E3 ubiquitin-protein ligase UBR5 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot O95071 (UBR5_HUMAN)

Last modified November 25, 2008. Version 88. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    E3 ubiquitin-protein ligase UBR5
    EC=6.3.2.-
Alternative name(s):
    E3 ubiquitin-protein ligase, HECT domain-containing 1
    Hyperplastic discs protein homolog
      Short name=hHYD
    Progestin-induced protein

Gene names

Name:	UBR5
Synonyms:	EDD, EDD1, HYD, KIAA0896

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	2799 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific amino-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation By similarity. May be involved in maturation and/or This protein may be involved in maturation and/or post-transcriptional regulation of mRNA. May play a role in control of cell cycle progression. May have tumor suppressor function. Regulates DNA topoisomerase II binding protein (TopBP1) for the DNA damage response. Plays an essential role in extraembryonic development.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Binds TOPBP1.
Subcellular location	Nucleus.
Tissue specificity	Widely expressed. Most abundant in testis and expressed at high levels in brain, pituitary and kidney.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR.
Miscellaneous	A cysteine residue is required for ubiquitin-thioester formation.
Sequence similarities	Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain. Contains 1 PABC domain. Contains 1 UBR-type zinc finger.

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Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Nucleus
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell proliferation Ref.1 Traceable author statement. Source: ProtInc progesterone receptor signaling pathway Inferred from direct assay. Source: HGNC protein modification process Inferred from electronic annotation. Source: InterPro response to DNA damage stimulus Inferred from direct assay. Source: HGNC ubiquitin-dependent protein catabolic process Ref.1 Traceable author statement. Source: ProtInc
Cellular component	nucleus Inferred from direct assay. Source: HGNC soluble fraction Ref.1 Traceable author statement. Source: ProtInc
Molecular function	RNA binding Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct ubiquitin-protein ligase activity Ref.1 Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
MAGED1	Q9Y5V3	1	EBI-358329,EBI-716006
MCRS1	Q96EZ8	1	EBI-358329,EBI-348259

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 2799

2799

E3 ubiquitin-protein ligase UBR5

PRO_0000086931

Regions

Domain

2377 – 2454

PABC

Domain

2462 – 2799

338

HECT

Zinc finger

1177 – 1245

UBR-type

Compositional bias

940 – 945

Poly-Glu

Compositional bias

980 – 985

Poly-Ser

Compositional bias

1528 – 1537

Poly-Ser

Compositional bias

1671 – 1681

Poly-Ser

Compositional bias

1762 – 1768

Poly-Ala

Compositional bias

1986 – 1997

Asp/Glu-rich (acidic)

Compositional bias

2036 – 2059

Pro-rich

Compositional bias

2329 – 2348

Arg/Glu-rich (mixed charge)

Compositional bias

2357 – 2366

Arg/Asp-rich (mixed charge)

Compositional bias

2489 – 2500

Asp/Glu-rich (acidic)

Compositional bias

2737 – 2757

Pro-rich

Sites

Active site

2768

Glycyl thioester intermediate By similarity

Amino acid modifications

Modified residue

287

Phosphoserine

Modified residue

327

Phosphoserine

Modified residue

598

Phosphoserine

Modified residue

1549

Phosphoserine

Modified residue

1746

Phosphotyrosine

Modified residue

2071

Phosphoserine

Experimental info

Mutagenesis

2768

C → A: Loss of ubiquitin binding

Sequence conflict

134

S → P in AAF88143. Ref.2

Sequence conflict

229

E → K in AAF88143. Ref.2

Sequence conflict

258

S → Y in AAF88143. Ref.2

Sequence conflict

374 – 375

IG → M in AAF88143. Ref.2

Sequence conflict

772

D → H in AAF88143. Ref.2

Sequence conflict

780

Q → R in AAF88143. Ref.2

Sequence conflict

884

D → G in AAF88143. Ref.2

Sequence conflict

1811

S → P in AAF88143. Ref.2

Sequence conflict

2144

L → H in AAF88143. Ref.2

Sequence conflict

2282

K → R in AAF88143. Ref.2

Sequence conflict

2474

Missing in BAA74919. Ref.3

Sequence conflict

2489

D → N in AAF88143. Ref.2

Secondary structure

2799

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

O95071-1 [UniParc].

Last modified October 1, 2001. Version 2.
Checksum: 871300DB404FF561
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FASTA

2,799

309,352

        10         20         30         40         50         60 
MTSIHFVVHP LPGTEDQLND RLREVSEKLN KYNLNSHPPL NVLEQATIKQ CVVGPNHAAF 

        70         80         90        100        110        120 
LLEDGRVCRI GFSVQPDRLE LGKPDNNDGS KLNSNSGAGR TSRPGRTSDS PWFLSGSETL 

       130        140        150        160        170        180 
GRLAGNTLGS RWSSGVGGSG GGSSGRSSAG ARDSRRQTRV IRTGRDRGSG LLGSQPQPVI 

       190        200        210        220        230        240 
PASVIPEELI SQAQVVLQGK SRSVIIRELQ RTNLDVNLAV NNLLSRDDED GDDGDDTASE 

       250        260        270        280        290        300 
SYLPGEDLMS LLDADIHSAH PSVIIDADAM FSEDISYFGY PSFRRSSLSR LGSSRVLLLP 

       310        320        330        340        350        360 
LERDSELLRE RESVLRLRER RWLDGASFDN ERGSTSKEGE PNLDKKNTPV QSPVSLGEDL 

       370        380        390        400        410        420 
QWWPDKDGTK FICIGALYSE LLAVSSKGEL YQWKWSESEP YRNAQNPSLH HPRATFLGLT 

       430        440        450        460        470        480 
NEKIVLLSAN SIRATVATEN NKVATWVDET LSSVASKLEH TAQTYSELQG ERIVSLHCCA 

       490        500        510        520        530        540 
LYTCAQLENS LYWWGVVPFS QRKKMLEKAR AKNKKPKSSA GISSMPNITV GTQVCLRNNP 

       550        560        570        580        590        600 
LYHAGAVAFS ISAGIPKVGV LMESVWNMND SCRFQLRSPE SLKNMEKASK TTEAKPESKQ 

       610        620        630        640        650        660 
EPVKTEMGPP PSPASTCSDA SSIASSASMP YKRRRSTPAP KEEEKVNEEQ WSLREVVFVE 

       670        680        690        700        710        720 
DVKNVPVGKV LKVDGAYVAV KFPGTSSNTN CQNSSGPDAD PSSLLQDCRL LRIDELQVVK 

       730        740        750        760        770        780 
TGGTPKVPDC FQRTPKKLCI PEKTEILAVN VDSKGVHAVL KTGNWVRYCI FDLATGKAEQ 

       790        800        810        820        830        840 
ENNFPTSSIA FLGQNERNVA IFTAGQESPI ILRDGNGTIY PMAKDCMGGI RDPDWLDLPP 

       850        860        870        880        890        900 
ISSLGMGVHS LINLPANSTI KKKAAVIIMA VEKQTLMQHI LRCDYEACRQ YLMNLEQAVV 

       910        920        930        940        950        960 
LEQNLQMLQT FISHRCDGNR NILHACVSVC FPTSNKETKE EEEAERSERN TFAERLSAVE 

       970        980        990       1000       1010       1020 
AIANAISVVS SNGPGNRAGS SSSRSLRLRE MMRRSLRAAG LGRHEAGASS SDHQDPVSPP 

      1030       1040       1050       1060       1070       1080 
IAPPSWVPDP PAMDPDGDID FILAPAVGSL TTAATGTGQG PSTSTIPGPS TEPSVVESKD 

      1090       1100       1110       1120       1130       1140 
RKANAHFILK LLCDSVVLQP YLRELLSAKD ARGMTPFMSA VSGRAYPAAI TILETAQKIA 

      1150       1160       1170       1180       1190       1200 
KAEISSSEKE EDVFMGMVCP SGTNPDDSPL YVLCCNDTCS FTWTGAEHIN QDIFECRTCG 

      1210       1220       1230       1240       1250       1260 
LLESLCCCTE CARVCHKGHD CKLKRTSPTA YCDCWEKCKC KTLIAGQKSA RLDLLYRLLT 

      1270       1280       1290       1300       1310       1320 
ATNLVTLPNS RGEHLLLFLV QTVARQTVEH CQYRPPRIRE DRNRKTASPE DSDMPDHDLE 

      1330       1340       1350       1360       1370       1380 
PPRFAQLALE RVLQDWNALK SMIMFGSQEN KDPLSASSRI GHLLPEEQVY LNQQSGTIRL 

      1390       1400       1410       1420       1430       1440 
DCFTHCLIVK CTADILLLDT LLGTLVKELQ NKYTPGRREE AIAVTMRFLR SVARVFVILS 

      1450       1460       1470       1480       1490       1500 
VEMASSKKKN NFIPQPIGKC KRVFQALLPY AVEELCNVAE SLIVPVRMGI ARPTAPFTLA 

      1510       1520       1530       1540       1550       1560 
STSIDAMQGS EELFSVEPLP PRPSSDQSSS SSQSQSSYII RNPQQRRISQ SQPVRGRDEE 

      1570       1580       1590       1600       1610       1620 
QDDIVSADVE EVEVVEGVAG EEDHHDEQEE HGEENAEAEG QHDEHDEDGS DMELDLLAAA 

      1630       1640       1650       1660       1670       1680 
ETESDSESNH SNQDNASGRR SVVTAATAGS EAGASSVPAF FSEDDSQSND SSDSDSSSSQ 

      1690       1700       1710       1720       1730       1740 
SDDIEQETFM LDEPLERTTN SSHANGAAQA PRSMQWAVRN TQHQRAASTA PSSTSTPAAS 

      1750       1760       1770       1780       1790       1800 
SAGLIYIDPS NLRRSGTIST SAAAAAAALE ASNASSYLTS ASSLARAYSI VIRQISDLMG 

