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Protein

Transmembrane prolyl 4-hydroxylase

Gene

P4HTM

Organism
Homo sapiens (Human)
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.1 Publication

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 bindingi328IronPROSITE-ProRule annotation1
Metal bindingi330IronPROSITE-ProRule annotation1
Metal bindingi374IronPROSITE-ProRule annotation1
Binding sitei4512-oxoglutaratePROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi198 – 2101Sequence analysisAdd BLAST13
Calcium bindingi237 – 2492Sequence analysisAdd BLAST13

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000178467.17
HGNCiHGNC:28858 P4HTM
MIMi614584 gene
neXtProtiNX_Q9NXG6

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 – 60CytoplasmicSequence analysisAdd BLAST60
Transmembranei61 – 81Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini82 – 502LumenalSequence analysisAdd BLAST421

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi54681
OpenTargetsiENSG00000178467
PharmGKBiPA164724295

Chemistry databases

ChEMBLiCHEMBL3047
DrugBankiDB00126 Vitamin C

Polymorphism and mutation databases

BioMutaiP4HTM
DMDMi32129516

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002066681 – 502Transmembrane prolyl 4-hydroxylaseAdd BLAST502

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi348N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi368N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi382N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ9NXG6
MaxQBiQ9NXG6
PaxDbiQ9NXG6
PeptideAtlasiQ9NXG6
PRIDEiQ9NXG6
ProteomicsDBi83095
83096 [Q9NXG6-2]
83097 [Q9NXG6-3]

PTM databases

iPTMnetiQ9NXG6
PhosphoSitePlusiQ9NXG6

Expressioni

Tissue specificityi

Widely expressed with highest levels in adult pancreas, heart, skeletal muscle, brain, placenta, kidney and adrenal gland. Expressed at lower levels in epiphyseal cartilage and in fibroblasts.2 Publications

Inductioni

By hypoxia in many cultured cell lines.1 Publication

Gene expression databases

BgeeiENSG00000178467 Expressed in 215 organ(s), highest expression level in pituitary gland
ExpressionAtlasiQ9NXG6 baseline and differential
GenevisibleiQ9NXG6 HS

Organism-specific databases

HPAiHPA007199

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi120100, 6 interactors
IntActiQ9NXG6, 1 interactor
STRINGi9606.ENSP00000341422

Chemistry databases

BindingDBiQ9NXG6

Structurei

3D structure databases

ProteinModelPortaliQ9NXG6
SMRiQ9NXG6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini185 – 220EF-hand 1Add BLAST36
Domaini224 – 259EF-hand 2Add BLAST36
Domaini310 – 460Fe2OG dioxygenasePROSITE-ProRule annotationAdd BLAST151

Keywords - Domaini

Repeat, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1591 Eukaryota
ENOG410XS5J LUCA
GeneTreeiENSGT00390000014570
HOGENOMiHOG000115323
InParanoidiQ9NXG6
KOiK06711
OMAiYVTVLFY
OrthoDBiEOG091G04NW
PhylomeDBiQ9NXG6
TreeFamiTF332923

Family and domain databases

CDDicd00051 EFh, 1 hit
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 (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9NXG6-1) [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
MAAAAVTGQR PETAAAEEAS RPQWAPPDHC QAQAAAGLGD GEDAPVRPLC
60 70 80 90 100
KPRGICSRAY FLVLMVFVHL YLGNVLALLL FVHYSNGDES SDPGPQHRAQ
110 120 130 140 150
GPGPEPTLGP LTRLEGIKVG HERKVQLVTD RDHFIRTLSL KPLLFEIPGF
160 170 180 190 200
LTDEECRLII HLAQMKGLQR SQILPTEEYE EAMSTMQVSQ LDLFRLLDQN
210 220 230 240 250
RDGHLQLREV LAQTRLGNGW WMTPESIQEM YAAIKADPDG DGVLSLQEFS
260 270 280 290 300
NMDLRDFHKY MRSHKAESSE LVRNSHHTWL YQGEGAHHIM RAIRQRVLRL
310 320 330 340 350
TRLSPEIVEL SEPLQVVRYG EGGHYHAHVD SGPVYPETIC SHTKLVANES
360 370 380 390 400
VPFETSCRYM TVLFYLNNVT GGGETVFPVA DNRTYDEMSL IQDDVDLRDT
410 420 430 440 450
RRHCDKGNLR VKPQQGTAVF WYNYLPDGQG WVGDVDDYSL HGGCLVTRGT
460 470 480 490 500
KWIANNWINV DPSRARQALF QQEMARLARE GGTDSQPEWA LDRAYRDARV

EL
Length:502
Mass (Da):56,661
Last modified:June 16, 2003 - v2
Checksum:iA2DAE4ACF4A2E18C
GO
Isoform 2 (identifier: Q9NXG6-2) [UniParc]FASTAAdd to basket
Also known as: b

The sequence of this isoform differs from the canonical sequence as follows:
     359-502: YMTVLFYLNN...RAYRDARVEL → QVSPNWGLPS...WLERGGYWSS

Note: No experimental confirmation available.
Show »
Length:423
Mass (Da):47,211
Checksum:i5540388F142E76E4
GO
Isoform 3 (identifier: Q9NXG6-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     358-358: R → RQVSPNWGLPSILRPGTPMTQAQPCTVGVPLGMGPGDHWVIPVSPWEHPQLGTCSVPPLPYS

Note: No experimental confirmation available.
Show »
Length:563
Mass (Da):63,112
Checksum:i9154ADD79EA6BE78
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C153H7C153_HUMAN
Transmembrane prolyl 4-hydroxylase
P4HTM
226Annotation score:
A0A0C4DGS7A0A0C4DGS7_HUMAN
Transmembrane prolyl 4-hydroxylase
P4HTM
139Annotation score:
V9GYK5V9GYK5_HUMAN
Transmembrane prolyl 4-hydroxylase
P4HTM
88Annotation score:
V9GY20V9GY20_HUMAN
Transmembrane prolyl 4-hydroxylase
P4HTM
157Annotation score:

Sequence cautioni

The sequence AAH60321 differs from that shown. Intron retention.Curated
The sequence BAA91045 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAD28518 differs from that shown. Intron retention.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti213Q → K in AAH47566 (PubMed:15489334).Curated1
Sequence conflicti240G → A in AAO43431 (PubMed:12163023).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_007573358R → RQVSPNWGLPSILRPGTPMT QAQPCTVGVPLGMGPGDHWV IPVSPWEHPQLGTCSVPPLP YS in isoform 3. 1 Publication1
Alternative sequenceiVSP_007574359 – 502YMTVL…ARVEL → QVSPNWGLPSILRPGTPMTQ AQPCTVGVPLGMGPGDHWVI PVSDALTSPHKLFTQWLERG GYWSS in isoform 2. 2 PublicationsAdd BLAST144

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY198406 mRNA Translation: AAO43431.1
AL713728 mRNA Translation: CAD28518.2 Sequence problems.
BC000580 mRNA Translation: AAH00580.1
BC011710 mRNA Translation: AAH11710.3
BC047566 mRNA Translation: AAH47566.1
BC060321 mRNA Translation: AAH60321.1 Sequence problems.
AK000269 mRNA Translation: BAA91045.1 Different initiation.
CCDSiCCDS2781.2 [Q9NXG6-3]
CCDS43089.1 [Q9NXG6-1]
RefSeqiNP_808807.2, NM_177938.2 [Q9NXG6-3]
NP_808808.1, NM_177939.2 [Q9NXG6-1]
UniGeneiHs.654944

Genome annotation databases

EnsembliENST00000343546; ENSP00000341422; ENSG00000178467 [Q9NXG6-3]
ENST00000383729; ENSP00000373235; ENSG00000178467 [Q9NXG6-1]
GeneIDi54681
KEGGihsa:54681
UCSCiuc003cvg.4 human [Q9NXG6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY198406 mRNA Translation: AAO43431.1
AL713728 mRNA Translation: CAD28518.2 Sequence problems.
BC000580 mRNA Translation: AAH00580.1
BC011710 mRNA Translation: AAH11710.3
BC047566 mRNA Translation: AAH47566.1
BC060321 mRNA Translation: AAH60321.1 Sequence problems.
AK000269 mRNA Translation: BAA91045.1 Different initiation.
CCDSiCCDS2781.2 [Q9NXG6-3]
CCDS43089.1 [Q9NXG6-1]
RefSeqiNP_808807.2, NM_177938.2 [Q9NXG6-3]
NP_808808.1, NM_177939.2 [Q9NXG6-1]
UniGeneiHs.654944

3D structure databases

ProteinModelPortaliQ9NXG6
SMRiQ9NXG6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120100, 6 interactors
IntActiQ9NXG6, 1 interactor
STRINGi9606.ENSP00000341422

Chemistry databases

BindingDBiQ9NXG6
ChEMBLiCHEMBL3047
DrugBankiDB00126 Vitamin C

PTM databases

iPTMnetiQ9NXG6
PhosphoSitePlusiQ9NXG6

Polymorphism and mutation databases

BioMutaiP4HTM
DMDMi32129516

Proteomic databases

EPDiQ9NXG6
MaxQBiQ9NXG6
PaxDbiQ9NXG6
PeptideAtlasiQ9NXG6
PRIDEiQ9NXG6
ProteomicsDBi83095
83096 [Q9NXG6-2]
83097 [Q9NXG6-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000343546; ENSP00000341422; ENSG00000178467 [Q9NXG6-3]
ENST00000383729; ENSP00000373235; ENSG00000178467 [Q9NXG6-1]
GeneIDi54681
KEGGihsa:54681
UCSCiuc003cvg.4 human [Q9NXG6-1]

Organism-specific databases

CTDi54681
DisGeNETi54681
EuPathDBiHostDB:ENSG00000178467.17
GeneCardsiP4HTM
HGNCiHGNC:28858 P4HTM
HPAiHPA007199
MIMi614584 gene
neXtProtiNX_Q9NXG6
OpenTargetsiENSG00000178467
PharmGKBiPA164724295
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1591 Eukaryota
ENOG410XS5J LUCA
GeneTreeiENSGT00390000014570
HOGENOMiHOG000115323
InParanoidiQ9NXG6
KOiK06711
OMAiYVTVLFY
OrthoDBiEOG091G04NW
PhylomeDBiQ9NXG6
TreeFamiTF332923

Miscellaneous databases

ChiTaRSiP4HTM human
GenomeRNAii54681
PROiPR:Q9NXG6
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000178467 Expressed in 215 organ(s), highest expression level in pituitary gland
ExpressionAtlasiQ9NXG6 baseline and differential
GenevisibleiQ9NXG6 HS

Family and domain databases

CDDicd00051 EFh, 1 hit
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_HUMAN
AccessioniPrimary (citable) accession number: Q9NXG6
Secondary accession number(s): Q6PAG6
, Q8TCJ9, Q8WV55, Q96F22, Q9BW77
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 16, 2003
Last sequence update: June 16, 2003
Last modified: November 7, 2018
This is version 159 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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