ZRAN1_BOVIN
ID ZRAN1_BOVIN Reviewed; 708 AA.
AC A6QP16;
DT 20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Ubiquitin thioesterase ZRANB1 {ECO:0000305};
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:Q9UGI0};
DE AltName: Full=Zinc finger Ran-binding domain-containing protein 1 {ECO:0000250|UniProtKB:Q9UGI0};
GN Name=ZRANB1 {ECO:0000250|UniProtKB:Q9UGI0};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal skin;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0007744|PDB:4S1Z}
RP X-RAY CRYSTALLOGRAPHY (3.03 ANGSTROMS) OF 2-33 IN COMPLEX WITH ZINC AND
RP UBIQUITIN.
RX PubMed=25752573; DOI=10.1016/j.molcel.2015.01.041;
RA Kristariyanto Y.A., Abdul Rehman S.A., Campbell D.G., Morrice N.A.,
RA Johnson C., Toth R., Kulathu Y.;
RT "K29-selective ubiquitin binding domain reveals structural basis of
RT specificity and heterotypic nature of K29 polyubiquitin.";
RL Mol. Cell 58:83-94(2015).
CC -!- FUNCTION: Ubiquitin thioesterase, which specifically hydrolyzes 'Lys-
CC 29'-linked and 'Lys-33'-linked diubiquitin (By similarity). Also
CC cleaves 'Lys-63'-linked chains, but with 40-fold less efficiency
CC compared to 'Lys-29'-linked ones (By similarity). Positive regulator of
CC the Wnt signaling pathway that deubiquitinates APC protein, a negative
CC regulator of Wnt-mediated transcription (By similarity). Acts as a
CC regulator of autophagy by mediating deubiquitination of PIK3C3/VPS34,
CC thereby promoting autophagosome maturation (By similarity). Plays a
CC role in the regulation of cell morphology and cytoskeletal organization
CC (By similarity). Required in the stress fiber dynamics and cell
CC migration (By similarity). {ECO:0000250|UniProtKB:Q9UGI0}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000250|UniProtKB:Q9UGI0};
CC -!- SUBUNIT: Interacts with TRAF6. Interacts with APC.
CC {ECO:0000250|UniProtKB:Q9UGI0}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9UGI0}. Nucleus
CC {ECO:0000250|UniProtKB:Q9UGI0}. Note=Enriched in punctate localization
CC in the cytoplasm. {ECO:0000250|UniProtKB:Q9UGI0}.
CC -!- DOMAIN: The RanBP2-type zinc fingers, also called NZFs, mediate the
CC interaction with ubiquitin and determine linkage specificity. RanBP2-
CC type zinc fingers 1 and 2 (also named NZF1 and NZF2) specifically
CC recognize and bind 'Lys-29'- and 'Lys-33'-linked ubiquitin. RanBP2-type
CC zinc finger 3 (also named NZF3) binds 'Lys-33'-linked ubiquitin and
CC shows weak binding to 'Lys-6'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin
CC chains but it does not interact with 'Lys-29'-linked chains.
CC {ECO:0000250|UniProtKB:Q9UGI0}.
CC -!- DOMAIN: The OTU domain mediates the deubiquitinating activity.
CC {ECO:0000250|UniProtKB:Q9UGI0}.
CC -!- DOMAIN: The second ankyrin repeat ANK 2 is termed AnkUBD, it interacts
CC with ubiquitin hydrophobic patch and contributes to linkage
CC specificity. {ECO:0000250|UniProtKB:Q9UGI0}.
CC -!- SIMILARITY: Belongs to the peptidase C64 family. {ECO:0000305}.
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DR EMBL; BC149099; AAI49100.1; -; mRNA.
DR RefSeq; NP_001094584.1; NM_001101114.1.
DR PDB; 4S1Z; X-ray; 3.03 A; F/G/H/I/J=2-33.
DR PDBsum; 4S1Z; -.
DR AlphaFoldDB; A6QP16; -.
DR SMR; A6QP16; -.
DR STRING; 9913.ENSBTAP00000004401; -.
DR MEROPS; C64.004; -.
DR PaxDb; A6QP16; -.
DR PRIDE; A6QP16; -.
DR Ensembl; ENSBTAT00000066427; ENSBTAP00000062474; ENSBTAG00000003395.
DR GeneID; 523338; -.
DR KEGG; bta:523338; -.
DR CTD; 54764; -.
DR VEuPathDB; HostDB:ENSBTAG00000003395; -.
DR VGNC; VGNC:37371; ZRANB1.
DR eggNOG; KOG4345; Eukaryota.
DR GeneTree; ENSGT00940000158045; -.
DR HOGENOM; CLU_013907_0_0_1; -.
