Fizzy-related protein homolog - Homo sapiens (Human)

Names and origin

Protein names

Recommended name:
    Fizzy-related protein homolog
      Short name=Fzr
Alternative name(s):
    Cdh1/Hct1 homolog
      Short name=hCDH1
    CDC20-like protein 1

Gene names

Name:	FZR1
Synonyms:	CDH1, FYR, FZR, KIAA1242

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	496 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Regulates ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) and may confer substrate specificity upon the complex. The APC/C-Cdh1 dimeric complex is activated during anaphase and telophase and remains active in degrading substrates until onset of the next S phase. Ref.9
Pathway	Protein modification; protein ubiquitination.
Subunit structure	The unphosphorylated form interacts with APC/C during mitosis. Ref.9
Subcellular location	Isoform 2: Nucleus. Ref.4 Isoform 3: Cytoplasm. Ref.4
Tissue specificity	Isoform 2 is expressed at high levels in heart, liver, spleen and some cancer cell lines wheras isoform 3 is expressed only at low levels in these tissues. Ref.4
Post-translational modification	Phosphorylated during mitosis, probably by maturation promoting factor (MPF). Ref.10 Ref.11 Ref.12
Sequence similarities	Belongs to the WD repeat CDC20/Fizzy family. Contains 7 WD repeats.
Sequence caution	The sequence AAD26623.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Sequence of unknown origin in the C-terminal part. The sequence AAD26624.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Sequence of unknown origin in the N-terminal part.

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Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat WD repeat
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	cell division Inferred from electronic annotation. Source: UniProtKB-KW mitosis Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of ubiquitin-protein ligase activity during mitotic cell cycle Inferred from Experiment. Source: Reactome positive regulation of ubiquitin-protein ligase activity during mitotic cell cycle Inferred from Experiment. Source: Reactome ubiquitin-dependent protein catabolic process Ref.9 Traceable author statement. Source: ProtInc
Cellular component	anaphase-promoting complex Ref.9 Traceable author statement. Source: ProtInc cytosol Inferred from Experiment. Source: Reactome nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	enzyme activator activity Ref.9 Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct
CDC14B	O60729	1	EBI-724997,EBI-970231
CDC27	P30260	2	EBI-724997,EBI-994813
CLSPN	Q9HAW4	3	EBI-724997,EBI-1369377
MAD2L2	Q9UI95	2	EBI-724997,EBI-77889

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Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UM11-1) 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 2 (identifier: Q9UM11-2) Also known as: CDH1alpha; Fzr1; The sequence of this isoform differs from the canonical sequence as follows: 481-483: Missing.
Note: Major.

Isoform 3 (identifier: Q9UM11-3) Also known as: CDH1beta; Fzr2; The sequence of this isoform differs from the canonical sequence as follows: 130-218: Missing. 481-483: Missing.
Note: Minor.

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 496

496

Fizzy-related protein homolog

PRO_0000051001

Regions

Repeat

182 – 222

41

WD 1

Repeat

227 – 266

40

WD 2

Repeat

269 – 306

38

WD 3

Repeat

311 – 350

40

WD 4

Repeat

353 – 395

43

WD 5

Repeat

397 – 438

42

WD 6

Repeat

441 – 480

40

WD 7

Amino acid modifications

Modified residue

32

1

Phosphothreonine Ref.12

Modified residue

36

1

Phosphoserine Ref.12

Modified residue

40

1

Phosphoserine Ref.12

Modified residue

91

1

Phosphotyrosine Ref.11

Modified residue

92

1

Phosphoserine Ref.11

Modified residue

137

1

Phosphoserine Ref.12

Modified residue

138

1

Phosphoserine Ref.12

Modified residue

146

1

Phosphoserine Ref.12

Modified residue

151

1

Phosphoserine Ref.12

Natural variations

Alternative sequence

130 – 218

89

Missing in isoform 3.

VSP_008503

Alternative sequence

481 – 483

3

Missing in isoform 2 and isoform 3.

