Q86YT6 (MIB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase MIB1
EC=6.3.2.-

Alternative name(s):
DAPK-interacting protein 1
Short name=DIP-1
Mind bomb homolog 1
Zinc finger ZZ type with ankyrin repeat domain protein 2

Gene names

Name:	MIB1
Synonyms:	DIP1, KIAA1323, ZZANK2

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	1006 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors. Probably mediates ubiquitination and subsequent proteasomal degradation of DAPK1, thereby antagonizing anti-apoptotic effects of DAPK1 to promote TNF-induced apoptosis By similarity. Mediates 'Lys-63'-linked polyubiquitination of TBK1, which probably participates in kinase activation.
Pathway	Protein modification; protein ubiquitination.
Subcellular location	Cytoplasm. Cell membrane By similarity. Note: Localizes to the plasma membrane By similarity. According to Ref.8, it is mitochondrial, however such localization remains unclear. Ref.8
Tissue specificity	Widely expressed at low level. Expressed at higher level in spinal cord, ovary, whole brain, and all specific brain regions examined. Ref.6
Post-translational modification	Ubiquitinated. Possibly via autoubiquitination By similarity. Ref.9
Miscellaneous	In epilepsy brain tissue, levels of expression are increased in the cytoplasm and microsomal fractions (endoplasmic reticulum).
Sequence similarities	Contains 9 ANK repeats. Contains 2 MIB/HERC2 domains. Contains 3 RING-type zinc fingers. Contains 1 ZZ-type zinc finger.
Sequence caution	The sequence AAH22403.1 differs from that shown. Reason: Erroneous initiation. The sequence AAN18023.1 differs from that shown. Reason: Frameshift at position 3. The sequence BAC11439.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Notch signaling pathway Ubl conjugation pathway
Cellular component	Cell membrane Cytoplasm Membrane
Domain	ANK repeat Coiled coil Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling pathway Traceable author statement. Source: Reactome blood vessel development Inferred from electronic annotation. Source: Compara heart looping Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara negative regulation of neuron differentiation Inferred from electronic annotation. Source: Compara neural tube formation Inferred from electronic annotation. Source: Compara positive regulation of endocytosis Inferred from electronic annotation. Source: Compara somitogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	centrosome Inferred from direct assay PubMed 21399614. Source: UniProtKB cytoplasmic vesicle Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome nuclear membrane Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular_function	ubiquitin-protein ligase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Azi2	Q9QYP6	2	EBI-2129148,EBI-6115874	From a different organism.
TBK1	Q9UHD2	2	EBI-2129148,EBI-356402

