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Q8C142 (ARH_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Low density lipoprotein receptor adapter protein 1
Alternative name(s):
Autosomal recessive hypercholesterolemia protein homolog
Gene names
Name:Ldlrap1
Synonyms:Arh
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length308 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non-polarized cells (fibroblasts). May be required for LDL binding and internalization but not for receptor clustering in coated pits. May facilitate the endocytocis of LDLR and LDLR-LDL complexes from coated pits by stabilizing the interaction between the receptor and the structural components of the pits. May also be involved in the internalization of other LDLR family members. Binds to phosphoinositides, which regulate clathrin bud assembly at the cell surface. Ref.5 Ref.6

Subunit structure

Interacts with LDLR. Binds to soluble clathrin trimers. Interacts with AP2B1; the interaction mediates the association with the AP-2 complex. Interacts with VLDLR. Ref.5

Subcellular location

Cytoplasm Ref.6.

Domain

The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1 By similarity.

Disruption phenotype

Mice are extremely sensitive to cholesterol intake. LDLR are expressed at normal levels, but are sequestered at the hepatocyte surface. LDL internalization defect is caused by the inability of the LDLR to enter the endocytic cycle. Ref.6

Sequence similarities

Contains 1 PID domain.

Sequence caution

The sequence AAH21467.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processCholesterol metabolism
Endocytosis
Lipid metabolism
Steroid metabolism
Sterol metabolism
   Cellular componentCytoplasm
   DiseaseAtherosclerosis
Hyperlipidemia
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processamyloid precursor protein metabolic process

Inferred from electronic annotation. Source: Ensembl

cholesterol homeostasis

Inferred from mutant phenotype Ref.5. Source: MGI

cholesterol metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of receptor-mediated endocytosis

Inferred from sequence or structural similarity. Source: UniProtKB

receptor internalization

Inferred from electronic annotation. Source: Ensembl

receptor-mediated endocytosis of low-density lipoprotein particle involved in cholesterol transport

Inferred from electronic annotation. Source: Ensembl

regulation of establishment of protein localization to plasma membrane

Inferred from electronic annotation. Source: Ensembl

regulation of protein binding

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentAP-1 adaptor complex

Inferred from electronic annotation. Source: Ensembl

AP-2 adaptor complex

Inferred from electronic annotation. Source: Ensembl

axon

Inferred from electronic annotation. Source: Ensembl

basal plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 17727637. Source: BHF-UCL

cytoplasmic side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

early endosome

Inferred from direct assay Ref.5. Source: MGI

neurofilament

Inferred from direct assay PubMed 17727637. Source: BHF-UCL

recycling endosome

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionbeta-amyloid binding

Inferred from physical interaction PubMed 17727637. Source: BHF-UCL

clathrin binding

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol-4,5-bisphosphate binding

Inferred from electronic annotation. Source: Ensembl

phosphotyrosine binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 17727637. Source: BHF-UCL

receptor binding

Inferred from sequence alignment PubMed 12221107. Source: MGI

signaling adaptor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 308308Low density lipoprotein receptor adapter protein 1
PRO_0000064676

Regions

Domain41 – 195155PID
Region248 – 27528AP-2 complex binding By similarity
Motif211 – 2155Clathrin box
Motif256 – 26510[DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue141Phosphoserine By similarity

Experimental info

Sequence conflict2601R → K in BAC26238. Ref.1
Sequence conflict2961S → G in AAH66808. Ref.4
Sequence conflict2961S → G in AAH67411. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q8C142 [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: 4183DA9594FD1F2C

FASTA30833,975
        10         20         30         40         50         60 
MDALKSAGRA LIRSPSLAKQ SWAGGRHRKL PENWTDTRET LLEGMVFSLK YLGMTLVERP 

        70         80         90        100        110        120 
KGEELSAAAV KRIVATAKAS GKKLQKVTLK VSPRGIILTD SLTSQLIENV SIYRISYCTA 

       130        140        150        160        170        180 
DKMHDKVFAY IAQSQQNESL ECHAFLCTKR KVAQAVTLTV AQAFKVAFEF WQVSKEEKEK 

       190        200        210        220        230        240 
REKANQEGGD VPGTRRDSTP SLKTLVATGN LLDLEEVAKA PLSTVSANTN NVDETPRPQV 

       250        260        270        280        290        300 
LGNNSVVWEL DDGLDEAFSR LAQSRTNPQV LDTGLSAQDI HYAQCLSPTD WDKPDSSGID 


QDDDVFTF 

« Hide

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Skin.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C3H/He and CD-1.
Tissue: Mammary gland, Neural stem cell and Osteoblast.
[5]"Normal sorting but defective endocytosis of the low density lipoprotein receptor in mice with autosomal recessive hypercholesterolemia."
Jones C., Hammer R.E., Li W.-P., Cohen J.C., Hobbs H.H., Herz J.
J. Biol. Chem. 278:29024-29030(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH LDLR AND VLDLR.
[6]"The modular adaptor protein ARH is required for low density lipoprotein (LDL) binding and internalization but not for LDL receptor clustering in coated pits."
Michaely P., Li W.-P., Anderson R.G.W., Cohen J.C., Hobbs H.H.
J. Biol. Chem. 279:34023-34031(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK029008 mRNA. Translation: BAC26238.1.
AK148340 mRNA. Translation: BAE28493.1.
AK159800 mRNA. Translation: BAE35380.1.
AK167290 mRNA. Translation: BAE39396.1.
AL645531 Genomic DNA. Translation: CAM17037.1.
CH466552 Genomic DNA. Translation: EDL30001.1.
BC021467 mRNA. Translation: AAH21467.1. Different initiation.
BC066808 mRNA. Translation: AAH66808.1.
BC067411 mRNA. Translation: AAH67411.1.
CCDSCCDS51327.1.
RefSeqNP_663529.2. NM_145554.2.
XP_006538486.1. XM_006538423.1.
UniGeneMm.482148.

3D structure databases

ProteinModelPortalQ8C142.
SMRQ8C142. Positions 42-174.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid221366. 1 interaction.

PTM databases

PhosphoSiteQ8C142.

Proteomic databases

MaxQBQ8C142.
PaxDbQ8C142.
PRIDEQ8C142.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000037828; ENSMUSP00000036749; ENSMUSG00000037295.
GeneID100017.
KEGGmmu:100017.
UCSCuc012dmx.1. mouse.

Organism-specific databases

CTD26119.
MGIMGI:2140175. Ldlrap1.

Phylogenomic databases

eggNOGNOG305324.
GeneTreeENSGT00530000062937.
HOGENOMHOG000030906.
HOVERGENHBG058060.
InParanoidQ3TW86.
KOK12474.
OMAWELDDGL.
OrthoDBEOG7RZ5QP.
TreeFamTF314159.

Gene expression databases

ArrayExpressQ8C142.
BgeeQ8C142.
GenevestigatorQ8C142.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR011993. PH_like_dom.
IPR006020. PTB/PI_dom.
[Graphical view]
PfamPF00640. PID. 1 hit.
[Graphical view]
SMARTSM00462. PTB. 1 hit.
[Graphical view]
PROSITEPS01179. PID. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio354215.
PROQ8C142.
SOURCESearch...

Entry information

Entry nameARH_MOUSE
AccessionPrimary (citable) accession number: Q8C142
Secondary accession number(s): Q3TW86, Q6NWV6, Q8VDQ0
Entry history
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 100 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot