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Protein

Low-density lipoprotein receptor class A domain-containing protein 4

Gene

LDLRAD4

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

Functioni

Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression. In the canonical TGF-beta pathway, ZFYVE9/SARA recruits the intracellular signal transducer and transcriptional modulators SMAD2 and SMAD3 to the TGF-beta receptor. Phosphorylated by the receptor, SMAD2 and SMAD3 then form a heteromeric complex with SMAD4 that translocates to the nucleus to regulate transcription. Through interaction with SMAD2 and SMAD3, LDLRAD4 may compete with ZFYVE9 and SMAD4 and prevent propagation of the intracellular signal.1 Publication

GO - Molecular functioni

  • R-SMAD binding Source: UniProtKB

GO - Biological processi

  • negative regulation of cell migration Source: UniProtKB
  • negative regulation of epithelial to mesenchymal transition Source: UniProtKB
  • negative regulation of pathway-restricted SMAD protein phosphorylation Source: UniProtKB
  • negative regulation of SMAD protein complex assembly Source: UniProtKB
  • negative regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB

Keywordsi

Molecular functionSignal transduction inhibitor

Names & Taxonomyi

Protein namesi
Recommended name:
Low-density lipoprotein receptor class A domain-containing protein 4
Gene namesi
Name:LDLRAD4
Synonyms:C18orf1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:1224. LDLRAD4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 64LumenalSequence analysisAdd BLAST64
Transmembranei65 – 85HelicalSequence analysisAdd BLAST21
Topological domaini86 – 306CytoplasmicSequence analysisAdd BLAST221

GO - Cellular componenti

  • early endosome membrane Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • intracellular membrane-bounded organelle Source: HPA
  • nucleoplasm Source: HPA

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi753.
OpenTargetsiENSG00000168675.
PharmGKBiPA25593.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001854441 – 306Low-density lipoprotein receptor class A domain-containing protein 4Add BLAST306

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi19 ↔ 38PROSITE-ProRule annotation
Disulfide bondi32 ↔ 47PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiO15165.
PeptideAtlasiO15165.
PRIDEiO15165.

PTM databases

iPTMnetiO15165.
PhosphoSitePlusiO15165.
SwissPalmiO15165.

Expressioni

Tissue specificityi

Expressed in lymphocytes.1 Publication

Gene expression databases

BgeeiENSG00000168675.
CleanExiHS_C18orf1.
ExpressionAtlasiO15165. baseline and differential.
GenevisibleiO15165. HS.

Organism-specific databases

HPAiHPA047633.
HPA054556.
HPA065246.

Interactioni

Subunit structurei

Interacts with PMEPA1. Interacts (via the SMAD interaction motif) with SMAD2 and SMAD3.1 Publication

GO - Molecular functioni

  • R-SMAD binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107209. 51 interactors.
IntActiO15165. 2 interactors.
STRINGi9606.ENSP00000352420.

Structurei

3D structure databases

ProteinModelPortaliO15165.
SMRiO15165.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 48LDL-receptor class APROSITE-ProRule annotationAdd BLAST33

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi180 – 183WW-binding 14
Motifi208 – 211SMAD interaction motif (SIM)4
Motifi252 – 255WW-binding 24

Domaini

The SMAD interaction motif is required for interaction with SMAD2 and SMAD3 and the negative regulation of TGF-beta signaling.1 Publication

Sequence similaritiesi

Belongs to the PMEPA1 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IDYQ. Eukaryota.
ENOG41126PF. LUCA.
GeneTreeiENSGT00390000000724.
HOGENOMiHOG000276535.
HOVERGENiHBG059833.
InParanoidiO15165.
OMAiPAYSEVM.
OrthoDBiEOG091G0HDA.
PhylomeDBiO15165.
TreeFamiTF331681.

Family and domain databases

InterProiView protein in InterPro
IPR023415. LDLR_class-A_CS.
IPR002172. LDrepeatLR_classA_rpt.
PfamiView protein in Pfam
PF00057. Ldl_recept_a. 1 hit.
SMARTiView protein in SMART
SM00192. LDLa. 1 hit.
SUPFAMiSSF57424. SSF57424. 1 hit.
PROSITEiView protein in PROSITE
PS01209. LDLRA_1. 1 hit.
PS50068. LDLRA_2. 1 hit.

Sequences (8)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Alpha-1 (identifier: O15165-1) [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
MPEAGFQATN AFTECKFTCT SGKCLYLGSL VCNQQNDCGD NSDEENCLLV
60 70 80 90 100
TEHPPPGIFN SELEFAQIII IVVVVTVMVV VIVCLLNHYK VSTRSFINRP
110 120 130 140 150
NQSRRREDGL PQEGCLWPSD SAAPRLGASE IMHAPRSRDR FTAPSFIQRD
160 170 180 190 200
RFSRFQPTYP YVQHEIDLPP TISLSDGEEP PPYQGPCTLQ LRDPEQQMEL
210 220 230 240 250
NRESVRAPPN RTIFDSDLID IAMYSGGPCP PSSNSGISAS TCSSNGRMEG
260 270 280 290 300
PPPTYSEVMG HHPGASFLHH QRSNAHRGSR LQFQQNNAES TIVPIKGKDR

KPGNLV
Length:306
Mass (Da):33,900
Last modified:January 1, 1998 - v1
Checksum:iF48EF66E329201BD
GO
Isoform Alpha-2 (identifier: O15165-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     113-130: Missing.

Show »
Length:288
Mass (Da):32,072
Checksum:iB7DEC603B9C5CA79
GO
Isoform Beta-1 (identifier: O15165-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: MPEAGFQATNAFTECKFTCTSGKCLYLGSLVCNQQNDCGDNSDEENCLLVTEHPPPGIFNS → MAA

Show »
Length:248
Mass (Da):27,600
Checksum:iB88763A5A86C970A
GO
Isoform Beta-2 (identifier: O15165-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: MPEAGFQATNAFTECKFTCTSGKCLYLGSLVCNQQNDCGDNSDEENCLLVTEHPPPGIFNS → MAA
     113-130: Missing.

Show »
Length:230
Mass (Da):25,772
Checksum:i4EA79478440BC7C0
GO
Isoform 5 (identifier: O15165-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-77: Missing.

Show »
Length:229
Mass (Da):25,560
Checksum:iD124C6E3503B031E
GO
Isoform 6 (identifier: O15165-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: MPEAGFQATN...EHPPPGIFNS → MSSDHLNNSTLKEAQFKDLFLKKA

Note: No experimental confirmation available.
Show »
Length:269
Mass (Da):30,075
Checksum:iBC8B8A807F64B908
GO
Isoform 7 (identifier: O15165-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: MPEAGFQATN...EHPPPGIFNS → MSSDHLNNSTLKEAQFKDLFLKKA
     113-130: Missing.

Note: No experimental confirmation available.
Show »
Length:251
Mass (Da):28,247
Checksum:iBD0751CEB806A1B7
GO
Isoform 8 (identifier: O15165-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-111: MPEAGFQATN...QSRRREDGLP → MRLDSHLECISST

Note: No experimental confirmation available.
Show »
Length:208
Mass (Da):23,053
Checksum:iC12FA9F28364B0C0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti125R → Q in AAH66971 (PubMed:15489334).Curated1
Sequence conflicti135P → T in AAH66971 (PubMed:15489334).Curated1
Sequence conflicti194P → T in AAH66971 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0547721 – 111MPEAG…EDGLP → MRLDSHLECISST in isoform 8. 1 PublicationAdd BLAST111
Alternative sequenceiVSP_0139011 – 77Missing in isoform 5. 1 PublicationAdd BLAST77
Alternative sequenceiVSP_0432531 – 61MPEAG…GIFNS → MSSDHLNNSTLKEAQFKDLF LKKA in isoform 6 and isoform 7. 2 PublicationsAdd BLAST61
Alternative sequenceiVSP_0064391 – 61MPEAG…GIFNS → MAA in isoform Beta-1 and isoform Beta-2. 1 PublicationAdd BLAST61
Alternative sequenceiVSP_006440113 – 130Missing in isoform Alpha-2, isoform Beta-2 and isoform 7. 3 PublicationsAdd BLAST18

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF009424 mRNA. Translation: AAC52023.1.
AF009425 mRNA. Translation: AAC52024.1.
AF009426 mRNA. Translation: AAC52025.1.
AF009427 mRNA. Translation: AAC52026.1.
AK055028 mRNA. Translation: BAG51451.1.
AP001010 Genomic DNA. No translation available.
AP002439 Genomic DNA. No translation available.
AP002505 Genomic DNA. No translation available.
AP005131 Genomic DNA. No translation available.
CH471113 Genomic DNA. Translation: EAX01514.1.
BC029958 mRNA. No translation available.
BC030199 mRNA. Translation: AAH30199.1.
BC066971 mRNA. Translation: AAH66971.1.
BX114947 mRNA. No translation available.
CCDSiCCDS32793.1. [O15165-1]
CCDS32794.1. [O15165-2]
CCDS32795.1. [O15165-6]
CCDS42415.1. [O15165-7]
CCDS62392.1. [O15165-5]
CCDS62393.1. [O15165-8]
RefSeqiNP_001003674.1. NM_001003674.3. [O15165-6]
NP_001003675.1. NM_001003675.3. [O15165-7]
NP_001263178.1. NM_001276249.1. [O15165-5]
NP_001263180.1. NM_001276251.1. [O15165-8]
NP_852146.1. NM_181481.4. [O15165-1]
NP_852147.1. NM_181482.4. [O15165-2]
XP_005258197.1. XM_005258140.1. [O15165-1]
XP_006722416.1. XM_006722353.1. [O15165-1]
XP_006722417.1. XM_006722354.1. [O15165-1]
XP_011524040.1. XM_011525738.1. [O15165-5]
XP_016881454.1. XM_017025965.1. [O15165-5]
XP_016881455.1. XM_017025966.1. [O15165-5]
XP_016881456.1. XM_017025967.1. [O15165-5]
XP_016881457.1. XM_017025968.1. [O15165-5]
XP_016881458.1. XM_017025969.1. [O15165-5]
XP_016881459.1. XM_017025970.1. [O15165-5]
XP_016881460.1. XM_017025971.1. [O15165-5]
UniGeneiHs.731853.
Hs.745141.

Genome annotation databases

EnsembliENST00000359446; ENSP00000352420; ENSG00000168675. [O15165-1]
ENST00000399848; ENSP00000382741; ENSG00000168675. [O15165-2]
ENST00000585931; ENSP00000466772; ENSG00000168675. [O15165-5]
ENST00000586765; ENSP00000474783; ENSG00000168675. [O15165-7]
ENST00000587757; ENSP00000466178; ENSG00000168675. [O15165-6]
ENST00000592991; ENSP00000466771; ENSG00000168675. [O15165-8]
GeneIDi753.
KEGGihsa:753.
UCSCiuc002ksb.4. human. [O15165-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiLRAD4_HUMAN
AccessioniPrimary (citable) accession number: O15165
Secondary accession number(s): B3KNT9
, E9PAY9, K7EN38, O15166, O15167, O15168, Q5U646, Q6NXP3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: January 1, 1998
Last modified: August 30, 2017
This is version 144 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: 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. SIMILARITY comments
    Index of protein domains and families