P21956 (MFGM_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	463 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	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
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 process	Angiogenesis Cell adhesion Fertilization
Cellular component	Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	EGF-like domain Repeat Signal
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis 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 single fertilization Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	external side of plasma membrane Inferred from direct assay PubMed 12000961. Source: MGI extracellular matrix Inferred from electronic annotation. Source: Compara extracellular space Inferred from direct assay PubMed 12000961. Source: MGI extrinsic to plasma membrane Inferred from direct assay PubMed 12000961. Source: MGI
Molecular_function	integrin 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Ref.1

Chain

23 – 463

441

Lactadherin

PRO_0000007653

Regions

Domain

24 – 61

38

EGF-like 1

Domain

64 – 108

45

EGF-like 2

Domain

148 – 303

156

F5/8 type C 1

Domain

308 – 463

156

F5/8 type C 2

Motif

87 – 89

3

Cell attachment site

Amino acid modifications

Glycosylation

61

1

N-linked (GlcNAc...) Potential

Glycosylation

266

1

N-linked (GlcNAc...) Potential

Glycosylation

316

1

N-linked (GlcNAc...) Potential

Glycosylation

426

1

N-linked (GlcNAc...) Potential

Disulfide bond

28 ↔ 39

By similarity

Disulfide bond

33 ↔ 49

By similarity

Disulfide bond

51 ↔ 60

By similarity

Disulfide bond

68 ↔ 79

By similarity

Disulfide bond

73 ↔ 96

By similarity

Disulfide bond

98 ↔ 107

By similarity

Disulfide bond

148 ↔ 303

By similarity

Disulfide bond

290 ↔ 294

By similarity

Disulfide bond

308 ↔ 463

By similarity

Natural variations

Alternative sequence

110 – 147

38

ETNYY…NLASR → G in isoform 2.

VSP_009880

Experimental info

Sequence conflict

35

1

N → D AA sequence Ref.1

Sequence conflict

168

1

S → Y in AAA39534. Ref.1

Sequence conflict

196

1

T → H in AAA39534. Ref.1

Sequence conflict

284

1

K → R in AAA39534. Ref.1

Sequence conflict

284

1

K → R in CAA72380. Ref.3

Sequence conflict

284

1

K → R in BAA35180. Ref.4

Sequence conflict

284

1

K → R in BAA76386. Ref.4

Sequence conflict

284

1

K → R in BAC40794. Ref.5

Sequence conflict

284

1

K → R in BAE42274. Ref.5

Sequence conflict

284

1

K → R in AAH03892. Ref.6

Sequence conflict

284

1

K → R in AAH03904. Ref.6

Sequence conflict

309

1

S → L in AAA39534. Ref.1

Sequence conflict

395

1

A → E in AAA39534. Ref.1

Secondary structure

1

.

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463

Helix Strand Turn

Details...

Beta strand

312 – 316

5

Beta strand

323 – 327

5

Beta strand

346 – 348

3

Beta strand

350 – 352

3

Beta strand

355 – 357

3

Beta strand

359 – 362

4

Beta strand

367 – 384

18

Beta strand

393 – 406

14

Beta strand

414 – 416

3

Turn

425 – 427

3

Beta strand

430 – 432

3

Beta strand

434 – 436

3

Beta strand

438 – 453

16

Beta strand

455 – 462

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified July 27, 2011. Version 3. Checksum: 6E19CBB494B22878	FASTA	463	51,241
	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
	Isoform 2 (Short) [UniParc]. Checksum: 0882EDA89B95C445	FASTA	426	47,169
	10 20 30 40 50 60 MQVSRVLAAL CGMLLCASGL FAASGDFCDS SLCLNGGTCL TGQDNDIYCL CPEGFTGLVC 70 80 90 100 110 120 NETERGPCSP NPCYNDAKCL VTLDTQRGDI FTEYICQCPV GYSGIHCETG CSTQLGMEGG 130 140 150 160 170 180 AIADSQISAS SVYMGFMGLQ RWGPELARLY RTGIVNAWTA SNYDSKPWIQ VNLLRKMRVS 190 200 210 220 230 240 GVMTQGASRA GRAEYLKTFK VAYSLDGRKF EFIQDESGGD KEFLGNLDNN SLKVNMFNPT 250 260 270 280 290 300 LEAQYIKLYP VSCHRGCTLR FELLGCELHG CSEPLGLKNN TIPDSQMSAS SSYKTWNLRA 310 320 330 340 350 360 FGWYPHLGRL DNQGKINAWT AQSNSAKEWL QVDLGTQRQV TGIITQGARD FGHIQYVASY 370 380 390 400 410 420 KVAHSDDGVQ WTVYEEQGSS KVFQGNLDNN SHKKNIFEKP FMARYVRVLP VSWHNRITLR LELLGC

References

	« Hide 'large scale' referencesShow '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. , 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.
+	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.

IPI

IPI00322712.
IPI00411071.

PIR

A36479.

RefSeq

NP_032620.2. NM_008594.2.

UniGene

Mm.1451.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2L9L	NMR	-	A	306-463	[»]

ProteinModelPortal

P21956.

SMR

P21956. Positions 28-463.

ModBase

Search...

PTM databases

PhosphoSite

P21956.

Proteomic databases

PaxDb

P21956.

PRIDE

P21956.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000032825; ENSMUSP00000032825; ENSMUSG00000030605.
ENSMUST00000107409; ENSMUSP00000103032; ENSMUSG00000030605.

GeneID

17304.

KEGG

mmu:17304.

Organism-specific databases

CTD

4240.

MGI

MGI:102768. Mfge8.

Phylogenomic databases

eggNOG

NOG151024.

GeneTree

ENSGT00670000097729.

HOGENOM

HOG000236278.

HOVERGEN

HBG002385.

InParanoid

Q3U8S9.

OMA

QYVAAYK.

OrthoDB

EOG47D9G6.

Gene expression databases

ArrayExpress

P21956.

Bgee

P21956.

CleanEx

MM_MFGE8.

Genevestigator

P21956.

GermOnline

ENSMUSG00000030605. Mus musculus.

Family and domain databases

InterPro

IPR000421. Coagulation_fac_5/8-C_type_dom.
IPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR008979. Galactose-bd-like.
IPR027060. Lactadherin.
[Graphical view]

PANTHER

PTHR10127:SF303. PTHR10127:SF303. 1 hit.

Pfam

PF00008. EGF. 1 hit.
PF00754. F5_F8_type_C. 2 hits.
PF12661. hEGF. 1 hit.
[Graphical view]

SMART

SM00181. EGF. 2 hits.
SM00231. FA58C. 2 hits.
[Graphical view]

SUPFAM

SSF49785. Gal_bind_like. 2 hits.

PROSITE

PS00022. 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]

ProtoNet

Search...

Other

ChiTaRS

MFGE8. mouse.

NextBio

291842.

SOURCE

Search...

Entry information

Entry name

MFGM_MOUSE

Accession

Primary (citable) accession number: P21956
Secondary accession number(s): P97800 , Q3TBN5, Q3U8S9, Q9R1X9, Q9WTS3

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 110 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program