Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O00507 (USP9Y_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Probable ubiquitin carboxyl-terminal hydrolase FAF-Y

EC=3.4.19.12
Alternative name(s):
Deubiquitinating enzyme FAF-Y
Fat facets protein-related, Y-linked
Ubiquitin thioesterase FAF-Y
Ubiquitin-specific protease 9, Y chromosome
Ubiquitin-specific-processing protease FAF-Y
Gene names
Name:USP9Y
Synonyms:DFFRY
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length2555 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

May function as a ubiquitin-protein or polyubiquitin hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. May therefore play an important role regulatory role at the level of protein turnover by preventing degradation of proteins through the removal of conjugated ubiquitin. Essential component of TGF-beta/BMP signaling cascade. Deubiquitinates monoubiquitinated SMAD4, opposing the activity of E3 ubiquitin-protein ligase TRIM33. Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade. Deubiqitination of SMAD4 by USP9X re-empowers its competence to mediate TGF-beta signaling By similarity.

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 SMAD4 By similarity.

Subcellular location

Cytoplasm By similarity.

Tissue specificity

Widely expressed in embryonic and adult tissues.

Involvement in disease

USP9Y is located in the 'azoospermia factor a' (AZFa) region on chromosome Y which is deleted in Sertoli cell-only syndrome. This is an infertility disorder in which no germ cells are visible in seminiferous tubules leading to azoospermia. However, AZFa deletions resulting in complete loss of USP9Y have also been found in normospermic men (Ref.7).

Spermatogenic failure Y-linked 2 (SPGFY2) [MIM:415000]: A disorder resulting in the absence (azoospermia) or reduction (oligozoospermia) of sperm in the semen, leading to male infertility.
Note: The disease may be caused by mutations affecting the gene represented in this entry. The role of USP9Y in spermatogenesis failure is uncertain. A 4-bp deletion in a splice-donor site, causing exon skipping and protein truncation has been observed in non-obstructive azoospermia (Ref.5). However, complete USP9Y deletion has been detected in individuals with no spermatogenic defects (Ref.7).

Sequence similarities

Belongs to the peptidase C19 family.

Contains 1 USP domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform Long (identifier: O00507-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Short (identifier: O00507-2)

The sequence of this isoform differs from the canonical sequence as follows:
     2071-2555: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 25552555Probable ubiquitin carboxyl-terminal hydrolase FAF-Y
PRO_0000080690

Regions

Domain1559 – 1958400USP

Sites

Active site15681Nucleophile By similarity
Active site18811Proton acceptor By similarity

Natural variations

Alternative sequence2071 – 2555485Missing in isoform Short.
VSP_005272
Natural variant651E → D.
Corresponds to variant rs7067496 [ dbSNP | Ensembl ].
VAR_055350
Natural variant2111R → C.
Corresponds to variant rs2032596 [ dbSNP | Ensembl ].
VAR_055351
Natural variant10351P → S.
Corresponds to variant rs20319 [ dbSNP | Ensembl ].
VAR_029328
Natural variant10601A → T. Ref.3
Corresponds to variant rs20320 [ dbSNP | Ensembl ].
VAR_016194
Natural variant17051A → S.
Corresponds to variant rs2032606 [ dbSNP | Ensembl ].
VAR_055352

Experimental info

Sequence conflict2061D → E in CAA73940. Ref.3
Sequence conflict2061D → E in CAA73941. Ref.3
Sequence conflict2821I → M in AAC51833. Ref.2
Sequence conflict5241D → Y in AAC51833. Ref.2
Sequence conflict5421S → A in AAC51833. Ref.2
Sequence conflict6661L → V in AAC51833. Ref.2
Sequence conflict8831R → C in CAA73940. Ref.3
Sequence conflict8831R → C in CAA73941. Ref.3
Sequence conflict9071S → F in CAA73940. Ref.3
Sequence conflict9071S → F in CAA73941. Ref.3
Sequence conflict9461D → N in CAA73940. Ref.3
Sequence conflict9461D → N in CAA73941. Ref.3
Sequence conflict10021E → K in CAA73940. Ref.3
Sequence conflict10021E → K in CAA73941. Ref.3
Sequence conflict10171R → K in CAA73940. Ref.3
Sequence conflict10171R → K in CAA73941. Ref.3
Sequence conflict1025 – 10273VAD → FAN in CAA73940. Ref.3
Sequence conflict1025 – 10273VAD → FAN in CAA73941. Ref.3
Sequence conflict1038 – 10392RD → KN in CAA73940. Ref.3
Sequence conflict1038 – 10392RD → KN in CAA73941. Ref.3
Sequence conflict10671K → N in CAA73940. Ref.3
Sequence conflict10671K → N in CAA73941. Ref.3
Sequence conflict12581V → F in CAA73940. Ref.3
Sequence conflict12581V → F in CAA73941. Ref.3
Sequence conflict17331Y → F in CAA73940. Ref.3
Sequence conflict17331Y → F in CAA73941. Ref.3
Sequence conflict19531L → P in CAA73940. Ref.3
Sequence conflict19531L → P in CAA73941. Ref.3
Sequence conflict20861R → G in AAC51833. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified May 5, 2009. Version 2.
Checksum: 421D47D5899F4415

