Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Protein lin-28 homolog A

Gene

Lin28a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 TUT4 and TUT7 uridylyltransferaseS. 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, PubMed:28671666). 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).9 Publications

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

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

GO - Biological processi

Keywordsi

Molecular functionRNA-binding
Biological processRNA-mediated gene silencing
LigandMetal-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1890546 Lin28a

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, 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
Mutagenesisi139 – 142CYNC → AYNA: Disrupts 5'-GGAG-3' motif interaction. Disrupts oligoU-addition to pre-miRNA pre-let-7 by TUT4. 1 Publication4
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
Mutagenesisi161 – 164CHFC → AHFA: Disrupts 5'-GGAG-3' motif interaction. Binds miRNA but not TUT4. 1 Publication4

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 Expressed in 77 organ(s), highest expression level in epiblast (generic)
CleanExiMM_LIN28
ExpressionAtlasiQ8K3Y3 baseline and differential
GenevisibleiQ8K3Y3 MM

Interactioni

Subunit structurei

Monomer (PubMed:22078496). During skeletal muscle differentiation, associated with translation initiation complexes in the polysomal compartment (By similarity). Directly interacts with EIF3S2 (PubMed:17473174). Interacts with NCL in an RNA-dependent manner (By similarity). Interacts with TUT4 in the presence of pre-let-7 RNA (PubMed:28671666).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Dis3l2Q8CI752EBI-11109197,EBI-16045218

GO - Molecular functioni

Protein-protein interaction databases

BioGridi219943, 8 interactors
DIPiDIP-48573N
IntActiQ8K3Y3, 17 interactors
STRINGi10090.ENSMUSP00000050488

Structurei

Secondary structure

1209
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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.2 Publications

Sequence similaritiesi

Belongs to the lin-28 family.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
GeneTreeiENSGT00930000150863
HOGENOMiHOG000047091
HOVERGENiHBG081922
InParanoidiQ8K3Y3
KOiK18754
OMAiCPERRRK
OrthoDBiEOG091G0RTY
PhylomeDBiQ8K3Y3
TreeFamiTF316240

Family and domain databases

CDDicd04458 CSP_CDS, 1 hit
InterProiView protein in InterPro
IPR011129 CSD
IPR002059 CSP_DNA-bd
IPR012340 NA-bd_OB-fold
IPR001878 Znf_CCHC
IPR036875 Znf_CCHC_sf
PfamiView protein in Pfam
PF00313 CSD, 1 hit
PF00098 zf-CCHC, 1 hit
PRINTSiPR00050 COLDSHOCK
SMARTiView protein in SMART
SM00357 CSP, 1 hit
SM00343 ZnF_C2HC, 2 hits
SUPFAMiSSF50249 SSF50249, 1 hit
SSF57756 SSF57756, 1 hit
PROSITEiView protein in PROSITE
PS51857 CSD_2, 1 hit
PS50158 ZF_CCHC, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BK51H3BK51_MOUSE
Protein lin-28 homolog A
Lin28a
83Annotation score:
H3BL11H3BL11_MOUSE
Protein lin-28 homolog A
Lin28a
81Annotation score:
H3BLC6H3BLC6_MOUSE
Protein lin-28 homolog A
Lin28a
75Annotation score:

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

Similar proteinsi

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, 8 interactors
DIPiDIP-48573N
IntActiQ8K3Y3, 17 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
GeneTreeiENSGT00930000150863
HOGENOMiHOG000047091
HOVERGENiHBG081922
InParanoidiQ8K3Y3
KOiK18754
OMAiCPERRRK
OrthoDBiEOG091G0RTY
PhylomeDBiQ8K3Y3
TreeFamiTF316240

Enzyme and pathway databases

ReactomeiR-MMU-452723 Transcriptional regulation of pluripotent stem cells

Miscellaneous databases

PROiPR:Q8K3Y3
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000050966 Expressed in 77 organ(s), highest expression level in epiblast (generic)
CleanExiMM_LIN28
ExpressionAtlasiQ8K3Y3 baseline and differential
GenevisibleiQ8K3Y3 MM

Family and domain databases

CDDicd04458 CSP_CDS, 1 hit
InterProiView protein in InterPro
IPR011129 CSD
IPR002059 CSP_DNA-bd
IPR012340 NA-bd_OB-fold
IPR001878 Znf_CCHC
IPR036875 Znf_CCHC_sf
PfamiView protein in Pfam
PF00313 CSD, 1 hit
PF00098 zf-CCHC, 1 hit
PRINTSiPR00050 COLDSHOCK
SMARTiView protein in SMART
SM00357 CSP, 1 hit
SM00343 ZnF_C2HC, 2 hits
SUPFAMiSSF50249 SSF50249, 1 hit
SSF57756 SSF57756, 1 hit
PROSITEiView protein in PROSITE
PS51857 CSD_2, 1 hit
PS50158 ZF_CCHC, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiLN28A_MOUSE
AccessioniPrimary (citable) accession number: Q8K3Y3
Secondary accession number(s): Q6NV62
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: October 1, 2002
Last modified: November 7, 2018
This is version 135 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again