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Q08431 (MFGM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lactadherin
Alternative name(s):
Breast epithelial antigen BA46
HMFG
MFGM
Milk fat globule-EGF factor 8
Short name=MFG-E8
SED1

Cleaved into the following 2 chains:

  1. Lactadherin short form
  2. Medin
Gene names
Name:MFGE8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length387 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays an important role in the maintenance of intestinal epithelial homeostasis and the promotion of mucosal healing. Promotes VEGF-dependent neovascularization By similarity. Contributes to phagocytic removal of apoptotic cells in many tissues. Specific ligand for the alpha-v/beta-3 and alpha-v/beta-5 receptors. Also binds to phosphatidylserine-enriched cell surfaces in a receptor-independent manner. Zona pellucida-binding protein which may play a role in gamete interaction. Binds specifically to rotavirus and inhibits its replication. Ref.15

Medin is the main constituent of aortic medial amyloid. Ref.15

Subcellular location

Membrane; Peripheral membrane protein. Secreted Ref.15.

Tissue specificity

Mammary epithelial cell surfaces and aortic media. Overexpressed in several carcinomas.

Domain

The F5/8 type C 2 domain mediates high-affinity binding to phosphatidylserine-containing membranes By similarity.

Post-translational modification

Medin has a ragged N-terminus with minor species starting at Pro-264 and Gly-273.

Sequence similarities

Contains 1 EGF-like domain.

Contains 2 F5/8 type C domains.

Ontologies

Keywords
   Biological processAngiogenesis
Cell adhesion
Fertilization
Host-virus interaction
   Cellular componentAmyloid
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainEGF-like domain
Repeat
Signal
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

cell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

phagocytosis, engulfment

Inferred from electronic annotation. Source: Ensembl

phagocytosis, recognition

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic cell clearance

Inferred from electronic annotation. Source: Ensembl

single fertilization

Inferred from electronic annotation. Source: UniProtKB-KW

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentexternal side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from electronic annotation. Source: Ensembl

extracellular vesicular exosome

Inferred from direct assay PubMed 21362503. Source: UniProtKB

extrinsic component of plasma membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionphosphatidylethanolamine binding

Inferred from electronic annotation. Source: Ensembl

phosphatidylserine binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q08431-1)

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 2 (identifier: Q08431-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q08431-3)

The sequence of this isoform differs from the canonical sequence as follows:
     291-342: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323
Chain24 – 387364Lactadherin
PRO_0000007650
Chain202 – 387186Lactadherin short form
PRO_0000007651
Chain268 – 31750Medin
PRO_0000007652

Regions

Domain24 – 6744EGF-like
Domain70 – 225156F5/8 type C 1
Domain230 – 387158F5/8 type C 2
Motif46 – 483Cell attachment site

Amino acid modifications

Glycosylation2281N-linked (GlcNAc...); atypical Ref.14
Glycosylation2381N-linked (GlcNAc...) Ref.14
Glycosylation3251N-linked (GlcNAc...) Ref.14
Glycosylation3291N-linked (GlcNAc...) Ref.14
Glycosylation3501N-linked (GlcNAc...) Ref.14
Disulfide bond27 ↔ 38 By similarity
Disulfide bond32 ↔ 55 By similarity
Disulfide bond57 ↔ 66 By similarity
Disulfide bond70 ↔ 225 By similarity
Disulfide bond212 ↔ 216 By similarity
Disulfide bond230 ↔ 387 By similarity

Natural variations

Alternative sequence1 – 7575Missing in isoform 2.
VSP_039108
Alternative sequence291 – 34252Missing in isoform 3.
VSP_039953
Natural variant31R → S.
Corresponds to variant rs4945 [ dbSNP | Ensembl ].
VAR_029794
Natural variant761M → L. Ref.4 Ref.5 Ref.7
Corresponds to variant rs1878326 [ dbSNP | Ensembl ].
VAR_024263

Experimental info

Sequence conflict2681R → W in CAD97938. Ref.5
Sequence conflict3521S → T in CAD97938. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: 2EE6571DEC83782D

FASTA38743,123
        10         20         30         40         50         60 
MPRPRLLAAL CGALLCAPSL LVALDICSKN PCHNGGLCEE ISQEVRGDVF PSYTCTCLKG 

        70         80         90        100        110        120 
YAGNHCETKC VEPLGMENGN IANSQIAASS VRVTFLGLQH WVPELARLNR AGMVNAWTPS 

       130        140        150        160        170        180 
SNDDNPWIQV NLLRRMWVTG VVTQGASRLA SHEYLKAFKV AYSLNGHEFD FIHDVNKKHK 

       190        200        210        220        230        240 
EFVGNWNKNA VHVNLFETPV EAQYVRLYPT SCHTACTLRF ELLGCELNGC ANPLGLKNNS 

       250        260        270        280        290        300 
IPDKQITASS SYKTWGLHLF SWNPSYARLD KQGNFNAWVA GSYGNDQWLQ VDLGSSKEVT 

       310        320        330        340        350        360 
GIITQGARNF GSVQFVASYK VAYSNDSANW TEYQDPRTGS SKIFPGNWDN HSHKKNLFET 

       370        380 
PILARYVRIL PVAWHNRIAL RLELLGC 

« Hide

Isoform 2 [UniParc].

Checksum: 9E3857A7E7096C8B
Show »

FASTA31235,189
Isoform 3 [UniParc].

Checksum: 20E84E5DB78E8E25
Show »

FASTA33537,523

References

« Hide 'large scale' references
[1]"Cloning and sequence analysis of human breast epithelial antigen BA46 reveals an RGD cell adhesion sequence presented on an epidermal growth factor-like domain."
Couto J.R., Taylor M.R., Godwin S.G., Ceriani R.L., Peterson J.A.
DNA Cell Biol. 15:281-286(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Mammary carcinoma and Mammary gland.
[2]"Characterization of human epididymal protein."
Sivashanmugam P., Richardson R.T., Hamil K.G., Hall S.H., French F.S., O'Rand M.G.
Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LEU-76.
[5]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LEU-76.
Tissue: Dermoid cancer and Pancreas.
[6]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Retina.
[7]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT LEU-76.
[8]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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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 3).
Tissue: Skin.
[10]"A Mr 46,000 human milk fat globule protein that is highly expressed in human breast tumors contains factor VIII-like domains."
Larocca D., Peterson J.A., Urrea R., Kuniyoshi J., Bistrain A.M., Ceriani R.L.
Cancer Res. 51:4994-4998(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 170-387.
Tissue: Mammary gland.
[11]"Isolation and characterization of full and truncated forms of human breast carcinoma protein BA46 from human milk fat globule membranes."
Giuffrida M.G., Cavaletto M., Giunta C., Conti A., Godovac-Zimmermann J.
J. Protein Chem. 17:143-148(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, CHARACTERIZATION.
Tissue: Milk.
[12]"Medin: an integral fragment of aortic smooth muscle cell-produced lactadherin forms the most common human amyloid."
Haeggqvist B., Naeslund J., Sletten K., Westermark G.T., Mucchiano G., Tjernberg L.O., Nordstedt C., Engstroem U., Westermark P.
Proc. Natl. Acad. Sci. U.S.A. 96:8669-8674(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 268-317, IDENTIFICATION OF MEDIN.
[13]"Lactadherin (formerly BA46), a membrane-associated glycoprotein expressed in human milk and breast carcinomas, promotes Arg-Gly-Asp (RGD)-dependent cell adhesion."
Taylor M.R., Couto J.R., Scallan C.D., Ceriani R.L., Peterson J.A.
DNA Cell Biol. 16:861-869(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[14]"Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry."
Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.
Proteomics 8:3833-3847(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-228; ASN-238; ASN-325; ASN-329 AND ASN-350.
Tissue: Milk.
[15]"SED1/MFG-E8: a bi-motif protein that orchestrates diverse cellular interactions."
Raymond A., Ensslin M.A., Shur B.D.
J. Cell. Biochem. 106:957-966(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U58516 mRNA. Translation: AAC50549.1.
AY141974 mRNA. Translation: AAN08508.1.
BT006948 mRNA. Translation: AAP35594.1.
AK312640 mRNA. Translation: BAG35524.1.
AK223182 mRNA. Translation: BAD96902.1.
AK222735 mRNA. Translation: BAD96455.1.
BX537974 mRNA. Translation: CAD97938.1.
AC067805 Genomic DNA. No translation available.
CH471101 Genomic DNA. Translation: EAX02026.1.
BC003610 mRNA. Translation: AAH03610.1.
S56151 mRNA. Translation: AAB19771.1.
CCDSCCDS10347.1. [Q08431-1]
CCDS45345.1. [Q08431-3]
PIRA47285.
RefSeqNP_001108086.1. NM_001114614.1.
NP_005919.2. NM_005928.2.
UniGeneHs.3745.

3D structure databases

ProteinModelPortalQ08431.
SMRQ08431. Positions 27-387.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110398. 2 interactions.
IntActQ08431. 1 interaction.
MINTMINT-5004478.
STRING9606.ENSP00000268150.

PTM databases

PhosphoSiteQ08431.

Polymorphism databases

DMDM2506380.

Proteomic databases

MaxQBQ08431.
PaxDbQ08431.
PRIDEQ08431.

Protocols and materials databases

DNASU4240.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000268150; ENSP00000268150; ENSG00000140545.
ENST00000566497; ENSP00000456281; ENSG00000140545.
GeneID4240.
KEGGhsa:4240.
UCSCuc002bnf.4. human. [Q08431-1]
uc002bnh.4. human. [Q08431-3]

Organism-specific databases

CTD4240.
GeneCardsGC15M089441.
H-InvDBHIX0012558.
HGNCHGNC:7036. MFGE8.
HPACAB002753.
HPA002807.
MIM602281. gene.
neXtProtNX_Q08431.
PharmGKBPA30772.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG151024.
HOGENOMHOG000236278.
HOVERGENHBG002385.
InParanoidQ08431.
KOK17253.
PhylomeDBQ08431.
TreeFamTF330156.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.

Gene expression databases

ArrayExpressQ08431.
BgeeQ08431.
CleanExHS_MFGE8.
GenevestigatorQ08431.

Family and domain databases

Gene3D2.60.120.260. 2 hits.
InterProIPR000421. Coagulation_fac_5/8-C_type_dom.
IPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR008979. Galactose-bd-like.
IPR027060. Lactadherin.
[Graphical view]
PANTHERPTHR10127:SF303. PTHR10127:SF303. 1 hit.
PfamPF00008. EGF. 1 hit.
PF00754. F5_F8_type_C. 2 hits.
[Graphical view]
SMARTSM00181. EGF. 1 hit.
SM00231. FA58C. 2 hits.
[Graphical view]
SUPFAMSSF49785. SSF49785. 2 hits.
PROSITEPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS01285. FA58C_1. 2 hits.
PS01286. FA58C_2. 2 hits.
PS50022. FA58C_3. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMFGE8. human.
GeneWikiMFGE8.
GenomeRNAi4240.
NextBio16719.
PROQ08431.
SOURCESearch...

Entry information

Entry nameMFGM_HUMAN
AccessionPrimary (citable) accession number: Q08431
Secondary accession number(s): B2R6M7 expand/collapse secondary AC list , Q53FU9, Q7Z3D2, Q9BTL9
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 1, 1997
Last modified: July 9, 2014
This is version 132 of the entry and version 2 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 15

Human chromosome 15: entries, gene names and cross-references to MIM