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Protein

Membrane cofactor protein

Gene

CD46

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

Functioni

Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue. May be involved in the fusion of the spermatozoa with the oocyte during fertilization. Also acts as a costimulatory factor for T-cells which induces the differentiation of CD4+ into T-regulatory 1 cells. T-regulatory 1 cells suppress immune responses by secreting interleukin-10, and therefore are thought to prevent autoimmunity.2 Publications
(Microbial infection) A number of viral and bacterial pathogens seem to bind MCP in order to exploit its immune regulation property and directly induce an immunosuppressive phenotype in T-cells. Acts as a receptor for adenovirus subgroup B2 and Ad3, cultured measles virus and herpesvirus 6 (PubMed:10972291, PubMed:12663806, PubMed:12724329, PubMed:12915534, PubMed:14566335, PubMed:15047806, PubMed:15078926, PubMed:15919905, PubMed:16254377). May act as a receptor for pathogenic bacteria Neisseria and Streptococcus pyogenes (PubMed:7708671, PubMed:9379894, PubMed:11260136, PubMed:11971006).13 Publications

GO - Molecular functioni

  • cadherin binding Source: UniProtKB
  • endopeptidase activity Source: Ensembl
  • enzyme inhibitor activity Source: Ensembl
  • receptor activity Source: ProtInc
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

  • adaptive immune response Source: UniProtKB
  • complement activation, classical pathway Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • interleukin-10 production Source: UniProtKB
  • negative regulation of complement activation Source: Ensembl
  • negative regulation of gene expression Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of interleukin-10 production Source: UniProtKB
  • positive regulation of memory T cell differentiation Source: UniProtKB
  • positive regulation of regulatory T cell differentiation Source: UniProtKB
  • positive regulation of T cell proliferation Source: UniProtKB
  • positive regulation of transforming growth factor beta production Source: UniProtKB
  • regulation of complement activation Source: Reactome
  • regulation of Notch signaling pathway Source: UniProtKB
  • sequestering of extracellular ligand from receptor Source: UniProtKB
  • single fertilization Source: UniProtKB-KW
  • T cell mediated immunity Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Host cell receptor for virus entry, Receptor

Keywords - Biological processi

Complement pathway, Fertilization, Host-virus interaction, Immunity, Innate immunity

Enzyme and pathway databases

BioCyciZFISH:ENSG00000117335-MONOMER.
ReactomeiR-HSA-977606. Regulation of Complement cascade.

Names & Taxonomyi

Protein namesi
Recommended name:
Membrane cofactor protein
Alternative name(s):
TLX
Trophoblast leukocyte common antigen
CD_antigen: CD46
Gene namesi
Name:CD46
Synonyms:MCP, MIC10
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:6953. CD46.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini35 – 343ExtracellularSequence analysisAdd BLAST309
Transmembranei344 – 366HelicalSequence analysisAdd BLAST23
Topological domaini367 – 392CytoplasmicSequence analysisAdd BLAST26

GO - Cellular componenti

  • basolateral plasma membrane Source: Ensembl
  • cell surface Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • Golgi apparatus Source: Ensembl
  • inner acrosomal membrane Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: AgBase
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Involvement in diseasei

Hemolytic uremic syndrome atypical 2 (AHUS2)3 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype. Patients with CD46 mutations seem to have an overall better prognosis compared to patients carrying CFH mutations.
Disease descriptionAn atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease.
See also OMIM:612922
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06365635C → Y in AHUS2. 1 PublicationCorresponds to variant rs121909591dbSNPEnsembl.1
Natural variantiVAR_026569165P → S in AHUS2; reduced cell surface expression. 1 PublicationCorresponds to variant rs759136081dbSNPEnsembl.1
Natural variantiVAR_063657216W → C in AHUS2. 1 Publication1
Natural variantiVAR_063658231P → R in AHUS2. 1 Publication1
Natural variantiVAR_026570240S → P in AHUS2; no change in cell surface expression but reduced activity. 1 PublicationCorresponds to variant rs121909589dbSNPEnsembl.1
Natural variantiVAR_026571271 – 272Missing in AHUS2; no cell surface expression. 1 Publication2

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi83N → Q: No effect on cytoprotective function. No effect on Neisseria binding. No effect on Measles virus binding. 3 Publications1
Mutagenesisi114N → Q: Strongly decreases cytoprotective function. Decreases Neisseria binding. Abolishes Measles virus binding. 3 Publications1
Mutagenesisi273N → Q: Strongly decreases cytoprotective function. Abolishes Neisseria binding. No effect on Measles virus binding. 3 Publications1

Keywords - Diseasei

Disease mutation, Hemolytic uremic syndrome

Organism-specific databases

DisGeNETi4179.
MalaCardsiCD46.
MIMi120920. gene+phenotype.
612922. phenotype.
OpenTargetsiENSG00000117335.
Orphaneti93576. Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly.
244242. HELLP syndrome.
PharmGKBiPA30700.