      1810       1820       1830       1840       1850       1860 
LIPKYNHLVY SQIPAAVKLT YQDAVNLQNY VEEKLIPTWN WMVSIMDSTE AQLRYGSALA 

      1870       1880       1890       1900       1910       1920 
SAGDPGHPNH PLHASQNSAR RERMTAREEA SLRTLEGRRR ATLLSARQGM MSARGDFLNY 

      1930       1940       1950       1960       1970       1980 
ALSLMRSHND EHSDVLPVLD VCSLKHVAYV FQALIYWIKA MNQQTTLDTP QLERKRTREL 

      1990       2000       2010       2020       2030       2040 
LELGIDNEDS EHENDDDTNQ SATLNDKDDD SLPAETGQNH PFFRRSDSMT FLGCIPPNPF 

      2050       2060       2070       2080       2090       2100 
EVPLAEAIPL ADQPHLLQPN ARKEDLFGRP SQGLYSSSAS SGKCLMEVTV DRNCLEVLPT 

      2110       2120       2130       2140       2150       2160 
KMSYAANLKN VMNMQNRQKK EGEEQPVLPE ETESSKPGPS AHDLAAQLKS SLLAEIGLTE 

      2170       2180       2190       2200       2210       2220 
SEGPPLTSFR PQCSFMGMVI SHDMLLGRWR LSLELFGRVF MEDVGAEPGS ILTELGGFEV 

      2230       2240       2250       2260       2270       2280 
KESKFRREME KLRNQQSRDL SLEVDRDRDL LIQQTMRQLN NHFGRRCATT PMAVHRVKVT 

      2290       2300       2310       2320       2330       2340 
FKDEPGEGSG VARSFYTAIA QAFLSNEKLP NLECIQNANK GTHTSLMQRL RNRGERDRER 

      2350       2360       2370       2380       2390       2400 
EREREMRRSS GLRAGSRRDR DRDFRRQLSI DTRPFRPASE GNPSDDPEPL PAHRQALGER 

      2410       2420       2430       2440       2450       2460 
LYPRVQAMQP AFASKITGML LELSPAQLLL LLASEDSLRA RVDEAMELII AHGRENGADS 

      2470       2480       2490       2500       2510       2520 
ILDLGLVDSS EKVQQENRKR HGSSRSVVDM DLDDTDDGDD NAPLFYQPGK RGFYTPRPGK 

      2530       2540       2550       2560       2570       2580 
NTEARLNCFR NIGRILGLCL LQNELCPITL NRHVIKVLLG RKVNWHDFAF FDPVMYESLR 

      2590       2600       2610       2620       2630       2640 
QLILASQSSD ADAVFSAMDL AFAIDLCKEE GGGQVELIPN GVNIPVTPQN VYEYVRKYAE 

      2650       2660       2670       2680       2690       2700 
HRMLVVAEQP LHAMRKGLLD VLPKNSLEDL TAEDFRLLVN GCGEVNVQML ISFTSFNDES 

      2710       2720       2730       2740       2750       2760 
GENAEKLLQF KRWFWSIVEK MSMTERQDLV YFWTSSPSLP ASEEGFQPMP SITIRPPDDQ 

      2770       2780       2790 
HLPTANTCIS RLYVPLYSSK QILKQKLLLA IKTKNFGFV

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References

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[1]	"Identification of a human HECT family protein with homology to the Drosophila tumor suppressor gene hyperplastic discs." Callaghan M.J., Russell A.J., Woollatt E., Sutherland G.R., Sutherland R.L., Watts C.K.W. Oncogene 17:3479-3491(1998) [PubMed: 10030672] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart and Placenta.
[2]	"Cooperation of HECT-domain ubiquitin ligase hHYD and DNA topoisomerase II-binding protein for DNA damage response." Honda Y., Tojo M., Matsuzaki K., Anan T., Matsumoto M., Ando M., Saya H., Nakao M. J. Biol. Chem. 277:3599-3605(2002) [PubMed: 11714696] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH TOPBP1. Tissue: Fetal brain.
[3]	"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:355-364(1998) [PubMed: 10048485] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed: 12168954] [Abstract] Cited for: SEQUENCE REVISION.
[5]	Ohara O., Nagase T., Kikuno R., Ishikawa K., Suyama M. Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[6]	"Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287, MASS SPECTROMETRY.
[7]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1746, MASS SPECTROMETRY.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1549, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-327, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2071, MASS SPECTROMETRY.
[11]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-598, MASS SPECTROMETRY. Tissue: Platelet.
[12]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1549, MASS SPECTROMETRY.
[13]	"X-ray structure of the human hyperplastic discs protein: an ortholog of the C-terminal domain of poly(A)-binding protein." Deo R.C., Sonenberg N., Burley S.K. Proc. Natl. Acad. Sci. U.S.A. 98:4414-4419(2001) [PubMed: 11287654] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.04 ANGSTROMS) OF 2391-2455, MUTAGENESIS OF CYS-2768.
+	Additional computationally mapped references.