DR InParanoid; A6QP16; -.
DR OrthoDB; 728724at2759; -.
DR TreeFam; TF323312; -.
DR Proteomes; UP000009136; Chromosome 26.
DR Bgee; ENSBTAG00000003395; Expressed in spermatid and 103 other tissues.
DR ExpressionAtlas; A6QP16; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0071947; P:protein deubiquitination involved in ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0035523; P:protein K29-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:1990168; P:protein K33-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0022604; P:regulation of cell morphogenesis; ISS:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR041294; AnkUBD.
DR InterPro; IPR003323; OTU_dom.
DR InterPro; IPR001876; Znf_RanBP2.
DR InterPro; IPR036443; Znf_RanBP2_sf.
DR Pfam; PF18418; AnkUBD; 1.
DR Pfam; PF02338; OTU; 1.
DR Pfam; PF00641; zf-RanBP; 2.
DR SMART; SM00547; ZnF_RBZ; 3.
DR SUPFAM; SSF90209; SSF90209; 2.
DR PROSITE; PS50802; OTU; 1.
DR PROSITE; PS01358; ZF_RANBP2_1; 3.
DR PROSITE; PS50199; ZF_RANBP2_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; ANK repeat; Cytoplasm; Hydrolase; Metal-binding; Nucleus;
KW Protease; Reference proteome; Repeat; Thiol protease;
KW Ubl conjugation pathway; Wnt signaling pathway; Zinc; Zinc-finger.
FT CHAIN 1..708
FT /note="Ubiquitin thioesterase ZRANB1"
FT /id="PRO_0000361553"
FT REPEAT 260..290
FT /note="ANK 1"
FT REPEAT 313..340
FT /note="ANK 2"
FT DOMAIN 432..592
FT /note="OTU"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT ZN_FING 3..33
FT /note="RanBP2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT ZN_FING 84..113
FT /note="RanBP2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT ZN_FING 149..178
FT /note="RanBP2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT REGION 38..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 200..223
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 50..65
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 202..217
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 443
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9UGI0"
FT ACT_SITE 585
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q6GQQ9"
FT BINDING 10
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322,
FT ECO:0000269|PubMed:25752573, ECO:0007744|PDB:4S1Z"
FT BINDING 13
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322,
FT ECO:0000269|PubMed:25752573, ECO:0007744|PDB:4S1Z"
FT BINDING 24
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322,
FT ECO:0000269|PubMed:25752573, ECO:0007744|PDB:4S1Z"
FT BINDING 27
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322,
FT ECO:0000269|PubMed:25752573, ECO:0007744|PDB:4S1Z"
FT BINDING 90
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT BINDING 104
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT BINDING 107
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT BINDING 155
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT BINDING 158
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT BINDING 169
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT BINDING 172
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT STRAND 11..13
FT /evidence="ECO:0007829|PDB:4S1Z"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:4S1Z"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:4S1Z"
SQ SEQUENCE 708 AA; 81047 MW; 386832570C7AEF03 CRC64;
MSERGIKWAC EYCTYENWPS AIKCTMCRAQ RPSGTIITED PFKSGSSDVG RDWDPSSTEG
GSSPLICPDS SARPRVKSSY SMENANKWSC HMCTYLNWPR AIRCTQCLSQ RRTRSPTESP
QSSGSGSRPV AFSVDPCEEY NDRNKLNTRT QHWTCSICTY ENWAKAKKCV VCDHPRPNNI
EAIEFAETEE ASSIINEQDR ARWRGSCSSG NSQRRSPPTM KRDSEVKMDF QRIELAGAVG
SKEELEVDFK KLKQIKNRMK KTDWLFLNAC VGVVEGDLAA IEAYKSSGGD IARQLTADEV
RLLNRPSAFD VGYTLVHLAI RFQRQDMLAI LLTEVSQQAA KCIPAMVCPE LTEQIRREIA
ASLHQRKGDF ACYFLTDLVT FTLPADIEDL PPTVQEKLFD EVLDRDVQKE LEEESPIINW
SLELATRLDS RLYALWNRTA GDCLLDSVLQ ATWGIYDKDS VLRKALHDSL HDCSHWFYTR
WKDWESWYSQ SFGLHFSLRE EQWQEDWAFI LSLASQPGAS LEQTHIFVLA HILRRPIIVY
GVKYYKSFRG ETLGYTRFQG VYLPLLWEQS FCWKSPIALG YTRGHFSALV AMENDGYGNR
GAGANLNTDD DVTITFLPLV DSERKLLHVH FLSAQELGNE EQQEKLLREW LDCCVTEGGV
LVAMQKSSRR RNHPLVTQMV EKWLDRYRQI RPCTSLSDGE EDEDDEDE
