UBR1

Protein identityUniProt · HPA

UniProt accession

Q8IWV7

Gene

UBR1

Ensembl

ENSG00000159459

Chromosome

15

Canonical length

1749 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Nucleoplasm,Vesicles,Cytosol

OverviewNCBI Gene

The N-end rule pathway is one proteolytic pathway of the ubiquitin system. The recognition component of this pathway, encoded by this gene, binds to a destabilizing N-terminal residue of a substrate protein and participates in the formation of a substrate-linked multiubiquitin chain. This leads to the eventual degradation of the substrate protein. The protein described in this record has a RING-type zinc finger and a UBR-type zinc finger. Mutations in this gene have been associated with Johanson-Blizzard syndrome. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1749 residues, UniProt reviewed canonical sequence.

>Q8IWV7|UBR1
     1  MADEEAGGTE RMEISAELPQ TPQRLASWWD QQVDFYTAFL HHLAQLVPEI YFAEMDPDLE
    61  KQEESVQMSI FTPLEWYLFG EDPDICLEKL KHSGAFQLCG RVFKSGETTY SCRDCAIDPT
   121  CVLCMDCFQD SVHKNHRYKM HTSTGGGFCD CGDTEAWKTG PFCVNHEPGR AGTIKENSRC
   181  PLNEEVIVQA RKIFPSVIKY VVEMTIWEEE KELPPELQIR EKNERYYCVL FNDEHHSYDH
   241  VIYSLQRALD CELAEAQLHT TAIDKEGRRA VKAGAYAACQ EAKEDIKSHS ENVSQHPLHV
   301  EVLHSEIMAH QKFALRLGSW MNKIMSYSSD FRQIFCQACL REEPDSENPC LISRLMLWDA
   361  KLYKGARKIL HELIFSSFFM EMEYKKLFAM EFVKYYKQLQ KEYISDDHDR SISITALSVQ
   421  MFTVPTLARH LIEEQNVISV ITETLLEVLP EYLDRNNKFN FQGYSQDKLG RVYAVICDLK
   481  YILISKPTIW TERLRMQFLE GFRSFLKILT CMQGMEEIRR QVGQHIEVDP DWEAAIAIQM
   541  QLKNILLMFQ EWCACDEELL LVAYKECHKA VMRCSTSFIS SSKTVVQSCG HSLETKSYRV
   601  SEDLVSIHLP LSRTLAGLHV RLSRLGAVSR LHEFVSFEDF QVEVLVEYPL RCLVLVAQVV
   661  AEMWRRNGLS LISQVFYYQD VKCREEMYDK DIIMLQIGAS LMDPNKFLLL VLQRYELAEA
   721  FNKTISTKDQ DLIKQYNTLI EEMLQVLIYI VGERYVPGVG NVTKEEVTMR EIIHLLCIEP
   781  MPHSAIAKNL PENENNETGL ENVINKVATF KKPGVSGHGV YELKDESLKD FNMYFYHYSK
   841  TQHSKAEHMQ KKRRKQENKD EALPPPPPPE FCPAFSKVIN LLNCDIMMYI LRTVFERAID
   901  TDSNLWTEGM LQMAFHILAL GLLEEKQQLQ KAPEEEVTFD FYHKASRLGS SAMNIQMLLE
   961  KLKGIPQLEG QKDMITWILQ MFDTVKRLRE KSCLIVATTS GSESIKNDEI THDKEKAERK
  1021  RKAEAARLHR QKIMAQMSAL QKNFIETHKL MYDNTSEMPG KEDSIMEEES TPAVSDYSRI
  1081  ALGPKRGPSV TEKEVLTCIL CQEEQEVKIE NNAMVLSACV QKSTALTQHR GKPIELSGEA
  1141  LDPLFMDPDL AYGTYTGSCG HVMHAVCWQK YFEAVQLSSQ QRIHVDLFDL ESGEYLCPLC
  1201  KSLCNTVIPI IPLQPQKINS ENADALAQLL TLARWIQTVL ARISGYNIRH AKGENPIPIF
  1261  FNQGMGDSTL EFHSILSFGV ESSIKYSNSI KEMVILFATT IYRIGLKVPP DERDPRVPML
  1321  TWSTCAFTIQ AIENLLGDEG KPLFGALQNR QHNGLKALMQ FAVAQRITCP QVLIQKHLVR
  1381  LLSVVLPNIK SEDTPCLLSI DLFHVLVGAV LAFPSLYWDD PVDLQPSSVS SSYNHLYLFH
  1441  LITMAHMLQI LLTVDTGLPL AQVQEDSEEA HSASSFFAEI SQYTSGSIGC DIPGWYLWVS
  1501  LKNGITPYLR CAALFFHYLL GVTPPEELHT NSAEGEYSAL CSYLSLPTNL FLLFQEYWDT
  1561  VRPLLQRWCA DPALLNCLKQ KNTVVRYPRK RNSLIELPDD YSCLLNQASH FRCPRSADDE
  1621  RKHPVLCLFC GAILCSQNIC CQEIVNGEEV GACIFHALHC GAGVCIFLKI RECRVVLVEG
  1681  KARGCAYPAP YLDEYGETDP GLKRGNPLHL SRERYRKLHL VWQQHCIIEE IARSQETNQM
  1741  LFGFNWQLL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against UBR1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

24 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about UBR1.

Disease | AllUniProt

Conditions UBR1 is implicated in, by any mechanism.

• Johanson-Blizzard syndrome (JBS) MIM:243800

Disease | GeneticClinVar

72 pathogenic / likely-pathogenic of 1,217 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Johanson-Blizzard syndrome
• UBR1-related disorder
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.35

gnomAD pLI

0.01

gnomAD missense Z

2.4

DepMap mean gene effect

-0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to L-leucine
• negative regulation of TOR signaling
• proteasome-mediated ubiquitin-dependent protein catabolic process
• protein ubiquitination
• ubiquitin-dependent protein catabolic process via the N-end rule pathway

Molecular functions

• L-leucine binding
• ubiquitin protein ligase activity
• zinc ion binding

Cellular components

• cytoplasm
• cytosol
• proteasome complex
• ubiquitin ligase complex

Protein domainsUniProt · Pfam · InterPro

• Zinc finger, UBR-type
• Adaptor protein ClpS, core
• Ribosomal protein bL12, C-terminal/adaptor protein ClpS-like
• Winged helix DNA-binding domain superfamily
• E3 ubiquitin-protein ligase UBR1-like
• E3 ubiquitin-protein ligase ELL-like
• E3 ubiquitin-protein ligase UBR-like, C-terminal
• E3 ubiquitin-protein ligase UBR1-like, winged-helix domain
• Putative zinc finger in N-recognin (UBR box)
• ATP-dependent Clp protease adaptor protein ClpS
• Proteolysis_6 C-terminal
• E3 ubiquitin-protein ligase UBR1-like, winged-helix domain
• E3 ubiquitin-protein ligase UBR1, UBR-box

KeywordsUniProt

• Acetylation
• Cytoplasm
• Metal-binding
• Phosphoprotein
• Transferase
• Ubl conjugation pathway
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

Protein binding partners of UBR1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RECQL4
• DNAJB11
• UBE2B