Reviewed, UniProtKB/Swiss-Prot Q9UJX5 (APC4_HUMAN)

Names and origin

Protein names

Recommended name:
    Anaphase-promoting complex subunit 4
      Short name=APC4
Alternative name(s):
    Cyclosome subunit 4

Gene names

Name:	ANAPC4
Synonyms:	APC4

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	808 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	The APC/C is composed of at least 12 subunits.
Sequence similarities	Belongs to the APC4 family.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis Ubl conjugation pathway
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	G2/M transition of mitotic cell cycle Ref.1 Traceable author statement. Source: ProtInc anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Inferred from Experiment. Source: Reactome cell division Inferred from electronic annotation. Source: UniProtKB-KW mitotic anaphase Ref.1 Traceable author statement. Source: ProtInc 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 protein K11-linked ubiquitination Ref.7 Inferred from direct assay. Source: UniProtKB
Cellular component	anaphase-promoting complex Ref.1 Ref.11 Inferred from direct assay. Source: UniProtKB cytosol Inferred from Experiment. Source: Reactome nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	ubiquitin-protein ligase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UJX5-1)

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: Q9UJX5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     542-551: DVIGKSMNQA → VSLKEMHVFV
     552-808: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 808	808	Anaphase-promoting complex subunit 4		PRO_0000064595
Amino acid modifications
	Modified residue	469	1	Phosphotyrosine Ref.6
	Modified residue	757	1	Phosphoserine
	Modified residue	758	1	Phosphoserine
	Modified residue	777	1	Phosphoserine Ref.8
	Modified residue	779	1	Phosphoserine Ref.6 Ref.8
Natural variations
	Alternative sequence	542 – 551	10	DVIGKSMNQA → VSLKEMHVFV in isoform 2.		VSP_008464
	Alternative sequence	552 – 808	257	Missing in isoform 2.		VSP_008465
	Natural variant	155	1	I → V in a colorectal cancer sample; somatic mutation. Ref.12		VAR_035792
	Natural variant	465	1	R → Q: dbSNP rs34811474.		VAR_054044
	Natural variant	800	1	E → G: dbSNP rs11550697.		VAR_054045
Experimental info
	Sequence conflict	286	1	R → C in AAF05752. Ref.1
	Sequence conflict	293 – 295	3	EKN → GKD in AAF05752. Ref.1
	Sequence conflict	756	1	E → G in AAH59383. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 2, 2008. Version 2. Checksum: 80362CC8D8B2063F	FASTA	808	92,116
	10 20 30 40 50 60 MLRFPTCFPS FRVVGEKQLP QEIIFLVWSP KRDLIALANT AGEVLLHRLA SFHRVWSFPP 70 80 90 100 110 120 NENTGKEVTC LAWRPDGKLL AFALADTKKI VLCDVEKPES LHSFSVEAPV SCMHWMEVTV 130 140 150 160 170 180 ESSVLTSFYN AEDESNLLLP KLPTLPKNYS NTSKIFSEEN SDEIIKLLGD VRLNILVLGG 190 200 210 220 230 240 SSGFIELYAY GMFKIARVTG IAGTCLALCL SSDLKSLSVV TEVSTNGASE VSYFQLETNL 250 260 270 280 290 300 LYSFLPEVTR MARKFTHISA LLQYINLSLT CMCEAWEEIL MQMDSRLTKF VQEKNTTTSV 310 320 330 340 350 360 QDEFMHLLLW GKASAELQTL LMNQLTVKGL KKLGQSIESS YSSIQKLVIS HLQSGSESLL 370 380 390 400 410 420 YHLSELKGMA SWKQKYEPLG LDAAGIEEAI TAVGSFILKA NELLQVIDSS MKNFKAFFRW 430 440 450 460 470 480 LYVAMLRMTE DHVLPELNKM TQKDITFVAE FLTEHFNEAP DLYNRKGKYF NVERVGQYLK 490 500 510 520 530 540 DEDDDLVSPP NTEGNQWYDF LQNSSHLKES PLLFPYYPRK SLHFVKRRME NIIDQCLQKP 550 560 570 580 590 600 ADVIGKSMNQ AICIPLYRDT RSEDSTRRLF KFPFLWNNKT SNLHYLLFTI LEDSLYKMCI 610 620 630 640 650 660 LRRHTDISQS VSNGLIAIKF GSFTYATTEK VRRSIYSCLD AQFYDDETVT VVLKDTVGRE 670 680 690 700 710 720 GRDRLLVQLP LSLVYNSEDS AEYQFTGTYS TRLDEQCSAI PTRTMHFEKH WRLLESMKAQ 730 740 750 760 770 780 YVAGNGFRKV SCVLSSNLRH VRVFEMDIDD EWELDESSDE EEEASNKPVK IKEEVLSESE 790 800 AENQQAGAAA LAPEIVIKVE KLDPELDS
	Isoform 2. Checksum: 16829B75DE9987DF	FASTA	551	62,639
	10 20 30 40 50 60 MLRFPTCFPS FRVVGEKQLP QEIIFLVWSP KRDLIALANT AGEVLLHRLA SFHRVWSFPP 70 80 90 100 110 120 NENTGKEVTC LAWRPDGKLL AFALADTKKI VLCDVEKPES LHSFSVEAPV SCMHWMEVTV 130 140 150 160 170 180 ESSVLTSFYN AEDESNLLLP KLPTLPKNYS NTSKIFSEEN SDEIIKLLGD VRLNILVLGG 190 200 210 220 230 240 SSGFIELYAY GMFKIARVTG IAGTCLALCL SSDLKSLSVV TEVSTNGASE VSYFQLETNL 250 260 270 280 290 300 LYSFLPEVTR MARKFTHISA LLQYINLSLT CMCEAWEEIL MQMDSRLTKF VQEKNTTTSV 310 320 330 340 350 360 QDEFMHLLLW GKASAELQTL LMNQLTVKGL KKLGQSIESS YSSIQKLVIS HLQSGSESLL 370 380 390 400 410 420 YHLSELKGMA SWKQKYEPLG LDAAGIEEAI TAVGSFILKA NELLQVIDSS MKNFKAFFRW 430 440 450 460 470 480 LYVAMLRMTE DHVLPELNKM TQKDITFVAE FLTEHFNEAP DLYNRKGKYF NVERVGQYLK 490 500 510 520 530 540 DEDDDLVSPP NTEGNQWYDF LQNSSHLKES PLLFPYYPRK SLHFVKRRME NIIDQCLQKP 550 AVSLKEMHVF V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a cullin homology region in a subunit of the anaphase-promoting complex." Yu H., Peters J.-M., King R.W., Page A.M., Hieter P., Kirschner M.W. Science 279:1219-1222(1998) [PubMed: 9469815] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBUNIT.
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 434-808 (ISOFORM 2). Tissue: Amygdala.
[6]	"Mitotic regulation of the human anaphase-promoting complex by phosphorylation." Kraft C., Herzog F., Gieffers C., Mechtler K., Hagting A., Pines J., Peters J.-M. EMBO J. 22:6598-6609(2003) [PubMed: 14657031] [Abstract] Cited for: PHOSPHORYLATION AT TYR-469 AND SER-779.
[7]	"Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex." Jin L., Williamson A., Banerjee S., Philipp I., Rape M. Cell 133:653-665(2008) [PubMed: 18485873] [Abstract] Cited for: FUNCTION OF THE APC/C.
[8]	"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 SER-777 AND SER-779, MASS SPECTROMETRY.
[9]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-779, MASS SPECTROMETRY.
[10]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-757 AND SER-758, MASS SPECTROMETRY. Tissue: T-cell.
[11]	"Localization of the coactivator Cdh1 and the cullin subunit Apc2 in a cryo-electron microscopy model of vertebrate APC/C." Dube P., Herzog F., Gieffers C., Sander B., Riedel D., Mueller S.A., Engel A., Peters J.-M., Stark H. Mol. Cell 20:867-879(2005) [PubMed: 16364912] [Abstract] Cited for: ELECTRON MICROSCOPY OF THE APC/C.
[12]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-155.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF191338 mRNA. Translation: AAF05752.1. AK292336 mRNA. Translation: BAF85025.1. CH471069 Genomic DNA. Translation: EAW92839.1. BC059383 mRNA. Translation: AAH59383.1. AL353932 mRNA. Translation: CAB89245.1.
IPI	IPI00002551. IPI00419201.
PIR	T48682.
RefSeq	NP_037499.2.
UniGene	Hs.152173
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q9UJX5.
PTM databases
PhosphoSite	Q9UJX5.
Proteomic databases
PRIDE	Q9UJX5.
Genome annotation databases
Ensembl	ENST00000315368; ENSP00000318775; ENSG00000053900; Homo sapiens. [Genome view]
GeneID	29945.
KEGG	hsa:29945.
Organism-specific databases
CTD	29945.
GeneCards	GC04P025055.
H-InvDB	HIX0020484.
HGNC	HGNC:19990. ANAPC4.
MIM	606947. gene.
PharmGKB	PA134894250.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG714578.
HOVERGEN	Q9UJX5.
InParanoid	Q9UJX5.
OMA	FVQEKNT.
OrthoDB	EOG9VQD8R.
Enzyme and pathway databases
Reactome	REACT_152. Cell Cycle, Mitotic. REACT_1538. Cell Cycle Checkpoints. REACT_6850. Cdc20:Phospho-APC/C mediated degradation of Cyclin A. REACT_8017. APC-Cdc20 mediated degradation of Nek2A. REACT_9035. APC/C:Cdh1-mediated degradation of Skp2.
Gene expression databases
ArrayExpress	Q9UJX5.
Bgee	Q9UJX5.
CleanEx	HS_ANAPC4.
Genevestigator	Q9UJX5.
GermOnline	ENSG00000053900. Homo sapiens.
Family and domain databases
InterPro	IPR017169. APC4. IPR015943. WD40/YVTN_repeat-like_dom. IPR011046. WD40_repeat-like_dom. [Graphical view]
Gene3D	G3DSA:2.130.10.10. WD40/YVTN_repeat-like. 1 hit.
PIRSF	PIRSF037303. APC4. 1 hit.
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

APC4_HUMAN

Accession

Primary (citable) accession number: Q9UJX5
Secondary accession number(s): A8K8H1, Q6PCC6, Q9NSH6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2003
Last sequence update:	September 2, 2008
Last modified:	December 15, 2009
This is version 69 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.