Primary Information |
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| BoMiProt ID | Bomi8266 |
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| Protein Name | Prolyl 4-hydroxylase subunit alpha-1/Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-1/4-PH alpha-1 |
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| Organism | Bos taurus |
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| Uniprot ID | Q1RMU3 |
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| Milk Fraction | Whey |
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| Ref Sequence ID | NP_001069238.1 |
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| Aminoacid Length | 534 |
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| Molecular Weight | 61010 |
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| FASTA Sequence |
Download |
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| Gene Name | P4HA1 |
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| Gene ID | 518288 |
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| Protein Existence Status | reviewed |
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Secondary Information |
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| 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. |
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| 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 |
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| PTMs | N-Linked Glycosylation at Asn |
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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
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| Predicted Disorder Regions | NA |
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| DisProt Annotation | |
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| TM Helix Prediction | No TM helices |
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| Significance of PTMs | N259 glycosylation on P4HA1 is required to alter P4HA1 binding Type I collagen. |
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| 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. |
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| 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. |
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