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Q99689 (FEZ1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Fasciculation and elongation protein zeta-1
Alternative name(s):
Zygin I
Zygin-1
Gene names
Name:FEZ1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length392 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May be involved in axonal outgrowth as component of the network of molecules that regulate cellular morphology and axon guidance machinery. Able to restore partial locomotion and axonal fasciculation to C.elegans unc-76 mutants in germline transformation experiments. May participate in the transport of mitochondria and other cargos along microtubules. Ref.9 Ref.10

Subunit structure

Homodimer; disulfide-linked. May form heterodimers with FEZ2. Interacts with the NH2-terminal variable region (V1) of PKC zeta and weakly with that of PKC epsilon By similarity. Interacts with UBE4B. Interacts with SAP30L. Interacts with SCOC and ULK1; SCOC interferes with ULK1-binding to FEZ1. Directly interacts with SCOC and UVRAG. Stabilizes the interaction between SCOC and UVRAG during amino acid starvation. Ref.6 Ref.7 Ref.9 Ref.10

Subcellular location

Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Cell membrane By similarity. Note: Colocalizes with both, alpha- and gamma-tubulin. Translocated from the plasma membrane to the cytoplasm by activation of the PKC zeta By similarity. Ref.8

Tissue specificity

Mainly expressed in brain.

Post-translational modification

Phosphorylated by protein kinase C zeta; which enhances interaction with UBE4B and polyubiquitination. Ref.6

Polyubiquitinated in a UBE4B-dependent manner; which does not lead to proteasomal degradation and may be important for neurogenic activity. Polyubiquitin linkage seems to be mainly through Lys-26.

Sequence similarities

Belongs to the zygin family.

Ontologies

Keywords
   Biological processTransport
   Cellular componentCell membrane
Cytoplasm
Cytoskeleton
Membrane
Microtubule
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainCoiled coil
   PTMDisulfide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaxon guidance

Traceable author statement Ref.1. Source: ProtInc

cell adhesion

Traceable author statement Ref.1. Source: ProtInc

cellular response to growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

establishment of mitochondrion localization

Inferred from electronic annotation. Source: Ensembl

nervous system development

Traceable author statement Ref.1. Source: ProtInc

positive regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron projection development

Inferred from electronic annotation. Source: Ensembl

transport

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentaxon

Inferred from electronic annotation. Source: Ensembl

centrosome

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay. Source: HPA

dendrite

Inferred from electronic annotation. Source: Ensembl

microtubule

Inferred from electronic annotation. Source: UniProtKB-KW

microtubule cytoskeleton

Inferred from direct assay. Source: HPA

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 14690447PubMed 15383276PubMed 16169070PubMed 17500595. Source: IntAct

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: Q99689-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Short (identifier: Q99689-2)

Also known as: FEZ1-T;

The sequence of this isoform differs from the canonical sequence as follows:
     105-392: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 392392Fasciculation and elongation protein zeta-1
PRO_0000189525

Regions

Coiled coil230 – 29869 Potential
Compositional bias95 – 984Poly-Glu
Compositional bias140 – 1456Poly-Glu
Compositional bias182 – 1865Poly-Glu

Amino acid modifications

Modified residue581Phosphoserine By similarity
Disulfide bond133Interchain Ref.9

Natural variations

Alternative sequence105 – 392288Missing in isoform Short.
VSP_006951
Natural variant1231D → E.
Corresponds to variant rs597570 [ dbSNP | Ensembl ].
VAR_020461

Experimental info

Mutagenesis2481E → A: No effect on SCOC--binding. Ref.10
Mutagenesis2541L → P: Loss of SCOC-binding. No effect on ULK1-binding. Ref.10
Mutagenesis2601L → P: Loss of SCOC-binding. No effect on ULK1-binding. Ref.10
Mutagenesis2641K → A: No effect on SCOC-binding. Ref.10

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 4226ED5EA17706F2

FASTA39245,119
        10         20         30         40         50         60 
MEAPLVSLDE EFEDLRPSCS EDPEEKPQCF YGSSPHHLED PSLSELENFS SEIISFKSME 

        70         80         90        100        110        120 
DLVNEFDEKL NVCFRNYNAK TENLAPVKNQ LQIQEEEETL QDEEVWDALT DNYIPSLSED 

       130        140        150        160        170        180 
WRDPNIEALN GNCSDTEIHE KEEEEFNEKS ENDSGINEEP LLTADQVIEE IEEMMQNSPD 

       190        200        210        220        230        240 
PEEEEEVLEE EDGGETSSQA DSVLLQEMQA LTQTFNNNWS YEGLRHMSGS ELTELLDQVE 

       250        260        270        280        290        300 
GAIRDFSEEL VQQLARRDEL EFEKEVKNSF ITVLIEVQNK QKEQRELMKK RRKEKGLSLQ 

       310        320        330        340        350        360 
SSRIEKGNQM PLKRFSMEGI SNILQSGIRQ TFGSSGTDKQ YLNTVIPYEK KASPPSVEDL 

       370        380        390 
QMLTNILFAM KEDNEKVPTL LTDYILKVLC PT 

« Hide

Isoform Short (FEZ1-T) [UniParc].

