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Q9BXS0 (COPA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 94. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Collagen alpha-1(XXV) chain
Alternative name(s):
Alzheimer disease amyloid-associated protein
Short name=AMY
CLAC-P

Cleaved into the following chain:

  1. Collagen-like Alzheimer amyloid plaque component
    Short name=CLAC
Gene names
Name:COL25A1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length654 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Inhibits fibrillization of beta amyloid peptide during the elongation phase. Has also been shown to assemble amyloid fibrils into protease-resistant aggregates. Binds heparin. Ref.4 Ref.6 Ref.7 Ref.8

Subunit structure

Forms homodimers and homotrimers. Binds to the fibrillized forms of beta amyloid peptide 40 (beta-APP40) and beta amyloid peptide 42 (beta-APP42). Found associated with beta-APP42 more frequently than with beta-APP40. Ref.1 Ref.4 Ref.5 Ref.8

Subcellular location

Membrane; Single-pass type II membrane protein Potential. Note: After proteolytic cleavage, CLAC is secreted.

Tissue specificity

Expressed predominantly in brain. Deposited preferentially in primitive or neuritic amyloid plaques which are typical of Alzheimer disease. Ref.1

Post-translational modification

Undergoes proteolytic cleavage by furin protease to yield the soluble collagen-like Alzheimer amyloid plaque component. Ref.1

Glycosylated. Ref.4

Hydroxylated on 11% of proline residues and 49% of lysine residues. Ref.1 Ref.4

Sequence similarities

Contains 7 collagen-like domains.

Caution

The pyrrolidone carboxylic acid reported in Ref.1 probably formed artifactually from Glu-113 during the extraction procedure in 70% formic acid. In Ref.4, the protein was found to have unblocked Glu at the N-terminus.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.1 (identifier: Q9BXS0-1)

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.
Isoform 2 Ref.1 (identifier: Q9BXS0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     616-654: GFRGVKGEKGEPGQPGLDGLDAPCQLGPDGLPMPGCWQK → VTSPSQHVPCLILLLLSALLFSLCDSI
Isoform 3 Ref.2 (identifier: Q9BXS0-3)

The sequence of this isoform differs from the canonical sequence as follows:
     141-146: Missing.
     326-340: Missing.
     589-640: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 654654Collagen alpha-1(XXV) chain
PRO_0000259611
Chain113 – 654542Collagen-like Alzheimer amyloid plaque component Ref.1 Ref.4
PRO_0000259612

Regions

Topological domain1 – 3333Cytoplasmic Potential
Transmembrane34 – 5421Helical; Signal-anchor for type II membrane protein; Potential
Topological domain55 – 654600Extracellular Potential
Domain121 – 16444Collagen-like 1
Domain192 – 24756Collagen-like 2
Domain249 – 30860Collagen-like 3
Domain311 – 37060Collagen-like 4
Domain372 – 42554Collagen-like 5
Domain447 – 50559Collagen-like 6
Domain571 – 63060Collagen-like 7
Region181 – 1888Interaction with beta amyloid peptide Ref.4

Sites

Site112 – 1132Cleavage; by furin Ref.1

Amino acid modifications

Modified residue1131Pyrrolidone carboxylic acid (Glu) Ref.1

Natural variations

Alternative sequence141 – 1466Missing in isoform 3. Ref.2
VSP_052197
Alternative sequence326 – 34015Missing in isoform 3. Ref.2
VSP_052198
Alternative sequence589 – 64052Missing in isoform 3. Ref.2
VSP_052199
Alternative sequence616 – 65439GFRGV…GCWQK → VTSPSQHVPCLILLLLSALL FSLCDSI in isoform 2. Ref.1
VSP_052200

Experimental info

Mutagenesis1091R → A: Not secreted. Ref.1
Mutagenesis1121R → A: Not secreted. Ref.1
Mutagenesis181 – 1888LIKRRLIK → VIKRRTFQ: Reduces binding to beta amyloid peptide. Ref.4
Mutagenesis181 – 1888Missing: Abolishes binding to beta amyloid peptide. Ref.4
Sequence conflict281A → S in AAK35008. Ref.1
Sequence conflict281A → S in AAK35009. Ref.2
Sequence conflict4271E → K in AAK35008. Ref.1
Sequence conflict4271E → K in AAK35009. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: D6DFB4FB157C05A2

FASTA65464,771
        10         20         30         40         50         60 
MLLKKHAGKG GGREPRSEDP TPAEQHCART MPPCAVLAAL LSVVAVVSCL YLGVKTNDLQ 

        70         80         90        100        110        120 
ARIAALESAK GAPSIHLLPD TLDHLKTMVQ EKVERLLAQK SYEHMAKIRI AREAPSECNC 

       130        140        150        160        170        180 
PAGPPGKRGK RGRRGESGPP GQPGPQGPPG PKGDKGEQGD QGPRMVFPKI NHGFLSADQQ 

       190        200        210        220        230        240 
LIKRRLIKGD QGQAGPPGPP GPPGPRGPPG DTGKDGPRGM PGVPGEPGKP GEQGLMGPLG 

       250        260        270        280        290        300 
PPGQKGSIGA PGIPGMNGQK GEPGLPGAVG QNGIPGPKGE PGEQGEKGDA GENGPKGDTG 

       310        320        330        340        350        360 
EKGDPGSSAA GIKGEPGESG RPGQKGEPGL PGLPGLPGIK GEPGFIGPQG EPGLPGLPGT 

       370        380        390        400        410        420 
KGERGEAGPP GRGERGEPGA PGPKGKQGES GTRGPKGSKG DRGEKGDSGA QGPRGPPGQK 

       430        440        450        460        470        480 
GDQGATEIID YNGNLHEALQ RITTLTVTGP PGPPGPQGLQ GPKGEQGSPG IPGMDGEQGL 

       490        500        510        520        530        540 
KGSKGDMGDP GMTGEKGGIG LPGLPGANGM KGEKGDSGMP GPQGPSIIGP PGPPGPHGPP 

       550        560        570        580        590        600 
GPMGPHGLPG PKGTDGPMGP HGPAGPKGER GEKGAMGEPG PRGPYGLPGK DGEPGLDGFP 

       610        620        630        640        650 
GPRGEKGDLG EKGEKGFRGV KGEKGEPGQP GLDGLDAPCQ LGPDGLPMPG CWQK 

« Hide

Isoform 2 [UniParc].

Checksum: 14B1AC4C9E55506F
Show »

FASTA64263,661
Isoform 3 [UniParc].

Checksum: D4F26C1293B70F3B
Show »

