LALBA_HUMAN
ID LALBA_HUMAN Reviewed; 142 AA.
AC P00709; Q6FGX0; Q9UDK4;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Alpha-lactalbumin;
DE AltName: Full=Lactose synthase B protein;
DE AltName: Full=Lysozyme-like protein 7;
DE Flags: Precursor;
GN Name=LALBA; Synonyms=LYZL7;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6285305; DOI=10.1093/nar/10.11.3503;
RA Hall L., Craig R.K., Edbrooke M.R., Campbell P.N.;
RT "Comparison of the nucleotide sequence of cloned human and guinea-pig pre-
RT alpha-lactalbumin cDNA with that of chick pre-lysozyme cDNA suggests
RT evolution from a common ancestral gene.";
RL Nucleic Acids Res. 10:3503-3515(1982).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2954544; DOI=10.1042/bj2420735;
RA Hall L., Emery D.C., Davies M.S., Parker D., Craig R.K.;
RT "Organization and sequence of the human alpha-lactalbumin gene.";
RL Biochem. J. 242:735-742(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Fujiwara Y., Takahashi R., Hirabayashi M., Ueda M., Muramatsu T.,
RA Yamanaka H., Sekikawa K.;
RT "Analysis of flanking sequence of human alpha-lactalbumin containing a
RT putative locus control region.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 20-142.
RX PubMed=5049057; DOI=10.1111/j.1432-1033.1972.tb01812.x;
RA Findlay J.B.C., Brew K.;
RT "The complete amino-acid sequence of human alpha-lactalbumin.";
RL Eur. J. Biochem. 27:65-86(1972).
RN [8]
RP PROTEIN SEQUENCE OF 78-81 AND 90-112.
RC TISSUE=Milk;
RX PubMed=1401360; DOI=10.1017/s0022029900030697;
RA Maynard F.;
RT "Identification of a new molecular form of human alpha-lactalbumin.";
RL J. Dairy Res. 59:425-429(1992).
RN [9]
RP GLYCOSYLATION AT ASN-90.
RA Cavaletto M., Giuffrida M.G., Giunta C., Conti A.;
RT "An unusual glycosylation site in alpha-lactalbumin from human milk.";
RL Protein Sci. 4 Suppl. 1:119-119(1995).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-64.
RC TISSUE=Milk;
RX PubMed=18780401; DOI=10.1002/pmic.200701057;
RA Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.;
RT "Identification of N-linked glycoproteins in human milk by hydrophilic
RT interaction liquid chromatography and mass spectrometry.";
RL Proteomics 8:3833-3847(2008).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
RX PubMed=1920433; DOI=10.1016/0022-2836(91)80073-4;
RA Acharya K.R., Ren J.S., Stuart D.I., Phillips D.C., Fenna R.E.;
RT "Crystal structure of human alpha-lactalbumin at 1.7-A resolution.";
RL J. Mol. Biol. 221:571-581(1991).
RN [12] {ECO:0007744|PDB:1HML}
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH CALCIUM AND ZINC.
RX PubMed=8366079; DOI=10.1016/s0021-9258(19)36512-3;
RA Ren J.S., Stuart D.I., Acharya K.R.;
RT "Alpha-lactalbumin possesses a distinct zinc binding site.";
RL J. Biol. Chem. 268:19292-19298(1993).
RN [13] {ECO:0007744|PDB:1A4V}
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 20-142 IN COMPLEX WITH CALCIUM.
RX PubMed=9537992; DOI=10.1021/bi973000t;
RA Chandra N., Brew K., Acharya K.R.;
RT "Structural evidence for the presence of a secondary calcium binding site
RT in human alpha-lactalbumin.";
RL Biochemistry 37:4767-4772(1998).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS).
RX PubMed=10080897; DOI=10.1006/jmbi.1999.2598;
RA Harata K., Abe Y., Muraki M.;
RT "Crystallographic evaluation of internal motion of human alpha-lactalbumin
RT refined by full-matrix least-squares method.";
RL J. Mol. Biol. 287:347-358(1999).
RN [15]
RP VARIANT VAL-46, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15866226; DOI=10.1016/j.jnutbio.2004.12.010;
RA Chowanadisai W., Kelleher S.L., Nemeth J.F., Yachetti S., Kuhlman C.F.,
RA Jackson J.G., Davis A.M., Lien E.L., Loennerdal B.;
RT "Detection of a single nucleotide polymorphism in the human alpha-
RT lactalbumin gene: implications for human milk proteins.";
RL J. Nutr. Biochem. 16:272-278(2005).
CC -!- FUNCTION: Regulatory subunit of lactose synthase, changes the substrate
CC specificity of galactosyltransferase in the mammary gland making
CC glucose a good acceptor substrate for this enzyme. This enables LS to
CC synthesize lactose, the major carbohydrate component of milk. In other
CC tissues, galactosyltransferase transfers galactose onto the N-
CC acetylglucosamine of the oligosaccharide chains in glycoproteins.
CC -!- SUBUNIT: Lactose synthase (LS) is a heterodimer of a catalytic
CC component, beta1,4-galactosyltransferase (beta4Gal-T1) and a regulatory
CC component, alpha-lactalbumin (LA).
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Mammary gland specific. Secreted in milk.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 22 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00680}.
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DR EMBL; J00270; AAA60345.1; -; mRNA.
DR EMBL; X05153; CAA28799.1; -; Genomic_DNA.
DR EMBL; X05153; CAA28800.1; -; Genomic_DNA.
DR EMBL; AB049976; BAC06860.1; -; Genomic_DNA.
DR EMBL; CR541987; CAG46784.1; -; mRNA.
DR EMBL; CR542017; CAG46814.1; -; mRNA.
DR EMBL; CH471111; EAW57990.1; -; Genomic_DNA.
DR EMBL; BC069103; AAH69103.1; -; mRNA.
DR EMBL; BC112316; AAI12317.1; -; mRNA.
DR EMBL; BC112318; AAI12319.1; -; mRNA.
DR CCDS; CCDS8765.1; -.
DR PIR; A27880; LAHU.
DR RefSeq; NP_002280.1; NM_002289.2.
DR PDB; 1A4V; X-ray; 1.80 A; A=20-142.
DR PDB; 1B9O; X-ray; 1.15 A; A=20-142.
DR PDB; 1CB3; NMR; -; A=120-130.
DR PDB; 1HML; X-ray; 1.70 A; A=1-142.
DR PDB; 3B0I; X-ray; 1.80 A; A=20-142.
DR PDB; 3B0O; X-ray; 1.61 A; A/B=21-142.
DR PDB; 4L41; X-ray; 2.70 A; A/B=19-142.
DR PDBsum; 1A4V; -.
DR PDBsum; 1B9O; -.
DR PDBsum; 1CB3; -.
DR PDBsum; 1HML; -.
DR PDBsum; 3B0I; -.
DR PDBsum; 3B0O; -.
DR PDBsum; 4L41; -.
DR AlphaFoldDB; P00709; -.
DR BMRB; P00709; -.
DR PCDDB; P00709; -.
DR SMR; P00709; -.
DR BioGRID; 110101; 7.
DR STRING; 9606.ENSP00000301046; -.
DR DrugBank; DB03796; Palmitic Acid.
DR Allergome; 1289; Hom s ALA.
DR GlyGen; P00709; 2 sites.
DR iPTMnet; P00709; -.
DR PhosphoSitePlus; P00709; -.
DR BioMuta; LALBA; -.
DR DMDM; 126001; -.
DR MassIVE; P00709; -.
DR PaxDb; P00709; -.
DR PeptideAtlas; P00709; -.
DR PRIDE; P00709; -.
DR ProteomicsDB; 51268; -.
DR Antibodypedia; 13654; 371 antibodies from 30 providers.
DR DNASU; 3906; -.
DR Ensembl; ENST00000301046.6; ENSP00000301046.2; ENSG00000167531.6.
DR GeneID; 3906; -.
DR KEGG; hsa:3906; -.
DR MANE-Select; ENST00000301046.6; ENSP00000301046.2; NM_002289.3; NP_002280.1.
DR UCSC; uc001rrt.3; human.
DR CTD; 3906; -.
DR DisGeNET; 3906; -.
DR GeneCards; LALBA; -.
DR HGNC; HGNC:6480; LALBA.
DR HPA; ENSG00000167531; Tissue enriched (breast).
DR MIM; 149750; gene.
DR neXtProt; NX_P00709; -.
DR OpenTargets; ENSG00000167531; -.
DR PharmGKB; PA30269; -.
DR VEuPathDB; HostDB:ENSG00000167531; -.
DR eggNOG; ENOG502T8BJ; Eukaryota.
DR GeneTree; ENSGT00940000161726; -.
DR InParanoid; P00709; -.
DR OMA; KCELSQV; -.
DR OrthoDB; 1551203at2759; -.
DR PhylomeDB; P00709; -.
DR TreeFam; TF324882; -.
DR BioCyc; MetaCyc:HS09571-MON; -.
DR PathwayCommons; P00709; -.
DR Reactome; R-HSA-5653890; Lactose synthesis.
DR SignaLink; P00709; -.
DR BioGRID-ORCS; 3906; 8 hits in 1060 CRISPR screens.
DR EvolutionaryTrace; P00709; -.
DR GeneWiki; Alpha-lactalbumin; -.
DR GenomeRNAi; 3906; -.
DR Pharos; P00709; Tbio.
DR PRO; PR:P00709; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P00709; protein.
DR Bgee; ENSG00000167531; Expressed in epithelium of mammary gland and 77 other tissues.
DR ExpressionAtlas; P00709; baseline and differential.
