TCO1_HUMAN
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 03-AUG-2022, entry version 186.
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}.
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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 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; P20061; -.
DR PeptideAtlas; P20061; -.
DR PRIDE; P20061; -.
DR ProteomicsDB; 53719; -.
DR Antibodypedia; 27835; 195 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 CTD; 6947; -.
DR DisGeNET; 6947; -.
DR GeneCards; TCN1; -.
DR HGNC; HGNC:11652; TCN1.
DR HPA; ENSG00000134827; Tissue enriched (salivary).
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; NMEAHNG; -.
DR OrthoDB; 1233171at2759; -.
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; 10 hits in 1079 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 123 other tissues.
DR Genevisible; P20061; HS.
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:0031419; F:cobalamin binding; IBA:GO_Central.
DR GO; GO:0015889; P:cobalamin transport; IBA:GO_Central.
DR GO; GO:0006824; P:cobalt ion transport; IEA:UniProtKB-KW.
DR InterPro; IPR002157; Cbl-bd_prot.
DR InterPro; IPR027954; DUF4430.
DR Pfam; PF01122; Cobalamin_bind; 1.
DR Pfam; PF14478; DUF4430; 1.
DR PROSITE; PS00468; COBALAMIN_BINDING; 1.
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
