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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

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini35 – 343309ExtracellularSequence analysisAdd
BLAST
Transmembranei344 – 36623HelicalSequence analysisAdd
BLAST
Topological domaini367 – 39226CytoplasmicSequence analysisAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti35 – 351C → Y in AHUS2. 1 Publication
Corresponds to variant rs121909591 [ dbSNP | Ensembl ].
VAR_063656
Natural varianti165 – 1651P → S in AHUS2; reduced cell surface expression. 1 Publication
Corresponds to variant rs759136081 [ dbSNP | Ensembl ].
VAR_026569
Natural varianti216 – 2161W → C in AHUS2. 1 Publication
VAR_063657
Natural varianti231 – 2311P → R in AHUS2. 1 Publication
VAR_063658
Natural varianti240 – 2401S → P in AHUS2; no change in cell surface expression but reduced activity. 1 Publication
Corresponds to variant rs121909589 [ dbSNP | Ensembl ].
VAR_026570
Natural varianti271 – 2722Missing in AHUS2; no cell surface expression. 1 Publication
VAR_026571

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi83 – 831N → Q: No effect on cytoprotective function. No effect on Neisseria binding. No effect on Measles virus binding. 3 Publications
Mutagenesisi114 – 1141N → Q: Strongly decreases cytoprotective function. Decreases Neisseria binding. Abolishes Measles virus binding. 3 Publications
Mutagenesisi273 – 2731N → Q: Strongly decreases cytoprotective function. Abolishes Neisseria binding. No effect on Measles virus binding. 3 Publications

Keywords - Diseasei

Disease mutation, Hemolytic uremic syndrome

Organism-specific databases

MalaCardsiCD46.
MIMi120920. gene+phenotype.
612922. phenotype.
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)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 34344 PublicationsAdd
BLAST
Chaini35 – 392358Membrane cofactor proteinPRO_0000006008Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi35 ↔ 80PROSITE-ProRule annotation
Disulfide bondi64 ↔ 94PROSITE-ProRule annotation
Glycosylationi83 – 831N-linked (GlcNAc...)
Disulfide bondi99 ↔ 141PROSITE-ProRule annotation
Glycosylationi114 – 1141N-linked (GlcNAc...)
Disulfide bondi127 ↔ 157PROSITE-ProRule annotation
Disulfide bondi162 ↔ 210PROSITE-ProRule annotation
Glycosylationi163 – 1631O-linked (GalNAc...)Sequence analysis
Disulfide bondi191 ↔ 223PROSITE-ProRule annotation
Disulfide bondi228 ↔ 270PROSITE-ProRule annotation
Disulfide bondi256 ↔ 283PROSITE-ProRule annotation
Glycosylationi273 – 2731N-linked (GlcNAc...)
Glycosylationi290 – 2901O-linked (GalNAc...)Sequence analysis
Glycosylationi291 – 2911O-linked (GalNAc...)Sequence analysis
Glycosylationi292 – 2921O-linked (GalNAc...)Sequence analysis
Glycosylationi298 – 2981O-linked (GalNAc...)Sequence analysis
Glycosylationi300 – 3001O-linked (GalNAc...)Sequence analysis
Glycosylationi302 – 3021O-linked (GalNAc...)Sequence analysis
Glycosylationi303 – 3031O-linked (GalNAc...)Sequence analysis
Glycosylationi304 – 3041O-linked (GalNAc...)Sequence analysis
Glycosylationi305 – 3051O-linked (GalNAc...)Sequence analysis
Glycosylationi306 – 3061O-linked (GalNAc...)Sequence analysis
Glycosylationi307 – 3071O-linked (GalNAc...)Sequence analysis
Glycosylationi309 – 3091O-linked (GalNAc...)Sequence analysis
Glycosylationi312 – 3121O-linked (GalNAc...)Sequence analysis
Glycosylationi313 – 3131O-linked (GalNAc...)Sequence analysis
Glycosylationi315 – 3151O-linked (GalNAc...)Sequence analysis
Glycosylationi320 – 3201O-linked (GalNAc...)Sequence analysis
Glycosylationi326 – 3261O-linked (GalNAc...)Sequence analysis
Isoform 3 (identifier: P15529-16)
Modified residuei321 – 3211Phosphotyrosine1 Publication
Isoform L (identifier: P15529-7)
Modified residuei340 – 3401Phosphotyrosine1 Publication
Isoform F (identifier: P15529-4)
Modified residuei354 – 3541Phosphotyrosine1 Publication
Isoform J (identifier: P15529-6)
Modified residuei355 – 3551Phosphotyrosine1 Publication
Isoform D (identifier: P15529-3)
Modified residuei369 – 3691Phosphotyrosine1 Publication
Isoform H (identifier: P15529-5)
Modified residuei370 – 3701Phosphotyrosine1 Publication
Isoform B (identifier: P15529-2)
Modified residuei384 – 3841Phosphotyrosine1 Publication

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.
PhosphoSiteiP15529.
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 interactions.
DIPiDIP-41232N.
IntActiP15529. 8 interactions.
MINTiMINT-222279.
STRINGi9606.ENSP00000313875.

Structurei

Secondary structure

1
392
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi42 – 487Combined sources
Beta strandi59 – 646Combined sources
Beta strandi68 – 703Combined sources
Beta strandi72 – 743Combined sources
Beta strandi77 – 804Combined sources
Beta strandi84 – 863Combined sources
Helixi91 – 933Combined sources
Beta strandi94 – 963Combined sources
Beta strandi108 – 1125Combined sources
Beta strandi115 – 1184Combined sources
Beta strandi122 – 1276Combined sources
Beta strandi131 – 1355Combined sources
Beta strandi137 – 14610Combined sources
Beta strandi148 – 1525Combined sources
Beta strandi156 – 1594Combined sources
Beta strandi171 – 1744Combined sources
Beta strandi183 – 1919Combined sources
Beta strandi195 – 1984Combined sources
Beta strandi201 – 2044Combined sources
Beta strandi206 – 2105Combined sources
Helixi212 – 2143Combined sources
Beta strandi215 – 2184Combined sources
Beta strandi222 – 2243Combined sources
Beta strandi236 – 2405Combined sources
Beta strandi251 – 2566Combined sources
Beta strandi260 – 2645Combined sources
Beta strandi266 – 2705Combined sources
Beta strandi276 – 2783Combined sources
Beta strandi282 – 2854Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 35-286.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15529.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini35 – 9662Sushi 1PROSITE-ProRule annotationAdd
BLAST
Domaini97 – 15963Sushi 2PROSITE-ProRule annotationAdd
BLAST
Domaini160 – 22566Sushi 3PROSITE-ProRule annotationAdd
BLAST
Domaini226 – 28560Sushi 4PROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi302 – 32625Ser/Thr-richAdd
BLAST

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.
GeneTreeiENSGT00840000129714.
HOVERGENiHBG006335.
InParanoidiP15529.
KOiK04007.
OMAiCKVVKCR.
OrthoDBiEOG091G0DWA.
PhylomeDBiP15529.
TreeFamiTF334137.

Family and domain databases

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti25 – 251V → A in CAE45719 (PubMed:17974005).Curated
Sequence conflicti108 – 1081G → S in CAD97694 (PubMed:17974005).Curated
Sequence conflicti159 – 1591K → S in CAD97694 (PubMed:17974005).Curated
Sequence conflicti162 – 1621C → R in CAI45983 (PubMed:17974005).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti13 – 131S → F.2 Publications
Corresponds to variant rs138843816 [ dbSNP | Ensembl ].
VAR_026567
Natural varianti35 – 351C → Y in AHUS2. 1 Publication
Corresponds to variant rs121909591 [ dbSNP | Ensembl ].
VAR_063656
Natural varianti59 – 591R → Q.1 Publication
Corresponds to variant rs780693519 [ dbSNP | Ensembl ].
VAR_026568
Natural varianti165 – 1651P → S in AHUS2; reduced cell surface expression. 1 Publication
Corresponds to variant rs759136081 [ dbSNP | Ensembl ].
VAR_026569
Natural varianti216 – 2161W → C in AHUS2. 1 Publication
VAR_063657
Natural varianti228 – 2281C → Y in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_035828
Natural varianti231 – 2311P → R in AHUS2. 1 Publication
VAR_063658
Natural varianti240 – 2401S → P in AHUS2; no change in cell surface expression but reduced activity. 1 Publication
Corresponds to variant rs121909589 [ dbSNP | Ensembl ].
VAR_026570
Natural varianti266 – 2661D → N.1 Publication
Corresponds to variant rs17006830 [ dbSNP | Ensembl ].
VAR_022262
Natural varianti271 – 2722Missing in AHUS2; no cell surface expression. 1 Publication
VAR_026571
Natural varianti324 – 3241P → L.1 Publication
Corresponds to variant rs41317833 [ dbSNP | Ensembl ].
VAR_022263
Natural varianti353 – 3531A → V.2 Publications
Corresponds to variant rs35366573 [ dbSNP | Ensembl ].
VAR_022264
Natural varianti355 – 3551V → G.1 Publication
VAR_022265

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei33 – 331D → G in isoform 3. CuratedVSP_019005
Alternative sequencei34 – 9663Missing in isoform 3. CuratedVSP_019006Add
BLAST
Alternative sequencei286 – 32944Missing in isoform K and isoform L. 1 PublicationVSP_009176Add
BLAST
Alternative sequencei286 – 31530Missing in isoform E, isoform F and isoform N. 5 PublicationsVSP_009175Add
BLAST
Alternative sequencei286 – 30015Missing in isoform C, isoform D, isoform I, isoform J and isoform M. 7 PublicationsVSP_009174Add
BLAST
Alternative sequencei301 – 3055Missing in isoform 2. CuratedVSP_001201
Alternative sequencei316 – 32914Missing in isoform G, isoform H, isoform I and isoform J. CuratedVSP_009177Add
BLAST
Alternative sequencei355 – 39238VVGVA…KFTSL → GKQMVELNMPLTRLNQPLQQ SREAE in isoform N. 1 PublicationVSP_009178Add
BLAST
Alternative sequencei355 – 36713Missing in isoform M. CuratedVSP_001202Add
BLAST
Alternative sequencei368 – 39225YLQRR…KFTSL → GKQMVELNMPLTRLNQPLQQ SREAE in isoform M. CuratedVSP_001203Add
BLAST
Alternative sequencei377 – 39216TYLTD…KFTSL → KADGGAEYATYQTKSTTPAE QRG in isoform B, isoform D, isoform F, isoform H, isoform J, isoform L and isoform 3. 8 PublicationsVSP_001204Add
BLAST

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]
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]
UniGeneiHs.510402.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 35-286.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiP15529.
PhosphoSiteiP15529.
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.
GeneCardsiCD46.
GeneReviewsiCD46.
HGNCiHGNC:6953. CD46.
HPAiCAB010401.
HPA016903.
MalaCardsiCD46.
MIMi120920. gene+phenotype.
612922. phenotype.
neXtProtiNX_P15529.
Orphaneti93576. Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly.
244242. HELLP syndrome.
PharmGKBiPA30700.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IY7G. Eukaryota.
ENOG4111CPD. LUCA.
GeneTreeiENSGT00840000129714.
HOVERGENiHBG006335.
InParanoidiP15529.
KOiK04007.
OMAiCKVVKCR.
OrthoDBiEOG091G0DWA.
PhylomeDBiP15529.
TreeFamiTF334137.

Enzyme and pathway databases

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

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: September 7, 2016
This is version 193 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.