P22830 (HEMH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ferrochelatase, mitochondrial
EC=4.99.1.1

Alternative name(s):
Heme synthase
Protoheme ferro-lyase

Gene names

Name:

FECH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	423 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the ferrous insertion into protoporphyrin IX.
Catalytic activity	Protoheme + 2 H+ = protoporphyrin + Fe2+.
Cofactor	Binds 1 2Fe-2S cluster.
Enzyme regulation	Inhibited by nitric oxide (NO). The 2Fe-2S cluster could act as a NO sensor.
Pathway	Porphyrin-containing compound metabolism; protoheme biosynthesis; protoheme from protoporphyrin-IX: step 1/1.
Subunit structure	Homodimer. Ref.14
Subcellular location	Mitochondrion inner membrane; Peripheral membrane protein; Matrix side.
Involvement in disease	Erythropoietic protoporphyria (EPP) [MIM:177000]: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Erythropoietic protoporphyria is marked by excessive protoporphyrin in erythrocytes, plasma, liver and feces, and by widely varying photosensitive skin changes ranging from a burning or pruritic sensation to erythema, edema and wheals. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27
Sequence similarities	Belongs to the ferrochelatase family.

Ontologies

Keywords
Biological process	Heme biosynthesis Porphyrin biosynthesis
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	2Fe-2S Iron Iron-sulfur Metal-binding
Molecular function	Lyase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol metabolic process Inferred from electronic annotation. Source: Compara detection of UV Inferred from electronic annotation. Source: Compara erythrocyte differentiation Inferred from electronic annotation. Source: Compara generation of precursor metabolites and energy Traceable author statement PubMed 1729699. Source: ProtInc heme biosynthetic process Traceable author statement. Source: Reactome iron ion homeostasis Inferred from electronic annotation. Source: Compara protoporphyrinogen IX metabolic process Inferred from direct assay PubMed 15123683. Source: BHF-UCL regulation of eIF2 alpha phosphorylation by heme Inferred from electronic annotation. Source: Compara regulation of hemoglobin biosynthetic process Inferred from electronic annotation. Source: Compara response to light stimulus Traceable author statement Ref.17. Source: ProtInc small molecule metabolic process Traceable author statement. Source: Reactome very-low-density lipoprotein particle assembly Inferred from electronic annotation. Source: Compara
Cellular_component	mitochondrial inner membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	2 iron, 2 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW ferrochelatase activity Inferred from direct assay PubMed 15123683. Source: BHF-UCL ferrous iron binding Traceable author statement PubMed 1729699. Source: ProtInc heme binding Inferred from electronic annotation. Source: Compara iron-responsive element binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P22830-1)

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.

Isoform 2 (identifier: P22830-2)

The sequence of this isoform differs from the canonical sequence as follows:
     64-64: K → KRYESNI

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 54

54

Mitochondrion Potential

Chain

55 – 423

369

Ferrochelatase, mitochondrial

PRO_0000008873

Sites

Active site

230

1

Active site

383

1

Metal binding

196

1

Iron-sulfur (2Fe-2S)

Metal binding

403

1

Iron-sulfur (2Fe-2S)

Metal binding

406

1

Iron-sulfur (2Fe-2S)

Metal binding

411

1

Iron-sulfur (2Fe-2S)

Natural variations

Alternative sequence

64

1

K → KRYESNI in isoform 2.

VSP_041208

Natural variant

55

1

G → C in EPP. Ref.16
Corresponds to variant rs3848519 [ dbSNP | Ensembl ].

VAR_002383

Natural variant

62

1

P → R in EPP. Ref.24

VAR_030553

Natural variant

71

1

I → K in EPP; enzyme totally inactive. Ref.20

VAR_030554

Natural variant

96

1

R → Q. Ref.1 Ref.2
Corresponds to variant rs1041951 [ dbSNP | Ensembl ].

