Q9UBG0 (MRC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C-type mannose receptor 2

Alternative name(s):
C-type lectin domain family 13 member E
Endocytic receptor 180
Macrophage mannose receptor 2
Urokinase-type plasminogen activator receptor-associated protein
Short name=UPAR-associated protein
Short name=Urokinase receptor-associated protein
CD_antigen=CD280

Gene names

Name:	MRC2
Synonyms:	CLEC13E, ENDO180, KIAA0709, UPARAP

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	1479 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	May play a role as endocytotic lectin receptor displaying calcium-dependent lectin activity. Internalizes glycosylated ligands from the extracellular space for release in an endosomal compartment via clathrin-mediated endocytosis. May be involved in plasminogen activation system controlling the extracellular level of PLAUR/PLAU, and thus may regulate protease activity at the cell surface. May contribute to cellular uptake, remodeling and degradation of extracellular collagen matrices. May play a role during cancer progression as well as in other chronic tissue destructive diseases acting on collagen turnover. May participate in remodeling of extracellular matrix co-operating with the matrix metalloproteinases (MMPs). Ref.2 Ref.10
Subunit structure	Interacts with C-terminal region of type I collagen/COL1A1 By similarity. Interacts directly with PLAUR/UPAR and PLAU/pro-UPA to form a tri-molecular complex. Interacts with collagen V. Ref.1
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Ubiquitous with low expression in brain, placenta, lung, kidney, pancreas, spleen, thymus and colon. Expressed in endothelial cells, fibroblasts and macrophages. Highly expressed in fetal lung and kidney. Ref.2 Ref.7
Domain	C-type lectin domains 3 to 8 are not required for calcium-dependent binding of mannose, fucose and N-acetylglucosamine. C-type lectin domain 2 is responsible for sugar-binding in a calcium-dependent manner. Ref.9 Ref.10 Fibronectin type-II domain mediates collagen-binding. Ref.9 Ref.10 Ricin B-type lectin domain contacts with the second C-type lectin domain By similarity. Ref.9 Ref.10
Post-translational modification	N-glycosylated. Ref.2
Sequence similarities	Contains 8 C-type lectin domains. Contains 1 fibronectin type-II domain. Contains 1 ricin B-type lectin domain.
Sequence caution	The sequence BAA31684.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Endocytosis
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium Lectin
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	endocytosis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	carbohydrate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 30	30	Potential
	Chain	31 – 1479	1449	C-type mannose receptor 2		PRO_0000046078
Regions
	Topological domain	31 – 1414	1384	Extracellular Potential
	Transmembrane	1415 – 1435	21	Helical; Potential
	Topological domain	1436 – 1479	44	Cytoplasmic Potential
	Domain	41 – 167	127	Ricin B-type lectin
	Domain	182 – 230	49	Fibronectin type-II
	Domain	244 – 360	117	C-type lectin 1
	Domain	389 – 505	117	C-type lectin 2
	Domain	528 – 644	117	C-type lectin 3
	Domain	678 – 809	132	C-type lectin 4
	Domain	832 – 951	120	C-type lectin 5
	Domain	979 – 1107	129	C-type lectin 6
	Domain	1132 – 1243	112	C-type lectin 7
	Domain	1273 – 1393	121	C-type lectin 8
Amino acid modifications
	Glycosylation	69	1	N-linked (GlcNAc...) Ref.11
	Glycosylation	140	1	N-linked (GlcNAc...) Potential
	Glycosylation	364	1	N-linked (GlcNAc...) Potential
	Glycosylation	588	1	N-linked (GlcNAc...) Potential
	Glycosylation	954	1	N-linked (GlcNAc...) Potential
	Glycosylation	1029	1	N-linked (GlcNAc...) Potential
	Glycosylation	1350	1	N-linked (GlcNAc...) Potential
	Disulfide bond	54 ↔ 68		By similarity
	Disulfide bond	93 ↔ 112		By similarity
	Disulfide bond	187 ↔ 213		By similarity
	Disulfide bond	201 ↔ 228		By similarity
	Disulfide bond	266 ↔ 359		By similarity
	Disulfide bond	335 ↔ 351		By similarity
	Disulfide bond	410 ↔ 504		By similarity
	Disulfide bond	481 ↔ 496		By similarity
	Disulfide bond	618 ↔ 635		By similarity
	Disulfide bond	704 ↔ 808		By similarity
	Disulfide bond	785 ↔ 800		By similarity
	Disulfide bond	853 ↔ 950		By similarity
	Disulfide bond	927 ↔ 942		By similarity
	Disulfide bond	1078 ↔ 1098		By similarity
	Disulfide bond	1220 ↔ 1234		By similarity
	Disulfide bond	1369 ↔ 1384		By similarity
	Cross-link	1142		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO-1) Ref.12
Natural variations
	Natural variant	43	1	V → I. Ref.2 Corresponds to variant rs2014055 [ dbSNP | Ensembl ].		VAR_025304
	Natural variant	1156	1	R → H. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6 Corresponds to variant rs2429387 [ dbSNP | Ensembl ].		VAR_025305
Experimental info
	Mutagenesis	472	1	N → D: Reduced sugar-binding activity. Ref.9
	Mutagenesis	1452	1	Y → A: No alteration of distribution and trafficking. Ref.8
	Mutagenesis	1464	1	E → A: Increased cell surface distribution. Ref.8
	Mutagenesis	1468 – 1469	2	LV → AA: Reduction of endocytotic activity; distribution almost restricted to the cell surface.

