UBP44_AILME
ID UBP44_AILME Reviewed; 711 AA.
AC D2HBJ8;
DT 13-JUL-2010, integrated into UniProtKB/Swiss-Prot.
DT 09-FEB-2010, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 44;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 44;
DE AltName: Full=Ubiquitin thioesterase 44;
DE AltName: Full=Ubiquitin-specific-processing protease 44;
GN Name=USP44; ORFNames=PANDA_007904;
OS Ailuropoda melanoleuca (Giant panda).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Ursidae; Ailuropoda.
OX NCBI_TaxID=9646;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20010809; DOI=10.1038/nature08696;
RA Li R., Fan W., Tian G., Zhu H., He L., Cai J., Huang Q., Cai Q., Li B.,
RA Bai Y., Zhang Z., Zhang Y., Wang W., Li J., Wei F., Li H., Jian M., Li J.,
RA Zhang Z., Nielsen R., Li D., Gu W., Yang Z., Xuan Z., Ryder O.A.,
RA Leung F.C., Zhou Y., Cao J., Sun X., Fu Y., Fang X., Guo X., Wang B.,
RA Hou R., Shen F., Mu B., Ni P., Lin R., Qian W., Wang G., Yu C., Nie W.,
RA Wang J., Wu Z., Liang H., Min J., Wu Q., Cheng S., Ruan J., Wang M.,
RA Shi Z., Wen M., Liu B., Ren X., Zheng H., Dong D., Cook K., Shan G.,
RA Zhang H., Kosiol C., Xie X., Lu Z., Zheng H., Li Y., Steiner C.C.,
RA Lam T.T., Lin S., Zhang Q., Li G., Tian J., Gong T., Liu H., Zhang D.,
RA Fang L., Ye C., Zhang J., Hu W., Xu A., Ren Y., Zhang G., Bruford M.W.,
RA Li Q., Ma L., Guo Y., An N., Hu Y., Zheng Y., Shi Y., Li Z., Liu Q.,
RA Chen Y., Zhao J., Qu N., Zhao S., Tian F., Wang X., Wang H., Xu L., Liu X.,
RA Vinar T., Wang Y., Lam T.W., Yiu S.M., Liu S., Zhang H., Li D., Huang Y.,
RA Wang X., Yang G., Jiang Z., Wang J., Qin N., Li L., Li J., Bolund L.,
RA Kristiansen K., Wong G.K., Olson M., Zhang X., Li S., Yang H., Wang J.,
RA Wang J.;
RT "The sequence and de novo assembly of the giant panda genome.";
RL Nature 463:311-317(2010).
CC -!- FUNCTION: Deubiquitinase that plays a key regulatory role in the
CC spindle assembly checkpoint or mitotic checkpoint by preventing
CC premature anaphase onset. Acts by specifically mediating
CC deubiquitination of CDC20, a negative regulator of the anaphase
CC promoting complex/cyclosome (APC/C). Deubiquitination of CDC20 leads to
CC stabilize the MAD2L1-CDC20-APC/C ternary complex (also named mitotic
CC checkpoint complex), thereby preventing premature activation of the
CC APC/C. Promotes association of MAD2L1 with CDC20 and reinforces the
CC spindle assembly checkpoint. Acts as a negative regulator of histone
CC H2B (H2BK120ub1) ubiquitination (By similarity). {ECO:0000250}.
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;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Note=Peaks in interphase,
CC with relatively low levels maintained throughout mitosis.
CC {ECO:0000250}.
CC -!- PTM: Dephosphorylated by CTDP1. {ECO:0000250}.
CC -!- PTM: Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked
CC polyubiquitination and is degraded by the proteasome. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP44 subfamily.
CC {ECO:0000305}.
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DR EMBL; GL192660; EFB15980.1; -; Genomic_DNA.
DR RefSeq; XP_011223301.1; XM_011224999.2.
DR AlphaFoldDB; D2HBJ8; -.
DR STRING; 9646.ENSAMEP00000002292; -.
DR PRIDE; D2HBJ8; -.
DR Ensembl; ENSAMET00000002387; ENSAMEP00000002292; ENSAMEG00000002189.
DR GeneID; 100470180; -.
DR KEGG; aml:100470180; -.
DR CTD; 84101; -.
DR eggNOG; KOG1867; Eukaryota.
DR GeneTree; ENSGT00940000160526; -.
DR HOGENOM; CLU_008279_13_1_1; -.
DR InParanoid; D2HBJ8; -.
DR OMA; HLLIFRE; -.
DR OrthoDB; 1230415at2759; -.
DR TreeFam; TF315281; -.
DR Proteomes; UP000008912; Unassembled WGS sequence.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; IEA:Ensembl.
DR GO; GO:1904667; P:negative regulation of ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR GO; GO:0090266; P:regulation of mitotic cell cycle spindle assembly checkpoint; ISS:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF02148; zf-UBP; 1.
DR SMART; SM00290; ZnF_UBP; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
DR PROSITE; PS50271; ZF_UBP; 1.
PE 3: Inferred from homology;
KW Cell cycle; Cell division; Hydrolase; Metal-binding; Mitosis; Nucleus;
KW Protease; Reference proteome; Thiol protease; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..711
FT /note="Ubiquitin carboxyl-terminal hydrolase 44"
FT /id="PRO_0000395810"
FT DOMAIN 272..677
FT /note="USP"
FT ZN_FING 5..102
FT /note="UBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT REGION 237..264
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 336..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 689..711
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 245..261
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 336..357
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 697..711
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 281
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 635
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT BINDING 7
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 9
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 29
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 32
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 41
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 44
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 49
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 56
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 60
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 66
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 79
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 82
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
SQ SEQUENCE 711 AA; 81364 MW; 00C0350EA2E949E1 CRC64;
MLTMDKCKHI GQLRLAQDHS ILNPQKWHCV DCNTTESIWA CLSCSHVACG RYIEEHALKH
FQESSHPVAL EVNEMYVFCY LCDDYVLNDN ATGDLKLLRS MLSAIKSQNY QCTTRSGRVL
RSMGTSDDTY YLHDGTQSLL QNEDQMYTAL WHRRRILMSK IFRTWFEQSP TGRKRQEEQF
QEKIAKREVK KRRQELEYQV KAELETIHPR KSLRLQGLAQ STTVEIVPVQ VPLQTPASPA
KDKVVSTSED VRLKKASDSS GKRRPIVTPG VTGLRNLGNT CYMNSVLQVL SHLLIFRQCF
LKLDLNQWLA VTASDKTRSP YKHPSITDTV YQMNECQETD TGSAPSRHPS LSLGLSGGAS
KSRKMELIQP REPSSQYISL CHELHTLFQV MWSGKWALVS PFAMLHSVWR LIPAFRGYAQ
QDAQEFLCEL LDKIQHELET TGTRLPALIP TSQRKLIKQV LNVVNNIFHG QLLSQVTCLA
CDNKSNTIEP FWDLSLEFPE RYQCNGKDIA SQPCRVTEML AKFTETEALE GKIYVCDHCN
SKRRRFSSKS VVLTEAQKQL MICHLPQVLR LHLKRFRWSG RNNREKIGVH VGFEEILNME
PYCCRESLKS LRPECFIYDL SAVVMHHGKG FGSGHYTAYC YNSEGGFWVH CNDSKLSMCT
MDEVCKAQAY ILFYTQRVTE NGHSKLLPPE LLSGSQHPNE EADTSSNEIL S
