dbPTM

TPOR_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	TPOR_HUMAN
UniProt AC	P40238
Protein Name	Thrombopoietin receptor
Gene Name	MPL
Organism	Homo sapiens (Human).
Sequence Length	635
Subcellular Localization	Cell membrane Single-pass type I membrane protein. Golgi apparatus . Cell surface .
Protein Description	Receptor for thrombopoietin that acts as a primary regulator of megakaryopoiesis and platelet production. May represent a regulatory molecule specific for TPO-R-dependent immune responses..
Protein Sequence	MPSWALFMVTSCLLLAPQNLAQVSSQDVSLLASDSEPLKCFSRTFEDLTCFWDEEEAAPSGTYQLLYAYPREKPRACPLSSQSMPHFGTRYVCQFPDQEEVRLFFPLHLWVKNVFLNQTRTQRVLFVDSVGLPAPPSIIKAMGGSQPGELQISWEEPAPEISDFLRYELRYGPRDPKNSTGPTVIQLIATETCCPALQRPHSASALDQSPCAQPTMPWQDGPKQTSPSREASALTAEGGSCLISGLQPGNSYWLQLRSEPDGISLGGSWGSWSLPVTVDLPGDAVALGLQCFTLDLKNVTCQWQQQDHASSQGFFYHSRARCCPRDRYPIWENCEEEEKTNPGLQTPQFSRCHFKSRNDSIIHILVEVTTAPGTVHSYLGSPFWIHQAVRLPTPNLHWREISSGHLELEWQHPSSWAAQETCYQLRYTGEGHQDWKVLEPPLGARGGTLELRPRSRYRLQLRARLNGPTYQGPWSSWSDPTRVETATETAWISLVTALHLVLGLSAVLGLLLLRWQFPAHYRRLRHALWPSLPDLHRVLGQYLRDTAALSPPKATVSDTCEEVEPSLLEILPKSSERTPLPLCSSQAQMDYRRLQPSCLGTMPLSVCPPMAESGSCCTTHIANHSYLPLSYWQQP

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
81	Phosphorylation	PRACPLSSQSMPHFG CCCCCCCCCCCCCCC	33.68	29038488
89	Phosphorylation	QSMPHFGTRYVCQFP CCCCCCCEEEEEECC	20.20	29038488
117	N-linked_Glycosylation	WVKNVFLNQTRTQRV EEEEHHHCCCCCCEE	29.70	UniProtKB CARBOHYD
137	Phosphorylation	VGLPAPPSIIKAMGG CCCCCCHHHHHHCCC	35.57	24719451
167	Phosphorylation	EISDFLRYELRYGPR CHHHHHHHHHHCCCC	22.82	17929957
178	N-linked_Glycosylation	YGPRDPKNSTGPTVI CCCCCCCCCCCCCHH	50.63	UniProtKB CARBOHYD
298	N-linked_Glycosylation	CFTLDLKNVTCQWQQ EEEEECCCCEEEEEE	41.44	UniProtKB CARBOHYD
358	N-linked_Glycosylation	RCHFKSRNDSIIHIL CCEEECCCCCEEEEE	55.24	UniProtKB CARBOHYD
531	Phosphorylation	LRHALWPSLPDLHRV HHHHHCCCCHHHHHH	40.74	27535140
546	Phosphorylation	LGQYLRDTAALSPPK HHHHHHHHHHCCCCC	13.85	19413330
550	Phosphorylation	LRDTAALSPPKATVS HHHHHHCCCCCCCCC	34.14	24719451
553	Ubiquitination	TAALSPPKATVSDTC HHHCCCCCCCCCCCC	61.14	22817900
573	Ubiquitination	SLLEILPKSSERTPL HHHHHCCCCCCCCCC	64.27	22817900
591	Phosphorylation	SSQAQMDYRRLQPSC CCHHHCCHHHHCHHH	7.71	16464493
610	Ubiquitination	PLSVCPPMAESGSCC CCCCCCCCCCCCCEE	3.79	22817900
626	Phosphorylation	THIANHSYLPLSYWQ EECCCCCCCCCCCCC	12.56	9122198
630	Ubiquitination	NHSYLPLSYWQQP-- CCCCCCCCCCCCC--	23.53	22817900
631	Phosphorylation	HSYLPLSYWQQP--- CCCCCCCCCCCC---	18.21	21527831

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
-	K	Ubiquitination	E3 ubiquitin ligase	CBL	P22681	PMID:19880496

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
553	K	ubiquitylation	19880496
Ubiquitination at Lys-553 and Lys-573 targets MPL for degradation by both the lysosomal and proteasomal pathways.
573	K	ubiquitylation	19880496
Ubiquitination at Lys-553 and Lys-573 targets MPL for degradation by both the lysosomal and proteasomal pathways.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of TPOR_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
ATX2L_HUMAN	ATXN2L	physical	11784712
SOCS1_HUMAN	SOCS1	physical	10517496

Drug and Disease Associations

Kegg Disease
H00227	Congenital amegakaryocytic thrombocytopenia (CAMT)
OMIM Disease
604498	Congenital amegakaryocytic thrombocytopenia (CAMT)
601977	Thrombocythemia 2 (THCYT2)
254450	Myelofibrosis with myeloid metaplasia (MMM)
Kegg Drug
D03978	Eltrombopag olamine (JAN/USAN); Promacta (TN)
D08990	Romiplostim (genetical recombination) (JAN); Romiplostim (USAN/INN); Nplate (TN); Romiplate (TN)
D09024	Totrombopag choline (USAN)
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of TPOR_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-546, AND MASSSPECTROMETRY.	19413330 [Abstract]
Ubiquitylation
Reference	PubMed
"Ubiquitination and degradation of the thrombopoietin receptor c-Mpl."; Saur S.J., Sangkhae V., Geddis A.E., Kaushansky K., Hitchcock I.S.; Blood 115:1254-1263(2010). Cited for: UBIQUITINATION AT LYS-553 AND LYS573.	19880496 [Abstract]