Sema domain

{{Pfam_box

| Symbol = Sema

| Name =

| image = PBB_Protein_SEMA3A_image.jpg

| width =250

| caption =Sema domain, immunoglobulin domain (Ig), short basic domain

| Pfam= PF01403

| InterPro= IPR001627

| SMART=

| PROSITE = PDOC51004

| SCOP = 1olz

| TCDB =

| OPM family=

| OPM protein=

| PDB=

| Membranome superfamily= 71

}}

The Sema domain is a structural domain of semaphorins, which are a large family of secreted and transmembrane proteins, some of which function as repellent signals during axon guidance. Sema domains also occur in the hepatocyte growth factor receptor (Uniprot: {{Uniprot|P08581}}), Plexin-A3 {{cite journal | vauthors = Winberg ML, Noordermeer JN, Tamagnone L, Comoglio PM, Spriggs MK, Tessier-Lavigne M, Goodman CS | title = Plexin A is a neuronal semaphorin receptor that controls axon guidance | journal = Cell | volume = 95 | issue = 7 | pages = 903–16 | date = December 1998 | pmid = 9875845 | doi = 10.1016/S0092-8674(00)81715-8 | s2cid = 14703056 | doi-access = free }} (Uniprot: {{Uniprot|P51805}}) and in viral proteins.

CD100 (also called SEMA4D) is associated with PTPase and serine kinase activity. CD100 increases PMA, CD3 and CD2 induced T cell proliferation, increases CD45 induced T cell adhesion, induces B cell homotypic adhesion and down-regulates B cell expression of CD23.

The Sema domain is characterised by a conserved set of cysteine residues, which form four disulfide bonds to stabilise the structure. The Sema domain fold is a variation of the beta propeller topology, with seven blades radially

arranged around a central axis. Each blade contains a four- stranded (strands A to D) antiparallel beta sheet. The inner strand of each blade (A) lines the channel at the centre of the propeller, with strands B and C of the same repeat radiating outward, and strand D of the next repeat forming the outer edge of the blade. The large size of the Sema domain is not due to a single inserted domain but results from the presence of additional secondary structure elements inserted in most of the blades. The Sema domain uses a 'loop and hook' system to close the circle between the first and the last blades. The blades are constructed sequentially with an N-terminal beta- strand closing the circle by providing the outermost strand (D) of the seventh (C-terminal) blade. The beta-propeller is further stabilized by an extension of the N-terminus, providing an additional, fifth beta-strand on the outer edge of blade 6.{{cite journal | vauthors = Antipenko A, Himanen JP, van Leyen K, Nardi-Dei V, Lesniak J, Barton WA, Rajashankar KR, Lu M, Hoemme C, Püschel AW, Nikolov DB | title = Structure of the semaphorin-3A receptor binding module | journal = Neuron | volume = 39 | issue = 4 | pages = 589–98 | date = August 2003 | pmid = 12925274 | doi = 10.1016/S0896-6273(03)00502-6 | s2cid = 9782923 | doi-access = free }}{{cite journal | vauthors = Love CA, Harlos K, Mavaddat N, Davis SJ, Stuart DI, Jones EY, Esnouf RM | title = The ligand-binding face of the semaphorins revealed by the high-resolution crystal structure of SEMA4D | journal = Nature Structural Biology | volume = 10 | issue = 10 | pages = 843–8 | date = October 2003 | pmid = 12958590 | doi = 10.1038/nsb977 | s2cid = 24468463 }}{{cite journal | vauthors = Stamos J, Lazarus RA, Yao X, Kirchhofer D, Wiesmann C | title = Crystal structure of the HGF beta-chain in complex with the Sema domain of the Met receptor | journal = The EMBO Journal | volume = 23 | issue = 12 | pages = 2325–35 | date = June 2004 | pmid = 15167892 | pmc = 423285 | doi = 10.1038/sj.emboj.7600243 }}