Q9BXS0 (COPA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

1. Collagen-like Alzheimer amyloid plaque component
   Short name=CLAC

Gene names

Name:

COL25A1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	654 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Amyloid Membrane
Coding sequence diversity	Alternative splicing
Domain	Collagen Repeat Signal-anchor Transmembrane Transmembrane helix
Ligand	Heparin-binding
PTM	Glycoprotein Hydroxylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	extracellular matrix organization Traceable author statement. Source: Reactome
Cellular_component	collagen Inferred from electronic annotation. Source: UniProtKB-KW endoplasmic reticulum lumen Traceable author statement. Source: Reactome extracellular space Inferred from direct assay Ref.1. Source: UniProtKB integral to plasma membrane Inferred from direct assay Ref.1. Source: MGI
Molecular_function	beta-amyloid binding Inferred from direct assay Ref.1Ref.5Ref.4Ref.8. Source: UniProtKB heparin binding Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 654	654	Collagen alpha-1(XXV) chain		PRO_0000259611
	Chain	113 – 654	542	Collagen-like Alzheimer amyloid plaque component Ref.1 Ref.4		PRO_0000259612
Regions
	Topological domain	1 – 33	33	Cytoplasmic Potential
	Transmembrane	34 – 54	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	55 – 654	600	Extracellular Potential
	Domain	121 – 164	44	Collagen-like 1
	Domain	192 – 247	56	Collagen-like 2
	Domain	249 – 308	60	Collagen-like 3
	Domain	311 – 370	60	Collagen-like 4
	Domain	372 – 425	54	Collagen-like 5
	Domain	447 – 505	59	Collagen-like 6
	Domain	571 – 630	60	Collagen-like 7
	Region	181 – 188	8	Interaction with beta amyloid peptide Ref.4
Sites
	Site	112 – 113	2	Cleavage; by furin Ref.1
Natural variations
	Alternative sequence	141 – 146	6	Missing in isoform 3. Ref.2		VSP_052197
	Alternative sequence	326 – 340	15	Missing in isoform 3. Ref.2		VSP_052198
	Alternative sequence	589 – 640	52	Missing in isoform 3. Ref.2		VSP_052199
	Alternative sequence	616 – 654	39	GFRGV…GCWQK → VTSPSQHVPCLILLLLSALL FSLCDSI in isoform 2. Ref.1		VSP_052200
Experimental info
	Mutagenesis	109	1	R → A: Not secreted. Ref.1
	Mutagenesis	112	1	R → A: Not secreted. Ref.1
	Mutagenesis	181 – 188	8	LIKRRLIK → VIKRRTFQ: Reduces binding to beta amyloid peptide. Ref.4
	Mutagenesis	181 – 188	8	Missing: Abolishes binding to beta amyloid peptide. Ref.4
	Sequence conflict	28	1	A → S in AAK35008. Ref.1
	Sequence conflict	28	1	A → S in AAK35009. Ref.2
	Sequence conflict	427	1	E → K in AAK35008. Ref.1
	Sequence conflict	427	1	E → K in AAK35009. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: D6DFB4FB157C05A2	FASTA	654	64,771
	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
	Isoform 2 [UniParc]. Checksum: 14B1AC4C9E55506F	FASTA	642	63,661
	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 GPRGEKGDLG EKGEKVTSPS QHVPCLILLL LSALLFSLCD SI
	Isoform 3 [UniParc]. Checksum: D4F26C1293B70F3B	FASTA	581	57,619
	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 GPPGPKGDKG EQGDQGPRMV FPKINHGFLS ADQQLIKRRL 190 200 210 220 230 240 IKGDQGQAGP PGPPGPPGPR GPPGDTGKDG PRGMPGVPGE PGKPGEQGLM GPLGPPGQKG 250 260 270 280 290 300 SIGAPGIPGM NGQKGEPGLP GAVGQNGIPG PKGEPGEQGE KGDAGENGPK GDTGEKGDPG 310 320 330 340 350 360 SSAAGIKGEP GESGRPGQKG EPGFIGPQGE PGLPGLPGTK GERGEAGPPG RGERGEPGAP 370 380 390 400 410 420 GPKGKQGESG TRGPKGSKGD RGEKGDSGAQ GPRGPPGQKG DQGATEIIDY NGNLHEALQR 430 440 450 460 470 480 ITTLTVTGPP GPPGPQGLQG PKGEQGSPGI PGMDGEQGLK GSKGDMGDPG MTGEKGGIGL 490 500 510 520 530 540 PGLPGANGMK GEKGDSGMPG PQGPSIIGPP GPPGPHGPPG PMGPHGLPGP KGTDGPMGPH 550 560 570 580 GPAGPKGERG EKGAMGEPGP RGPYGLPLGP DGLPMPGCWQ K

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00186946. IPI00942774. IPI00953070.
RefSeq	NP_115907.2. NM_032518.2. NP_942014.1. NM_198721.2.
UniGene	Hs.658842.
3D structure databases
ProteinModelPortal	Q9BXS0.
SMR	Q9BXS0. Positions 560-596.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000329626.
PTM databases
PhosphoSite	Q9BXS0.
Polymorphism databases
DMDM	296434459.
Proteomic databases
PaxDb	Q9BXS0.
PRIDE	Q9BXS0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000399126; ENSP00000382077; ENSG00000188517. ENST00000399132; ENSP00000382083; ENSG00000188517.
GeneID	84570.
KEGG	hsa:84570.
UCSC	uc003hze.1. human. uc003hzg.3. human.
Organism-specific databases
CTD	84570.
GeneCards	GC04M109731.
H-InvDB	HIX0004434.
HGNC	HGNC:18603. COL25A1.
HPA	HPA029107.
MIM	610004. gene.
neXtProt	NX_Q9BXS0.
PharmGKB	PA134912284.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG12793.
HOGENOM	HOG000085653.
HOVERGEN	HBG101380.
OrthoDB	EOG4K3KWH.
Enzyme and pathway databases
Reactome	REACT_118779. Extracellular matrix organization.
Gene expression databases
ArrayExpress	Q9BXS0.
Bgee	Q9BXS0.
CleanEx	HS_COL25A1.
Genevestigator	Q9BXS0.
Family and domain databases
InterPro	IPR008160. Collagen. [Graphical view]
Pfam	PF01391. Collagen. 7 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	84570.
NextBio	74464.
SOURCE	Search...

Entry information

Entry name

COPA1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.