FEZ1_HUMAN
ID FEZ1_HUMAN Reviewed; 392 AA.
AC Q99689; O00679; O00728; Q6IBI7;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Fasciculation and elongation protein zeta-1;
DE AltName: Full=Zygin I;
DE AltName: Full=Zygin-1;
GN Name=FEZ1;
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] (ISOFORMS LONG AND SHORT).
RX PubMed=9096408; DOI=10.1073/pnas.94.7.3414;
RA Bloom L., Horvitz H.R.;
RT "The Caenorhabditis elegans gene unc-76 and its human homologs define a new
RT gene family involved in axonal outgrowth and fasciculation.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:3414-3419(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RA Sugita S., von Poser C., Rosahl T.W., Hata Y., Suedhof T.C.;
RT "Zigins: a family of synaptotagmin-interacting proteins related to unc-
RT 76.";
RL Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC TISSUE=Pancreas;
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 [6]
RP INTERACTION WITH UBE4B, PHOSPHORYLATION, AND UBIQUITINATION.
RX PubMed=15466860; DOI=10.1074/jbc.m402916200;
RA Okumura F., Hatakeyama S., Matsumoto M., Kamura T., Nakayama K.;
RT "Functional regulation of FEZ1 by the U-box-type ubiquitin ligase E4B
RT contributes to neuritogenesis.";
RL J. Biol. Chem. 279:53533-53543(2004).
RN [7]
RP SUBUNIT, AND INTERACTION WITH SAP30L.
RX PubMed=16484223; DOI=10.1074/jbc.m513280200;
RA Assmann E.M., Alborghetti M.R., Camargo M.E.R., Kobarg J.;
RT "FEZ1 dimerization and interaction with transcription regulatory proteins
RT involves its coiled-coil region.";
RL J. Biol. Chem. 281:9869-9881(2006).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=18439996; DOI=10.1016/j.yexcr.2008.02.012;
RA Lanza D.C., Trindade D.M., Assmann E.M., Kobarg J.;
RT "Over-expression of GFP-FEZ1 causes generation of multi-lobulated nuclei
RT mediated by microtubules in HEK293 cells.";
RL Exp. Cell Res. 314:2028-2039(2008).
RN [9]
RP FUNCTION, SUBUNIT, INTERACTION WITH SCOC, AND DISULFIDE BOND.
RX PubMed=20812761; DOI=10.1021/pr100314q;
RA Alborghetti M.R., Furlan A.S., Silva J.C., Paes Leme A.F., Torriani I.C.,
RA Kobarg J.;
RT "Human FEZ1 protein forms a disulfide bond mediated dimer: implications for
RT cargo transport.";
RL J. Proteome Res. 9:4595-4603(2010).
RN [10]
RP FUNCTION, INTERACTION WITH SCOC; ULK1 AND UVRAG, AND MUTAGENESIS OF
RP GLU-248; LEU-254; LEU-260 AND LYS-264.
RX PubMed=22354037; DOI=10.1038/emboj.2012.36;
RA McKnight N.C., Jefferies H.B., Alemu E.A., Saunders R.E., Howell M.,
RA Johansen T., Tooze S.A.;
RT "Genome-wide siRNA screen reveals amino acid starvation-induced autophagy
RT requires SCOC and WAC.";
RL EMBO J. 31:1931-1946(2012).
RN [11]
RP INTERACTION WITH SCOC.
RX PubMed=24098481; DOI=10.1371/journal.pone.0076355;
RA Behrens C., Binotti B., Schmidt C., Robinson C.V., Chua J.J., Kuhnel K.;
RT "Crystal structure of the human short coiled coil protein and insights into
RT SCOC-FEZ1 complex formation.";
RL PLoS ONE 8:E76355-E76355(2013).
CC -!- FUNCTION: May be involved in axonal outgrowth as component of the
CC network of molecules that regulate cellular morphology and axon
CC guidance machinery. Able to restore partial locomotion and axonal
CC fasciculation to C.elegans unc-76 mutants in germline transformation
CC experiments. May participate in the transport of mitochondria and other
CC cargos along microtubules. {ECO:0000269|PubMed:20812761,
CC ECO:0000269|PubMed:22354037}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. May form heterodimers with FEZ2.
CC Interacts with the NH2-terminal variable region (V1) of PKC zeta and
CC weakly with that of PKC epsilon (By similarity). Interacts with UBE4B.
CC Interacts with SAP30L. Interacts with SCOC and ULK1; SCOC interferes
CC with ULK1-binding to FEZ1. Directly interacts with SCOC and UVRAG.
CC Stabilizes the interaction between SCOC and UVRAG during amino acid
CC starvation. {ECO:0000250, ECO:0000269|PubMed:15466860,
CC ECO:0000269|PubMed:16484223, ECO:0000269|PubMed:20812761,
CC ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:24098481}.
CC -!- INTERACTION:
CC Q99689; Q9P2H0: CEP126; NbExp=2; IntAct=EBI-396435, EBI-473176;
CC Q99689; P42858: HTT; NbExp=6; IntAct=EBI-396435, EBI-466029;
CC Q99689; Q96PY6: NEK1; NbExp=2; IntAct=EBI-396435, EBI-373615;
CC Q99689; O14530: TXNDC9; NbExp=2; IntAct=EBI-396435, EBI-707554;
CC Q99689; P17210: Khc; Xeno; NbExp=3; IntAct=EBI-396435, EBI-102445;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000269|PubMed:18439996}. Cell membrane
CC {ECO:0000250}. Note=Colocalizes with both, alpha- and gamma-tubulin.
CC Translocated from the plasma membrane to the cytoplasm by activation of
CC the PKC zeta (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=Q99689-1; Sequence=Displayed;
CC Name=Short; Synonyms=FEZ1-T;
CC IsoId=Q99689-2; Sequence=VSP_006951;
CC -!- TISSUE SPECIFICITY: Mainly expressed in brain.
CC -!- PTM: Phosphorylated by protein kinase C zeta; which enhances
CC interaction with UBE4B and polyubiquitination.
CC {ECO:0000269|PubMed:15466860}.
CC -!- PTM: Polyubiquitinated in a UBE4B-dependent manner; which does not lead
CC to proteasomal degradation and may be important for neurogenic
CC activity. Polyubiquitin linkage seems to be mainly through Lys-26.
CC {ECO:0000269|PubMed:15466860}.
CC -!- SIMILARITY: Belongs to the zygin family. {ECO:0000305}.
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DR EMBL; U60060; AAC51282.1; -; mRNA.
DR EMBL; U60062; AAC51284.1; -; mRNA.
DR EMBL; U69139; AAB40660.1; -; mRNA.
DR EMBL; CR456817; CAG33098.1; -; mRNA.
DR EMBL; CR541954; CAG46752.1; -; mRNA.
DR EMBL; BC009545; AAH09545.1; -; mRNA.
DR CCDS; CCDS31716.1; -. [Q99689-1]
DR CCDS; CCDS44758.1; -. [Q99689-2]
DR RefSeq; NP_005094.1; NM_005103.4. [Q99689-1]
DR RefSeq; NP_072043.1; NM_022549.3. [Q99689-2]
DR RefSeq; XP_005271791.1; XM_005271734.2. [Q99689-1]
DR RefSeq; XP_005271792.1; XM_005271735.2. [Q99689-1]
DR AlphaFoldDB; Q99689; -.
DR BioGRID; 114997; 79.
DR CORUM; Q99689; -.
DR DIP; DIP-32494N; -.
DR IntAct; Q99689; 60.
DR MINT; Q99689; -.
DR STRING; 9606.ENSP00000278919; -.
DR iPTMnet; Q99689; -.
DR PhosphoSitePlus; Q99689; -.
DR BioMuta; FEZ1; -.
DR DMDM; 13431526; -.
DR EPD; Q99689; -.
DR jPOST; Q99689; -.
DR MassIVE; Q99689; -.
DR MaxQB; Q99689; -.
DR PaxDb; Q99689; -.
DR PeptideAtlas; Q99689; -.
DR PRIDE; Q99689; -.
DR ProteomicsDB; 78401; -. [Q99689-1]
DR ProteomicsDB; 78402; -. [Q99689-2]
DR Antibodypedia; 32949; 205 antibodies from 33 providers.
DR DNASU; 9638; -.
DR Ensembl; ENST00000278919.8; ENSP00000278919.3; ENSG00000149557.14. [Q99689-1]
DR Ensembl; ENST00000366139.3; ENSP00000393425.2; ENSG00000149557.14. [Q99689-2]
DR Ensembl; ENST00000524435.1; ENSP00000431521.1; ENSG00000149557.14. [Q99689-2]
DR Ensembl; ENST00000648911.1; ENSP00000497070.1; ENSG00000149557.14. [Q99689-1]
DR GeneID; 9638; -.
DR KEGG; hsa:9638; -.
DR MANE-Select; ENST00000278919.8; ENSP00000278919.3; NM_005103.5; NP_005094.1.
DR UCSC; uc001qbx.4; human. [Q99689-1]
DR CTD; 9638; -.
DR DisGeNET; 9638; -.
DR GeneCards; FEZ1; -.
DR HGNC; HGNC:3659; FEZ1.
DR HPA; ENSG00000149557; Tissue enhanced (brain).
DR MIM; 604825; gene.
DR neXtProt; NX_Q99689; -.
DR OpenTargets; ENSG00000149557; -.