Polymorphism and mutation databases

BioMutaiCD46.
DMDMi41019474.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 344 PublicationsAdd BLAST34
ChainiPRO_000000600835 – 392Membrane cofactor proteinAdd BLAST358

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi35 ↔ 80PROSITE-ProRule annotation
Disulfide bondi64 ↔ 94PROSITE-ProRule annotation
Glycosylationi83N-linked (GlcNAc...)1
Disulfide bondi99 ↔ 141PROSITE-ProRule annotation
Glycosylationi114N-linked (GlcNAc...)1
Disulfide bondi127 ↔ 157PROSITE-ProRule annotation
Disulfide bondi162 ↔ 210PROSITE-ProRule annotation
Glycosylationi163O-linked (GalNAc...)Sequence analysis1
Disulfide bondi191 ↔ 223PROSITE-ProRule annotation
Disulfide bondi228 ↔ 270PROSITE-ProRule annotation
Disulfide bondi256 ↔ 283PROSITE-ProRule annotation
Glycosylationi273N-linked (GlcNAc...)1
Glycosylationi290O-linked (GalNAc...)Sequence analysis1
Glycosylationi291O-linked (GalNAc...)Sequence analysis1
Glycosylationi292O-linked (GalNAc...)Sequence analysis1
Glycosylationi298O-linked (GalNAc...)Sequence analysis1
Glycosylationi300O-linked (GalNAc...)Sequence analysis1
Glycosylationi302O-linked (GalNAc...)Sequence analysis1
Glycosylationi303O-linked (GalNAc...)Sequence analysis1
Glycosylationi304O-linked (GalNAc...)Sequence analysis1
Glycosylationi305O-linked (GalNAc...)Sequence analysis1
Glycosylationi306O-linked (GalNAc...)Sequence analysis1
Glycosylationi307O-linked (GalNAc...)Sequence analysis1
Glycosylationi309O-linked (GalNAc...)Sequence analysis1
Glycosylationi312O-linked (GalNAc...)Sequence analysis1
Glycosylationi313O-linked (GalNAc...)Sequence analysis1
Glycosylationi315O-linked (GalNAc...)Sequence analysis1
Glycosylationi320O-linked (GalNAc...)Sequence analysis1
Glycosylationi326O-linked (GalNAc...)Sequence analysis1
Isoform 3 (identifier: P15529-16)
Modified residuei321Phosphotyrosine1 Publication1
Isoform L (identifier: P15529-7)
Modified residuei340Phosphotyrosine1 Publication1
Isoform F (identifier: P15529-4)
Modified residuei354Phosphotyrosine1 Publication1
Isoform J (identifier: P15529-6)
Modified residuei355Phosphotyrosine1 Publication1
Isoform D (identifier: P15529-3)
Modified residuei369Phosphotyrosine1 Publication1
Isoform H (identifier: P15529-5)
Modified residuei370Phosphotyrosine1 Publication1
Isoform B (identifier: P15529-2)
Modified residuei384Phosphotyrosine1 Publication1

Post-translational modificationi

N-glycosylated on Asn-83; Asn-114 and Asn-273 in most tissues, but probably less N-glycosylated in testis. N-glycosylation on Asn-114 and Asn-273 is required for cytoprotective function. N-glycosylation on Asn-114 is required for Measles virus binding. N-glycosylation on Asn-273 is required for Neisseria binding. N-glycosylation is not required for human adenovirus binding.
Extensively O-glycosylated in the Ser/Thr-rich domain. O-glycosylation is required for Neisseria binding but not for Measles virus or human adenovirus binding.
In epithelial cells, isoforms B/D/F/H/J/L/3 are phosphorylated by YES1 in response to infection by Neisseria gonorrhoeae; which promotes infectivity. In T-cells, these isoforms may be phosphorylated by LCK.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP15529.
MaxQBiP15529.
PaxDbiP15529.
PeptideAtlasiP15529.
PRIDEiP15529.
TopDownProteomicsiP15529-4. [P15529-4]

PTM databases

iPTMnetiP15529.
PhosphoSitePlusiP15529.
SwissPalmiP15529.

