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   27-MAR-2024, entry version 204.
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; 8.
DR   STRING; 9606.ENSP00000301046; -.
DR   DrugBank; DB03796; Palmitic Acid.
DR   Allergome; 1289; Hom s ALA.
DR   GlyCosmos; P00709; 2 sites, No reported glycans.
DR   GlyGen; P00709; 2 sites.
DR   iPTMnet; P00709; -.
DR   PhosphoSitePlus; P00709; -.
DR   BioMuta; LALBA; -.
DR   DMDM; 126001; -.
DR   MassIVE; P00709; -.
DR   PaxDb; 9606-ENSP00000301046; -.
DR   PeptideAtlas; P00709; -.
DR   ProteomicsDB; 51268; -.
DR   Antibodypedia; 13654; 427 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   AGR; HGNC:6480; -.
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; 5344399at2759; -.
DR   PhylomeDB; P00709; -.
DR   TreeFam; TF324882; -.
DR   BioCyc; MetaCyc:HS09571-MONOMER; -.
DR   PathwayCommons; P00709; -.
DR   Reactome; R-HSA-5653890; Lactose synthesis.
DR   SignaLink; P00709; -.
DR   BioGRID-ORCS; 3906; 9 hits in 1139 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 male germ line stem cell (sensu Vertebrata) in testis and 78 other cell types or tissues.
DR   ExpressionAtlas; P00709; baseline and differential.
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   CDD; cd16898; LYZ_LA; 1.
DR   Gene3D; 1.10.530.10; -; 1.
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:SF32; ALPHA-LACTALBUMIN; 1.
DR   PANTHER; PTHR11407; LYSOZYME C; 1.
DR   Pfam; PF00062; Lys; 1.
DR   PRINTS; PR00136; LACTALBUMIN.
DR   PRINTS; PR00135; LYZLACT.
DR   SMART; SM00263; LYZ1; 1.
DR   SUPFAM; SSF53955; Lysozyme-like; 1.
DR   PROSITE; PS00128; GLYCOSYL_HYDROL_F22_1; 1.
DR   PROSITE; PS51348; GLYCOSYL_HYDROL_F22_2; 1.
DR   Genevisible; P00709; HS.
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
//