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List of -TEMs -PEMs -NEMs

TEMs TEM1 TEM2 TEM3 TEM4 TEM5 TEM6 TEM7 TEM8 TEM9 TEM10 TEM11 TEM12 TEM13 TEM14 TEM15 TEM16 TEM17 TEM18 TEM19 TEM20 TEM21_1 TEM21_2 TEM22 TEM23 TEM24 TEM25 TEM26 TEM27 TEM28 TEM29 TEM30 TEM31_1 TEM31_2 TEM32 TEM33 TEM34 TEM35 TEM36 TEM37 TEM38 TEM39 TEM40 TEM41 TEM42 TEM43 TEM44 TEM45 TEM46

Summary -Overview of TEMs -extracellular TEMs -intrac. & membrane TEMs -TEM tissue distribution

Supplementary -SAGE -Seq.analysis Methods

FAQ

Tumor Endothelial Marker Report: TEM1 (Endosialin)

	TEM domain structure

	TEM Sequence Analysis

name	from	to	source/E	description
SignalP	1	18	SignalP
C-type Lectin	25	167	Y. Wolfs SCOP PSSM, E=6e-18 Pfam:E = 7.8e-11	The C-lectin domain in TEM1 contains a WIGL motif, which is found in internalized transmembrane proteins.
potential Sushi	176	230	PFAM, E = 0.72	This Sushi domain (SCR repeat) hit is weak, with crucial cystein residues being conserved. SCR repeats are found as selectin complement-binding repeats. Due to the lack of essential basic residues in the potential sushi domain of TEM1 a heparin-binding function for this domain is not supported.
EGF	235	271	Pfam, E = 4.6e-06	The EGF domain of TEM1 includes six cysteine residues which have been shown (in EGF) to be involved in disulfide bonds. The main structure is a two-stranded beta-sheet followed by a loop to a C-terminal short two-stranded sheet.
EGF	275	310	Pfam, E = 2.1	SMART E=2.08e-03 This EGF domain is a potential Calcium-binding EGF-like domain.
EGF	316	350	Pfam, E = 1.6e-05	This EGF domain is a potential calcium-binding EGF-like domain. Ca is beliefed to mediate thrmbin binding by the EGF6 domain of thrombomodulin. Important residues for Ca-binding by the EGF6 domain are D423-D425-E426-N439. These are also found in a similar position in EGF3 of TEM1. The region in TEM1 containing the EGF domains is as well related to Fibulin-1 in its EGF-like 6 to EGF-like 8 domains. It has been shown that the calcium binding activity of fibulin-1 is contained within EGF-like modules 5-9 and that EGF-like modules 5 and 6 bind fibulin-1 and fibronectin.
LCR	363	380	SEG	LCR(DE), negatively charged
mucin-like	400	603	SEG25, BLASTP	LCR(P)
APOLAR	609	627	SEG,toppred2=0.834	LCR(PAL)
APOLAR	655	678	SEG,toppred2=0.929	LCR(ALP)
TM	686	706	toppred2=2.332
cytoplasmic	706	757		LCR (P= 12%), few large hydrophobic residue (<18%)
757

	Remarks

• CLASSIFICATION: TEM1 is a C-lectin superfamily member. Although the domain-composition is selectin-like the domain-organization (selectins: Lectin-Egf-(nx)sushi) is different.

• HOMOLOGUES: Although no protein with homology over the complete length of TEM1 can be found up to date, the extracellular part shows regions of homology with proteins of the C-lectin family which share a similar domain organization in the extreme N-terminal part spanning over a C-type lectin domain, Sushi domain and 3 EGF domains: thrombomodulin (XP_009595.1), C1qRp (CAC00597).
  The first 20-350aa (lectin+3xEGF) are homologous to the N-terminal 350(lectin+3xEGF) out of 600 aa (lectin+6xEGF) in Thrombomodulin. The human thrombomodulin precursor starts with an 18-residue signal peptide domain, followed by the NH2-terminal domain, a domain with six epidermal growth factor-like structures (300-337, 343-380, 381-419, 421-461, 463-496, 497-537), an O- glycosylation site-rich domain, a 24-residue transmembrane domain and a cytoplasmic domain.