Miscellaneous databases

PMAP-CutDBP15529.

Expressioni

Tissue specificityi

Expressed by all cells except erythrocytes.

Gene expression databases

BgeeiENSG00000117335.
ExpressionAtlasiP15529. baseline and differential.
GenevisibleiP15529. HS.

Organism-specific databases

HPAiCAB010401.
HPA016903.

Interactioni

Subunit structurei

Interacts with C3b (PubMed:1717583, PubMed:3260937). Interacts with C4b (PubMed:1717583).2 Publications
(Microbial infection) Interacts with measles virus H protein.1 Publication
(Microbial infection) Interacts with human herpesvirus 6 GH protein (PubMed:12663806, PubMed:12724329).2 Publications
(Microbial infection) Interacts with human adenovirus B/D fiber protein (PubMed:12915534, PubMed:14566335, PubMed:15047806, PubMed:15078926, PubMed:15919905, PubMed:16254377).6 Publications
(Microbial infection) Binds to Streptococcus pyogenes M protein and to type IV pili from Neisseria (PubMed:7708671, PubMed:9379894, PubMed:11260136, PubMed:11971006).4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
JAG1P785045EBI-2623451,EBI-2847071

GO - Molecular functioni

  • cadherin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110346. 11 interactors.
DIPiDIP-41232N.
IntActiP15529. 8 interactors.
MINTiMINT-222279.
STRINGi9606.ENSP00000313875.

Structurei

Secondary structure

1392
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi42 – 48Combined sources7
Beta strandi59 – 64Combined sources6
Beta strandi68 – 70Combined sources3
Beta strandi72 – 74Combined sources3
Beta strandi77 – 80Combined sources4
Beta strandi84 – 86Combined sources3
Helixi91 – 93Combined sources3
Beta strandi94 – 96Combined sources3
Beta strandi108 – 112Combined sources5
Beta strandi115 – 118Combined sources4
Beta strandi122 – 127Combined sources6
Beta strandi131 – 135Combined sources5
Beta strandi137 – 146Combined sources10
Beta strandi148 – 152Combined sources5
Beta strandi156 – 159Combined sources4
Beta strandi171 – 174Combined sources4
Beta strandi183 – 191Combined sources9
Beta strandi195 – 198Combined sources4
Beta strandi201 – 204Combined sources4
Beta strandi206 – 210Combined sources5
Helixi212 – 214Combined sources3
Beta strandi215 – 218Combined sources4
Beta strandi222 – 224Combined sources3
Beta strandi236 – 240Combined sources5
Beta strandi251 – 256Combined sources6
Beta strandi260 – 264Combined sources5
Beta strandi266 – 270Combined sources5
Beta strandi276 – 278Combined sources3
Beta strandi282 – 285Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CKLX-ray3.10A/B/C/D/E/F35-160[»]
1HR4model-A159-284[»]
2O39X-ray2.85C/D35-160[»]
3INBX-ray3.10C/D35-160[»]
3L89X-ray3.50M/N/O/P/Q/R/S/T/U/V/W/X35-160[»]
3O8EX-ray2.84B/D35-286[»]
5FO8X-ray2.40C35-286[»]
ProteinModelPortaliP15529.
SMRiP15529.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15529.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 96Sushi 1PROSITE-ProRule annotationAdd BLAST62
Domaini97 – 159Sushi 2PROSITE-ProRule annotationAdd BLAST63
Domaini160 – 225Sushi 3PROSITE-ProRule annotationAdd BLAST66
Domaini226 – 285Sushi 4PROSITE-ProRule annotationAdd BLAST60

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi302 – 326Ser/Thr-richAdd BLAST25

Domaini

Sushi domains 1 and 2 are required for interaction with human adenovirus B PIV/FIBER protein and with Measles virus H protein. Sushi domains 2 and 3 are required for Herpesvirus 6 binding. Sushi domain 3 is required for Neisseria binding. Sushi domains 3 and 4 are required for interaction with Streptococcus pyogenes M protein and are the most important for interaction with C3b and C4b.

Sequence similaritiesi

Contains 4 Sushi (CCP/SCR) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Sushi, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IY7G. Eukaryota.
ENOG4111CPD. LUCA.
GeneTreeiENSGT00760000118803.
HOVERGENiHBG006335.
InParanoidiP15529.
KOiK04007.
OMAiCKVVKCR.
OrthoDBiEOG091G0DWA.
PhylomeDBiP15529.
TreeFamiTF334137.