Checksum: A614EFAFF872EAF8
Show »

FASTA10412,074

References

« Hide 'large scale' references
[1]"The Caenorhabditis elegans gene unc-76 and its human homologs define a new gene family involved in axonal outgrowth and fasciculation."
Bloom L., Horvitz H.R.
Proc. Natl. Acad. Sci. U.S.A. 94:3414-3419(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
[2]"Zigins: a family of synaptotagmin-interacting proteins related to unc-76."
Sugita S., von Poser C., Rosahl T.W., Hata Y., Suedhof T.C.
Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
[4]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
Tissue: Pancreas.
[6]"Functional regulation of FEZ1 by the U-box-type ubiquitin ligase E4B contributes to neuritogenesis."
Okumura F., Hatakeyama S., Matsumoto M., Kamura T., Nakayama K.
J. Biol. Chem. 279:53533-53543(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBE4B, PHOSPHORYLATION, UBIQUITINATION.
[7]"FEZ1 dimerization and interaction with transcription regulatory proteins involves its coiled-coil region."
Assmann E.M., Alborghetti M.R., Camargo M.E.R., Kobarg J.
J. Biol. Chem. 281:9869-9881(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, INTERACTION WITH SAP30L.
[8]"Over-expression of GFP-FEZ1 causes generation of multi-lobulated nuclei mediated by microtubules in HEK293 cells."
Lanza D.C., Trindade D.M., Assmann E.M., Kobarg J.
Exp. Cell Res. 314:2028-2039(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[9]"Human FEZ1 protein forms a disulfide bond mediated dimer: implications for cargo transport."
Alborghetti M.R., Furlan A.S., Silva J.C., Paes Leme A.F., Torriani I.C., Kobarg J.
J. Proteome Res. 9:4595-4603(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, INTERACTION WITH SCOC, DISULFIDE BOND.
[10]"Genome-wide siRNA screen reveals amino acid starvation-induced autophagy requires SCOC and WAC."
McKnight N.C., Jefferies H.B., Alemu E.A., Saunders R.E., Howell M., Johansen T., Tooze S.A.
EMBO J. 31:1931-1946(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SCOC; ULK1 AND UVRAG, MUTAGENESIS OF GLU-248; LEU-254; LEU-260 AND LYS-264.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U60060 mRNA. Translation: AAC51282.1.
U60062 mRNA. Translation: AAC51284.1.
U69139 mRNA. Translation: AAB40660.1.
CR456817 mRNA. Translation: CAG33098.1.
CR541954 mRNA. Translation: CAG46752.1.
BC009545 mRNA. Translation: AAH09545.1.
CCDSCCDS31716.1. [Q99689-1]
CCDS44758.1. [Q99689-2]
RefSeqNP_005094.1. NM_005103.4. [Q99689-1]
NP_072043.1. NM_022549.3. [Q99689-2]
XP_005271791.1. XM_005271734.1. [Q99689-1]
XP_005271792.1. XM_005271735.1. [Q99689-1]
UniGeneHs.224008.
Hs.732083.

3D structure databases

ProteinModelPortalQ99689.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114997. 56 interactions.
DIPDIP-32494N.
IntActQ99689. 38 interactions.
MINTMINT-1403506.
STRING9606.ENSP00000278919.

PTM databases

PhosphoSiteQ99689.

Polymorphism databases

DMDM13431526.

Proteomic databases

PaxDbQ99689.
PRIDEQ99689.

Protocols and materials databases

DNASU9638.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000278919; ENSP00000278919; ENSG00000149557. [Q99689-1]
ENST00000366139; ENSP00000393425; ENSG00000149557. [Q99689-2]
ENST00000524435; ENSP00000431521; ENSG00000149557. [Q99689-2]
GeneID9638.
KEGGhsa:9638.
UCSCuc001qbx.3. human. [Q99689-1]
uc001qby.2. human. [Q99689-2]

Organism-specific databases

CTD9638.
GeneCardsGC11M125349.
HGNCHGNC:3659. FEZ1.
HPAHPA038490.
MIM604825. gene.
neXtProtNX_Q99689.
PharmGKBPA28100.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG273183.
HOGENOMHOG000019494.
HOVERGENHBG005657.
OMAEMMENSP.
OrthoDBEOG7CCBRQ.
PhylomeDBQ99689.
TreeFamTF313128.

Gene expression databases

ArrayExpressQ99689.
BgeeQ99689.
CleanExHS_FEZ1.
GenevestigatorQ99689.

Family and domain databases

InterProIPR011680. FEZ.
IPR015642. FEZ_1.
[Graphical view]
PANTHERPTHR12394. PTHR12394. 1 hit.
PTHR12394:SF4. PTHR12394:SF4. 1 hit.
PfamPF07763. FEZ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFEZ1. human.
GeneWikiFEZ1.
GenomeRNAi9638.
NextBio36177.
PROQ99689.
SOURCESearch...

Entry information

Entry nameFEZ1_HUMAN
AccessionPrimary (citable) accession number: Q99689
Secondary accession number(s): O00679, O00728, Q6IBI7
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: May 1, 1997
Last modified: July 9, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM