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Q9UGI0 (ZRAN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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:
Ubiquitin thioesterase ZRANB1

EC=3.4.19.12
Alternative name(s):
TRAF-binding domain-containing protein
Short name=hTrabid
Zinc finger Ran-binding domain-containing protein 1
Gene names
Name:ZRANB1
Synonyms:TRABID
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length708 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Specifically hydrolyzes 'Lys-29'-linked and 'Lys-33'-linked diubiquitin. Also cleaves 'Lys-63'-linked chains, but with 40-fold less efficiency compared to 'Lys-29'-linked ones. Positive regulator of the Wnt signaling pathway that deubiquitinates APC protein, a negative regulator of Wnt-mediated transcription. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the stress fiber dynamics and cell migration. May also modulate TNF-alpha signaling. Ref.6 Ref.7 Ref.8 Ref.9

Catalytic activity

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). Ref.8

Subunit structure

Interacts with APC and TRAF6. Ref.1 Ref.6

Subcellular location

Cytoplasm. Nucleus. Note: Enriched in punctate localization in the cytoplasm. Ref.1 Ref.6 Ref.7

Tissue specificity

Widely expressed. Ref.1

Domain

The OTU domain mediates the deubiquitinating activity. Ref.6 Ref.9

The RanBP2-type zinc fingers mediate the specific interaction with 'Lys-63'-linked ubiquitin. Ref.6 Ref.9

The second ankyrin repeat ANK 2 is termed AnkUBD, it interacts with ubiquitin hydrophobic patch and contributes to linkage specificity. Ref.6 Ref.9

The RanBP2-type zinc fingers, also called NZFs, may provide additional ubiquitin-binding sites when hydrolyzing long 'Lys-63'-linked chains. Ref.6 Ref.9

Sequence similarities

Belongs to the peptidase C64 family.

Contains 2 ANK repeats.

Contains 1 OTU domain.

Contains 3 RanBP2-type zinc fingers.

Sequence caution

The sequence BAG64010.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processUbl conjugation pathway
Wnt signaling pathway
   Cellular componentCytoplasm
Nucleus
   DomainANK repeat
Repeat
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Protease
Thiol protease
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

cell migration

Inferred from mutant phenotype Ref.7. Source: UniProtKB

cytoskeleton organization

Inferred from mutant phenotype Ref.7. Source: UniProtKB

positive regulation of Wnt signaling pathway

Inferred from mutant phenotype Ref.6. Source: UniProtKB

protein K29-linked deubiquitination

Inferred from direct assay Ref.8. Source: UniProtKB

protein K33-linked deubiquitination

Inferred from direct assay Ref.8. Source: UniProtKB

protein K63-linked deubiquitination

Inferred from direct assay Ref.8. Source: UniProtKB

protein deubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype Ref.6. Source: BHF-UCL

regulation of cell morphogenesis

Inferred from mutant phenotype Ref.7. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay Ref.7. Source: UniProtKB

nucleus

Inferred from direct assay Ref.1. Source: HGNC

   Molecular_functionK63-linked polyubiquitin binding

Inferred from direct assay Ref.6. Source: BHF-UCL

ubiquitin thiolesterase activity

Inferred from mutant phenotype Ref.6. Source: UniProtKB

ubiquitin-specific protease activity

Inferred from direct assay Ref.8. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

UBCP0CG482EBI-527853,EBI-3390054

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 708708Ubiquitin thioesterase ZRANB1
PRO_0000065595

Regions

Repeat260 – 29031ANK 1
Repeat313 – 34028ANK 2
Domain432 – 592161OTU
Zinc finger3 – 3331RanBP2-type 1
Zinc finger84 – 11330RanBP2-type 2
Zinc finger149 – 17830RanBP2-type 3
Region392 – 641250TRAF-binding

