Q8C142 (ARH_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Low density lipoprotein receptor adapter protein 1

Alternative name(s):
Autosomal recessive hypercholesterolemia protein homolog

Gene names

Name:	Ldlrap1
Synonyms:	Arh

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	308 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Cholesterol metabolism Endocytosis Lipid metabolism Steroid metabolism Sterol metabolism
Cellular component	Cytoplasm
Disease	Atherosclerosis Hyperlipidemia
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	amyloid precursor protein metabolic process Inferred from electronic annotation. Source: Compara 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: Compara receptor-mediated endocytosis of low-density lipoprotein particle involved in cholesterol transport Inferred from electronic annotation. Source: Compara regulation of establishment of protein localization to plasma membrane Inferred from electronic annotation. Source: Compara regulation of protein binding Inferred from electronic annotation. Source: Compara
Cellular_component	AP-1 adaptor complex Inferred from electronic annotation. Source: Compara AP-2 adaptor complex Inferred from electronic annotation. Source: Compara basal plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB cytosol Inferred from sequence or structural similarity. Source: UniProtKB early endosome Inferred from direct assay Ref.5. Source: MGI internal side of plasma membrane Inferred from electronic annotation. Source: Compara neurofilament Inferred from direct assay PubMed 17727637. Source: BHF-UCL recycling endosome Inferred from electronic annotation. Source: Compara
Molecular_function	beta-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: Compara phosphotyrosine binding Inferred from sequence or structural similarity. Source: UniProtKB receptor binding Inferred from sequence alignment PubMed 12221107. Source: MGI signaling adaptor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 308	308	Low density lipoprotein receptor adapter protein 1		PRO_0000064676
Regions
	Domain	41 – 195	155	PID
	Region	248 – 275	28	AP-2 complex binding By similarity
	Motif	211 – 215	5	Clathrin box
	Motif	256 – 265	10	[DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif
Amino acid modifications
	Modified residue	14	1	Phosphoserine By similarity
	Modified residue	198	1	Phosphoserine Ref.7 Ref.8
Experimental info
	Sequence conflict	260	1	R → K in BAC26238. Ref.1
	Sequence conflict	296	1	S → G in AAH66808. Ref.4
	Sequence conflict	296	1	S → G in AAH67411. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q8C142 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: 4183DA9594FD1F2C	FASTA	308	33,975
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
[7]	"Specific phosphopeptide enrichment with immobilized titanium ion affinity chromatography adsorbent for phosphoproteome analysis." Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H. J. Proteome Res. 7:3957-3967(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-198, MASS SPECTROMETRY. Tissue: Liver.
[8]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-198, MASS SPECTROMETRY. Tissue: Melanoma.
+	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.
IPI	IPI00454119.
RefSeq	NP_663529.2. NM_145554.2.
UniGene	Mm.482148.
3D structure databases
ProteinModelPortal	Q8C142.
SMR	Q8C142. Positions 42-174.
ModBase	Search...
PTM databases
PhosphoSite	Q8C142.
Proteomic databases
PaxDb	Q8C142.
PRIDE	Q8C142.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000037828; ENSMUSP00000036749; ENSMUSG00000037295.
GeneID	100017.
KEGG	mmu:100017.
Organism-specific databases
CTD	26119.
MGI	MGI:2140175. Ldlrap1.
Phylogenomic databases
eggNOG	NOG305324.
GeneTree	ENSGT00530000062937.
HOGENOM	HOG000030906.
HOVERGEN	HBG058060.
InParanoid	Q3TW86.
KO	K12474.
OMA	WELDDGL.
OrthoDB	EOG46Q6T7.
Gene expression databases
ArrayExpress	Q8C142.
Bgee	Q8C142.
Genevestigator	Q8C142.
GermOnline	ENSMUSG00000037295. Mus musculus.
Family and domain databases
Gene3D	2.30.29.30. 1 hit.
InterPro	IPR011993. PH_like_dom. IPR006020. PTyr_interaction_dom. [Graphical view]
Pfam	PF00640. PID. 1 hit. [Graphical view]
SMART	SM00462. PTB. 1 hit. [Graphical view]
PROSITE	PS01179. PID. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	354215.
SOURCE	Search...

Entry information

Entry name

ARH_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 88 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program