MFGM_BOVIN
ID MFGM_BOVIN Reviewed; 427 AA.
AC Q95114; P79344; Q27959;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 25-MAY-2022, entry version 132.
DE RecName: Full=Lactadherin;
DE AltName: Full=BP47;
DE AltName: Full=Components 15/16;
DE AltName: Full=MFGM;
DE AltName: Full=MGP57/53;
DE AltName: Full=Milk fat globule-EGF factor 8;
DE Short=MFG-E8;
DE AltName: Full=PAS-6/PAS-7 glycoprotein;
DE AltName: Full=SED1;
DE AltName: Full=Sperm surface protein SP47;
DE Flags: Precursor;
GN Name=MFGE8;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND GLYCOSYLATION AT
RP SER-27; THR-34; ASN-59 AND ASN-227.
RC STRAIN=Holstein; TISSUE=Mammary gland;
RX PubMed=8856064; DOI=10.1111/j.1432-1033.1996.0628h.x;
RA Hvarregaard J., Andersen M.H., Berglund L., Rasmussen J.T., Petersen T.E.;
RT "Characterization of glycoprotein PAS-6/7 from membranes of bovine milk fat
RT globules.";
RL Eur. J. Biochem. 240:628-636(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 18-427.
RC TISSUE=Mammary gland;
RX PubMed=8541316; DOI=10.1016/0304-4165(95)00110-7;
RA Aoki N., Kishi M., Taniguchi Y., Adachi T., Nakamura R., Matsuda T.;
RT "Molecular cloning of glycoprotein antigens MGP57/53 recognized by
RT monoclonal antibodies raised against bovine milk fat globule membrane.";
RL Biochim. Biophys. Acta 1245:385-391(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 19-427, AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=9546740; DOI=10.1095/biolreprod58.4.1057;
RA Ensslin M.A., Vogel T., Calvete J.J., Thole H.H., Schmidtke J., Matsuda T.,
RA Toepfer-Petersen E.;
RT "Molecular cloning and characterization of P47, a novel boar sperm-
RT associated zona pellucida-binding protein homologous to a family of
RT mammalian secretory proteins.";
RL Biol. Reprod. 58:1057-1064(1998).
RN [4]
RP PROTEIN SEQUENCE OF 140-146; 174-187; 233-246 AND 422-427.
RC TISSUE=Milk;
RX PubMed=8485470;
RA Mather I.H., Banghart L.R., Lane W.S.;
RT "The major fat-globule membrane proteins, bovine components 15/16 and
RT guinea-pig GP 55, are homologous to MGF-E8, a murine glycoprotein
RT containing epidermal growth factor-like and factor V/VIII-like sequences.";
RL Biochem. Mol. Biol. Int. 29:545-554(1993).
RN [5]
RP PROTEIN SEQUENCE OF 383-394.
RX PubMed=1643094; DOI=10.1016/0167-4838(92)90325-8;
RA Kim D.H., Kanno C., Mizokami Y.;
RT "Purification and characterization of major glycoproteins, PAS-6 and PAS-7,
RT from bovine milk fat globule membrane.";
RL Biochim. Biophys. Acta 1122:203-211(1992).
RN [6]
RP FUNCTION.
RX PubMed=10821695; DOI=10.1021/bi992221r;
RA Andersen M.H., Graversen H., Fedosov S.N., Petersen T.E., Rasmussen J.T.;
RT "Functional analyses of two cellular binding domains of bovine
RT lactadherin.";
RL Biochemistry 39:6200-6206(2000).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 270-427.
RX PubMed=17583728; DOI=10.1016/j.jmb.2007.05.054;
RA Lin L., Huai Q., Huang M., Furie B., Furie B.C.;
RT "Crystal structure of the bovine lactadherin C2 domain, a membrane binding
RT motif, shows similarity to the C2 domains of factor V and factor VIII.";
RL J. Mol. Biol. 371:717-724(2007).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS) OF 270-427.
