O95450 (ATS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 2
Short name=ADAM-TS 2
Short name=ADAM-TS2
Short name=ADAMTS-2
EC=3.4.24.14

Alternative name(s):
Procollagen I N-proteinase
Short name=PC I-NP
Procollagen I/II amino propeptide-processing enzyme
Procollagen N-endopeptidase
Short name=pNPI

Gene names

Name:	ADAMTS2
Synonyms:	PCINP, PCPNI

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	1211 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Cleaves the propeptides of type I and II collagen prior to fibril assembly. Does not act on type III collagen. May also play a role in development that is independent of its role in collagen biosynthesis.
Catalytic activity	Cleaves the N-propeptide of collagen chain alpha-1(I) at Pro-|-Gln and of alpha-1(II) and alpha-2(I) at Ala-|-Gln.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	May belong to a multimeric complex. Binds specifically to collagen type XIV By similarity.
Subcellular location	Secreted › extracellular space › extracellular matrix By similarity.
Tissue specificity	Expressed at high level in skin, bone, tendon and aorta and at low levels in thymus and brain.
Domain	The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.
Post-translational modification	The precursor is cleaved by a furin endopeptidase By similarity. Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Also can be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion By similarity.
Involvement in disease	Ehlers-Danlos syndrome 7C (EDS7C) [MIM:225410]: A connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. Marked by extremely fragile tissues, hyperextensible skin and easy bruising. Facial skin contains numerous folds, as in the cutis laxa syndrome. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1
Sequence similarities	Contains 1 disintegrin domain. Contains 1 peptidase M12B domain. Contains 1 PLAC domain. Contains 4 TSP type-1 domains.
Caution	Has sometimes been referred to as ADAMTS3.

Ontologies

Keywords
Biological process	Collagen degradation
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Ehlers-Danlos syndrome
Domain	Repeat Signal
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	collagen catabolic process Inferred from electronic annotation. Source: UniProtKB-KW collagen fibril organization Inferred from electronic annotation. Source: Compara extracellular matrix organization Traceable author statement. Source: Reactome lung development Inferred from electronic annotation. Source: Compara protein processing Inferred from electronic annotation. Source: Compara proteolysis Inferred from electronic annotation. Source: UniProtKB-KW skin development Inferred from electronic annotation. Source: Compara spermatogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular region Traceable author statement. Source: Reactome proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metalloendopeptidase activity Traceable author statement Ref.1. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform LpNPI (identifier: O95450-1)

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 SpNPI (identifier: O95450-2)

The sequence of this isoform differs from the canonical sequence as follows:
     544-566: HCFKGHCIWLTPDILKRDGSWGA → FRPGAVAHACYPSTLGGQGRWIA
     567-1211: Missing.

Note: Has no significant N-procollagen peptidase activity.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 29	29	Potential
	Propeptide	30 – 253	224	By similarity		PRO_0000029158
	Chain	254 – 1211	958	A disintegrin and metalloproteinase with thrombospondin motifs 2		PRO_0000029159
Regions
	Domain	266 – 470	205	Peptidase M12B
	Domain	480 – 560	81	Disintegrin
	Domain	561 – 616	56	TSP type-1 1
	Domain	854 – 912	59	TSP type-1 2
	Domain	914 – 971	58	TSP type-1 3
	Domain	975 – 1029	55	TSP type-1 4
	Domain	1059 – 1097	39	PLAC
	Region	723 – 851	129	Spacer
	Motif	691 – 693	3	Cell attachment site Potential
	Compositional bias	40 – 43	4	Poly-Ala
	Compositional bias	185 – 188	4	Poly-Glu
	Compositional bias	618 – 722	105	Cys-rich
Sites
	Active site	409	1	By similarity
	Metal binding	408	1	Zinc; catalytic By similarity
	Metal binding	412	1	Zinc; catalytic By similarity
	Metal binding	418	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	112	1	N-linked (GlcNAc...) Potential
	Glycosylation	251	1	N-linked (GlcNAc...) Potential
	Glycosylation	949	1	N-linked (GlcNAc...) Potential
	Glycosylation	993	1	N-linked (GlcNAc...) Potential
	Glycosylation	1031	1	N-linked (GlcNAc...) Potential
	Glycosylation	1098	1	N-linked (GlcNAc...) Potential
	Glycosylation	1145	1	N-linked (GlcNAc...) Potential
	Glycosylation	1150	1	N-linked (GlcNAc...) Potential
	Disulfide bond	386 ↔ 465		By similarity
	Disulfide bond	425 ↔ 451		By similarity
	Disulfide bond	573 ↔ 610		By similarity
	Disulfide bond	577 ↔ 615		By similarity
	Disulfide bond	588 ↔ 600		By similarity
	Disulfide bond	987 ↔ 1023		By similarity
	Disulfide bond	991 ↔ 1028		By similarity
	Disulfide bond	1002 ↔ 1012		By similarity
Natural variations
	Alternative sequence	544 – 566	23	HCFKG…GSWGA → FRPGAVAHACYPSTLGGQGR WIA in isoform SpNPI.		VSP_005497
	Alternative sequence	567 – 1211	645	Missing in isoform SpNPI.		VSP_005498
	Natural variant	74	1	V → M. Corresponds to variant rs2271211 [ dbSNP | Ensembl ].		VAR_047927
	Natural variant	241	1	R → H. Corresponds to variant rs11750821 [ dbSNP | Ensembl ].		VAR_047928
	Natural variant	245	1	V → I. Corresponds to variant rs398829 [ dbSNP | Ensembl ].		VAR_020058
	Natural variant	331	1	E → K. Corresponds to variant rs17667857 [ dbSNP | Ensembl ].		VAR_047929
	Natural variant	665	1	G → R. Corresponds to variant rs35372714 [ dbSNP | Ensembl ].		VAR_047930
	Natural variant	827	1	R → Q. Corresponds to variant rs35445112 [ dbSNP | Ensembl ].		VAR_047931
	Natural variant	1177	1	P → S. Corresponds to variant rs1054480 [ dbSNP | Ensembl ].		VAR_020059
Experimental info
	Sequence conflict	1001	1	L → P in CAA05880. Ref.1
	Sequence conflict	1089	1	C → S in CAA05880. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform LpNPI [UniParc]. Last modified December 16, 2008. Version 2. Checksum: 6C4F2C2D46A1F925	FASTA	1,211	134,755
	10 20 30 40 50 60 MDPPAGAARR LLCPALLLLL LLLPPPLLPP PPPPANARLA AAADPPGGPL GHGAERILAV 70 80 90 100 110 120 PVRTDAQGRL VSHVVSAATS RAGVRARRAA PVRTPSFPGG NEEEPGSHLF YNVTVFGRDL 130 140 150 160 170 180 HLRLRPNARL VAPGATMEWQ GEKGTTRVEP LLGSCLYVGD VAGLAEASSV ALSNCDGLAG 190 200 210 220 230 240 LIRMEEEEFF IEPLEKGLAA QEAEQGRVHV VYRRPPTSPP LGGPQALDTG ASLDSLDSLS 250 260 270 280 290 300 RALGVLEEHA NSSRRRARRH AADDDYNIEV LLGVDDSVVQ FHGKEHVQKY LLTLMNIVNE 310 320 330 340 350 360 IYHDESLGAH INVVLVRIIL LSYGKSMSLI EIGNPSQSLE NVCRWAYLQQ KPDTGHDEYH 370 380 390 400 410 420 DHAIFLTRQD FGPSGMQGYA PVTGMCHPVR SCTLNHEDGF SSAFVVAHET GHVLGMEHDG 430 440 450 460 470 480 QGNRCGDEVR LGSIMAPLVQ AAFHRFHWSR CSQQELSRYL HSYDCLLDDP FAHDWPALPQ 490 500 510 520 530 540 LPGLHYSMNE QCRFDFGLGY MMCTAFRTFD PCKQLWCSHP DNPYFCKTKK GPPLDGTMCA 550 560 570 580 590 600 PGKHCFKGHC IWLTPDILKR DGSWGAWSPF GSCSRTCGTG VKFRTRQCDN PHPANGGRTC 610 620 630 640 650 660 SGLAYDFQLC SRQDCPDSLA DFREEQCRQW DLYFEHGDAQ HHWLPHEHRD AKERCHLYCE 670 680 690 700 710 720 SRETGEVVSM KRMVHDGTRC SYKDAFSLCV RGDCRKVGCD GVIGSSKQED KCGVCGGDNS 730 740 750 760 770 780 HCKVVKGTFT RSPKKHGYIK MFEIPAGARH LLIQEVDATS HHLAVKNLET GKFILNEEND 790 800 810 820 830 840 VDASSKTFIA MGVEWEYRDE DGRETLQTMG PLHGTITVLV IPVGDTRVSL TYKYMIHEDS 850 860 870 880 890 900 LNVDDNNVLE EDSVVYEWAL KKWSPCSKPC GGGSQFTKYG CRRRLDHKMV HRGFCAALSK 910 920 930 940 950 960 PKAIRRACNP QECSQPVWVT GEWEPCSQTC GRTGMQVRSV RCIQPLHDNT TRSVHAKHCN 970 980 990 1000 1010 1020 DARPESRRAC SRELCPGRWR AGPWSQCSVT CGNGTQERPV LCRTADDSFG ICQEERPETA 1030 1040 1050 1060 1070 1080 RTCRLGPCPR NISDPSKKSY VVQWLSRPDP DSPIRKISSK GHCQGDKSIF CRMEVLSRYC 1090 1100 1110 1120 1130 1140 SIPGYNKLCC KSCNLYNNLT NVEGRIEPPP GKHNDIDVFM PTLPVPTVAM EVRPSPSTPL 1150 1160 1170 1180 1190 1200 EVPLNASSTN ATEDHPETNA VDEPYKIHGL EDEVQPPNLI PRRPSPYEKT RNQRIQELID 1210 EMRKKEMLGK F
	Isoform SpNPI [UniParc]. Checksum: 4D0D641B94307BA2	FASTA	566	61,756
	10 20 30 40 50 60 MDPPAGAARR LLCPALLLLL LLLPPPLLPP PPPPANARLA AAADPPGGPL GHGAERILAV 70 80 90 100 110 120 PVRTDAQGRL VSHVVSAATS RAGVRARRAA PVRTPSFPGG NEEEPGSHLF YNVTVFGRDL 130 140 150 160 170 180 HLRLRPNARL VAPGATMEWQ GEKGTTRVEP LLGSCLYVGD VAGLAEASSV ALSNCDGLAG 190 200 210 220 230 240 LIRMEEEEFF IEPLEKGLAA QEAEQGRVHV VYRRPPTSPP LGGPQALDTG ASLDSLDSLS 250 260 270 280 290 300 RALGVLEEHA NSSRRRARRH AADDDYNIEV LLGVDDSVVQ FHGKEHVQKY LLTLMNIVNE 310 320 330 340 350 360 IYHDESLGAH INVVLVRIIL LSYGKSMSLI EIGNPSQSLE NVCRWAYLQQ KPDTGHDEYH 370 380 390 400 410 420 DHAIFLTRQD FGPSGMQGYA PVTGMCHPVR SCTLNHEDGF SSAFVVAHET GHVLGMEHDG 430 440 450 460 470 480 QGNRCGDEVR LGSIMAPLVQ AAFHRFHWSR CSQQELSRYL HSYDCLLDDP FAHDWPALPQ 490 500 510 520 530 540 LPGLHYSMNE QCRFDFGLGY MMCTAFRTFD PCKQLWCSHP DNPYFCKTKK GPPLDGTMCA 550 560 PGKFRPGAVA HACYPSTLGG QGRWIA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene." Colige A., Sieron A.L., Li S.-W., Schwarze U., Petty E., Wertelecki W., Wilcox W., Krakow D., Cohn D.H., Reardon W., Byers P.H., Lapiere C.M., Prockop D.J., Nusgens B.V. Am. J. Hum. Genet. 65:308-317(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LPNPI AND SPNPI), INVOLVEMENT IN EDS7C. Tissue: Skin.