• DOMAIN ARCHITECTURE: TEM1 is a proposed Type I transmembrane protein. The N-terminal half of the extracellular region contains a C-type lectin domain, Sushi domain and 3 EGF domains, and is followed by O- glycosylation site-rich LCR acidic span, a mucine-like proline-rich region of unknown function. The short cytoplasmic domain shows no homology to other proteins.

• FUNCTION: The exact function of TEM1 can only be suggested by our sequence analysis results in general terms. If the difference in domain order compared with selectins is not critical, endosialin may have a role in recruiting blood cells to the endothelium. Given the similarity to C1qR and the existence of the WIGL motif (Psi-blast of the C-lectin domain), it can be hypothesized that Tem1 has a function in internalization. It is known that the homologous protein C1qR binds SPA a defense collagene and cross-reacts with collagen (Peerschke et al). The EGF domain region of Tem1 shows similarity to the fibronectin binding region of fibulin (see below). But the nature of the ligand(s) of Tem1 remains unknown.

     As EGF-like modules have been shown within a number of other proteins to mediate protein/protein interactions, it is proposed for the EGF-domains of TEM1. Tem1 EGF domains are likely, Ca-binding domains. The EGF-domain containing Tem1 region (Pblast of this region) shows closest homology to the first 3 EGF domains of thrombomodulin, which are of unknown binding specificity.(Thrombomodulin EGF domains 5 and 6 are known to bind thrombin and thus to inhibit the procoagulant functions of thrombin and enhances thrombin-catalyzed activation of anticoagulant protein C.) The region is as well related to Fibulin-1 in EGF-like 6 to EGF-like 8 domains. It has been shown that the calcium binding activity of fibulin-1 is contained within EGF-like modules 5-9 and that EGF-like modules 5 and 6 bind fibulin-1 and fibronectin.

     The sushi domain has been linked with heparin binding but the basic residues that are proposed to play a essential role in heparin-binding are not conserved in TEM1sushi. These are located in the the linker domain preceding the SCR domain and in the hypervariable domain, both marked with arrows in the alignment. In the case of SCR7 of human/murine/bovine fH and SCR2 of fHR-3 the alignment contains 4 residues preceeding the sushi domain: a cystein-residue of the preceeding SCR domain and a 3 aa linker containing basic residues that have been proposed to play an essential role in heparin-binding. The cystein-residue aligns aritificially and belongs to a preceeding EGF domain. Due to the lack of essential basic residues in Tem1sushi heparin-binding function for this domain is not supported.

• ADDITIONAL MATERIALS:
  Psi-blast of the C-lectin domain.
  Pblast of the EGF-domain containing region.
  Alignment of the sushi domain with known heparin-binding domains.
  

