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P21757 (MSRE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Macrophage scavenger receptor types I and II
Alternative name(s):
Macrophage acetylated LDL receptor I and II
Scavenger receptor class A member 1
CD_antigen=CD204
Gene names
Name:MSR1
Synonyms:SCARA1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length451 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Membrane glycoproteins implicated in the pathologic deposition of cholesterol in arterial walls during atherogenesis. Two types of receptor subunits exist. These receptors mediate the endocytosis of a diverse group of macromolecules, including modified low density lipoproteins (LDL). Isoform III does not internalize acetylated LDL.

Subunit structure

Homotrimer.

Subcellular location

Membrane; Single-pass type II membrane protein.

Tissue specificity

Isoform I, isoform II and isoform III are expressed in monocyte-derived macrophages. Ref.2

Involvement in disease

Prostate cancer (PC) [MIM:176807]: A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma.
Note: The disease may be caused by mutations affecting the gene represented in this entry. MSR1 variants may play a role in susceptibility to prostate cancer. MSR1 variants have been found in individuals with prostate cancer and co-segregate with the disease in some families. Ref.9

Barrett esophagus (BE) [MIM:614266]: A condition characterized by a metaplastic change in which normal esophageal squamous epithelium is replaced by a columnar and intestinal-type epithelium. Patients with Barrett esophagus have an increased risk of esophageal adenocarcinoma. The main cause of Barrett esophagus is gastroesophageal reflux. The retrograde movement of acid and bile salts from the stomach into the esophagus causes prolonged injury to the esophageal epithelium and induces chronic esophagitis, which in turn is believed to trigger the pathologic changes.
Note: The disease may be caused by mutations affecting the gene represented in this entry. Genetic variants in MSR1 have been found in individuals with Barrett esophagus and are thought to contribute to disease susceptibility. Ref.12

Sequence similarities

Contains 1 collagen-like domain.

Contains 1 SRCR domain.

Ontologies

Keywords
   Biological processEndocytosis
   Cellular componentLDL
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainCoiled coil
Collagen
Signal-anchor
Transmembrane
Transmembrane helix
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcholesterol transport

Inferred from sequence or structural similarity PubMed 12376530. Source: BHF-UCL

lipoprotein transport

Inferred from electronic annotation. Source: Ensembl

plasma lipoprotein particle clearance

Inferred from sequence or structural similarity PubMed 12376530. Source: BHF-UCL

positive regulation of cholesterol storage

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of macrophage derived foam cell differentiation

Inferred from sequence or structural similarity PubMed 12376530. Source: BHF-UCL

receptor-mediated endocytosis

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcollagen

Inferred from electronic annotation. Source: UniProtKB-KW

cytosol

Inferred from electronic annotation. Source: Ensembl

endocytic vesicle membrane

Traceable author statement. Source: Reactome

integral component of plasma membrane

Traceable author statement Ref.7. Source: ProtInc

low-density lipoprotein particle

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionlow-density lipoprotein particle binding

Inferred from sequence or structural similarity PubMed 12376530. Source: BHF-UCL

scavenger receptor activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

HOOK3Q86VS84EBI-1776976,EBI-1777078
Hook3Q7TQ772EBI-1776976,EBI-1777000From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform I (identifier: P21757-1)

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 II (identifier: P21757-2)

The sequence of this isoform differs from the canonical sequence as follows:
     345-358: TPFTKVRLVGGSGP → RPVQLTDHIRAGPS
     359-451: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Isoform III (identifier: P21757-3)

The sequence of this isoform differs from the canonical sequence as follows:
     345-408: TPFTKVRLVGGSGPHEGRVEILHSGQWGTICDDRWEVRVGQVVCRSLGYPGVQAVHKAAHFGQG → S

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 451451Macrophage scavenger receptor types I and II
PRO_0000181627

Regions

Topological domain1 – 5050Cytoplasmic Potential
Transmembrane51 – 7626Helical; Signal-anchor for type II membrane protein; Potential
Topological domain77 – 451375Extracellular Potential
Domain273 – 34169Collagen-like
Domain350 – 450101SRCR
Region77 – 10933Spacer Probable
Coiled coil171 – 25585 Potential

Amino acid modifications

Modified residue271Phosphoserine By similarity
Glycosylation821N-linked (GlcNAc...) Potential
Glycosylation1021N-linked (GlcNAc...) Potential
Glycosylation1431N-linked (GlcNAc...) Potential
Glycosylation1841N-linked (GlcNAc...) Potential
Glycosylation2211N-linked (GlcNAc...) Ref.11
Glycosylation2491N-linked (GlcNAc...) Potential
Glycosylation2671N-linked (GlcNAc...) Potential
Disulfide bond375 ↔ 439 Ref.8
Disulfide bond388 ↔ 449 Ref.8
Disulfide bond419 ↔ 429 Ref.8

Natural variations

Alternative sequence345 – 40864TPFTK…HFGQG → S in isoform III.
VSP_036842
Alternative sequence345 – 35814TPFTK…GGSGP → RPVQLTDHIRAGPS in isoform II.
VSP_006229
Alternative sequence359 – 45193Missing in isoform II.
VSP_006230
Natural variant231F → C. Ref.3
Corresponds to variant rs35175081 [ dbSNP | Ensembl ].
VAR_025190
Natural variant361P → A Found in a family with prostate cancer. Ref.9
VAR_066581
Natural variant411S → Y Found in patients with prostate cancer. Ref.9
Corresponds to variant rs145597376 [ dbSNP | Ensembl ].
VAR_066582
Natural variant1131V → A Found in patients with prostate cancer. Ref.9
Corresponds to variant rs117359034 [ dbSNP | Ensembl ].
VAR_066583
Natural variant1741D → Y Found in patients with prostate cancer. Ref.9
Corresponds to variant rs72552387 [ dbSNP | Ensembl ].
VAR_066584
Natural variant2541L → V Found in patients with Barrett esophagus. Ref.12
VAR_066585
Natural variant2691T → I.
Corresponds to variant rs13306543 [ dbSNP | Ensembl ].
VAR_052061
Natural variant2751P → A. Ref.3 Ref.9
Corresponds to variant rs3747531 [ dbSNP | Ensembl ].
VAR_025191
Natural variant3691G → S Found in a family with prostate cancer. Ref.9
VAR_066586
Natural variant4411H → R Found in patients with prostate cancer. Ref.9
Corresponds to variant rs138749399 [ dbSNP | Ensembl ].
VAR_066587

Sequences

Sequence LengthMass (Da)Tools
Isoform I [UniParc].

Last modified May 1, 1991. Version 1.
Checksum: 915C03B56653BB41

FASTA45149,762
        10         20         30         40         50         60 
MEQWDHFHNQ QEDTDSCSES VKFDARSMTA LLPPNPKNSP SLQEKLKSFK AALIALYLLV 

        70         80         90        100        110        120 
FAVLIPLIGI VAAQLLKWET KNCSVSSTNA NDITQSLTGK GNDSEEEMRF QEVFMEHMSN 

       130        140        150        160        170        180 
MEKRIQHILD MEANLMDTEH FQNFSMTTDQ RFNDILLQLS TLFSSVQGHG NAIDEISKSL 

       190        200        210        220        230        240 
ISLNTTLLDL QLNIENLNGK IQENTFKQQE EISKLEERVY NVSAEIMAMK EEQVHLEQEI 

       250        260        270        280        290        300 
KGEVKVLNNI TNDLRLKDWE HSQTLRNITL IQGPPGPPGE KGDRGPTGES GPRGFPGPIG 

       310        320        330        340        350        360 
PPGLKGDRGA IGFPGSRGLP GYAGRPGNSG PKGQKGEKGS GNTLTPFTKV RLVGGSGPHE 

       370        380        390        400        410        420 
GRVEILHSGQ WGTICDDRWE VRVGQVVCRS LGYPGVQAVH KAAHFGQGTG PIWLNEVFCF 

       430        440        450 
GRESSIEECK IRQWGTRACS HSEDAGVTCT L 

« Hide

Isoform II [UniParc].

Checksum: 5F8593EF21189917
Show »

FASTA35839,584
Isoform III [UniParc].

Checksum: D6A20BCE57BFBC46
Show »

FASTA38842,942

References

« Hide 'large scale' references
[1]"Human macrophage scavenger receptors: primary structure, expression, and localization in atherosclerotic lesions."
Matsumoto A., Naito M., Itakura H., Ikemoto S., Asaoka H., Hayakawa I., Kanamori H., Aburatani H., Takaku F., Suzuki H., Kobari Y., Miyai T., Takahashi K., Cohen E.H., Wydro R., Housman D.E., Kodama T.
Proc. Natl. Acad. Sci. U.S.A. 87:9133-9137(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS I AND II).
[2]"A naturally occurring isoform of the human macrophage scavenger receptor (SR-A) gene generated by alternative splicing blocks modified LDL uptake."
Gough P.J., Greaves D.R., Gordon S.
J. Lipid Res. 39:531-543(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM III), TISSUE SPECIFICITY.
[3]NIEHS SNPs program
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-23 AND ALA-275.
[4]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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 I).
Tissue: Testis.
[7]"Structure, organization, and chromosomal mapping of the human macrophage scavenger receptor gene."
Emi M., Asaoka H., Matsumoto A., Itakura H., Kurihara Y., Wada Y., Kanamori H., Yazaki Y., Takahashi E., Lepert M.
J. Biol. Chem. 268:2120-2125(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 155-272.
[8]"Structures of class A macrophage scavenger receptors. Electron microscopic study of flexible, multidomain, fibrous proteins and determination of the disulfide bond pattern of the scavenger receptor cysteine-rich domain."
Resnick D., Chatterton J.E., Schwartz K., Slayter H., Krieger M.
J. Biol. Chem. 271:26924-26930(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS IN SRCR DOMAIN.
[9]"Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk."
Xu J., Zheng S.L., Komiya A., Mychaleckyj J.C., Isaacs S.D., Hu J.J., Sterling D., Lange E.M., Hawkins G.A., Turner A., Ewing C.M., Faith D.A., Johnson J.R., Suzuki H., Bujnovszky P., Wiley K.E., DeMarzo A.M., Bova G.S. expand/collapse author list , Chang B., Hall M.C., McCullough D.L., Partin A.W., Kassabian V.S., Carpten J.D., Bailey-Wilson J.E., Trent J.M., Ohar J., Bleecker E.R., Walsh P.C., Isaacs W.B., Meyers D.A.
Nat. Genet. 32:321-325(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN PC, VARIANTS ALA-36; TYR-41; ALA-113; TYR-174; ALA-275; SER-369 AND ARG-441.
[10]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[11]"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-221.
Tissue: Liver.
[12]"Germline mutations in MSR1, ASCC1, and CTHRC1 in patients with Barrett esophagus and esophageal adenocarcinoma."
Orloff M., Peterson C., He X., Ganapathi S., Heald B., Yang Y.R., Bebek G., Romigh T., Song J.H., Wu W., David S., Cheng Y., Meltzer S.J., Eng C.
JAMA 306:410-419(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN BE, VARIANT VAL-254.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D90187 mRNA. Translation: BAA14208.1.
D90188 mRNA. Translation: BAA14209.1.
AF037351 mRNA. Translation: AAC09251.1.
DQ144993 Genomic DNA. Translation: AAZ38715.1.
AC023396 Genomic DNA. No translation available.
CH471080 Genomic DNA. Translation: EAW63832.1.
CH471080 Genomic DNA. Translation: EAW63830.1.
CH471080 Genomic DNA. Translation: EAW63833.1.
CH471080 Genomic DNA. Translation: EAW63834.1.
BC063878 mRNA. Translation: AAH63878.1.
D13263 Genomic DNA. No translation available.
PIRA38415.
B38415.
RefSeqNP_002436.1. NM_002445.3.
NP_619729.1. NM_138715.2.
NP_619730.1. NM_138716.2.
UniGeneHs.147635.

3D structure databases

ProteinModelPortalP21757.
SMRP21757. Positions 268-344, 346-450.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110587. 3 interactions.
IntActP21757. 3 interactions.
STRING9606.ENSP00000262101.

Chemistry

BindingDBP21757.
ChEMBLCHEMBL5811.

PTM databases

PhosphoSiteP21757.

Polymorphism databases

DMDM127357.

Proteomic databases

PaxDbP21757.
PRIDEP21757.

Protocols and materials databases

DNASU4481.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262101; ENSP00000262101; ENSG00000038945. [P21757-1]
ENST00000350896; ENSP00000262100; ENSG00000038945. [P21757-3]
ENST00000355282; ENSP00000347430; ENSG00000038945. [P21757-3]
ENST00000381998; ENSP00000371428; ENSG00000038945. [P21757-2]
GeneID4481.
KEGGhsa:4481.
UCSCuc003wwz.3. human. [P21757-1]
uc003wxa.3. human. [P21757-3]
uc003wxb.3. human. [P21757-2]

Organism-specific databases

CTD4481.
GeneCardsGC08M016009.
HGNCHGNC:7376. MSR1.
HPAHPA000272.
MIM153622. gene.
176807. phenotype.
614266. phenotype.
neXtProtNX_P21757.
Orphanet1232. Barrett esophagus.
PharmGKBPA31181.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG150350.
HOGENOMHOG000085659.
HOVERGENHBG002473.
InParanoidP21757.
KOK06558.
OrthoDBEOG7V1FQV.
PhylomeDBP21757.
TreeFamTF330855.

Enzyme and pathway databases

ReactomeREACT_160300. Binding and Uptake of Ligands by Scavenger Receptors.

Gene expression databases

ArrayExpressP21757.
BgeeP21757.
CleanExHS_MSR1.
GenevestigatorP21757.

Family and domain databases

Gene3D3.10.250.10. 1 hit.
InterProIPR008160. Collagen.
IPR003543. Macro_scav_rcpt.
IPR001190. SRCR.
IPR017448. SRCR-like_dom.
[Graphical view]
PfamPF01391. Collagen. 1 hit.
PF03523. Macscav_rec. 1 hit.
PF00530. SRCR. 1 hit.
[Graphical view]
PRINTSPR01408. MACSCAVRCPTR.
PR00258. SPERACTRCPTR.
SMARTSM00202. SR. 1 hit.
[Graphical view]
SUPFAMSSF56487. SSF56487. 1 hit.
PROSITEPS00420. SRCR_1. 1 hit.
PS50287. SRCR_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMSR1.
GenomeRNAi4481.
NextBio17337.
PROP21757.
SOURCESearch...

Entry information

Entry nameMSRE_HUMAN
AccessionPrimary (citable) accession number: P21757
Secondary accession number(s): D3DSP3 expand/collapse secondary AC list , O60505, P21759, Q45F10
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: May 1, 1991
Last modified: April 16, 2014
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries