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Protein

Transmembrane prolyl 4-hydroxylase

Gene

P4htm

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates HIF1A at 'Pro-402' and 'Pro-564'. May function as a cellular oxygen sensor and, under normoxic conditions, may target HIF through the hydroxylation for proteasomal degradation via the von Hippel-Lindau ubiquitination complex (By similarity).By similarity

Catalytic activityi

An HIF alpha chain L-proline + 2-oxoglutarate + O2 = An HIF alpha chain trans-4-hydroxy-L-proline + succinate + CO2.

Cofactori

Protein has several cofactor binding sites:
  • Fe2+PROSITE-ProRule annotationNote: Binds 1 Fe2+ ion per subunit.PROSITE-ProRule annotation
  • L-ascorbateBy similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi329IronPROSITE-ProRule annotation1
Metal bindingi331IronPROSITE-ProRule annotation1
Metal bindingi375IronPROSITE-ProRule annotation1
Binding sitei4522-oxoglutaratePROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi199 – 2111Sequence analysisAdd BLAST13
Calcium bindingi238 – 2502Sequence analysisAdd BLAST13

GO - Molecular functioni

GO - Biological processi

  • peptidyl-proline hydroxylation to 4-hydroxy-L-proline Source: GO_Central
  • regulation of erythrocyte differentiation Source: MGI

Keywordsi

Molecular functionDioxygenase, Oxidoreductase
LigandCalcium, Iron, Metal-binding, Vitamin C, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane prolyl 4-hydroxylase (EC:1.14.11.-)
Short name:
P4H-TM
Alternative name(s):
Hypoxia-inducible factor prolyl hydroxylase 4
Short name:
HIF-PH4
Short name:
HIF-prolyl hydroxylase 4
Short name:
HPH-4
Gene namesi
Name:P4htm
Synonyms:Ph4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1921693 P4htm

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 61CytoplasmicSequence analysisAdd BLAST61
Transmembranei62 – 82Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini83 – 503LumenalSequence analysisAdd BLAST421

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002066691 – 503Transmembrane prolyl 4-hydroxylaseAdd BLAST503

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi349N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi369N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi383N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Glycosylated.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8BG58
PRIDEiQ8BG58

PTM databases

iPTMnetiQ8BG58
PhosphoSitePlusiQ8BG58

Expressioni

Gene expression databases

BgeeiENSMUSG00000006675 Expressed in 209 organ(s), highest expression level in retina
CleanExiMM_4933406E20RIK
ExpressionAtlasiQ8BG58 baseline and differential
GenevisibleiQ8BG58 MM

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000006853

Structurei

3D structure databases

ProteinModelPortaliQ8BG58
SMRiQ8BG58
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini186 – 221EF-hand 1Add BLAST36
Domaini225 – 260EF-hand 2Add BLAST36
Domaini310 – 461Fe2OG dioxygenasePROSITE-ProRule annotationAdd BLAST152

Keywords - Domaini

Repeat, Signal-anchor, Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiKOG1591 Eukaryota
ENOG410XS5J LUCA
GeneTreeiENSGT00390000014570
HOGENOMiHOG000115323
InParanoidiQ8BG58
KOiK06711
OMAiYVTVLFY
OrthoDBiEOG091G04NW
PhylomeDBiQ8BG58
TreeFamiTF332923

Family and domain databases

InterProiView protein in InterPro
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
IPR005123 Oxoglu/Fe-dep_dioxygenase
IPR006620 Pro_4_hyd_alph
PfamiView protein in Pfam
PF13640 2OG-FeII_Oxy_3, 1 hit
PF13499 EF-hand_7, 1 hit
SMARTiView protein in SMART
SM00702 P4Hc, 1 hit
SUPFAMiSSF47473 SSF47473, 1 hit
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 2 hits
PS51471 FE2OG_OXY, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8BG58-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAAAVATVQR PEAETVEEAS NLQWPLPPEH RPSGAATRPG DSEDAPVRPL
60 70 80 90 100
CKPRGICSRA YFLVLMVFVH LYLGNVLALL LFVHYSNGDE STDPGPQRRE
110 120 130 140 150
QSPQPVPTLG PLTRLEGIKV GYERKVQVVA GRDHFIRTLS LKPLLFEIPG
160 170 180 190 200
FLSDEECRLI IHLAQMKGLQ RSQILPTEEY EEAMSAMQVS QLDLFQLLDQ
210 220 230 240 250
NHDGRLQLRE VLAQTRLGNG RWMTPENIQE MYSAIKADPD GDGVLSLQEF
260 270 280 290 300
SNMDLRDFHK YMRSHKAESN ELVRNSHHTW LHQGEGAHHV MRAIRQRVLR
310 320 330 340 350
LTRLSPEIVE FSEPLQVVRY GEGGHYHAHV DSGPVYPETI CSHTKLVANE
360 370 380 390 400
SVPFETSCRY MTVLFYLNNV TGGGETVFPV ADNRTYDEMS LIQDDVDLRD
410 420 430 440 450
TRRHCDKGNL RVKPQQGTAV FWYNYLPDGQ GWVGEVDDYS LHGGCLVTRG
460 470 480 490 500
TKWIANNWIN VDPSRARQAL FQQEMARLAR EGGMDSQPEW ALDRAYSDAR

VEL
Length:503
Mass (Da):57,049
Last modified:March 1, 2003 - v1
Checksum:iC220CA0840F1BAFF
GO
Isoform 2 (identifier: Q8BG58-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     212-225: LAQTRLGNGRWMTP → RTPPAMWVGTGEN
     226-503: Missing.

Note: No experimental confirmation available.
Show »
Length:224
Mass (Da):25,056
Checksum:i9270F11DE15FFE6B
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A6YX56A0A0A6YX56_MOUSE
Transmembrane prolyl 4-hydroxylase
P4htm
225Annotation score:
A0A0A6YXH5A0A0A6YXH5_MOUSE
Transmembrane prolyl 4-hydroxylase
P4htm
144Annotation score:

Sequence cautioni

The sequence BAB30379 differs from that shown. Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated
The sequence BAC30172 differs from that shown. Reason: Frameshift at position 9.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_007575212 – 225LAQTR…RWMTP → RTPPAMWVGTGEN in isoform 2. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_007576226 – 503Missing in isoform 2. 1 PublicationAdd BLAST278

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK046783 mRNA Translation: BAC32866.1
AK047714 mRNA Translation: BAC33135.1
AK016685 mRNA Translation: BAB30379.2 Sequence problems.
AK038927 mRNA Translation: BAC30172.1 Sequence problems.
CCDSiCCDS23533.1 [Q8BG58-1]
RefSeqiNP_083220.3, NM_028944.3 [Q8BG58-1]
UniGeneiMm.226534

Genome annotation databases

EnsembliENSMUST00000006853; ENSMUSP00000006853; ENSMUSG00000006675 [Q8BG58-1]
GeneIDi74443
KEGGimmu:74443
UCSCiuc009rqk.1 mouse [Q8BG58-1]
uc009rql.1 mouse [Q8BG58-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK046783 mRNA Translation: BAC32866.1
AK047714 mRNA Translation: BAC33135.1
AK016685 mRNA Translation: BAB30379.2 Sequence problems.
AK038927 mRNA Translation: BAC30172.1 Sequence problems.
CCDSiCCDS23533.1 [Q8BG58-1]
RefSeqiNP_083220.3, NM_028944.3 [Q8BG58-1]
UniGeneiMm.226534

3D structure databases

ProteinModelPortaliQ8BG58
SMRiQ8BG58
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000006853

PTM databases

iPTMnetiQ8BG58
PhosphoSitePlusiQ8BG58

Proteomic databases

PaxDbiQ8BG58
PRIDEiQ8BG58

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000006853; ENSMUSP00000006853; ENSMUSG00000006675 [Q8BG58-1]
GeneIDi74443
KEGGimmu:74443
UCSCiuc009rqk.1 mouse [Q8BG58-1]
uc009rql.1 mouse [Q8BG58-2]

Organism-specific databases

CTDi54681
MGIiMGI:1921693 P4htm

Phylogenomic databases

eggNOGiKOG1591 Eukaryota
ENOG410XS5J LUCA
GeneTreeiENSGT00390000014570
HOGENOMiHOG000115323
InParanoidiQ8BG58
KOiK06711
OMAiYVTVLFY
OrthoDBiEOG091G04NW
PhylomeDBiQ8BG58
TreeFamiTF332923

Miscellaneous databases

PROiPR:Q8BG58
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000006675 Expressed in 209 organ(s), highest expression level in retina
CleanExiMM_4933406E20RIK
ExpressionAtlasiQ8BG58 baseline and differential
GenevisibleiQ8BG58 MM

Family and domain databases

InterProiView protein in InterPro
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
IPR005123 Oxoglu/Fe-dep_dioxygenase
IPR006620 Pro_4_hyd_alph
PfamiView protein in Pfam
PF13640 2OG-FeII_Oxy_3, 1 hit
PF13499 EF-hand_7, 1 hit
SMARTiView protein in SMART
SM00702 P4Hc, 1 hit
SUPFAMiSSF47473 SSF47473, 1 hit
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 2 hits
PS51471 FE2OG_OXY, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiP4HTM_MOUSE
AccessioniPrimary (citable) accession number: Q8BG58
Secondary accession number(s): Q8CAF1, Q9D499
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 16, 2003
Last sequence update: March 1, 2003
Last modified: November 7, 2018
This is version 123 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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