P19812

EV
Gene name
UBR1 (PTR1, YGR184C, G7168)
Protein name
E3 ubiquitin-protein ligase UBR1
Names
N-end-recognizing protein, N-recognin-1, RING-type E3 ubiquitin transferase UBR1
Species
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
KEGG Pathway
sce:YGR184C
EC number
2.3.2.27: Aminoacyltransferases
Protein Class
UBIQUITIN LIGASE E3 ALPHA-RELATED (PTHR21497)

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.

Autoinhibitory domains (AIDs)

1678-1950 (UBLC-containing C-terminal fragment) EV

Target domain

1-1140 (N-terminal region containing three substrate-binding sites)

Relief mechanism

Ligand binding

Assay

Deletion assay, Mutagenesis experiment

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

13 structures for P19812

Entry ID Method Resolution Chain Position Source
3NIH X-ray 210 A A 115-194 PDB
3NII X-ray 210 A A 115-194 PDB
3NIJ X-ray 210 A A 115-194 PDB
3NIK X-ray 185 A A/B/D/F 115-194 PDB
3NIL X-ray 175 A A/B/D/F 115-194 PDB
3NIM X-ray 200 A A/B/D/F 115-194 PDB
3NIN X-ray 210 A A/B 115-194 PDB
3NIS X-ray 168 A A/B/D/F 115-194 PDB
3NIT X-ray 260 A A 107-194 PDB
6KGI X-ray 104 A B 113-194 PDB
7MEX EM 335 A A 1-1950 PDB
7MEY EM 367 A A 1-1950 PDB
AF-P19812-F1 Predicted AlphaFoldDB

40 variants for P19812

Variant ID(s) Position Change Description Diseaes Association Provenance
s07-865583 59 S>N No SGRP
s07-865523 79 E>G No SGRP
s07-865504 85 D>E No SGRP
s07-865435 108 D>E No SGRP
s07-865099 220 I>M No SGRP
s07-864137 541 Q>R No SGRP
s07-864006 585 E>K No SGRP
s07-863954 602 E>V No SGRP
s07-863216 848 R>H No SGRP
s07-863214 849 D>N No SGRP
s07-863068 897 I>M No SGRP
s07-862858 967 L>F No SGRP
s07-862620 1047 V>I No SGRP
s07-862613 1049 K>R No SGRP
s07-862542 1073 I>L No SGRP
s07-862496 1088 E>G No SGRP
s07-862470 1097 N>H No SGRP
s07-862308 1151 D>N No SGRP
s07-862076 1228 S>L No SGRP
s07-862041 1240 H>Y No SGRP
s07-862001 1253 N>S No SGRP
s07-861983 1259 W>L No SGRP
s07-861915 1282 E>K No SGRP
s07-861810 1317 A>T No SGRP
s07-861720 1347 M>L No SGRP
s07-861480 1427 Y>H No SGRP
s07-861459 1434 S>G No SGRP
s07-861420 1447 V>L No SGRP
s07-861392 1456 I>T No SGRP
s07-861252 1503 T>A No SGRP
s07-861221 1513 F>S No SGRP
s07-861195 1522 Q>E No SGRP
s07-861047 1571 F>S No SGRP
s07-860867 1631 E>G No SGRP
s07-860841 1640 T>A No SGRP
s07-860826 1645 I>V No SGRP
s07-860817 1648 H>Y No SGRP
s07-860602 1719 M>I No SGRP
s07-860352 1803 V>I No SGRP
s07-860140 1873 E>D No SGRP

1 associated diseases with P19812

[MIM: 616576]: Immunodeficiency, common variable, 12, with autoimmunity (CVID12)

A primary immunodeficiency characterized by hypogammaglobulinemia and recurrent bacterial infections. About half of patients develop autoimmune features, including cytopenia, as well as generalized inflammation and lymphoproliferation manifest as lymphadenopathy or hepatosplenomegaly. {ECO:0000269|PubMed:26279205}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID
  • A primary immunodeficiency characterized by hypogammaglobulinemia and recurrent bacterial infections. About half of patients develop autoimmune features, including cytopenia, as well as generalized inflammation and lymphoproliferation manifest as lymphadenopathy or hepatosplenomegaly. {ECO:0000269|PubMed:26279205}. Note=The disease is caused by variants affecting the gene represented in this entry.

