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Q9BXS0

- COPA1_HUMAN

UniProt

Q9BXS0 - COPA1_HUMAN

Protein

Collagen alpha-1(XXV) chain

Gene

COL25A1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 98 (01 Oct 2014)
      Sequence version 2 (18 May 2010)
      Previous versions | rss
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    Functioni

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei112 – 1132Cleavage; by furin

    GO - Molecular functioni

    1. beta-amyloid binding Source: UniProtKB
    2. heparin binding Source: UniProtKB

    GO - Biological processi

    1. collagen catabolic process Source: Reactome
    2. extracellular matrix disassembly Source: Reactome
    3. extracellular matrix organization Source: Reactome

    Keywords - Ligandi

    Heparin-binding

    Enzyme and pathway databases

    ReactomeiREACT_121139. Collagen biosynthesis and modifying enzymes.
    REACT_150401. Collagen degradation.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Collagen alpha-1(XXV) chain
    Alternative name(s):
    Alzheimer disease amyloid-associated protein
    Short name:
    AMY
    CLAC-P
    Cleaved into the following chain:
    Gene namesi
    Name:COL25A1Imported
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:18603. COL25A1.

    Subcellular locationi

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

    GO - Cellular componenti

    1. collagen trimer Source: UniProtKB-KW
    2. endoplasmic reticulum lumen Source: Reactome
    3. extracellular region Source: MGI
    4. extracellular space Source: UniProtKB
    5. integral component of membrane Source: UniProtKB
    6. integral component of plasma membrane Source: MGI
    7. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Amyloid, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi109 – 1091R → A: Not secreted. 2 Publications
    Mutagenesisi112 – 1121R → A: Not secreted. 2 Publications
    Mutagenesisi181 – 1888LIKRRLIK → VIKRRTFQ: Reduces binding to beta amyloid peptide. 1 Publication
    Mutagenesisi181 – 1888Missing: Abolishes binding to beta amyloid peptide. 1 Publication

    Organism-specific databases

    PharmGKBiPA134912284.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 654654Collagen alpha-1(XXV) chainPRO_0000259611Add
    BLAST
    Chaini113 – 654542Collagen-like Alzheimer amyloid plaque component2 PublicationsPRO_0000259612Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei113 – 1131Pyrrolidone carboxylic acid (Glu)1 Publication

    Post-translational modificationi

    Undergoes proteolytic cleavage by furin protease to yield the soluble collagen-like Alzheimer amyloid plaque component.1 Publication
    Glycosylated.1 Publication
    Hydroxylated on 11% of proline residues and 49% of lysine residues.2 Publications

    Keywords - PTMi

    Glycoprotein, Hydroxylation, Pyrrolidone carboxylic acid

    Proteomic databases

    MaxQBiQ9BXS0.
    PaxDbiQ9BXS0.
    PRIDEiQ9BXS0.

    PTM databases

    PhosphoSiteiQ9BXS0.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    BgeeiQ9BXS0.
    CleanExiHS_COL25A1.
    GenevestigatoriQ9BXS0.

    Organism-specific databases

    HPAiHPA029107.

    Interactioni

    Subunit structurei

    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-APP40.4 Publications

    Protein-protein interaction databases

    BioGridi124143. 2 interactions.
    STRINGi9606.ENSP00000329626.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9BXS0.
    SMRiQ9BXS0. Positions 606-639.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3333CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini55 – 654600ExtracellularSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei34 – 5421Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini121 – 16444Collagen-like 1Sequence AnalysisAdd
    BLAST
    Domaini192 – 24756Collagen-like 2Sequence AnalysisAdd
    BLAST
    Domaini249 – 30860Collagen-like 3Sequence AnalysisAdd
    BLAST
    Domaini311 – 37060Collagen-like 4Sequence AnalysisAdd
    BLAST
    Domaini372 – 42554Collagen-like 5Sequence AnalysisAdd
    BLAST
    Domaini447 – 50559Collagen-like 6Sequence AnalysisAdd
    BLAST
    Domaini571 – 63060Collagen-like 7Sequence AnalysisAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni181 – 1888Interaction with beta amyloid peptide1 Publication

    Sequence similaritiesi

    Contains 7 collagen-like domains.Sequence Analysis

    Keywords - Domaini

    Collagen, Repeat, Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG12793.
    HOGENOMiHOG000085653.
    HOVERGENiHBG101380.
    OMAiHHILVED.
    OrthoDBiEOG7D59P1.
    PhylomeDBiQ9BXS0.
    TreeFamiTF338175.

    Family and domain databases

    InterProiIPR029575. CLAC-P.
    IPR008160. Collagen.
    [Graphical view]
    PANTHERiPTHR24023:SF412. PTHR24023:SF412. 1 hit.
    PfamiPF01391. Collagen. 7 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. Align

    Isoform 11 Publication (identifier: Q9BXS0-1) [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

    MLLKKHAGKG GGREPRSEDP TPAEQHCART MPPCAVLAAL LSVVAVVSCL    50
    YLGVKTNDLQ ARIAALESAK GAPSIHLLPD TLDHLKTMVQ EKVERLLAQK 100
    SYEHMAKIRI AREAPSECNC PAGPPGKRGK RGRRGESGPP GQPGPQGPPG 150
    PKGDKGEQGD QGPRMVFPKI NHGFLSADQQ LIKRRLIKGD QGQAGPPGPP 200
    GPPGPRGPPG DTGKDGPRGM PGVPGEPGKP GEQGLMGPLG PPGQKGSIGA 250
    PGIPGMNGQK GEPGLPGAVG QNGIPGPKGE PGEQGEKGDA GENGPKGDTG 300
    EKGDPGSSAA GIKGEPGESG RPGQKGEPGL PGLPGLPGIK GEPGFIGPQG 350
    EPGLPGLPGT KGERGEAGPP GRGERGEPGA PGPKGKQGES GTRGPKGSKG 400
    DRGEKGDSGA QGPRGPPGQK GDQGATEIID YNGNLHEALQ RITTLTVTGP 450
    PGPPGPQGLQ GPKGEQGSPG IPGMDGEQGL KGSKGDMGDP GMTGEKGGIG 500
    LPGLPGANGM KGEKGDSGMP GPQGPSIIGP PGPPGPHGPP GPMGPHGLPG 550
    PKGTDGPMGP HGPAGPKGER GEKGAMGEPG PRGPYGLPGK DGEPGLDGFP 600
    GPRGEKGDLG EKGEKGFRGV KGEKGEPGQP GLDGLDAPCQ LGPDGLPMPG 650
    CWQK 654
    Length:654
    Mass (Da):64,771
    Last modified:May 18, 2010 - v2
    Checksum:iD6DFB4FB157C05A2
    GO
    Isoform 21 Publication (identifier: Q9BXS0-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         616-654: GFRGVKGEKGEPGQPGLDGLDAPCQLGPDGLPMPGCWQK → VTSPSQHVPCLILLLLSALLFSLCDSI

    Show »
    Length:642
    Mass (Da):63,661
    Checksum:i14B1AC4C9E55506F
    GO
    Isoform 31 Publication (identifier: Q9BXS0-3) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:581
    Mass (Da):57,619
    Checksum:iD4F26C1293B70F3B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti28 – 281A → S in AAK35008. (PubMed:11927537)Curated
    Sequence conflicti28 – 281A → S in AAK35009. (PubMed:14656069)Curated
    Sequence conflicti427 – 4271E → K in AAK35008. (PubMed:11927537)Curated
    Sequence conflicti427 – 4271E → K in AAK35009. (PubMed:14656069)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei141 – 1466Missing in isoform 3. 1 PublicationVSP_052197
    Alternative sequencei326 – 34015Missing in isoform 3. 1 PublicationVSP_052198Add
    BLAST
    Alternative sequencei589 – 64052Missing in isoform 3. 1 PublicationVSP_052199Add
    BLAST
    Alternative sequencei616 – 65439GFRGV…GCWQK → VTSPSQHVPCLILLLLSALL FSLCDSI in isoform 2. 1 PublicationVSP_052200Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS43258.1. [Q9BXS0-1]
    CCDS43259.1. [Q9BXS0-2]
    RefSeqiNP_115907.2. NM_032518.2. [Q9BXS0-2]
    NP_942014.1. NM_198721.3. [Q9BXS0-1]
    UniGeneiHs.658842.

    Genome annotation databases

    EnsembliENST00000399126; ENSP00000382077; ENSG00000188517. [Q9BXS0-2]
    ENST00000399132; ENSP00000382083; ENSG00000188517. [Q9BXS0-1]
    GeneIDi84570.
    KEGGihsa:84570.
    UCSCiuc003hze.2. human. [Q9BXS0-1]
    uc003hzg.4. human. [Q9BXS0-2]

    Polymorphism databases

    DMDMi296434459.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSi CCDS43258.1. [Q9BXS0-1 ]
    CCDS43259.1. [Q9BXS0-2 ]
    RefSeqi NP_115907.2. NM_032518.2. [Q9BXS0-2 ]
    NP_942014.1. NM_198721.3. [Q9BXS0-1 ]
    UniGenei Hs.658842.

    3D structure databases

    ProteinModelPortali Q9BXS0.
    SMRi Q9BXS0. Positions 606-639.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 124143. 2 interactions.
    STRINGi 9606.ENSP00000329626.

    PTM databases

    PhosphoSitei Q9BXS0.

    Polymorphism databases

    DMDMi 296434459.

    Proteomic databases

    MaxQBi Q9BXS0.
    PaxDbi Q9BXS0.
    PRIDEi Q9BXS0.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000399126 ; ENSP00000382077 ; ENSG00000188517 . [Q9BXS0-2 ]
    ENST00000399132 ; ENSP00000382083 ; ENSG00000188517 . [Q9BXS0-1 ]
    GeneIDi 84570.
    KEGGi hsa:84570.
    UCSCi uc003hze.2. human. [Q9BXS0-1 ]
    uc003hzg.4. human. [Q9BXS0-2 ]

    Organism-specific databases

    CTDi 84570.
    GeneCardsi GC04M109731.
    H-InvDB HIX0004434.
    HGNCi HGNC:18603. COL25A1.
    HPAi HPA029107.
    MIMi 610004. gene.
    neXtProti NX_Q9BXS0.
    PharmGKBi PA134912284.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG12793.
    HOGENOMi HOG000085653.
    HOVERGENi HBG101380.
    OMAi HHILVED.
    OrthoDBi EOG7D59P1.
    PhylomeDBi Q9BXS0.
    TreeFami TF338175.

    Enzyme and pathway databases

    Reactomei REACT_121139. Collagen biosynthesis and modifying enzymes.
    REACT_150401. Collagen degradation.

    Miscellaneous databases

    GeneWikii Collagen,_type_XXV,_alpha_1.
    GenomeRNAii 84570.
    NextBioi 74464.
    PROi Q9BXS0.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9BXS0.
    CleanExi HS_COL25A1.
    Genevestigatori Q9BXS0.

    Family and domain databases

    InterProi IPR029575. CLAC-P.
    IPR008160. Collagen.
    [Graphical view ]
    PANTHERi PTHR24023:SF412. PTHR24023:SF412. 1 hit.
    Pfami PF01391. Collagen. 7 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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)

    Entry informationi

    Entry nameiCOPA1_HUMAN
    AccessioniPrimary (citable) accession number: Q9BXS0
    Secondary accession number(s): A8MPZ6, Q9BXR9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 31, 2006
    Last sequence update: May 18, 2010
    Last modified: October 1, 2014
    This is version 98 of the entry and version 2 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

    Caution

    The pyrrolidone carboxylic acid reported in PubMed:11927537 probably formed artifactually from Glu-113 during the extraction procedure in 70% formic acid. In PubMed:15522881, the protein was found to have unblocked Glu at the N-terminus.Curated

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 4
      Human chromosome 4: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3