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Q99689

- FEZ1_HUMAN

UniProt

Q99689 - FEZ1_HUMAN

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Protein

Fasciculation and elongation protein zeta-1

Gene

FEZ1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Biological processi

  1. axon guidance Source: ProtInc
  2. cell adhesion Source: ProtInc
  3. cellular response to growth factor stimulus Source: Ensembl
  4. establishment of mitochondrion localization Source: Ensembl
  5. nervous system development Source: ProtInc
  6. positive regulation of neuron differentiation Source: Ensembl
  7. positive regulation of neuron projection development Source: Ensembl
  8. transport Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Fasciculation and elongation protein zeta-1
Alternative name(s):
Zygin I
Zygin-1
Gene namesi
Name:FEZ1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:3659. FEZ1.

Subcellular locationi

Cytoplasmcytoskeletonmicrotubule organizing centercentrosome 1 Publication. 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).By similarity

GO - Cellular componenti

  1. axon Source: Ensembl
  2. centrosome Source: Ensembl
  3. cytoplasm Source: HPA
  4. dendrite Source: Ensembl
  5. microtubule Source: UniProtKB-KW
  6. microtubule cytoskeleton Source: HPA
  7. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Microtubule

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi248 – 2481E → A: No effect on SCOC--binding. 1 Publication
Mutagenesisi254 – 2541L → P: Loss of SCOC-binding. No effect on ULK1-binding. 1 Publication
Mutagenesisi260 – 2601L → P: Loss of SCOC-binding. No effect on ULK1-binding. 1 Publication
Mutagenesisi264 – 2641K → A: No effect on SCOC-binding. 1 Publication

Organism-specific databases

PharmGKBiPA28100.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 392392Fasciculation and elongation protein zeta-1PRO_0000189525Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei58 – 581PhosphoserineBy similarity
Disulfide bondi133 – 133Interchain1 Publication

Post-translational modificationi

Phosphorylated by protein kinase C zeta; which enhances interaction with UBE4B and polyubiquitination.1 Publication
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-26.1 Publication

Keywords - PTMi

Disulfide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ99689.
PRIDEiQ99689.

PTM databases

PhosphoSiteiQ99689.

Expressioni

Tissue specificityi

Mainly expressed in brain.

Gene expression databases

BgeeiQ99689.
CleanExiHS_FEZ1.
ExpressionAtlasiQ99689. baseline and differential.
GenevestigatoriQ99689.

Organism-specific databases

HPAiHPA038490.

Interactioni

Subunit structurei

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.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HTTP428585EBI-396435,EBI-466029
KIAA1377Q9P2H02EBI-396435,EBI-473176
NEK1Q96PY62EBI-396435,EBI-373615
TXNDC9O145302EBI-396435,EBI-707554

Protein-protein interaction databases

BioGridi114997. 56 interactions.
DIPiDIP-32494N.
IntActiQ99689. 38 interactions.
MINTiMINT-1403506.
STRINGi9606.ENSP00000278919.

Structurei

3D structure databases

ProteinModelPortaliQ99689.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili230 – 29869Sequence AnalysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi95 – 984Poly-Glu
Compositional biasi140 – 1456Poly-Glu
Compositional biasi182 – 1865Poly-Glu

Sequence similaritiesi

Belongs to the zygin family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiNOG273183.
GeneTreeiENSGT00390000017627.
HOGENOMiHOG000019494.
HOVERGENiHBG005657.
InParanoidiQ99689.
OMAiEMMENSP.
OrthoDBiEOG7CCBRQ.
PhylomeDBiQ99689.
TreeFamiTF313128.

Family and domain databases

InterProiIPR011680. FEZ.
IPR015642. FEZ_1.
[Graphical view]
PANTHERiPTHR12394. PTHR12394. 1 hit.
PTHR12394:SF4. PTHR12394:SF4. 1 hit.
PfamiPF07763. FEZ. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform Long (identifier: Q99689-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MEAPLVSLDE EFEDLRPSCS EDPEEKPQCF YGSSPHHLED PSLSELENFS
60 70 80 90 100
SEIISFKSME DLVNEFDEKL NVCFRNYNAK TENLAPVKNQ LQIQEEEETL
110 120 130 140 150
QDEEVWDALT DNYIPSLSED WRDPNIEALN GNCSDTEIHE KEEEEFNEKS
160 170 180 190 200
ENDSGINEEP LLTADQVIEE IEEMMQNSPD PEEEEEVLEE EDGGETSSQA
210 220 230 240 250
DSVLLQEMQA LTQTFNNNWS YEGLRHMSGS ELTELLDQVE GAIRDFSEEL
260 270 280 290 300
VQQLARRDEL EFEKEVKNSF ITVLIEVQNK QKEQRELMKK RRKEKGLSLQ
310 320 330 340 350
SSRIEKGNQM PLKRFSMEGI SNILQSGIRQ TFGSSGTDKQ YLNTVIPYEK
360 370 380 390
KASPPSVEDL QMLTNILFAM KEDNEKVPTL LTDYILKVLC PT
Length:392
Mass (Da):45,119
Last modified:May 1, 1997 - v1
Checksum:i4226ED5EA17706F2
GO
Isoform Short (identifier: Q99689-2) [UniParc]FASTAAdd to Basket