FASTA2,555291,077
        10         20         30         40         50         60 
MTAITHGSPV GGNDSQGQVL DGQSQHLFQQ NQTSSPDSSN ENSVATPPPE EQGQGDAPPQ 

        70         80         90        100        110        120 
HEDEEPAFPH TELANLDDMI NRPRWVVPVL PKGELEVLLE AAIDLSVKGL DVKSEACQRF 

       130        140        150        160        170        180 
FRDGLTISFT KILMDEAVSG WKFEIHRCII NNTHRLVELC VAKLSQDWFP LLELLAMALN 

       190        200        210        220        230        240 
PHCKFHIYNG TRPCELISSN AQLPEDELFA RSSDPRSPKG WLVDLINKFG TLNGFQILHD 

       250        260        270        280        290        300 
RFFNGSALNI QIIAALIKPF GQCYEFLSQH TLKKYFIPVI EIVPHLLENL TDEELKKEAK 

       310        320        330        340        350        360 
NEAKNDALSM IIKSLKNLAS RISGQDETIK NLEIFRLKMI LRLLQISSFN GKMNALNEIN 

       370        380        390        400        410        420 
KVISSVSYYT HRHSNPEEEE WLTAERMAEW IQQNNILSIV LQDSLHQPQY VEKLEKILRF 

       430        440        450        460        470        480 
VIKEKALTLQ DLDNIWAAQA GKHEAIVKNV HDLLAKLAWD FSPGQLDHLF DCFKASWTNA 

       490        500        510        520        530        540 
SKKQREKLLE LIRRLAEDDK DGVMAHKVLN LLWNLAQSDD VPVDIMDLAL SAHIKILDYS 

       550        560        570        580        590        600 
CSQDRDAQKI QWIDHFIEEL RTNDKWVIPA LKQIREICSL FGEASQNLSQ TQRSPHIFYR 

       610        620        630        640        650        660 
HDLINQLQQN HALVTLVAEN LATYMNSIRL YAGDHEDYDP QTVRLGSRYS HVQEVQERLN 

       670        680        690        700        710        720 
FLRFLLKDGQ LWLCAPQAKQ IWKCLAENAV YLCDREACFK WYSKLMGDEP DLDPDINKDF 

       730        740        750        760        770        780 
FESNVLQLDP SLLTENGMKC FERFFKAVNC RERKLIAKRR SYMMDDLELI GLDYLWRVVI 

       790        800        810        820        830        840 
QSSDEIANRA IDLLKEIYTN LGPRLKANQV VIHEDFIQSC FDRLKASYDT LCVFDGDKNS 

       850        860        870        880        890        900 
INCARQEAIR MVRVLTVIKE YINECDSDYH KERMILPMSR AFRGKHLSLI VRFPNQGRQV 

       910        920        930        940        950        960 
DELDIWSHTN DTIGSVRRCI VNRIKANVAH KKIELFVGGE LIDSEDDRKL IGQLNLKDKS 

       970        980        990       1000       1010       1020 
LITAKLTQIN FNMPSSPDSS SDSSTASPGN HRNHYNDGPN LEVESCLPGV IMSVHPRYIS 

      1030       1040       1050       1060       1070       1080 
FLWQVADLGS NLNMPPLRDG ARVLMKLMPP DRTAVEKLRA VCLDHAKLGE GKLSPPLDSL 

      1090       1100       1110       1120       1130       1140 
FFGPSASQVL YLTEVVYALL MPAGVPLTDG SSDFQVHFLK SGGLPLVLSM LIRNNFLPNT 

      1150       1160       1170       1180       1190       1200 
DMETRRGAYL NALKIAKLLL TAIGYGHVRA VAEACQPVVD GTDPITQINQ VTHDQAVVLQ 

      1210       1220       1230       1240       1250       1260 
SALQSIPNPS SECVLRNESI LLAQEISNEA SRYMPDICVI RAIQKIIWAS ACGALGLVFS 

      1270       1280       1290       1300       1310       1320 
PNEEITKIYQ MTTNGSNKLE VEDEQVCCEA LEVMTLCFAL LPTALDALSK EKAWQTFIID 

      1330       1340       1350       1360       1370       1380 
LLLHCPSKTV RQLAQEQFFL MCTRCCMGHR PLLFFITLLF TILGSTAREK GKYSGDYFTL 

      1390       1400       1410       1420       1430       1440 
LRHLLNYAYN GNINIPNAEV LLVSEIDWLK RIRDNVKNTG ETGVEEPILE GHLGVTKELL 

      1450       1460       1470       1480       1490       1500 
AFQTSEKKYH FGCEKGGANL IKELIDDFIF PASKVYLQYL RSGELPAEQA IPVCSSPVTI 

      1510       1520       1530       1540       1550       1560 
NAGFELLVAL AIGCVRNLKQ IVDCLTEMYY MGTAITTCEA LTEWEYLPPV GPRPPKGFVG 

      1570       1580       1590       1600       1610       1620 
LKNAGATCYM NSVIQQLYMI PSIRNSILAI EGTGSDLHDD MFGDEKQDSE SNVDPRDDVF 

      1630       1640       1650       1660       1670       1680 
GYPHQFEDKP ALSKTEDRKE YNIGVLRHLQ VIFGHLAASQ LQYYVPRGFW KQFRLWGEPV 

      1690       1700       1710       1720       1730       1740 
NLREQHDALE FFNSLVDSLD EALKALGHPA ILSKVLGGSF ADQKICQGCP HRYECEESFT 

      1750       1760       1770       1780       1790       1800 
TLNVDIRNHQ NLLDSLEQYI KGDLLEGANA YHCEKCDKKV DTVKRLLIKK LPRVLAIQLK 

      1810       1820       1830       1840       1850       1860 
RFDYDWEREC AIKFNDYFEF PRELDMGPYT VAGVANLERD NVNSENELIE QKEQSDNETA 

      1870       1880       1890       1900       1910       1920 
GGTKYRLVGV LVHSGQASGG HYYSYIIQRN GKDDQTDHWY KFDDGDVTEC KMDDDEEMKN 

      1930       1940       1950       1960       1970       1980 
QCFGGEYMGE VFDHMMKRMS YRRQKRWWNA YILFYEQMDM IDEDDEMIRY ISELTIARPH 

      1990       2000       2010       2020       2030       2040 
QIIMSPAIER SVRKQNVKFM HNRLQYSLEY FQFVKKLLTC NGVYLNPAPG QDYLLPEAEE 

      2050       2060       2070       2080       2090       2100 
ITMISIQLAA RFLFTTGFHT KKIVRGPASD WYDALCVLLR HSKNVRFWFT HNVLFNVSNR 

      2110       2120       2130       2140       2150       2160 
FSEYLLECPS AEVRGAFAKL IVFIAHFSLQ DGSCPSPFAS PGPSSQACDN LSLSDHLLRA 

      2170       2180       2190       2200       2210       2220 
TLNLLRREVS EHGHHLQQYF NLFVMYANLG VAEKTQLLKL NVPATFMLVS LDEGPGPPIK 

      2230       2240       2250       2260       2270       2280 
YQYAELGKLY SVVSQLIRCC NVSSTMQSSI NGNPPLPNPF GDLNLSQPIM PIQQNVLDIL 

      2290       2300       2310       2320       2330       2340 
FVRTSYVKKI IEDCSNSEDT IKLLRFCSWE NPQFSSTVLS ELLWQVAYSY TYELRPYLDL 

      2350       2360       2370       2380       2390       2400 
LFQILLIEDS WQTHRIHNAL KGIPDDRDGL FDTIQRSKNH YQKRAYQCIK CMVALFSSCP 

      2410       2420       2430       2440       2450       2460 
VAYQILQGNG DLKRKWTWAV EWLGDELERR PYTGNPQYSY NNWSPPVQSN ETANGYFLER 

      2470       2480       2490       2500       2510       2520 
SHSARMTLAK ACELCPEEEP DDQDAPDEHE PSPSEDAPLY PHSPASQYQQ NNHVHGQPYT 

      2530       2540       2550 
GPAAHHLNNP QKTGQRTQEN YEGNEEVSSP QMKDQ 

« Hide

Isoform Short [UniParc].

