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Protein

E3 ubiquitin-protein ligase Midline-1

Gene

MID1

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

Functioni

Has E3 ubiquitin ligase activity towards IGBP1, promoting its monoubiquitination, which results in deprotection of the catalytic subunit of protein phosphatase PP2A, and its subsequent degradation by polyubiquitination.3 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi119Zinc 11
Metal bindingi122Zinc 11
Metal bindingi134Zinc 21
Metal bindingi137Zinc 21
Metal bindingi142Zinc 11
Metal bindingi145Zinc 11
Metal bindingi150Zinc 21
Metal bindingi159Zinc 21

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri10 – 60RING-typePROSITE-ProRule annotationAdd BLAST51
Zinc fingeri116 – 165B box-type 1PROSITE-ProRule annotationAdd BLAST50
Zinc fingeri172 – 212B box-type 2PROSITE-ProRule annotationAdd BLAST41

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • microtubule binding Source: UniProtKB
  • phosphoprotein binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • transferase activity Source: UniProtKB-KW
  • ubiquitin protein ligase binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • interferon-gamma-mediated signaling pathway Source: Reactome
  • microtubule cytoskeleton organization Source: ProtInc
  • negative regulation of microtubule depolymerization Source: Ensembl
  • pattern specification process Source: ProtInc
  • positive regulation of stress-activated MAPK cascade Source: UniProtKB
  • protein localization to microtubule Source: UniProtKB

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-877300 Interferon gamma signaling

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase Midline-1 (EC:2.3.2.27)
Alternative name(s):
Midin
Putative transcription factor XPRF
RING finger protein 59
RING finger protein Midline-1
RING-type E3 ubiquitin transferase Midline-1Curated
Tripartite motif-containing protein 18
Gene namesi
Name:MID1
Synonyms:FXY, RNF59, TRIM18, XPRF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000101871.14
HGNCiHGNC:7095 MID1
MIMi300552 gene
neXtProtiNX_O15344

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Microtubule

Pathology & Biotechi

Involvement in diseasei

Opitz GBBB syndrome 1 (GBBB1)4 Publications
The disease is caused by mutations affecting the gene represented in this entry. MID1 mutations produce proteins with a decreased affinity for microtubules.
Disease descriptionA congenital midline malformation syndrome characterized by hypertelorism, genital-urinary defects such as hypospadias in males and splayed labia in females, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and congenital heart defects.
See also OMIM:300000
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_013758266C → R in GBBB1. 1 Publication1
Natural variantiVAR_025495295L → P in GBBB1. 1 PublicationCorresponds to variant dbSNP:rs104894866EnsemblClinVar.1
Natural variantiVAR_025496391 – 392LC → R in GBBB1. 1 Publication2
Natural variantiVAR_013759438Missing in GBBB1. 1 Publication1
Natural variantiVAR_013760534V → VFIDSGRHL in GBBB1. 1
Natural variantiVAR_013761536I → T in GBBB1. 1 Publication1
Natural variantiVAR_013762626L → P in GBBB1. 1 PublicationCorresponds to variant dbSNP:rs28934611EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi4281
GeneReviewsiMID1
MalaCardsiMID1
MIMi300000 phenotype
OpenTargetsiENSG00000101871
Orphaneti306597 X-linked Opitz G/BBB syndrome
PharmGKBiPA30816

Polymorphism and mutation databases

BioMutaiMID1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000562271 – 667E3 ubiquitin-protein ligase Midline-1Add BLAST667

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei92PhosphoserineCombined sources1
Modified residuei96PhosphoserineCombined sources1
Modified residuei511PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on serine and threonine residues.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO15344
MaxQBiO15344
PaxDbiO15344
PeptideAtlasiO15344
PRIDEiO15344
ProteomicsDBi48594
48595 [O15344-2]

PTM databases

iPTMnetiO15344
PhosphoSitePlusiO15344

Expressioni

Tissue specificityi

In the fetus, highest expression found in kidney, followed by brain and lung. Expressed at low levels in fetal liver. In the adult, most abundant in heart, placenta and brain.

Inductioni

A retroviral element acts as an alternative tissue-specific promoter for this gene. The LTR of an HERV-E element enhances the expression in placenta and embryonic kidney.

