ID TCO1_HUMAN Reviewed; 433 AA. AC P20061; A8KAC5; Q8WV77; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2007, sequence version 2. DT 27-MAR-2024, entry version 195. DE RecName: Full=Transcobalamin-1; DE Short=TC-1; DE AltName: Full=Haptocorrin; DE Short=HC; DE AltName: Full=Protein R; DE AltName: Full=Transcobalamin I; DE Short=TC I; DE Short=TCI; DE Flags: Precursor; GN Name=TCN1; Synonyms=TC1; 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], AND TISSUE SPECIFICITY. RX PubMed=2777761; DOI=10.1016/s0021-9258(18)71539-1; RA Johnston J., Bollekens J., Allen R.H., Berliner N.; RT "Structure of the cDNA encoding transcobalamin I, a neutrophil granule RT protein."; RL J. Biol. Chem. 264:15754-15757(1989). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [4] 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 [5] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-216. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [6] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-216 AND ASN-369. RC TISSUE=Saliva; RX PubMed=16740002; DOI=10.1021/pr050492k; RA Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A.; RT "Identification of N-linked glycoproteins in human saliva by glycoprotein RT capture and mass spectrometry."; RL J. Proteome Res. 5:1493-1503(2006). RN [7] {ECO:0007744|PDB:4KKI, ECO:0007744|PDB:4KKJ} RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) IN COMPLEX WITH CYANOCOBALAMIN, RP DISULFIDE BONDS, COBALAMIN-BINDING SITES, AND GLYCOSYLATION AT ASN-216; RP ASN-316; ASN-337; ASN-343; ASN-349; ASN-354 AND ASN-369. RX PubMed=23846701; DOI=10.1074/jbc.m113.483271; RA Furger E., Frei D.C., Schibli R., Fischer E., Prota A.E.; RT "Structural basis for universal corrinoid recognition by the cobalamin RT transport protein haptocorrin."; RL J. Biol. Chem. 288:25466-25476(2013). CC -!- FUNCTION: Binds vitamin B12 with femtomolar affinity and protects it CC from the acidic environment of the stomach. CC -!- INTERACTION: CC P20061; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-2557232, EBI-1055254; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Produced by the salivary glands of the oral cavity, CC in response to ingestion of food. Major constituent of secondary CC granules in neutrophils. {ECO:0000269|PubMed:2777761}. CC -!- PTM: Contains about 30% carbohydrates. CC -!- SIMILARITY: Belongs to the eukaryotic cobalamin transport proteins CC family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J05068; AAA61058.1; -; mRNA. DR EMBL; AK292990; BAF85679.1; -; mRNA. DR EMBL; AP002347; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471076; EAW73861.1; -; Genomic_DNA. DR CCDS; CCDS7978.1; -. DR PIR; A34227; A34227. DR RefSeq; NP_001053.2; NM_001062.3. DR PDB; 4KKI; X-ray; 2.35 A; A=1-433. DR PDB; 4KKJ; X-ray; 3.00 A; A=1-433. DR PDBsum; 4KKI; -. DR PDBsum; 4KKJ; -. DR AlphaFoldDB; P20061; -. DR SMR; P20061; -. DR BioGRID; 112807; 13. DR IntAct; P20061; 3. DR STRING; 9606.ENSP00000257264; -. DR DrugBank; DB00115; Cyanocobalamin. DR DrugBank; DB00200; Hydroxocobalamin. DR DrugCentral; P20061; -. DR GlyConnect; 1830; 10 N-Linked glycans (2 sites). DR GlyCosmos; P20061; 8 sites, 10 glycans. DR GlyGen; P20061; 9 sites, 10 N-linked glycans (2 sites). DR iPTMnet; P20061; -. DR PhosphoSitePlus; P20061; -. DR BioMuta; TCN1; -. DR DMDM; 146345530; -. DR jPOST; P20061; -. DR MassIVE; P20061; -. DR PaxDb; 9606-ENSP00000257264; -. DR PeptideAtlas; P20061; -. DR PRIDE; P20061; -. DR ProteomicsDB; 53719; -. DR Antibodypedia; 27835; 214 antibodies from 22 providers. DR DNASU; 6947; -. DR Ensembl; ENST00000257264.4; ENSP00000257264.3; ENSG00000134827.8. DR GeneID; 6947; -. DR KEGG; hsa:6947; -. DR MANE-Select; ENST00000257264.4; ENSP00000257264.3; NM_001062.4; NP_001053.2. DR UCSC; uc001noj.3; human. DR AGR; HGNC:11652; -. DR CTD; 6947; -. DR DisGeNET; 6947; -. DR GeneCards; TCN1; -. DR HGNC; HGNC:11652; TCN1. DR HPA; ENSG00000134827; Tissue enhanced (bone marrow, gallbladder, salivary gland). DR MalaCards; TCN1; -. DR MIM; 189905; gene. DR neXtProt; NX_P20061; -. DR OpenTargets; ENSG00000134827; -. DR PharmGKB; PA36403; -. DR VEuPathDB; HostDB:ENSG00000134827; -. DR eggNOG; ENOG502QT7B; Eukaryota. DR GeneTree; ENSGT00530000063370; -. DR HOGENOM; CLU_052188_0_0_1; -. DR InParanoid; P20061; -. DR OMA; TMNQSKY; -. DR OrthoDB; 5361436at2759; -. DR PhylomeDB; P20061; -. DR TreeFam; TF333092; -. DR PathwayCommons; P20061; -. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-9758881; Uptake of dietary cobalamins into enterocytes. DR Reactome; R-HSA-9758890; Transport of RCbl within the body. DR SignaLink; P20061; -. DR BioGRID-ORCS; 6947; 11 hits in 1160 CRISPR screens. DR ChiTaRS; TCN1; human. DR GeneWiki; Haptocorrin; -. DR GenomeRNAi; 6947; -. DR Pharos; P20061; Tbio. DR PRO; PR:P20061; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P20061; Protein. DR Bgee; ENSG00000134827; Expressed in pancreatic ductal cell and 125 other cell types or tissues. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome. DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome. DR GO; GO:0140355; F:cargo receptor ligand activity; EXP:Reactome. DR GO; GO:0031419; F:cobalamin binding; IBA:GO_Central. DR GO; GO:0140313; F:molecular sequestering activity; EXP:Reactome. DR GO; GO:0015889; P:cobalamin transport; IBA:GO_Central. DR GO; GO:0006824; P:cobalt ion transport; IEA:UniProtKB-KW. DR Gene3D; 1.50.10.20; -; 1. DR Gene3D; 2.170.130.30; -; 1. DR InterPro; IPR002157; Cbl-bd_prot. DR InterPro; IPR027954; Transcobalamin-like_C. DR PANTHER; PTHR10559:SF13; TRANSCOBALAMIN-1; 1. DR PANTHER; PTHR10559; TRANSCOBALAMIN-1/GASTRIC INTRINSIC FACTOR; 1. DR Pfam; PF01122; Cobalamin_bind; 1. DR Pfam; PF14478; DUF4430; 1. DR PROSITE; PS00468; COBALAMIN_BINDING; 1. DR Genevisible; P20061; HS. PE 1: Evidence at protein level; KW 3D-structure; Cobalt; Cobalt transport; Disulfide bond; Glycoprotein; KW Ion transport; Reference proteome; Secreted; Signal; Transport. FT SIGNAL 1..23 FT CHAIN 24..433 FT /note="Transcobalamin-1" FT /id="PRO_0000005561" FT REGION 24..310 FT /note="Globular N-terminal alpha domain" FT REGION 311..332 FT /note="Flexible linker" FT REGION 333..433 FT /note="Globular C-terminal beta domain" FT BINDING 142..146 FT /ligand="cyanocob(III)alamin" FT /ligand_id="ChEBI:CHEBI:17439" FT /evidence="ECO:0000269|PubMed:23846701, FT ECO:0007744|PDB:4KKI" FT BINDING 186 FT /ligand="cyanocob(III)alamin" FT /ligand_id="ChEBI:CHEBI:17439" FT /evidence="ECO:0000269|PubMed:23846701, FT ECO:0007744|PDB:4KKI" FT BINDING 240 FT /ligand="cyanocob(III)alamin" FT /ligand_id="ChEBI:CHEBI:17439" FT /evidence="ECO:0000269|PubMed:23846701, FT ECO:0007744|PDB:4KKI" FT BINDING 289 FT /ligand="cyanocob(III)alamin" FT /ligand_id="ChEBI:CHEBI:17439" FT /evidence="ECO:0000269|PubMed:23846701, FT ECO:0007744|PDB:4KKI" FT BINDING 385..386 FT /ligand="cyanocob(III)alamin" FT /ligand_id="ChEBI:CHEBI:17439" FT /evidence="ECO:0000269|PubMed:23846701, FT ECO:0007744|PDB:4KKI" FT BINDING 402..404 FT /ligand="cyanocob(III)alamin" FT /ligand_id="ChEBI:CHEBI:17439" FT /evidence="ECO:0000269|PubMed:23846701, FT ECO:0007744|PDB:4KKI" FT BINDING 411 FT /ligand="cyanocob(III)alamin" FT /ligand_id="ChEBI:CHEBI:17439" FT /evidence="ECO:0000269|PubMed:23846701, FT ECO:0007744|PDB:4KKI" FT BINDING 433 FT /ligand="cyanocob(III)alamin" FT /ligand_id="ChEBI:CHEBI:17439" FT /evidence="ECO:0000269|PubMed:23846701, FT ECO:0007744|PDB:4KKI" FT CARBOHYD 