ID   VPREB_HUMAN             Reviewed;         145 AA.
AC   P12018; B5MCG2;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2000, sequence version 2.
DT   24-JAN-2024, entry version 192.
DE   RecName: Full=Immunoglobulin iota chain;
DE   AltName: Full=CD179 antigen-like family member A;
DE   AltName: Full=Protein VPreB1;
DE   AltName: Full=V(pre)B protein;
DE            Short=VpreB protein;
DE   AltName: CD_antigen=CD179a;
DE   Flags: Precursor;
GN   Name=VPREB1; Synonyms=VPREB;
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 [GENOMIC DNA].
RX   PubMed=7935499; DOI=10.1016/0161-5890(94)90105-8;
RA   Guelpa-Fonlupt V., Bossy D., Alzari P., Fumoux F., Fougereau M., Schiff C.;
RT   "The human pre-B cell receptor: structural constraints for a tentative
RT   model of the pseudo-light (psi L) chain.";
RL   Mol. Immunol. 31:1099-1108(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9074928; DOI=10.1101/gr.7.3.250;
RA   Kawasaki K., Minoshima S., Nakato E., Shibuya K., Shintani A.,
RA   Schmeits J.L., Wang J., Shimizu N.;
RT   "One-megabase sequence analysis of the human immunoglobulin lambda gene
RT   locus.";
RL   Genome Res. 7:250-261(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA   Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA   Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA   Beare D.M., Dunham I.;
RT   "A genome annotation-driven approach to cloning the human ORFeome.";
RL   Genome Biol. 5:R84.1-R84.11(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10591208; DOI=10.1038/990031;
RA   Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA   Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA   Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA   Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA   Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA   Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA   Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA   Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA   Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA   Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA   Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA   Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA   Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA   Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA   Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA   Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA   Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA   Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA   Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA   Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA   Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA   Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA   Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA   Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA   Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA   Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA   Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA   Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA   Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA   Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA   Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA   Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA   Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA   McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA   Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA   Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA   Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA   Wright H.;
RT   "The DNA sequence of human chromosome 22.";
RL   Nature 402:489-495(1999).
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 [GENOMIC DNA] OF 1-139.
RX   PubMed=3258819; DOI=10.1002/j.1460-2075.1988.tb02789.x;
RA   Bauer S.R., Kudo A., Melchers F.;
RT   "Structure and pre-B lymphocyte restricted expression of the VpreB in
RT   humans and conservation of its structure in other mammalian species.";
RL   EMBO J. 7:111-116(1988).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 21-119 IN COMPLEX WITH IGLL1,
RP   SUBUNIT, AND DISULFIDE BOND.
RX   PubMed=17431183; DOI=10.1126/science.1139412;
RA   Bankovich A.J., Raunser S., Juo Z.S., Walz T., Davis M.M., Garcia K.C.;
RT   "Structural insight into pre-B cell receptor function.";
RL   Science 316:291-294(2007).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 95-108, AND DISULFIDE BOND.
RX   PubMed=18287279; DOI=10.1110/ps.073269808;
RA   Morstadt L., Bohm A., Yuksel D., Kumar K., Stollar B.D., Baleja J.D.;
RT   "Engineering and characterization of a single chain surrogate light chain
RT   variable domain.";
RL   Protein Sci. 17:458-465(2008).
CC   -!- FUNCTION: Associates with the Ig-mu chain to form a molecular complex
CC       that is expressed on the surface of pre-B-cells. This complex
CC       presumably regulates Ig gene rearrangements in the early steps of B-
CC       cell differentiation.
CC   -!- SUBUNIT: Interacts with IGLL1 (PubMed:17431183). Interacts with
CC       SYNV1/HRD1 (via N-terminus); this interaction leads to increased VPREB1
CC       ubiquitination and degradation in pre-B cells, possibly through a
CC       lysosomal, not proteasomal, pathway (By similarity).
CC       {ECO:0000250|UniProtKB:P13372, ECO:0000269|PubMed:17431183}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC       {ECO:0000250|UniProtKB:P13372}.
CC   -!- TISSUE SPECIFICITY: Only expressed by pre-B-cells.
CC   -!- SIMILARITY: Belongs to the immunoglobulin superfamily. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=VPREB1;
CC       URL="https://en.wikipedia.org/wiki/VPREB1";
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DR   EMBL; S74019; AAB32118.1; -; Genomic_DNA.
DR   EMBL; D86992; BAA19987.1; -; Genomic_DNA.
DR   EMBL; D88270; BAA20030.1; -; Genomic_DNA.
DR   EMBL; CR456609; CAG30495.1; -; mRNA.
DR   EMBL; CH471095; EAW59498.1; -; Genomic_DNA.
DR   EMBL; M34927; AAA61292.1; -; Genomic_DNA.
DR   CCDS; CCDS13798.1; -.
DR   PIR; I57832; I57832.
DR   PIR; S00258; S00258.
DR   RefSeq; NP_009059.1; NM_007128.3.
DR   PDB; 2H32; X-ray; 2.70 A; A=20-145.
DR   PDB; 2H3N; X-ray; 2.30 A; A/C=21-119.
DR   PDB; 3BJ9; X-ray; 2.00 A; 1=22-121.
DR   PDBsum; 2H32; -.
DR   PDBsum; 2H3N; -.
DR   PDBsum; 3BJ9; -.
DR   AlphaFoldDB; P12018; -.
DR   SMR; P12018; -.
DR   BioGRID; 113280; 1.
DR   CORUM; P12018; -.
DR   IntAct; P12018; 1.
DR   STRING; 9606.ENSP00000385361; -.
DR   iPTMnet; P12018; -.
DR   PhosphoSitePlus; P12018; -.
DR   BioMuta; VPREB1; -.
DR   DMDM; 9911096; -.
DR   PaxDb; 9606-ENSP00000385361; -.
DR   PeptideAtlas; P12018; -.
DR   ProteomicsDB; 52817; -.
DR   TopDownProteomics; P12018; -.
DR   Antibodypedia; 23612; 201 antibodies from 26 providers.
DR   DNASU; 7441; -.
DR   Ensembl; ENST00000403807.4; ENSP00000385361.3; ENSG00000169575.5.
DR   GeneID; 7441; -.
DR   KEGG; hsa:7441; -.
DR   MANE-Select; ENST00000403807.4; ENSP00000385361.3; NM_007128.4; NP_009059.1.
DR   UCSC; uc002zvx.2; human.
DR   AGR; HGNC:12709; -.
DR   CTD; 7441; -.
DR   DisGeNET; 7441; -.
DR   GeneCards; VPREB1; -.
DR   HGNC; HGNC:12709; VPREB1.
DR   HPA; ENSG00000169575; Tissue enriched (bone).
DR   MIM; 605141; gene.
DR   neXtProt; NX_P12018; -.
DR   OpenTargets; ENSG00000169575; -.
DR   PharmGKB; PA37324; -.
DR   VEuPathDB; HostDB:ENSG00000169575; -.
DR   eggNOG; ENOG502RTXJ; Eukaryota.
DR   GeneTree; ENSGT00940000161017; -.
DR   HOGENOM; CLU_077975_4_0_1; -.
DR   InParanoid; P12018; -.
DR   OMA; FYSIFWY; -.
DR   OrthoDB; 4068101at2759; -.
DR   PhylomeDB; P12018; -.
DR   TreeFam; TF352061; -.
DR   PathwayCommons; P12018; -.
DR   Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR   SignaLink; P12018; -.
DR   BioGRID-ORCS; 7441; 16 hits in 1138 CRISPR screens.
DR   EvolutionaryTrace; P12018; -.
DR   GeneWiki; VPREB1; -.
DR   GenomeRNAi; 7441; -.
DR   Pharos; P12018; Tbio.
DR   PRO; PR:P12018; -.
DR   Proteomes; UP000005640; Chromosome 22.
DR   RNAct; P12018; Protein.
