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Protein

PDZ and LIM domain protein 4

Gene

PDLIM4

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

Functioni

Isoform 1: Suppresses SRC activation by recognizing and binding to active SRC and facilitating PTPN13-mediated dephosphorylation of SRC 'Tyr-419' leading to its inactivation. Inactivated SRC dissociates from this protein allowing the initiation of a new SRC inactivation cycle (PubMed:19307596). Involved in reorganization of the actin cytoskeleton (PubMed:21636573). In nonmuscle cells, binds to ACTN1 (alpha-actinin-1), increases the affinity of ACTN1 to F-actin (filamentous actin), and promotes formation of actin stress fibers. Involved in regulation of the synaptic AMPA receptor transport in dendritic spines of hippocampal pyramidal neurons directing the receptors toward an insertion at the postsynaptic membrane. Links endosomal surface-internalized GRIA1-containing AMPA receptors to the alpha-actinin/actin cytoskeleton. Increases AMPA receptor-mediated excitatory postsynaptic currents in neurons (By similarity).By similarity2 Publications
Isoform 2: Involved in reorganization of the actin cytoskeleton and in regulation of cell migration. In response to oxidative stress, binds to NQO1, which stabilizes it and protects it from ubiquitin-independent degradation by the core 20S proteasome. Stabilized protein is able to heterodimerize with isoform 1 changing the subcellular location of it from cytoskeleton and nuclei to cytosol, leading to loss of isoforms 1 ability to induce formation of actin stress fibers. Counteracts the effects produced by isoform 1 on organization of actin cytoskeleton and cell motility to fine-tune actin cytoskeleton rearrangement and to attenuate cell migration.1 Publication

GO - Molecular functioni

  • alpha-actinin binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • protein homodimerization activity Source: UniProtKB
  • protein phosphatase binding Source: UniProtKB

GO - Biological processi

Keywordsi

LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
PDZ and LIM domain protein 4
Alternative name(s):
LIM protein RIL
Reversion-induced LIM protein
Gene namesi
Name:PDLIM4
Synonyms:RIL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000131435.12.
HGNCiHGNC:16501. PDLIM4.

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

Cell junction, Cell projection, Cytoplasm, Cytoskeleton, Endosome, Membrane, Nucleus, Synapse, Synaptosome

Pathology & Biotechi

Organism-specific databases

DisGeNETi8572.
MalaCardsiPDLIM4.
OpenTargetsiENSG00000131435.
PharmGKBiPA134869796.

Polymorphism and mutation databases

BioMutaiPDLIM4.
DMDMi20141642.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000758731 – 330PDZ and LIM domain protein 4Add BLAST330

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei112PhosphoserineCombined sources1
Modified residuei116PhosphoserineBy similarity1
Modified residuei120PhosphoserineBy similarity1
Modified residuei135PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on tyrosine residue(s). Can be dephosphorylated by PTPN13.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP50479.
MaxQBiP50479.
PaxDbiP50479.
PeptideAtlasiP50479.
PRIDEiP50479.

PTM databases

iPTMnetiP50479.
PhosphoSitePlusiP50479.

Expressioni

Tissue specificityi

Isoform 2 is found in brain.1 Publication

Inductioni

Isoform 2 expression is up-regulated by UV irradiation and to a lesser extent by oxidative stress.1 Publication

Gene expression databases

BgeeiENSG00000131435.
CleanExiHS_PDLIM4.
ExpressionAtlasiP50479. baseline and differential.
GenevisibleiP50479. HS.

Organism-specific databases

HPAiHPA011912.

Interactioni

Subunit structurei

Homodimer (PubMed:25158098). Interacts with PTPN13 (PubMed:19307596). Interacts (via C-terminus only or via combined C-terminus and LIM domain, but not LIM domain only) with PTPN13 (via the second or fourth PDZ domains). Found in a complex with PTPN13 and TRIP6 (By similarity). Interacts (via PDZ domain) with ACTN1 and ACTN2 (via C-terminal SDL residues) (By similarity). Interacts (via PDZ domain) with TRIP6 (via the second LIM domain or via the third LIM domain plus C-terminus) (PubMed:10826496). Interacts (via LIM domain) with GRIA1 (via C-terminus); this interaction as well as the interaction with alpha-actinin is required for their colocalization in early endosomes. Interacts with PDLIM1 (By similarity). Forms (via LIM domain) a heterodimer with PDLIM3 (By similarity). Interacts directly with SRC (via kinase domain and to a lesser extent the SH2 domain) (PubMed:19307596). Isoform 2 interacts with NQO1. NQO1-stabilized isoform 2 heterodimerizes with isoform 1 (PubMed:21636573).By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AMTP48728-44EBI-372861,EBI-14394829

GO - Molecular functioni

  • alpha-actinin binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein phosphatase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114140. 4 interactors.
IntActiP50479. 15 interactors.
MINTiMINT-1437771.
STRINGi9606.ENSP00000253754.

Structurei

Secondary structure

1330
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 11Combined sources9
Beta strandi15 – 20Combined sources6
Helixi21 – 23Combined sources3
Beta strandi25 – 32Combined sources8
Beta strandi34 – 36Combined sources3
Helixi37 – 40Combined sources4
Beta strandi48 – 52Combined sources5
Turni57 – 59Combined sources3
Helixi62 – 70Combined sources9
Beta strandi74 – 81Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EEGNMR-A1-81[»]
2V1WX-ray1.90A/B1-85[»]
4Q2OX-ray2.10A/B/C/D/E/F1-84[»]
ProteinModelPortaliP50479.
SMRiP50479.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP50479.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 84PDZPROSITE-ProRule annotationCombined sources1 PublicationAdd BLAST84
Domaini253 – 312LIM zinc-bindingPROSITE-ProRule annotationAdd BLAST60

Keywords - Domaini

LIM domain

Phylogenomic databases

eggNOGiKOG1703. Eukaryota.
ENOG410XRD4. LUCA.
GeneTreeiENSGT00590000082980.
HOGENOMiHOG000290704.
HOVERGENiHBG061371.
InParanoidiP50479.
OMAiHIDPEAQ.
OrthoDBiEOG091G0A6C.
PhylomeDBiP50479.
TreeFamiTF106408.

Family and domain databases

InterProiView protein in InterPro
IPR031847. DUF4749.
IPR001478. PDZ.
IPR036034. PDZ_sf.
IPR001781. Znf_LIM.
PfamiView protein in Pfam
PF15936. DUF4749. 1 hit.
PF00412. LIM. 1 hit.
PF00595. PDZ. 1 hit.
SMARTiView protein in SMART
SM00132. LIM. 1 hit.
SM00228. PDZ. 1 hit.
SUPFAMiSSF50156. SSF50156. 1 hit.
PROSITEiView protein in PROSITE
PS00478. LIM_DOMAIN_1. 1 hit.
PS50023. LIM_DOMAIN_2. 1 hit.
PS50106. PDZ. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: P50479-1) [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
MPHSVTLRGP SPWGFRLVGG RDFSAPLTIS RVHAGSKAAL AALCPGDLIQ
60 70 80 90 100
AINGESTELM THLEAQNRIK GCHDHLTLSV SRPEGRSWPS APDDSKAQAH
110 120 130 140 150
RIHIDPEIQD GSPTTSRRPS GTGTGPEDGR PSLGSPYGQP PRFPVPHNGS
160 170 180 190 200
SEATLPAQMS TLHVSPPPSA DPARGLPRSR DCRVDLGSEV YRMLREPAEP
210 220 230 240 250
VAAEPKQSGS FRYLQGMLEA GEGGDWPGPG GPRNLKPTAS KLGAPLSGLQ
260 270 280 290 300
GLPECTRCGH GIVGTIVKAR DKLYHPECFM CSDCGLNLKQ RGYFFLDERL
310 320 330
YCESHAKARV KPPEGYDVVA VYPNAKVELV
Length:330
Mass (Da):35,398
Last modified:January 23, 2002 - v2
Checksum:i68FCA8FD93700E7B
GO
Isoform 2 (identifier: P50479-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     225-330: DWPGPGGPRN...VYPNAKVELV → APSSRHGTSSTIPSASCAVTAA

Show »
Length:246
Mass (Da):25,854
Checksum:i202F54C12328320E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti20Missing in CAA63767 (Ref. 1) Curated1
Sequence conflicti39A → S in CAA63767 (Ref. 1) Curated1
Sequence conflicti139Q → K in CAA63767 (Ref. 1) Curated1
Sequence conflicti174 – 182RGLPRSRDC → EASRGAGS in CAA63767 (Ref. 1) Curated9
Sequence conflicti269A → E in CAA63767 (Ref. 1) Curated1

Polymorphismi

Genetic variations in PDLIM4 may be correlated with bone mineral density (BMD). Low BMD is a risk factor for osteoporotic fracture. Osteoporosis is characterized by reduced bone mineral density, disruption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035205118R → G1 PublicationCorresponds to variant dbSNP:rs17851430Ensembl.1
Natural variantiVAR_050167142R → C1 PublicationCorresponds to variant dbSNP:rs1050805Ensembl.1
Natural variantiVAR_035206184V → I. Corresponds to variant dbSNP:rs175218Ensembl.1
Natural variantiVAR_035207259G → C1 PublicationCorresponds to variant dbSNP:rs4877Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003124225 – 330DWPGP…KVELV → APSSRHGTSSTIPSASCAVT AA in isoform 2. 2 PublicationsAdd BLAST106

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X93510 mRNA. Translation: CAA63767.1.
AF153882 mRNA. Translation: AAD38070.1.
AF154335 mRNA. Translation: AAD34646.1.
U82997 Genomic DNA. Translation: AAC52072.1.
AK313508 mRNA. Translation: BAG36288.1.
BT007019 mRNA. Translation: AAP35665.1.
CH471062 Genomic DNA. Translation: EAW62349.1.
CH471062 Genomic DNA. Translation: EAW62351.1.
BC003096 mRNA. Translation: AAH03096.1.
BC016765 mRNA. Translation: AAH16765.1.
CCDSiCCDS4152.1. [P50479-1]
CCDS47261.1. [P50479-2]
RefSeqiNP_001124499.1. NM_001131027.1. [P50479-2]
NP_003678.2. NM_003687.3. [P50479-1]
UniGeneiHs.424312.

Genome annotation databases

EnsembliENST00000253754; ENSP00000253754; ENSG00000131435. [P50479-1]
ENST00000379018; ENSP00000368303; ENSG00000131435. [P50479-2]
GeneIDi8572.
KEGGihsa:8572.
UCSCiuc003kwn.4. human. [P50479-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPDLI4_HUMAN
AccessioniPrimary (citable) accession number: P50479
Secondary accession number(s): B2R8U1
, Q53Y39, Q96AT8, Q9BTW8, Q9Y292
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2002
Last modified: November 22, 2017
This is version 156 of the entry and version 2 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 5
    Human chromosome 5: 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