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Protein

E3 UFM1-protein ligase 1

Gene

UFL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 protein ligase that mediates ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to substrate proteins, a post-translational modification on lysine residues of proteins that may play a crucial role in a number of cellular processes. Mediates DDRGK1 ufmylation and may regulate the proteasomal degradation of DDRGK1 and CDK5RAP3 thereby modulating NF-kappa-B signaling (PubMed:20018847, PubMed:20164180, PubMed:20228063, PubMed:25219498). May also through TRIP4 ufmylation play a role in nuclear receptors-mediated transcription (PubMed:25219498). May play a role in the unfolded protein response, mediating the ufmylation of multiple proteins in response to endoplasmic reticulum stress (PubMed:23152784).5 Publications

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • UFM1 transferase activity Source: UniProtKB

GO - Biological processi

  • negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • negative regulation of protein ubiquitination Source: UniProtKB
  • osteoblast differentiation Source: UniProtKB
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of glial cell proliferation Source: Ensembl
  • protein K69-linked ufmylation Source: UniProtKB
  • protein ufmylation Source: UniProtKB
  • regulation of intracellular estrogen receptor signaling pathway Source: UniProtKB
  • regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
  • regulation of protein localization Source: MGI
  • response to endoplasmic reticulum stress Source: MGI
  • response to L-glutamate Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000014123-MONOMER.
ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 UFM1-protein ligase 1Curated (EC:6.3.2.-1 Publication)
Alternative name(s):
Novel LZAP-binding protein1 Publication
Regulator of C53/LZAP and DDRGK1
Gene namesi
Name:UFL1Imported
Synonyms:KIAA0776Imported, NLBP1 Publication, RCAD1 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:23039. UFL1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB-SubCell
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: MGI
  • membrane Source: UniProtKB
  • neuron projection Source: Ensembl
  • nucleus Source: HPA
  • protein complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi23376.
OpenTargetsiENSG00000014123.
PharmGKBiPA134937763.

Polymorphism and mutation databases

BioMutaiUFL1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000507712 – 794E3 UFM1-protein ligase 1Add BLAST793

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei433Omega-N-methylarginineBy similarity1
Modified residuei458PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated, leading to its degradation by the proteasome. Interaction with CDK5RAP3 protects each other against ubiquitination and degradation via the proteasome.1 Publication

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO94874.
MaxQBiO94874.
PaxDbiO94874.
PeptideAtlasiO94874.
PRIDEiO94874.

PTM databases

iPTMnetiO94874.
PhosphoSitePlusiO94874.
SwissPalmiO94874.

Expressioni

Tissue specificityi

Ubiquitously expressed, with a high expression in liver (at protein level). Low expression in several invasive hepatocellular carcinomas, such Hep-G2, Hep 3B2.1-7, HLE and PLC.1 Publication

Inductioni

Up-regulated by thapsigargin.1 Publication

Gene expression databases

BgeeiENSG00000014123.
CleanExiHS_KIAA0776.
GenevisibleiO94874. HS.

Organism-specific databases

HPAiHPA030558.
HPA030559.
HPA030560.

Interactioni

Subunit structurei

Interacts with DDRGK1 (PubMed:20018847, PubMed:20164180, PubMed:25219498). Interacts with UFC1 (PubMed:20018847). Interacts with RELA (PubMed:20164180). Interacts with TRIP4 (PubMed:25219498). Interacts with CDK5RAP3; the interaction is direct (PubMed:20164180, PubMed:20228063).4 Publications

Protein-protein interaction databases

BioGridi116953. 19 interactors.
IntActiO94874. 15 interactors.
MINTiMINT-4995005.
STRINGi9606.ENSP00000358283.

Structurei

3D structure databases

ProteinModelPortaliO94874.
SMRiO94874.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 212Required for E3 UFM1-protein ligase activity1 PublicationAdd BLAST211
Regioni2 – 200Mediates interaction with DDRGK11 PublicationAdd BLAST199
Regioni121 – 250Involved in CDK5RAP3-binding1 PublicationAdd BLAST130
Regioni200 – 400Mediates interaction with TRIP41 PublicationAdd BLAST201

Sequence similaritiesi

Belongs to the UFL1 family.Curated

Phylogenomic databases

eggNOGiKOG2235. Eukaryota.
ENOG410XSRX. LUCA.
GeneTreeiENSGT00390000002112.
HOGENOMiHOG000007320.
HOVERGENiHBG106513.
InParanoidiO94874.
OMAiISKEMRD.
OrthoDBiEOG091G03AN.
PhylomeDBiO94874.
TreeFamiTF319116.

Family and domain databases

InterProiIPR018611. E3_UFM1_ligase_1.
[Graphical view]
PfamiPF09743. DUF2042. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O94874-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MADAWEEIRR LAADFQRAQF AEATQRLSER NCIEIVNKLI AQKQLEVVHT
60 70 80 90 100
LDGKEYITPA QISKEMRDEL HVRGGRVNIV DLQQVINVDL IHIENRIGDI
110 120 130 140 150
IKSEKHVQLV LGQLIDENYL DRLAEEVNDK LQESGQVTIS ELCKTYDLPG
160 170 180 190 200
NFLTQALTQR LGRIISGHID LDNRGVIFTE AFVARHKARI RGLFSAITRP
210 220 230 240 250
TAVNSLISKY GFQEQLLYSV LEELVNSGRL RGTVVGGRQD KAVFVPDIYS
260 270 280 290 300
RTQSTWVDSF FRQNGYLEFD ALSRLGIPDA VSYIKKRYKT TQLLFLKAAC
310 320 330 340 350
VGQGLVDQVE ASVEEAISSG TWVDIAPLLP TSLSVEDAAI LLQQVMRAFS
360 370 380 390 400
KQASTVVFSD TVVVSEKFIN DCTELFRELM HQKAEKEMKN NPVHLITEED
410 420 430 440 450
LKQISTLESV STSKKDKKDE RRRKATEGSG SMRGGGGGNA REYKIKKVKK
460 470 480 490 500
KGRKDDDSDD ESQSSHTGKK KPEISFMFQD EIEDFLRKHI QDAPEEFISE
510 520 530 540 550
LAEYLIKPLN KTYLEVVRSV FMSSTTSASG TGRKRTIKDL QEEVSNLYNN
560 570 580 590 600
IRLFEKGMKF FADDTQAALT KHLLKSVCTD ITNLIFNFLA SDLMMAVDDP
610 620 630 640 650
AAITSEIRKK ILSKLSEETK VALTKLHNSL NEKSIEDFIS CLDSAAEACD
660 670 680 690 700
IMVKRGDKKR ERQILFQHRQ ALAEQLKVTE DPALILHLTS VLLFQFSTHS
710 720 730 740 750
MLHAPGRCVP QIIAFLNSKI PEDQHALLVK YQGLVVKQLV SQSKKTGQGD
760 770 780 790
YPLNNELDKE QEDVASTTRK ELQELSSSIK DLVLKSRKSS VTEE
Length:794
Mass (Da):89,595
Last modified:June 21, 2005 - v2
Checksum:iC6C1777455551991
GO
Isoform 2 (identifier: O94874-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: Missing.

Note: No experimental confirmation available.
Show »
Length:729
Mass (Da):82,098
Checksum:iCC168D0709E0D82A
GO
Isoform 3 (identifier: O94874-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     508-509: PL → QV
     510-794: Missing.

Note: No experimental confirmation available.
Show »
Length:509
Mass (Da):57,583
Checksum:i84F3FC58B6D8F072
GO

Sequence cautioni

The sequence AAH15377 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated
The sequence BAA34496 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034037137V → F.Corresponds to variant rs28372909dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0387591 – 65Missing in isoform 2. 1 PublicationAdd BLAST65
Alternative sequenceiVSP_038760508 – 509PL → QV in isoform 3. 1 Publication2
Alternative sequenceiVSP_038761510 – 794Missing in isoform 3. 1 PublicationAdd BLAST285

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB018319 mRNA. Translation: BAA34496.1. Different initiation.
AK295934 mRNA. Translation: BAG58719.1.
AL590404, AL132776 Genomic DNA. Translation: CAH73710.1.
AL132776, AL590404 Genomic DNA. Translation: CAI20401.1.
CH471051 Genomic DNA. Translation: EAW48507.1.
BC015377 mRNA. Translation: AAH15377.1. Sequence problems.
BC028608 mRNA. Translation: AAH28608.1.
BC036379 mRNA. Translation: AAH36379.1.
CCDSiCCDS5034.1. [O94874-1]
RefSeqiNP_056138.1. NM_015323.4. [O94874-1]
UniGeneiHs.149367.

Genome annotation databases

EnsembliENST00000369278; ENSP00000358283; ENSG00000014123. [O94874-1]
GeneIDi23376.
KEGGihsa:23376.
UCSCiuc003por.4. human. [O94874-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB018319 mRNA. Translation: BAA34496.1. Different initiation.
AK295934 mRNA. Translation: BAG58719.1.
AL590404, AL132776 Genomic DNA. Translation: CAH73710.1.
AL132776, AL590404 Genomic DNA. Translation: CAI20401.1.
CH471051 Genomic DNA. Translation: EAW48507.1.
BC015377 mRNA. Translation: AAH15377.1. Sequence problems.
BC028608 mRNA. Translation: AAH28608.1.
BC036379 mRNA. Translation: AAH36379.1.
CCDSiCCDS5034.1. [O94874-1]
RefSeqiNP_056138.1. NM_015323.4. [O94874-1]
UniGeneiHs.149367.

3D structure databases

ProteinModelPortaliO94874.
SMRiO94874.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116953. 19 interactors.
IntActiO94874. 15 interactors.
MINTiMINT-4995005.
STRINGi9606.ENSP00000358283.

PTM databases

iPTMnetiO94874.
PhosphoSitePlusiO94874.
SwissPalmiO94874.

Polymorphism and mutation databases

BioMutaiUFL1.

Proteomic databases

EPDiO94874.
MaxQBiO94874.
PaxDbiO94874.
PeptideAtlasiO94874.
PRIDEiO94874.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000369278; ENSP00000358283; ENSG00000014123. [O94874-1]
GeneIDi23376.
KEGGihsa:23376.
UCSCiuc003por.4. human. [O94874-1]

Organism-specific databases

CTDi23376.
DisGeNETi23376.
GeneCardsiUFL1.
H-InvDBHIX0018113.
HGNCiHGNC:23039. UFL1.
HPAiHPA030558.
HPA030559.
HPA030560.
MIMi613372. gene.
neXtProtiNX_O94874.
OpenTargetsiENSG00000014123.
PharmGKBiPA134937763.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2235. Eukaryota.
ENOG410XSRX. LUCA.
GeneTreeiENSGT00390000002112.
HOGENOMiHOG000007320.
HOVERGENiHBG106513.
InParanoidiO94874.
OMAiISKEMRD.
OrthoDBiEOG091G03AN.
PhylomeDBiO94874.
TreeFamiTF319116.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000014123-MONOMER.
ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

GenomeRNAii23376.
PROiO94874.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000014123.
CleanExiHS_KIAA0776.
GenevisibleiO94874. HS.

Family and domain databases

InterProiIPR018611. E3_UFM1_ligase_1.
[Graphical view]
PfamiPF09743. DUF2042. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUFL1_HUMAN
AccessioniPrimary (citable) accession number: O94874
Secondary accession number(s): A0PJ53
, B4DJ57, C0H5X5, Q8N765, Q9NTQ0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 21, 2005
Last sequence update: June 21, 2005
Last modified: November 30, 2016
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families
  6. Uncharacterized protein families (UPF)
    List of uncharacterized protein family (UPF) entries

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.