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Protein

E3 ubiquitin-protein ligase makorin-1

Gene

MKRN1

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

Functioni

E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. These substrates include FILIP1, p53/TP53, CDKN1A and TERT. Keeps cells alive by suppressing p53/TP53 under normal conditions, but stimulates apoptosis by repressing CDKN1A under stress conditions. Acts as a negative regulator of telomerase. Has negative and positive effects on RNA polymerase II-dependent transcription.2 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.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri55 – 82C3H1-type 1PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri84 – 111C3H1-type 2PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri208 – 235C3H1-type 3PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri281 – 335RING-typePROSITE-ProRule annotationAdd BLAST55
Zinc fingeri364 – 393C3H1-type 4PROSITE-ProRule annotationAdd BLAST30

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • poly(A) RNA binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: FlyBase
  • zinc ion binding Source: InterPro

GO - Biological processi

  • protein polyubiquitination Source: FlyBase
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000133606-MONOMER.
ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase makorin-1 (EC:6.3.2.-)
Alternative name(s):
RING finger protein 61
Gene namesi
Name:MKRN1
Synonyms:RNF61
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:7112. MKRN1.

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi307H → E: Loss of E3 ligase activity, but no effect on transcription regulation. 1 Publication1

Organism-specific databases

DisGeNETi23608.
OpenTargetsiENSG00000133606.
PharmGKBiPA30831.

Polymorphism and mutation databases

BioMutaiMKRN1.
DMDMi67477468.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000559521 – 482E3 ubiquitin-protein ligase makorin-1Add BLAST482

Post-translational modificationi

Auto-ubiquitinated; which leads to proteasomal degradation.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ9UHC7.
PaxDbiQ9UHC7.
PeptideAtlasiQ9UHC7.
PRIDEiQ9UHC7.

PTM databases

iPTMnetiQ9UHC7.
PhosphoSitePlusiQ9UHC7.

Expressioni

Tissue specificityi

Ubiquitous.2 Publications

Inductioni

Frequently induced in esophageal squamous cell carcinoma (SCC) tissues.1 Publication

Gene expression databases

BgeeiENSG00000133606.
CleanExiHS_MKRN1.
ExpressionAtlasiQ9UHC7. baseline and differential.
GenevisibleiQ9UHC7. HS.

Organism-specific databases

HPAiHPA000567.

Interactioni

Subunit structurei

Interacts with p53/TP53 and CDKN1A. Interacts with TERT, modulating telomere length homeostasis.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CDKN1AP389365EBI-373524,EBI-375077
TP53P046378EBI-373524,EBI-366083

Protein-protein interaction databases

BioGridi117141. 69 interactors.
IntActiQ9UHC7. 21 interactors.
MINTiMINT-1365598.
STRINGi9606.ENSP00000255977.

Structurei

3D structure databases

ProteinModelPortaliQ9UHC7.
SMRiQ9UHC7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni236 – 263Makorin-type Cys-HisAdd BLAST28

Sequence similaritiesi

Contains 4 C3H1-type zinc fingers.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri55 – 82C3H1-type 1PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri84 – 111C3H1-type 2PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri208 – 235C3H1-type 3PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri281 – 335RING-typePROSITE-ProRule annotationAdd BLAST55
Zinc fingeri364 – 393C3H1-type 4PROSITE-ProRule annotationAdd BLAST30

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1039. Eukaryota.
ENOG410XRM0. LUCA.
GeneTreeiENSGT00390000014093.
HOVERGENiHBG066965.
InParanoidiQ9UHC7.
KOiK15687.
OMAiPIVEMNM.
OrthoDBiEOG091G07DG.
PhylomeDBiQ9UHC7.
TreeFamiTF315108.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
4.10.1000.10. 3 hits.
InterProiIPR031644. MKRN1_C.
IPR018957. Znf_C3HC4_RING-type.
IPR000571. Znf_CCCH.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF15815. MKRN1_C. 1 hit.
PF00097. zf-C3HC4. 1 hit.
PF00642. zf-CCCH. 3 hits.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
SM00356. ZnF_C3H1. 4 hits.
[Graphical view]
SUPFAMiSSF90229. SSF90229. 3 hits.
PROSITEiPS50103. ZF_C3H1. 4 hits.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UHC7-1) [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
MAEAATPGTT ATTSGAGAAA ATAAAASPTP IPTVTAPSLG AGGGGGGSDG
60 70 80 90 100
SGGGWTKQVT CRYFMHGVCK EGDNCRYSHD LSDSPYSVVC KYFQRGYCIY
110 120 130 140 150
GDRCRYEHSK PLKQEEATAT ELTTKSSLAA SSSLSSIVGP LVEMNTGEAE
160 170 180 190 200
SRNSNFATVG AGSEDWVNAI EFVPGQPYCG RTAPSCTEAP LQGSVTKEES
210 220 230 240 250
EKEQTAVETK KQLCPYAAVG ECRYGENCVY LHGDSCDMCG LQVLHPMDAA
260 270 280 290 300
QRSQHIKSCI EAHEKDMELS FAVQRSKDMV CGICMEVVYE KANPSERRFG
310 320 330 340 350
ILSNCNHTYC LKCIRKWRSA KQFESKIIKS CPECRITSNF VIPSEYWVEE
360 370 380 390 400
KEEKQKLILK YKEAMSNKAC RYFDEGRGSC PFGGNCFYKH AYPDGRREEP
410 420 430 440 450
QRQKVGTSSR YRAQRRNHFW ELIEERENSN PFDNDEEEVV TFELGEMLLM
460 470 480
LLAAGGDDEL TDSEDEWDLF HDELEDFYDL DL
Length:482
Mass (Da):53,349
Last modified:June 7, 2005 - v3
Checksum:iAE8FAF010A5CDFC0
GO
Isoform 2 (identifier: Q9UHC7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-64: Missing.

Note: No experimental confirmation available.
Show »
Length:418
Mass (Da):47,639
Checksum:i6423024B2BCEF41A
GO
Isoform 3 (identifier: Q9UHC7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     366-412: SNKACRYFDE...QKVGTSSRYR → RYEHCSLFSS...DFPGQFILSP
     413-482: Missing.

Note: No experimental confirmation available.
Show »
Length:412
Mass (Da):45,020
Checksum:iC3A472C85E91F480
GO
Isoform 4 (identifier: Q9UHC7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     330-482: Missing.

Note: No experimental confirmation available.
Show »
Length:329
Mass (Da):35,224
Checksum:i5F8EE84A4F929F6A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti149A → R in AAF17214 (PubMed:10931946).Curated1
Sequence conflicti197K → E in BAG54426 (PubMed:14702039).Curated1
Sequence conflicti274 – 275QR → S in AAF17214 (PubMed:10931946).Curated2
Sequence conflicti395 – 396GR → AG in AAF17487 (PubMed:10843807).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_012161243V → L.3 PublicationsCorresponds to variant rs2272095dbSNPEnsembl.1
Natural variantiVAR_057214439V → A.Corresponds to variant rs1062786dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0403611 – 64Missing in isoform 2. 1 PublicationAdd BLAST64
Alternative sequenceiVSP_040362330 – 482Missing in isoform 4. 2 PublicationsAdd BLAST153
Alternative sequenceiVSP_040363366 – 412SNKAC…SSRYR → RYEHCSLFSSEEPNRAWVHF EKNGAALYTPTSFLPFFDFP GQFILSP in isoform 3. 1 PublicationAdd BLAST47
Alternative sequenceiVSP_040364413 – 482Missing in isoform 3. 1 PublicationAdd BLAST70

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF192784 mRNA. Translation: AAF17487.1.
AF192793
, AF192789, AF192790, AF192791, AF192792 Genomic DNA. Translation: AAF18979.1.
AM236048 mRNA. Translation: CAJ84705.1.
AF117233 mRNA. Translation: AAF17214.1.
AL136812 mRNA. Translation: CAB66746.1.
AK127030 mRNA. Translation: BAG54426.1.
AK315552 mRNA. Translation: BAG37929.1.
AC069335 Genomic DNA. No translation available.
CH236950 Genomic DNA. Translation: EAL24026.1.
CH471070 Genomic DNA. Translation: EAW83949.1.
BC025955 mRNA. Translation: AAH25955.1.
BC037400 mRNA. Translation: AAH37400.1.
BC064838 mRNA. Translation: AAH64838.1.
AB209298 mRNA. Translation: BAD92535.1.
CCDSiCCDS47725.1. [Q9UHC7-4]
CCDS5860.1. [Q9UHC7-1]
RefSeqiNP_001138597.1. NM_001145125.1. [Q9UHC7-4]
NP_038474.2. NM_013446.3. [Q9UHC7-1]
XP_011514299.1. XM_011515997.2. [Q9UHC7-2]
XP_011514300.1. XM_011515998.1. [Q9UHC7-2]
UniGeneiHs.744883.

Genome annotation databases

EnsembliENST00000255977; ENSP00000255977; ENSG00000133606. [Q9UHC7-1]
ENST00000443720; ENSP00000416369; ENSG00000133606. [Q9UHC7-4]
ENST00000474576; ENSP00000417863; ENSG00000133606. [Q9UHC7-2]
GeneIDi23608.
KEGGihsa:23608.
UCSCiuc003vvt.2. human. [Q9UHC7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF192784 mRNA. Translation: AAF17487.1.
AF192793
, AF192789, AF192790, AF192791, AF192792 Genomic DNA. Translation: AAF18979.1.
AM236048 mRNA. Translation: CAJ84705.1.
AF117233 mRNA. Translation: AAF17214.1.
AL136812 mRNA. Translation: CAB66746.1.
AK127030 mRNA. Translation: BAG54426.1.
AK315552 mRNA. Translation: BAG37929.1.
AC069335 Genomic DNA. No translation available.
CH236950 Genomic DNA. Translation: EAL24026.1.
CH471070 Genomic DNA. Translation: EAW83949.1.
BC025955 mRNA. Translation: AAH25955.1.
BC037400 mRNA. Translation: AAH37400.1.
BC064838 mRNA. Translation: AAH64838.1.
AB209298 mRNA. Translation: BAD92535.1.
CCDSiCCDS47725.1. [Q9UHC7-4]
CCDS5860.1. [Q9UHC7-1]
RefSeqiNP_001138597.1. NM_001145125.1. [Q9UHC7-4]
NP_038474.2. NM_013446.3. [Q9UHC7-1]
XP_011514299.1. XM_011515997.2. [Q9UHC7-2]
XP_011514300.1. XM_011515998.1. [Q9UHC7-2]
UniGeneiHs.744883.

3D structure databases

ProteinModelPortaliQ9UHC7.
SMRiQ9UHC7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117141. 69 interactors.
IntActiQ9UHC7. 21 interactors.
MINTiMINT-1365598.
STRINGi9606.ENSP00000255977.

PTM databases

iPTMnetiQ9UHC7.
PhosphoSitePlusiQ9UHC7.

Polymorphism and mutation databases

BioMutaiMKRN1.
DMDMi67477468.

Proteomic databases

EPDiQ9UHC7.
PaxDbiQ9UHC7.
PeptideAtlasiQ9UHC7.
PRIDEiQ9UHC7.

Protocols and materials databases

DNASUi23608.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000255977; ENSP00000255977; ENSG00000133606. [Q9UHC7-1]
ENST00000443720; ENSP00000416369; ENSG00000133606. [Q9UHC7-4]
ENST00000474576; ENSP00000417863; ENSG00000133606. [Q9UHC7-2]
GeneIDi23608.
KEGGihsa:23608.
UCSCiuc003vvt.2. human. [Q9UHC7-1]

Organism-specific databases

CTDi23608.
DisGeNETi23608.
GeneCardsiMKRN1.
HGNCiHGNC:7112. MKRN1.
HPAiHPA000567.
MIMi607754. gene.
neXtProtiNX_Q9UHC7.
OpenTargetsiENSG00000133606.
PharmGKBiPA30831.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1039. Eukaryota.
ENOG410XRM0. LUCA.
GeneTreeiENSGT00390000014093.
HOVERGENiHBG066965.
InParanoidiQ9UHC7.
KOiK15687.
OMAiPIVEMNM.
OrthoDBiEOG091G07DG.
PhylomeDBiQ9UHC7.
TreeFamiTF315108.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000133606-MONOMER.
ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

ChiTaRSiMKRN1. human.
GenomeRNAii23608.
PROiQ9UHC7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000133606.
CleanExiHS_MKRN1.
ExpressionAtlasiQ9UHC7. baseline and differential.
GenevisibleiQ9UHC7. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
4.10.1000.10. 3 hits.
InterProiIPR031644. MKRN1_C.
IPR018957. Znf_C3HC4_RING-type.
IPR000571. Znf_CCCH.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF15815. MKRN1_C. 1 hit.
PF00097. zf-C3HC4. 1 hit.
PF00642. zf-CCCH. 3 hits.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
SM00356. ZnF_C3H1. 4 hits.
[Graphical view]
SUPFAMiSSF90229. SSF90229. 3 hits.
PROSITEiPS50103. ZF_C3H1. 4 hits.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMKRN1_HUMAN
AccessioniPrimary (citable) accession number: Q9UHC7
Secondary accession number(s): A4D1T7
, B3KXB4, Q256Y7, Q59G11, Q6GSF1, Q9H0G0, Q9UEZ7, Q9UHW2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: June 7, 2005
Last modified: November 30, 2016
This is version 149 of the entry and version 3 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 7
    Human chromosome 7: 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. 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.