Q08431 (MFGM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	387 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	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.
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 process	Angiogenesis Cell adhesion Fertilization Host-virus interaction
Cellular component	Amyloid Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	EGF-like domain Repeat Signal
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW cell adhesion Traceable author statement. Source: ProtInc interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW single fertilization Inferred from electronic annotation. Source: UniProtKB-KW
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23
	Chain	24 – 387	364	Lactadherin		PRO_0000007650
	Chain	202 – 387	186	Lactadherin short form		PRO_0000007651
	Chain	268 – 317	50	Medin		PRO_0000007652
Regions
	Domain	24 – 67	44	EGF-like
	Domain	70 – 225	156	F5/8 type C 1
	Domain	230 – 387	158	F5/8 type C 2
	Motif	46 – 48	3	Cell attachment site
Amino acid modifications
	Glycosylation	228	1	N-linked (GlcNAc...) Ref.14
	Glycosylation	238	1	N-linked (GlcNAc...) Ref.14
	Glycosylation	325	1	N-linked (GlcNAc...) Ref.14
	Glycosylation	329	1	N-linked (GlcNAc...) Ref.14
	Glycosylation	350	1	N-linked (GlcNAc...) Ref.14
	Disulfide bond	27 ↔ 38		By similarity
	Disulfide bond	32 ↔ 55		By similarity
	Disulfide bond	57 ↔ 66		By similarity
	Disulfide bond	70 ↔ 225		By similarity
	Disulfide bond	212 ↔ 216		By similarity
	Disulfide bond	230 ↔ 387		By similarity
Natural variations
	Alternative sequence	1 – 75	75	Missing in isoform 2.		VSP_039108
	Alternative sequence	291 – 342	52	Missing in isoform 3.		VSP_039953
	Natural variant	3	1	R → S. Corresponds to variant rs4945 [ dbSNP | Ensembl ].		VAR_029794
	Natural variant	76	1	M → L. Ref.4 Ref.5 Ref.7 Corresponds to variant rs1878326 [ dbSNP | Ensembl ].		VAR_024263
Experimental info
	Sequence conflict	268	1	R → W in CAD97938. Ref.5
	Sequence conflict	352	1	S → T in CAD97938. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 2EE6571DEC83782D	FASTA	387	43,123
	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
	Isoform 2 [UniParc]. Checksum: 9E3857A7E7096C8B	FASTA	312	35,189
	10 20 30 40 50 60 MENGNIANSQ IAASSVRVTF LGLQHWVPEL ARLNRAGMVN AWTPSSNDDN PWIQVNLLRR 70 80 90 100 110 120 MWVTGVVTQG ASRLASHEYL KAFKVAYSLN GHEFDFIHDV NKKHKEFVGN WNKNAVHVNL 130 140 150 160 170 180 FETPVEAQYV RLYPTSCHTA CTLRFELLGC ELNGCANPLG LKNNSIPDKQ ITASSSYKTW 190 200 210 220 230 240 GLHLFSWNPS YARLDKQGNF NAWVAGSYGN DQWLQVDLGS SKEVTGIITQ GARNFGSVQF 250 260 270 280 290 300 VASYKVAYSN DSANWTEYQD PRTGSSKIFP GNWDNHSHKK NLFETPILAR YVRILPVAWH 310 NRIALRLELL GC
	Isoform 3 [UniParc]. Checksum: 20E84E5DB78E8E25	FASTA	335	37,523
	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 IFPGNWDNHS 310 320 330 HKKNLFETPI LARYVRILPV AWHNRIALRL ELLGC

References

	« Hide 'large scale' referencesShow '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: 8639264] [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. , 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: 14702039] [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: 17974005] [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. , 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: 16572171] [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. , 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: 15489334] [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: 1909932] [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: 9535276] [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: 10411933] [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: 9260929] [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: 18780401] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-228; ASN-238; ASN-325; ASN-329 AND ASN-350, MASS SPECTROMETRY. 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: 19204935] [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.
IPI	IPI00002236. IPI00334005. IPI00966900.
PIR	A47285.
RefSeq	NP_001108086.1. NM_001114614.1. NP_005919.2. NM_005928.2.
UniGene	Hs.3745.
3D structure databases
ProteinModelPortal	Q08431.
SMR	Q08431. Positions 21-387.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q08431. 1 interaction.
STRING	Q08431.
PTM databases
PhosphoSite	Q08431.
Polymorphism databases
DMDM	2506380.
Proteomic databases
PRIDE	Q08431.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000268150; ENSP00000268150; ENSG00000140545. ENST00000268151; ENSP00000268151; ENSG00000140545.
GeneID	4240.
KEGG	hsa:4240.
Organism-specific databases
CTD	4240.
GeneCards	GC15M089441.
H-InvDB	HIX0012558.
HGNC	HGNC:7036. MFGE8.
HPA	CAB002753. HPA002807.
MIM	602281. gene.
neXtProt	NX_Q08431.
PharmGKB	PA30772.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18806.
GeneTree	ENSGT00550000074267.
HOGENOM	HBG714573.
HOVERGEN	HBG002385.
InParanoid	Q08431.
OrthoDB	EOG47D9G6.
Enzyme and pathway databases
Pathway_Interaction_DB	avb3_integrin_pathway. Integrins in angiogenesis.
Reactome	REACT_75925. Amyloids.
Gene expression databases
ArrayExpress	Q08431.
Bgee	Q08431.
CleanEx	HS_MFGE8.
Genevestigator	Q08431.
GermOnline	ENSG00000140545. Homo sapiens.
Family and domain databases
InterPro	IPR000421. Coagulation_fac_5/8-C_type_dom. IPR006209. EGF. IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. IPR008979. Galactose-bd-like. [Graphical view]
Pfam	PF00008. EGF. 1 hit. PF00754. F5_F8_type_C. 2 hits. [Graphical view]
SMART	SM00181. EGF. 1 hit. SM00231. FA58C. 2 hits. [Graphical view]
SUPFAM	SSF49785. Gal_bind_like. 2 hits.
PROSITE	PS00022. 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]
ProtoNet	Search...
Other
NextBio	16719.
SOURCE	Search...

Entry information

Entry name

MFGM_HUMAN

Accession

Primary (citable) accession number: Q08431
Secondary accession number(s): B2R6M7 , Q53FU9, Q7Z3D2, Q9BTL9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	November 1, 1997
Last modified:	January 25, 2012
This is version 106 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.