Sequences

	Sequence		Length	Mass (Da)
	Q9UBG0 [UniParc]. Last modified January 11, 2011. Version 2. Checksum: AAAA5286F91DF7E7	FASTA	1,479	166,674
	10 20 30 40 50 60 MGPGRPAPAP WPRHLLRCVL LLGCLHLGRP GAPGDAALPE PNVFLIFSHG LQGCLEAQGG 70 80 90 100 110 120 QVRVTPACNT SLPAQRWKWV SRNRLFNLGT MQCLGTGWPG TNTTASLGMY ECDREALNLR 130 140 150 160 170 180 WHCRTLGDQL SLLLGARTSN ISKPGTLERG DQTRSGQWRI YGSEEDLCAL PYHEVYTIQG 190 200 210 220 230 240 NSHGKPCTIP FKYDNQWFHG CTSTGREDGH LWCATTQDYG KDERWGFCPI KSNDCETFWD 250 260 270 280 290 300 KDQLTDSCYQ FNFQSTLSWR EAWASCEQQG ADLLSITEIH EQTYINGLLT GYSSTLWIGL 310 320 330 340 350 360 NDLDTSGGWQ WSDNSPLKYL NWESDQPDNP SEENCGVIRT ESSGGWQNRD CSIALPYVCK 370 380 390 400 410 420 KKPNATAEPT PPDRWANVKV ECEPSWQPFQ GHCYRLQAEK RSWQESKKAC LRGGGDLVSI 430 440 450 460 470 480 HSMAELEFIT KQIKQEVEEL WIGLNDLKLQ MNFEWSDGSL VSFTHWHPFE PNNFRDSLED 490 500 510 520 530 540 CVTIWGPEGR WNDSPCNQSL PSICKKAGQL SQGAAEEDHG CRKGWTWHSP SCYWLGEDQV 550 560 570 580 590 600 TYSEARRLCT DHGSQLVTIT NRFEQAFVSS LIYNWEGEYF WTALQDLNST GSFFWLSGDE 610 620 630 640 650 660 VMYTHWNRDQ PGYSRGGCVA LATGSAMGLW EVKNCTSFRA RYICRQSLGT PVTPELPGPD 670 680 690 700 710 720 PTPSLTGSCP QGWASDTKLR YCYKVFSSER LQDKKSWVQA QGACQELGAQ LLSLASYEEE 730 740 750 760 770 780 HFVANMLNKI FGESEPEIHE QHWFWIGLNR RDPRGGQSWR WSDGVGFSYH NFDRSRHDDD 790 800 810 820 830 840 DIRGCAVLDL ASLQWVAMQC DTQLDWICKI PRGTDVREPD DSPQGRREWL RFQEAEYKFF 850 860 870 880 890 900 EHHSTWAQAQ RICTWFQAEL TSVHSQAELD FLSHNLQKFS RAQEQHWWIG LHTSESDGRF 910 920 930 940 950 960 RWTDGSIINF ISWAPGKPRP VGKDKKCVYM TASREDWGDQ RCLTALPYIC KRSNVTKETQ 970 980 990 1000 1010 1020 PPDLPTTALG GCPSDWIQFL NKCFQVQGQE PQSRVKWSEA QFSCEQQEAQ LVTITNPLEQ 1030 1040 1050 1060 1070 1080 AFITASLPNV TFDLWIGLHA SQRDFQWVEQ EPLMYANWAP GEPSGPSPAP SGNKPTSCAV 1090 1100 1110 1120 1130 1140 VLHSPSAHFT GRWDDRSCTE ETHGFICQKG TDPSLSPSPA ALPPAPGTEL SYLNGTFRLL 1150 1160 1170 1180 1190 1200 QKPLRWHDAL LLCESRNASL AYVPDPYTQA FLTQAARGLR TPLWIGLAGE EGSRRYSWVS 1210 1220 1230 1240 1250 1260 EEPLNYVGWQ DGEPQQPGGC TYVDVDGAWR TTSCDTKLQG AVCGVSSGPP PPRRISYHGS 1270 1280 1290 1300 1310 1320 CPQGLADSAW IPFREHCYSF HMELLLGHKE ARQRCQRAGG AVLSILDEME NVFVWEHLQS 1330 1340 1350 1360 1370 1380 YEGQSRGAWL GMNFNPKGGT LVWQDNTAVN YSNWGPPGLG PSMLSHNSCY WIQSNSGLWR 1390 1400 1410 1420 1430 1440 PGACTNITMG VVCKLPRAEQ SSFSPSALPE NPAALVVVLM AVLLLLALLT AALILYRRRQ 1450 1460 1470 SIERGAFEGA RYSRSSSSPT EATEKNILVS DMEMNEQQE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A urokinase receptor-associated protein with specific collagen binding properties." Behrendt N., Jensen O.N., Engelholm L.H., Moertz E., Mann M., Danoe K. J. Biol. Chem. 275:1993-2002(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 350-360, IDENTIFICATION BY MASS SPECTROMETRY, SUBUNIT, VARIANT HIS-1156.
