Reviewed, UniProtKB/Swiss-Prot O00308 (WWP2_HUMAN)

Names and originHide

Protein names

Recommended name:
NEDD4-like E3 ubiquitin-protein ligase WWP2
EC=6.3.2.-

Alternative name(s):
WW domain-containing protein 2
Atrophin-1-interacting protein 2
Short name=AIP2

Gene names

Name:

WWP2

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 attributesHide

Sequence length	870 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)Hide

Function	E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates By similarity.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Binds SCNN1A, SCNN1B, SCNN1G, WBP1, WBP2, DRPLA and adenovirus type 2 PIII. Interacts with NDFIP1 in vitro. Ref.1 Ref.6 Ref.7 Ref.8 Ref.9
Tissue specificity	Detected in heart, throughout the brain, placenta, lung, liver, muscle, kidney and pancreas. Ref.6
Miscellaneous	A cysteine residue is required for ubiquitin-thioester formation.
Sequence similarities	Contains 1 C2 domain. Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain. Contains 4 WW domains.

OntologiesHide

Keywords
Biological process	Host-virus interaction Ubl conjugation pathway
Domain	Repeat
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	entry of virus into host cell Ref.8 Traceable author statement. Source: UniProtKB negative regulation of gene expression Inferred from mutant phenotype. Source: UniProtKB negative regulation of protein transport Inferred from mutant phenotype. Source: UniProtKB negative regulation of transporter activity Inferred from direct assay. Source: UniProtKB protein ubiquitination Inferred from direct assay. Source: UniProtKB
Cellular component	ubiquitin ligase complex Traceable author statement. Source: ProtInc
Molecular function	protein binding Ref.6 Inferred from physical interaction. Source: UniProtKB ubiquitin-protein ligase activity Inferred from mutant phenotype. Source: UniProtKB
Complete GO annotation...

Binary interactionsHide

With	Entry	#Exp.	IntAct	Notes
RPS27A	P62988	1	EBI-743923,EBI-413034

Sequence annotation (Features)Hide

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 870	870	NEDD4-like E3 ubiquitin-protein ligase WWP2		PRO_0000120338
Regions
	Domain	20 – 100	81	C2
	Domain	300 – 333	34	WW 1
	Domain	330 – 363	34	WW 2
	Domain	405 – 437	33	WW 3
	Domain	444 – 477	34	WW 4
	Domain	536 – 870	335	HECT
Sites
	Active site	838	1	Glycyl thioester intermediate By similarity
Amino acid modifications
	Modified residue	211	1	Phosphoserine Ref.10 Ref.11 Ref.13
Experimental info
	Sequence conflict	136	1	E → K in AAC51325. Ref.1
	Sequence conflict	394 – 395	2	SS → FW in AAC51325. Ref.1

SequencesHide

	Sequence		Length	Mass (Da)
	O00308-1 [UniParc]. Last modified June 20, 2003. Version 2. Checksum: FCCD75CBA61F2204	FASTA	870	98,912
	10 20 30 40 50 60 MASASSSRAG VALPFEKSQL TLKVVSAKPK VHNRQPRINS YVEVAVDGLP SETKKTGKRI 70 80 90 100 110 120 GSSELLWNEI IILNVTAQSH LDLKVWSCHT LRNELLGTAS VNLSNVLKNN GGKMENMQLT 130 140 150 160 170 180 LNLQTENKGS VVSGGELTIF LDGPTVDLGN VPNGSALTDG SQLPSRDSSG TAVAPENRHQ 190 200 210 220 230 240 PPSTNCFGGR SRTHRHSGAS ARTTPATGEQ SPGARSRHRQ PVKNSGHSGL ANGTVNDEPT 250 260 270 280 290 300 TATDPEEPSV VGVTSPPAAP LSVTPNPNTT SLPAPATPAE GEEPSTSGTQ QLPAAAQAPD 310 320 330 340 350 360 ALPAGWEQRE LPNGRVYYVD HNTKTTTWER PLPPGWEKRT DPRGRFYYVD HNTRTTTWQR 370 380 390 400 410 420 PTAEYVRNYE QWQSQRNQLQ GAMQHFSQRF LYQSSSASTD HDPLGPLPPG WEKRQDNGRV 430 440 450 460 470 480 YYVNHNTRTT QWEDPRTQGM IQEPALPPGW EMKYTSEGVR YFVDHNTRTT TFKDPRPGFE 490 500 510 520 530 540 SGTKQGSPGA YDRSFRWKYH QFRFLCHSNA LPSHVKISVS RQTLFEDSFQ QIMNMKPYDL 550 560 570 580 590 600 RRRLYIIMRG EEGLDYGGIA REWFFLLSHE VLNPMYCLFE YAGKNNYCLQ INPASSINPD 610 620 630 640 650 660 HLTYFRFIGR FIAMALYHGK FIDTGFTLPF YKRMLNKRPT LKDLESIDPE FYNSIVWIKE 670 680 690 700 710 720 NNLEECGLEL YFIQDMEILG KVTTHELKEG GESIRVTEEN KEEYIMLLTD WRFTRGVEEQ 730 740 750 760 770 780 TKAFLDGFNE VAPLEWLRYF DEKELELMLC GMQEIDMSDW QKSTIYRHYT KNSKQIQWFW 790 800 810 820 830 840 QVVKEMDNEK RIRLLQFVTG TCRLPVGGFA ELIGSNGPQK FCIDKVGKET WLPRSHTCFN 850 860 870 RLDLPPYKSY EQLREKLLYA IEETEGFGQE

