Search by BoMiProt ID - Bomi8266


Primary Information

BoMiProt ID Bomi8266
Protein Name Prolyl 4-hydroxylase subunit alpha-1/Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-1/4-PH alpha-1
Organism Bos taurus
Uniprot IdQ1RMU3
Milk FractionWhey
Ref Sequence Id NP_001069238.1
Aminoacid Length 534
Molecular Weight 61010
Fasta Sequence https://www.uniprot.org/uniprot/Q1RMU3.fasta
Gene Name P4HA1
Gene Id 518288
Protein Existence Status reviewed

Secondary Information

Protein Function P4HA1 is an interesting potential prognostic marker and therapeutic target in primary melanomas, influencing many aspects of melanoma tumor progression.P4H alpha 1 subunit (P4HA1) protein expression is induced in triple-negative breast cancer (TNBC) and HER2 positive breast cancer.
Biochemical Properties P4HA1 encodes one of the alpha subunits of prolyl 4‐hydroxylase, a key enzyme in the synthesis of collagens, composed of two identical alpha subunits and two beta subunits. A dimer of P4HA1 forms the catalytically active site of prolyl 4‐hydroxylase I enzyme, which is the most common form in many cell types and tissues 
PTMs N-Linked Glycosylation at Asn
Site(s) of PTM(s)

N-glycosylation, O-glycosylation,
Phosphorylation
>sp|Q1RMU3|P4HA1_BOVIN Prolyl 4-hydroxylase subunit alpha-1 OS=Bos taurus OX=9913 GN=P4HA1 PE=1 SV=1 MIWYILVVGILLPQSLAHPGFFTSIGQMTDLIHTEKDLVTSLKDYIKAEEDKLEQIKKWA EKLDRLTSTATKDPEGFVGHPVNAFKLMKRLNTEWSELENLVLKDMSDGFISN*113LTIQRQY FPNDEDQVGAAKALLRLQDTYNLDTDTISKGDLPGVKHKSFLTVEDCFELGKVAYTEADY YHTELWMEQALRQLDEGEVSTVDKVSVLDYLSYAVYQQGDLDKALLLTKKLLELDPEHQR ANGNLKYFEYIMAKEKDAN*259KSSSDDQSDQKTTLKKKGAAVDYLPERQKYEMLCRGEGIKM TPRRQKKLFCRYHDGNRNPKFILAPAKQEDEWDKPRIIRFHDIISDAEIEVVKDLAKPRL RRATISNPITGDLETVHYRISKSAWLSGYENPVVSRINMRIQDLTGLDVSTAEELQVANY GVGGQYEPHFDFARKDEPDAFKELGTGNRIATWLFYMSDVLAGGATVFPEVGASVWPKKG TAVFWYNLFASGEGDYSTRHAACPVLVGNKWVSNKWLHERGQEFRRPCTLSELE
Predicted Disorder Regions NA
DisProt Annotation
TM Helix Prediction No TM helices
Significance of PTMs N259 glycosylation on P4HA1 is required to alter P4HA1 binding Type I collagen.
Additional Comments P4HA1 depletion in melanoma cells reduced cell adhesion, invasion, and viability in vitro.P4HA1 knockdown reduced melanoma tumor invasion as well as the deposition of collagens, particularly type IV collagen, in the interstitial extracellular matrix and in the basement membranes of tumor blood vessels, leading to vessel wall rupture and hemorrhages.
Bibliography 1.Eriksson J, Le Joncour V, Jahkola T, Juteau S, Laakkonen P, Saksela O, Hölttä E. Prolyl 4-hydroxylase subunit alpha 1 (P4HA1) is a biomarker of poor prognosis in primary melanomas, and its depletion inhibits melanoma cell invasion and disrupts tumor blood vessel walls. Mol Oncol. 2020 Apr;14(4):742-762. doi: 10.1002/1878-0261.12649. Epub 2020 Feb 28. PMID: 32053263; PMCID: PMC7138405. 2.Xiong G, Stewart RL, Chen J, Gao T, Scott TL, Samayoa LM, O'Connor K, Lane AN, Xu R. Collagen prolyl 4-hydroxylase 1 is essential for HIF-1α stabilization and TNBC chemoresistance. Nat Commun. 2018 Oct 26;9(1):4456. doi: 10.1038/s41467-018-06893-9. PMID: 30367042; PMCID: PMC6203834. 3.Myllyharju J (2003) Prolyl 4‐hydroxylases, the key enzymes of collagen biosynthesis. Matrix Biol 22, 15–24. 4.R. Shi, W. Hu, Y. Zhang, S. Gao,A.H. Smith, J. Ye, L. Cai, L.M. Graham, C. Li, Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit a1 promote hydroxylation and secretion of type I collagen, Cell. Mol. Life Sci. 76 (2019) 3449e3464.