DR PharmGKB; PA28100; -.
DR VEuPathDB; HostDB:ENSG00000149557; -.
DR eggNOG; KOG3919; Eukaryota.
DR GeneTree; ENSGT00390000017627; -.
DR HOGENOM; CLU_041596_0_0_1; -.
DR InParanoid; Q99689; -.
DR OMA; EKPRCLY; -.
DR OrthoDB; 1186463at2759; -.
DR PhylomeDB; Q99689; -.
DR TreeFam; TF313128; -.
DR PathwayCommons; Q99689; -.
DR SignaLink; Q99689; -.
DR BioGRID-ORCS; 9638; 9 hits in 1074 CRISPR screens.
DR ChiTaRS; FEZ1; human.
DR GeneWiki; FEZ1; -.
DR GenomeRNAi; 9638; -.
DR Pharos; Q99689; Tbio.
DR PRO; PR:Q99689; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q99689; protein.
DR Bgee; ENSG00000149557; Expressed in inferior olivary complex and 188 other tissues.
DR ExpressionAtlas; Q99689; baseline and differential.
DR Genevisible; Q99689; HS.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005813; C:centrosome; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IDA:GO_Central.
DR GO; GO:0030426; C:growth cone; IEA:Ensembl.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043015; F:gamma-tubulin binding; IEA:Ensembl.
DR GO; GO:0005080; F:protein kinase C binding; IEA:Ensembl.
DR GO; GO:0047485; F:protein N-terminus binding; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; TAS:ProtInc.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl.
DR GO; GO:0030010; P:establishment of cell polarity; IEA:Ensembl.
DR GO; GO:0051654; P:establishment of mitochondrion localization; IEA:Ensembl.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0070584; P:mitochondrion morphogenesis; IEA:Ensembl.
DR GO; GO:1902902; P:negative regulation of autophagosome assembly; IMP:GO_Central.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0061881; P:positive regulation of anterograde axonal transport of mitochondrion; IEA:Ensembl.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR InterPro; IPR011680; FEZ.
DR InterPro; IPR015642; FEZ_1.
DR PANTHER; PTHR12394; PTHR12394; 1.
DR PANTHER; PTHR12394:SF4; PTHR12394:SF4; 1.
DR Pfam; PF07763; FEZ; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Coiled coil; Cytoplasm; Cytoskeleton;
KW Disulfide bond; Membrane; Microtubule; Phosphoprotein; Reference proteome;
KW Transport; Ubl conjugation.
FT CHAIN 1..392
FT /note="Fasciculation and elongation protein zeta-1"
FT /id="PRO_0000189525"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 175..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 230..298
FT /evidence="ECO:0000255"
FT COMPBIAS 9..23
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 175..196
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K0X8"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97577"
FT MOD_RES 316
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K0X8"
FT DISULFID 133
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:20812761"
FT VAR_SEQ 105..392
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:9096408"
FT /id="VSP_006951"
FT VARIANT 123
FT /note="D -> E (in dbSNP:rs597570)"
FT /id="VAR_020461"
FT MUTAGEN 248
FT /note="E->A: No effect on SCOC--binding."
FT /evidence="ECO:0000269|PubMed:22354037"
FT MUTAGEN 254
FT /note="L->P: Loss of SCOC-binding. No effect on ULK1-
FT binding."
FT /evidence="ECO:0000269|PubMed:22354037"
FT MUTAGEN 260
FT /note="L->P: Loss of SCOC-binding. No effect on ULK1-
FT binding."
FT /evidence="ECO:0000269|PubMed:22354037"
FT MUTAGEN 264
FT /note="K->A: No effect on SCOC-binding."
FT /evidence="ECO:0000269|PubMed:22354037"
SQ SEQUENCE 392 AA; 45119 MW; 4226ED5EA17706F2 CRC64;
MEAPLVSLDE EFEDLRPSCS EDPEEKPQCF YGSSPHHLED PSLSELENFS SEIISFKSME
DLVNEFDEKL NVCFRNYNAK TENLAPVKNQ LQIQEEEETL QDEEVWDALT DNYIPSLSED
WRDPNIEALN GNCSDTEIHE KEEEEFNEKS ENDSGINEEP LLTADQVIEE IEEMMQNSPD
PEEEEEVLEE EDGGETSSQA DSVLLQEMQA LTQTFNNNWS YEGLRHMSGS ELTELLDQVE
GAIRDFSEEL VQQLARRDEL EFEKEVKNSF ITVLIEVQNK QKEQRELMKK RRKEKGLSLQ
SSRIEKGNQM PLKRFSMEGI SNILQSGIRQ TFGSSGTDKQ YLNTVIPYEK KASPPSVEDL
QMLTNILFAM KEDNEKVPTL LTDYILKVLC PT