160 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 216 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:16740002, ECO:0000269|PubMed:23846701" FT CARBOHYD 316 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:23846701" FT CARBOHYD 337 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:23846701" FT CARBOHYD 343 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:23846701" FT CARBOHYD 349 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:23846701" FT CARBOHYD 354 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:23846701" FT CARBOHYD 369 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16740002, FT ECO:0000269|PubMed:23846701" FT DISULFID 26..265 FT /evidence="ECO:0000269|PubMed:23846701" FT DISULFID 105..308 FT /evidence="ECO:0000269|PubMed:23846701" FT DISULFID 155..197 FT /evidence="ECO:0000269|PubMed:23846701" FT DISULFID 388..393 FT /evidence="ECO:0000269|PubMed:23846701" FT VARIANT 35 FT /note="R -> H (in dbSNP:rs34528912)" FT /id="VAR_031923" FT VARIANT 301 FT /note="D -> Y (in dbSNP:rs34324219)" FT /id="VAR_031924" FT CONFLICT 119 FT /note="I -> T (in Ref. 1; AAA61058)" FT /evidence="ECO:0000305" FT HELIX 30..36 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 37..45 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 46..48 FT /evidence="ECO:0007829|PDB:4KKI" FT STRAND 50..52 FT /evidence="ECO:0007829|PDB:4KKJ" FT HELIX 55..63 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 69..85 FT /evidence="ECO:0007829|PDB:4KKI" FT TURN 87..89 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 92..102 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 108..110 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 111..115 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 118..135 FT /evidence="ECO:0007829|PDB:4KKI" FT TURN 136..138 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 144..156 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 163..169 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 175..177 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 185..203 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 213..229 FT /evidence="ECO:0007829|PDB:4KKI" FT STRAND 238..240 FT /evidence="ECO:0007829|PDB:4KKI" FT TURN 241..243 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 244..252 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 255..257 FT /evidence="ECO:0007829|PDB:4KKI" FT TURN 260..262 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 265..277 FT /evidence="ECO:0007829|PDB:4KKI" FT TURN 278..281 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 284..294 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 299..301 FT /evidence="ECO:0007829|PDB:4KKI" FT STRAND 333..353 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 358..368 FT /evidence="ECO:0007829|PDB:4KKI" FT HELIX 370..373 FT /evidence="ECO:0007829|PDB:4KKI" FT STRAND 375..379 FT /evidence="ECO:0007829|PDB:4KKI" FT STRAND 381..389 FT /evidence="ECO:0007829|PDB:4KKI" FT TURN 396..399 FT /evidence="ECO:0007829|PDB:4KKI" FT STRAND 400..406 FT /evidence="ECO:0007829|PDB:4KKI" FT TURN 415..417 FT /evidence="ECO:0007829|PDB:4KKI" FT STRAND 426..432 FT /evidence="ECO:0007829|PDB:4KKI" SQ SEQUENCE 433 AA; 48207 MW; CF1052BE3DBA929A CRC64; MRQSHQLPLV GLLLFSFIPS QLCEICEVSE ENYIRLKPLL NTMIQSNYNR GTSAVNVVLS LKLVGIQIQT LMQKMIQQIK YNVKSRLSDV SSGELALIIL ALGVCRNAEE NLIYDYHLID KLENKFQAEI ENMEAHNGTP LTNYYQLSLD VLALCLFNGN YSTAEVVNHF TPENKNYYFG SQFSVDTGAM AVLALTCVKK SLINGQIKAD EGSLKNISIY TKSLVEKILS EKKENGLIGN TFSTGEAMQA LFVSSDYYNE NDWNCQQTLN TVLTEISQGA FSNPNAAAQV LPALMGKTFL DINKDSSCVS ASGNFNISAD EPITVTPPDS QSYISVNYSV RINETYFTNV TVLNGSVFLS VMEKAQKMND TIFGFTMEER SWGPYITCIQ GLCANNNDRT YWELLSGGEP LSQGAGSYVV RNGENLEVRW SKY //