VSP_008504

Experimental info

Sequence conflict

259

1

A → S in AAF20266. Ref.3

Sequence conflict

275

1

G → W in AAF20266. Ref.3

Sequence conflict

326

1

Q → H in BAA86954. Ref.2

Sequence conflict

326

1

Q → H in BAA86955. Ref.2

Sequence conflict

341

1

N → I in AAF20266. Ref.3

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified October 3, 2003. Version 2. Checksum: F6C8FDAF81D8103A Show »	FASTA	496	55,179
10 20 30 40 50 60 MDQDYERRLL RQIVIQNENT MPRVTEMRRT LTPASSPVSS PSKHGDRFIP SRAGANWSVN 70 80 90 100 110 120 FHRINENEKS PSQNRKAKDA TSDNGKDGLA YSALLKNELL GAGIEKVQDP QTEDRRLQPS 130 140 150 160 170 180 TPEKKGLFTY SLSTKRSSPD DGNDVSPYSL SPVSNKSQKL LRSPRKPTRK ISKIPFKVLD 190 200 210 220 230 240 APELQDDFYL NLVDWSSLNV LSVGLGTCVY LWSACTSQVT RLCDLSVEGD SVTSVGWSER 250 260 270 280 290 300 GNLVAVGTHK GFVQIWDAAA GKKLSMLEGH TARVGALAWN AEQLSSGSRD RMILQRDIRT 310 320 330 340 350 360 PPLQSERRLQ GHRQEVCGLK WSTDHQLLAS GGNDNKLLVW NHSSLSPVQQ YTEHLAAVKA 370 380 390 400 410 420 IAWSPHQHGL LASGGGTADR CIRFWNTLTG QPLQCIDTGS QVCNLAWSKH ANELVSTHGY 430 440 450 460 470 480 SQNQILVWKY PSLTQVAKLT GHSYRVLYLA MSPDGEAIVT GAGDETLRFW NVFSKTRSTK 490 VKWESVSVLN LFTRIR « Hide
Isoform 2 (CDH1alpha) (Fzr1). Checksum: 7C6A947EBB8A6D5C Show »	FASTA	493	54,766
10 20 30 40 50 60 MDQDYERRLL RQIVIQNENT MPRVTEMRRT LTPASSPVSS PSKHGDRFIP SRAGANWSVN 70 80 90 100 110 120 FHRINENEKS PSQNRKAKDA TSDNGKDGLA YSALLKNELL GAGIEKVQDP QTEDRRLQPS 130 140 150 160 170 180 TPEKKGLFTY SLSTKRSSPD DGNDVSPYSL SPVSNKSQKL LRSPRKPTRK ISKIPFKVLD 190 200 210 220 230 240 APELQDDFYL NLVDWSSLNV LSVGLGTCVY LWSACTSQVT RLCDLSVEGD SVTSVGWSER 250 260 270 280 290 300 GNLVAVGTHK GFVQIWDAAA GKKLSMLEGH TARVGALAWN AEQLSSGSRD RMILQRDIRT 310 320 330 340 350 360 PPLQSERRLQ GHRQEVCGLK WSTDHQLLAS GGNDNKLLVW NHSSLSPVQQ YTEHLAAVKA 370 380 390 400 410 420 IAWSPHQHGL LASGGGTADR CIRFWNTLTG QPLQCIDTGS QVCNLAWSKH ANELVSTHGY 430 440 450 460 470 480 SQNQILVWKY PSLTQVAKLT GHSYRVLYLA MSPDGEAIVT GAGDETLRFW NVFSKTRSTK 490 ESVSVLNLFT RIR « Hide
Isoform 3 (CDH1beta) (Fzr2). Checksum: A793194D88777035 Show »	FASTA	404	44,874
10 20 30 40 50 60 MDQDYERRLL RQIVIQNENT MPRVTEMRRT LTPASSPVSS PSKHGDRFIP SRAGANWSVN 70 80 90 100 110 120 FHRINENEKS PSQNRKAKDA TSDNGKDGLA YSALLKNELL GAGIEKVQDP QTEDRRLQPS 130 140 150 160 170 180 TPEKKGLFTV TRLCDLSVEG DSVTSVGWSE RGNLVAVGTH KGFVQIWDAA AGKKLSMLEG 190 200 210 220 230 240 HTARVGALAW NAEQLSSGSR DRMILQRDIR TPPLQSERRL QGHRQEVCGL KWSTDHQLLA 250 260 270 280 290 300 SGGNDNKLLV WNHSSLSPVQ QYTEHLAAVK AIAWSPHQHG LLASGGGTAD RCIRFWNTLT 310 320 330 340 350 360 GQPLQCIDTG SQVCNLAWSK HANELVSTHG YSQNQILVWK YPSLTQVAKL TGHSYRVLYL 370 380 390 400 AMSPDGEAIV TGAGDETLRF WNVFSKTRST KESVSVLNLF TRIR « Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Activation of the human anaphase-promoting complex by proteins of the CDC20/Fizzy family." Kramer E.R., Gieffers C., Hoelzl G., Hengstschlaeger M., Peters J.-M. Curr. Biol. 8:1207-1210(1998) [PubMed: 9811605] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Parathyroid adenoma.
[2]	"Human homologue of Fizzy-related protein." Kotani S., Oyamatu T., Todokoro K. Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND ISOFORM 3).
[3]	"Identification of a human homolog of the Drosophila fizzy-related protein." Sudo T., Saya H. Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Brain.