DR   Bgee; ENSG00000169575; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 22 other cell types or tissues.
DR   ExpressionAtlas; P12018; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0006955; P:immune response; IBA:GO_Central.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR   InterPro; IPR007110; Ig-like_dom.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR003599; Ig_sub.
DR   InterPro; IPR013106; Ig_V-set.
DR   PANTHER; PTHR23267:SF11; IMMUNOGLOBULIN IOTA CHAIN; 1.
DR   PANTHER; PTHR23267; IMMUNOGLOBULIN LIGHT CHAIN; 1.
DR   Pfam; PF07686; V-set; 1.
DR   SMART; SM00409; IG; 1.
DR   SMART; SM00406; IGv; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 1.
DR   PROSITE; PS50835; IG_LIKE; 1.
DR   Genevisible; P12018; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Disulfide bond; Endoplasmic reticulum; Immunoglobulin domain;
KW   Reference proteome; Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   CHAIN           20..145
FT                   /note="Immunoglobulin iota chain"
FT                   /id="PRO_0000015000"
FT   DOMAIN          20..132
FT                   /note="Ig-like V-type"
FT   REGION          20..41
FT                   /note="Framework-1"
FT   REGION          42..56
FT                   /note="Complementarity-determining-1"
FT   REGION          57..70
FT                   /note="Framework-2"
FT   REGION          71..81
FT                   /note="Complementarity-determining-2"
FT   REGION          82..115
FT                   /note="Framework-3"
FT   REGION          121..145
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   DISULFID        41..115
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT                   ECO:0000269|PubMed:17431183, ECO:0000269|PubMed:18287279"
FT   VARIANT         76
FT                   /note="D -> N (in dbSNP:rs1320)"
FT                   /id="VAR_024503"
FT   VARIANT         122
FT                   /note="S -> L (in dbSNP:rs11089979)"
FT                   /id="VAR_029133"
FT   VARIANT         132
FT                   /note="E -> K (in dbSNP:rs5995720)"
FT                   /id="VAR_029134"
FT   CONFLICT        10
FT                   /note="L -> H (in Ref. 6; AAA61292)"
FT                   /evidence="ECO:0000305"
FT   STRAND          22..24
FT                   /evidence="ECO:0007829|PDB:2H32"
FT   STRAND          27..32
FT                   /evidence="ECO:0007829|PDB:3BJ9"
FT   STRAND          37..43
FT                   /evidence="ECO:0007829|PDB:3BJ9"
FT   STRAND          45..47
FT                   /evidence="ECO:0007829|PDB:3BJ9"
FT   HELIX           49..51
FT                   /evidence="ECO:0007829|PDB:3BJ9"
FT   STRAND          54..59
FT                   /evidence="ECO:0007829|PDB:3BJ9"
FT   STRAND          66..73
FT                   /evidence="ECO:0007829|PDB:3BJ9"
FT   STRAND          76..79
FT                   /evidence="ECO:0007829|PDB:3BJ9"
FT   STRAND          87..92
FT                   /evidence="ECO:0007829|PDB:3BJ9"
FT   HELIX           93..95
FT                   /evidence="ECO:0007829|PDB:3BJ9"
FT   STRAND          97..102
FT                   /evidence="ECO:0007829|PDB:3BJ9"
FT   HELIX           107..109
FT                   /evidence="ECO:0007829|PDB:3BJ9"
FT   STRAND          111..117
FT                   /evidence="ECO:0007829|PDB:3BJ9"
SQ   SEQUENCE   145 AA;  16605 MW;  197665B13AF64D46 CRC64;
     MSWAPVLLML FVYCTGCGPQ PVLHQPPAMS SALGTTIRLT CTLRNDHDIG VYSVYWYQQR
     PGHPPRFLLR YFSQSDKSQG PQVPPRFSGS KDVARNRGYL SISELQPEDE AMYYCAMGAR
     SSEKEERERE WEEEMEPTAA RTRVP
//