Tumor Endothelial Marker Report: TEM25 (BMP1)

TEM domain structure

	TEM domain structure

TEM Sequence Analysis

name from to source/E description

SignalP 1 23

PROPEP 2 120 SEG45 LCR(LAD-RS). This propeptide sequence is cleaved to give the active protease.

Astacin 128 321 Pfam, E = 3.5e-115 The zinc_protease family M12A domain is the catalytic domain, with zinc binding motif.

CUB 322 431 Pfam, E = 7.9e-58 The CUB domain of TEM25 contains four conserved cysteines that are proposed to form two disulfide bridges (C1-C2, C3-C4).

CUB 435 544 Pfam, E = 9.6e-65 The CUB domain of TEM25 contains four conserved cysteines that are proposed to form two disulfide bridges (C1-C2, C3-C4).

EGF
EGFCa 551 587 Pfam, E = 1.7e-06

CUB 591 700 Pfam, E = 2.1e-59 The CUB domain of TEM25 contains four conserved cysteines that are proposed to form two disulfide bridges (C1-C2, C3-C4).

EGF
EGFCa 707 742 Pfam,E = 0.00011

CUB 747 856 Pfam, E = 2.7e-58 The CUB domain of TEM25 contains four conserved cysteines that are proposed to form two disulfide bridges (C1-C2, C3-C4).

CUB 860 973 Pfam,E = 1.7e-48 The CUB domain of TEM25 contains four conserved cysteines that are proposed to form two disulfide bridges (C1-C2, C3-C4).

986

	TEM Sequence Analysis

name	from	to	source/E	description
SignalP	1	23
PROPEP	2	120	SEG45	LCR(LAD-RS). This propeptide sequence is cleaved to give the active protease.
Astacin	128	321	Pfam, E = 3.5e-115	The zinc_protease family M12A domain is the catalytic domain, with zinc binding motif.
CUB	322	431	Pfam, E = 7.9e-58	The CUB domain of TEM25 contains four conserved cysteines that are proposed to form two disulfide bridges (C1-C2, C3-C4).
CUB	435	544	Pfam, E = 9.6e-65	The CUB domain of TEM25 contains four conserved cysteines that are proposed to form two disulfide bridges (C1-C2, C3-C4).
EGF EGFCa	551	587	Pfam, E = 1.7e-06
CUB	591	700	Pfam, E = 2.1e-59	The CUB domain of TEM25 contains four conserved cysteines that are proposed to form two disulfide bridges (C1-C2, C3-C4).
EGF EGFCa	707	742	Pfam,E = 0.00011
CUB	747	856	Pfam, E = 2.7e-58	The CUB domain of TEM25 contains four conserved cysteines that are proposed to form two disulfide bridges (C1-C2, C3-C4).
CUB	860	973	Pfam,E = 1.7e-48	The CUB domain of TEM25 contains four conserved cysteines that are proposed to form two disulfide bridges (C1-C2, C3-C4).
986

Remarks

	Remarks

CLASSIFICATION: Superfamily metzincins.
DOMAIN ARCHITECTURE: BMP consists of an N-terminal domain with sequence similarity to the astacin family of metalloproteases and a C-terminal region composed of two EGF-like repeats and five copies of the CUB repeat.
GENE STRUCTURE: BMP-1 and the larger protein mammalian Tolloid (mTLD) are products of a single mammalian gene that is alternatively spliced to give this geneproducts. The domain structure of mTLD is identical to the Drosophila Tld, while BMP-1 misses C-terminal EGF and CUB domains. Homozygous mutants for the corresponding gene, Tll, are embryonic lethal, with death at mid-gestation from cardiac failure and a unique constellation of developmental defects that are apparently confined solely to the heart. Constant features are incomplete formation of the muscular interventricular septum and an abnormal and novel positioning of the heart and aorta (Clark,1999).
TARGETS:
- BMP1 processes type I-III procollagens. Without cleavage of the C-propeptides, the procollagens are not incorporated into fibrils.
- BMP1 processes laminin 5gamma2 chains. This suggests that BMP-1 activity facilitates basement membrane assembly.
- Probiglycan (Scott, 2000).
FUNCTION: Fibrillar collagen types I-III are synthesized as procollagens, precursors containing N- and C-terminal propeptides that are cleaved extracellularly to yield mature triple helical monomers capable of associating into fibrils. BMP-1 is involved in the processing of several procollagens to collagens (Prockop, 1998).
REGULATION: TGF-beta 1 was shown to elevates levels of BMP-1 and mTldn in fibrogenic cells and keratinocytes.