Family and domain databases

CDDicd00033. CCP. 4 hits.
InterProiIPR017341. CD46.
IPR000436. Sushi_SCR_CCP_dom.
[Graphical view]
PfamiPF00084. Sushi. 4 hits.
[Graphical view]
PIRSFiPIRSF037971. TLX_CD46. 1 hit.
SMARTiSM00032. CCP. 4 hits.
[Graphical view]
SUPFAMiSSF57535. SSF57535. 4 hits.
PROSITEiPS50923. SUSHI. 4 hits.
[Graphical view]

Sequences (16)i

Sequence statusi: Complete.

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

This entry describes 16 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist. The complete sequences of the isoforms are not known. Isoforms are classified as alpha (isoform C and isoform D), beta (isoform E and isoform F), gamma (isoform A and isoform B) and delta (isoform N). Isoforms gamma are preferentially expressed in EBV-B cells and leukemic cells. Isoforms alpha (66 kDa) and isoforms beta (56 kDa) are found in all tissues except sperm. Isoform delta is expressed in spermatozoa. The exon 9 is specifically deleted in some placentae isoforms. All tissues differentially splice exon 13.
Isoform A (identifier: P15529-1) [UniParc]FASTAAdd to basket
Also known as: no del, ABC1

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
MEPPGRRECP FPSWRFPGLL LAAMVLLLYS FSDACEEPPT FEAMELIGKP
60 70 80 90 100
KPYYEIGERV DYKCKKGYFY IPPLATHTIC DRNHTWLPVS DDACYRETCP
110 120 130 140 150
YIRDPLNGQA VPANGTYEFG YQMHFICNEG YYLIGEEILY CELKGSVAIW
160 170 180 190 200
SGKPPICEKV LCTPPPKIKN GKHTFSEVEV FEYLDAVTYS CDPAPGPDPF
210 220 230 240 250
SLIGESTIYC GDNSVWSRAA PECKVVKCRF PVVENGKQIS GFGKKFYYKA
260 270 280 290 300
TVMFECDKGF YLDGSDTIVC DSNSTWDPPV PKCLKVLPPS STKPPALSHS
310 320 330 340 350
VSTSSTTKSP ASSASGPRPT YKPPVSNYPG YPKPEEGILD SLDVWVIAVI
360 370 380 390
VIAIVVGVAV ICVVPYRYLQ RRKKKGTYLT DETHREVKFT SL
Length:392
Mass (Da):43,747
Last modified:January 16, 2004 - v3
Checksum:i85FE0CF100EA703E
GO
Isoform B (identifier: P15529-2) [UniParc]FASTAAdd to basket
Also known as: del 13, ABC2

The sequence of this isoform differs from the canonical sequence as follows:
     377-392: TYLTDETHREVKFTSL → KADGGAEYATYQTKSTTPAEQRG

Show »
Length:399
Mass (Da):44,238
Checksum:i8E4C641F2BD8AC15
GO
Isoform C (identifier: P15529-11) [UniParc]FASTAAdd to basket
Also known as: del 7, BC1

The sequence of this isoform differs from the canonical sequence as follows:
     286-300: Missing.

Show »
Length:377
Mass (Da):42,248
Checksum:i2CA6F61752570B57
GO
Isoform D (identifier: P15529-3) [UniParc]FASTAAdd to basket
Also known as: del 7-13, BC2

The sequence of this isoform differs from the canonical sequence as follows:
     286-300: Missing.
     377-392: TYLTDETHREVKFTSL → KADGGAEYATYQTKSTTPAEQRG

Show »
Length:384
Mass (Da):42,738
Checksum:iF45B03CBB466AA8C
GO
Isoform E (identifier: P15529-12) [UniParc]FASTAAdd to basket
Also known as: del 7-8, C1

The sequence of this isoform differs from the canonical sequence as follows:
     286-315: Missing.

Show »
Length:362
Mass (Da):40,868
Checksum:iAA3F3F3110E8727D
GO
Isoform F (identifier: P15529-4) [UniParc]FASTAAdd to basket
Also known as: del 7-8-13, C2

The sequence of this isoform differs from the canonical sequence as follows:
     286-315: Missing.
     377-392: TYLTDETHREVKFTSL → KADGGAEYATYQTKSTTPAEQRG

Show »
Length:369
Mass (Da):41,359
Checksum:i3BD3000428BBA2EA
GO
Isoform G (identifier: P15529-13) [UniParc]FASTAAdd to basket
Also known as: del 9

The sequence of this isoform differs from the canonical sequence as follows:
     316-329: Missing.

