Q6WKZ8

SS
Gene name
Ubr2 (Kiaa0349)
Protein name
E3 ubiquitin-protein ligase UBR2
Names
EC 2.3.2.27 , N-recognin-2 , RING-type E3 ubiquitin transferase UBR2 , Ubiquitin-protein ligase E3-alpha-2 , Ubiquitin-protein ligase E3-alpha-II
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:224826
EC number
2.3.2.27: Aminoacyltransferases
Protein Class

Descriptions

In Saccharomyces cerevisiae, RING domain-containing Ub ligase UBR1 recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. Binding of dipeptides with destabilizing N-terminal residues to two substrate-binding sites of UBR1 causes dissociation of the C-terminal autoinhibitory domain of UBR1 from its N-terminal region that contains all three substrate-binding sites. This dissociation allows the interaction between UBR1 and CUP9, a transcriptional repressor of the peptide transporter PTR2, thereby accelerating the UBR1-dependent degradation of CUP9 and increasing the cell's capacity to import peptides. An aspect of autoinhibition characteristic of yeast UBR1 also is observed with mouse UBR1.

Autoinhibitory domains (AIDs)

1498-1755 (C-terminal fragment) SS

Target domain

0-1040 (N-terminal region containing three substrate-binding sites)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q6WKZ8

Entry ID Method Resolution Chain Position Source
AF-Q6WKZ8-F1 Predicted AlphaFoldDB

79 variants for Q6WKZ8

Variant ID(s) Position Change Description Diseaes Association Provenance
rs227607340 35 N>S No EVA
rs3389468153 58 P>H No EVA
rs3389448267 68 I>V No EVA
rs3389469946 71 G>* No EVA
rs3389417724 121 C>Y No EVA
rs3389427088 134 R>K No EVA
rs49463073 137 R>Q No EVA
rs3389467749 144 G>* No EVA
rs3389468114 154 T>I No EVA
rs3389417808 164 Q>E No EVA
rs3389467717 165 K>T No EVA
rs3389381480 169 S>C No EVA
rs3389470965 241 Q>* No EVA
rs3389417721 282 Q>* No EVA
rs3389448311 286 V>I No EVA
rs3389484658 334 I>N No EVA
rs3389417743 356 M>I No EVA
rs3407568803 375 M>T No EVA
rs3389427082 376 S>I No EVA
rs3389468164 394 K>E No EVA
rs3389475812 399 L>* No EVA
rs3389459304 399 L>M No EVA
rs3389469934 402 D>E No EVA
rs3407720213 411 A>E No EVA
rs3389480302 411 A>V No EVA
rs3389467721 419 V>I No EVA
rs234990707 432 L>I No EVA
rs3389417764 437 L>V No EVA
rs3389461624 466 L>F No EVA
rs3389462787 468 A>V No EVA
rs3389427103 494 D>G* No EVA
rs3389417765 497 R>G No EVA
rs3389435882 537 A>S No EVA
rs3389448289 564 E>* No EVA
rs3389480322 611 H>N No EVA
rs3389475791 667 W>R No EVA
rs3389459257 682 H>Q No EVA
rs3389448265 689 E>* No EVA
rs3389417727 700 T>R No EVA
rs3389469992 733 F>I No EVA
rs3389470945 819 H>D No EVA
rs3389480316 897 M>T No EVA
rs3407386676 929 G>V No EVA
rs3389462791 1012 A>S No EVA
rs3389467723 1014 A>E No EVA
rs3389484699 1023 S>L No EVA
rs3389459282 1024 R>I No EVA
rs3389427109 1052 M>I No EVA
rs3389468160 1060 N>S No EVA
rs3389469914 1105 F>I No EVA
rs3389417729 1112 Q>L No EVA
rs3389381468 1128 A>E No EVA
rs47095543 1145 A>E No EVA
rs48559383 1232 S>G No EVA
rs48563645 1264 H>D No EVA
rs108082475 1265 N>S No EVA
rs221842193 1270 S>P No EVA
rs3413124500 1275 T>A No EVA
rs3389467780 1286 G>R No EVA
rs3389427121 1310 T>M No EVA
rs3389475718 1333 W>L No EVA
rs3389435872 1334 G>E No EVA
rs3389484678 1385 V>I No EVA
rs3389467776 1431 D>E No EVA
rs246413321 1438 A>T No EVA
rs3389417789 1453 I>T No EVA
rs3389467753 1455 Q>H No EVA
rs3389467786 1505 W>C No EVA
rs3389448312 1540 T>R No EVA
rs3389417782 1562 E>G No EVA
rs3389459281 1567 M>I No EVA
rs3389417802 1636 C>* No EVA
rs3389461664 1643 Q>L No EVA
rs3389435848 1656 V>I No EVA
rs3389435873 1686 G>D No EVA
rs3389448293 1719 E>V No EVA
rs264306578 1726 K>M No EVA
rs264306578 1726 K>R No EVA
rs3389448304 1746 T>I No EVA

