Q9UGI0 (ZRAN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	708 AA.
Sequence status	Complete.
Protein existence	Evidence 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
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).
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 The RanBP2-type zinc fingers mediate the specific interaction with 'Lys-63'-linked ubiquitin. Ref.6 The second ankyrin repeat ANK 2 is termed AnkUBD, it interacts with ubiquitin hydrophobic patch and contributes to linkage specificity. Ref.6 The RanBP2-type zinc fingers, also called NZFs, may provide additional ubiquitin-binding sites when hydrolyzing long 'Lys-63'-linked chains. Ref.6
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 process	Ubl conjugation pathway Wnt signaling pathway
Cellular component	Cytoplasm Nucleus
Domain	ANK repeat Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Protease Thiol protease
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor 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 receptor signaling pathway Inferred from mutant phenotype Ref.6. Source: UniProtKB protein K63-linked deubiquitination Inferred from mutant phenotype Ref.6. 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_component	cytoplasm Inferred from direct assay Ref.7. Source: UniProtKB nucleus Inferred from direct assay Ref.1. Source: HGNC
Molecular_function	K63-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.6. Source: BHF-UCL zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 708

708

Ubiquitin thioesterase ZRANB1

PRO_0000065595

Regions

Repeat

260 – 290

31

ANK 1

Repeat

313 – 340

28

ANK 2

Domain

432 – 592

161

OTU

Zinc finger

3 – 33

31

RanBP2-type 1

Zinc finger

84 – 113

30

RanBP2-type 2

Zinc finger

149 – 178

30

RanBP2-type 3

Region

392 – 641

250

TRAF-binding

Sites

Active site

443

1

Nucleophile Ref.8

Active site

585

1

Proton acceptor By similarity

Experimental info

Mutagenesis

10

1

C → 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

Mutagenesis

14 – 15

2

TY → 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

Mutagenesis

90

1

C → 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

Mutagenesis

94 – 95

2

TY → 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

Mutagenesis

155

1

C → 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

Mutagenesis

159 – 160

2

TY → 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.

Mutagenesis

443

1

C → S: Abolishes the deubiquitinating activity but not the binding to ubiquitin chains. Ref.6

Sequence conflict

374

1

F → I in CAB64449. Ref.1

Sequence conflict

384

1

P → A in CAB64449. Ref.1

Sequence conflict

602

1

A → P in BAG64010. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

708

Helix Strand Turn

Details...

Helix

249 – 257

9

Helix

261 – 275

15

Helix

278 – 285

8

Turn

286 – 288

3

Helix

297 – 303

7

Turn

306 – 308

3

Helix

315 – 321

7

Helix

325 – 340

16

Helix

344 – 347

4

Helix

349 – 361

13

Beta strand

363 – 365

3

Beta strand

373 – 376

4

Helix

385 – 389

5

Helix

392 – 402

11

Helix

405 – 412

8

Beta strand

415 – 419

5

Helix

422 – 425

4

Turn

426 – 428

3

Beta strand

432 – 435

4

Helix

443 – 450

8

Turn

451 – 453

3

Helix

458 – 460

3

Helix

461 – 472

12

Helix

474 – 491

18

Helix

500 – 513

14

Helix

523 – 532

10

Beta strand

537 – 541

5

Beta strand

560 – 562

3

Helix

569 – 571

3

Beta strand

577 – 582

6

Beta strand

585 – 592

8

Beta strand

612 – 620

9

Turn

634 – 636

3

Helix

640 – 650

11

Beta strand

653 – 655

3

Beta strand

661 – 668

8

Turn

669 – 671

3

Helix

674 – 688

15

Sequences

	Sequence		Length	Mass (Da)
	Q9UGI0 [UniParc]. Last modified November 4, 2008. Version 2. Checksum: DBB831697F450248	FASTA	708	80,967
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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]	"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, ANKYRIN 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.

IPI

IPI00005347.

RefSeq

NP_060050.2. NM_017580.2.

UniGene

Hs.595158.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3ZRH	X-ray	2.23	A	245-697	[»]

ProteinModelPortal

Q9UGI0.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33806N.

IntAct

Q9UGI0. 24 interactions.

MINT

MINT-6783281.

STRING

9606.ENSP00000352676.

Protein family/group databases

MEROPS

C64.004.

PTM databases

PhosphoSite

Q9UGI0.

Polymorphism databases

DMDM

212276487.

Proteomic databases

PaxDb

Q9UGI0.

PRIDE

Q9UGI0.

Protocols and materials databases

DNASU

54764.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000359653; ENSP00000352676; ENSG00000019995.

GeneID

54764.

KEGG

hsa:54764.

UCSC

uc001lic.3. human.

Organism-specific databases

CTD

54764.

GeneCards

GC10P126620.

H-InvDB

HIX0009289.

HGNC

HGNC:18224. ZRANB1.

HPA

HPA029239.
HPA029240.
HPA029241.

MIM

611749. gene.

neXtProt

NX_Q9UGI0.

PharmGKB

PA134933584.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG253754.

HOGENOM

HOG000006743.

HOVERGEN

HBG058978.

InParanoid

Q9UGI0.

KO

K11862.

OMA

EIGNEEQ.

OrthoDB

EOG441Q9X.

PhylomeDB

Q9UGI0.

Gene expression databases

Bgee

Q9UGI0.

CleanEx

HS_ZRANB1.

Genevestigator

Q9UGI0.

GermOnline

ENSG00000019995. Homo sapiens.

Family and domain databases

InterPro

IPR003323. OTU.
IPR001876. Znf_RanBP2.
[Graphical view]

Pfam

PF02338. OTU. 1 hit.
PF00641. zf-RanBP. 2 hits.
[Graphical view]

SMART

SM00547. ZnF_RBZ. 3 hits.
[Graphical view]

PROSITE

PS50088. ANK_REPEAT. False negative.
PS50802. OTU. 1 hit.
PS01358. ZF_RANBP2_1. 3 hits.
PS50199. ZF_RANBP2_2. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

54764.

NextBio

57405.

SOURCE

Search...

Entry information

Entry name

ZRAN1_HUMAN

Accession

Primary (citable) accession number: Q9UGI0
Secondary accession number(s): B4DZ98 , D3DRF4, Q5SQP6, Q69YK3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 4, 2008
Last modified:	May 29, 2013
This is version 115 of the entry and version 2 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.