Checksum: 70219CB0CCD269C5
Show »

FASTA2,070235,723

References

« Hide 'large scale' references
[1]"The Drosophila developmental gene fat facets has a human homologue in Xp11.4 which escapes X-inactivation and has related sequences on Yq11.2."
Jones M.H., Furlong R.A., Burkin H., Chalmers I.J., Brown G.M., Khwaja O., Affara N.A.
Hum. Mol. Genet. 5:1695-1701(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Testis.
[2]"Functional coherence of the human Y chromosome."
Lahn B.T., Page D.C.
Science 278:675-680(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Characterisation of the coding sequence and fine mapping of the human DFFRY gene and comparative expression analysis and mapping to the Sxrb interval of the mouse Y chromosome of the Dffry gene."
Brown G.M., Furlong R.A., Sargent C.A., Erickson R.P., Longepied G., Mitchell M., Jones M.H., Hargreave T.B., Cooke H.J., Affara N.A.
Hum. Mol. Genet. 7:97-107(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], GENE MAPPING, VARIANT THR-1060.
Tissue: Fetal brain, Retina and Testis.
[4]"The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes."
Skaletsky H., Kuroda-Kawaguchi T., Minx P.J., Cordum H.S., Hillier L.W., Brown L.G., Repping S., Pyntikova T., Ali J., Bieri T., Chinwalla A., Delehaunty A., Delehaunty K., Du H., Fewell G., Fulton L., Fulton R., Graves T.A. expand/collapse author list , Hou S.-F., Latrielle P., Leonard S., Mardis E., Maupin R., McPherson J., Miner T., Nash W., Nguyen C., Ozersky P., Pepin K., Rock S., Rohlfing T., Scott K., Schultz B., Strong C., Tin-Wollam A., Yang S.-P., Waterston R.H., Wilson R.K., Rozen S., Page D.C.
Nature 423:825-837(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"An azoospermic man with a de novo point mutation in the Y-chromosomal gene USP9Y."
Sun C., Skaletsky H., Birren B., Devon K., Tang Z., Silber S., Oates R., Page D.C.
Nat. Genet. 23:429-432(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN SPERMATOGENIC FAILURE.
[6]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[7]"Spermatogenesis in a man with complete deletion of USP9Y."
Luddi A., Margollicci M., Gambera L., Serafini F., Cioni M., De Leo V., Balestri P., Piomboni P.
N. Engl. J. Med. 360:881-885(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: LACK OF INVOLVEMENT IN SPERMATOGENIC FAILURE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF000986 mRNA. Translation: AAC51833.1.
Y13618 mRNA. Translation: CAA73940.1.
Y13619 mRNA. Translation: CAA73941.1.
AC002531 Genomic DNA. No translation available.
CCDSCCDS14781.1. [O00507-1]
RefSeqNP_004645.2. NM_004654.3. [O00507-1]
UniGeneHs.598540.

3D structure databases

ProteinModelPortalO00507.
SMRO00507. Positions 1557-1995.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113892. 7 interactions.
IntActO00507. 5 interactions.
MINTMINT-7230431.
STRING9606.ENSP00000342812.

Protein family/group databases

MEROPSC19.028.

PTM databases

PhosphoSiteO00507.

Proteomic databases

MaxQBO00507.
PaxDbO00507.
PRIDEO00507.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000338981; ENSP00000342812; ENSG00000114374. [O00507-1]
GeneID8287.
KEGGhsa:8287.
UCSCuc004fst.1. human. [O00507-1]

Organism-specific databases

CTD8287.
GeneCardsGC0YP014813.
GeneReviewsUSP9Y.
HGNCHGNC:12633. USP9Y.
MIM400005. gene.
415000. phenotype.
neXtProtNX_O00507.
Orphanet1646. Partial chromosome Y deletion.
PharmGKBPA37258.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5077.
HOGENOMHOG000231283.
HOVERGENHBG073749.
InParanoidO00507.
KOK11840.
OMARNIATIN.
OrthoDBEOG722J7K.
PhylomeDBO00507.
TreeFamTF323966.

Gene expression databases

BgeeO00507.
CleanExHS_USP10.
HS_USP9Y.
GenevestigatorO00507.

Family and domain databases

InterProIPR016024. ARM-type_fold.
IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[Graphical view]
PfamPF00443. UCH. 1 hit.
[Graphical view]
SUPFAMSSF48371. SSF48371. 3 hits.
PROSITEPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiUSP9Y.
GenomeRNAi8287.
NextBio31053.
PROO00507.
SOURCESearch...

Entry information

Entry nameUSP9Y_HUMAN
AccessionPrimary (citable) accession number: O00507
Secondary accession number(s): O14601
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 5, 2009
Last modified: July 9, 2014
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome Y

Human chromosome Y: entries, gene names and cross-references to MIM