VAR_012028

Natural variant

139

1

Q → L in EPP; autosomal recessive EPP; enzyme retains 18% of activity. Ref.26

VAR_030555

Natural variant

151

1

S → P in EPP; enzyme totally inactive. Ref.20

VAR_030556

Natural variant

178

1

E → K in EPP. Ref.25

VAR_030557

Natural variant

182

1

L → R in EPP; enzyme totally inactive. Ref.23

VAR_030558

Natural variant

186

1

I → T in EPP. Ref.19

VAR_002384

Natural variant

191

1

Y → H in EPP; enzyme retains 72% of activity. Ref.20

VAR_030559

Natural variant

192

1

P → T in EPP; enzyme totally inactive. Ref.20

VAR_030560

Natural variant

236

1

C → Y in EPP; enzyme retains 12% of activity. Ref.26

VAR_030561

Natural variant

260

1

F → L in EPP; autosomal recessive EPP; enzyme retains 52% of activity. Ref.26

VAR_030562

Natural variant

264

1

S → L in EPP. Ref.27

VAR_054629

Natural variant

267

1

M → I in EPP; unchanged activity; but increased thermolability. Ref.16

VAR_002385

Natural variant

283

1

T → I in EPP; enzyme almost inactive. Ref.20

VAR_030563

Natural variant

288

1

M → K in EPP; enzyme totally inactive. Ref.20

VAR_030564

Natural variant

334

1

P → L in EPP; autosomal recessive EPP; enzyme retains 19% of activity. Ref.20 Ref.25

VAR_030565

Natural variant

362

1

V → G in EPP. Ref.18

VAR_030566

Natural variant

379

1

K → N in EPP; autosomal recessive EPP; enzyme retains 37% of activity. Ref.26

VAR_030567

Natural variant

386

1

H → P in EPP; loss of activity. Ref.21

VAR_002386

Natural variant

406

1

C → S in EPP; enzyme almost inactive. Ref.22

VAR_030568

Natural variant

406

1

C → Y in EPP; enzyme almost inactive. Ref.22

VAR_030569

Natural variant

408 – 411

4

NPVC → KSVG in EPP; no detectable enzymatic activity.

VAR_030570

Natural variant

417

1

F → S in EPP; reduced activity. Ref.17

VAR_002387

Natural variant

417

1

Missing in EPP; enzyme totally inactive. Ref.20

VAR_030571

Experimental info

Mutagenesis

196

1

C → S: Loss of activity.

Mutagenesis

360

1

C → S: No loss of activity.

Mutagenesis

395

1

C → S: No loss of activity.

Mutagenesis

403

1

C → D or H: Loss of activity.

Mutagenesis

406

1

C → D, H or S: Loss of activity.

Mutagenesis

411

1

C → H or S: Loss of activity.

Mutagenesis

417

1

F → L: Decreased activity.

Mutagenesis

417

1

F → Y or W: Greatly reduced activity.

Sequence conflict

228

1

P → S in BAC03882. Ref.4

Secondary structure

1

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423

Helix Strand Turn

Details...

