TRBM_HUMAN » Thrombomodulin

TRBM_HUMAN » Thrombomodulin
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
TRBM_HUMAN » Thrombomodulin » TM; Fetomodulin;
Hydrophobic Thickness 36.8 ± 5.6 Å
Tilt Angle 26 ± 0°
ΔGtransfer -23.2 kcal/mol
ΔGfold -19.1 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome
Topology Out
TM Segments 512-539 (512-542)
Pathways

Complement and coagulation cascades (KEGG)

Hemostasis (Reactome)
PDB 1zaq (364-407), 1dqb (364-444), 1tmr (389-405), 1adx (405-444), 2adx (405-444), 1fge (425-444), 1egt (427-444), 1fgd (427-444), 1dx5 (I/J/K/L=363-480), 1hlt (R=426-444), 3gis (X/Y/Z=363-483)
OPM none
Complexes none
Interactions

IEX1, Complex: IEX1:TRBM, PubMed
Domains

AA: 41-169, PDBID: 1H8U, Subunit A, Seq Identity:23%, Lectin C-type domain

AA: 245-280, PDBID: 3S94, Subunit A, Seq Identity:48%, Coagulation Factor Xa inhibitory site

AA: 305-328, PDBID: 1HJ7, Subunit A, Seq Identity:46%, Complement Clr-like EGF-like
UniProt annotation for TRBM_HUMAN » Thrombomodulin
FUNCTION: Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin generated.

TISSUE SPECIFICITY: Endothelial cells are unique in synthesizing thrombomodulin.

DISEASE: Thrombophilia due to thrombomodulin defect (THPH12) OMIM: A hemostatic disorder characterized by a tendency to thrombosis. disease may be caused by mutations affecting the gene represented in this entry. The role of thrombomodulin in thrombosis is controversial. It is likely that genetic or environmental risk factors in addition to THBD variation are involved in the pathogenesis of venous thrombosis.

DISEASE: Hemolytic uremic syndrome atypical 6 (AHUS6) OMIM: An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. associated with variations affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype.

UniProt features for TRBM_HUMAN » Thrombomodulin
SIGNAL 1 18
CHAIN 19 575 Thrombomodulin.
DOMAIN 31 169 C-type lectin.
DOMAIN 241 281 EGF-like 1.
DOMAIN 284 324 EGF-like 2.
DOMAIN 325 363 EGF-like 3; calcium-binding (Potential).
DOMAIN 365 405 EGF-like 4.
DOMAIN 404 440 EGF-like 5.
DOMAIN 441 481 EGF-like 6; calcium-binding (Potential).
DISULFID 137 158 By similarity.
DISULFID 245 256 By similarity.
DISULFID 252 265 By similarity.
DISULFID 267 280 By similarity.
DISULFID 288 296 By similarity.
DISULFID 292 308 By similarity.
DISULFID 310 323 By similarity.
DISULFID 329 340 By similarity.
DISULFID 336 349 By similarity.
DISULFID 351 362 By similarity.
DISULFID 369 378 By similarity.
DISULFID 374 388 By similarity.
DISULFID 390 404
DISULFID 408 413
DISULFID 417 425
DISULFID 427 439
DISULFID 445 455 By similarity.
DISULFID 451 464 By similarity.
DISULFID 466 480 By similarity.
Amino Acid Sequence for TRBM_HUMAN » Thrombomodulin
MLGVLVLGAL ALAGLGFPAP AEPQPGGSQC VEHDCFALYP GPATFLNASQ ICDGLRGHLM TVRSSVAADV ISLLLNGDGG VGRRRLWIGL QLPPGCGDPK RLGPLRGFQW VTGDNNTSYS RWARLDLNGA PLCGPLCVAV SAAEATVPSE PIWEEQQCEV KADGFLCEFH FPATCRPLAV EPGAAAAAVS ITYGTPFAAR GADFQALPVG SSAAVAPLGL QLMCTAPPGA VQGHWAREAP GAWDCSVENG GCEHACNAIP GAPRCQCPAG AALQADGRSC TASATQSCND LCEHFCVPNP DQPGSYSCMC ETGYRLAADQ HRCEDVDDCI LEPSPCPQRC VNTQGGFECH CYPNYDLVDG ECVEPVDPCF RANCEYQCQP LNQTSYLCVC AEGFAPIPHE PHRCQMFCNQ TACPADCDPN TQASCECPEG YILDDGFICT DIDECENGGF CSGVCHNLPG TFECICGPDS ALARHIGTDC DSGKVDGGDS GSGEPPPSPT PGSTLTPPAV GLVHSGLLIG ISIASLCLVV ALLALLCHLR KKQGAARAKM EYKCAAPSKE VVLQHVRTER TPQRL