260..282
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 288..310
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 316..338
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 344..366
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 372..394
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 400..423
FT /note="C2H2-type 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 428..475
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 28..43
FT /note="Engrailed homology 1 repressor"
FT /evidence="ECO:0000250"
FT COMPBIAS 436..466
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 144..193
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026732"
FT VAR_SEQ 265..268
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_026733"
FT VARIANT 278
FT /note="H -> Y (in HH22; partial loss of function;
FT dbSNP:rs587777739)"
FT /evidence="ECO:0000269|PubMed:25192046"
FT /id="VAR_071918"
SQ SEQUENCE 475 AA; 52038 MW; A26945A0C4E9316A CRC64;
MDSSCHNATT KMLATAPARG NMMSTSKPLA FSIERIMART PEPKALPVPH FLQGALPKGE
PKHSLHLNSS IPCMIPFVPV AYDTSPKAGV TGSEPRKASL EAPAAPAAVP SAPAFSCSDL
LNCALSLKGD LARDALPLQQ YKLVRPRVVN HSSFHAMGAL CYLNRGDGPC HPAAGVNIHP
VASYFLSSPL HPQPKTYLAE RNKLVVPAVE KYPSGVAFKD LSQAQLQHYM KESAQLLSEK
IAFKTSDFSR GSPNAKPKVF TCEVCGKVFN AHYNLTRHMP VHTGARPFVC KVCGKGFRQA
STLCRHKIIH TQEKPHKCNQ CGKAFNRSST LNTHTRIHAG YKPFVCEFCG KGFHQKGNYK
NHKLTHSGEK QFKCNICNKA FHQVYNLTFH MHTHNDKKPF TCPTCGKGFC RNFDLKKHVR
KLHDSSLGLA RTPAGEPGTE PPPPLPQQPP MTLPPLQPPL PTPGPLQPGL HQGHQ