RX PubMed=18160406; DOI=10.1074/jbc.m705195200;
RA Shao C., Novakovic V.A., Head J.F., Seaton B.A., Gilbert G.E.;
RT "Crystal structure of lactadherin C2 domain at 1.7A resolution with
RT mutational and computational analyses of its membrane-binding motif.";
RL J. Biol. Chem. 283:7230-7241(2008).
CC -!- FUNCTION: Contributes to phagocytic removal of apoptotic cells in many
CC tissues. Plays an important role in the maintenance of intestinal
CC epithelial homeostasis and the promotion of mucosal healing. Promotes
CC VEGF-dependent neovascularization (By similarity). Specific ligand for
CC the alpha-v/beta-3 and alpha-v/beta-5 receptors. Also binds to
CC phosphatidylserine-enriched cell surfaces in a receptor-independent
CC manner. Zona pellucida-binding protein which may play a role in gamete
CC interaction. {ECO:0000250, ECO:0000269|PubMed:10821695}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P79385};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P79385}. Secreted
CC {ECO:0000250|UniProtKB:P79385}. Cytoplasmic vesicle, secretory vesicle,
CC acrosome membrane {ECO:0000250|UniProtKB:P79385}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:P79385}. Note=Located in the acrosomal
CC region of zona-pellucida bound sperm. {ECO:0000250|UniProtKB:P79385}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=Q95114-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q95114-2; Sequence=VSP_001398;
CC -!- TISSUE SPECIFICITY: Milk and spermatozoan. Also present in epididymis,
CC kidney, heart, lymphatic gland and spleen but not esophagus, small
CC intestine, muscle and liver. {ECO:0000269|PubMed:9546740}.
CC -!- DOMAIN: The F5/8 type C 2 domain mediates high-affinity binding to
CC phosphatidylserine-containing membranes. {ECO:0000250}.
CC -!- PTM: The two O-linked glycans consist of Gal, GlcNAc and Fuc, with
CC probably Fuc as reducing terminal sugar. {ECO:0000269|PubMed:8856064}.
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DR EMBL; X91895; CAA62997.1; -; mRNA.
DR EMBL; S80643; AAB35894.2; -; mRNA.
DR EMBL; Y11719; CAA72406.1; -; mRNA.
DR PIR; S74211; S74211.
DR RefSeq; NP_788783.1; NM_176610.1.
DR PDB; 2PQS; X-ray; 2.40 A; A/B/C/D=270-427.
DR PDB; 3BN6; X-ray; 1.67 A; A=270-427.
DR PDBsum; 2PQS; -.
DR PDBsum; 3BN6; -.
DR AlphaFoldDB; Q95114; -.
DR SMR; Q95114; -.
DR CORUM; Q95114; -.
DR STRING; 9913.ENSBTAP00000004272; -.
DR iPTMnet; Q95114; -.
DR PaxDb; Q95114; -.
DR PeptideAtlas; Q95114; -.
DR PRIDE; Q95114; -.
DR GeneID; 281913; -.
DR KEGG; bta:281913; -.
DR CTD; 4240; -.
DR eggNOG; ENOG502RXUZ; Eukaryota.
DR InParanoid; Q95114; -.
DR EvolutionaryTrace; Q95114; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0002080; C:acrosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0007338; P:single fertilization; IEA:UniProtKB-KW.
DR CDD; cd00057; FA58C; 2.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000421; FA58C.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR Pfam; PF00008; EGF; 2.
DR Pfam; PF00754; F5_F8_type_C; 2.
DR SMART; SM00181; EGF; 2.
DR SMART; SM00231; FA58C; 2.
DR SUPFAM; SSF49785; SSF49785; 2.
DR PROSITE; PS00022; EGF_1; 2.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS50026; EGF_3; 2.
DR PROSITE; PS01285; FA58C_1; 2.
DR PROSITE; PS01286; FA58C_2; 2.
