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Overview

Uniprot IDQ9H0E7
Protein NameUbiquitin carboxyl-terminal hydrolase 44
Gene NameUSP44
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
550 KRRRFSSKPVVLTEA

Function

Deubiquitinase that plays a key regulatory role in the spindle assembly checkpoint or mitotic checkpoint by preventing premature anaphase onset. Acts by specifically mediating deubiquitination of CDC20, a negative regulator of the anaphase promoting complex/cyclosome (APC/C) (PubMed:17443180). Deubiquitination of CDC20 leads to stabilize the MAD2L1-CDC20-APC/C ternary complex (also named mitotic checkpoint complex), thereby preventing premature activation of the APC/C (PubMed:17443180). Promotes association of MAD2L1 with CDC20 and reinforces the spindle assembly checkpoint (PubMed:17443180). Also promotes the deubiquitination of histone H2A and H2B (PubMed:23615962, PubMed:27880911). Recruited to RNF8/RNF168-ubiquitinated chromatin surrounding double stranded breaks (DSBs), promotes hydrolysis of such ubiquitin conjugates, thus negatively regulating protein recruitment to damaged chromatin (PubMed:23615962). Participates in nucleotide excision repair (NER) pathway by deubiquitinating DDB2 to prevent its premature degradation so it can remain on damaged chromatin (By similarity). Promotes FOXP3 stabilization through 'Lys-48'-linked deubiquitination leading to increased stability and increased regulatory T-cell lineage stability (PubMed:32644293). Also plays a positive role in innate immune response to DNA viruses by deubiquitinating STING1, selectively removing its 'Lys-48'-linked polyubiquitin chains and stabilizing it (PubMed:31968013)

Protein Sequence

10 MLAMDTCKHV 20 GQLQLAQDHS 30 SLNPQKWHCV 40 DCNTTESIWA 50 CLSCSHVACG 60 RYIEEHALKH 70 FQESSHPVAL 80 EVNEMYVFCY 90 LCDDYVLNDN 100 TTGDLKLLRR 110 TLSAIKSQNY 120 HCTTRSGRFL 130 RSMGTGDDSY 140 FLHDGAQSLL 150 QSEDQLYTAL 160 WHRRRILMGK 170 IFRTWFEQSP 180 IGRKKQEEPF 190 QEKIVVKREV 200 KKRRQELEYQ 210 VKAELESMPP 220 RKSLRLQGLA 230 QSTIIEIVSV 240 QVPAQTPASP 250 AKDKVLSTSE 260 NEISQKVSDS 270 SVKRRPIVTP 280 GVTGLRNLGN 290 TCYMNSVLQV 300 LSHLLIFRQC 310 FLKLDLNQWL 320 AMTASEKTRS 330 CKHPPVTDTV 340 VYQMNECQEK 350 DTGFVCSRQS 360 SLSSGLSGGA 370 SKGRKMELIQ 380 PKEPTSQYIS 390 LCHELHTLFQ 400 VMWSGKWALV 410 SPFAMLHSVW 420 RLIPAFRGYA 430 QQDAQEFLCE 440 LLDKIQRELE 450 TTGTSLPALI 460 PTSQRKLIKQ 470 VLNVVNNIFH 480 GQLLSQVTCL 490 ACDNKSNTIE 500 PFWDLSLEFP 510 ERYQCSGKDI 520 ASQPCLVTEM 530 LAKFTETEAL 540 EGKIYVCDQC 550 NSKRRRFSSK 560 PVVLTEAQKQ 570 LMICHLPQVL 580 RLHLKRFRWS 590 GRNNREKIGV 600 HVGFEEILNM 610 EPYCCRETLK 620 SLRPECFIYD 630 LSAVVMHHGK 640 GFGSGHYTAY 650 CYNSEGGFWV 660 HCNDSKLSMC 670 TMDEVCKAQA 680 YILFYTQRVT 690 ENGHSKLLPP 700 ELLLGSQHPN 710 EDADTSSNEI LS

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0001650 fibrillar center
Cellular Component GO:0072686 mitotic spindle
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Molecular Function GO:0004843 cysteine-type deubiquitinase activity
Molecular Function GO:0101005 deubiquitinase activity
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0140374 antiviral innate immune response
Biological Process GO:0051301 cell division
Biological Process GO:0007059 chromosome segregation
Biological Process GO:0045841 negative regulation of mitotic metaphase/anaphase transition
Biological Process GO:1904667 negative regulation of ubiquitin protein ligase activity
Biological Process GO:0006289 nucleotide-excision repair
Biological Process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process GO:0016579 protein deubiquitination
Biological Process GO:0010564 regulation of cell cycle process
Biological Process GO:0090266 regulation of mitotic cell cycle spindle assembly checkpoint
Biological Process GO:0045066 regulatory T cell differentiation

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.