[2]	"Endo180, an endocytic recycling glycoprotein related to the macrophage mannose receptor is expressed on fibroblasts, endothelial cells and macrophages and functions as a lectin receptor." Sheikh H., Yarwood H., Ashworth A., Isacke C.M. J. Cell Sci. 113:1021-1032(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PHOSPHORYLATION, GLYCOSYLATION, TISSUE SPECIFICITY, VARIANTS ILE-43 AND HIS-1156.
[3]	"Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:169-176(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT HIS-1156. Tissue: Brain.
[4]	"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].
[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], VARIANT HIS-1156.
[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], VARIANT HIS-1156.
[7]	"Characterization of a novel member of the macrophage mannose receptor type C lectin family." Wu K., Yuan J., Lasky L.A. J. Biol. Chem. 271:21323-21330(1996) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"The C-type lectin receptor Endo180 displays internalization and recycling properties distinct from other members of the mannose receptor family." Howard M.J., Isacke C.M. J. Biol. Chem. 277:32320-32331(2002) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TYR-1452; GLU-1464 AND 1468-LEU-VAL-1469.
[9]	"Characterization of sugar binding by the mannose receptor family member, Endo180." East L., Rushton S., Taylor M.E., Isacke C.M. J. Biol. Chem. 277:50469-50475(2002) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAIN, MUTAGENESIS OF ASN-472.
[10]	"Identification and characterization of the endocytic transmembrane glycoprotein Endo180 as a novel collagen receptor." Wienke D., MacFadyen J.R., Isacke C.M. Mol. Biol. Cell 14:3592-3604(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DOMAIN.
[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-69, MASS SPECTROMETRY. Tissue: Liver.
[12]	"In vivo identification of sumoylation sites by a signature tag and cysteine-targeted affinity purification." Blomster H.A., Imanishi S.Y., Siimes J., Kastu J., Morrice N.A., Eriksson J.E., Sistonen L. J. Biol. Chem. 285:19324-19329(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-1142. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Web resources

Functional Glycomics Gateway - Glycan Binding

Endo180

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF107292 mRNA. Translation: AAF14192.1. AF134838 mRNA. Translation: AAD30280.1. AB014609 mRNA. Translation: BAA31684.2. Different initiation. AC080038 Genomic DNA. No translation available. CH471109 Genomic DNA. Translation: EAW94341.1. CH471109 Genomic DNA. Translation: EAW94342.1. BC146647 mRNA. Translation: AAI46648.1. BC150212 mRNA. Translation: AAI50213.1. BC153884 mRNA. Translation: AAI53885.1.
IPI	IPI00005707.
RefSeq	NP_006030.2. NM_006039.4.
UniGene	Hs.7835.
3D structure databases
ProteinModelPortal	Q9UBG0.
SMR	Q9UBG0. Positions 161-361, 381-645, 681-811, 828-952, 972-1109, 1132-1235.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UBG0. 1 interaction.
STRING	9606.ENSP00000307513.
PTM databases
PhosphoSite	Q9UBG0.
Polymorphism databases
DMDM	74720063.
Proteomic databases
PaxDb	Q9UBG0.
PRIDE	Q9UBG0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000303375; ENSP00000307513; ENSG00000011028.
GeneID	9902.
KEGG	hsa:9902.
UCSC	uc002jad.3. human.
Organism-specific databases
CTD	9902.
GeneCards	GC17P060704.
H-InvDB	HIX0018596. HIX0027238.
HGNC	HGNC:16875. MRC2.
HPA	HPA041991.
MIM	612264. gene.
neXtProt	NX_Q9UBG0.
PharmGKB	PA134988161.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG288621.
HOGENOM	HOG000231191.
HOVERGEN	HBG053606.
InParanoid	Q9UBG0.
KO	K06560.
OMA	MEMNEQQ.
OrthoDB	EOG415GCH.
PhylomeDB	Q9UBG0.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q9UBG0.
Bgee	Q9UBG0.
CleanEx	HS_MRC2.
Genevestigator	Q9UBG0.
Family and domain databases
Gene3D	2.10.10.10. 1 hit. 3.10.100.10. 8 hits.
InterPro	IPR001304. C-type_lectin. IPR016186. C-type_lectin-like. IPR018378. C-type_lectin_CS. IPR016187. C-type_lectin_fold. IPR000562. FN_type2_col-bd. IPR013806. Kringle-like. IPR000772. Ricin_B_lectin. [Graphical view]
Pfam	PF00040. fn2. 1 hit. PF00059. Lectin_C. 8 hits. [Graphical view]
SMART	SM00034. CLECT. 8 hits. SM00059. FN2. 1 hit. SM00458. RICIN. 1 hit. [Graphical view]
SUPFAM	SSF56436. C-type_lectin_fold. 8 hits. SSF57440. Kringle-like. 1 hit. SSF50370. RicinB_like. 1 hit.
PROSITE	PS00615. C_TYPE_LECTIN_1. 3 hits. PS50041. C_TYPE_LECTIN_2. 8 hits. PS00023. FN2_1. 1 hit. PS51092. FN2_2. 1 hit. PS50231. RICIN_B_LECTIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MRC2. human.
GenomeRNAi	9902.
NextBio	37337.
SOURCE	Search...

Entry information

Entry name

MRC2_HUMAN

Accession

Primary (citable) accession number: Q9UBG0
Secondary accession number(s): A6H8K4 , D3DU08, Q7LGE7, Q9Y5P9

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 7, 2006
Last sequence update:	January 11, 2011
Last modified:	May 1, 2013
This is version 93 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.