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Protein

Vitamin D-binding protein

Gene

GC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in vitamin D transport and storage, scavenging of extracellular G-actin, enhancement of the chemotactic activity of C5 alpha for neutrophils in inflammation and macrophage activation.1 Publication

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • calcidiol binding Source: UniProtKB
  • vitamin D binding Source: ProtInc
  • vitamin transporter activity Source: InterPro

GO - Biological processi

  • vitamin D metabolic process Source: Reactome
  • vitamin transport Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Transport

Keywords - Ligandi

Actin-binding, Vitamin D

Enzyme and pathway databases

BioCyciZFISH:ENSG00000145321-MONOMER.
ReactomeiR-HSA-196791. Vitamin D (calciferol) metabolism.

Names & Taxonomyi

Protein namesi
Recommended name:
Vitamin D-binding protein
Short name:
DBP
Short name:
VDB
Alternative name(s):
Gc protein-derived macrophage activating factor1 Publication
Short name:
Gc-MAF
Short name:
GcMAF1 Publication
Gc-globulin
Group-specific component
Short name:
Gc1 Publication
Vitamin D-binding protein-macrophage activating factor
Short name:
DBP-maf
Gene namesi
Name:GC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:4187. GC.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • extracellular space Source: UniProtKB
  • lysosomal lumen Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi2638.
PharmGKBiPA28601.

Chemistry databases

ChEMBLiCHEMBL2259.
DrugBankiDB01436. Alfacalcidol.
DB00169. Cholecalciferol.
DB04224. Oleic Acid.

Polymorphism and mutation databases

BioMutaiGC.
DMDMi139641.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 162 PublicationsAdd BLAST16
ChainiPRO_000000110217 – 474Vitamin D-binding proteinAdd BLAST458

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi29 ↔ 75
Disulfide bondi74 ↔ 83PROSITE-ProRule annotation
Disulfide bondi96 ↔ 112
Disulfide bondi111 ↔ 122
Disulfide bondi145 ↔ 190
Disulfide bondi189 ↔ 198
Disulfide bondi220 ↔ 266
Disulfide bondi265 ↔ 273
Disulfide bondi286 ↔ 300
Disulfide bondi299 ↔ 311
Disulfide bondi335 ↔ 376
Disulfide bondi375 ↔ 384
Disulfide bondi407 ↔ 453
Disulfide bondi452 ↔ 462

Post-translational modificationi

Allele GC*1S is O-glycosylated at Thr-436 (PubMed:20079467). The trisaccharide sugar moiety can be modified by the successive removal of neuraminic acid and galactose leaving an O-linked N-acetyl-galactosamine. This conversion is thought to produce a macrophage-activating factor (Gc-MAF). Only a minor proportion of plasma GC is O-glycosylated (PubMed:17360250). The potential N-glycosylation site predicted at Asn-288 is thought to be nonglycosylated.1 Publication2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP02774.
PaxDbiP02774.
PeptideAtlasiP02774.
PRIDEiP02774.

2D gel databases

DOSAC-COBS-2DPAGEP02774.
REPRODUCTION-2DPAGEIPI00555812.
P02774.
SWISS-2DPAGEP02774.

PTM databases

iPTMnetiP02774.
PhosphoSitePlusiP02774.
UniCarbKBiP02774.

Expressioni

Tissue specificityi

Expressed in the liver. Found in plasma, ascites, cerebrospinal fluid and urine.1 Publication2 Publications

Gene expression databases

BgeeiENSG00000145321.
CleanExiHS_GC.
ExpressionAtlasiP02774. baseline and differential.
GenevisibleiP02774. HS.

Organism-specific databases

HPAiCAB008596.
HPA001526.
HPA019855.

Interactioni

Subunit structurei

Associates with membrane-bound immunoglobulin on the surface of B-lymphocytes and with IgG Fc receptor on the membranes of T-lymphocytes.

GO - Molecular functioni

  • actin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108908. 20 interactors.
DIPiDIP-17038N.
IntActiP02774. 8 interactors.
MINTiMINT-239255.
STRINGi9606.ENSP00000421725.

Chemistry databases

BindingDBiP02774.

Structurei

Secondary structure

1474
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi23 – 35Combined sources13
Helixi37 – 51Combined sources15
Helixi57 – 74Combined sources18
Beta strandi76 – 79Combined sources4
Turni80 – 82Combined sources3
Helixi83 – 94Combined sources12
Beta strandi97 – 99Combined sources3
Helixi108 – 111Combined sources4
Helixi116 – 125Combined sources10
Helixi141 – 150Combined sources10
Helixi152 – 166Combined sources15
Helixi172 – 190Combined sources19
Beta strandi192 – 194Combined sources3
Helixi195 – 226Combined sources32
Helixi228 – 242Combined sources15
Helixi248 – 265Combined sources18
Helixi273 – 289Combined sources17
Turni290 – 292Combined sources3
Helixi294 – 299Combined sources6
Beta strandi302 – 304Combined sources3
Helixi305 – 314Combined sources10
Helixi331 – 335Combined sources5
Beta strandi336 – 338Combined sources3
Helixi340 – 351Combined sources12
Helixi358 – 373Combined sources16
Turni374 – 377Combined sources4
Helixi381 – 406Combined sources26
Turni407 – 412Combined sources6
Helixi415 – 429Combined sources15
Helixi435 – 452Combined sources18
Helixi459 – 470Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J78X-ray2.31A/B17-474[»]
1J7EX-ray2.55A/B17-474[»]
1KW2X-ray2.15A/B17-474[»]
1KXPX-ray2.10D17-474[»]
1LOTX-ray2.50A17-474[»]
1MA9X-ray2.40A17-474[»]
ProteinModelPortaliP02774.
SMRiP02774.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP02774.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 208Albumin 1PROSITE-ProRule annotationAdd BLAST192
Domaini209 – 394Albumin 2PROSITE-ProRule annotationAdd BLAST186
Domaini395 – 474Albumin 3PROSITE-ProRule annotationAdd BLAST80

Sequence similaritiesi

Belongs to the ALB/AFP/VDB family.PROSITE-ProRule annotation
Contains 3 albumin domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410II89. Eukaryota.
ENOG4111PH6. LUCA.
HOGENOMiHOG000140946.
HOVERGENiHBG009729.
InParanoidiP02774.
KOiK12258.
OrthoDBiEOG091G059U.
PhylomeDBiP02774.
TreeFamiTF335561.

Family and domain databases

CDDicd00015. ALBUMIN. 1 hit.
InterProiIPR000264. ALB/AFP/VDB.
IPR020858. Serum_albumin-like.
IPR020857. Serum_albumin_CS.
IPR014760. Serum_albumin_N.
IPR000213. VitD-bd.
IPR015247. VitD-bind_III.
[Graphical view]
PfamiPF00273. Serum_albumin. 2 hits.
PF09164. VitD-bind_III. 1 hit.
[Graphical view]
PRINTSiPR00802. SERUMALBUMIN.
PR00804. VITAMNDBNDNG.
SMARTiSM00103. ALBUMIN. 2 hits.
[Graphical view]
SUPFAMiSSF48552. SSF48552. 3 hits.
PROSITEiPS00212. ALBUMIN_1. 1 hit.
PS51438. ALBUMIN_2. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P02774-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKRVLVLLLA VAFGHALERG RDYEKNKVCK EFSHLGKEDF TSLSLVLYSR
60 70 80 90 100
KFPSGTFEQV SQLVKEVVSL TEACCAEGAD PDCYDTRTSA LSAKSCESNS
110 120 130 140 150
PFPVHPGTAE CCTKEGLERK LCMAALKHQP QEFPTYVEPT NDEICEAFRK
160 170 180 190 200
DPKEYANQFM WEYSTNYGQA PLSLLVSYTK SYLSMVGSCC TSASPTVCFL
210 220 230 240 250
KERLQLKHLS LLTTLSNRVC SQYAAYGEKK SRLSNLIKLA QKVPTADLED
260 270 280 290 300
VLPLAEDITN ILSKCCESAS EDCMAKELPE HTVKLCDNLS TKNSKFEDCC
310 320 330 340 350
QEKTAMDVFV CTYFMPAAQL PELPDVELPT NKDVCDPGNT KVMDKYTFEL
360 370 380 390 400
SRRTHLPEVF LSKVLEPTLK SLGECCDVED STTCFNAKGP LLKKELSSFI
410 420 430 440 450
DKGQELCADY SENTFTEYKK KLAERLKAKL PDATPKELAK LVNKRSDFAS
460 470
NCCSINSPPL YCDSEIDAEL KNIL
Length:474
Mass (Da):52,964
Last modified:July 21, 1986 - v1
Checksum:i6AD8F163B551F1E4
GO
Isoform 2 (identifier: P02774-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-122: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:352
Mass (Da):39,542
Checksum:i13170DD8F989B341
GO
Isoform 3 (identifier: P02774-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLWSWSEERGGAARLSGRKM

Note: No experimental confirmation available.
Show »
Length:493
Mass (Da):55,123
Checksum:iC4738F41F3B76713
GO

Sequence cautioni

The sequence BAG60654 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti168G → E in AAA52173 (PubMed:2416779).Curated1
Sequence conflicti183L → P in AK309595 (PubMed:14702039).Curated1
Sequence conflicti327E → R in AAA52173 (PubMed:2416779).Curated1

Polymorphismi

Over 80 variants of human DBP have been identified. The three most common alleles are called GC*1F, GC*1S, and GC*2. The sequence shown is that of the GC*2 allele.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_000548432D → E in allele GC*1S. 6 PublicationsCorresponds to variant rs7041dbSNPEnsembl.1
Natural variantiVAR_000549436K → T in allele GC*1F, allele GC*1A1 and allele GC*1S. Combined sources9 PublicationsCorresponds to variant rs4588dbSNPEnsembl.1
Natural variantiVAR_014120445R → C in allele GC*2A9. 1 Publication1
Natural variantiVAR_014121445R → H in allele GC*1A1. 3 PublicationsCorresponds to variant rs9016dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0384271 – 122Missing in isoform 2. 1 PublicationAdd BLAST122
Alternative sequenceiVSP_0445231M → MLWSWSEERGGAARLSGRKM in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12654 mRNA. Translation: AAA52173.1.
X03178 mRNA. Translation: CAA26938.1.
S67480
, S67474, S67476, S67478, S67479, S67526 Genomic DNA. Translation: AAB29423.1.
L10641 Genomic DNA. Translation: AAA61704.1.
AK290827 mRNA. Translation: BAF83516.1.
AK298433 mRNA. Translation: BAG60654.1. Sequence problems.
AK309595 mRNA. No translation available.
AK315853 mRNA. Translation: BAF98744.1.
AK223458 mRNA. Translation: BAD97178.1.
AC024722 Genomic DNA. No translation available.
CH471057 Genomic DNA. Translation: EAX05645.1.
BC057228 mRNA. Translation: AAH57228.1.
M17156 Genomic DNA. Translation: AAA19662.2.
S77129 Genomic DNA. Translation: AAD14249.1. Sequence problems.
S77130 Genomic DNA. Translation: AAD14250.1. Sequence problems.
CCDSiCCDS3550.1. [P02774-1]
CCDS56332.1. [P02774-3]
PIRiA94076. VYHUD.
RefSeqiNP_000574.2. NM_000583.3.
NP_001191235.1. NM_001204306.1.
NP_001191236.1. NM_001204307.1.
UniGeneiHs.418497.

