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Q86YT6 (MIB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1006 AA.
Sequence statusComplete.
Protein existenceEvidence 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

Involvement in disease

Left ventricular non-compaction 7 (LVNC7) [MIM:615092]: A disease due to an arrest of myocardial morphogenesis. It is characterized by a hypertrophic left ventricle with deep trabeculations and with poor systolic function, with or without associated left ventricular dilation. In some cases, it is associated with other congenital heart anomalies.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11

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 processNotch signaling pathway
Ubl conjugation pathway
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainANK repeat
Coiled coil
Repeat
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
   PTMUbl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNotch signaling pathway

Traceable author statement. Source: Reactome

blood vessel development

Inferred from electronic annotation. Source: Ensembl

heart looping

Inferred from electronic annotation. Source: Ensembl

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

neural tube formation

Inferred from electronic annotation. Source: Ensembl

positive regulation of endocytosis

Inferred from electronic annotation. Source: Ensembl

somitogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcentrosome

Inferred from direct assay PubMed 21399614. Source: UniProtKB

cytoplasmic vesicle

Inferred from electronic annotation. Source: Ensembl

cytosol

Traceable author statement. Source: Reactome

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

postsynaptic density

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionubiquitin-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

Azi2Q9QYP62EBI-2129148,EBI-6115874From a different organism.
TBK1Q9UHD22EBI-2129148,EBI-356402

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10061006E3 ubiquitin-protein ligase MIB1
PRO_0000055943

Regions

Domain6 – 7469MIB/HERC2 1
Domain143 – 22179MIB/HERC2 2
Repeat430 – 46031ANK 1
Repeat463 – 49230ANK 2
Repeat496 – 52530ANK 3
Repeat529 – 55830ANK 4
Repeat562 – 59130ANK 5
Repeat595 – 62733ANK 6
Repeat631 – 66131ANK 7
Repeat665 – 69430ANK 8
Repeat698 – 72932ANK 9
Zinc finger79 – 12648ZZ-type
Zinc finger819 – 85436RING-type 1
Zinc finger866 – 90136RING-type 2
Zinc finger963 – 99634RING-type 3
Coiled coil935 – 96228 Potential

Natural variations

Natural variant1741R → H Found in a patient with severe mental retardation, psychomotor delay, no speech, sleep disturbances, feeding problems, abnormal breething, deep-set eyes and short philtrum. Ref.10
VAR_069385
Natural variant9431V → F in LVNC7. Ref.11
VAR_069620

Experimental info

Sequence conflict3271E → K in AAN18023. Ref.2
Sequence conflict3981S → F in AAN18023. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q86YT6 [UniParc].

Last modified June 1, 2003. Version 1.
Checksum: 5D7D0D91AF98FF18

FASTA1,006110,136
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.
[10]"Diagnostic exome sequencing in persons with severe intellectual disability."
de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G., Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C., del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G., Veltman J.A., Vissers L.E.
N. Engl. J. Med. 367:1921-1929(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HIS-174.
[11]"Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy."
Luxan G., Casanova J.C., Martinez-Poveda B., Prados B., D'Amato G., MacGrogan D., Gonzalez-Rajal A., Dobarro D., Torroja C., Martinez F., Izquierdo-Garcia J.L., Fernandez-Friera L., Sabater-Molina M., Kong Y.Y., Pizarro G., Ibanez B., Medrano C., Garcia-Pavia P. expand/collapse author list , Gimeno J.R., Monserrat L., Jimenez-Borreguero L.J., de la Pompa J.L.
Nat. Med. 19:193-201(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LVNC7 PHE-943.
+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.
RefSeqNP_065825.1. NM_020774.3.
UniGeneHs.140903.

3D structure databases

ProteinModelPortalQ86YT6.
SMRQ86YT6. Positions 15-70, 154-216, 382-779, 851-908, 953-1003.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121593. 35 interactions.
IntActQ86YT6. 13 interactions.
MINTMINT-2841371.

PTM databases

PhosphoSiteQ86YT6.

Polymorphism databases

DMDM68565512.

Proteomic databases

PaxDbQ86YT6.
PRIDEQ86YT6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261537; ENSP00000261537; ENSG00000101752.
GeneID57534.
KEGGhsa:57534.
UCSCuc002ktp.3. human.

Organism-specific databases

CTD57534.
GeneCardsGC18P019284.
HGNCHGNC:21086. MIB1.
HPACAB037044.
HPA019100.
MIM608677. gene.
615092. phenotype.
neXtProtNX_Q86YT6.
Orphanet54260. Left ventricular noncompaction.
PharmGKBPA134862722.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0666.
HOVERGENHBG068386.
InParanoidQ86YT6.
KOK10645.
OMAHDAISKE.
OrthoDBEOG7WHH8P.
PhylomeDBQ86YT6.
TreeFamTF324147.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
SignaLinkQ86YT6.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ86YT6.
BgeeQ86YT6.
CleanExHS_MIB1.
GenevestigatorQ86YT6.

Family and domain databases

Gene3D1.25.40.20. 4 hits.
3.30.40.10. 1 hit.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR010606. Mib_Herc2.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR000433. Znf_ZZ.
[Graphical view]
PfamPF00023. Ank. 1 hit.
PF12796. Ank_2. 3 hits.
PF06701. MIB_HERC2. 2 hits.
PF00569. ZZ. 1 hit.
[Graphical view]
PRINTSPR01415. ANKYRIN.
SMARTSM00248. ANK. 9 hits.
SM00184. RING. 3 hits.
SM00291. ZnF_ZZ. 1 hit.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 6 hits.
PS51416. MIB_HERC2. 2 hits.
PS50089. ZF_RING_2. 3 hits.
PS01357. ZF_ZZ_1. 1 hit.
PS50135. ZF_ZZ_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMIB1_(gene).
GenomeRNAi57534.
NextBio63948.
PROQ86YT6.
SOURCESearch...

Entry information

Entry nameMIB1_HUMAN
AccessionPrimary (citable) accession number: Q86YT6
Secondary accession number(s): B0YJ38 expand/collapse secondary AC list , 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: April 16, 2014
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM