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Protein

E3 ubiquitin-protein ligase UHRF1

Gene

UHRF1

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

Functioni

Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. May be involved in DNA repair.9 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei316Histone H3K4me01
Binding sitei327Histone H3R2me01
Binding sitei330Histone H3R2me01
Binding sitei469Methylcytosine1
Sitei479Required to confer preferential recognition of cytosine over thymine1
Sitei489Required to discriminate between hemimethylated DNA versus symmetrically methylated DNA1
Sitei491Required for affinity and specificity for 5-mCpG sequence1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri310 – 366PHD-typePROSITE-ProRule annotationAdd BLAST57
Zinc fingeri724 – 763RING-typePROSITE-ProRule annotationAdd BLAST40

GO - Molecular functioni

  • core promoter proximal region sequence-specific DNA binding Source: BHF-UCL
  • hemi-methylated DNA-binding Source: UniProtKB
  • histone binding Source: UniProtKB
  • identical protein binding Source: BHF-UCL
  • ligase activity Source: UniProtKB-KW
  • methylated histone binding Source: UniProtKB
  • methyl-CpG binding Source: UniProtKB
  • nucleosomal histone binding Source: BHF-UCL
  • transcription factor activity, sequence-specific DNA binding Source: ProtInc
  • ubiquitin protein ligase activity Source: BHF-UCL
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • cell proliferation Source: BHF-UCL
  • DNA repair Source: UniProtKB-KW
  • histone monoubiquitination Source: BHF-UCL
  • histone ubiquitination Source: UniProtKB
  • maintenance of DNA methylation Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of cellular protein metabolic process Source: BHF-UCL
  • positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • protein autoubiquitination Source: UniProtKB
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: UniProtKB
  • regulation of methylation-dependent chromatin silencing Source: GO_Central
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Ligase, Repressor

Keywords - Biological processi

Cell cycle, DNA damage, DNA repair, Transcription, Transcription regulation, Ubl conjugation pathway

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000034063-MONOMER.
ReactomeiR-HSA-5334118. DNA methylation.
SignaLinkiQ96T88.
SIGNORiQ96T88.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase UHRF1 (EC:6.3.2.-)
Alternative name(s):
Inverted CCAAT box-binding protein of 90 kDa
Nuclear protein 95
Nuclear zinc finger protein Np95
Short name:
HuNp95
Short name:
hNp95
RING finger protein 106
Transcription factor ICBP90
Ubiquitin-like PHD and RING finger domain-containing protein 1
Short name:
hUHRF1
Ubiquitin-like-containing PHD and RING finger domains protein 1
Gene namesi
Name:UHRF1
Synonyms:ICBP90, NP95, RNF106
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:12556. UHRF1.

Subcellular locationi

GO - Cellular componenti

  • euchromatin Source: UniProtKB
  • heterochromatin Source: UniProtKB
  • nuclear chromatin Source: UniProtKB
  • nuclear heterochromatin Source: GO_Central
  • nuclear matrix Source: BHF-UCL
  • nucleus Source: BHF-UCL
  • replication fork Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in UHRF1 may be a cause of cancers. Overexpressed in many different forms of human cancers, including bladder, breast, cervical, colorectal and prostate cancers, as well as pancreatic adenocarcinomas, rhabdomyosarcomas and gliomas. Plays an important role in the correlation of histone modification and gene silencing in cancer progression. Expression is associated with a poor prognosis in patients with various cancers, suggesting that it participates in cancer progression.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi142D → A: Impaired binding to histone H3 without affecting the protein folding; when associated with A-153. 1 Publication1
Mutagenesisi145D → A: Impaired binding to histone H3. 1 Publication1
Mutagenesisi152F → A: Impaired binding to histone H3. 1 Publication1
Mutagenesisi153E → A: Impaired binding to histone H3 without affecting the protein folding; when associated with A-142. 1 Publication1
Mutagenesisi188Y → A: Impaired binding to histone H3. 2 Publications1
Mutagenesisi190D → A: Slightly impaired binding to histone H3. 1 Publication1
Mutagenesisi191Y → A: Impaired binding to histone H3. 1 Publication1
Mutagenesisi295 – 296RR → AA: Disrupts the simultaneous binding to H3R2me0 and H3K9me3. 1 Publication2
Mutagenesisi298S → A: Diminishes phosphorylation by PKA. 1 Publication1
Mutagenesisi330Q → A or K: Does not affect ability to bind histone H3 peptide. 1 Publication1
Mutagenesisi334 – 335DE → AA: Abolishes binding to histone H3. 1 Publication2
Mutagenesisi334D → A: Impaired binding to histone H3. 3 Publications1
Mutagenesisi337D → A: Impaired binding to histone H3. 3 Publications1
Mutagenesisi433R → A: Does not affect ability to bind DNA. 1 Publication1
Mutagenesisi443R → A: Decreased ability to bind DNA. 1 Publication1
Mutagenesisi448G → D: Decreased affinity for DNA. 1 Publication1
Mutagenesisi466Y → G: Decreased ability to bind DNA. 1 Publication1
Mutagenesisi469D → G: Abolishes ability to bind hemimethylated DNA. 1
Mutagenesisi489N → A: Abolishes specificity to hemimethylated DNA. 1 Publication1
Mutagenesisi491R → A: Decreased binding to methylated DNA but does not affect ability to bind DNA. 2 Publications1
Mutagenesisi639S → A: Prevents phosphorylation by CDK1 during M phase, leading to increased stability. 1 Publication1
Mutagenesisi639S → D: Mimics phosphorylation; impaired interaction with USP7, leading to decreased stability. 1 Publication1
Mutagenesisi651S → A: No effect on in vitro phosphorylation by PKA. 1 Publication1
Mutagenesisi666S → A: No effect on in vitro phosphorylation by PKA. 1 Publication1
Mutagenesisi741H → A: Abolishes E3 ubiquitin-protein ligase activity. 1 Publication1

Organism-specific databases

DisGeNETi29128.
OpenTargetsiENSG00000276043.
PharmGKBiPA37196.

Chemistry databases

ChEMBLiCHEMBL2424510.

Polymorphism and mutation databases

BioMutaiUHRF1.
DMDMi67462077.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000561441 – 793E3 ubiquitin-protein ligase UHRF1Add BLAST793

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei76PhosphoserineCombined sources1
Modified residuei91PhosphoserineCombined sources1
Modified residuei95PhosphoserineBy similarity1
Modified residuei165PhosphoserineBy similarity1
Modified residuei287PhosphoserineCombined sources1
Modified residuei298Phosphoserine; by PKA2 Publications1
Modified residuei368PhosphoserineCombined sources1
Cross-linki385Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei399N6-acetyllysineCombined sources1
Modified residuei546N6-acetyllysine; alternateCombined sources1
Cross-linki546Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei639Phosphoserine; by CDK1Combined sources1 Publication1
Modified residuei651PhosphoserineCombined sources1
Cross-linki670Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei707PhosphoserineCombined sources1
Modified residuei709PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation at Ser-298 of the linker region decreases the binding to H3K9me3. Phosphorylation at Ser-639 by CDK1 during M phase impairs interaction with USP7, preventing deubiquitination and leading to degradation by the proteasome.3 Publications
Ubiquitinated; which leads to proteasomal degradation. Autoubiquitinated; interaction with USP7 leads to deubiquitination and prevents degradation. Ubiquitination and degradation takes place during M phase, when phosphorylation at Ser-639 prevents intereaction with USP7 and subsequent deubiquitination. Polyubiquitination may be stimulated by DNA damage.4 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ96T88.
MaxQBiQ96T88.
PeptideAtlasiQ96T88.
PRIDEiQ96T88.

PTM databases

iPTMnetiQ96T88.
PhosphoSitePlusiQ96T88.

Expressioni

Tissue specificityi

Expressed in thymus, bone marrow, testis, lung and heart. Overexpressed in breast cancer.3 Publications

Developmental stagei

Expressed in fetal thymus, liver and kidney.1 Publication

Inductioni

Up-regulated in proliferating cells, and down-regulated in quiescent cells. Down-regulated upon adriamycin-induced DNA damage, in a p53/TP53 and CDKN1A-dependent way. Induced by E2F1 transcription factor.4 Publications

Gene expression databases

CleanExiHS_UHRF1.
ExpressionAtlasiQ96T88. baseline and differential.
GenevisibleiQ96T88. HS.

Organism-specific databases

HPAiHPA049408.

Interactioni

Subunit structurei

Interacts with DNMT3A and DNMT3B (By similarity). Interacts with DNMT1; the interaction is direct. Interacts with USP7; leading to its deubiquitination. Interacts with histone H3. Interacts with HDAC1, but not with HDAC2. Interacts with UHRF1BP1. Interacts with PML. Interacts with EHMT2. Binds hemimethylated CpG containing oligonucleotides.By similarity10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DNMT1P2635812EBI-1548946,EBI-719459
DNMT3AQ9Y6K17EBI-1548946,EBI-923653
DNMT3BQ9UBC37EBI-1548946,EBI-80125

GO - Molecular functioni

  • histone binding Source: UniProtKB
  • identical protein binding Source: BHF-UCL
  • methylated histone binding Source: UniProtKB
  • nucleosomal histone binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi118893. 66 interactors.
IntActiQ96T88. 15 interactors.
MINTiMINT-2815626.

Chemistry databases

BindingDBiQ96T88.

Structurei

Secondary structure

1793
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi1 – 7Combined sources7
Beta strandi13 – 19Combined sources7
Helixi25 – 36Combined sources12
Helixi40 – 42Combined sources3
Beta strandi43 – 47Combined sources5
Turni58 – 62Combined sources5
Beta strandi68 – 73Combined sources6
Turni127 – 129Combined sources3
Beta strandi140 – 144Combined sources5
Turni146 – 148Combined sources3
Beta strandi151 – 161Combined sources11
Beta strandi164 – 167Combined sources4
Turni179 – 181Combined sources3
Beta strandi182 – 188Combined sources7
Helixi192 – 194Combined sources3
Beta strandi196 – 200Combined sources5
Helixi201 – 203Combined sources3
Beta strandi204 – 206Combined sources3
Beta strandi210 – 212Combined sources3
Helixi214 – 216Combined sources3
Beta strandi222 – 227Combined sources6
Beta strandi229 – 231Combined sources3
Beta strandi237 – 248Combined sources12
Beta strandi253 – 260Combined sources8
Beta strandi262 – 272Combined sources11
Helixi274 – 276Combined sources3
Beta strandi277 – 279Combined sources3
Beta strandi283 – 286Combined sources4
Turni303 – 307Combined sources5
Beta strandi309 – 311Combined sources3
Turni314 – 316Combined sources3
Turni319 – 321Combined sources3
Beta strandi323 – 325Combined sources3
Helixi327 – 329Combined sources3
Beta strandi330 – 332Combined sources3
Turni334 – 336Combined sources3
Beta strandi339 – 341Combined sources3
Helixi342 – 344Combined sources3
Beta strandi345 – 347Combined sources3
Beta strandi354 – 356Combined sources3
Turni361 – 363Combined sources3
Beta strandi417 – 419Combined sources3
Beta strandi429 – 432Combined sources4
Helixi433 – 438Combined sources6
Turni439 – 442Combined sources4
Beta strandi448 – 452Combined sources5
Turni453 – 455Combined sources3
Beta strandi456 – 462Combined sources7
Beta strandi473 – 479Combined sources7
Turni487 – 489Combined sources3
Helixi503 – 511Combined sources9
Beta strandi512 – 514Combined sources3
Turni518 – 520Combined sources3
Helixi527 – 529Combined sources3
Beta strandi533 – 538Combined sources6
Helixi539 – 544Combined sources6
Beta strandi546 – 548Combined sources3
Beta strandi550 – 568Combined sources19
Beta strandi572 – 582Combined sources11
Helixi592 – 601Combined sources10
Helixi611 – 617Combined sources7
Helixi678 – 686Combined sources9
Helixi688 – 690Combined sources3
Helixi691 – 699Combined sources9
Beta strandi706 – 708Combined sources3
Helixi710 – 721Combined sources12
Turni725 – 727Combined sources3
Beta strandi728 – 730Combined sources3
Beta strandi732 – 736Combined sources5
Beta strandi742 – 744Combined sources3
Helixi745 – 753Combined sources9
Turni760 – 762Combined sources3
Helixi776 – 785Combined sources10
Turni787 – 792Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2FAZX-ray2.00A/B1-76[»]
2L3RNMR-A126-285[»]
2LGGNMR-A298-366[»]
2LGKNMR-A298-366[»]
2LGLNMR-A298-366[»]
2PB7X-ray1.90A408-643[»]
3ASKX-ray2.90A/B/C/D134-367[»]
3ASLX-ray1.41A298-367[»]
3BI7X-ray1.70A414-617[»]
3CLZX-ray2.20A/B/C/D414-617[»]
3DB3X-ray2.40A126-285[»]
3DB4X-ray2.40A126-285[»]
3DWHX-ray1.95A414-617[»]
3FL2X-ray1.75A672-793[»]
3SHBX-ray1.80A298-366[»]
3SOUX-ray1.80A/B298-367[»]
3SOWX-ray1.95A/B298-367[»]
3SOXX-ray2.65A/B298-367[»]
3T6RX-ray1.95A/B299-364[»]
3ZVYX-ray1.95A/B296-367[»]
3ZVZX-ray1.45B314-367[»]
4GY5X-ray2.96A/B/C/D134-366[»]
4QQDX-ray2.28A/B126-285[»]
5C6DX-ray2.29C/D634-665[»]
5IAYNMR-A134-285[»]
B642-657[»]
ProteinModelPortaliQ96T88.
SMRiQ96T88.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96T88.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 78Ubiquitin-likePROSITE-ProRule annotationAdd BLAST78
Domaini419 – 582YDGPROSITE-ProRule annotationAdd BLAST164

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni133 – 209Tudor-like 1Add BLAST77
Regioni216 – 283Tudor-like 2Add BLAST68
Regioni296 – 301Linker6
Regioni333 – 337Histone H3R2me0 binding5
Regioni353 – 355Histone H3R2me0 binding3
Regioni445 – 446Required to promote base flippingBy similarity2
Regioni463 – 464Methylcytosine binding2
Regioni466 – 469Required for formation of a 5-methylcytosine-binding pocket4
Regioni478 – 481Required for formation of a 5-methylcytosine-binding pocket4

Domaini

The tudor-like regions specifically recognize and bind histone H3 unmethylated at 'Arg-2' (H3R2me0), while the PHD-type zinc finger specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3). The tudor-like regions simultaneously recognizes H3K9me3 through a conserved aromatic cage in the first tudor-like subdomain and unmodified H3K4 (H3K4me0) within a groove between the tandem subdomains (PubMed:21489993, PubMed:21777816 and PubMed:22100450). The linker region plays a role in the formation of a histone H3-binding hole between the reader modules formed by the tudor-like regions and the PHD-type zinc finger by making extended contacts with the tandem tudor-like regions (PubMed:22837395).1 Publication
The YDG domain (also named SRA domain) specifically recognizes and binds hemimethylated DNA at replication forks (DNA that is only methylated on the mother strand of replicating DNA) (PubMed:17673620). It contains a binding pocket that accommodates the 5-methylcytosine that is flipped out of the duplex DNA. 2 specialized loops reach through the resulting gap in the DNA from both the major and the minor grooves to read the other 3 bases of the CpG duplex. The major groove loop confers both specificity for the CpG dinucleotide and discrimination against methylation of deoxycytidine of the complementary strand (PubMed:18772889). The YDG domain also recognizes and binds 5-hydroxymethylcytosine (5hmC) (PubMed:21731699).3 Publications
The RING finger is required for ubiquitin ligase activity.By similarity

Sequence similaritiesi

Contains 1 PHD-type zinc finger.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
Contains 1 ubiquitin-like domain.PROSITE-ProRule annotation
Contains 1 YDG domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri310 – 366PHD-typePROSITE-ProRule annotationAdd BLAST57
Zinc fingeri724 – 763RING-typePROSITE-ProRule annotationAdd BLAST40

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

GeneTreeiENSGT00390000008296.
HOGENOMiHOG000124662.
HOVERGENiHBG059298.
InParanoidiQ96T88.
KOiK10638.
PhylomeDBiQ96T88.

Family and domain databases

Gene3Di2.30.280.10. 1 hit.
2.30.30.30. 1 hit.
3.30.40.10. 2 hits.
InterProiIPR015947. PUA-like_domain.
IPR014722. Rib_L2_dom2.
IPR003105. SRA_YDG.
IPR021991. TTD_dom.
IPR029071. Ubiquitin-rel_dom.
IPR000626. Ubiquitin_dom.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF00628. PHD. 1 hit.
PF02182. SAD_SRA. 1 hit.
PF12148. TTD. 1 hit.
PF00240. ubiquitin. 1 hit.
[Graphical view]
SMARTiSM00249. PHD. 1 hit.
SM00184. RING. 2 hits.
SM00466. SRA. 1 hit.
SM00213. UBQ. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF57903. SSF57903. 1 hit.
SSF88697. SSF88697. 1 hit.
PROSITEiPS50053. UBIQUITIN_2. 1 hit.
PS51015. YDG. 1 hit.
PS01359. ZF_PHD_1. 1 hit.
PS50016. ZF_PHD_2. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96T88-1) [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
MWIQVRTMDG RQTHTVDSLS RLTKVEELRR KIQELFHVEP GLQRLFYRGK
60 70 80 90 100
QMEDGHTLFD YEVRLNDTIQ LLVRQSLVLP HSTKERDSEL SDTDSGCCLG
110 120 130 140 150
QSESDKSSTH GEAAAETDSR PADEDMWDET ELGLYKVNEY VDARDTNMGA
160 170 180 190 200
WFEAQVVRVT RKAPSRDEPC SSTSRPALEE DVIYHVKYDD YPENGVVQMN
210 220 230 240 250
SRDVRARART IIKWQDLEVG QVVMLNYNPD NPKERGFWYD AEISRKRETR
260 270 280 290 300
TARELYANVV LGDDSLNDCR IIFVDEVFKI ERPGEGSPMV DNPMRRKSGP
310 320 330 340 350
SCKHCKDDVN RLCRVCACHL CGGRQDPDKQ LMCDECDMAF HIYCLDPPLS
360 370 380 390 400
SVPSEDEWYC PECRNDASEV VLAGERLRES KKKAKMASAT SSSQRDWGKG
410 420 430 440 450
MACVGRTKEC TIVPSNHYGP IPGIPVGTMW RFRVQVSESG VHRPHVAGIH
460 470 480 490 500
GRSNDGAYSL VLAGGYEDDV DHGNFFTYTG SGGRDLSGNK RTAEQSCDQK
510 520 530 540 550
LTNTNRALAL NCFAPINDQE GAEAKDWRSG KPVRVVRNVK GGKNSKYAPA
560 570 580 590 600
EGNRYDGIYK VVKYWPEKGK SGFLVWRYLL RRDDDEPGPW TKEGKDRIKK
610 620 630 640 650
LGLTMQYPEG YLEALANRER EKENSKREEE EQQEGGFASP RTGKGKWKRK
660 670 680 690 700
SAGGGPSRAG SPRRTSKKTK VEPYSLTAQQ SSLIREDKSN AKLWNEVLAS
710 720 730 740 750
LKDRPASGSP FQLFLSKVEE TFQCICCQEL VFRPITTVCQ HNVCKDCLDR
760 770 780 790
SFRAQVFSCP ACRYDLGRSY AMQVNQPLQT VLNQLFPGYG NGR
Length:793
Mass (Da):89,814
Last modified:December 1, 2001 - v1
Checksum:iE65B15657525C89F
GO
Isoform 2 (identifier: Q96T88-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGVFAVPPLSSDTM

Note: No experimental confirmation available.
Show »
Length:806
Mass (Da):91,116
Checksum:iBFE365939E846398
GO

Sequence cautioni

The sequence BAB15177 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti383K → E in BAF82078 (PubMed:14702039).Curated1
Sequence conflicti383K → N in AAF28469 (PubMed:10646863).Curated1
Sequence conflicti457A → S in AAF28469 (PubMed:10646863).Curated1
Sequence conflicti675S → N in BAF82078 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022554240D → H.1 PublicationCorresponds to variant rs17886098dbSNPEnsembl.1
Natural variantiVAR_022555379E → K.2 PublicationsCorresponds to variant rs17885791dbSNPEnsembl.1
Natural variantiVAR_022556638A → T.2 PublicationsCorresponds to variant rs17883331dbSNPEnsembl.1
Natural variantiVAR_022557642T → M.1 PublicationCorresponds to variant rs17884843dbSNPEnsembl.1
Natural variantiVAR_022558713L → F.1 PublicationCorresponds to variant rs17883563dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0443941M → MGVFAVPPLSSDTM in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF129507 mRNA. Translation: AAF28469.1.
AB177623 mRNA. Translation: BAF36719.1.
AB177624 mRNA. Translation: BAF36720.1.
AB075601 mRNA. Translation: BAC20576.1.
AF274048 mRNA. Translation: AAK55744.1.
EF560733 mRNA. Translation: ABQ59043.1.
AK025578 mRNA. Translation: BAB15177.1. Different initiation.
AK289389 mRNA. Translation: BAF82078.1.
AK314579 mRNA. Translation: BAG37156.1.
AY787925 Genomic DNA. Translation: AAV40831.1.
AC027319 Genomic DNA. No translation available.
AC053467 Genomic DNA. Translation: AAF64067.1.
CH471139 Genomic DNA. Translation: EAW69187.1.
BC113875 mRNA. Translation: AAI13876.2.
CCDSiCCDS74262.1. [Q96T88-2]
CCDS74263.1. [Q96T88-1]
RefSeqiNP_001041666.1. NM_001048201.2. [Q96T88-1]
NP_001276979.1. NM_001290050.1. [Q96T88-1]
NP_001276980.1. NM_001290051.1. [Q96T88-1]
NP_001276981.1. NM_001290052.1. [Q96T88-1]
NP_037414.3. NM_013282.4.
UniGeneiHs.108106.

Genome annotation databases

EnsembliENST00000612630; ENSP00000484739; ENSG00000276043. [Q96T88-1]
ENST00000615884; ENSP00000478601; ENSG00000276043. [Q96T88-1]
ENST00000616255; ENSP00000478348; ENSG00000276043. [Q96T88-1]
ENST00000624301; ENSP00000485604; ENSG00000276043. [Q96T88-1]
GeneIDi29128.
KEGGihsa:29128.
UCSCiuc032hkj.2. human. [Q96T88-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF129507 mRNA. Translation: AAF28469.1.
AB177623 mRNA. Translation: BAF36719.1.
AB177624 mRNA. Translation: BAF36720.1.
AB075601 mRNA. Translation: BAC20576.1.
AF274048 mRNA. Translation: AAK55744.1.
EF560733 mRNA. Translation: ABQ59043.1.
AK025578 mRNA. Translation: BAB15177.1. Different initiation.
AK289389 mRNA. Translation: BAF82078.1.
AK314579 mRNA. Translation: BAG37156.1.
AY787925 Genomic DNA. Translation: AAV40831.1.
AC027319 Genomic DNA. No translation available.
AC053467 Genomic DNA. Translation: AAF64067.1.
CH471139 Genomic DNA. Translation: EAW69187.1.
BC113875 mRNA. Translation: AAI13876.2.
CCDSiCCDS74262.1. [Q96T88-2]
CCDS74263.1. [Q96T88-1]
RefSeqiNP_001041666.1. NM_001048201.2. [Q96T88-1]
NP_001276979.1. NM_001290050.1. [Q96T88-1]
NP_001276980.1. NM_001290051.1. [Q96T88-1]
NP_001276981.1. NM_001290052.1. [Q96T88-1]
NP_037414.3. NM_013282.4.
UniGeneiHs.108106.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2FAZX-ray2.00A/B1-76[»]
2L3RNMR-A126-285[»]
2LGGNMR-A298-366[»]
2LGKNMR-A298-366[»]
2LGLNMR-A298-366[»]
2PB7X-ray1.90A408-643[»]
3ASKX-ray2.90A/B/C/D134-367[»]
3ASLX-ray1.41A298-367[»]
3BI7X-ray1.70A414-617[»]
3CLZX-ray2.20A/B/C/D414-617[»]
3DB3X-ray2.40A126-285[»]
3DB4X-ray2.40A126-285[»]
3DWHX-ray1.95A414-617[»]
3FL2X-ray1.75A672-793[»]
3SHBX-ray1.80A298-366[»]
3SOUX-ray1.80A/B298-367[»]
3SOWX-ray1.95A/B298-367[»]
3SOXX-ray2.65A/B298-367[»]
3T6RX-ray1.95A/B299-364[»]
3ZVYX-ray1.95A/B296-367[»]
3ZVZX-ray1.45B314-367[»]
4GY5X-ray2.96A/B/C/D134-366[»]
4QQDX-ray2.28A/B126-285[»]
5C6DX-ray2.29C/D634-665[»]
5IAYNMR-A134-285[»]
B642-657[»]
ProteinModelPortaliQ96T88.
SMRiQ96T88.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118893. 66 interactors.
IntActiQ96T88. 15 interactors.
MINTiMINT-2815626.

Chemistry databases

BindingDBiQ96T88.
ChEMBLiCHEMBL2424510.

PTM databases

iPTMnetiQ96T88.
PhosphoSitePlusiQ96T88.

Polymorphism and mutation databases

BioMutaiUHRF1.
DMDMi67462077.

Proteomic databases

EPDiQ96T88.
MaxQBiQ96T88.
PeptideAtlasiQ96T88.
PRIDEiQ96T88.

Protocols and materials databases

DNASUi29128.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000612630; ENSP00000484739; ENSG00000276043. [Q96T88-1]
ENST00000615884; ENSP00000478601; ENSG00000276043. [Q96T88-1]
ENST00000616255; ENSP00000478348; ENSG00000276043. [Q96T88-1]
ENST00000624301; ENSP00000485604; ENSG00000276043. [Q96T88-1]
GeneIDi29128.
KEGGihsa:29128.
UCSCiuc032hkj.2. human. [Q96T88-1]

Organism-specific databases

CTDi29128.
DisGeNETi29128.
GeneCardsiUHRF1.
HGNCiHGNC:12556. UHRF1.
HPAiHPA049408.
MIMi607990. gene.
neXtProtiNX_Q96T88.
OpenTargetsiENSG00000276043.
PharmGKBiPA37196.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00390000008296.
HOGENOMiHOG000124662.
HOVERGENiHBG059298.
InParanoidiQ96T88.
KOiK10638.
PhylomeDBiQ96T88.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000034063-MONOMER.
ReactomeiR-HSA-5334118. DNA methylation.
SignaLinkiQ96T88.
SIGNORiQ96T88.

Miscellaneous databases

EvolutionaryTraceiQ96T88.
GeneWikiiUHRF1.
GenomeRNAii29128.
PROiQ96T88.
SOURCEiSearch...

Gene expression databases

CleanExiHS_UHRF1.
ExpressionAtlasiQ96T88. baseline and differential.
GenevisibleiQ96T88. HS.

Family and domain databases

Gene3Di2.30.280.10. 1 hit.
2.30.30.30. 1 hit.
3.30.40.10. 2 hits.
InterProiIPR015947. PUA-like_domain.
IPR014722. Rib_L2_dom2.
IPR003105. SRA_YDG.
IPR021991. TTD_dom.
IPR029071. Ubiquitin-rel_dom.
IPR000626. Ubiquitin_dom.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF00628. PHD. 1 hit.
PF02182. SAD_SRA. 1 hit.
PF12148. TTD. 1 hit.
PF00240. ubiquitin. 1 hit.
[Graphical view]
SMARTiSM00249. PHD. 1 hit.
SM00184. RING. 2 hits.
SM00466. SRA. 1 hit.
SM00213. UBQ. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF57903. SSF57903. 1 hit.
SSF88697. SSF88697. 1 hit.
PROSITEiPS50053. UBIQUITIN_2. 1 hit.
PS51015. YDG. 1 hit.
PS01359. ZF_PHD_1. 1 hit.
PS50016. ZF_PHD_2. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUHRF1_HUMAN
AccessioniPrimary (citable) accession number: Q96T88
Secondary accession number(s): A0JBR2
, A8K024, B2RBA9, Q2HIX7, Q8J022, Q9H6S6, Q9P115, Q9P1U7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: December 1, 2001
Last modified: November 2, 2016
This is version 150 of the entry and version 1 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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.