No associated diseases with Q6WKZ8

4 regional properties for Q6WKZ8

Type Name Position InterPro Accession
domain Zinc finger, UBR-type 97 - 168 IPR003126
domain Adaptor protein ClpS, core 223 - 300 IPR003769
domain E3 ubiquitin-protein ligase UBR-like, C-terminal 1312 - 1730 IPR044046
domain E3 ubiquitin-protein ligase UBR2, UBR-box 98 - 167 IPR047508

Functions

Description
EC Number 2.3.2.27 Aminoacyltransferases
Subcellular Localization
  • Nucleus
  • Chromosome
  • Associated with chromatin during meiosis
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

4 GO annotations of cellular component

Name Definition
chromatin The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
ubiquitin ligase complex A protein complex that includes a ubiquitin-protein ligase and enables ubiquitin protein ligase activity. The complex also contains other proteins that may confer substrate specificity on the complex.

4 GO annotations of molecular function

Name Definition
histone ubiquitin ligase activity Catalysis of the transfer of ubiquitin to a histone substrate.
leucine binding Binding to 2-amino-4-methylpentanoic acid.
ubiquitin protein ligase activity Catalysis of the transfer of ubiquitin to a substrate protein via the reaction X-ubiquitin + S -> X + S-ubiquitin, where X is either an E2 or E3 enzyme, the X-ubiquitin linkage is a thioester bond, and the S-ubiquitin linkage is an amide bond
zinc ion binding Binding to a zinc ion (Zn).

11 GO annotations of biological process

Name Definition
cellular response to leucine Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a leucine stimulus.
heterochromatin formation An epigenetic gene silencing mechanism in which chromatin is compacted into heterochromatin, resulting in a chromatin conformation refractory to transcription. This process starts with heterochromatin nucleation, its spreading, and ends with heterochromatin boundary formation.
male meiosis I A cell cycle process comprising the steps by which a cell progresses through male meiosis I, the first meiotic division in the male germline.
male meiotic nuclear division A cell cycle process by which the cell nucleus divides as part of a meiotic cell cycle in the male germline.
negative regulation of TOR signaling Any process that stops, prevents, or reduces the frequency, rate or extent of TOR signaling.
protein ubiquitination The process in which one or more ubiquitin groups are added to a protein.
reciprocal meiotic recombination The cell cycle process in which double strand breaks are formed and repaired through a single or double Holliday junction intermediate. This results in the equal exchange of genetic material between non-sister chromatids in a pair of homologous chromosomes. These reciprocal recombinant products ensure the proper segregation of homologous chromosomes during meiosis I and create genetic diversity.
retrotransposon silencing Any process that decreases the frequency, rate or extent of retrotransposition. Retrotransposons are a subset of transposable elements that use an RNA intermediate and reverse transcribe themselves into the genome.
spermatogenesis The developmental process by which male germ line stem cells self renew or give rise to successive cell types resulting in the development of a spermatozoa.
ubiquitin-dependent protein catabolic process The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of a ubiquitin group, or multiple ubiquitin groups, to the protein.
ubiquitin-dependent protein catabolic process via the N-end rule pathway The chemical reactions and pathways resulting in the breakdown of a protein or peptide covalently tagged with ubiquitin, via the N-end rule pathway. In the N-end rule pathway, destabilizing N-terminal residues (N-degrons) in substrates are recognized by E3 ligases (N-recognins), whereupon the substrates are linked to ubiquitin and then delivered to the proteasome for degradation.

