UniProt functional annotation for P01042



	UniProt functional annotation for P01042

UniProt code: P01042.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: (1) Kininogens are inhibitors of thiol proteases; (2) HMW- kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; (3) HMW-kininogen inhibits the thrombin- and plasmin-induced aggregation of thrombocytes; (4) the active peptide bradykinin that is released from HMW-kininogen shows a variety of physiological effects: (4A) influence in smooth muscle contraction, (4B) induction of hypotension, (4C) natriuresis and diuresis, (4D) decrease in blood glucose level, (4E) it is a mediator of inflammation and causes (4E1) increase in vascular permeability, (4E2) stimulation of nociceptors (4E3) release of other mediators of inflammation (e.g. prostaglandins), (4F) it has a cardioprotective effect (directly via bradykinin action, indirectly via endothelium-derived relaxing factor action); (5) LMW-kininogen inhibits the aggregation of thrombocytes; (6) LMW-kininogen is in contrast to HMW-kininogen not involved in blood clotting.

Subcellular location: Secreted, extracellular space.

Tissue specificity: Secreted in plasma. T-kinin is detected in malignant ovarian, colon and breast carcinomas, but not in benign tumors. {ECO:0000269|PubMed:2076202}.

Ptm: Bradykinin is released from kininogen by plasma kallikrein.

Ptm: Hydroxylation of Pro-383 occurs prior to the release of bradykinin. {ECO:0000269|PubMed:3182782, ECO:0000269|PubMed:3366244}.

Ptm: Phosphorylated by FAM20C in the extracellular medium. {ECO:0000269|PubMed:26091039}.

Ptm: N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. {ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:3484703}.

Polymorphism: The T-kinin peptide is missing residues 378 to 380, probably as a result of a naturally occurring variant. The complete sequence of the T-kinin peptide is therefore ISRPPGFSPFR. This peptide is associated with malignant tumors but not with benign ones. {ECO:0000269|PubMed:3828072}.

Disease: High molecular weight kininogen deficiency (HMWK deficiency) [MIM:228960]: Autosomal recessive coagulation defect. Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface-mediated activation of fibrinolysis. Note=The disease is caused by variants affecting the gene represented in this entry.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		(1) Kininogens are inhibitors of thiol proteases; (2) HMW- kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; (3) HMW-kininogen inhibits the thrombin- and plasmin-induced aggregation of thrombocytes; (4) the active peptide bradykinin that is released from HMW-kininogen shows a variety of physiological effects: (4A) influence in smooth muscle contraction, (4B) induction of hypotension, (4C) natriuresis and diuresis, (4D) decrease in blood glucose level, (4E) it is a mediator of inflammation and causes (4E1) increase in vascular permeability, (4E2) stimulation of nociceptors (4E3) release of other mediators of inflammation (e.g. prostaglandins), (4F) it has a cardioprotective effect (directly via bradykinin action, indirectly via endothelium-derived relaxing factor action); (5) LMW-kininogen inhibits the aggregation of thrombocytes; (6) LMW-kininogen is in contrast to HMW-kininogen not involved in blood clotting.


Subcellular location:		Secreted, extracellular space.
Tissue specificity:		Secreted in plasma. T-kinin is detected in malignant ovarian, colon and breast carcinomas, but not in benign tumors. {ECO:0000269\|PubMed:2076202}.
Ptm:		Bradykinin is released from kininogen by plasma kallikrein.
Ptm:		Hydroxylation of Pro-383 occurs prior to the release of bradykinin. {ECO:0000269\|PubMed:3182782, ECO:0000269\|PubMed:3366244}.
Ptm:		Phosphorylated by FAM20C in the extracellular medium. {ECO:0000269\|PubMed:26091039}.
Ptm:		N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. {ECO:0000269\|PubMed:12754519, ECO:0000269\|PubMed:14760718, ECO:0000269\|PubMed:16335952, ECO:0000269\|PubMed:19139490, ECO:0000269\|PubMed:19159218, ECO:0000269\|PubMed:19838169, ECO:0000269\|PubMed:3484703}.
Polymorphism:		The T-kinin peptide is missing residues 378 to 380, probably as a result of a naturally occurring variant. The complete sequence of the T-kinin peptide is therefore ISRPPGFSPFR. This peptide is associated with malignant tumors but not with benign ones. {ECO:0000269\|PubMed:3828072}.
Disease:		High molecular weight kininogen deficiency (HMWK deficiency) [MIM:228960]: Autosomal recessive coagulation defect. Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface-mediated activation of fibrinolysis. Note=The disease is caused by variants affecting the gene represented in this entry.