Show »
Length:378
Mass (Da):42,193
Checksum:iAE60F628C4DC271C
GO
Isoform H (identifier: P15529-5) [UniParc]FASTAAdd to basket
Also known as: del 9-13

The sequence of this isoform differs from the canonical sequence as follows:
     316-329: Missing.
     377-392: TYLTDETHREVKFTSL → KADGGAEYATYQTKSTTPAEQRG

Show »
Length:385
Mass (Da):42,683
Checksum:i45FB279DC30B895E
GO
Isoform I (identifier: P15529-14) [UniParc]FASTAAdd to basket
Also known as: del 7-9

The sequence of this isoform differs from the canonical sequence as follows:
     286-300: Missing.
     316-329: Missing.

Show »
Length:363
Mass (Da):40,693
Checksum:iE48C0E7C0A616FF1
GO
Isoform J (identifier: P15529-6) [UniParc]FASTAAdd to basket
Also known as: del 7-9-13

The sequence of this isoform differs from the canonical sequence as follows:
     286-300: Missing.
     316-329: Missing.
     377-392: TYLTDETHREVKFTSL → KADGGAEYATYQTKSTTPAEQRG

Show »
Length:370
Mass (Da):41,183
Checksum:iCC2FD6E11C9A81E4
GO
Isoform K (identifier: P15529-15) [UniParc]FASTAAdd to basket
Also known as: del 7-8-9

The sequence of this isoform differs from the canonical sequence as follows:
     286-329: Missing.

Show »
Length:348
Mass (Da):39,313
Checksum:iA6F0D0E7C4203DDF
GO
Isoform L (identifier: P15529-7) [UniParc]FASTAAdd to basket
Also known as: del 7-8-9-13

The sequence of this isoform differs from the canonical sequence as follows:
     286-329: Missing.
     377-392: TYLTDETHREVKFTSL → KADGGAEYATYQTKSTTPAEQRG

Show »
Length:355
Mass (Da):39,804
Checksum:i86C83A0D515EDF86
GO
Isoform M (identifier: P15529-8) [UniParc]FASTAAdd to basket
Also known as: del 7-12a-13

The sequence of this isoform differs from the canonical sequence as follows:
     286-300: Missing.
     355-367: Missing.
     368-392: YLQRRKKKGTYLTDETHREVKFTSL → GKQMVELNMPLTRLNQPLQQSREAE

Show »
Length:364
Mass (Da):40,705
Checksum:iB09E917D96F2C0DC
GO
Isoform N (identifier: P15529-9) [UniParc]FASTAAdd to basket
Also known as: del 7-8-12-13

The sequence of this isoform differs from the canonical sequence as follows:
     286-315: Missing.
     355-392: VVGVAVICVVPYRYLQRRKKKGTYLTDETHREVKFTSL → GKQMVELNMPLTRLNQPLQQSREAE

Note: No experimental confirmation available.
Show »
Length:349
Mass (Da):39,325
Checksum:i8EFCEDA30D3C818E
GO
Isoform 2 (identifier: P15529-10) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     301-305: Missing.

Show »
Length:387
Mass (Da):43,286
Checksum:i20E7721BB47CA27C
GO
Isoform 3 (identifier: P15529-16) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     33-33: D → G
     34-96: Missing.
     377-392: TYLTDETHREVKFTSL → KADGGAEYATYQTKSTTPAEQRG

Show »
Length:336
Mass (Da):36,826
Checksum:iF57541078036A7EA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti25V → A in CAE45719 (PubMed:17974005).Curated1
Sequence conflicti108G → S in CAD97694 (PubMed:17974005).Curated1
Sequence conflicti159K → S in CAD97694 (PubMed:17974005).Curated1
Sequence conflicti162C → R in CAI45983 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02656713S → F.2 PublicationsCorresponds to variant rs138843816dbSNPEnsembl.1
Natural variantiVAR_06365635C → Y in AHUS2. 1 PublicationCorresponds to variant rs121909591dbSNPEnsembl.1
Natural variantiVAR_02656859R → Q.1 PublicationCorresponds to variant rs780693519dbSNPEnsembl.1
Natural variantiVAR_026569165P → S in AHUS2; reduced cell surface expression. 1 PublicationCorresponds to variant rs759136081dbSNPEnsembl.1
Natural variantiVAR_063657216W → C in AHUS2. 1 Publication1
Natural variantiVAR_035828228C → Y in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_063658231P → R in AHUS2. 1 Publication1
Natural variantiVAR_026570240S → P in AHUS2; no change in cell surface expression but reduced activity. 1 PublicationCorresponds to variant rs121909589dbSNPEnsembl.1
Natural variantiVAR_022262266D → N.1 PublicationCorresponds to variant rs17006830dbSNPEnsembl.1
Natural variantiVAR_026571271 – 272Missing in AHUS2; no cell surface expression. 1 Publication2
Natural variantiVAR_022263324P → L.1 PublicationCorresponds to variant rs41317833dbSNPEnsembl.1
Natural variantiVAR_022264353A → V.2 PublicationsCorresponds to variant rs35366573dbSNPEnsembl.1
Natural variantiVAR_022265355V → G.1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01900533D → G in isoform 3. Curated1
Alternative sequenceiVSP_01900634 – 96Missing in isoform 3. CuratedAdd BLAST63
Alternative sequenceiVSP_009176286 – 329Missing in isoform K and isoform L. 1 PublicationAdd BLAST44
Alternative sequenceiVSP_009175286 – 315Missing in isoform E, isoform F and isoform N. 5 PublicationsAdd BLAST30
Alternative sequenceiVSP_009174286 – 300Missing in isoform C, isoform D, isoform I, isoform J and isoform M. 7 PublicationsAdd BLAST15
Alternative sequenceiVSP_001201301 – 305Missing in isoform 2. Curated5
Alternative sequenceiVSP_009177316 – 329Missing in isoform G, isoform H, isoform I and isoform J. CuratedAdd BLAST14
Alternative sequenceiVSP_009178355 – 392VVGVA…KFTSL → GKQMVELNMPLTRLNQPLQQ SREAE in isoform N. 1 PublicationAdd BLAST38
Alternative sequenceiVSP_001202355 – 367Missing in isoform M. CuratedAdd BLAST13
Alternative sequenceiVSP_001203368 – 392YLQRR…KFTSL → GKQMVELNMPLTRLNQPLQQ SREAE in isoform M. CuratedAdd BLAST25
Alternative sequenceiVSP_001204377 – 392TYLTD…KFTSL → KADGGAEYATYQTKSTTPAE QRG in isoform B, isoform D, isoform F, isoform H, isoform J, isoform L and isoform 3. 8 PublicationsAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00651 mRNA. Translation: CAA68675.1.
M58050 mRNA. Translation: AAA62833.1.
X59405 mRNA. No translation available.
X59406 mRNA. No translation available.
X59407 mRNA. No translation available.
X59408 mRNA. No translation available.
X59409 mRNA. No translation available.
X59410 mRNA. No translation available.
S51940 mRNA. Translation: AAB24802.1.
D84105 mRNA. Translation: BAA12224.1.
EF076055 mRNA. Translation: ABK81635.1.
EF076056 mRNA. Translation: ABK81636.1.
EF076057 mRNA. Translation: ABK81637.1.
EF076058 mRNA. Translation: ABK81638.1.
AK291227 mRNA. Translation: BAF83916.1.
BX537451 mRNA. Translation: CAD97694.1.
BX640613 mRNA. Translation: CAE45719.1.
BX649050 mRNA. Translation: CAI45983.1.
AK222822 mRNA. Translation: BAD96542.1.
AY916779 Genomic DNA. Translation: AAW82433.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73947.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73948.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73949.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73950.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73951.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73952.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73953.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73954.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18804.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18805.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18806.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18807.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18808.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18809.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18810.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18811.1.
CH471100 Genomic DNA. Translation: EAW93465.1.
CH471100 Genomic DNA. Translation: EAW93470.1.
CH471100 Genomic DNA. Translation: EAW93476.1.
BC030594 mRNA. Translation: AAH30594.1.
AF209712 mRNA. Translation: AAF73844.1.
AF209713 mRNA. Translation: AAF73845.1.
AF209714 mRNA. Translation: AAF73846.1.
S65879 Genomic DNA. Translation: AAD13968.1.
CCDSiCCDS1479.1. [P15529-9]
CCDS1480.1. [P15529-3]
CCDS1481.1. [P15529-4]
CCDS1482.1. [P15529-2]
CCDS1484.1. [P15529-7]
CCDS1485.1. [P15529-1]
CCDS31008.1. [P15529-11]
CCDS31009.1. [P15529-12]
PIRiG02913.
I54479.
I57998.
S01896.
RefSeqiNP_002380.3. NM_002389.4. [P15529-1]
NP_722548.1. NM_153826.3. [P15529-3]
NP_758860.1. NM_172350.2. [P15529-9]
NP_758861.1. NM_172351.2. [P15529-11]
NP_758862.1. NM_172352.2. [P15529-12]
NP_758863.1. NM_172353.2. [P15529-4]
NP_758869.1. NM_172359.2. [P15529-2]
NP_758871.1. NM_172361.2. [P15529-7]
XP_011507865.1. XM_011509563.1. [P15529-5]
XP_011507866.1. XM_011509564.1. [P15529-6]
XP_016856797.1. XM_017001308.1. [P15529-13]
XP_016856798.1. XM_017001309.1. [P15529-14]
XP_016856799.1. XM_017001310.1. [P15529-15]
UniGeneiHs.510402.

Genome annotation databases

EnsembliENST00000322875; ENSP00000313875; ENSG00000117335. [P15529-2]
ENST00000322918; ENSP00000314664; ENSG00000117335. [P15529-9]
ENST00000354848; ENSP00000346912; ENSG00000117335. [P15529-3]
ENST00000357714; ENSP00000350346; ENSG00000117335. [P15529-4]
ENST00000358170; ENSP00000350893; ENSG00000117335. [P15529-1]
ENST00000360212; ENSP00000353342; ENSG00000117335. [P15529-7]
ENST00000367041; ENSP00000356008; ENSG00000117335. [P15529-12]
ENST00000367042; ENSP00000356009; ENSG00000117335. [P15529-11]
ENST00000367047; ENSP00000356014; ENSG00000117335. [P15529-16]
ENST00000480003; ENSP00000418471; ENSG00000117335. [P15529-6]
GeneIDi4179.
KEGGihsa:4179.
UCSCiuc001hgc.4. human. [P15529-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00651 mRNA. Translation: CAA68675.1.
M58050 mRNA. Translation: AAA62833.1.
X59405 mRNA. No translation available.
X59406 mRNA. No translation available.
X59407 mRNA. No translation available.
X59408 mRNA. No translation available.
X59409 mRNA. No translation available.
X59410 mRNA. No translation available.
S51940 mRNA. Translation: AAB24802.1.
D84105 mRNA. Translation: BAA12224.1.
EF076055 mRNA. Translation: ABK81635.1.
EF076056 mRNA. Translation: ABK81636.1.
EF076057 mRNA. Translation: ABK81637.1.
EF076058 mRNA. Translation: ABK81638.1.
AK291227 mRNA. Translation: BAF83916.1.
BX537451 mRNA. Translation: CAD97694.1.
BX640613 mRNA. Translation: CAE45719.1.
BX649050 mRNA. Translation: CAI45983.1.
AK222822 mRNA. Translation: BAD96542.1.
AY916779 Genomic DNA. Translation: AAW82433.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73947.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73948.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73949.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73950.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73951.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73952.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73953.1.
AL365178, AL035209 Genomic DNA. Translation: CAH73954.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18804.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18805.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18806.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18807.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18808.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18809.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18810.1.
AL035209, AL365178 Genomic DNA. Translation: CAI18811.1.
CH471100 Genomic DNA. Translation: EAW93465.1.
CH471100 Genomic DNA. Translation: EAW93470.1.
CH471100 Genomic DNA. Translation: EAW93476.1.
BC030594 mRNA. Translation: AAH30594.1.
AF209712 mRNA. Translation: AAF73844.1.
AF209713 mRNA. Translation: AAF73845.1.
AF209714 mRNA. Translation: AAF73846.1.
S65879 Genomic DNA. Translation: AAD13968.1.
CCDSiCCDS1479.1. [P15529-9]
CCDS1480.1. [P15529-3]
CCDS1481.1. [P15529-4]
CCDS1482.1. [P15529-2]
CCDS1484.1. [P15529-7]
CCDS1485.1. [P15529-1]
CCDS31008.1. [P15529-11]
CCDS31009.1. [P15529-12]
PIRiG02913.
I54479.
I57998.
S01896.
RefSeqiNP_002380.3. NM_002389.4. [P15529-1]
NP_722548.1. NM_153826.3. [P15529-3]
NP_758860.1. NM_172350.2. [P15529-9]
NP_758861.1. NM_172351.2. [P15529-11]
NP_758862.1. NM_172352.2. [P15529-12]
NP_758863.1. NM_172353.2. [P15529-4]
NP_758869.1. NM_172359.2. [P15529-2]
NP_758871.1. NM_172361.2. [P15529-7]
XP_011507865.1. XM_011509563.1. [P15529-5]
XP_011507866.1. XM_011509564.1. [P15529-6]
XP_016856797.1. XM_017001308.1. [P15529-13]
XP_016856798.1. XM_017001309.1. [P15529-14]
XP_016856799.1. XM_017001310.1. [P15529-15]
UniGeneiHs.510402.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CKLX-ray3.10A/B/C/D/E/F35-160[»]
1HR4model-A159-284[»]
2O39X-ray2.85C/D35-160[»]
3INBX-ray3.10C/D35-160[»]
3L89X-ray3.50M/N/O/P/Q/R/S/T/U/V/W/X35-160[»]
3O8EX-ray2.84B/D35-286[»]
5FO8X-ray2.40C35-286[»]
ProteinModelPortaliP15529.
SMRiP15529.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110346. 11 interactors.
DIPiDIP-41232N.
IntActiP15529. 8 interactors.
MINTiMINT-222279.
STRINGi9606.ENSP00000313875.