DR PROSITE; PS50022; FA58C_3; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Angiogenesis; Cell adhesion;
KW Cytoplasmic vesicle; Direct protein sequencing; Disulfide bond;
KW EGF-like domain; Fertilization; Glycoprotein; Membrane; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1..18
FT CHAIN 19..427
FT /note="Lactadherin"
FT /id="PRO_0000007649"
FT DOMAIN 20..59
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 62..106
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 109..265
FT /note="F5/8 type C 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DOMAIN 270..427
FT /note="F5/8 type C 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT MOTIF 85..87
FT /note="Cell attachment site"
FT CARBOHYD 27
FT /note="O-linked (Fuc...) serine; in PAS-6"
FT /evidence="ECO:0000269|PubMed:8856064"
FT CARBOHYD 34
FT /note="O-linked (Fuc...) threonine; in PAS-7"
FT /evidence="ECO:0000269|PubMed:8856064"
FT CARBOHYD 59
FT /note="N-linked (GlcNAc...) (hybrid) asparagine; in PAS-6
FT and PAS-7"
FT /evidence="ECO:0000269|PubMed:8856064"
FT CARBOHYD 227
FT /note="N-linked (GlcNAc...) (high mannose) asparagine; in
FT PAS-6"
FT /evidence="ECO:0000269|PubMed:8856064"
FT DISULFID 24..35
FT /evidence="ECO:0000250"
FT DISULFID 29..47
FT /evidence="ECO:0000250"
FT DISULFID 49..58
FT /evidence="ECO:0000250"
FT DISULFID 66..77
FT /evidence="ECO:0000250"
FT DISULFID 71..94
FT /evidence="ECO:0000250"
FT DISULFID 96..105
FT /evidence="ECO:0000250"
FT DISULFID 109..265
FT /evidence="ECO:0000269|PubMed:8856064"
FT DISULFID 252..256
FT /evidence="ECO:0000269|PubMed:8856064"
FT DISULFID 270..427
FT /evidence="ECO:0000269|PubMed:8856064"
FT VAR_SEQ 169..221
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_001398"
FT CONFLICT 19
FT /note="A -> F (in Ref. 1; CAA62997)"
FT /evidence="ECO:0000305"
FT CONFLICT 28
FT /note="L -> Q (in Ref. 1; CAA62997)"
FT /evidence="ECO:0000305"
FT HELIX 283..285
FT /evidence="ECO:0007829|PDB:3BN6"
FT STRAND 286..289
FT /evidence="ECO:0007829|PDB:3BN6"
FT HELIX 294..296
FT /evidence="ECO:0007829|PDB:3BN6"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:3BN6"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:3BN6"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:3BN6"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:3BN6"
FT STRAND 329..345
FT /evidence="ECO:0007829|PDB:3BN6"
FT STRAND 347..349
FT /evidence="ECO:0007829|PDB:3BN6"
FT STRAND 352..369
FT /evidence="ECO:0007829|PDB:3BN6"
FT STRAND 388..391
FT /evidence="ECO:0007829|PDB:3BN6"
FT STRAND 394..417
FT /evidence="ECO:0007829|PDB:3BN6"
FT STRAND 419..426
FT /evidence="ECO:0007829|PDB:3BN6"
SQ SEQUENCE 427 AA; 47411 MW; 4CBBEE3A1DC4EB24 CRC64;
MPCPRLLAAL FCSSGLFAAS GDFCDSSLCL HGGTCLLNED RTPPFYCLCP EGFTGLLCNE
TEHGPCFPNP CHNDAECQVT DDSHRGDVFI QYICKCPLGY VGIHCETTCT SPLGMQTGAI
ADSQISASSM HLGFMGLQRW APELARLHQT GIVNAWTSGN YDKNPWIQVN LMRKMWVTGV
VTQGASRAGS AEYLKTFKVA YSTDGRQFQF IQVAGRSGDK IFIGNVNNSG LKINLFDTPL
ETQYVRLVPI ICHRGCTLRF ELLGCELNGC TEPLGLKDNT IPNKQITASS YYKTWGLSAF
SWFPYYARLD NQGKFNAWTA QTNSASEWLQ IDLGSQKRVT GIITQGARDF GHIQYVAAYR
VAYGDDGVTW TEYKDPGASE SKIFPGNMDN NSHKKNIFET PFQARFVRIQ PVAWHNRITL
RVELLGC