4 regional properties for P19812

Type Name Position InterPro Accession
domain ACT domain 36 - 114 IPR002912
binding_site Aromatic amino acid hydroxylase, iron/copper binding site 281 - 292 IPR018301
domain Aromatic amino acid hydroxylase, C-terminal 106 - 452 IPR019774
domain Eukaryotic phenylalanine-4-hydroxylase, catalytic domain 119 - 424 IPR041912

Functions

Description
EC Number 2.3.2.27 Aminoacyltransferases
Subcellular Localization
PANTHER Family PTHR21497 UBIQUITIN LIGASE E3 ALPHA-RELATED
PANTHER Subfamily PTHR21497:SF26 E3 UBIQUITIN-PROTEIN LIGASE UBR1
PANTHER Protein Class ubiquitin-protein ligase
protein modifying enzyme
PANTHER Pathway Category No pathway information available

4 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
proteasome regulatory particle, base subcomplex The subcomplex of the proteasome regulatory particle that directly associates with the proteasome core complex.
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.
UBR1-RAD6 ubiquitin ligase complex A ubiquitin ligase complex consisting of UBR1 and RAD6 components. It polyubiquitinates proteins containing non-acetylated N-terminal residues causing their subsequent degradation by the proteasome as part of the Ac/N-End Rule pathway. It recognizes non-acetylated N-terminal methionine if it is followed by a hydrophobic residue. Additionally, it acts in an N-end rule independent manner as a component of a novel quality control pathway for proteins synthesized on cytosolic ribosomes.

4 GO annotations of molecular function

Name Definition
proteasome regulatory particle binding Binding to a proteasome regulatory particle.
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
ubiquitin-protein transferase activity Catalysis of the transfer of ubiquitin from one protein to another via the reaction X-Ub + Y --> Y-Ub + X, where both X-Ub and Y-Ub are covalent linkages.
zinc ion binding Binding to a zinc ion (Zn).