5 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P19812 UBR1 E3 ubiquitin-protein ligase UBR1 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) EV
Q9VX91 Ubr1 E3 ubiquitin-protein ligase UBR1 Drosophila melanogaster (Fruit fly) PR
Q8IWV7 UBR1 E3 ubiquitin-protein ligase UBR1 Homo sapiens (Human) SS
Q8IWV8 UBR2 E3 ubiquitin-protein ligase UBR2 Homo sapiens (Human) SS
O70481 Ubr1 E3 ubiquitin-protein ligase UBR1 Mus musculus (Mouse) EV
10 20 30 40 50 60
MASEMEPEVQ AIDRSLLECS AEEIAGRWLQ ATDLNREVYQ HLAHCVPKIY CRGPNPFPQK
70 80 90 100 110 120
EDTLAQHILL GPMEWYICAE DPALGFPKLE QANKPSHLCG RVFKVGEPTY SCRDCAVDPT
130 140 150 160 170 180
CVLCMECFLG SIHRDHRYRM TTSGGGGFCD CGDTEAWKEG PYCQKHKLSS SEVVEEEDPL
190 200 210 220 230 240
VHLSEDVIAR TYNIFAIMFR YAVDILTWEK ESELPEDLEV AEKSDTYYCM LFNDEVHTYE
250 260 270 280 290 300
QVIYTLQKAV NCTQKEAIGF ATTVDRDGRR SVRYGDFQYC DQAKTVIVRN TSRQTKPLKV
310 320 330 340 350 360
QVMHSSVAAH QNFGLKALSW LGSVIGYSDG LRRILCQVGL QEGPDGENSS LVDRLMLNDS
370 380 390 400 410 420
KLWKGARSVY HQLFMSSLLM DLKYKKLFAL RFAKNYRQLQ RDFMEDDHER AVSVTALSVQ
430 440 450 460 470 480
FFTAPTLARM LLTEENLMTV IIKAFMDHLK HRDAQGRFQF ERYTALQAFK FRRVQSLILD
490 500 510 520 530 540
LKYVLISKPT EWSDELRQKF LQGFDAFLEL LKCMQGMDPI TRQVGQHIEM EPEWEAAFTL
550 560 570 580 590 600
QMKLTHVISM VQDWCALDEK VLIEAYKKCL AVLTQCHGGF TDGEQPITLS ICGHSVETIR
610 620 630 640 650 660
YCVSQEKVSI HLPISRLLAG LHVLLSKSEV AYKFPELLPL SELSPPMLIE HPLRCLVLCA
670 680 690 700 710 720
QVHAGMWRRN GFSLVNQIYY YHNVKCRREM FDKDIVMLQT GVSMMDPNHF LMIMLSRFEL
730 740 750 760 770 780
YQLFSTPDYG KRFSSEVTHK DVVQQNNTLI EEMLYLIIML VGERFNPGVG QVAATDEIKR
790 800 810 820 830 840
EIIHQLSIKP MAHSELVKSL PEDENKETGM ESVIESVAHF KKPGLTGRGM YELKPECAKE
850 860 870 880 890 900
FNLYFYHFSR AEQSKAEEAQ RKLKRENKED TALPPPALPP FCPLFASLVN ILQCDVMLYI
910 920 930 940 950 960
MGTILQWAVE HHGSAWSESM LQRVLHLIGM ALQEEKHHLE NAVEGHVQTF TFTQKISKPG
970 980 990 1000 1010 1020
DAPHNSPSIL AMLETLQNAP SLEAHKDMIR WLLKMFNAIK KIRECSSSSP VAEAEGTIME
1030 1040 1050 1060 1070 1080
ESSRDKDKAE RKRKAEIARL RREKIMAQMS EMQRHFIDEN KELFQQTLEL DTSASATLDS
1090 1100 1110 1120 1130 1140
SPPVSDAALT ALGPAQTQVP EPRQFVTCIL CQEEQEVTVG SRAMVLAAFV QRSTVLSKDR
1150 1160 1170 1180 1190 1200
TKTIADPEKY DPLFMHPDLS CGTHTGSCGH VMHAHCWQRY FDSVQAKEQR RQQRLRLHTS
1210 1220 1230 1240 1250 1260
YDVENGEFLC PLCECLSNTV IPLLLPPRSI LSRRLNFSDQ PDLAQWTRAV TQQIKVVQML
1270 1280 1290 1300 1310 1320
RRKHNAADTS SSEDTEAMNI IPIPEGFRPD FYPRNPYSDS IKEMLTTFGT AAYKVGLKVH
1330 1340 1350 1360 1370 1380
PNEGDPRVPI LCWGTCAYTI QSIERILSDE EKPVFGPLPC RLDDCLRSLT RFAAAHWTVA
1390 1400 1410 1420 1430 1440
LLPVVQGHFC KLFASLVPSD SYEDLPCILD IDMFHLLVGL VLAFPALQCQ DFSGSSLATG
1450 1460 1470 1480 1490 1500
DLHIFHLVTM AHIVQILLTS CTEENGMDQE NPTGEEELAI LSLHKTLHQY TGSALKEAPS
1510 1520 1530 1540 1550 1560
GWHLWRSVRA AIMPFLKCSA LFFHYLNGVP APPDLQVSGT SHFEHLCNYL SLPTNLIHLF
1570 1580 1590 1600 1610 1620
QENSDIMNSL IESWCQNSEV KRYLNGERGA ISYPRGANKL IDLPEDYSSL INQASNFSCP
1630 1640 1650 1660 1670 1680
KSGGDKSRAP TLCLVCGSLL CSQSYCCQAE LEGEDVGACT AHTYSCGSGA GIFLRVRECQ
1690 1700 1710 1720 1730 1740
VLFLAGKTKG CFYSPPYLDD YGETDQGLRR GNPLHLCQER FRKIQKLWQQ HSITEEIGHA
1750
QEANQTLVGI DWQHL