[2]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ003125 mRNA. Translation: CAA05880.1. AC008544 Genomic DNA. No translation available. AC010216 Genomic DNA. No translation available. AC109479 Genomic DNA. No translation available.
IPI	IPI00012366. IPI00030757.
RefSeq	NP_055059.2. NM_014244.4. NP_067610.1. NM_021599.2.
UniGene	Hs.23871.
3D structure databases
ProteinModelPortal	O95450.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95450. 1 interaction.
STRING	9606.ENSP00000251582.
Protein family/group databases
MEROPS	M12.301.
PTM databases
PhosphoSite	O95450.
Proteomic databases
PaxDb	O95450.
PRIDE	O95450.
Protocols and materials databases
DNASU	9509.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000251582; ENSP00000251582; ENSG00000087116. ENST00000274609; ENSP00000274609; ENSG00000087116.
GeneID	9509.
KEGG	hsa:9509.
UCSC	uc003mjw.3. human. uc011dgm.2. human.
Organism-specific databases
CTD	9509.
GeneCards	GC05M178537.
HGNC	HGNC:218. ADAMTS2.
HPA	HPA028444.
MIM	225410. phenotype. 604539. gene.
neXtProt	NX_O95450.
Orphanet	1901. Ehlers-Danlos syndrome, dermatosparaxis type.
PharmGKB	PA24546.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG307411.
HOGENOM	HOG000034222.
HOVERGEN	HBG004314.
InParanoid	O95450.
KO	K08618.
OMA	GGGSQFT.
OrthoDB	EOG4VDPXQ.
PhylomeDB	O95450.
Enzyme and pathway databases
Reactome	REACT_118779. Extracellular matrix organization.
Gene expression databases
Bgee	O95450.
CleanEx	HS_ADAMTS2.
Genevestigator	O95450.
GermOnline	ENSG00000087116. Homo sapiens.
Family and domain databases
Gene3D	3.40.390.10. 1 hit.
InterPro	IPR010294. ADAM_spacer1. IPR024079. MetalloPept_cat_dom. IPR013275. Pept_M12B_ADAM-TS2. IPR001590. Peptidase_M12B. IPR013273. Peptidase_M12B_ADAM-TS. IPR002870. Peptidase_M12B_N. IPR010909. PLAC. IPR000884. Thrombospondin_1_rpt. [Graphical view]
Pfam	PF05986. ADAM_spacer1. 1 hit. PF01562. Pep_M12B_propep. 1 hit. PF01421. Reprolysin. 1 hit. PF00090. TSP_1. 4 hits. [Graphical view]
PRINTS	PR01859. ADAMTS2. PR01857. ADAMTSFAMILY.
SMART	SM00209. TSP1. 4 hits. [Graphical view]
SUPFAM	SSF82895. TSP1. 4 hits.
PROSITE	PS50215. ADAM_MEPRO. 1 hit. PS00427. DISINTEGRIN_1. False negative. PS50214. DISINTEGRIN_2. False negative. PS50900. PLAC. 1 hit. PS50092. TSP1. 4 hits. PS00142. ZINC_PROTEASE. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ADAMTS2. human.
GenomeRNAi	9509.
NextBio	35632.
SOURCE	Search...

Entry information

Entry name

ATS2_HUMAN

Accession

Primary (citable) accession number: O95450

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	December 16, 2008
Last modified:	May 1, 2013
This is version 141 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.