ReferencesHide

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of novel human WW domain-containing proteins by cloning of ligand targets." Pirozzi G., McConnell S.J., Uveges A.J., Carter J.M., Sparks A.B., Kay B.K., Fowlkes D.M. J. Biol. Chem. 272:14611-14616(1997) [PubMed: 9169421] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH WBP1; WBP2; SCNN1A; SCNN1B AND SCNN1G. Tissue: Bone marrow and Brain.
[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]. Tissue: Testis.
[3]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Ovary and Placenta.
[6]	"Atrophin-1, the DRPLA gene product, interacts with two families of WW domain-containing proteins." Wood J.D., Yuan J., Margolis R.L., Colomer V., Duan K., Kushi J., Kaminsky Z., Kleiderlein J.J. Jr., Sharp A.H., Ross C.A. Mol. Cell. Neurosci. 11:149-160(1998) [PubMed: 9647693] [Abstract] Cited for: INTERACTION WITH DRPLA, TISSUE SPECIFICITY.
[7]	"Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channel." McDonald F.J., Western A.H., McNeil J.D., Thomas B.C., Olson D.R., Snyder P.M. Am. J. Physiol. 283:F431-F436(2002) [PubMed: 12167593] [Abstract] Cited for: INTERACTION WITH SCNN1A; SCNN1B AND SCNN1G.
[8]	"Adenovirus protein involved in virus internalization recruits ubiquitin-protein ligases." Galinier R., Gout E., Lortat-Jacob H., Wood J., Chroboczek J. Biochemistry 41:14299-14305(2002) [PubMed: 12450395] [Abstract] Cited for: INTERACTION WITH ADENOVIRUS TYPE 2 PIII.
[9]	"N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel Golgi-associated protein." Harvey K.F., Shearwin-Whyatt L.M., Fotia A., Parton R.G., Kumar S. J. Biol. Chem. 277:9307-9317(2002) [PubMed: 11748237] [Abstract] Cited for: INTERACTION WITH NDFIP1.
[10]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"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-211, MASS SPECTROMETRY. Tissue: Embryonic kidney.
+	Additional computationally mapped references.

Cross-referencesHide

Sequence databases
EMBL GenBank DDBJ	U96114 mRNA. Translation: AAC51325.1. AK312792 mRNA. Translation: BAG35653.1. AC026468 Genomic DNA. No translation available. CH471092 Genomic DNA. Translation: EAW83287.1. BC000108 mRNA. Translation: AAH00108.1. BC013645 mRNA. Translation: AAH13645.1. BC064531 mRNA. Translation: AAH64531.1.
IPI	IPI00013010.
RefSeq	NP_008945.2. NP_955455.1. NP_955456.1.
UniGene	Hs.408458
3D structure databases
SMR	O00308. Positions 16-147, 302-331, 326-437, 402-477, 495-865.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00308. 9 interactions.
MINT	MINT-148449.
STRING	O00308.
PTM databases
PhosphoSite	O00308.
Proteomic databases
PRIDE	O00308.
Genome annotation databases
Ensembl	ENST00000356003; ENSP00000348283; ENSG00000198373; Homo sapiens. [Genome view] ENST00000359154; ENSP00000352069; ENSG00000198373; Homo sapiens. [Genome view] ENST00000448661; ENSP00000396871; ENSG00000198373; Homo sapiens. [Genome view]
GeneID	11060.
KEGG	hsa:11060.
UCSC	uc002exu.1. human.
Organism-specific databases
CTD	11060.
GeneCards	GC16P068353.
HGNC	HGNC:16804. WWP2.
MIM	602308. gene.
PharmGKB	PA128394764.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG14571.
HOGENOM	HBG607874.
HOVERGEN	HBG004134.
InParanoid	O00308.
OMA	DMSDWQK.
OrthoDB	EOG9RBT45.
PhylomeDB	O00308.
Gene expression databases
ArrayExpress	O00308.
Bgee	O00308.
CleanEx	HS_WWP2.
Genevestigator	O00308.
GermOnline	ENSG00000198373. Homo sapiens.
Family and domain databases
InterPro	IPR000008. C2_Ca-dep. IPR008973. C2_Ca/lipid-bd_dom_CaLB. IPR000569. HECT. IPR001202. WW_Rsp5_WWP. [Graphical view]
Pfam	PF00632. HECT. 1 hit. PF00397. WW. 4 hits. [Graphical view]
SMART	SM00239. C2. 1 hit. SM00119. HECTc. 1 hit. SM00456. WW. 4 hits. [Graphical view]
SUPFAM	SSF49562. C2_CaLB. 1 hit. SSF56204. HECT. 1 hit. SSF51045. WW_Rsp5_WWP. 4 hits.
PROSITE	PS50004. C2. False negative. PS50237. HECT. 1 hit. PS01159. WW_DOMAIN_1. 4 hits. PS50020. WW_DOMAIN_2. 4 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	42023.
SOURCE	Search...

Entry informationHide

Entry name

WWP2_HUMAN

Accession

Primary (citable) accession number: O00308
Secondary accession number(s): A6NEP1 , B2R706, Q96CZ2, Q9BWN6

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2003
Last sequence update:	June 20, 2003
Last modified:	July 13, 2010
This is version 96 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.