10 GO annotations of biological process

Name Definition
cytoplasm protein quality control by the ubiquitin-proteasome system The chemical reactions and pathways resulting in the breakdown of misfolded proteins in the cytoplasm, which are targeted to cytoplasmic proteasomes for degradation.
mitochondria-associated ubiquitin-dependent protein catabolic process The chemical reactions and pathways resulting in the breakdown of proteins transported from mitochondria and targeted to cytoplasmic proteasomes for degradation as a response to oxidative stress conditions.
protein monoubiquitination Addition of a single ubiquitin group to a protein.
protein polyubiquitination Addition of multiple ubiquitin groups to a protein, forming a ubiquitin chain.
protein ubiquitination The process in which one or more ubiquitin groups are added to a protein.
regulation of dipeptide transport Any process that modulates the rate, frequency or extent of dipeptide transport. Dipeptide transport is the directed movement of a dipeptide, a combination of two amino acids by means of a peptide (-CO-NH-) link, into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
ribosome-associated ubiquitin-dependent protein catabolic process The chemical reactions and pathways resulting in the breakdown of a protein or peptide encoded by an aberrant message and associated with a stalled ribosome. Degradation is initiated by the covalent attachment of a ubiquitin group, or multiple ubiquitin groups, to the ribosome-associated protein.
stress-induced homeostatically regulated protein degradation pathway A stress-inducible protein catabolic pathway that promotes protein quality control by accelerating the degradation of misfolded ER membrane and cytosolic proteins, as well as native proteins. The pathway starts with the activation, by stress, of the Nma111p/Ynm3p serine protease, which cleaves the stress-induced hydrophilin Roq1p, resulting in the generation of a Roq1p cleavage product that selectively interacts with Ubr1p, an E3 ubiquitin ligase. Interaction with the Ubr1p type-1 substrate binding site reprograms the substrate specificity of this ubiquitin ligase resulting in the selective proteasome-mediated degradation of misfolded and native proteins. The pathway ends with degradation of the protein by the cytoplasmic proteasome. Currently, NMA111, ROQ1, UBR1, RAD6, and CDC48 are considered to be involved in this quality control pathway.
ubiquitin-dependent ERAD pathway The series of steps necessary to target endoplasmic reticulum (ER)-resident proteins for degradation by the cytoplasmic proteasome. Begins with recognition of the ER-resident protein, includes retrotranslocation (dislocation) of the protein from the ER to the cytosol, protein ubiquitination necessary for correct substrate transfer, transport of the protein to the proteasome, and ends with degradation of the protein by the cytoplasmic proteasome.
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
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
Q6WKZ8 Ubr2 E3 ubiquitin-protein ligase UBR2 Mus musculus (Mouse) SS
10 20 30 40 50 60
MSVADDDLGS LQGHIRRTLR SIHNLPYFRY TRGPTERADM SRALKEFIYR YLYFVISNSG
70 80 90 100 110 120
ENLPTLFNAH PKQKLSNPEL TVFPDSLEDA VDIDKITSQQ TIPFYKIDES RIGDVHKHTG
130 140 150 160 170 180
RNCGRKFKIG EPLYRCHECG CDDTCVLCIH CFNPKDHVNH HVCTDICTEF TSGICDCGDE
190 200 210 220 230 240
EAWNSPLHCK AEEQENDISE DPATNADIKE EDVWNDSVNI ALVELVLAEV FDYFIDVFNQ
250 260 270 280 290 300
NIEPLPTIQK DITIKLREMT QQGKMYERAQ FLNDLKYEND YMFDGTTTAK TSPSNSPEAS
310 320 330 340 350 360
PSLAKIDPEN YTVIIYNDEY HNYSQATTAL RQGVPDNVHI DLLTSRIDGE GRAMLKCSQD
370 380 390 400 410 420
LSSVLGGFFA VQTNGLSATL TSWSEYLHQE TCKYIILWIT HCLNIPNSSF QTTFRNMMGK
430 440 450 460 470 480
TLCSEYLNAT ECRDMTPVVE KYFSNKFDKN DPYRYIDLSI LADGNQIPLG HHKILPESST
490 500 510 520 530 540
HSLSPLINDV ETPTSRTYSN TRLQHILYFD NRYWKRLRKD IQNVIIPTLA SSNLYKPIFC
550 560 570 580 590 600
QQVVEIFNHI TRSVAYMDRE PQLTAIRECV VQLFTCPTNA KNIFENQSFL DIVWSIIDIF
610 620 630 640 650 660
KEFCKVEGGV LIWQRVQKSN LTKSYSISFK QGLYTVETLL SKVHDPNIPL RPKEIISLLT
670 680 690 700 710 720
LCKLFNGAWK IKRKEGEHVL HEDQNFISYL EYTTSIYSII QTAEKVSEKS KDSIDSKLFL
730 740 750 760 770 780
NAIRIISSFL GNRSLTYKLI YDSHEVIKFS VSHERVAFMN PLQTMLSFLI EKVSLKDAYE
790 800 810 820 830 840
ALEDCSDFLK ISDFSLRSVV LCSQIDVGFW VRNGMSVLHQ ASYYKNNPEL GSYSRDIHLN
850 860 870 880 890 900
QLAILWERDD IPRIIYNILD RWELLDWFTG EVDYQHTVYE DKISFIIQQF IAFIYQILTE
910 920 930 940 950 960
RQYFKTFSSL KDRRMDQIKN SIIYNLYMKP LSYSKLLRSV PDYLTEDTTE FDEALEEVSV
970 980 990 1000 1010 1020
FVEPKGLADN GVFKLKASLY AKVDPLKLLN LENEFESSAT IIKSHLAKDK DEIAKVVLIP
1030 1040 1050 1060 1070 1080
QVSIKQLDKD ALNLGAFTRN TVFAKVVYKL LQVCLDMEDS TFLNELLHLV HGIFRDDELI
1090 1100 1110 1120 1130 1140
NGKDSIPEAY LSKPICNLLL SIANAKSDVF SESIVRKADY LLEKMIMKKP NELFESLIAS
1150 1160 1170 1180 1190 1200
FGNQYVNDYK DKKLRQGVNL QETEKERKRR LAKKHQARLL AKFNNQQTKF MKEHESEFDE
1210 1220 1230 1240 1250 1260
QDNDVDMVGE KVYESEDFTC ALCQDSSSTD FFVIPAYHDH SPIFRPGNIF NPNEFMPMWD
1270 1280 1290 1300 1310 1320
GFYNDDEKQA YIDDDVLEAL KENGSCGSRK VFVSCNHHIH HNCFKRYVQK KRFSSNAFIC
1330 1340 1350 1360 1370 1380
PLCQTFSNCT LPLCQTSKAN TGLSLDMFLE SELSLDTLSR LFKPFTEENY RTINSIFSLM
1390 1400 1410 1420 1430 1440
ISQCQGFDKA VRKRANFSHK DVSLILSVHW ANTISMLEIA SRLEKPYSIS FFRSREQKYK
1450 1460 1470 1480 1490 1500
TLKNILVCIM LFTFVIGKPS MEFEPYPQQP DTVWNQNQLF QYIVRSALFS PVSLRQTVTE
1510 1520 1530 1540 1550 1560
ALTTFSRQFL RDFLQGLSDA EQVTKLYAKA SKIGDVLKVS EQMLFALRTI SDVRMEGLDS
1570 1580 1590 1600 1610 1620
ESIIYDLAYT FLLKSLLPTI RRCLVFIKVL HELVKDSENE TLVINGHEVE EELEFEDTAE
1630 1640 1650 1660 1670 1680
FVNKALKMIT EKESLVDLLT TQESIVSHPY LENIPYEYCG IIKLIDLSKY LNTYVTQSKE
1690 1700 1710 1720 1730 1740
IKLREERSQH MKNADNRLDF KICLTCGVKV HLRADRHEMT KHLNKNCFKP FGAFLMPNSS
1750 1760 1770 1780 1790 1800
EVCLHLTQPP SNIFISAPYL NSHGEVGRNA MRRGDLTTLN LKRYEHLNRL WINNEIPGYI
1810 1820 1830 1840 1850 1860
SRVMGDEFRV TILSNGFLFA FNREPRPRRI PPTDEDDEDM EEGEDGFFTE GNDEMDVDDE
1870 1880 1890 1900 1910 1920
TGQAANLFGV GAEGIAGGGV RDFFQFFENF RNTLQPQGNG DDDAPQNPPP ILQFLGPQFD
1930 1940
GATIIRNTNP RNLDEDDSDD NDDSDEREIW