	Sequence Information

TEM	TEM1
Reliability of Gen2Tag mapping	Cid->tag (Hs.195727) frequency: tem1: CATG-GGGGCTGCCCA=21/21 (EST, oriented) tem1: CATG-GGGGCTGCCCA=2/2 (cDNA)
Analysis	BlastP against nr Output Created by a Suite of Single Sequence Analysis Techniques
Protein Description	SEQ.SOURCE: gi|9857400|gb|AAG00867.1|AF279142_1 tumor endothelial marker 1 precursor
Protein Sequence	MLLRLLLAWAAAGPTLGQDPWAAEPRAACGPSSCYALFPRRRTFLEAWRACRELGGDLATPRTPEEAQRV DSLVGAGPASRLLWIGLQRQARQCQLQRPLRGFTWTTGDQDTAFTNWAQPASGGPCPAQRCVALEASGEH RWLEGSCTLAVDGYLCQFGFEGACPALQDEAGQAGPAVYTTPFHLVSTEFEWLPFGSVAAVQCQAGRGAS LLCVKQPEGGVGWSRAGPLCLGTGCSPDNGGCEHECVEEVDGHVSCRCTEGFRLAADGRSCEDPCAQAPC EQQCEPGGPQGYSCHCRLGFRPAEDDPHRCVDTDECQIAGVCQQMCVNYVGGFECYCSEGHELEADGISC SPAGAMGAQASQDLGDELLDDGEDEEDEDEAWKAFNGGWTEMPGILWMEPTQPPDFALAYRPSFPEDREP QIPYPEPTWPPPLSAPRVPYHSSVLSVTRPVVVSATHPTLPSAHQPPVIPATHPALSRDHQIPVIAANYP DLPSAYQPGILSVSHSAQPPAHQPPMISTKYPELFPAHQSPMFPDTRVAGTQTTTHLPGIPPNHAPLVTT LGAQLPPQAPDALVLRTQATQLPIIPTAQPSLTTTSRSPVSPAHQISVPAATQPAALPTLLPSQSPTNQT SPISPTHPHSKAPQIPREDGPSPKLALWLPSPAPTAAPTALGEAGLAEHSQRDDRWLLVALLVPTCVFLV VLLALGIVYCTRCGPHAPNKRITDCYRWVIHAGSKSPTEPMPPRGSLTGVQTCRTSV
SAGE-Tag	CATG-GGGGCTGCCCA
EST/cluster Description	UNIGEN CLUSTER: Hs.195727 : tumor endothelial marker 1 precursor SEQ.SOURCE: gi|9966884|ref|NM_020404.1| Homo sapiens tumor endothelial marker 1 MARKINGS: TEM1 Tag in red first Poly-A-signal following the Tag in bold
EST/cluster Sequence	TCGCGATGCTGCTGCGCCTGTTGCTGGCCTGGGCGGCCGCAGGGCCCACACTGGGCCAGGACCCCTGGGC TGCTGAGCCCCGTGCCGCCTGCGGCCCCAGCAGCTGCTACGCTCTCTTCCCACGGCGCCGCACCTTCCTG GAGGCCTGGCGGGCCTGCCGCGAGCTGGGGGGCGACCTGGCCACTCCTCGGACCCCCGAGGAGGCCCAGC GTGTGGACAGCCTGGTGGGTGCGGGCCCAGCCAGCCGGCTGCTGTGGATCGGGCTGCAGCGGCAGGCCCG GCAATGCCAGCTGCAGCGCCCACTGCGCGGCTTCACGTGGACCACAGGGGACCAGGACACGGCTTTCACC AACTGGGCCCAGCCAGCCTCTGGAGGCCCCTGCCCGGCCCAGCGCTGTGTGGCCCTGGAGGCAAGTGGCG AGCACCGCTGGCTGGAGGGCTCGTGCACGCTGGCTGTCGACGGCTACCTGTGCCAGTTTGGCTTCGAGGG CGCCTGCCCGGCGCTGCAAGATGAGGCGGGCCAGGCCGGCCCAGCCGTGTATACCACGCCCTTCCACCTG GTCTCCACAGAGTTTGAGTGGCTGCCCTTCGGCTCTGTGGCCGCTGTGCAGTGCCAGGCTGGCAGGGGAG CCTCTCTGCTCTGCGTGAAGCAGCCTGAGGGAGGTGTGGGCTGGTCACGGGCTGGGCCCCTGTGCCTGGG GACTGGCTGCAGCCCTGACAACGGGGGCTGCGAACACGAATGTGTGGAGGAGGTGGATGGTCACGTGTCC TGCCGCTGCACTGAGGGCTTCCGGCTGGCAGCAGACGGGCGCAGTTGCGAGGACCCCTGTGCCCAGGCTC CGTGCGAGCAGCAGTGTGAGCCCGGTGGGCCACAAGGCTACAGCTGCCACTGTCGCCTGGGTTTCCGGCC AGCGGAGGATGATCCGCACCGCTGTGTGGACACAGATGAGTGCCAGATTGCCGGTGTGTGCCAGCAGATG TGTGTCAACTACGTTGGTGGCTTCGAGTGTTATTGTAGCGAGGGACATGAGCTGGAGGCTGATGGCATCA GCTGCAGCCCTGCAGGGGCCATGGGTGCCCAGGCTTCCCAGGACCTCGGAGATGAGTTGCTGGATGACGG GGAGGATGAGGAAGATGAAGACGAGGCCTGGAAGGCCTTCAACGGTGGCTGGACGGAGATGCCTGGGATC CTGTGGATGGAGCCTACGCAGCCGCCTGACTTTGCCCTGGCCTATAGACCGAGCTTCCCAGAGGACAGAG AGCCACAGATACCCTACCCGGAGCCCACCTGGCCACCCCCGCTCAGTGCCCCCAGGGTCCCCTACCACTC CTCAGTGCTCTCCGTCACCCGGCCTGTGGTGGTCTCTGCCACGCATCCCACACTGCCTTCTGCCCACCAG CCTCCTGTGATCCCTGCCACACACCCAGCTTTGTCCCGTGACCACCAGATCCCCGTGATCGCAGCCAACT ATCCAGATCTGCCTTCTGCCTACCAACCCGGTATTCTCTCTGTCTCTCATTCAGCACAGCCTCCTGCCCA CCAGCCCCCTATGATCTCAACCAAATATCCGGAGCTCTTCCCTGCCCACCAGTCCCCCATGTTTCCAGAC ACCCGGGTCGCTGGCACCCAGACCACCACTCATTTGCCTGGAATCCCACCTAACCATGCCCCTCTGGTCA CCACCCTCGGTGCCCAGCTACCCCCTCAAGCCCCAGATGCCCTTGTCCTCAGAACCCAGGCCACCCAGCT TCCCATTATCCCAACTGCCCAGCCCTCTCTGACCACCACCTCCAGGTCCCCTGTGTCTCCTGCCCATCAA ATCTCTGTGCCTGCTGCCACCCAGCCCGCAGCCCTCCCCACCCTCCTGCCCTCTCAGAGCCCCACTAACC AGACCTCACCCATCAGCCCTACACATCCCCATTCCAAAGCCCCCCAAATCCCAAGGGAAGATGGCCCCAG TCCCAAGTTGGCCCTGTGGCTGCCCTCACCAGCTCCCACAGCAGCCCCAACAGCCCTGGGGGAGGCTGGT CTTGCCGAGCACAGCCAGAGGGATGACCGGTGGCTGCTGGTGGCACTCCTGGTGCCAACGTGTGTCTTTT TGGTGGTCCTGCTTGCACTGGGCATCGTGTACTGCACCCGCTGTGGCCCCCATGCACCCAACAAGCGCAT CACTGACTGCTATCGCTGGGTCATCCATGCTGGGAGCAAGAGCCCAACAGAACCCATGCCCCCCAGGGGC AGCCTCACAGGGGTGCAGACCTGCAGAACCAGCGTGTGATGGGGTGCAGACCCCCCTCATGGAGTATGGG GCGCTGGACACATGGCCGGGGCTGCACCAGGGACCCATGGGGGCTGCCCAGCTGGACAGATGGCTTCCTG CTCCCCAGGCCCAGCCAGGGTCCTCTCTCAACCACTAGACTTGGCTCTCAGGAACTCTGCTTCCTGGCCC AGCGCTCGTGACCAAGGATACACCAAAGCCCTTAAGACCTCAGGGGGCGGGTGCTGGGGTCTTCTCCAAT AAATGGGGTGTCAACCTTAAAAAAAAAAAAAAAAAAAAAAAAAAA
Genomic Sequence Description
Genomic Sequence

	Literature

PubMed: 11084048	Endosialin: Molecular cloning and characterization of a C-type lectin-like cell surface receptor of tumor endothelium. Christian S, Ahorn H, Koehler A, Eisenhaber F, Rodi HP, Garin-Chesa P, Park JE, Rettig WJ, Lenter MC. J Biol Chem. 2000 Nov 17.
PubMed: 10934210	Molecular and cellular properties of the rat AA4 antigen, a C-type lectin-like receptor with structural homology to thrombomodulin. Dean YD, McGreal EP, Akatsu H, Gasque P. J Biol Chem. 2000 Nov 3;275(44):34382-92
PubMed: 10648005	Structural and functional evidence for microglial expression of C1qR(P), the C1q receptor that enhances phagocytosis Webster SD, Park M, Fonseca MI, Tenner AJ J Leukoc Biol. 2000 Jan;67(1):109-16.
PubMed: 1438285	Identification of endosialin, a cell surface glycoprotein of vascular endothelial cells in human cancer. Rettig WJ, Garin-Chesa P, Healey JH, Su SL, Jaffe EA, Old LJ. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10832-6.
PubMed: 2212670	Platelet C1q receptor interactions with collagen- and C1q-coated surfaces. Peerschke EI, Ghebrehiwet B. J Immunol. 1990 Nov 1;145(9):2984-8.
PubMed: 10902165	Pinpointing the putative heparin/sialic acid-binding residues in the "sushi" domain 7 of factor H: a molecular modeling study. S. Ranganathan, D.A. Male, R.J. Ormsby, E. Giannakis and D.L. Gordon. Pac. Symp. Biocomput., 5, 155-167.