Beta strand

69 – 75

7

Helix

82 – 84

3

Helix

85 – 93

9

Turn

96 – 98

3

Helix

104 – 125

22

Helix

132 – 150

19

Helix

152 – 154

3

Beta strand

156 – 169

14

Helix

170 – 179

10

Beta strand

183 – 190

8

Turn

196 – 198

3

Helix

199 – 212

14

Beta strand

218 – 224

7

Helix

231 – 245

15

Turn

250 – 252

3

Helix

253 – 255

3

Beta strand

257 – 263

7

Helix

267 – 270

4

Turn

271 – 273

3

Helix

276 – 290

15

Turn

291 – 293

3

Beta strand

297 – 302

6

Beta strand

306 – 308

3

Beta strand

310 – 314

5

Helix

315 – 324

10

Beta strand

329 – 333

5

Helix

345 – 348

4

Helix

350 – 359

10

Beta strand

364 – 367

4

Beta strand

371 – 373

3

Helix

375 – 391

17

Helix

397 – 400

4

Helix

410 – 419

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 10, 2005. Version 2. Checksum: 3FD50965E8DEABCE	FASTA	423	47,862
	10 20 30 40 50 60 MRSLGANMAA ALRAAGVLLR DPLASSSWRV CQPWRWKSGA AAAAVTTETA QHAQGAKPQV 70 80 90 100 110 120 QPQKRKPKTG ILMLNMGGPE TLGDVHDFLL RLFLDRDLMT LPIQNKLAPF IAKRRTPKIQ 130 140 150 160 170 180 EQYRRIGGGS PIKIWTSKQG EGMVKLLDEL SPNTAPHKYY IGFRYVHPLT EEAIEEMERD 190 200 210 220 230 240 GLERAIAFTQ YPQYSCSTTG SSLNAIYRYY NQVGRKPTMK WSTIDRWPTH HLLIQCFADH 250 260 270 280 290 300 ILKELDHFPL EKRSEVVILF SAHSLPMSVV NRGDPYPQEV SATVQKVMER LEYCNPYRLV 310 320 330 340 350 360 WQSKVGPMPW LGPQTDESIK GLCERGRKNI LLVPIAFTSD HIETLYELDI EYSQVLAKEC 370 380 390 400 410 420 GVENIRRAES LNGNPLFSKA LADLVHSHIQ SNELCSKQLT LSCPLCVNPV CRETKSFFTS QQL
	Isoform 2 [UniParc]. Checksum: E1CBA7E0055A24F5	FASTA	429	48,625
	10 20 30 40 50 60 MRSLGANMAA ALRAAGVLLR DPLASSSWRV CQPWRWKSGA AAAAVTTETA QHAQGAKPQV 70 80 90 100 110 120 QPQKRYESNI RKPKTGILML NMGGPETLGD VHDFLLRLFL DRDLMTLPIQ NKLAPFIAKR 130 140 150 160 170 180 RTPKIQEQYR RIGGGSPIKI WTSKQGEGMV KLLDELSPNT APHKYYIGFR YVHPLTEEAI 190 200 210 220 230 240 EEMERDGLER AIAFTQYPQY SCSTTGSSLN AIYRYYNQVG RKPTMKWSTI DRWPTHHLLI 250 260 270 280 290 300 QCFADHILKE LDHFPLEKRS EVVILFSAHS LPMSVVNRGD PYPQEVSATV QKVMERLEYC 310 320 330 340 350 360 NPYRLVWQSK VGPMPWLGPQ TDESIKGLCE RGRKNILLVP IAFTSDHIET LYELDIEYSQ 370 380 390 400 410 420 VLAKECGVEN IRRAESLNGN PLFSKALADL VHSHIQSNEL CSKQLTLSCP LCVNPVCRET KSFFTSQQL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and sequence analysis of cDNA encoding human ferrochelatase." Nakahashi Y., Taketani S., Okuda M., Inoue K., Tokunaga R. Biochem. Biophys. Res. Commun. 173:748-755(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLN-96.
[2]	"Ferrochelatase: complete human gene sequence, amplifiable polymorphisms and molecular study of 12 families with erythropoietic protoporphyria." Gouya L.M., Martin C., Deybach J.-C., Puy H.V. Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-96.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Placenta and Trachea.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[7]	"A single promoter directs both housekeeping and erythroid preferential expression of the human ferrochelatase gene." Tugores A., Magness S.T., Brenner D.A. J. Biol. Chem. 269:30789-30797(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
[8]	"Molecular analysis of ferrochelatase gene in erythropoietic protoporphyria." Di Pierro E., Martinez di Montemuros F., Moriondo V., Cappellini M.D. Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
[9]	"Mammalian ferrochelatase. Expression and characterization of normal and two human protoporphyric ferrochelatases." Dailey H.A., Sellers V.M., Dailey T.A. J. Biol. Chem. 269:390-395(1994) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION, MUTAGENESIS.
[10]	"Site-directed mutagenesis and spectroscopic characterization of human ferrochelatase: identification of residues coordinating the [2Fe-2S] cluster." Crouse B.R., Sellers V.M., Finnegan M.G., Dailey H.A., Johnson M.K. Biochemistry 35:16222-16229(1996) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF CYSTEINES COORDINATING THE 2FE-2S CLUSTER.
[11]	"Evidence that the fourth ligand to the 2Fe-2S cluster in animal ferrochelatase is a cysteine. Characterization of the enzyme from Drosophila melanogaster." Sellers V.M., Wang K.-F., Johnson M.K., Dailey H.A. J. Biol. Chem. 273:22311-22316(1998) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF CYSTEINES COORDINATING THE 2FE-2S CLUSTER.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis." Wu C.-K., Dailey H.A., Rose J.P., Burden A., Sellers V.M., Wang B.-C. Nat. Struct. Biol. 8:156-160(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[14]	"Substrate interactions with human ferrochelatase." Medlock A., Swartz L., Dailey T.A., Dailey H.A., Lanzilotta W.N. Proc. Natl. Acad. Sci. U.S.A. 104:1789-1793(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 65-423 ALONE AND IN COMPLEX WITH PROTOPORPHYRIN IX, SUBUNIT, IRON-SULFUR CLUSTER.