DR Genevisible; P00709; HS.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004461; F:lactose synthase activity; IEA:Ensembl.
DR GO; GO:0003796; F:lysozyme activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0042742; P:defense response to bacterium; TAS:ProtInc.
DR GO; GO:0005989; P:lactose biosynthetic process; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR001916; Glyco_hydro_22.
DR InterPro; IPR019799; Glyco_hydro_22_CS.
DR InterPro; IPR000545; Lactalbumin.
DR InterPro; IPR023346; Lysozyme-like_dom_sf.
DR PANTHER; PTHR11407; PTHR11407; 1.
DR PANTHER; PTHR11407:SF32; PTHR11407:SF32; 1.
DR Pfam; PF00062; Lys; 1.
DR PRINTS; PR00136; LACTALBUMIN.
DR PRINTS; PR00135; LYZLACT.
DR SMART; SM00263; LYZ1; 1.
DR SUPFAM; SSF53955; SSF53955; 1.
DR PROSITE; PS00128; GLYCOSYL_HYDROL_F22_1; 1.
DR PROSITE; PS51348; GLYCOSYL_HYDROL_F22_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Lactose biosynthesis; Metal-binding; Milk protein;
KW Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:5049057"
FT CHAIN 20..142
FT /note="Alpha-lactalbumin"
FT /id="PRO_0000018444"
FT DOMAIN 20..142
FT /note="C-type lysozyme"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00680"
FT BINDING 57
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9537992,
FT ECO:0007744|PDB:1A4V"
FT BINDING 58
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9537992,
FT ECO:0007744|PDB:1A4V"
FT BINDING 68
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:8366079,
FT ECO:0007744|PDB:1HML"
FT BINDING 98
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:8366079,
FT ECO:0000269|PubMed:9537992, ECO:0007744|PDB:1A4V,
FT ECO:0007744|PDB:1HML"
FT BINDING 100
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9537992,
FT ECO:0007744|PDB:1A4V"
FT BINDING 101
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:8366079,
FT ECO:0000269|PubMed:9537992, ECO:0007744|PDB:1A4V,
FT ECO:0007744|PDB:1HML"
FT BINDING 102
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9537992,
FT ECO:0007744|PDB:1A4V"
FT BINDING 103
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:8366079,
FT ECO:0000269|PubMed:9537992, ECO:0007744|PDB:1A4V,
FT ECO:0007744|PDB:1HML"
FT BINDING 106
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:8366079,
FT ECO:0000269|PubMed:9537992, ECO:0007744|PDB:1A4V,
FT ECO:0007744|PDB:1HML"
FT BINDING 107
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:8366079,
FT ECO:0000269|PubMed:9537992, ECO:0007744|PDB:1A4V,
FT ECO:0007744|PDB:1HML"
FT BINDING 135
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:8366079,
FT ECO:0007744|PDB:1HML"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:18780401"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine; atypical; partial"
FT /evidence="ECO:0000269|Ref.9"
FT DISULFID 25..139
FT DISULFID 47..130
FT DISULFID 80..96
FT DISULFID 92..110
FT VARIANT 46
FT /note="I -> V (in dbSNP:rs2232565)"
FT /evidence="ECO:0000269|PubMed:15866226"
FT /id="VAR_024526"
FT CONFLICT 99
FT /note="F -> K (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 24..30
FT /evidence="ECO:0007829|PDB:1B9O"
FT HELIX 32..34
FT /evidence="ECO:0007829|PDB:1B9O"
FT HELIX 37..39
FT /evidence="ECO:0007829|PDB:1B9O"
FT HELIX 42..53
FT /evidence="ECO:0007829|PDB:1B9O"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:1B9O"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:1B9O"
FT TURN 70..73
FT /evidence="ECO:0007829|PDB:1B9O"
FT TURN 76..78
FT /evidence="ECO:0007829|PDB:1B9O"
FT STRAND 79..81
FT /evidence="ECO:0007829|PDB:1B9O"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:4L41"
FT STRAND 91..95
FT /evidence="ECO:0007829|PDB:4L41"
FT HELIX 96..100
FT /evidence="ECO:0007829|PDB:1B9O"
FT HELIX 105..117
FT /evidence="ECO:0007829|PDB:1B9O"
FT TURN 118..120
FT /evidence="ECO:0007829|PDB:1B9O"
FT HELIX 121..124
FT /evidence="ECO:0007829|PDB:1B9O"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:3B0O"
FT HELIX 134..137
FT /evidence="ECO:0007829|PDB:1B9O"
SQ SEQUENCE 142 AA; 16225 MW; 647F448733B06D65 CRC64;
MRFFVPLFLV GILFPAILAK QFTKCELSQL LKDIDGYGGI ALPELICTMF HTSGYDTQAI
VENNESTEYG LFQISNKLWC KSSQVPQSRN ICDISCDKFL DDDITDDIMC AKKILDIKGI
DYWLAHKALC TEKLEQWLCE KL