Genome annotation databases

EnsembliENST00000273951; ENSP00000273951; ENSG00000145321.
ENST00000504199; ENSP00000421725; ENSG00000145321.
GeneIDi2638.
KEGGihsa:2638.
UCSCiuc003hge.4. human. [P02774-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12654 mRNA. Translation: AAA52173.1.
X03178 mRNA. Translation: CAA26938.1.
S67480
, S67474, S67476, S67478, S67479, S67526 Genomic DNA. Translation: AAB29423.1.
L10641 Genomic DNA. Translation: AAA61704.1.
AK290827 mRNA. Translation: BAF83516.1.
AK298433 mRNA. Translation: BAG60654.1. Sequence problems.
AK309595 mRNA. No translation available.
AK315853 mRNA. Translation: BAF98744.1.
AK223458 mRNA. Translation: BAD97178.1.
AC024722 Genomic DNA. No translation available.
CH471057 Genomic DNA. Translation: EAX05645.1.
BC057228 mRNA. Translation: AAH57228.1.
M17156 Genomic DNA. Translation: AAA19662.2.
S77129 Genomic DNA. Translation: AAD14249.1. Sequence problems.
S77130 Genomic DNA. Translation: AAD14250.1. Sequence problems.
CCDSiCCDS3550.1. [P02774-1]
CCDS56332.1. [P02774-3]
PIRiA94076. VYHUD.
RefSeqiNP_000574.2. NM_000583.3.
NP_001191235.1. NM_001204306.1.
NP_001191236.1. NM_001204307.1.
UniGeneiHs.418497.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J78X-ray2.31A/B17-474[»]
1J7EX-ray2.55A/B17-474[»]
1KW2X-ray2.15A/B17-474[»]
1KXPX-ray2.10D17-474[»]
1LOTX-ray2.50A17-474[»]
1MA9X-ray2.40A17-474[»]
ProteinModelPortaliP02774.
SMRiP02774.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108908. 20 interactors.
DIPiDIP-17038N.
IntActiP02774. 8 interactors.
MINTiMINT-239255.
STRINGi9606.ENSP00000421725.

Chemistry databases

BindingDBiP02774.
ChEMBLiCHEMBL2259.
DrugBankiDB01436. Alfacalcidol.
DB00169. Cholecalciferol.
DB04224. Oleic Acid.

PTM databases

iPTMnetiP02774.
PhosphoSitePlusiP02774.
UniCarbKBiP02774.

Polymorphism and mutation databases

BioMutaiGC.
DMDMi139641.

2D gel databases

DOSAC-COBS-2DPAGEP02774.
REPRODUCTION-2DPAGEIPI00555812.
P02774.
SWISS-2DPAGEP02774.

Proteomic databases

EPDiP02774.
PaxDbiP02774.
PeptideAtlasiP02774.
PRIDEiP02774.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000273951; ENSP00000273951; ENSG00000145321.
ENST00000504199; ENSP00000421725; ENSG00000145321.
GeneIDi2638.
KEGGihsa:2638.
UCSCiuc003hge.4. human. [P02774-1]

Organism-specific databases

CTDi2638.
DisGeNETi2638.
GeneCardsiGC.
HGNCiHGNC:4187. GC.
HPAiCAB008596.
HPA001526.
HPA019855.
MIMi139200. gene.
neXtProtiNX_P02774.
PharmGKBiPA28601.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410II89. Eukaryota.
ENOG4111PH6. LUCA.
HOGENOMiHOG000140946.
HOVERGENiHBG009729.
InParanoidiP02774.
KOiK12258.
OrthoDBiEOG091G059U.
PhylomeDBiP02774.
TreeFamiTF335561.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000145321-MONOMER.
ReactomeiR-HSA-196791. Vitamin D (calciferol) metabolism.

Miscellaneous databases

ChiTaRSiGC. human.
EvolutionaryTraceiP02774.
GeneWikiiVitamin_D-binding_protein.
GenomeRNAii2638.
PROiP02774.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145321.
CleanExiHS_GC.
ExpressionAtlasiP02774. baseline and differential.
GenevisibleiP02774. HS.

Family and domain databases

CDDicd00015. ALBUMIN. 1 hit.
InterProiIPR000264. ALB/AFP/VDB.
IPR020858. Serum_albumin-like.
IPR020857. Serum_albumin_CS.
IPR014760. Serum_albumin_N.
IPR000213. VitD-bd.
IPR015247. VitD-bind_III.
[Graphical view]
PfamiPF00273. Serum_albumin. 2 hits.
PF09164. VitD-bind_III. 1 hit.
[Graphical view]
PRINTSiPR00802. SERUMALBUMIN.
PR00804. VITAMNDBNDNG.
SMARTiSM00103. ALBUMIN. 2 hits.
[Graphical view]
SUPFAMiSSF48552. SSF48552. 3 hits.
PROSITEiPS00212. ALBUMIN_1. 1 hit.
PS51438. ALBUMIN_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVTDB_HUMAN
AccessioniPrimary (citable) accession number: P02774
Secondary accession number(s): B4DPP2
, D6RAK8, Q16309, Q16310, Q53F31, Q6GTG1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 30, 2016
This is version 190 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.