[15]	"Erythropoietic protoporphyria." Cox T.M. J. Inherit. Metab. Dis. 20:258-269(1997) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON VARIANTS EPP.
[16]	"Human erythropoietic protoporphyria: two point mutations in the ferrochelatase gene." Lamoril J., Boulechfar S., de Verneuil H., Grandchamp B., Nordmann Y., Deybach J.-C. Biochem. Biophys. Res. Commun. 181:594-599(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EPP CYS-55 AND ILE-267.
[17]	"A molecular defect in human protoporphyria." Brenner D.A., Didier J.M., Frasier F., Christensen S.R., Evans G.A., Dailey H.A. Am. J. Hum. Genet. 50:1203-1210(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EPP SER-417.
[18]	"Recessive inheritance of erythropoietic protoporphyria with liver failure." Sarkany R.P.E., Alexander G.J.M.A., Cox T.M. Lancet 343:1394-1396(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EPP GLY-362.
[19]	"A novel mutation in the ferrochelatase gene associated with erythropoietic protoporphyria." Imoto S., Tanizawa Y., Sata Y., Kaku K., Oka Y. Br. J. Haematol. 94:191-197(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EPP THR-186.
[20]	"Systematic analysis of molecular defects in the ferrochelatase gene from patients with erythropoietic protoporphyria." Ruefenacht U.B., Gouya L., Schneider-Yin X., Puy H., Schaefer B.W., Aquaron R., Nordmann Y., Minder E.I., Deybach J.-C. Am. J. Hum. Genet. 62:1341-1352(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EPP LYS-71; PRO-151; HIS-191; THR-192; ILE-283; LYS-288; LEU-334 AND PHE-417 DEL, CHARACTERIZATION OF VARIANTS EPP LYS-71; PRO-151; HIS-191; THR-192; ILE-283; LYS-288; LEU-334 AND PHE-417 DEL.
[21]	"Mutations in the ferrochelatase gene of four Spanish patients with erythropoietic protoporphyria." Gouya L., Schneider-Yin X., Rufenacht U., Herrero C., Lecha M., Mascaro J.M., Puy H., Deybach J.-C., Minder E.I. J. Invest. Dermatol. 111:406-409(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EPP PRO-386.
[22]	"Mutations in the iron-sulfur cluster ligands of the human ferrochelatase lead to erythropoietic protoporphyria." Schneider-Yin X., Gouya L., Dorsey M., Ruefenacht U., Deybach J.-C., Ferreira G.C. Blood 96:1545-1549(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EPP SER-406; TYR-406 AND 408-LYS-SER--GLY-411, CHARACTERIZATION OF VARIANTS EPP SER-406; TYR-406 AND 408-LYS-SER--GLY-411.
[23]	"New missense mutation in the human ferrochelatase gene in a family with erythropoietic protoporphyria: functional studies and correlation of genotype and phenotype." Ruefenacht U.B., Gregor A., Gouya L., Tarczynska-Nosal S., Schneider-Yin X., Deybach J.-C. Clin. Chem. 47:1112-1113(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EPP ARG-182, CHARACTERIZATION OF VARIANT EPP ARG-182.
[24]	"Erythropoietic protoporphyria: altered phenotype after bone marrow transplantation for myelogenous leukemia in a patient heteroallelic for ferrochelatase gene mutations." Poh-Fitzpatrick M.B., Wang X., Anderson K.E., Bloomer J.R., Bolwell B., Lichtin A.E. J. Am. Acad. Dermatol. 46:861-866(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EPP ARG-62.
[25]	"Novel mutations and phenotypic effect of the splice site modulator IVS3-48C in nine Swedish families with erythropoietic protoporphyria." Wiman A., Floderus Y., Harper P. J. Hum. Genet. 48:70-76(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EPP LYS-178 AND LEU-334.
[26]	"Autosomal recessive erythropoietic protoporphyria in the United Kingdom: prevalence and relationship to liver disease." Whatley S.D., Mason N.G., Khan M., Zamiri M., Badminton M.N., Missaoui W.N., Dailey T.A., Dailey H.A., Douglas W.S., Wainwright N.J., Elder G.H. J. Med. Genet. 41:E105-E105(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EPP LEU-139; TYR-236; LEU-260 AND ASN-379, CHARACTERIZATION OF VARIANTS EPP LEU-139; TYR-236; LEU-260 AND ASN-379.
[27]	"Heterogeneity of mutations in the ferrochelatase gene in Italian patients with erythropoietic protoporphyria." Aurizi C., Schneider-Yin X., Sorge F., Macri A., Minder E.I., Biolcati G. Mol. Genet. Metab. 90:402-407(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT EPP LEU-264.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Ferrochelatase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D00726 mRNA. Translation: BAA00628.1.
AJ250235 Genomic DNA. Translation: CAB65962.1.
BT019958 mRNA. Translation: AAV38761.1.
AK092416 mRNA. Translation: BAC03882.1.
AK292937 mRNA. Translation: BAF85626.1.
CH471096 Genomic DNA. Translation: EAW63046.1.
BC039841 mRNA. Translation: AAH39841.2.
L36178 Genomic DNA. Translation: AAA64787.1.
AF495859 Genomic DNA. Translation: AAM18070.1.

IPI

IPI00027776.
IPI00554589.

PIR

A36403.

RefSeq

NP_000131.2. NM_000140.3.
NP_001012533.1. NM_001012515.2.

UniGene

Hs.365365.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HRK	X-ray	2.00	A/B	65-423	[»]
2HRC	X-ray	1.70	A/B	65-423	[»]
2HRE	X-ray	2.50	A/B/C/D	65-423	[»]
2PNJ	X-ray	2.35	A/B	65-423	[»]
2PO5	X-ray	2.20	A/B	65-423	[»]
2PO7	X-ray	2.20	A/B	65-423	[»]
2QD1	X-ray	2.20	A/B/C/D	65-423	[»]
2QD2	X-ray	2.20	A/B	65-423	[»]
2QD3	X-ray	2.20	A/B	65-423	[»]
2QD4	X-ray	2.00	A/B	65-423	[»]
2QD5	X-ray	2.30	A/B	65-423	[»]
3AQI	X-ray	1.70	A/B	65-423	[»]
3HCN	X-ray	1.60	A/B	65-423	[»]
3HCO	X-ray	1.80	A/B	65-423	[»]
3HCP	X-ray	2.00	A/B	65-423	[»]
3HCR	X-ray	2.20	A/B	65-423	[»]
4F4D	X-ray	1.80	A/B	65-423	[»]
4F4G	X-ray	2.50	A/B	65-423	[»]

ProteinModelPortal

P22830.

ModBase

Search...

Protein-protein interaction databases

IntAct

P22830. 5 interactions.

STRING

9606.ENSP00000372326.

PTM databases

PhosphoSite

P22830.

Polymorphism databases

DMDM

85701348.

Proteomic databases

PaxDb

P22830.

PRIDE

P22830.

Protocols and materials databases

DNASU

2235.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262093; ENSP00000262093; ENSG00000066926.
ENST00000382873; ENSP00000372326; ENSG00000066926.

GeneID

2235.

KEGG

hsa:2235.

UCSC

uc002lgp.4. human.
uc002lgq.4. human.

Organism-specific databases

CTD

2235.

GeneCards

GC18M055191.

HGNC

HGNC:3647. FECH.

HPA

CAB033205.

MIM

177000. phenotype.
612386. gene.

neXtProt

NX_P22830.

Orphanet

79278. Erythropoietic protoporphyria.

PharmGKB

PA28087.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0276.

HOGENOM

HOG000060727.

HOVERGEN

HBG051898.

KO

K01772.

OMA

TLYELDM.

OrthoDB

EOG4GXFN0.

PhylomeDB

P22830.

Enzyme and pathway databases

BRENDA

4.99.1.1. 2681.

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P22830.

UniPathway

UPA00252; UER00325.

Gene expression databases

ArrayExpress

P22830.

Bgee

P22830.

CleanEx

HS_FECH.

Genevestigator

P22830.

GermOnline

ENSG00000066926. Homo sapiens.

Family and domain databases

InterPro

IPR001015. Ferrochelatase.
IPR019772. Ferrochelatase_AS.
[Graphical view]

PANTHER

PTHR11108. PTHR11108. 1 hit.

Pfam

PF00762. Ferrochelatase. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00109. hemH. 1 hit.

PROSITE

PS00534. FERROCHELATASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

FECH. human.

EvolutionaryTrace

P22830.

GenomeRNAi

2235.

NextBio

9047.

SOURCE

Search...

Entry information

Entry name

HEMH_HUMAN

Accession

Primary (citable) accession number: P22830
Secondary accession number(s): A8KA72, Q8IXN1, Q8NAN0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	May 10, 2005
Last modified:	May 29, 2013
This is version 147 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.