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Protein

Transmembrane prolyl 4-hydroxylase

Gene

P4HTM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Ligandi

Calcium, Iron, Metal-binding, Vitamin C

Enzyme and pathway databases

BioCyciZFISH:ENSG00000178467-MONOMER.

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

HGNCiHGNC:28858. P4HTM.

Subcellular locationi

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

GO - Cellular componenti

Complete GO annotation...

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...)Sequence analysis1
Glycosylationi368N-linked (GlcNAc...)Sequence analysis1
Glycosylationi382N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ9NXG6.
PaxDbiQ9NXG6.
PeptideAtlasiQ9NXG6.
PRIDEiQ9NXG6.

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.
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

Sequence similaritiesi

Contains 2 EF-hand domains.Curated
Contains 1 Fe2OG dioxygenase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1591. Eukaryota.
ENOG410XS5J. LUCA.
GeneTreeiENSGT00390000014570.
HOGENOMiHOG000115323.
InParanoidiQ9NXG6.
KOiK06711.
OMAiNMDLRDF.
OrthoDBiEOG091G04NW.
PhylomeDBiQ9NXG6.
TreeFamiTF332923.

Family and domain databases

CDDicd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
IPR006620. Pro_4_hyd_alph.
[Graphical view]
PfamiPF13640. 2OG-FeII_Oxy_3. 1 hit.
PF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTiSM00702. P4Hc. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS51471. FE2OG_OXY. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

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

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

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

MaxQBiQ9NXG6.
PaxDbiQ9NXG6.
PeptideAtlasiQ9NXG6.
PRIDEiQ9NXG6.

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.
GeneCardsiP4HTM.
HGNCiHGNC:28858. P4HTM.
HPAiHPA007199.
MIMi614584. gene.
neXtProtiNX_Q9NXG6.
OpenTargetsiENSG00000178467.
PharmGKBiPA164724295.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1591. Eukaryota.
ENOG410XS5J. LUCA.
GeneTreeiENSGT00390000014570.
HOGENOMiHOG000115323.
InParanoidiQ9NXG6.
KOiK06711.
OMAiNMDLRDF.
OrthoDBiEOG091G04NW.
PhylomeDBiQ9NXG6.
TreeFamiTF332923.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000178467-MONOMER.

Miscellaneous databases

ChiTaRSiP4HTM. human.
GenomeRNAii54681.
PROiQ9NXG6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000178467.
ExpressionAtlasiQ9NXG6. baseline and differential.
GenevisibleiQ9NXG6. HS.

Family and domain databases

CDDicd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
IPR006620. Pro_4_hyd_alph.
[Graphical view]
PfamiPF13640. 2OG-FeII_Oxy_3. 1 hit.
PF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTiSM00702. P4Hc. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS51471. FE2OG_OXY. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiP4HTM_HUMAN
AccessioniPrimary (citable) accession number: Q9NXG6
Secondary accession number(s): Q6PAG6
, Q8TCJ9, Q8WV55, Q96F22, Q9BW77
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 16, 2003
Last sequence update: June 16, 2003
Last modified: November 30, 2016
This is version 149 of the entry and version 2 of the sequence. [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
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.