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P21956 (MFGM_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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):
MFGM
Milk fat globule-EGF factor 8
Short name=MFG-E8
SED1
Sperm surface protein SP47
Short name=MP47
Gene names
Name:Mfge8
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length463 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity. Plays an important role in the maintenance of intestinal epithelial homeostasis and the promotion of mucosal healing. Promotes VEGF-dependent neovascularization. Ref.7 Ref.8

Subcellular location

Membrane; Peripheral membrane protein. Secreted Ref.1.

Tissue specificity

Mammary epithelial cell surfaces and spermatozoan. Isoform 2 is present in brain, heart, kidney and spleen and at low levels in lung, liver, small intestine and testis. Ref.1 Ref.4

Developmental stage

Isoform 1 and isoform 2 are detectable in mammary tissue from non-pregnant animals, with isoform 2 being predominant. Levels of isoform 1 increase during gestation and lactation while levels of isoform 2 decrease. Ref.1 Ref.4

Induction

Isoform 1 is induced by insulin, prolactin and hydrocortisone in mammary epithelial cells. Expression of isoform 2 is repressed by the same treatment. Ref.4

Domain

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

Post-translational modification

N-glycosylated. Isoform 1 also exists in both an O-glycosylated and a non-O-glycosylated form. Ref.4

Sequence similarities

Contains 2 EGF-like domains.

Contains 2 F5/8 type C domains.

Ontologies

Keywords
   Biological processAngiogenesis
Cell adhesion
Fertilization
   Cellular componentMembrane
Secreted
   Coding sequence diversityAlternative splicing
   DomainEGF-like domain
Repeat
Signal
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete 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 direct assay PubMed 12000961. Source: MGI

phagocytosis, recognition

Inferred from direct assay PubMed 12000961. Source: MGI

positive regulation of apoptotic cell clearance

Inferred from direct assay PubMed 20826760. Source: BHF-UCL

positive regulation of phagocytosis

Inferred from direct assay PubMed 12000961. Source: MGI

single fertilization

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentexternal side of plasma membrane

Inferred from direct assay PubMed 12000961. Source: MGI

extracellular matrix

Inferred from electronic annotation. Source: Ensembl

extracellular space

Inferred from direct assay PubMed 12000961. Source: MGI

extracellular vesicular exosome

Inferred from electronic annotation. Source: Ensembl

extrinsic component of plasma membrane

Inferred from direct assay PubMed 12000961. Source: MGI

   Molecular_functionintegrin binding

Inferred from direct assay PubMed 20826760. Source: BHF-UCL

phosphatidylethanolamine binding

Inferred from direct assay PubMed 12000961. Source: MGI

phosphatidylserine binding

Inferred from direct assay PubMed 12000961. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P21956-1)

Also known as: Long;

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: P21956-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     110-147: ETNYYNLDGEYMFTTAVPNTAVPTPAPTPDLSNNLASR → G

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Ref.1
Chain23 – 463441Lactadherin
PRO_0000007653

Regions

Domain24 – 6138EGF-like 1
Domain64 – 10845EGF-like 2
Domain148 – 303156F5/8 type C 1
Domain308 – 463156F5/8 type C 2
Motif87 – 893Cell attachment site

Amino acid modifications

Glycosylation611N-linked (GlcNAc...) Potential
Glycosylation2661N-linked (GlcNAc...) Potential
Glycosylation3161N-linked (GlcNAc...) Potential
Glycosylation4261N-linked (GlcNAc...) Potential
Disulfide bond28 ↔ 39 By similarity
Disulfide bond33 ↔ 49 By similarity
Disulfide bond51 ↔ 60 By similarity
Disulfide bond68 ↔ 79 By similarity
Disulfide bond73 ↔ 96 By similarity
Disulfide bond98 ↔ 107 By similarity
Disulfide bond148 ↔ 303 By similarity
Disulfide bond290 ↔ 294 By similarity
Disulfide bond308 ↔ 463 Ref.9

