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 27-MAR-2024, entry version 144. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 29. 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; 9606-ENSP00000411145; -. DR PeptideAtlas; A0PJY2; -. DR ProteomicsDB; 71; -. [A0PJY2-1] DR ProteomicsDB; 72; -. [A0PJY2-2] DR ProteomicsDB; 73; -. [A0PJY2-3] DR Antibodypedia; 31725; 134 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 AGR; HGNC:22788; -. DR CTD; 389549; -. DR DisGeNET; 389549; -. DR GeneCards; FEZF1; -. DR GeneReviews; FEZF1; -. DR HGNC; HGNC:22788; FEZF1. DR HPA; ENSG00000128610; Tissue enhanced (brain, pituitary gland, testis). 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; 2896453at2759; -. DR PhylomeDB; A0PJY2; -. DR TreeFam; TF316780; -. DR PathwayCommons; A0PJY2; -. DR SignaLink; A0PJY2; -. DR BioGRID-ORCS; 389549; 9 hits in 1164 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 male germ line stem cell (sensu Vertebrata) in testis and 41 other cell types or 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:0045893; P:positive regulation of DNA-templated transcription; IEA:Ensembl. DR GO; GO:0045666; P:positive regulation of neuron differentiation; 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 Gene3D; 3.30.160.60; Classic Zinc Finger; 6. DR InterPro; IPR036236; Znf_C2H2_sf. DR InterPro; IPR013087; Znf_C2H2_type. DR PANTHER; PTHR24393:SF34; FEZ FAMILY ZINC FINGER PROTEIN ERM; 1. DR PANTHER; PTHR24393; ZINC FINGER PROTEIN; 1. DR Pfam; PF00096; zf-C2H2; 5. DR Pfam; PF13912; zf-C2H2_6; 1. DR SMART; SM00355; ZnF_C2H2; 6. DR SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 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 //