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1006	1006	E3 ubiquitin-protein ligase MIB1		PRO_0000055943
Regions
	Domain	6 – 74	69	MIB/HERC2 1
	Domain	143 – 221	79	MIB/HERC2 2
	Repeat	430 – 460	31	ANK 1
	Repeat	463 – 492	30	ANK 2
	Repeat	496 – 525	30	ANK 3
	Repeat	529 – 558	30	ANK 4
	Repeat	562 – 591	30	ANK 5
	Repeat	595 – 627	33	ANK 6
	Repeat	631 – 661	31	ANK 7
	Repeat	665 – 694	30	ANK 8
	Repeat	698 – 729	32	ANK 9
	Zinc finger	79 – 126	48	ZZ-type
	Zinc finger	819 – 854	36	RING-type 1
	Zinc finger	866 – 901	36	RING-type 2
	Zinc finger	963 – 996	34	RING-type 3
	Coiled coil	935 – 962	28	Potential
Experimental info
	Sequence conflict	327	1	E → K in AAN18023. Ref.2
	Sequence conflict	398	1	S → F in AAN18023. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q86YT6 [UniParc]. Last modified June 1, 2003. Version 1. Checksum: 5D7D0D91AF98FF18	FASTA	1,006	110,136
	10 20 30 40 50 60 MSNSRNNRVM VEGVGARVVR GPDWKWGKQD GGEGHVGTVR SFESPEEVVV VWDNGTAANY 70 80 90 100 110 120 RCSGAYDLRI LDSAPTGIKH DGTMCDTCRQ QPIIGIRWKC AECTNYDLCT VCYHGDKHHL 130 140 150 160 170 180 RHRFYRITTP GSERVLLESR RKSKKITARG IFAGARVVRG VDWQWEDQDG GNGRRGKVTE 190 200 210 220 230 240 IQDWSASSPH SAAYVLWDNG AKNLYRVGFE GMSDLKCVQD AKGGSFYRDH CPVLGEQNGN 250 260 270 280 290 300 RNPGGLQIGD LVNIDLDLEI VQSLQHGHGG WTDGMFETLT TTGTVCGIDE DHDIVVQYPS 310 320 330 340 350 360 GNRWTFNPAV LTKANIVRSG DAAQGAEGGT SQFQVGDLVQ VCYDLERIKL LQRGHGEWAE 370 380 390 400 410 420 AMLPTLGKVG RVQQIYSDSD LKVEVCGTSW TYNPAAVSKV ASAGSAISNA SGERLSQLLK 430 440 450 460 470 480 KLFETQESGD LNEELVKAAA NGDVAKVEDL LKRPDVDVNG QCAGHTAMQA ASQNGHVDIL 490 500 510 520 530 540 KLLLKQNVDV EAEDKDGDRA VHHAAFGDEG AVIEVLHRGS ADLNARNKRR QTPLHIAVNK 550 560 570 580 590 600 GHLQVVKTLL DFGCHPSLQD SEGDTPLHDA ISKKRDDILA VLLEAGADVT ITNNNGFNAL 610 620 630 640 650 660 HHAALRGNPS AMRVLLSKLP RPWIVDEKKD DGYTALHLAA LNNHVEVAEL LVHQGNANLD 670 680 690 700 710 720 IQNVNQQTAL HLAVERQHTQ IVRLLVRAGA KLDIQDKDGD TPLHEALRHH TLSQLRQLQD 730 740 750 760 770 780 MQDVGKVDAA WEPSKNTLIM GLGTQGAEKK SAASIACFLA ANGADLSIRN KKGQSPLDLC 790 800 810 820 830 840 PDPNLCKALA KCHKEKVSGQ VGSRSPSMIS NDSETLEECM VCSDMKRDTL FGPCGHIATC 850 860 870 880 890 900 SLCSPRVKKC LICKEQVQSR TKIEECVVCS DKKAAVLFQP CGHMCACENC ANLMKKCVQC 910 920 930 940 950 960 RAVVERRVPF IMCCGGKSSE DATDDISSGN IPVLQKDKDN TNVNADVQKL QQQLQDIKEQ 970 980 990 1000 TMCPVCLDRL KNMIFLCGHG TCQLCGDRMS ECPICRKAIE RRILLY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta." Itoh M., Kim C.-H., Palardy G., Oda T., Jiang Y.-J., Maust D., Yeo S.-Y., Lorick K., Wright G.J., Ariza-McNaughton L., Weissman A.M., Lewis J., Chandrasekharappa S.C., Chitnis A.B. Dev. Cell 4:67-82(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Yoo K.-W., Chitnis A., Kim C.-H. Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	NHLBI resequencing and genotyping service (RS&G) Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [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]. Tissue: Lung.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 195-1006. Tissue: Amygdala and Endometrial tumor.
[6]	"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 611-1006, TISSUE SPECIFICITY. Tissue: Brain.
[7]	"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] OF 627-1006. Tissue: Placenta.
[8]	"Death-associated protein kinase expression in human temporal lobe epilepsy." Henshall D.C., Schindler C.K., So N.K., Lan J.-Q., Meller R., Simon R.P. Ann. Neurol. 55:485-494(2004) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE SUBCELLULAR LOCATION.
[9]	"Mapping a dynamic innate immunity protein interaction network regulating type I interferon production." Li S., Wang L., Berman M., Kong Y.Y., Dorf M.E. Immunity 35:426-440(2011) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION OF TBK1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY149908 mRNA. Translation: AAN75493.1. AY147849 mRNA. Translation: AAN18023.1. Frameshift. EF444995 Genomic DNA. Translation: ACA06016.1. BC022403 mRNA. Translation: AAH22403.1. Different initiation. BC110581 mRNA. Translation: AAI10582.1. BC110582 mRNA. Translation: AAI10583.1. CR749635 mRNA. Translation: CAH18429.1. AL713705 mRNA. Translation: CAD28502.1. AB037744 mRNA. Translation: BAA92561.1. AK075157 mRNA. Translation: BAC11439.1. Different initiation.
IPI	IPI00183054.
RefSeq	NP_065825.1. NM_020774.2.
UniGene	Hs.140903. Hs.658808.
3D structure databases
ProteinModelPortal	Q86YT6.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q86YT6. 12 interactions.
MINT	MINT-2841371.
PTM databases
PhosphoSite	Q86YT6.
Polymorphism databases
DMDM	68565512.
Proteomic databases
PaxDb	Q86YT6.
PRIDE	Q86YT6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261537; ENSP00000261537; ENSG00000101752.
GeneID	57534.
KEGG	hsa:57534.
UCSC	uc002ktp.3. human.
Organism-specific databases
CTD	57534.
GeneCards	GC18P019321.
HGNC	HGNC:21086. MIB1.
HPA	HPA019100.
MIM	608677. gene.
neXtProt	NX_Q86YT6.
Orphanet	54260. Left ventricular noncompaction.
PharmGKB	PA134862722.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0666.
HOVERGEN	HBG068386.
InParanoid	Q86YT6.
KO	K10645.
OMA	HDAISKE.
OrthoDB	EOG461435.
PhylomeDB	Q86YT6.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
SignaLink	Q86YT6.
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	Q86YT6.
Bgee	Q86YT6.
CleanEx	HS_MIB1.
Genevestigator	Q86YT6.
Family and domain databases
Gene3D	1.25.40.20. 4 hits. 3.30.40.10. 1 hit.
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR010606. Mib_Herc2. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. IPR000433. Znf_ZZ. [Graphical view]
Pfam	PF00023. Ank. 2 hits. PF12796. Ank_2. 3 hits. PF06701. MIB_HERC2. 2 hits. PF00569. ZZ. 1 hit. [Graphical view]
PRINTS	PR01415. ANKYRIN.
SMART	SM00248. ANK. 9 hits. SM00184. RING. 3 hits. SM00291. ZnF_ZZ. 1 hit. [Graphical view]
SUPFAM	SSF48403. ANK. 1 hit.
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 6 hits. PS51416. MIB_HERC2. 2 hits. PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. 3 hits. PS01357. ZF_ZZ_1. 1 hit. PS50135. ZF_ZZ_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	57534.
NextBio	63948.
SOURCE	Search...

Entry information

Entry name

MIB1_HUMAN

Accession

Primary (citable) accession number: Q86YT6
Secondary accession number(s): B0YJ38 , Q2TB37, Q68D01, Q6YI51, Q8NBY0, Q8TCB5, Q8TCL7, Q9P2M3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2005
Last sequence update:	June 1, 2003
Last modified:	May 29, 2013
This is version 103 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.