Natural variations

Alternative sequence110 – 14738ETNYY…NLASR → G in isoform 2.
VSP_009880

Experimental info

Sequence conflict351N → D AA sequence Ref.1
Sequence conflict1681S → Y in AAA39534. Ref.1
Sequence conflict1961T → H in AAA39534. Ref.1
Sequence conflict2841K → R in AAA39534. Ref.1
Sequence conflict2841K → R in CAA72380. Ref.3
Sequence conflict2841K → R in BAA35180. Ref.4
Sequence conflict2841K → R in BAA76386. Ref.4
Sequence conflict2841K → R in BAC40794. Ref.5
Sequence conflict2841K → R in BAE42274. Ref.5
Sequence conflict2841K → R in AAH03892. Ref.6
Sequence conflict2841K → R in AAH03904. Ref.6
Sequence conflict3091S → L in AAA39534. Ref.1
Sequence conflict3951A → E in AAA39534. Ref.1

Secondary structure

............................. 463
Helix Strand Turn

Details...

Sequences

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

Last modified July 27, 2011. Version 3.
Checksum: 6E19CBB494B22878

FASTA46351,241
        10         20         30         40         50         60 
MQVSRVLAAL CGMLLCASGL FAASGDFCDS SLCLNGGTCL TGQDNDIYCL CPEGFTGLVC 

        70         80         90        100        110        120 
NETERGPCSP NPCYNDAKCL VTLDTQRGDI FTEYICQCPV GYSGIHCETE TNYYNLDGEY 

       130        140        150        160        170        180 
MFTTAVPNTA VPTPAPTPDL SNNLASRCST QLGMEGGAIA DSQISASSVY MGFMGLQRWG 

       190        200        210        220        230        240 
PELARLYRTG IVNAWTASNY DSKPWIQVNL LRKMRVSGVM TQGASRAGRA EYLKTFKVAY 

       250        260        270        280        290        300 
SLDGRKFEFI QDESGGDKEF LGNLDNNSLK VNMFNPTLEA QYIKLYPVSC HRGCTLRFEL 

       310        320        330        340        350        360 
LGCELHGCSE PLGLKNNTIP DSQMSASSSY KTWNLRAFGW YPHLGRLDNQ GKINAWTAQS 

       370        380        390        400        410        420 
NSAKEWLQVD LGTQRQVTGI ITQGARDFGH IQYVASYKVA HSDDGVQWTV YEEQGSSKVF 

       430        440        450        460 
QGNLDNNSHK KNIFEKPFMA RYVRVLPVSW HNRITLRLEL LGC 

« Hide

Isoform 2 (Short) [UniParc].

Checksum: 0882EDA89B95C445
Show »

FASTA42647,169

References

« Hide 'large scale' references
[1]"cDNA cloning of a mouse mammary epithelial cell surface protein reveals the existence of epidermal growth factor-like domains linked to factor VIII-like sequences."
Stubbs J.D., Lekutis C., Singer K.L., Bui A., Yuzuki D., Srinivasan U., Parry G.
Proc. Natl. Acad. Sci. U.S.A. 87:8417-8421(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 23-35, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
Strain: BALB/c.
Tissue: Mammary gland.
[2]Ensslin M.A.
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]"Molecular cloning and characterization of P47, a novel boar sperm-associated zona pellucida-binding protein homologous to a family of mammalian secretory proteins."
Ensslin M.A., Vogel T., Calvete J.J., Thole H.H., Schmidtke J., Matsuda T., Toepfer-Petersen E.
Biol. Reprod. 58:1057-1064(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 23-463 (ISOFORM 2).
Tissue: Testis.
[4]"Lactation-dependent expression of an mRNA splice variant with an exon for a multiply O-glycosylated domain of mouse milk fat globule glycoprotein MFG-E8."
Oshima K., Aoki N., Negi M., Kishi M., Kitajima K., Matsuda T.
Biochem. Biophys. Res. Commun. 254:522-528(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION, GLYCOSYLATION.
Strain: BALB/c.
Tissue: Mammary gland.
[5]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Strain: C57BL/6J and NOD.
Tissue: Bone marrow and Dendritic cell.
[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 2).
Strain: FVB/N.
Tissue: Mammary gland.
[7]"Lactadherin promotes VEGF-dependent neovascularization."
Silvestre J.S., Thery C., Hamard G., Boddaert J., Aguilar B., Delcayre A., Houbron C., Tamarat R., Blanc-Brude O., Heeneman S., Clergue M., Duriez M., Merval R., Levy B., Tedgui A., Amigorena S., Mallat Z.
Nat. Med. 11:499-506(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ITGB3 AND ITGB5, FUNCTION IN NEOVASCULARIZATION.
[8]"Milk fat globule-EGF factor 8/lactadherin plays a crucial role in maintenance and repair of murine intestinal epithelium."
Bu H.F., Zuo X.L., Wang X., Ensslin M.A., Koti V., Hsueh W., Raymond A.S., Shur B.D., Tan X.D.
J. Clin. Invest. 117:3673-3683(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN GUT EPITHELIAL REPAIR.
[9]"NMR solution structure of C2 domain of MFG-E8 and insights into its molecular recognition with phosphatidylserine."
Ye H., Li B., Subramanian V., Choi B.H., Liang Y., Harikishore A., Chakraborty G., Baek K., Yoon H.S.
Biochim. Biophys. Acta 1828:1083-1093(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 306-463, DISULFIDE BOND.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M38337 mRNA. Translation: AAA39534.1.
Y11684 mRNA. Translation: CAA72380.2.
AB021130 mRNA. Translation: BAA35180.1.
AB025280 mRNA. Translation: BAA76386.1.
AK089211 mRNA. Translation: BAC40794.1.
AK152088 mRNA. Translation: BAE30938.1.
AK171143 mRNA. Translation: BAE42274.1.
BC003892 mRNA. Translation: AAH03892.1.
BC003904 mRNA. Translation: AAH03904.1.
PIRA36479.
RefSeqNP_032620.2. NM_008594.2.
UniGeneMm.1451.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2L9LNMR-A306-463[»]
ProteinModelPortalP21956.
SMRP21956. Positions 24-463.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP21956. 1 interaction.
MINTMINT-4101815.

PTM databases

PhosphoSiteP21956.

Proteomic databases

PaxDbP21956.
PRIDEP21956.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000032825; ENSMUSP00000032825; ENSMUSG00000030605. [P21956-1]
ENSMUST00000107409; ENSMUSP00000103032; ENSMUSG00000030605. [P21956-2]
GeneID17304.
KEGGmmu:17304.
UCSCuc009hxz.1. mouse. [P21956-1]
uc009hyb.1. mouse. [P21956-2]

Organism-specific databases

CTD4240.
MGIMGI:102768. Mfge8.

Phylogenomic databases

eggNOGNOG151024.
GeneTreeENSGT00740000114988.
HOGENOMHOG000236278.
HOVERGENHBG002385.
InParanoidQ3U8S9.
KOK17253.
OMAVAWHNRI.
OrthoDBEOG7ZWD1D.
TreeFamTF330156.

Gene expression databases

ArrayExpressP21956.
BgeeP21956.
CleanExMM_MFGE8.
GenevestigatorP21956.

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. 2 hits.
PF00754. F5_F8_type_C. 2 hits.
PF12661. hEGF. 1 hit.
[Graphical view]
SMARTSM00181. EGF. 2 hits.
SM00231. FA58C. 2 hits.
[Graphical view]
SUPFAMSSF49785. SSF49785. 2 hits.
PROSITEPS00022. EGF_1. 2 hits.
PS01186. EGF_2. 2 hits.
PS50026. EGF_3. 2 hits.
PS01285. FA58C_1. 2 hits.
PS01286. FA58C_2. 2 hits.
PS50022. FA58C_3. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMFGE8. mouse.
NextBio291842.
PROP21956.
SOURCESearch...

Entry information

Entry nameMFGM_MOUSE
AccessionPrimary (citable) accession number: P21956
Secondary accession number(s): P97800 expand/collapse secondary AC list , Q3TBN5, Q3U8S9, Q9R1X9, Q9WTS3
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 120 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot