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Protein

Collagen alpha-1(XXV) chain

Gene

COL25A1

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

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
Complete GO annotation...

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 Componenti: 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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3333CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei34 – 5421Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini55 – 654600ExtracellularSequence AnalysisAdd
BLAST

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
Complete GO annotation...

Keywords - Cellular componenti

Amyloid, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi109 – 1091R → A: Not secreted. 1 Publication
Mutagenesisi112 – 1121R → A: Not secreted. 1 Publication
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.
ExpressionAtlasiQ9BXS0. baseline and differential.
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...

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.
GeneTreeiENSGT00780000121854.
HOGENOMiHOG000085653.
HOVERGENiHBG101380.
InParanoidiQ9BXS0.
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. AlignAdd to basket

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

        10         20         30         40         50
MLLKKHAGKG GGREPRSEDP TPAEQHCART MPPCAVLAAL LSVVAVVSCL
60 70 80 90 100
YLGVKTNDLQ ARIAALESAK GAPSIHLLPD TLDHLKTMVQ EKVERLLAQK
110 120 130 140 150
SYEHMAKIRI AREAPSECNC PAGPPGKRGK RGRRGESGPP GQPGPQGPPG
160 170 180 190 200
PKGDKGEQGD QGPRMVFPKI NHGFLSADQQ LIKRRLIKGD QGQAGPPGPP
210 220 230 240 250
GPPGPRGPPG DTGKDGPRGM PGVPGEPGKP GEQGLMGPLG PPGQKGSIGA
260 270 280 290 300
PGIPGMNGQK GEPGLPGAVG QNGIPGPKGE PGEQGEKGDA GENGPKGDTG
310 320 330 340 350
EKGDPGSSAA GIKGEPGESG RPGQKGEPGL PGLPGLPGIK GEPGFIGPQG
360 370 380 390 400
EPGLPGLPGT KGERGEAGPP GRGERGEPGA PGPKGKQGES GTRGPKGSKG
410 420 430 440 450
DRGEKGDSGA QGPRGPPGQK GDQGATEIID YNGNLHEALQ RITTLTVTGP
460 470 480 490 500
PGPPGPQGLQ GPKGEQGSPG IPGMDGEQGL KGSKGDMGDP GMTGEKGGIG
510 520 530 540 550
LPGLPGANGM KGEKGDSGMP GPQGPSIIGP PGPPGPHGPP GPMGPHGLPG
560 570 580 590 600
PKGTDGPMGP HGPAGPKGER GEKGAMGEPG PRGPYGLPGK DGEPGLDGFP
610 620 630 640 650
GPRGEKGDLG EKGEKGFRGV KGEKGEPGQP GLDGLDAPCQ LGPDGLPMPG

CWQK
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi124143. 2 interactions.
STRINGi9606.ENSP00000329626.

PTM databases

PhosphoSiteiQ9BXS0.

Polymorphism databases

DMDMi296434459.

Proteomic databases

MaxQBiQ9BXS0.
PaxDbiQ9BXS0.
PRIDEiQ9BXS0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi84570.
GeneCardsiGC04M109731.
H-InvDBHIX0004434.
HGNCiHGNC:18603. COL25A1.
HPAiHPA029107.
MIMi610004. gene.
neXtProtiNX_Q9BXS0.
PharmGKBiPA134912284.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG12793.
GeneTreeiENSGT00780000121854.
HOGENOMiHOG000085653.
HOVERGENiHBG101380.
InParanoidiQ9BXS0.
OrthoDBiEOG7D59P1.
PhylomeDBiQ9BXS0.
TreeFamiTF338175.

Enzyme and pathway databases

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

Miscellaneous databases

GeneWikiiCollagen,_type_XXV,_alpha_1.
GenomeRNAii84570.
NextBioi74464.
PROiQ9BXS0.
SOURCEiSearch...

Gene expression databases

BgeeiQ9BXS0.
CleanExiHS_COL25A1.
ExpressionAtlasiQ9BXS0. baseline and differential.
GenevestigatoriQ9BXS0.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  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(2001) [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(2002) [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(2004) [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(2004) [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(2003) [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(2004) [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(2004) [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(2004) [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(2004)

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: February 4, 2015
This is version 102 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

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 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.