Q99689 (FEZ1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fasciculation and elongation protein zeta-1

Alternative name(s):
Zygin I
Zygin-1

Gene names

Name:

FEZ1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	392 AA.
Sequence status	Complete.
Protein existence	Evidence 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; difulfide-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	Cytoplasm › cytoskeleton › centrosome. Cell membrane By similarity. Note: Co-localizes 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 process	Transport
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane Microtubule
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil
PTM	Disulfide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon 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: Compara establishment of mitochondrion localization Inferred from electronic annotation. Source: Compara positive regulation of neuron differentiation Inferred from electronic annotation. Source: Compara positive regulation of neuron projection development Inferred from electronic annotation. Source: Compara transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	axon Inferred from electronic annotation. Source: Compara centrosome Inferred from electronic annotation. Source: Compara cytoplasm Inferred from direct assay. Source: HPA dendrite Inferred from electronic annotation. Source: Compara 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
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HTT	P42858	3	EBI-396435,EBI-466029
KIAA1377	Q9P2H0	2	EBI-396435,EBI-473176
NEK1	Q96PY6	2	EBI-396435,EBI-373615
TXNDC9	O14530	2	EBI-396435,EBI-707554

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 392	392	Fasciculation and elongation protein zeta-1		PRO_0000189525
Regions
	Coiled coil	230 – 298	69	Potential
	Compositional bias	95 – 98	4	Poly-Glu
	Compositional bias	140 – 145	6	Poly-Glu
	Compositional bias	182 – 186	5	Poly-Glu
Amino acid modifications
	Modified residue	58	1	Phosphoserine By similarity
	Modified residue	316	1	Phosphoserine By similarity
	Disulfide bond	133		Interchain Ref.9
Natural variations
	Alternative sequence	105 – 392	288	Missing in isoform Short.		VSP_006951
	Natural variant	123	1	D → E. Corresponds to variant rs597570 [ dbSNP | Ensembl ].		VAR_020461
Experimental info
	Mutagenesis	248	1	E → A: No effect on SCOC--binding. Ref.10
	Mutagenesis	254	1	L → P: Loss of SCOC-binding. No effect on ULK1-binding. Ref.10
	Mutagenesis	260	1	L → P: Loss of SCOC-binding. No effect on ULK1-binding. Ref.10
	Mutagenesis	264	1	K → A: No effect on SCOC-binding. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 4226ED5EA17706F2	FASTA	392	45,119
	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
	Isoform Short (FEZ1-T) [UniParc]. Checksum: A614EFAFF872EAF8	FASTA	104	12,074
	10 20 30 40 50 60 MEAPLVSLDE EFEDLRPSCS EDPEEKPQCF YGSSPHHLED PSLSELENFS SEIISFKSME 70 80 90 100 DLVNEFDEKL NVCFRNYNAK TENLAPVKNQ LQIQEEEETL QDEE

References

	« Hide 'large scale' referencesShow '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.
IPI	IPI00017070. IPI00910476.
RefSeq	NP_005094.1. NM_005103.4. NP_072043.1. NM_022549.3.
UniGene	Hs.224008. Hs.732083.
3D structure databases
ProteinModelPortal	Q99689.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-32494N.
IntAct	Q99689. 30 interactions.
MINT	MINT-1403506.
STRING	9606.ENSP00000278919.
PTM databases
PhosphoSite	Q99689.
Polymorphism databases
DMDM	13431526.
Proteomic databases
PaxDb	Q99689.
PRIDE	Q99689.
Protocols and materials databases
DNASU	9638.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000278919; ENSP00000278919; ENSG00000149557. ENST00000366139; ENSP00000393425; ENSG00000149557. ENST00000524435; ENSP00000431521; ENSG00000149557.
GeneID	9638.
KEGG	hsa:9638.
UCSC	uc001qbx.3. human. uc001qby.2. human.
Organism-specific databases
CTD	9638.
GeneCards	GC11M125349.
HGNC	HGNC:3659. FEZ1.
HPA	HPA038490.
MIM	604825. gene.
neXtProt	NX_Q99689.
PharmGKB	PA28100.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG273183.
HOGENOM	HOG000019494.
HOVERGEN	HBG005657.
OMA	EMMENSP.
OrthoDB	EOG4SF967.
PhylomeDB	Q99689.
Gene expression databases
ArrayExpress	Q99689.
Bgee	Q99689.
CleanEx	HS_FEZ1.
Genevestigator	Q99689.
GermOnline	ENSG00000149557. Homo sapiens.
Family and domain databases
InterPro	IPR011680. FEZ. IPR015642. FEZ_1. [Graphical view]
PANTHER	PTHR12394. PTHR12394. 1 hit. PTHR12394:SF4. PTHR12394:SF4. 1 hit.
Pfam	PF07763. FEZ. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	FEZ1. human.
GenomeRNAi	9638.
NextBio	36177.
SOURCE	Search...

Entry information

Entry name

FEZ1_HUMAN

Accession

Primary (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:	April 3, 2013
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.