P07306 (ASGR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Asialoglycoprotein receptor 1
Short name=ASGP-R 1
Short name=ASGPR 1

Alternative name(s):
C-type lectin domain family 4 member H1
Hepatic lectin H1
Short name=HL-1

Gene names

Name:	ASGR1
Synonyms:	CLEC4H1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	291 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-acetylgalactosamine units. After ligand binding to the receptor, the resulting complex is internalized and transported to a sorting organelle, where receptor and ligand are disassociated. The receptor then returns to the cell membrane surface.
Subunit structure	Interacts with LASS2. Ref.8
Subcellular location	Isoform H1a: Membrane; Single-pass type II membrane protein Ref.4. Isoform H1b: Secreted Ref.4.
Tissue specificity	Expressed exclusively in hepatic parenchymal cells.
Post-translational modification	Phosphorylated on a cytoplasmic Ser residue.
Miscellaneous	Calcium is required for ligand binding.
Sequence similarities	Contains 1 C-type lectin domain.

Ontologies

Keywords
Biological process	Endocytosis
Cellular component	Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Coiled coil Signal-anchor Transmembrane Transmembrane helix
Ligand	Calcium Lectin Metal-binding
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to extracellular stimulus Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement PubMed 10734069. Source: ProtInc
Molecular_function	asialoglycoprotein receptor activity Traceable author statement PubMed 8439566. Source: ProtInc carbohydrate binding Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CERS2	Q96G23	3	EBI-1172335,EBI-1057080

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform H1a (identifier: P07306-1)

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.

Isoform H1b (identifier: P07306-2)

Also known as: sASGPR;

The sequence of this isoform differs from the canonical sequence as follows:
     24-63: GPPPPQPLLQRLCSGPRLLLLSLGLSLLLLVVVCVIGSQN → D

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 291

290

Asialoglycoprotein receptor 1

PRO_0000046650

Regions

Topological domain

2 – 40

39

Cytoplasmic Probable

Transmembrane

41 – 61

21

Helical; Signal-anchor for type II membrane protein; Probable

Topological domain

62 – 291

230

Extracellular Probable

Domain

161 – 278

118

C-type lectin

Coiled coil

61 – 123

63

Potential

Motif

5 – 8

4

Endocytosis signal Potential

Sites

Metal binding

191

1

Calcium 1; via carbonyl oxygen

Metal binding

197

1

Calcium 1

Metal binding

216

1

Calcium 2

Metal binding

240

1

Calcium 3

Metal binding

242

1

Calcium 3

Metal binding

243

1

Calcium 2

Metal binding

253

1

Calcium 2; via carbonyl oxygen

Metal binding

253

1

Calcium 3

Metal binding

254

1

Calcium 2

Metal binding

265

1

Calcium 3

Metal binding

266

1

Calcium 3

Metal binding

278

1

Calcium 1

Binding site

240

1

Carbohydrate

Binding site

244

1

Carbohydrate

Binding site

253

1

Carbohydrate

Amino acid modifications

Lipidation

36

1

S-palmitoyl cysteine Ref.7

Glycosylation

79

1

N-linked (GlcNAc...) Ref.9

Glycosylation

147

1

N-linked (GlcNAc...) Ref.9

Disulfide bond

154 ↔ 165

Disulfide bond

182 ↔ 277

Disulfide bond

255 ↔ 269

Natural variations

Alternative sequence

24 – 63

40

GPPPP…IGSQN → D in isoform H1b.

VSP_044480

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

291

Helix Strand Turn

Details...

Beta strand

159 – 161

3

Beta strand

164 – 168

5

Helix

175 – 184

10

Helix

195 – 205

11

Beta strand

210 – 215

6

Beta strand

248 – 251

4

Beta strand

255 – 258

4

Beta strand

264 – 267

4

Beta strand

273 – 280

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform H1a [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 9B825527B2FC1FD0	FASTA	291	33,186
	10 20 30 40 50 60 MTKEYQDLQH LDNEESDHHQ LRKGPPPPQP LLQRLCSGPR LLLLSLGLSL LLLVVVCVIG 70 80 90 100 110 120 SQNSQLQEEL RGLRETFSNF TASTEAQVKG LSTQGGNVGR KMKSLESQLE KQQKDLSEDH 130 140 150 160 170 180 SSLLLHVKQF VSDLRSLSCQ MAALQGNGSE RTCCPVNWVE HERSCYWFSR SGKAWADADN 190 200 210 220 230 240 YCRLEDAHLV VVTSWEEQKF VQHHIGPVNT WMGLHDQNGP WKWVDGTDYE TGFKNWRPEQ 250 260 270 280 290 PDDWYGHGLG GGEDCAHFTD DGRWNDDVCQ RPYRWVCETE LDKASQEPPL L
	Isoform H1b (sASGPR) [UniParc]. Checksum: B0F8C6FA80E1CCF2	FASTA	252	29,144
	10 20 30 40 50 60 MTKEYQDLQH LDNEESDHHQ LRKDSQLQEE LRGLRETFSN FTASTEAQVK GLSTQGGNVG 70 80 90 100 110 120 RKMKSLESQL EKQQKDLSED HSSLLLHVKQ FVSDLRSLSC QMAALQGNGS ERTCCPVNWV 130 140 150 160 170 180 EHERSCYWFS RSGKAWADAD NYCRLEDAHL VVVTSWEEQK FVQHHIGPVN TWMGLHDQNG 190 200 210 220 230 240 PWKWVDGTDY ETGFKNWRPE QPDDWYGHGL GGGEDCAHFT DDGRWNDDVC QRPYRWVCET 250 ELDKASQEPP LL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of human asialoglycoprotein receptor cDNA. An internal signal sequence for membrane insertion." Spiess M., Schwartz A.L., Lodish H.F. J. Biol. Chem. 260:1979-1982(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM H1A).
[2]	"An internal signal sequence: the asialoglycoprotein receptor membrane anchor." Spiess M., Lodish H.F. Cell 44:177-185(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM H1A).
[3]	"Human asialoglycoprotein receptor 1 gene is expressed in SH-SY5Y human neuroblastoma cells." Wang H., Gao X., Li L., Lou H., Huang Y., Wang B., Han J. Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM H1A).
[4]	"A new splice variant of the major subunit of human asialoglycoprotein receptor encodes a secreted form in hepatocytes." Liu J., Hu B., Yang Y., Ma Z., Yu Y., Liu S., Wang B., Zhao X., Lu M., Yang D. PLoS ONE 5:E12934-E12934(2010) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM H1B), ALTERNATIVE SPLICING, SUBCELLULAR LOCATION (ISOFORM H1B). Tissue: Liver.
[5]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORM H1A). Tissue: Liver.
[7]	"Fatty acylation of the rat and human asialoglycoprotein receptors. A conserved cytoplasmic cysteine residue is acylated in all receptor subunits." Zeng F.Y., Weigel P.H. J. Biol. Chem. 271:32454-32460(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PALMITOYLATION AT CYS-36.
[8]	"Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene LAG1." Pan H., Qin W.-X., Huo K.-K., Wan D.-F., Yu Y., Xu Z.-G., Hu Q.-D., Gu K.T., Zhou X.-M., Jiang H.-Q., Zhang P.-P., Huang Y., Li Y.-Y., Gu J.-R. Genomics 77:58-64(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LASS2.
[9]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-79 AND ASN-147, MASS SPECTROMETRY. Tissue: Liver.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"Crystal structure of the carbohydrate recognition domain of the H1 subunit of the asialoglycoprotein receptor." Meier M., Bider M.D., Malashkevich V.N., Spiess M., Burkhard P. J. Mol. Biol. 300:857-865(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 154-281.
+	Additional computationally mapped references.

Web resources

Functional Glycomics Gateway - Glycan Binding

Hepatic asialoglycoprotein receptor subunit 1

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M10058 mRNA. Translation: AAA51785.1.
AB070933 mRNA. Translation: BAB83508.1.
FJ410292 mRNA. Translation: ACQ90237.1.
AC120057 Genomic DNA. No translation available.
BC032130 mRNA. Translation: AAH32130.1.

IPI

IPI00215926.

PIR

LNHU1. A22509.

RefSeq

NP_001184145.1. NM_001197216.2.
NP_001662.1. NM_001671.4.

UniGene

Hs.12056.
Hs.731669.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DV8	X-ray	2.30	A	154-281	[»]

ProteinModelPortal

P07306.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07306. 5 interactions.

STRING

9606.ENSP00000269299.

PTM databases

PhosphoSite

P07306.

Polymorphism databases

DMDM

126132.

Proteomic databases

PaxDb

P07306.

PRIDE

P07306.

Protocols and materials databases

DNASU

432.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000269299; ENSP00000269299; ENSG00000141505.
ENST00000574388; ENSP00000459169; ENSG00000141505.

GeneID

432.

KEGG

hsa:432.

UCSC

uc002ges.4. human.

Organism-specific databases

CTD

432.

GeneCards

GC17M007017.

HGNC

HGNC:742. ASGR1.

HPA

HPA011954.
HPA012852.

MIM

108360. gene.

neXtProt

NX_P07306.

PharmGKB

PA25042.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG278574.

HOGENOM

HOG000034093.

HOVERGEN

HBG000270.

InParanoid

P07306.

KO

K10063.

OMA

SCQMAVL.

OrthoDB

EOG4V171K.

PhylomeDB

P07306.

Gene expression databases

ArrayExpress

P07306.

Bgee

P07306.

CleanEx

HS_ASGR1.

Genevestigator

P07306.

GermOnline

ENSG00000141505. Homo sapiens.

Family and domain databases

Gene3D

3.10.100.10. 1 hit.

InterPro

IPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR018378. C-type_lectin_CS.
IPR016187. C-type_lectin_fold.
IPR005640. Lectin_N.
[Graphical view]

Pfam

PF00059. Lectin_C. 1 hit.
PF03954. Lectin_N. 1 hit.
[Graphical view]

SMART

SM00034. CLECT. 1 hit.
[Graphical view]

SUPFAM

SSF56436. C-type_lectin_fold. 1 hit.

PROSITE

PS00615. C_TYPE_LECTIN_1. 1 hit.
PS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P07306.

ChEMBL

CHEMBL2084.

EvolutionaryTrace

P07306.

GenomeRNAi

432.

NextBio

1803.

SOURCE

Search...

Entry information

Entry name

ASGR1_HUMAN

Accession

Primary (citable) accession number: P07306
Secondary accession number(s): I3L1X1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 138 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.