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Protein

Protein lin-28 homolog A

Gene

Lin28a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

RNA-binding protein that inhibits processing of pre-let-7 miRNAs and regulates translation of mRNAs that control developmental timing, pluripotency and metabolism (PubMed:17473174, PubMed:18604195, PubMed:18566191, PubMed:18292307, PubMed:19703396, PubMed:23102813, PubMed:24209617). Seems to recognize a common structural G-quartet (G4) feature in its miRNA and mRNA targets (PubMed:26045559). 'Translational enhancer' that drives specific mRNAs to polysomes and increases the efficiency of protein synthesis. Its association with the translational machinery and target mRNAs results in an increased number of initiation events per molecule of mRNA and, indirectly, in mRNA stabilization. Binds IGF2 mRNA, MYOD1 mRNA, ARBP/36B4 ribosomal protein mRNA and its own mRNA. Essential for skeletal muscle differentiation program through the translational up-regulation of IGF2 expression (PubMed:17473174). Suppressor of microRNA (miRNA) biogenesis, including that of let-7, miR107, miR-143 and miR-200c. Specifically binds the miRNA precursors (pre-miRNAs), recognizing an 5'-GGAG-3' motif found in pre-miRNA terminal loop, and recruits ZCCHC11/TUT4 uridylyltransferase. This results in the terminal uridylation of target pre-miRNAs. Uridylated pre-miRNAs fail to be processed by Dicer and undergo degradation. The repression of let-7 expression is required for normal development and contributes to maintain the pluripotent state by preventing let-7-mediated differentiation of embryonic stem cells (PubMed:19703396). Localized to the periendoplasmic reticulum area, binds to a large number of spliced mRNAs and inhibits the translation of mRNAs destined for the ER, reducing the synthesis of transmembrane proteins, ER or Golgi lumen proteins, and secretory proteins (PubMed:23102813). Binds to and enhances the translation of mRNAs for several metabolic enzymes, such as PFKP, PDHA1 or SDHA, increasing glycolysis and oxidative phosphorylation. Which, with the let-7 repression may enhance tissue repair in adult tissue (PubMed:24209617).8 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri137 – 154CCHC-type 1PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri159 – 176CCHC-type 2PROSITE-ProRule annotationAdd BLAST18

GO - Molecular functioni

  • DNA binding Source: InterPro
  • G-quadruplex RNA binding Source: UniProtKB
  • miRNA binding Source: UniProtKB
  • mRNA binding Source: MGI
  • RNA binding Source: UniProtKB
  • sequence-specific mRNA binding Source: UniProtKB
  • translation initiation factor binding Source: MGI
  • zinc ion binding Source: InterPro

GO - Biological processi

  • germ cell development Source: MGI
  • miRNA catabolic process Source: UniProtKB
  • miRNA metabolic process Source: MGI
  • negative regulation of glial cell differentiation Source: MGI
  • negative regulation of translation Source: UniProtKB
  • positive regulation of cell proliferation involved in kidney development Source: BHF-UCL
  • positive regulation of neuron differentiation Source: MGI
  • positive regulation of translation Source: MGI
  • pre-miRNA processing Source: UniProtKB
  • regulation of gene silencing by miRNA Source: MGI
  • regulation of transcription, DNA-templated Source: InterPro
  • RNA 3'-end processing Source: MGI
  • stem cell differentiation Source: UniProtKB
  • stem cell population maintenance Source: MGI
Complete GO annotation...

Keywords - Biological processi

RNA-mediated gene silencing

Keywords - Ligandi

Metal-binding, RNA-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-452723. Transcriptional regulation of pluripotent stem cells.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein lin-28 homolog A
Short name:
Lin-28A
Alternative name(s):
Testis-expressed protein 17
Gene namesi
Name:Lin28a
Synonyms:Lin28, Tex17
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1890546. Lin28a.

Subcellular locationi

  • Cytoplasm By similarity
  • Rough endoplasmic reticulum 1 Publication
  • Nucleusnucleolus

  • Note: Predominantly cytoplasmic. Shuttles between the cytoplasm and the nucleus. Localizes to cytoplasmic processing bodies and stress granules (By similarity). Nucleolar localization observed in 10-15% of the nuclei in differentiated myotubes.By similarity

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytoplasmic mRNA processing body Source: UniProtKB
  • cytoplasmic stress granule Source: UniProtKB
  • nucleolus Source: MGI
  • nucleus Source: UniProtKB
  • rough endoplasmic reticulum Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi42G → S: Erroneous subcellular location. No positive effect on terminal myogenic differentiation. 1 Publication1
Mutagenesisi44 – 47Missing : Erroneous subcellular location. No positive effect on terminal myogenic differentiation. 1 Publication4
Mutagenesisi81M → I: Erroneous subcellular location; when associated with Q-85. No positive effect on terminal myogenic differentiation; when associated with Q-85. 1 Publication1
Mutagenesisi85R → Q: Erroneous subcellular location; when associated with I-81. No positive effect on terminal myogenic differentiation; when associated with I-81. 1 Publication1
Mutagenesisi119G → R: Erroneous subcellular location; when associated with S-124. No positive effect on terminal myogenic differentiation; when associated with S-124. 1 Publication1
Mutagenesisi124P → S: Erroneous subcellular location; when associated with R-119. No positive effect on terminal myogenic differentiation; when associated with R-119. 1 Publication1
Mutagenesisi138 – 139Missing : No effect on subcellular location; when associated with S-142. Normal terminal myogenic differentiation; when associated with S-142. 1 Publication2
Mutagenesisi142C → S: No effect on subcellular location; when associated with 44-C--F-47. Normal terminal myogenic differentiation; when associated with 44-C--F-47. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002537882 – 209Protein lin-28 homolog AAdd BLAST208

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylglycineBy similarity1
Modified residuei3PhosphoserineBy similarity1
Modified residuei120PhosphoserineBy similarity1
Modified residuei200PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ8K3Y3.
PaxDbiQ8K3Y3.
PeptideAtlasiQ8K3Y3.
PRIDEiQ8K3Y3.

PTM databases

iPTMnetiQ8K3Y3.
PhosphoSitePlusiQ8K3Y3.

Expressioni

Tissue specificityi

Expressed in embryonic stem cells (ES cells), spermatagonia and testis. Expressed in numerous epithelial tissues including the epithelia of the small intestine, the intralobular duct epithelium of the mammary gland and the epithelia of Henle's loop in the kidney and in the collecting duct (at protein level). Also expressed in the myocardium and skeletal muscle (at protein level).4 Publications

Developmental stagei

Strongly expressed throughout the whole embryo at 6.5 dpc, including the embryonic and extraembryonic ectoderm and endoderm (at protein level). Subsequently expressed in the ectoderm, endoderm and mesoderm at 7.5 dpc (at protein level). At 9.5 dpc, expressed in epithelia covering the first branchial arch and the coelomic cavity, the myocardium of the developing heart, the neuroepithelium and some extraembryonic tissues such as the visceral yolk sac (at protein level). Expression persists in a variety of epithelial tissues at 10.5 dpc. At 15.5 dpc, expression is lost in bronchial epithelium and becomes weaker in neuroepithelium, while increasing in the myotome of somites, the foregut epithelium, stratified epithelium and some kidney tubules (at protein level). At 17.5 dpc, expression persists in the myocardium and in the epithelium covering the body surface and skeletal muscles (at protein level). Expression is reduced during differentiation of ES cells. In adult primary myoblasts, barely detectable during proliferation, but dramatically up-regulated during terminal differentiation. Induced as early as 24 hours after differentiation signal and remains high as late as 7 days of differentiation. Little expression in resting muscle, but strongly up-regulated during regeneration of skeletal muscle fibers. Expression decreases when regeneration is histologically and functionally complete.4 Publications

Inductioni

Negatively regulated by the microRNA miR-125b in response to retinoic acid.2 Publications

Gene expression databases

BgeeiENSMUSG00000050966.
CleanExiMM_LIN28.
ExpressionAtlasiQ8K3Y3. baseline and differential.
GenevisibleiQ8K3Y3. MM.

Interactioni

Subunit structurei

Monomer. During skeletal muscle differentiation, associated with translation initiation complexes in the polysomal compartment. Directly interacts with EIF3S2. Interacts with NCL in an RNA-dependent manner. Interacts with ZCCHC11/TUT4 in the presence of pre-let-7 RNA.By similarity2 Publications

GO - Molecular functioni

  • translation initiation factor binding Source: MGI

Protein-protein interaction databases

BioGridi219943. 7 interactors.
DIPiDIP-48573N.
IntActiQ8K3Y3. 3 interactors.
STRINGi10090.ENSMUSP00000050488.

Structurei

Secondary structure

1209
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi38 – 48Combined sources11
Turni49 – 52Combined sources4
Beta strandi53 – 61Combined sources9
Beta strandi64 – 75Combined sources12
Helixi76 – 78Combined sources3
Beta strandi81 – 84Combined sources4
Beta strandi92 – 100Combined sources9
Beta strandi103 – 111Combined sources9
Helixi112 – 114Combined sources3
Turni124 – 126Combined sources3
Turni140 – 142Combined sources3
Helixi149 – 151Combined sources3
Turni162 – 164Combined sources3
Helixi171 – 173Combined sources3
Turni175 – 178Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3TRZX-ray2.90A/B/C/D/E/F31-187[»]
3TS0X-ray2.76A/B33-187[»]
3TS2X-ray2.01A/B31-187[»]
ProteinModelPortaliQ8K3Y3.
SMRiQ8K3Y3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini39 – 112CSDAdd BLAST74

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni113 – 136Flexible linkerAdd BLAST24

Domaini

The CSD domain is required for function in muscle differentiation.1 Publication
The CCHC zinc fingers interact with the GGAG motif at the 3' end of let-7 miRNAs precursors, more generally they bind the 5'-NGNNG-3' consensus motif with micromolar affinity. The CSD domain recognizes the loop at the 5' end. The flexible linker allows accommodating variable sequences and lengths among let-7 family members.1 Publication

Sequence similaritiesi

Belongs to the lin-28 family.Curated
Contains 2 CCHC-type zinc fingers.PROSITE-ProRule annotation
Contains 1 CSD (cold-shock) domain.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri137 – 154CCHC-type 1PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri159 – 176CCHC-type 2PROSITE-ProRule annotationAdd BLAST18

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG3070. Eukaryota.
COG1278. LUCA.
GeneTreeiENSGT00860000133704.
HOGENOMiHOG000047091.
HOVERGENiHBG081922.
InParanoidiQ8K3Y3.
KOiK18754.
OMAiSGICKWF.
OrthoDBiEOG091G0RTY.
PhylomeDBiQ8K3Y3.
TreeFamiTF316240.

Family and domain databases

CDDicd04458. CSP_CDS. 1 hit.
Gene3Di4.10.60.10. 1 hit.
InterProiIPR011129. Cold_shock_prot.
IPR002059. CSP_DNA-bd.
IPR012340. NA-bd_OB-fold.
IPR001878. Znf_CCHC.
[Graphical view]
PfamiPF00313. CSD. 1 hit.
PF00098. zf-CCHC. 1 hit.
[Graphical view]
PRINTSiPR00050. COLDSHOCK.
SMARTiSM00357. CSP. 1 hit.
SM00343. ZnF_C2HC. 2 hits.
[Graphical view]
SUPFAMiSSF50249. SSF50249. 1 hit.
SSF57756. SSF57756. 1 hit.
PROSITEiPS50158. ZF_CCHC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q8K3Y3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSVSNQQFA GGCAKAAEKA PEEAPPDAAR AADEPQLLHG AGICKWFNVR
60 70 80 90 100
MGFGFLSMTA RAGVALDPPV DVFVHQSKLH MEGFRSLKEG EAVEFTFKKS
110 120 130 140 150
AKGLESIRVT GPGGVFCIGS ERRPKGKNMQ KRRSKGDRCY NCGGLDHHAK
160 170 180 190 200
ECKLPPQPKK CHFCQSINHM VASCPLKAQQ GPSSQGKPAY FREEEEEIHS

PALLPEAQN
Length:209
Mass (Da):22,720
Last modified:October 1, 2002 - v1
Checksum:i4BD14DCAF13CD659
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti194E → D in AAH68304 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF521097 mRNA. Translation: AAM77749.1.
BC068304 mRNA. Translation: AAH68304.1.
CCDSiCCDS18761.1.
RefSeqiNP_665832.1. NM_145833.1.
UniGeneiMm.302567.

