GenomeNet

Database: UniProt
Entry: Q95114
LinkDB: Q95114
Original site: Q95114 
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   16-JAN-2019, entry version 120.
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;
OC   Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia;
OC   Pecora; Bovidae; Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND
RP   GLYCOSYLATION AT 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.,
RA   Petersen T.E.;
RT   "Characterization of glycoprotein PAS-6/7 from membranes of bovine
RT   milk fat 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
RT   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.,
RA   Matsuda T., 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
RT   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
RT   PAS-7, 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.,
RA   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
RT   binding motif, shows similarity to the C2 domains of factor V and
RT   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
CC       many tissues. Plays an important role in the maintenance of
CC       intestinal epithelial homeostasis and the promotion of mucosal
CC       healing. Promotes VEGF-dependent neovascularization (By
CC       similarity). Specific ligand for the alpha-v/beta-3 and alpha-
CC       v/beta-5 receptors. Also binds to phosphatidylserine-enriched cell
CC       surfaces in a receptor-independent manner. Zona pellucida-binding
CC       protein which may play a role in gamete interaction. {ECO:0000250,
CC       ECO:0000269|PubMed:10821695}.
CC   -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein.
CC       Secreted {ECO:0000250}.
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
CC       epididymis, kidney, heart, lymphatic gland and spleen but not
CC       esophagus, small intestine, muscle and liver.
CC       {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.
CC       {ECO:0000269|PubMed:8856064}.
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   UniGene; Bt.5250; -.
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   ProteinModelPortal; 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; ENOG410IFBC; Eukaryota.
DR   eggNOG; ENOG41114BV; LUCA.
DR   HOVERGEN; HBG002385; -.
DR   InParanoid; Q95114; -.
DR   KO; K17253; -.
DR   OrthoDB; 441415at2759; -.
DR   EvolutionaryTrace; Q95114; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; 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   Gene3D; 2.60.120.260; -; 2.
DR   InterPro; IPR013032; EGF-like_CS.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR000421; FA58C.
DR   InterPro; IPR008979; Galactose-bd-like_sf.
DR   InterPro; IPR027060; Lactadherin.
DR   PANTHER; PTHR44122:SF1; PTHR44122:SF1; 2.
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   Complete proteome; Direct protein sequencing; Disulfide bond;
KW   EGF-like domain; Fertilization; Glycoprotein; Membrane;
KW   Reference proteome; Repeat; Secreted; Signal.
FT   SIGNAL        1     18
FT   CHAIN        19    427       Lactadherin.
FT                                /FTId=PRO_0000007649.
FT   DOMAIN       20     59       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN       62    106       EGF-like 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      109    265       F5/8 type C 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00081}.
FT   DOMAIN      270    427       F5/8 type C 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00081}.
FT   MOTIF        85     87       Cell attachment site.
FT   CARBOHYD     27     27       O-linked (Fuc...) serine; in PAS-6.
FT                                {ECO:0000269|PubMed:8856064}.
FT   CARBOHYD     34     34       O-linked (Fuc...) threonine; in PAS-7.
FT                                {ECO:0000269|PubMed:8856064}.
FT   CARBOHYD     59     59       N-linked (GlcNAc...) (hybrid) asparagine;
FT                                in PAS-6 and PAS-7.
FT                                {ECO:0000269|PubMed:8856064}.
FT   CARBOHYD    227    227       N-linked (GlcNAc...) (high mannose)
FT                                asparagine; in PAS-6.
FT                                {ECO:0000269|PubMed:8856064}.
FT   DISULFID     24     35       {ECO:0000250}.
FT   DISULFID     29     47       {ECO:0000250}.
FT   DISULFID     49     58       {ECO:0000250}.
FT   DISULFID     66     77       {ECO:0000250}.
FT   DISULFID     71     94       {ECO:0000250}.
FT   DISULFID     96    105       {ECO:0000250}.
FT   DISULFID    109    265       {ECO:0000269|PubMed:8856064}.
FT   DISULFID    252    256       {ECO:0000269|PubMed:8856064}.
FT   DISULFID    270    427       {ECO:0000269|PubMed:8856064}.
FT   VAR_SEQ     169    221       Missing (in isoform Short).
FT                                {ECO:0000305}.
FT                                /FTId=VSP_001398.
FT   CONFLICT     19     19       A -> F (in Ref. 1; CAA62997).
FT                                {ECO:0000305}.
FT   CONFLICT     28     28       L -> Q (in Ref. 1; CAA62997).
FT                                {ECO:0000305}.
FT   HELIX       283    285       {ECO:0000244|PDB:3BN6}.
FT   STRAND      286    289       {ECO:0000244|PDB:3BN6}.
FT   HELIX       294    296       {ECO:0000244|PDB:3BN6}.
FT   HELIX       298    300       {ECO:0000244|PDB:3BN6}.
FT   HELIX       304    306       {ECO:0000244|PDB:3BN6}.
FT   STRAND      313    315       {ECO:0000244|PDB:3BN6}.
FT   STRAND      317    319       {ECO:0000244|PDB:3BN6}.
FT   STRAND      329    345       {ECO:0000244|PDB:3BN6}.
FT   STRAND      347    349       {ECO:0000244|PDB:3BN6}.
FT   STRAND      352    369       {ECO:0000244|PDB:3BN6}.
FT   STRAND      388    391       {ECO:0000244|PDB:3BN6}.
FT   STRAND      394    417       {ECO:0000244|PDB:3BN6}.
FT   STRAND      419    426       {ECO:0000244|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
//
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