Sequence Information

TEM TEM25

Reliability of Gen2Tag mapping

Cid->tag (Hs.1274) frequency:
tem39: CATG-TCCCCCAGGA=44/55 (ESTs)

Analysis
BlastP against nr

Output Created by a Suite of Single Sequence Analysis Techniques

Protein Description

SEQ.SOURCE: gi|5453579|ref|NP_006120.1| bone morphogenetic protein 1, isoform 4, precursor; PCP

Protein Sequence

MPGVARLPLLLGLLLLPRPGRPLDLADYTYDLAEEDDSEPLNYKDPCKAAAFLGDIALDEEDLRAFQVQQ AVDLRRHTARKSSIKAAVPGNTSTPSCQSTNGQPQRGACGRWRGRSRSRRAATSRPERVWPDGVIPFVIG GNFTGSQRAVFRQAMRHWEKHTCVTFLERTDEDSYIVFTYRPCGCCSYVGRRGGGPQAISIGKNCDKFGI VVHELGHVVGFWHEHTRPDRDRHVSIVRENIQPGQEYNFLKMEPQEVESLGETYDFDSIMHYARNTFSRG IFLDTIVPKYEVNGVKPPIGQRTRLSKGDIAQARKLYKCPACGETLQDSTGNFSSPEYPNGYSAHMHCVW RISVTPGEKIILNFTSLDLYRSRLCWYDYVEVRDGFWRKAPLRGRFCGSKLPEPIVSTDSRLWVEFRSSS NWVGKGFFAVYEAICGGDVKKDYGHIQSPNYPDDYRPSKVCIWRIQVSEGFHVGLTFQSFEIERHDSCAY DYLEVRDGHSESSTLIGRYCGYEKPDDIKSTSSRLWLKFVSDGSINKAGFAVNFFKEVDECSRPNRGGCE QRCLNTLGSYKCSCDPGYELAPDKRRCEAACGGFLTKLNGSITSPGWPKEYPPNKNCIWQLVAPTQYRIS LQFDFFETEGNDVCKYDFVEVRSGLTADSKLHGKFCGSEKPEVITSQYNNMRVEFKSDNTVSKKGFKAHF FSDKDECSKDNGGCQQDCVNTFGSYECQCRSGFVLHDNKHDCKEAGCDHKVTSTSGTITSPNWPDKYPSK KECTWAISSTPGHRVKLTFMEMDIESQPECAYDHLEVFDGRDAKAPVLGRFCGSKKPEPVLATGSRMFLR FYSDNSVQRKGFQASHATECGGQVRADVKTKDLYSHAQFGDNNYPGGVDCEWVIVAEEGYGVELVFQTFE VEEETDCGYDYMELFDGYDSTAPRLGRYCGSGPPEEVYSAGDSVLVKFHSDDTITKKGFHLRYTSTKFQD TLHSRK

SAGE-Tag CATG-TCCCCCAGGAG

EST/cluster Description

UNIGEN CLUSTER: UniGene Cluster Hs.1274 BMP1

SEQ.SOURCE: gi|1245356|gb|U50330.1|U50330 Human procollagen C-proteinase (pCP-2) mRNA
gi|5902809|ref|NM_006129.2| Homo sapiens bone morphogenetic protein 1 (BMP1)
transcript variant BMP1-3, mRNA

ANALYSIS: Blastn against Estdb shows that the CATG following the Tag is a sequencing error
(Position 3495 of the query)

MARKINGS: TEM25 Tag in red
CATG following the Tag in bold
first Poly-A-signal following the Tag in bold

EST/cluster Sequence

ATGCCCGGCGTGGCCCGCCTGCCGCTGCTGCTCGGGCTGCTGCTGCTCCCGCGTCCCGGCCGGCCGCTGG ACTTGGCCGACTACACCTATGACCTGGCGGAGGAGGACGACTCGGAGCCCCTCAACTACAAAGACCCCTG CAAGGCGGCTGCCTTTCTTGGGGACATTGCCCTGGACGAAGAGGACCTGAGGGCCTTCCAGGTACAGCAG GCTGTGGATCTCAGACGGCACACAGCTCGTAAGTCCTCCATCAAAGCTGCAGTTCCAGGAAACACTTCTA CCCCCAGCTGCCAGAGCACCAACGGGCAGCCTCAGAGGGGAGCCTGTGGGAGATGGAGAGGTAGATCCCG TAGCCGGCGGGCGGCGACGTCCCGACCAGAGCGTGTGTGGCCCGATGGGGTCATCCCCTTTGTCATTGGG GGAAACTTCACTGGTAGCCAGAGGGCAGTCTTCCGGCAGGCCATGAGGCACTGGGAGAAGCACACCTGTG TCACCTTCCTGGAGCGCACTGACGAGGACAGCTATATTGTGTTCACCTATCGACCTTGCGGGTGCTGCTC CTACGTGGGTCGCCGCGGCGGGGGCCCCCAGGCCATCTCCATCGGCAAGAACTGTGACAAGTTCGGCATT GTGGTCCACGAGCTGGGCCACGTCGTCGGCTTCTGGCACGAACACACTCGGCCAGACCGGGACCGCCACG TTTCCATCGTTCGTGAGAACATCCAGCCAGGGCAGGAGTATAACTTCCTGAAGATGGAGCCTCAGGAGGT GGAGTCCCTGGGGGAGACCTATGACTTCGACAGCATCATGCATTACGCTCGGAACACATTCTCCAGGGGC ATCTTCCTGGATACCATTGTCCCCAAGTATGAGGTGAACGGGGTGAAACCTCCCATTGGCCAAAGGACAC GGCTCAGCAAGGGGGACATTGCCCAAGCCCGCAAGCTTTACAAGTGCCCAGCCTGTGGAGAGACCCTGCA AGACAGCACAGGCAACTTCTCCTCCCCTGAATACCCCAATGGCTACTCTGCTCACATGCACTGCGTGTGG CGCATCTCTGTCACACCCGGGGAGAAGATCATCCTGAACTTCACGTCCCTGGACCTGTACCGCAGCCGCC TGTGCTGGTACGACTATGTGGAGGTCCGAGATGGCTTCTGGAGGAAGGCGCCCCTCCGAGGCCGCTTCTG CGGGTCCAAACTCCCTGAGCCTATCGTCTCCACTGACAGCCGCCTCTGGGTTGAATTCCGCAGCAGCAGC AATTGGGTTGGAAAGGGCTTCTTTGCAGTCTACGAAGCCATCTGCGGGGGTGATGTGAAAAAGGACTATG GCCACATTCAATCGCCCAACTACCCAGACGATTACCGGCCCAGCAAAGTCTGCATCTGGCGGATCCAGGT GTCTGAGGGCTTCCACGTGGGCCTCACATTCCAGTCCTTTGAGATTGAGCGCCACGACAGCTGTGCCTAC GACTATCTGGAGGTGCGCGACGGGCACAGTGAGAGCAGCACCCTCATCGGGCGCTACTGTGGCTATGAGA AGCCTGATGACATCAAGAGCACGTCCAGCCGCCTCTGGCTCAAGTTCGTCTCTGACGGGTCCATTAACAA AGCGGGCTTTGCCGTCAACTTTTTCAAAGAGGTGGACGAGTGCTCTCGGCCCAACCGCGGGGGCTGTGAG