Q8NEZ5 (FBX22_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
F-box only protein 22

Alternative name(s):
F-box protein FBX22p44

Gene names

Name:	FBXO22
Synonyms:	FBX22

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	403 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Promotes the proteasome-dependent degradation of key sarcomeric proteins, such as alpha-actinin (ACTN2) and filamin-C (FLNC), essential for maintenance of normal contractile function. Ref.8
Subunit structure	Directly interacts with SKP1 and CUL1. Ref.8
Subcellular location	Cytoplasm › myofibril › sarcomere › Z line By similarity.
Tissue specificity	Predominantly expressed in liver, also enriched in cardiac muscle. Ref.8
Sequence similarities	Contains 1 F-box domain.
Sequence caution	The sequence AAH39024.1 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to starvation Inferred from electronic annotation. Source: Compara nucleocytoplasmic transport Inferred from electronic annotation. Source: Compara positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: Compara positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: Compara protein polyubiquitination Inferred from electronic annotation. Source: Compara regulation of myotube differentiation Inferred from electronic annotation. Source: Compara ubiquitin-dependent protein catabolic process Traceable author statement Ref.5. Source: ProtInc
Cellular_component	Z disc Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: Compara
Molecular_function	ubiquitin-protein ligase activity Traceable author statement PubMed 10531037. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q8NEZ5-1)

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: Q8NEZ5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     47-403: Missing.

Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 3 (identifier: Q8NEZ5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     266-276: NPLDIDASGVV → YVLCASDFVCE
     277-403: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 403	403	F-box only protein 22		PRO_0000119906
Regions
	Domain	21 – 67	47	F-box
Amino acid modifications
	Modified residue	194	1	N6-acetyllysine Ref.6
Natural variations
	Alternative sequence	47 – 403	357	Missing in isoform 2.		VSP_041821
	Alternative sequence	266 – 276	11	NPLDIDASGVV → YVLCASDFVCE in isoform 3.		VSP_013058
	Alternative sequence	277 – 403	127	Missing in isoform 3.		VSP_013059
Experimental info
	Sequence conflict	4 – 11	8	VGCCGECR → AGACGGP in AAF04523. Ref.5
	Sequence conflict	349	1	F → L in AAH32540. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: D96712BAA1149D8D	FASTA	403	44,508
	10 20 30 40 50 60 MEPVGCCGEC RGSSVDPRST FVLSNLAEVV ERVLTFLPAK ALLRVACVCR LWRECVRRVL 70 80 90 100 110 120 RTHRSVTWIS AGLAEAGHLE GHCLVRVVAE ELENVRILPH TVLYMADSET FISLEECRGH 130 140 150 160 170 180 KRARKRTSME TALALEKLFP KQCQVLGIVT PGIVVTPMGS GSNRPQEIEI GESGFALLFP 190 200 210 220 230 240 QIEGIKIQPF HFIKDPKNLT LERHQLTEVG LLDNPELRVV LVFGYNCCKV GASNYLQQVV 250 260 270 280 290 300 STFSDMNIIL AGGQVDNLSS LTSEKNPLDI DASGVVGLSF SGHRIQSATV LLNEDVSDEK 310 320 330 340 350 360 TAEAAMQRLK AANIPEHNTI GFMFACVGRG FQYYRAKGNV EADAFRKFFP SVPLFGFFGN 370 380 390 400 GEIGCDRIVT GNFILRKCNE VKDDDLFHSY TTIMALIHLG SSK
	Isoform 2 [UniParc]. Checksum: 1D49258F07775FA2	FASTA	46	4,922
	10 20 30 40 MEPVGCCGEC RGSSVDPRST FVLSNLAEVV ERVLTFLPAK ALLRVA
	Isoform 3 [UniParc]. Checksum: 0E9B0CE3E208358B	FASTA	276	30,589
	10 20 30 40 50 60 MEPVGCCGEC RGSSVDPRST FVLSNLAEVV ERVLTFLPAK ALLRVACVCR LWRECVRRVL 70 80 90 100 110 120 RTHRSVTWIS AGLAEAGHLE GHCLVRVVAE ELENVRILPH TVLYMADSET FISLEECRGH 130 140 150 160 170 180 KRARKRTSME TALALEKLFP KQCQVLGIVT PGIVVTPMGS GSNRPQEIEI GESGFALLFP 190 200 210 220 230 240 QIEGIKIQPF HFIKDPKNLT LERHQLTEVG LLDNPELRVV LVFGYNCCKV GASNYLQQVV 250 260 270 STFSDMNIIL AGGQVDNLSS LTSEKYVLCA SDFVCE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"FBX22p44: a novel human F-box protein predominantly expressed in the liver." Tan P., Pan Z.-Q. Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[3]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORMS 1 AND 2). Tissue: Brain, Colon and Lung.
[5]	"Identification of a family of human F-box proteins." Cenciarelli C., Chiaur D.S., Guardavaccaro D., Parks W., Vidal M., Pagano M. Curr. Biol. 9:1177-1179(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-82.
[6]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-194, MASS SPECTROMETRY.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"F-box and leucine-rich repeat protein 22 is a cardiac-enriched F-box protein that regulates sarcomeric protein turnover and is essential for maintenance of contractile function in vivo." Spaich S., Will R.D., Just S., Spaich S., Kuhn C., Frank D., Berger I.M., Wiemann S., Korn B., Koegl M., Backs J., Katus H.A., Rottbauer W., Frey N. Circ. Res. 111:1504-1516(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH SKP1 AND CUL1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY005144 mRNA. Translation: AAF89095.1. AK024048 mRNA. Translation: BAB14798.1. AC027104 Genomic DNA. No translation available. BC032540 mRNA. Translation: AAH32540.1. BC020204 mRNA. Translation: AAH20204.2. BC039024 mRNA. Translation: AAH39024.1. Sequence problems. BC041691 mRNA. Translation: AAH41691.1. AF174602 Genomic DNA. Translation: AAF04523.1.
IPI	IPI00169168. IPI00183208. IPI00554605.
RefSeq	NP_036302.1. NM_012170.3. NP_671717.1. NM_147188.2.
UniGene	Hs.591115.
3D structure databases
ProteinModelPortal	Q8NEZ5.
SMR	Q8NEZ5. Positions 24-57.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8NEZ5. 2 interactions.
STRING	9606.ENSP00000307833.
PTM databases
PhosphoSite	Q8NEZ5.
Polymorphism databases
DMDM	30580428.
Proteomic databases
PaxDb	Q8NEZ5.
PRIDE	Q8NEZ5.
Protocols and materials databases
DNASU	26263.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000308275; ENSP00000307833; ENSG00000167196. ENST00000453211; ENSP00000396442; ENSG00000167196. ENST00000540507; ENSP00000439270; ENSG00000167196. ENST00000569022; ENSP00000457531; ENSG00000167196.
GeneID	26263.
KEGG	hsa:26263.
UCSC	uc002bbj.2. human. uc002bbk.3. human.
Organism-specific databases
CTD	26263.
GeneCards	GC15P076196.
HGNC	HGNC:13593. FBXO22.
MIM	609096. gene.
neXtProt	NX_Q8NEZ5.
PharmGKB	PA28035.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG26261.
HOGENOM	HOG000285967.
HOVERGEN	HBG051570.
InParanoid	Q8NEZ5.
KO	K10302.
OMA	CCKVGAS.
OrthoDB	EOG46T320.
PhylomeDB	Q8NEZ5.
Gene expression databases
ArrayExpress	Q8NEZ5.
Bgee	Q8NEZ5.
CleanEx	HS_FBXO22.
Genevestigator	Q8NEZ5.
GermOnline	ENSG00000167196. Homo sapiens.
Family and domain databases
InterPro	IPR001810. F-box_dom_cyclin-like. IPR019494. FIST_C_domain. [Graphical view]
Pfam	PF00646. F-box. 1 hit. PF10442. FIST_C. 1 hit. [Graphical view]
SMART	SM00256. FBOX. 1 hit. [Graphical view]
SUPFAM	SSF81383. F-box_dom_Skp2-like. 1 hit.
PROSITE	PS50181. FBOX. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	26263.
NextBio	48531.
SOURCE	Search...

Entry information

Entry name

FBX22_HUMAN

Accession

Primary (citable) accession number: Q8NEZ5
Secondary accession number(s): Q0D2P8 , Q6PIL5, Q8IXW3, Q9H824, Q9UKC0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 9, 2003
Last sequence update:	October 1, 2002
Last modified:	May 1, 2013
This is version 88 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.