Also known as: FEZ1-T

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

Show »
Length:104
Mass (Da):12,074
Checksum:iA614EFAFF872EAF8
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti123 – 1231D → E.
Corresponds to variant rs597570 [ dbSNP | Ensembl ].
VAR_020461

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei105 – 392288Missing in isoform Short. 1 PublicationVSP_006951Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS31716.1. [Q99689-1]
CCDS44758.1. [Q99689-2]
RefSeqiNP_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]
UniGeneiHs.224008.
Hs.732083.

Genome annotation databases

EnsembliENST00000278919; ENSP00000278919; ENSG00000149557. [Q99689-1]
ENST00000366139; ENSP00000393425; ENSG00000149557. [Q99689-2]
ENST00000524435; ENSP00000431521; ENSG00000149557. [Q99689-2]
GeneIDi9638.
KEGGihsa:9638.
UCSCiuc001qbx.3. human. [Q99689-1]
uc001qby.2. human. [Q99689-2]

Polymorphism databases

DMDMi13431526.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS31716.1. [Q99689-1 ]
CCDS44758.1. [Q99689-2 ]
RefSeqi NP_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 ]
UniGenei Hs.224008.
Hs.732083.

3D structure databases

ProteinModelPortali Q99689.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114997. 56 interactions.
DIPi DIP-32494N.
IntActi Q99689. 38 interactions.
MINTi MINT-1403506.
STRINGi 9606.ENSP00000278919.

PTM databases

PhosphoSitei Q99689.

Polymorphism databases

DMDMi 13431526.

Proteomic databases

PaxDbi Q99689.
PRIDEi Q99689.

Protocols and materials databases

DNASUi 9638.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000278919 ; ENSP00000278919 ; ENSG00000149557 . [Q99689-1 ]
ENST00000366139 ; ENSP00000393425 ; ENSG00000149557 . [Q99689-2 ]
ENST00000524435 ; ENSP00000431521 ; ENSG00000149557 . [Q99689-2 ]
GeneIDi 9638.
KEGGi hsa:9638.
UCSCi uc001qbx.3. human. [Q99689-1 ]
uc001qby.2. human. [Q99689-2 ]

Organism-specific databases

CTDi 9638.
GeneCardsi GC11M125316.
HGNCi HGNC:3659. FEZ1.
HPAi HPA038490.
MIMi 604825. gene.
neXtProti NX_Q99689.
PharmGKBi PA28100.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG273183.
GeneTreei ENSGT00390000017627.
HOGENOMi HOG000019494.
HOVERGENi HBG005657.
InParanoidi Q99689.
OMAi EMMENSP.
OrthoDBi EOG7CCBRQ.
PhylomeDBi Q99689.
TreeFami TF313128.

Miscellaneous databases

ChiTaRSi FEZ1. human.
GeneWikii FEZ1.
GenomeRNAii 9638.
NextBioi 36177.
PROi Q99689.
SOURCEi Search...

Gene expression databases

Bgeei Q99689.
CleanExi HS_FEZ1.
ExpressionAtlasi Q99689. baseline and differential.
Genevestigatori Q99689.

Family and domain databases

InterProi IPR011680. FEZ.
IPR015642. FEZ_1.
[Graphical view ]
PANTHERi PTHR12394. PTHR12394. 1 hit.
PTHR12394:SF4. PTHR12394:SF4. 1 hit.
Pfami PF07763. FEZ. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiFEZ1_HUMAN
AccessioniPrimary (citable) accession number: Q99689
Secondary accession number(s): O00679, O00728, Q6IBI7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: May 1, 1997
Last modified: October 29, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3