PTM databases

iPTMnetiP15529.
PhosphoSitePlusiP15529.
SwissPalmiP15529.

Polymorphism and mutation databases

BioMutaiCD46.
DMDMi41019474.

Proteomic databases

EPDiP15529.
MaxQBiP15529.
PaxDbiP15529.
PeptideAtlasiP15529.
PRIDEiP15529.
TopDownProteomicsiP15529-4. [P15529-4]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000322875; ENSP00000313875; ENSG00000117335. [P15529-2]
ENST00000322918; ENSP00000314664; ENSG00000117335. [P15529-9]
ENST00000354848; ENSP00000346912; ENSG00000117335. [P15529-3]
ENST00000357714; ENSP00000350346; ENSG00000117335. [P15529-4]
ENST00000358170; ENSP00000350893; ENSG00000117335. [P15529-1]
ENST00000360212; ENSP00000353342; ENSG00000117335. [P15529-7]
ENST00000367041; ENSP00000356008; ENSG00000117335. [P15529-12]
ENST00000367042; ENSP00000356009; ENSG00000117335. [P15529-11]
ENST00000367047; ENSP00000356014; ENSG00000117335. [P15529-16]
ENST00000480003; ENSP00000418471; ENSG00000117335. [P15529-6]
GeneIDi4179.
KEGGihsa:4179.
UCSCiuc001hgc.4. human. [P15529-1]

Organism-specific databases

CTDi4179.
DisGeNETi4179.
GeneCardsiCD46.
GeneReviewsiCD46.
HGNCiHGNC:6953. CD46.
HPAiCAB010401.
HPA016903.
MalaCardsiCD46.
MIMi120920. gene+phenotype.
612922. phenotype.
neXtProtiNX_P15529.
OpenTargetsiENSG00000117335.
Orphaneti93576. Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly.
244242. HELLP syndrome.
PharmGKBiPA30700.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IY7G. Eukaryota.
ENOG4111CPD. LUCA.
GeneTreeiENSGT00760000118803.
HOVERGENiHBG006335.
InParanoidiP15529.
KOiK04007.
OMAiCKVVKCR.
OrthoDBiEOG091G0DWA.
PhylomeDBiP15529.
TreeFamiTF334137.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000117335-MONOMER.
ReactomeiR-HSA-977606. Regulation of Complement cascade.

Miscellaneous databases

ChiTaRSiCD46. human.
EvolutionaryTraceiP15529.
GeneWikiiCD46.
GenomeRNAii4179.
PMAP-CutDBP15529.
PROiP15529.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000117335.
ExpressionAtlasiP15529. baseline and differential.
GenevisibleiP15529. HS.

Family and domain databases

CDDicd00033. CCP. 4 hits.
InterProiIPR017341. CD46.
IPR000436. Sushi_SCR_CCP_dom.
[Graphical view]
PfamiPF00084. Sushi. 4 hits.
[Graphical view]
PIRSFiPIRSF037971. TLX_CD46. 1 hit.
SMARTiSM00032. CCP. 4 hits.
[Graphical view]
SUPFAMiSSF57535. SSF57535. 4 hits.
PROSITEiPS50923. SUSHI. 4 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMCP_HUMAN
AccessioniPrimary (citable) accession number: P15529
Secondary accession number(s): A0T1T0
, A0T1T1, A0T1T2, Q15429, Q53GV9, Q5HY94, Q5VWS6, Q5VWS7, Q5VWS8, Q5VWS9, Q5VWT0, Q5VWT1, Q5VWT2, Q6N0A1, Q7Z3R5, Q9NNW2, Q9NNW3, Q9NNW4, Q9UCJ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: January 16, 2004
Last modified: November 30, 2016
This is version 196 of the entry and version 3 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 cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.