CAGCGGTGCCTCAACACCCTGGGCAGCTACAAGTGCAGCTGTGACCCCGGGTACGAGCTGGCCCCAGACA AGCGCCGCTGTGAGGCTGCTTGTGGCGGATTCCTCACCAAGCTCAACGGCTCCATCACCAGCCCGGGCTG GCCCAAGGAGTACCCCCCCAACAAGAACTGCATCTGGCAGCTGGTGGCCCCCACCCAGTACCGCATCTCC CTGCAGTTTGACTTCTTTGAGACAGAGGGCAATGATGTGTGCAAGTACGACTTCGTGGAGGTGCGCAGTG GACTCACAGCTGACTCCAAGCTGCATGGCAAGTTCTGTGGTTCTGAGAAGCCCGAGGTCATCACCTCCCA GTACAACAACATGCGCGTGGAGTTCAAGTCCGACAACACCGTGTCCAAAAAGGGCTTCAAGGCCCACTTC TTCTCAGACAAGGACGAGTGCTCCAAGGATAACGGCGGCTGCCAGCAGGACTGCGTCAACACGTTCGGCA GTTATGAGTGCCAATGCCGCAGTGGCTTCGTCCTCCATGACAACAAGCACGACTGCAAAGAAGCCGGCTG TGACCACAAGGTGACATCCACCAGTGGTACCATCACCAGCCCCAACTGGCCTGACAAGTATCCCAGCAAG AAGGAGTGCACGTGGGCCATCTCCAGCACCCCCGGGCACCGGGTCAAGCTGACCTTCATGGAGATGGACA TCGAGTCCCAGCCTGAGTGTGCCTACGACCACCTAGAGGTGTTCGACGGGCGAGACGCCAAGGCCCCCGT CCTCGGCCGCTTCTGTGGGAGCAAGAAGCCCGAGCCCGTCCTGGCCACAGGCAGCCGCATGTTCCTGCGC TTCTACTCAGATAACTCGGTCCAGCGAAAGGGCTTCCAGGCCTCCCACGCCACAGAGTGCGGGGGCCAGG TACGGGCAGACGTGAAGACCAAGGACCTTTACTCCCACGCCCAGTTTGGCGACAACAACTACCCTGGGGG TGTGGACTGTGAGTGGGTCATTGTGGCCGAGGAAGGCTACGGCGTGGAGCTCGTGTTCCAGACCTTTGAG GTGGAGGAGGAGACCGACTGCGGCTATGACTACATGGAGCTCTTCGACGGCTACGACAGCACAGCCCCCA GGCTGGGGCGCTACTGTGGCTCAGGGCCTCCTGAGGAGGTGTACTCGGCGGGAGATTCTGTCCTGGTGAA GTTCCACTCGGATGACACCATCACCAAAAAAGGTTTCCACCTGCGATACACCAGCACCAAGTTCCAGGAC ACACTCCACAGCAGGAAGTGACCACTGCCTGAGCAGGGGCGGGGACTGGAGCCTGCTGCCCTTGGTCGCC TAGACTGGATAGTGGGGGTGGGCGGAACGCAACGCACCATCCCTCTCCCCCAGGCCCCAGGACCTGCAGG GCCAATGGCCTGGTGAGACTGTCCATAGGAGGTGGGGGAACTGGACTCCGGCATAAGCCACTTCCCCACA AACCCCCACCAGCAAGGGGCTGGGGCCAGGGAGCAGAGCTTCCACAAGACATTTCGAAGTCATCATTCCT CTCTTAGGGGGCCCTGCCTGGTGGCAAGAGGGAATGTCAGCAGGACCCCATCGCCATCCCTGTGTCTCTA CACGCTGTATTGTGTATCACCGGGGGCATTATTTTCATTGTAATGTTCATTTCCCACCCCTGCTCCAGCC TCGATTTGGTTTTATTTTGAGCCCCCATTCCACCACAGTTTCCTGGGGCACAAGTGTCTGTGCATGTCCC CCAGGAGCCACCGTGGGGAGCCGATGGGGAGGGGATGGAGAAACAAGACAGGGCTTCTCTCAGCCCATGG CCGGTCAGCCACACCAGGGCACCGCAGCCAATAAACCGAAAGTGTT

Genomic Sequence Description

Genomic Sequence

	Sequence Information

Literature

	Literature

PubMed: 10806203 Bone morphogenetic protein 1 is an extracellular processing enzyme of the laminin 5 gamma 2 chain.
Amano S, Scott IC, Takahara K, Koch M, Champliaud MF, Gerecke DR, Keene DR, Hudson DL, Nishiyama T, Lee S, Greenspan DS, Burgeson RE
J Biol Chem 2000 Jul 28;275(30):22728-35

PubMed: 9524360 Procollagen N-proteinase and procollagen C-proteinase. Two unusual metalloproteinases that are essential for procollagen processing probably have important roles in development and cell signaling.
Prockop DJ, Sieron AL, Li SW.
Matrix Biol 1998 Feb;16(7):399-408

PubMed: 9247707 Hatakeyama S, Gao YH, Ohara-Nemoto Y, Kataoka H, Satoh M.
Expression of bone morphogenetic proteins of human neoplastic epithelial cells.
Biochem Mol Biol Int. 1997 Jul;42(3):497-505.

PubMed: 7670368 The astacin family of metalloendopeptidases.
Bond JS, Beynon R
J. Protein Sci. 1995 Jul;4(7):1247-61.

PubMed: 7798260 Bone morphogenetic protein-1 and a mammalian tolloid homologue (mTld) are encoded by alternatively spliced transcripts which are differentially expressed in some tissues
K Takahara, GE Lyons, and DS Greenspan
J. Biol. Chem. 1994 269: 32572-32578.

PubMed: 8510165 The CUB domain. A widespread module in developmentally regulated proteins.
Bork P, Beckmann G.
J Mol Biol. 1993 May 20;231(2):539-45.

FAQ

PubMed: 10806203	Bone morphogenetic protein 1 is an extracellular processing enzyme of the laminin 5 gamma 2 chain. Amano S, Scott IC, Takahara K, Koch M, Champliaud MF, Gerecke DR, Keene DR, Hudson DL, Nishiyama T, Lee S, Greenspan DS, Burgeson RE J Biol Chem 2000 Jul 28;275(30):22728-35
PubMed: 9524360	Procollagen N-proteinase and procollagen C-proteinase. Two unusual metalloproteinases that are essential for procollagen processing probably have important roles in development and cell signaling. Prockop DJ, Sieron AL, Li SW. Matrix Biol 1998 Feb;16(7):399-408
PubMed: 9247707	Hatakeyama S, Gao YH, Ohara-Nemoto Y, Kataoka H, Satoh M. Expression of bone morphogenetic proteins of human neoplastic epithelial cells. Biochem Mol Biol Int. 1997 Jul;42(3):497-505.
PubMed: 7670368	The astacin family of metalloendopeptidases. Bond JS, Beynon R J. Protein Sci. 1995 Jul;4(7):1247-61.
PubMed: 7798260	Bone morphogenetic protein-1 and a mammalian tolloid homologue (mTld) are encoded by alternatively spliced transcripts which are differentially expressed in some tissues K Takahara, GE Lyons, and DS Greenspan J. Biol. Chem. 1994 269: 32572-32578.
PubMed: 8510165	The CUB domain. A widespread module in developmentally regulated proteins. Bork P, Beckmann G. J Mol Biol. 1993 May 20;231(2):539-45.