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Protein

Protein lin-28 homolog A

Gene

LIN28A

Organism
Homo sapiens (Human)
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. Seems to recognize a common structural G-quartet (G4) feature in its miRNA and mRNA targets (Probable). '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. 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:18951094, PubMed:19703396, PubMed:22118463, PubMed:22898984). 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. 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 (By similarity).By similarityCurated4 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

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

RNA-mediated gene silencing

Keywords - Ligandi

Metal-binding, RNA-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000131914-MONOMER.
ReactomeiR-HSA-452723. Transcriptional regulation of pluripotent stem cells.
SignaLinkiQ9H9Z2.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein lin-28 homolog A
Short name:
Lin-28A
Alternative name(s):
Zinc finger CCHC domain-containing protein 1
Gene namesi
Name:LIN28A
Synonyms:CSDD1, LIN28, ZCCHC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:15986. LIN28A.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytoplasmic mRNA processing body Source: UniProtKB
  • cytoplasmic stress granule Source: UniProtKB
  • cytosol Source: Reactome
  • nucleolus Source: UniProtKB-SubCell
  • 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
Mutagenesisi46W → A: Does not affect localization to cytoplasmic processing bodies; when associated with A-55 and A-73. 1 Publication1
Mutagenesisi55F → A: Does not affect localization to cytoplasmic processing bodies; when associated with A-46 and A-73. 1 Publication1
Mutagenesisi73F → A: Does not affect localization to cytoplasmic processing bodies; when associated with A-46 and A-55. 1 Publication1
Mutagenesisi147H → A: Abolishes ability to suppress pre-let-7 biogenesis and localization to cytoplasmic processing bodies without affecting pre-let-7 binding; when associated with A-169. 2 Publications1
Mutagenesisi169H → A: Abolishes ability to suppress pre-let-7 biogenesis and localization to cytoplasmic processing bodies without affecting pre-let-7 binding; when associated with A-147. 2 Publications1

Organism-specific databases

DisGeNETi79727.
OpenTargetsiENSG00000131914.
PharmGKBiPA165751523.

Polymorphism and mutation databases

BioMutaiLIN28A.
DMDMi74752750.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002537872 – 209Protein lin-28 homolog AAdd BLAST208

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylglycineCombined sources1
Modified residuei3PhosphoserineCombined sources1
Modified residuei120PhosphoserineCombined sources1
Modified residuei200PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9H9Z2.
PaxDbiQ9H9Z2.
PeptideAtlasiQ9H9Z2.
PRIDEiQ9H9Z2.

PTM databases

iPTMnetiQ9H9Z2.
PhosphoSitePlusiQ9H9Z2.

Expressioni

Tissue specificityi

Expressed in embryonic stem cells, placenta and testis. Tends to be up-regulated in HER2-overexpressing breast tumors.4 Publications

Developmental stagei

Expressed in fetal liver. Expression decreases during differentiation of ES cells or upon induction of neuronal differentiation by retinoic acid.3 Publications

Inductioni

Can be negatively regulated by the interaction of microRNAs miR-125a and miR-125b with at least two miRNA responsive elements (miREs) in the 3'-UTR of this gene. These interactions may reduce both translation efficiency and mRNA abundance. Negatively regulated by retinoic acid.2 Publications

Gene expression databases

BgeeiENSG00000131914.
CleanExiHS_LIN28.
GenevisibleiQ9H9Z2. HS.

Organism-specific databases

HPAiCAB020785.

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 (By similarity). Interacts with ZCCHC11/TUT4 in the presence of pre-let-7 RNA.By similarity3 Publications

Protein-protein interaction databases

BioGridi122842. 89 interactors.
IntActiQ9H9Z2. 2 interactors.
STRINGi9606.ENSP00000254231.

Structurei

Secondary structure

1209
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi140 – 142Combined sources3
Beta strandi145 – 147Combined sources3
Turni149 – 151Combined sources3
Turni162 – 164Combined sources3
Beta strandi167 – 169Combined sources3
Turni171 – 173Combined sources3
Helixi176 – 178Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CQFNMR-A137-186[»]
2LI8NMR-A124-186[»]
ProteinModelPortaliQ9H9Z2.
SMRiQ9H9Z2.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H9Z2.

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.By similarity
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.

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.
InParanoidiQ9H9Z2.
KOiK18754.
OMAiSGICKWF.
OrthoDBiEOG091G0RTY.
PhylomeDBiQ9H9Z2.
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.

Q9H9Z2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSVSNQQFA GGCAKAAEEA PEEAPEDAAR AADEPQLLHG AGICKWFNVR
60 70 80 90 100
MGFGFLSMTA RAGVALDPPV DVFVHQSKLH MEGFRSLKEG EAVEFTFKKS
110 120 130 140 150
AKGLESIRVT GPGGVFCIGS ERRPKGKSMQ KRRSKGDRCY NCGGLDHHAK
160 170 180 190 200
ECKLPPQPKK CHFCQSISHM VASCPLKAQQ GPSAQGKPTY FREEEEEIHS

PTLLPEAQN
Length:209
Mass (Da):22,743
Last modified:March 1, 2001 - v1
Checksum:iFA5EF6DD33FABF54
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF521099 mRNA. Translation: AAM77751.1.
AK022519 mRNA. Translation: BAB14075.1.
AL513365 Genomic DNA. Translation: CAI21500.1.
BC028566 mRNA. Translation: AAH28566.1.
CCDSiCCDS280.1.
RefSeqiNP_078950.1. NM_024674.5.
XP_011540450.1. XM_011542148.1.
UniGeneiHs.86154.

Genome annotation databases

EnsembliENST00000254231; ENSP00000254231; ENSG00000131914.
ENST00000326279; ENSP00000363314; ENSG00000131914.
GeneIDi79727.
KEGGihsa:79727.
UCSCiuc001bmj.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF521099 mRNA. Translation: AAM77751.1.
AK022519 mRNA. Translation: BAB14075.1.
AL513365 Genomic DNA. Translation: CAI21500.1.
BC028566 mRNA. Translation: AAH28566.1.
CCDSiCCDS280.1.
RefSeqiNP_078950.1. NM_024674.5.
XP_011540450.1. XM_011542148.1.
UniGeneiHs.86154.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CQFNMR-A137-186[»]
2LI8NMR-A124-186[»]
ProteinModelPortaliQ9H9Z2.
SMRiQ9H9Z2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122842. 89 interactors.
IntActiQ9H9Z2. 2 interactors.
STRINGi9606.ENSP00000254231.

PTM databases

iPTMnetiQ9H9Z2.
PhosphoSitePlusiQ9H9Z2.

Polymorphism and mutation databases

BioMutaiLIN28A.
DMDMi74752750.

Proteomic databases

EPDiQ9H9Z2.
PaxDbiQ9H9Z2.
PeptideAtlasiQ9H9Z2.
PRIDEiQ9H9Z2.

Protocols and materials databases

DNASUi79727.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000254231; ENSP00000254231; ENSG00000131914.
ENST00000326279; ENSP00000363314; ENSG00000131914.
GeneIDi79727.
KEGGihsa:79727.
UCSCiuc001bmj.4. human.

Organism-specific databases

CTDi79727.
DisGeNETi79727.
GeneCardsiLIN28A.
HGNCiHGNC:15986. LIN28A.
HPAiCAB020785.
MIMi611043. gene.
neXtProtiNX_Q9H9Z2.
OpenTargetsiENSG00000131914.
PharmGKBiPA165751523.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3070. Eukaryota.
COG1278. LUCA.
GeneTreeiENSGT00860000133704.
HOGENOMiHOG000047091.
HOVERGENiHBG081922.
InParanoidiQ9H9Z2.
KOiK18754.
OMAiSGICKWF.
OrthoDBiEOG091G0RTY.
PhylomeDBiQ9H9Z2.
TreeFamiTF316240.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000131914-MONOMER.
ReactomeiR-HSA-452723. Transcriptional regulation of pluripotent stem cells.
SignaLinkiQ9H9Z2.

Miscellaneous databases

EvolutionaryTraceiQ9H9Z2.
GeneWikiiLIN28.
GenomeRNAii79727.
PROiQ9H9Z2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000131914.
CleanExiHS_LIN28.
GenevisibleiQ9H9Z2. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q9H9Z2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: March 1, 2001
Last modified: November 30, 2016
This is version 141 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

Miscellaneous

Overexpressed in primary tumors (overall frequency approximately 15%), overexpression being linked to repression of let-7 family miRNAs and derepression of let-7 targets. Facilitates cellular transformation in vitro, and overexpression is associated with advanced disease across multiple tumor types.
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.By similarity

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.