Q9H0E7 (UBP44_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin carboxyl-terminal hydrolase 44
EC=3.4.19.12

Alternative name(s):
Deubiquitinating enzyme 44
Ubiquitin thioesterase 44
Ubiquitin-specific-processing protease 44

Gene names

Name:

USP44

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	712 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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). 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. Promotes association of MAD2L1 with CDC20 and reinforces the spindle assembly checkpoint. Acts as a negative regulator of histone H2B (H2BK120ub1) ubiquitination. Ref.6 Ref.10
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.5 Ref.6 Ref.7
Subcellular location	Nucleus. Note: Peaks in interphase, with relatively low levels maintained throughout mitosis By similarity. Ref.7
Tissue specificity	Expressed in testis. Expressed at high levels in T-cell acute lymphoblastic leukemia. Ref.5 Ref.9
Developmental stage	Elevated in mitosis; levels increase in mitotic cells and rapidly decrease once cells have completed chromosome attachment and exit from mitosis. Ref.6
Induction	Transcriptionally regulated by POU5F1/OCT4 in embryonic stem cells and embryonal carcinoma cells. Ref.8
Post-translational modification	Dephosphorylated by CTDP1. Ref.6 Ref.11 Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination and is degraded by the proteasome. Ref.7
Sequence similarities	Belongs to the peptidase C19 family. USP44 subfamily. Contains 1 UBP-type zinc finger.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anaphase Inferred from mutant phenotype Ref.6. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW mitosis Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of mitotic anaphase-promoting complex activity Inferred from mutant phenotype Ref.6. Source: UniProtKB proteasomal ubiquitin-dependent protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB protein deubiquitination Inferred from direct assay Ref.6Ref.7. Source: UniProtKB regulation of mitotic cell cycle spindle assembly checkpoint Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	nucleus Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	ubiquitin thiolesterase activity Inferred from mutant phenotype Ref.6Ref.7. Source: UniProtKB ubiquitin-specific protease activity Inferred from direct assay Ref.6Ref.7. Source: UniProtKB 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 – 712	712	Ubiquitin carboxyl-terminal hydrolase 44		PRO_0000080673
Regions
	Zinc finger	27 – 88	62	UBP-type
Sites
	Active site	282	1	Nucleophile
	Active site	636	1	Proton acceptor By similarity
Amino acid modifications
	Modified residue	169	1	Phosphoserine Probable
	Modified residue	239	1	Phosphoserine Probable
	Modified residue	269	1	Phosphothreonine Probable
	Modified residue	401	1	Phosphoserine Probable
Natural variations
	Natural variant	91	1	T → A. Ref.1 Ref.2 Ref.4 Corresponds to variant rs3812813 [ dbSNP | Ensembl ].		VAR_017125
	Natural variant	316	1	E → Q. Corresponds to variant rs7305024 [ dbSNP | Ensembl ].		VAR_057043
	Natural variant	348	1	R → G. Corresponds to variant rs7135642 [ dbSNP | Ensembl ].		VAR_057044
Experimental info
	Mutagenesis	282	1	C → S or A: Abolishes deubiquitinase activity. Ref.6 Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Q9H0E7 [UniParc]. Last modified July 13, 2010. Version 2. Checksum: A8211DFAD78EE731	FASTA	712	81,185
	10 20 30 40 50 60 MLAMDTCKHV GQLQLAQDHS SLNPQKWHCV DCNTTESIWA CLSCSHVACG RYIEEHALKH 70 80 90 100 110 120 FQESSHPVAL EVNEMYVFCY LCDDYVLNDN TTGDLKLLRR TLSAIKSQNY HCTTRSGRFL 130 140 150 160 170 180 RSMGTGDDSY FLHDGAQSLL QSEDQLYTAL WHRRRILMGK IFRTWFEQSP IGRKKQEEPF 190 200 210 220 230 240 QEKIVVKREV KKRRQELEYQ VKAELESMPP RKSLRLQGLA QSTIIEIVSV QVPAQTPASP 250 260 270 280 290 300 AKDKVLSTSE NEISQKVSDS SVKRRPIVTP GVTGLRNLGN TCYMNSVLQV LSHLLIFRQC 310 320 330 340 350 360 FLKLDLNQWL AMTASEKTRS CKHPPVTDTV VYQMNECQEK DTGFVCSRQS SLSSGLSGGA 370 380 390 400 410 420 SKGRKMELIQ PKEPTSQYIS LCHELHTLFQ VMWSGKWALV SPFAMLHSVW RLIPAFRGYA 430 440 450 460 470 480 QQDAQEFLCE LLDKIQRELE TTGTSLPALI PTSQRKLIKQ VLNVVNNIFH GQLLSQVTCL 490 500 510 520 530 540 ACDNKSNTIE PFWDLSLEFP ERYQCSGKDI ASQPCLVTEM LAKFTETEAL EGKIYVCDQC 550 560 570 580 590 600 NSKRRRFSSK PVVLTEAQKQ LMICHLPQVL RLHLKRFRWS GRNNREKIGV HVGFEEILNM 610 620 630 640 650 660 EPYCCRETLK SLRPECFIYD LSAVVMHHGK GFGSGHYTAY CYNSEGGFWV HCNDSKLSMC 670 680 690 700 710 TMDEVCKAQA YILFYTQRVT ENGHSKLLPP ELLLGSQHPN EDADTSSNEI LS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-91. Tissue: Testis.
[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], VARIANT ALA-91. Tissue: Testis.
[3]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-91. Tissue: Testis.
[5]	"Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases." Quesada V., Diaz-Perales A., Gutierrez-Fernandez A., Garabaya C., Cal S., Lopez-Otin C. Biochem. Biophys. Res. Commun. 314:54-62(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, ENZYME ACTIVITY.
[6]	"Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities." Stegmeier F., Rape M., Draviam V.M., Nalepa G., Sowa M.E., Ang X.L., McDonald E.R. III, Li M.Z., Hannon G.J., Sorger P.K., Kirschner M.W., Harper J.W., Elledge S.J. Nature 446:876-881(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION, DEVELOPMENTAL STAGE, MUTAGENESIS OF CYS-282.
[7]	"K48- and K63-linked polyubiquitination of deubiquitinating enzyme USP44." Suresh B., Ramakrishna S., Lee H.J., Choi J.H., Kim J.Y., Ahn W.S., Baek K.H. Cell Biol. Int. 34:799-808(2010) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, UBIQUITINATION, MUTAGENESIS OF CYS-282.
[8]	"A data integration approach to mapping OCT4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cells." Jung M., Peterson H., Chavez L., Kahlem P., Lehrach H., Vilo J., Adjaye J. PLoS ONE 5:E10709-E10709(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[9]	"Overexpression of ubiquitin specific protease 44 (USP44) induces chromosomal instability and is frequently observed in human T-cell leukemia." Zhang Y., van Deursen J., Galardy P.J. PLoS ONE 6:E23389-E23389(2011) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[10]	"RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation." Fuchs G., Shema E., Vesterman R., Kotler E., Wolchinsky Z., Wilder S., Golomb L., Pribluda A., Zhang F., Haj-Yahya M., Feldmesser E., Brik A., Yu X., Hanna J., Aberdam D., Domany E., Oren M. Mol. Cell 46:662-673(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit." Visconti R., Palazzo L., Della Monica R., Grieco D. Nat. Commun. 3:894-894(2012) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-169; SER-239; THR-269 AND SER-401, DEPHOSPHORYLATION.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AL136825 mRNA. Translation: CAB66759.1. AK315697 mRNA. Translation: BAG38060.1. AC018475 Genomic DNA. No translation available. BC030704 mRNA. Translation: AAH30704.1.
IPI	IPI00030306.
RefSeq	NP_001035862.1. NM_001042403.1. NP_115523.2. NM_032147.2.
UniGene	Hs.646421.
3D structure databases
ProteinModelPortal	Q9H0E7.
SMR	Q9H0E7. Positions 29-86, 268-678.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H0E7. 11 interactions.
STRING	9606.ENSP00000258499.
Protein family/group databases
MEROPS	C19.057.
PTM databases
PhosphoSite	Q9H0E7.
Polymorphism databases
DMDM	300669621.
Proteomic databases
PaxDb	Q9H0E7.
PRIDE	Q9H0E7.
Protocols and materials databases
DNASU	84101.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000258499; ENSP00000258499; ENSG00000136014. ENST00000393091; ENSP00000376806; ENSG00000136014. ENST00000537435; ENSP00000442629; ENSG00000136014.
GeneID	84101.
KEGG	hsa:84101.
UCSC	uc001teg.3. human.
Organism-specific databases
CTD	84101.
GeneCards	GC12M095910.
H-InvDB	HIX0010895.
HGNC	HGNC:20064. USP44.
HPA	HPA026543.
MIM	610993. gene.
neXtProt	NX_Q9H0E7.
PharmGKB	PA134931457.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5077.
HOGENOM	HOG000015084.
HOVERGEN	HBG018027.
InParanoid	Q9H0E7.
KO	K11834.
OMA	AIKSQNY.
OrthoDB	EOG4XGZZK.
PhylomeDB	Q9H0E7.
Gene expression databases
ArrayExpress	Q9H0E7.
Bgee	Q9H0E7.
CleanEx	HS_USP44.
Genevestigator	Q9H0E7.
GermOnline	ENSG00000136014. Homo sapiens.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. IPR013083. Znf_RING/FYVE/PHD. IPR001607. Znf_UBP. [Graphical view]
Pfam	PF00443. UCH. 1 hit. PF02148. zf-UBP. 1 hit. [Graphical view]
SMART	SM00290. ZnF_UBP. 1 hit. [Graphical view]
PROSITE	PS00972. UCH_2_1. 1 hit. PS00973. UCH_2_2. 1 hit. PS50235. UCH_2_3. 1 hit. PS50271. ZF_UBP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	84101.
NextBio	73349.
SOURCE	Search...

Entry information

Entry name

UBP44_HUMAN

Accession

Primary (citable) accession number: Q9H0E7
Secondary accession number(s): B2RDW3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2003
Last sequence update:	July 13, 2010
Last modified:	May 1, 2013
This is version 103 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.