Genome annotation databases

EnsembliENSMUST00000051674; ENSMUSP00000050488; ENSMUSG00000050966.
GeneIDi83557.
KEGGimmu:83557.
UCSCiuc008vdw.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF521097 mRNA. Translation: AAM77749.1.
BC068304 mRNA. Translation: AAH68304.1.
CCDSiCCDS18761.1.
RefSeqiNP_665832.1. NM_145833.1.
UniGeneiMm.302567.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3TRZX-ray2.90A/B/C/D/E/F31-187[»]
3TS0X-ray2.76A/B33-187[»]
3TS2X-ray2.01A/B31-187[»]
ProteinModelPortaliQ8K3Y3.
SMRiQ8K3Y3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi219943. 7 interactors.
DIPiDIP-48573N.
IntActiQ8K3Y3. 3 interactors.
STRINGi10090.ENSMUSP00000050488.

PTM databases

iPTMnetiQ8K3Y3.
PhosphoSitePlusiQ8K3Y3.

Proteomic databases

MaxQBiQ8K3Y3.
PaxDbiQ8K3Y3.
PeptideAtlasiQ8K3Y3.
PRIDEiQ8K3Y3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000051674; ENSMUSP00000050488; ENSMUSG00000050966.
GeneIDi83557.
KEGGimmu:83557.
UCSCiuc008vdw.1. mouse.

Organism-specific databases

CTDi79727.
MGIiMGI:1890546. Lin28a.

Phylogenomic databases

eggNOGiKOG3070. Eukaryota.
COG1278. LUCA.
GeneTreeiENSGT00860000133704.
HOGENOMiHOG000047091.
HOVERGENiHBG081922.
InParanoidiQ8K3Y3.
KOiK18754.
OMAiSGICKWF.
OrthoDBiEOG091G0RTY.
PhylomeDBiQ8K3Y3.
TreeFamiTF316240.

Enzyme and pathway databases

ReactomeiR-MMU-452723. Transcriptional regulation of pluripotent stem cells.

Miscellaneous databases

PROiQ8K3Y3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000050966.
CleanExiMM_LIN28.
ExpressionAtlasiQ8K3Y3. baseline and differential.
GenevisibleiQ8K3Y3. MM.

Family and domain databases

CDDicd04458. CSP_CDS. 1 hit.
Gene3Di4.10.60.10. 1 hit.
InterProiIPR011129. Cold_shock_prot.
IPR002059. CSP_DNA-bd.
IPR012340. NA-bd_OB-fold.
IPR001878. Znf_CCHC.
[Graphical view]
PfamiPF00313. CSD. 1 hit.
PF00098. zf-CCHC. 1 hit.
[Graphical view]
PRINTSiPR00050. COLDSHOCK.
SMARTiSM00357. CSP. 1 hit.
SM00343. ZnF_C2HC. 2 hits.
[Graphical view]
SUPFAMiSSF50249. SSF50249. 1 hit.
SSF57756. SSF57756. 1 hit.
PROSITEiPS50158. ZF_CCHC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLN28A_MOUSE
AccessioniPrimary (citable) accession number: Q8K3Y3
Secondary accession number(s): Q6NV62
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: October 1, 2002
Last modified: November 30, 2016
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Reactivation of LIN28A expression enhances tissue repair in some adult tissues by reprogramming cellular bioenergetics. Improves hair regrowth by promoting anagen in hair follicle and accelerates regrowth of cartilage, bone and mesenchyme after ear and digit injuries.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.