Gene expression databases

BgeeiENSG00000101871
CleanExiHS_MID1
ExpressionAtlasiO15344 baseline and differential
GenevisibleiO15344 HS

Organism-specific databases

HPAiHPA003715

Interactioni

Subunit structurei

Homodimer or heterodimer with MID2. Interacts with IGBP1.2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • microtubule binding Source: UniProtKB
  • phosphoprotein binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110427, 81 interactors
IntActiO15344, 39 interactors
MINTiO15344
STRINGi9606.ENSP00000312678

Structurei

Secondary structure

1667
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi112 – 114Combined sources3
Beta strandi124 – 126Combined sources3
Beta strandi132 – 134Combined sources3
Turni135 – 138Combined sources4
Beta strandi139 – 141Combined sources3
Helixi143 – 149Combined sources7
Beta strandi154 – 156Combined sources3
Beta strandi161 – 163Combined sources3
Beta strandi179 – 181Combined sources3
Beta strandi185 – 187Combined sources3
Turni188 – 191Combined sources4
Beta strandi192 – 194Combined sources3
Helixi196 – 200Combined sources5
Beta strandi205 – 207Combined sources3
Helixi325 – 346Combined sources22
Beta strandi352 – 355Combined sources4
Helixi356 – 374Combined sources19

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DQ5NMR-A168-214[»]
2FFWNMR-A87-164[»]
2JUNNMR-A114-214[»]
5IM8NMR-A320-379[»]
ProteinModelPortaliO15344
SMRiO15344
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15344

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini320 – 379COSPROSITE-ProRule annotationAdd BLAST60
Domaini381 – 484Fibronectin type-IIIPROSITE-ProRule annotationAdd BLAST104
Domaini482 – 659B30.2/SPRYPROSITE-ProRule annotationAdd BLAST178

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili205 – 264Sequence analysisAdd BLAST60

Sequence similaritiesi

Belongs to the TRIM/RBCC family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri10 – 60RING-typePROSITE-ProRule annotationAdd BLAST51
Zinc fingeri116 – 165B box-type 1PROSITE-ProRule annotationAdd BLAST50
Zinc fingeri172 – 212B box-type 2PROSITE-ProRule annotationAdd BLAST41

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ITFU Eukaryota
ENOG410Z43Q LUCA
GeneTreeiENSGT00760000118878
HOGENOMiHOG000049193
HOVERGENiHBG056432
InParanoidiO15344
KOiK08285
OMAiWALCRCH
OrthoDBiEOG091G02K9
PhylomeDBiO15344
TreeFamiTF333654

Family and domain databases

CDDicd00021 BBOX, 1 hit
cd00063 FN3, 1 hit
Gene3Di2.60.40.10, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR001870 B30.2/SPRY
IPR003649 Bbox_C
IPR003879 Butyrophylin_SPRY
IPR013320 ConA-like_dom_sf
IPR017903 COS_domain
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR013783 Ig-like_fold
IPR027727 MID1
IPR006574 PRY
IPR003877 SPRY_dom
IPR027370 Znf-RING_LisH
IPR000315 Znf_B-box
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR44073:SF3 PTHR44073:SF3, 1 hit
PfamiView protein in Pfam
PF00041 fn3, 1 hit
PF13765 PRY, 1 hit
PF00622 SPRY, 1 hit
PF00643 zf-B_box, 1 hit
PF13445 zf-RING_UBOX, 1 hit
PRINTSiPR01407 BUTYPHLNCDUF
SMARTiView protein in SMART
SM00502 BBC, 1 hit
SM00336 BBOX, 2 hits
SM00060 FN3, 1 hit
SM00184 RING, 1 hit
SM00449 SPRY, 1 hit
SUPFAMiSSF49265 SSF49265, 1 hit
SSF49899 SSF49899, 1 hit
PROSITEiView protein in PROSITE
PS50188 B302_SPRY, 1 hit
PS51262 COS, 1 hit
PS50853 FN3, 1 hit
PS50119 ZF_BBOX, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: O15344-1) [UniParc]FASTAAdd to basket
Also known as: Alpha

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
METLESELTC PICLELFEDP LLLPCAHSLC FNCAHRILVS HCATNESVES
60 70 80 90 100
ITAFQCPTCR HVITLSQRGL DGLKRNVTLQ NIIDRFQKAS VSGPNSPSET
110 120 130 140 150
RRERAFDANT MTSAEKVLCQ FCDQDPAQDA VKTCVTCEVS YCDECLKATH
160 170 180 190 200
PNKKPFTGHR LIEPIPDSHI RGLMCLEHED EKVNMYCVTD DQLICALCKL
210 220 230 240 250
VGRHRDHQVA ALSERYDKLK QNLESNLTNL IKRNTELETL LAKLIQTCQH
260 270 280 290 300
VEVNASRQEA KLTEECDLLI EIIQQRRQII GTKIKEGKVM RLRKLAQQIA
310 320 330 340 350
NCKQCIERSA SLISQAEHSL KENDHARFLQ TAKNITERVS MATASSQVLI
360 370 380 390 400
PEINLNDTFD TFALDFSREK KLLECLDYLT APNPPTIREE LCTASYDTIT
410 420 430 440 450
VHWTSDDEFS VVSYELQYTI FTGQANVVSL CNSADSWMIV PNIKQNHYTV
460 470 480 490 500
HGLQSGTKYI FMVKAINQAG SRSSEPGKLK TNSQPFKLDP KSAHRKLKVS
510 520 530 540 550
HDNLTVERDE SSSKKSHTPE RFTSQGSYGV AGNVFIDSGR HYWEVVISGS
560 570 580 590 600
TWYAIGLAYK SAPKHEWIGK NSASWALCRC NNNWVVRHNS KEIPIEPAPH
610 620 630 640 650
LRRVGILLDY DNGSIAFYDA LNSIHLYTFD VAFAQPVCPT FTVWNKCLTI
660
ITGLPIPDHL DCTEQLP
Length:667
Mass (Da):75,251
Last modified:January 1, 1998 - v1
Checksum:i673C5120018BA619
GO
Isoform 2 (identifier: O15344-2) [UniParc]FASTAAdd to basket
Also known as: Beta

The sequence of this isoform differs from the canonical sequence as follows:
     553-667: Missing.

Show »
Length:552
Mass (Da):62,288
Checksum:iFD4D4C0EA5915DB2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti228T → P in AAC32999 (PubMed:9722948).Curated1
Sequence conflicti484Q → P in AAC32998 (PubMed:9722948).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_013758266C → R in GBBB1. 1 Publication1
Natural variantiVAR_025495295L → P in GBBB1. 1 PublicationCorresponds to variant dbSNP:rs104894866EnsemblClinVar.1
Natural variantiVAR_025496391 – 392LC → R in GBBB1. 1 Publication2
Natural variantiVAR_013759438Missing in GBBB1. 1 Publication1
Natural variantiVAR_013760534V → VFIDSGRHL in GBBB1. 1
Natural variantiVAR_013761536I → T in GBBB1. 1 Publication1
Natural variantiVAR_013762626L → P in GBBB1. 1 PublicationCorresponds to variant dbSNP:rs28934611EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005735553 – 667Missing in isoform 2. 2 PublicationsAdd BLAST115

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y13667 mRNA Translation: CAA74018.1
AF035360 mRNA Translation: AAB99951.1
AF041206 mRNA Translation: AAC32998.1
AF041207 mRNA Translation: AAC32999.1
AF041208 mRNA Translation: AAC33000.1
AF041209 mRNA Translation: AAC33001.1
AF041210 mRNA Translation: AAC33002.1
AF230976 mRNA Translation: AAG50191.1
AF230977 mRNA Translation: AAG50192.1
AF269101 mRNA Translation: AAG33130.1
AK315095 mRNA Translation: BAG37559.1
CH471074 Genomic DNA Translation: EAW98780.1
BC053626 mRNA Translation: AAH53626.1
CCDSiCCDS14138.1 [O15344-1]
PIRiT09482
RefSeqiNP_000372.1, NM_000381.3 [O15344-1]
NP_001092094.1, NM_001098624.2 [O15344-1]
NP_001180206.1, NM_001193277.1 [O15344-1]
NP_001180207.1, NM_001193278.1
NP_001180208.1, NM_001193279.1
NP_001180209.1, NM_001193280.1
NP_001180210.1, NM_001193281.1
NP_001334662.1, NM_001347733.1 [O15344-1]
NP_150632.1, NM_033290.3 [O15344-1]
XP_016885025.1, XM_017029536.1 [O15344-1]
XP_016885029.1, XM_017029540.1 [O15344-2]
UniGeneiHs.27695
Hs.460482
Hs.689953
Hs.738954

Genome annotation databases

EnsembliENST00000317552; ENSP00000312678; ENSG00000101871 [O15344-1]
ENST00000380779; ENSP00000370156; ENSG00000101871 [O15344-1]
ENST00000380780; ENSP00000370157; ENSG00000101871 [O15344-1]
ENST00000380782; ENSP00000370159; ENSG00000101871 [O15344-2]
ENST00000380785; ENSP00000370162; ENSG00000101871 [O15344-1]
ENST00000380787; ENSP00000370164; ENSG00000101871 [O15344-1]
ENST00000453318; ENSP00000414521; ENSG00000101871 [O15344-1]
GeneIDi4281
KEGGihsa:4281
UCSCiuc004cte.5 human [O15344-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiTRI18_HUMAN
AccessioniPrimary (citable) accession number: O15344
Secondary accession number(s): B2RCG2, O75361, Q9BZX5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 30, 2002
Last sequence update: January 1, 1998
Last modified: June 20, 2018
This is version 194 of the entry and version 1 of the sequence. See 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 X
    Human chromosome X: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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