Sites

Active site4431Nucleophile Ref.9
Active site5851Proton acceptor By similarity

Experimental info

Mutagenesis101C → A: Abolishes the binding to ubiquitin chains but not the deubiquitinating activity; when associated with 14-LV-15; A-90; 94-LV-95; A-155 and 159-LV-160. Ref.6
Mutagenesis14 – 152TY → LV: Abolishes the binding to ubiquitin chains but not the deubiquitinating activity; when associated with A-10; A-90; 94-LV-95; A-155 and 159-LV-160. Ref.6
Mutagenesis901C → A: Abolishes the binding to ubiquitin chains but not the deubiquitinating activity; when associated with A-10; 14-LV-15; 94-LV-95; A-155 and 159-LV-160. Ref.6
Mutagenesis94 – 952TY → LV: Abolishes the binding to ubiquitin chains but not the deubiquitinating activity; when associated with A-10; 14-LV-15; A-90; A-155 and 159-LV-160. Ref.6
Mutagenesis1551C → A: Abolishes the binding to ubiquitin chains but not the deubiquitinating activity; when associated with A-10; 14-LV-15; A-90; 94-LV-95 and 159-LV-160. Ref.6
Mutagenesis159 – 1602TY → LV: Abolishes the binding to ubiquitin chains but not the deubiquitinating activity; when associated with A-10; 14-LV-15; A-90; 94-LV-95; and A-155.
Mutagenesis4431C → S: Abolishes the deubiquitinating activity but not the binding to ubiquitin chains. Ref.6
Sequence conflict3741F → I in CAB64449. Ref.1
Sequence conflict3841P → A in CAB64449. Ref.1
Sequence conflict6021A → P in BAG64010. Ref.2

Secondary structure

........................................................................ 708
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UGI0 [UniParc].

Last modified November 4, 2008. Version 2.
Checksum: DBB831697F450248

FASTA70880,967
        10         20         30         40         50         60 
MSERGIKWAC EYCTYENWPS AIKCTMCRAQ RPSGTIITED PFKSGSSDVG RDWDPSSTEG 

        70         80         90        100        110        120 
GSSPLICPDS SARPRVKSSY SMENANKWSC HMCTYLNWPR AIRCTQCLSQ RRTRSPTESP 

       130        140        150        160        170        180 
QSSGSGSRPV AFSVDPCEEY NDRNKLNTRT QHWTCSVCTY ENWAKAKRCV VCDHPRPNNI 

       190        200        210        220        230        240 
EAIELAETEE ASSIINEQDR ARWRGSCSSG NSQRRSPPAT KRDSEVKMDF QRIELAGAVG 

       250        260        270        280        290        300 
SKEELEVDFK KLKQIKNRMK KTDWLFLNAC VGVVEGDLAA IEAYKSSGGD IARQLTADEV 

       310        320        330        340        350        360 
RLLNRPSAFD VGYTLVHLAI RFQRQDMLAI LLTEVSQQAA KCIPAMVCPE LTEQIRREIA 

       370        380        390        400        410        420 
ASLHQRKGDF ACYFLTDLVT FTLPADIEDL PPTVQEKLFD EVLDRDVQKE LEEESPIINW 

       430        440        450        460        470        480 
SLELATRLDS RLYALWNRTA GDCLLDSVLQ ATWGIYDKDS VLRKALHDSL HDCSHWFYTR 

       490        500        510        520        530        540 
WKDWESWYSQ SFGLHFSLRE EQWQEDWAFI LSLASQPGAS LEQTHIFVLA HILRRPIIVY 

       550        560        570        580        590        600 
GVKYYKSFRG ETLGYTRFQG VYLPLLWEQS FCWKSPIALG YTRGHFSALV AMENDGYGNR 

       610        620        630        640        650        660 
GAGANLNTDD DVTITFLPLV DSERKLLHVH FLSAQELGNE EQQEKLLREW LDCCVTEGGV 