[4]	"Differential expression, localization and activity of two alternatively spliced isoforms of human APC regulator CDH1." Zhou Y., Ching Y.-P., Ng R.W.M., Jin D.-Y. Biochem. J. 374:349-358(2003) [PubMed: 12797865] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[5]	"Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O. DNA Res. 6:337-345(1999) [PubMed: 10574462] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[7]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[9]	"Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1." Fang G., Yu H., Kirschner M.W. Mol. Cell 2:163-171(1998) [PubMed: 9734353] [Abstract] Cited for: FUNCTION, INTERACTION WITH APC/C.
[10]	"Regulation of APC activity by phosphorylation and regulatory factors." Kotani S., Tanaka H., Yasuda H., Todokoro K. J. Cell Biol. 146:791-800(1999) [PubMed: 10459014] [Abstract] Cited for: PHOSPHORYLATION.
[11]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-91 AND SER-92, MASS SPECTROMETRY.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-32; SER-36; SER-40; SER-137; SER-138; SER-146 AND SER-151, MASS SPECTROMETRY.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	AF102508 mRNA. Translation: AAD26624.1. Different initiation. AF102507 mRNA. Translation: AAD26623.1. Different termination. AB013462 mRNA. Translation: BAA86954.1. AB013463 mRNA. Translation: BAA86955.1. AF080397 mRNA. Translation: AAF20266.1. AF083810 mRNA. Translation: AAD52030.1. AF433157 mRNA. Translation: AAL28117.1. BT007115 mRNA. Translation: AAP35779.1. AC005787 Genomic DNA. Translation: AAC62835.1. AC005786 Genomic DNA. Translation: AAC62836.1. AB033068 mRNA. Translation: BAA86556.1. Different initiation. BC013413 mRNA. Translation: AAH13413.1.
IPI	IPI00043958. IPI00099464. IPI00383919.
RefSeq	NP_001129669.1. NP_001129670.1. NP_057347.2.
UniGene	Hs.413133
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UM11. 6 interactions.
PTM databases
PhosphoSite	Q9UM11.
Proteomic databases
PRIDE	Q9UM11.
Genome annotation databases
Ensembl	ENSG00000105325. Homo sapiens. [Contig view]
GeneID	51343.
Organism-specific databases
GeneCards	GC19P003473.
H-InvDB	HIX0014640.
HGNC	HGNC:24824. FZR1.
MIM	603619. gene.
PharmGKB	PA134896003.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9UM11.
OMA	Q9UM11. RSSPDDG.
Enzyme and pathway databases
Reactome	REACT_152. Cell Cycle, Mitotic. REACT_383. DNA Replication. REACT_9035. APC/C:Cdh1-mediated degradation of Skp2.
Gene expression databases
ArrayExpress	Q9UM11.
Bgee	Q9UM11.
CleanEx	HS_CDH1.
GermOnline	ENSG00000105325. Homo sapiens.
Family and domain databases
InterPro	IPR015943. WD40/YVTN_repeat-like. IPR001680. WD40_repeat. IPR019782. WD40_repeat_2. IPR019775. WD40_repeat_CS. IPR017986. WD40_repeat_region. IPR019781. WD40_repeat_sg. [Graphical view]
Gene3D	G3DSA:2.130.10.10. WD40/YVTN_repeat-like. 1 hit.
Pfam	PF00400. WD40. 4 hits. [Graphical view]
ProDom	PD004563. Fizzy. 1 hit. PD000018. WD40. 2 hits. [Graphical view] [Entries sharing at least one domain]
SMART	SM00320. WD40. 6 hits. [Graphical view]
PROSITE	PS00678. WD_REPEATS_1. 2 hits. PS50082. WD_REPEATS_2. 3 hits. PS50294. WD_REPEATS_REGION. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	54790.
SOURCE	Search...

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Entry information

Entry name

FZR_HUMAN

Accession

Primary (citable) accession number: Q9UM11
Secondary accession number(s): O75869

Q9Y2T8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2003
Last sequence update:	October 3, 2003
Last modified:	June 16, 2009
This is version 82 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

MIM cross-references

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents