Q13829 (BACD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 2
Short name=hBACURD2

Alternative name(s):
BTB/POZ domain-containing protein TNFAIP1
Protein B12
Tumor necrosis factor, alpha-induced protein 1, endothelial

Gene names

Name:	TNFAIP1
Synonyms:	BACURD2, EDP1

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

General annotation (Comments)

Function	Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in regulation of cytoskeleton structure. The BCR(BACURD2) E3 ubiquitin ligase complex mediates the ubiquitination of RHOA, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and cell migration. Its interaction with RHOB may regulate apoptosis. May enhance the PCNA-dependent DNA polymerase delta activity. Ref.10 Ref.12
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Component of the BCR(BACURD2) E3 ubiquitin ligase complex, at least composed of CUL3, TNFAIP1/BACURD2 and RBX1. Interacts with RHOA; with a preference for RhoA-GDP. Interacts with RHOB. Interacts with PCNA. Interacts with CSNK2B. Ref.10 Ref.11 Ref.12
Subcellular location	Cytoplasm. Nucleus. Endosome. Note: Colocalizes with RHOB in endosomes. Ref.10 Ref.11
Induction	By TNF, IL1B/interleukin-1 beta and bacterial lipopolysaccharides (LPS).
Post-translational modification	Phosphorylation at Ser-280 by CK2 facilitates the nucleus localization and increases interaction with PCNA.
Sequence similarities	Belongs to the BACURD family. Contains 1 BTB (POZ) domain.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Endosome Nucleus
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication Inferred from sequence or structural similarity. Source: UniProtKB apoptotic process Traceable author statement Ref.10. Source: UniProtKB cell migration Inferred from mutant phenotype Ref.12. Source: UniProtKB embryo development Inferred from sequence or structural similarity. Source: UniProtKB immune response Inferred from expression pattern Ref.1. Source: UniProtKB negative regulation of Rho protein signal transduction Inferred from mutant phenotype Ref.12. Source: UniProtKB positive regulation of DNA replication Inferred from electronic annotation. Source: Compara proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay Ref.12. Source: UniProtKB protein homooligomerization Inferred from electronic annotation. Source: InterPro protein ubiquitination Inferred from direct assay Ref.12. Source: UniProtKB stress fiber assembly Inferred from mutant phenotype Ref.12. Source: UniProtKB
Cellular_component	Cul3-RING ubiquitin ligase complex Inferred from direct assay Ref.12. Source: UniProtKB endosome Inferred from direct assay Ref.10. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA
Molecular_function	GTP-Rho binding Inferred from direct assay Ref.10Ref.12. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RHOB	P62745	5	EBI-2505861,EBI-602647

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 316	316	BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 2		PRO_0000191300
Regions
	Domain	28 – 96	69	BTB
Amino acid modifications
	Modified residue	278	1	Phosphoserine Ref.9 Ref.13
	Modified residue	280	1	Phosphoserine; by CK2 Ref.9 Ref.11
Experimental info
	Mutagenesis	71 – 73	3	ILI → AAA: Abolishes interaction with CUL3 and induces abnormal actin stress fibers. Ref.12
	Mutagenesis	142	1	S → A: Does not affect phosphorylation level; when associated with A-237. Ref.11
	Mutagenesis	237	1	T → A: Does not affect phosphorylation level; when associated with A-142. Ref.11
	Mutagenesis	265	1	S → A: Does not affect phosphorylation level. Ref.11
	Mutagenesis	278	1	S → A: Slightly impairs phosphorylation level. Ref.11
	Mutagenesis	280	1	S → A: Strongly impairs phosphorylation level. Ref.11

Sequences

	Sequence		Length	Mass (Da)
	Q13829 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: D20B810A00507DCF	FASTA	316	36,204
	10 20 30 40 50 60 MSGDTCLCPA SGAKPKLSGF KGGGLGNKYV QLNVGGSLYY TTVRALTRHD TMLKAMFSGR 70 80 90 100 110 120 MEVLTDKEGW ILIDRCGKHF GTILNYLRDD TITLPQNRQE IKELMAEAKY YLIQGLVNMC 130 140 150 160 170 180 QSALQDKKDS YQPVCNIPII TSLKEEERLI ESSTKPVVKL LYNRSNNKYS YTSNSDDHLL 190 200 210 220 230 240 KNIELFDKLS LRFNGRVLFI KDVIGDEICC WSFYGQGRKL AEVCCTSIVY ATEKKQTKVE 250 260 270 280 290 300 FPEARIYEET LNVLLYETPR VPDNSLLEAT SRSRSQASPS EDEETFELRD RVRRIHVKRY 310 STYDDRQLGH QSTHRD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of a novel tumor necrosis factor-alpha-induced endothelial primary response gene." Wolf F.W., Marks R.M., Sarma V., Byers M.G., Katz R.W., Shows T.B., Dixit V.M. J. Biol. Chem. 267:1317-1326(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Endothelial cell.
[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]. Tissue: Amygdala.
[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].
[4]	"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 (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	SeattleSNPs variation discovery resource Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[9]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-278 AND SER-280, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"RhoB induces apoptosis via direct interaction with TNFAIP1 in HeLa cells." Kim D.M., Chung K.S., Choi S.J., Jung Y.J., Park S.K., Han G.H., Ha J.S., Song K.B., Choi N.S., Kim H.M., Won M., Seo Y.S. Int. J. Cancer 125:2520-2527(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RHOB.
[11]	"CK2 phosphorylates TNFAIP1 to affect its subcellular localization and interaction with PCNA." Yang L., Liu N., Hu X., Zhang W., Wang T., Li H., Zhang B., Xiang S., Zhou J., Zhang J. Mol. Biol. Rep. 37:2967-2973(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CSNK2B AND PCNA, PHOSPHORYLATION AT SER-280, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-142; THR-237; SER-265; SER-278 AND SER-280.
[12]	"Cullin mediates degradation of RhoA through evolutionarily conserved BTB adaptors to control actin cytoskeleton structure and cell movement." Chen Y., Yang Z., Meng M., Zhao Y., Dong N., Yan H., Liu L., Ding M., Peng H.B., Shao F. Mol. Cell 35:841-855(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE COMPLEX, INTERACTION WITH RHOA, MUTAGENESIS OF 71-ILE--ILE-73.
[13]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-278, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	M80783 mRNA. Translation: AAA58385.1. AK312387 mRNA. Translation: BAG35304.1. CR456819 mRNA. Translation: CAG33100.1. BT020121 mRNA. Translation: AAV38924.1. AY065346 Genomic DNA. Translation: AAL38649.1. AC002094 Genomic DNA. No translation available. CH471159 Genomic DNA. Translation: EAW51077.1. BC001643 mRNA. Translation: AAH01643.1. BC001949 mRNA. Translation: AAH01949.1.
IPI	IPI00015819.
RefSeq	NP_066960.1. NM_021137.4.
UniGene	Hs.76090.
3D structure databases
ProteinModelPortal	Q13829.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13829. 4 interactions.
STRING	9606.ENSP00000226225.
PTM databases
PhosphoSite	Q13829.
Polymorphism databases
DMDM	2833248.
Proteomic databases
PaxDb	Q13829.
PRIDE	Q13829.
Protocols and materials databases
DNASU	7126.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000226225; ENSP00000226225; ENSG00000109079. ENST00000576850; ENSP00000459080; ENSG00000262447.
GeneID	7126.
KEGG	hsa:7126.
UCSC	uc002hax.2. human.
Organism-specific databases
CTD	7126.
GeneCards	GC17P026662.
HGNC	HGNC:11894. TNFAIP1.
HPA	HPA013333. HPA014641.
MIM	191161. gene.
neXtProt	NX_Q13829.
PharmGKB	PA36591.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG257745.
HOGENOM	HOG000294088.
HOVERGEN	HBG052219.
InParanoid	Q13829.
KO	K15074.
OMA	EMSGDTC.
OrthoDB	EOG4MPHQM.
PhylomeDB	Q13829.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	Q13829.
Bgee	Q13829.
CleanEx	HS_TNFAIP1.
Genevestigator	Q13829.
GermOnline	ENSG00000109079. Homo sapiens.
Family and domain databases
Gene3D	3.30.710.10. 1 hit.
InterPro	IPR000210. BTB/POZ-like. IPR011333. BTB/POZ_fold. IPR003131. T1-type_BTB. [Graphical view]
Pfam	PF02214. K_tetra. 1 hit. [Graphical view]
SMART	SM00225. BTB. 1 hit. [Graphical view]
SUPFAM	SSF54695. BTB/POZ_fold. 1 hit.
PROSITE	PS50097. BTB. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	7126.
NextBio	27887.
SOURCE	Search...

Entry information

Entry name

BACD2_HUMAN

Accession

Primary (citable) accession number: Q13829
Secondary accession number(s): Q5TZQ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 111 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.