       670        680        690        700 
LVAMQKSSRR RNHPLVTQMV EKWLDRYRQI RPCTSLSDGE EDEDDEDE 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and characterization of two novel A20-like proteins."
Evans P.C., Taylor E.R., Coadwell J., Heyninck K., Beyaert R., Kilshaw P.J.
Biochem. J. 357:617-623(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH TRAF6.
Tissue: Umbilical vein 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. 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].
Tissue: Testis.
[3]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [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. expand/collapse author list , 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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 151-708.
Tissue: Melanoma.
[6]"Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains."
Tran H., Hamada F., Schwarz-Romond T., Bienz M.
Genes Dev. 22:528-542(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH APC, DOMAIN, MUTAGENESIS OF CYS-10; 14-THR-TYR-15; CYS-90; 94-THR-TYR-95; CYS-155; 159-THR-TYR-160 AND CYS-443.
[7]"Identification and characterization of a set of conserved and new regulators of cytoskeletal organisation, cell morphology and migration."
Bai S.W., Herrera-Abreu M.T., Rohn J.L., Racine V., Tajadura V., Suryavanshi N., Bechtel S., Wiemann S., Baum B., Ridley A.J.
BMC Biol. 9:54-54(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[8]"OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis."
Mevissen T.E., Hospenthal M.K., Geurink P.P., Elliott P.R., Akutsu M., Arnaudo N., Ekkebus R., Kulathu Y., Wauer T., El Oualid F., Freund S.M., Ovaa H., Komander D.
Cell 154:169-184(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY.
[9]"An ankyrin-repeat ubiquitin-binding domain determines TRABID's specificity for atypical ubiquitin chains."
Licchesi J.D., Mieszczanek J., Mevissen T.E., Rutherford T.J., Akutsu M., Virdee S., El Oualid F., Chin J.W., Ovaa H., Bienz M., Komander D.
Nat. Struct. Mol. Biol. 19:62-71(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.23 ANGSTROMS) OF 245-697, FUNCTION, LINKAGE SPECIFICITY, ACTIVE SITE, DOMAIN ANK REPEATS.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ252060 mRNA. Translation: CAB64449.1.
AK302810 mRNA. Translation: BAG64010.1. Different initiation.
AL731577, AL731571 Genomic DNA. Translation: CAH72159.1.
AL731571, AL731577 Genomic DNA. Translation: CAI16103.1.
CH471066 Genomic DNA. Translation: EAW49252.1.
CH471066 Genomic DNA. Translation: EAW49253.1.
AL832925 mRNA. Translation: CAH10620.1.
RefSeqNP_060050.2. NM_017580.2.
XP_005269983.1. XM_005269926.2.
UniGeneHs.595158.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3ZRHX-ray2.23A245-697[»]
ProteinModelPortalQ9UGI0.
SMRQ9UGI0. Positions 7-35, 85-112, 149-176, 245-692.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120139. 26 interactions.
DIPDIP-33806N.
IntActQ9UGI0. 25 interactions.
MINTMINT-6783281.
STRING9606.ENSP00000352676.

Protein family/group databases

MEROPSC64.004.

PTM databases

PhosphoSiteQ9UGI0.

Polymorphism databases

DMDM212276487.

Proteomic databases

PaxDbQ9UGI0.
PRIDEQ9UGI0.

Protocols and materials databases

DNASU54764.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000359653; ENSP00000352676; ENSG00000019995.
GeneID54764.
KEGGhsa:54764.
UCSCuc001lic.3. human.

Organism-specific databases

CTD54764.
GeneCardsGC10P126620.
H-InvDBHIX0009289.
HGNCHGNC:18224. ZRANB1.
HPAHPA029239.
HPA029240.
HPA029241.
MIM611749. gene.
neXtProtNX_Q9UGI0.
PharmGKBPA134933584.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG253754.
HOGENOMHOG000006743.
HOVERGENHBG058978.
InParanoidQ9UGI0.
KOK11862.
OMACSICTYE.
OrthoDBEOG7R56SB.
PhylomeDBQ9UGI0.
TreeFamTF323312.

Gene expression databases

BgeeQ9UGI0.
CleanExHS_ZRANB1.
GenevestigatorQ9UGI0.

Family and domain databases

InterProIPR003323. OTU.
IPR001876. Znf_RanBP2.
[Graphical view]
PfamPF02338. OTU. 1 hit.
PF00641. zf-RanBP. 2 hits.
[Graphical view]
SMARTSM00547. ZnF_RBZ. 3 hits.
[Graphical view]
PROSITEPS50802. OTU. 1 hit.
PS01358. ZF_RANBP2_1. 3 hits.
PS50199. ZF_RANBP2_2. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi54764.
NextBio57405.
PROQ9UGI0.
SOURCESearch...

Entry information

Entry nameZRAN1_HUMAN
AccessionPrimary (citable) accession number: Q9UGI0
Secondary accession number(s): B4DZ98 expand/collapse secondary AC list , D3DRF4, Q5SQP6, Q69YK3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 4, 2008
Last modified: April 16, 2014
This is version 123 of the entry and version 2 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

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM