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Overview

Uniprot IDQ96NU7
Protein NameProbable imidazolonepropionase
Gene NameAMDHD1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
214 IINNHLPKLKELGRN

Function

Catalyzes the hydrolytic cleavage of the carbon-nitrogen bond in imidazolone-5-propanoate to form N-formimidoyl-L-glutamate. This reaction represents the third step of the universal histidine degradation pathway. In addition to its metabolic role, functions as a tumor suppressor by promoting TGF-beta signaling. Mechanistically, inhibits ubiquitination and proteasomal degradation of SMAD4, thereby stabilizing the protein. Enhances SMAD2/3 phosphorylation and increases TGF-beta-dependent transcriptional responses. Consequently, promotes apoptosis and induces cell cycle arrest in tumor cells (PubMed:39143229)

Protein Sequence

10 MASGHSLLLE 20 NAQQVVLVCA 30 RGERFLARDA 40 LRSLAVLEGA 50 SLVVGKDGFI 60 KAIGPADVIQ 70 RQFSGETFEE 80 IIDCSGKCIL 90 PGLVDAHTHP 100 VWAGERVHEF 110 AMKLAGATYM 120 EIHQAGGGIH 130 FTVERTRQAT 140 EEELFRSLQQ 150 RLQCMMRAGT 160 TLVECKSGYG 170 LDLETELKML 180 RVIERARREL 190 DIGISATYCG 200 AHSVPKGKTA 210 TEAADDIINN 220 HLPKLKELGR 230 NGEIHVDNID 240 VFCEKGVFDL 250 DSTRRILQRG 260 KDIGLQINFH 270 GDELHPMKAA 280 ELGAELGAQA 290 ISHLEEVSDE 300 GIVAMATARC 310 SAILLPTTAY 320 MLRLKQPRAR 330 KMLDEGVIVA 340 LGSDFNPNAY 350 CFSMPMVMHL 360 ACVNMRMSMP 370 EALAAATINA 380 AYALGKSHTH 390 GSLEVGKQGD 400 LIIINSSRWE 410 HLIYQFGGHH 420 ELIEYVIAKG KLIYKT

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005829 cytosol
Molecular Function GO:0016812 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides
Molecular Function GO:0050480 imidazolonepropionase activity
Molecular Function GO:0046872 metal ion binding
Biological Process GO:0006548 L-histidine catabolic process
Biological Process GO:0019556 L-histidine catabolic process to glutamate and formamide
Biological Process GO:0019557 L-histidine catabolic process to glutamate and formate

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.