FASTA58157,619

References

« Hide 'large scale' references
[1]"CLAC: a novel Alzheimer amyloid plaque component derived from a transmembrane precursor, CLAC-P/collagen type XXV."
Hashimoto T., Wakabayashi T., Watanabe A., Kowa H., Hosoda R., Nakamura A., Kanazawa I., Arai T., Takio K., Mann D.M.A., Iwatsubo T.
EMBO J. 21:1524-1534(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 131-152 AND 156-214, INTERACTION WITH BETA AMYLOID PEPTIDE, TISSUE SPECIFICITY, CLEAVAGE, HYDROXYLATION, PYROGLUTAMATE FORMATION AT GLU-113, MUTAGENESIS OF ARG-109 AND ARG-112.
[2]"Molecular identification of AMY, an Alzheimer disease amyloid-associated protein."
Soederberg L., Zhukareva V., Bogdanovic N., Hashimoto T., Winblad B., Iwatsubo T., Lee V.M.Y., Trojanowski J.Q., Naeslund J.
J. Neuropathol. Exp. Neurol. 62:1108-1117(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide-binding site."
Soederberg L., Kakuyama H., Moeller A., Ito A., Winblad B., Tjernberg L.O., Naeslund J.
J. Biol. Chem. 280:1007-1015(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF CLAC N-TERMINUS, PROTEIN SEQUENCE OF 182-191 AND 445-452, FUNCTION, SUBUNIT, INTERACTION WITH BETA AMYLOID PEPTIDE, GLYCOSYLATION, HYDROXYLATION, MUTAGENESIS OF 181-LEU--LYS-188.
[5]"Mostly separate distributions of CLAC- versus Abeta40- or thioflavin S-reactivities in senile plaques reveal two distinct subpopulations of beta-amyloid deposits."
Kowa H., Sakakura T., Matsuura Y., Wakabayashi T., Mann D.M.A., Duff K., Tsuji S., Hashimoto T., Iwatsubo T.
Am. J. Pathol. 165:273-281(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BETA AMYLOID PEPTIDE.
[6]"CLAC binds to aggregated Abeta and Abeta fragments, and attenuates fibril elongation."
Kakuyama H., Soederberg L., Horigome K., Winblad B., Dahlqvist C., Naeslund J., Tjernberg L.O.
Biochemistry 44:15602-15609(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Collagenous Alzheimer amyloid plaque component assembles amyloid fibrils into protease resistant aggregates."
Soederberg L., Dahlqvist C., Kakuyama H., Thyberg J., Ito A., Winblad B., Naeslund J., Tjernberg L.O.
FEBS J. 272:2231-2236(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"CLAC binds to amyloid beta peptides through the positively charged amino acid cluster within the collagenous domain 1 and inhibits formation of amyloid fibrils."
Osada Y., Hashimoto T., Nishimura A., Matsuo Y., Wakabayashi T., Iwatsubo T.
J. Biol. Chem. 280:8596-8605(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH BETA AMYLOID PEPTIDE.
[9]Erratum
Osada Y., Hashimoto T., Nishimura A., Matsuo Y., Wakabayashi T., Iwatsubo T.
J. Biol. Chem. 280:15484-15484(2005)
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF293340 mRNA. Translation: AAK35008.1.
AF293341 mRNA. Translation: AAK35009.1.
AC097473 Genomic DNA. No translation available.
AC073427 Genomic DNA. No translation available.
AC095066 Genomic DNA. No translation available.
AC004701 Genomic DNA. No translation available.
AC004051 Genomic DNA. No translation available.
RefSeqNP_115907.2. NM_032518.2.
NP_942014.1. NM_198721.3.
UniGeneHs.658842.

3D structure databases

ProteinModelPortalQ9BXS0.
SMRQ9BXS0. Positions 606-639.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124143. 2 interactions.
STRING9606.ENSP00000329626.

PTM databases

PhosphoSiteQ9BXS0.

Polymorphism databases

DMDM296434459.

Proteomic databases

PaxDbQ9BXS0.
PRIDEQ9BXS0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000399126; ENSP00000382077; ENSG00000188517. [Q9BXS0-2]
ENST00000399132; ENSP00000382083; ENSG00000188517. [Q9BXS0-1]
GeneID84570.
KEGGhsa:84570.
UCSCuc003hze.2. human. [Q9BXS0-1]
uc003hzg.4. human. [Q9BXS0-2]

Organism-specific databases

CTD84570.
GeneCardsGC04M109731.
H-InvDBHIX0004434.
HGNCHGNC:18603. COL25A1.
HPAHPA029107.
MIM610004. gene.
neXtProtNX_Q9BXS0.
PharmGKBPA134912284.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG12793.
HOGENOMHOG000085653.
HOVERGENHBG101380.
OrthoDBEOG7D59P1.
PhylomeDBQ9BXS0.
TreeFamTF338175.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

BgeeQ9BXS0.
CleanExHS_COL25A1.
GenevestigatorQ9BXS0.

Family and domain databases

InterProIPR008160. Collagen.
[Graphical view]
PfamPF01391. Collagen. 7 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCollagen,_type_XXV,_alpha_1.
GenomeRNAi84570.
NextBio74464.
PROQ9BXS0.
SOURCESearch...

Entry information

Entry nameCOPA1_HUMAN
AccessionPrimary (citable) accession number: Q9BXS0
Secondary accession number(s): A8MPZ6, Q9BXR9
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: May 18, 2010
Last modified: April 16, 2014
This is version 94 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM