P21757 (MSRE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	451 AA.
Sequence status	Complete.
Protein existence	Evidence 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 actetylated 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 process	Endocytosis
Cellular component	LDL Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Collagen Signal-anchor Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol transport Inferred from sequence or structural similarity PubMed 12376530. Source: BHF-UCL lipoprotein transport Inferred from electronic annotation. Source: Compara 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 response to chemical stimulus Inferred from electronic annotation. Source: Compara
Cellular_component	collagen Inferred from electronic annotation. Source: UniProtKB-KW cytoplasmic vesicle Inferred from electronic annotation. Source: Compara cytosol Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.7. Source: ProtInc low-density lipoprotein particle Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	low-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
HOOK3	Q86VS8	4	EBI-1776976,EBI-1777078
Hook3	Q7TQ77	2	EBI-1776976,EBI-1777000	From 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 451	451	Macrophage scavenger receptor types I and II		PRO_0000181627
Regions
	Topological domain	1 – 50	50	Cytoplasmic Potential
	Transmembrane	51 – 76	26	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	77 – 451	375	Extracellular Potential
	Domain	273 – 341	69	Collagen-like
	Domain	350 – 450	101	SRCR
	Region	77 – 109	33	Spacer Probable
	Coiled coil	171 – 255	85	Potential
Amino acid modifications
	Modified residue	27	1	Phosphoserine By similarity
	Modified residue	29	1	Phosphothreonine By similarity
	Glycosylation	82	1	N-linked (GlcNAc...) Potential
	Glycosylation	102	1	N-linked (GlcNAc...) Potential
	Glycosylation	143	1	N-linked (GlcNAc...) Potential
	Glycosylation	184	1	N-linked (GlcNAc...) Potential
	Glycosylation	221	1	N-linked (GlcNAc...) Ref.11
	Glycosylation	249	1	N-linked (GlcNAc...) Potential
	Glycosylation	267	1	N-linked (GlcNAc...) Potential
	Disulfide bond	375 ↔ 439		Ref.8
	Disulfide bond	388 ↔ 449		Ref.8
	Disulfide bond	419 ↔ 429		Ref.8
Natural variations
	Alternative sequence	345 – 408	64	TPFTK…HFGQG → S in isoform III.		VSP_036842
	Alternative sequence	345 – 358	14	TPFTK…GGSGP → RPVQLTDHIRAGPS in isoform II.		VSP_006229
	Alternative sequence	359 – 451	93	Missing in isoform II.		VSP_006230
	Natural variant	23	1	F → C. Ref.3 Corresponds to variant rs35175081 [ dbSNP | Ensembl ].		VAR_025190
	Natural variant	36	1	P → A Found in a family with prostate cancer. Ref.9		VAR_066581
	Natural variant	41	1	S → Y Found in patients with prostate cancer. Ref.9 Corresponds to variant rs145597376 [ dbSNP | Ensembl ].		VAR_066582
	Natural variant	113	1	V → A Found in patients with prostate cancer. Ref.9 Corresponds to variant rs117359034 [ dbSNP | Ensembl ].		VAR_066583
	Natural variant	174	1	D → Y Found in patients with prostate cancer. Ref.9 Corresponds to variant rs72552387 [ dbSNP | Ensembl ].		VAR_066584
	Natural variant	254	1	L → V Found in patients with Barrett esophagus. Ref.12		VAR_066585
	Natural variant	269	1	T → I. Corresponds to variant rs13306543 [ dbSNP | Ensembl ].		VAR_052061
	Natural variant	275	1	P → A. Ref.3 Ref.9 Corresponds to variant rs3747531 [ dbSNP | Ensembl ].		VAR_025191
	Natural variant	369	1	G → S Found in a family with prostate cancer. Ref.9		VAR_066586
	Natural variant	441	1	H → R Found in patients with prostate cancer. Ref.9 Corresponds to variant rs138749399 [ dbSNP | Ensembl ].		VAR_066587

Sequences

	Sequence		Length	Mass (Da)
	Isoform I [UniParc]. Last modified May 1, 1991. Version 1. Checksum: 915C03B56653BB41	FASTA	451	49,762
	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
	Isoform II [UniParc]. Checksum: 5F8593EF21189917	FASTA	358	39,584
	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 PPGLKGDRGA IGFPGSRGLP GYAGRPGNSG PKGQKGEKGS GNTLRPVQLT DHIRAGPS
	Isoform III [UniParc]. Checksum: D6A20BCE57BFBC46	FASTA	388	42,942
	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 GNTLSTGPIW LNEVFCFGRE 370 380 SSIEECKIRQ WGTRACSHSE DAGVTCTL

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, MASS SPECTROMETRY. 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

NIEHS-SNPs

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.
IPI	IPI00012740. IPI00071002. IPI00939301.
PIR	A38415. B38415.
RefSeq	NP_002436.1. NM_002445.3. NP_619729.1. NM_138715.2. NP_619730.1. NM_138716.2.
UniGene	Hs.147635.
3D structure databases
ProteinModelPortal	P21757.
ModBase	Search...
Protein-protein interaction databases
IntAct	P21757. 3 interactions.
STRING	9606.ENSP00000262101.
PTM databases
PhosphoSite	P21757.
Polymorphism databases
DMDM	127357.
Proteomic databases
PaxDb	P21757.
PRIDE	P21757.
Protocols and materials databases
DNASU	4481.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262101; ENSP00000262101; ENSG00000038945. ENST00000350896; ENSP00000262100; ENSG00000038945. ENST00000355282; ENSP00000347430; ENSG00000038945. ENST00000381998; ENSP00000371428; ENSG00000038945.
GeneID	4481.
KEGG	hsa:4481.
UCSC	uc003wwz.3. human. uc003wxa.3. human. uc003wxb.3. human.
Organism-specific databases
CTD	4481.
GeneCards	GC08M016009.
HGNC	HGNC:7376. MSR1.
HPA	HPA000272.
MIM	153622. gene. 176807. phenotype. 614266. phenotype.
neXtProt	NX_P21757.
Orphanet	1232. Barrett esophagus.
PharmGKB	PA31181.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG150350.
HOGENOM	HOG000085659.
HOVERGEN	HBG002473.
InParanoid	P21757.
KO	K06558.
OrthoDB	EOG4RJG1J.
PhylomeDB	P21757.
Gene expression databases
ArrayExpress	P21757.
Bgee	P21757.
CleanEx	HS_MSR1.
Genevestigator	P21757.
GermOnline	ENSG00000038945. Homo sapiens.
Family and domain databases
InterPro	IPR008160. Collagen. IPR003543. Macro_scav_rcpt. IPR001190. Srcr_rcpt. IPR017448. Srcr_rcpt-rel. [Graphical view]
Pfam	PF01391. Collagen. 1 hit. PF03523. Macscav_rec. 1 hit. PF00530. SRCR. 1 hit. [Graphical view]
PRINTS	PR01408. MACSCAVRCPTR. PR00258. SPERACTRCPTR.
SMART	SM00202. SR. 1 hit. [Graphical view]
SUPFAM	SSF56487. Srcr_receptor. 1 hit.
PROSITE	PS00420. SRCR_1. 1 hit. PS50287. SRCR_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P21757.
ChEMBL	CHEMBL5811.
GenomeRNAi	4481.
NextBio	17337.
SOURCE	Search...

Entry information

Entry name

MSRE_HUMAN

Accession

Primary (citable) accession number: P21757
Secondary accession number(s): D3DSP3 , O60505, P21759, Q45F10

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	May 1, 1991
Last modified:	May 1, 2013
This is version 136 of the entry and version 1 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.