Reviewed, UniProtKB/Swiss-Prot P69891 (HBG1_HUMAN)

Names and origin

Protein names

Recommended name:
    Hemoglobin subunit gamma-1
Alternative name(s):
    Hemoglobin gamma-1 chain
    Gamma-1-globin
    Hemoglobin gamma-A chain
    Hb F Agamma

Gene names

Name:

HBG1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	147 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	Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.
Subunit structure	Heterotetramer of two alpha chains and two gamma chains in fetal hemoglobin (Hb F). In the case of deletions affecting one or more of the alpha chains the excess gamma chains form homotetramers that exhibit neither Bohr effect nor heme-heme cooperativity (hemoglobin Bart's).
Tissue specificity	Red blood cells.
Developmental stage	Expressed until four or five weeks after birth.
Post-translational modification	Acetylation of Gly-2 converts Hb F to the minor Hb F1.
Involvement in disease	Some gamma variants can cause severe jaundice and cyanosis in premature and new born babies.
Sequence similarities	Belongs to the globin family.

Ontologies

Keywords
Biological process	Oxygen transport Transport
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	Heme Iron Metal-binding
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	oxygen transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	hemoglobin complex Inferred from electronic annotation. Source: InterPro
Molecular function	heme binding Inferred from electronic annotation. Source: InterPro oxygen binding Inferred from electronic annotation. Source: InterPro oxygen transporter activity Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GABARAPL2	P60520	1	EBI-1056789,EBI-720116

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 147

146

Hemoglobin subunit gamma-1

PRO_0000053253

Sites

Metal binding

64

1

Iron (heme distal ligand)

Metal binding

93

1

Iron (heme proximal ligand)

Site

142

1

Susceptible to oxidation; in form M Probable

Amino acid modifications

Modified residue

2

1

N-acetylglycine; in form Hb F1 Ref.8

Natural variations

Natural variant

3

1

H → Q in Macedonia-I.

VAR_003124

Natural variant

6

1

E → K in Texas-1.

VAR_003125

Natural variant

7

1

E → G in Izumi/Kotobuki.

VAR_003127

Natural variant

7

1

E → Q in Pordenone.

VAR_003128

Natural variant

13

1

T → R in Calluna.

VAR_003130

Natural variant

23

1

D → G in Kuala Lumpur.

VAR_003135

Natural variant

26

1

G → R in Xinjiang; unstable.

VAR_003138

Natural variant

37

1

P → R in Pendergrass.

VAR_003141

Natural variant

38

1

W → G in Cobb.

VAR_003142

Natural variant

40

1

Q → R in Bonaire.

VAR_003143

Natural variant

41

1

R → K in Woodstock.

VAR_003145

Natural variant

44

1

D → N in Fukuyama.

VAR_003147

Natural variant

54

1

A → D in Beech island.

VAR_003149

Natural variant

62

1

K → E in Jamaica.

VAR_003153

Natural variant

73

1

G → R in Iwata.

VAR_003158

Natural variant

74

1

D → H in Xin-su.

VAR_003160

Natural variant

74

1

D → N in Forest Park; associated with T-76.

VAR_003159

Natural variant

76

1

I → T in Sardinia/Forest Park; associated with N-74. dbSNP rs1061234.

VAR_003161

Natural variant

80

1

D → N in Dammam.

VAR_003163

Natural variant

81

1

D → N in Yamaguchi.

VAR_003165

Natural variant

81

1

D → Y in Victoria jubilee.

VAR_003164

Natural variant

98

1

H → R in Dickinson.

VAR_003168

Natural variant

122

1

E → K in Siena/Hull.

VAR_003173

Natural variant

129

1

A → T in Baskent.

VAR_003175

Natural variant

135

1

V → M in Jiangsu.

VAR_003177

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

147

Helix Strand Turn

Details...

Helix

6 – 17

12

Helix

21 – 35

15

Helix

37 – 46

10

Helix

52 – 57

6

Helix

59 – 75

17

Helix

76 – 81

6

Helix

82 – 85

4

Helix

87 – 94

8

Turn

95 – 97

3

Helix

101 – 119

19

Helix

120 – 122

3

Helix

125 – 142

18

Helix

144 – 146

3

Sequences

	Sequence		Length	Mass (Da)
	P69891-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 8FCDC3DA1B416DDE	FASTA	147	16,140
	10 20 30 40 50 60 MGHFTEEDKA TITSLWGKVN VEDAGGETLG RLLVVYPWTQ RFFDSFGNLS SASAIMGNPK 70 80 90 100 110 120 VKAHGKKVLT SLGDAIKHLD DLKGTFAQLS ELHCDKLHVD PENFKLLGNV LVTVLAIHFG 130 140 KEFTPEVQAS WQKMVTAVAS ALSSRYH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human fetal G gamma- and A gamma-globin genes: complete nucleotide sequences suggest that DNA can be exchanged between these duplicated genes." Slightom J.L., Blechl A.E., Smithies O. Cell 21:627-638(1980) [PubMed: 7438203] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"A history of the human fetal globin gene duplication." Shen S., Slightom J.L., Smithies O. Cell 26:191-203(1981) [PubMed: 7332928] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-76. Tissue: Lung and Placenta.
[4]	Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-60; 67-77 AND 84-145, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[5]	"The M gamma chain of human fetal hemoglobin is an A gamma chain with an in vitro modification of gamma 141 leucine to hydroxyleucine." Wilson J.B., Brennan S.O., Allen J., Shaw J.G., Gu L.H., Huisman T.H. J. Chromatogr. A 617:37-42(1993) [PubMed: 7690768] [Abstract] Cited for: OXIDATION AT LEU-142.
[6]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[7]	"Oligomerization and ligand binding in a homotetrameric hemoglobin: two high-resolution crystal structures of hemoglobin Bart's (gamma(4)), a marker for alpha-thalassemia." Kidd R.D., Baker H.M., Mathews A.J., Brittain T., Baker E.N. Protein Sci. 10:1739-1749(2001) [PubMed: 11514664] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF HOMOTETRAMER.
[8]	"Human fetal hemoglobin F 1. Acetylation status." Stegink L.D., Meyer P.D., Brummel M.C. J. Biol. Chem. 246:3001-3007(1971) [PubMed: 5554303] [Abstract] Cited for: ACETYLATION AT GLY-2.
[9]	"Hb F-Baskent or alpha 2A gamma 128(H6)Ala-->Thr." Altay C., Gurgey A., Wilson J.B., Hu H., Webber B.B., Kutlar F., Huisman T.H.J. Hemoglobin 12:87-89(1988) [PubMed: 2454900] [Abstract] Cited for: VARIANT BASKENT THR-129.
[10]	"Hb F-Beech Island or alpha 2A gamma 2(53)(D4)Ala-->Asp." Chen S.S., Wilson J.B., Webber B.B., Huisman T.H.J. Hemoglobin 9:525-529(1985) [PubMed: 2417989] [Abstract] Cited for: VARIANT BEECH ISLAND ASP-54.
[11]	"Hb F-Bonaire-Ga or alpha 2 A gamma 2 39(C5) Gln replaced by Arg, characterized by high pressure liquid chromatographic and microsequencing procedures." Nakatsuji T., Headlee M., Lam H., Wilson J.B., Huisman T.H.J. Hemoglobin 6:599-606(1982) [PubMed: 6186637] [Abstract] Cited for: VARIANT BONAIRE ARG-40.
[12]	"Hb F-Calluna or alpha 2 gamma 2(12 Thr replaced by Arg; 75Ile; 136Ala) in a Caucasian baby." Nakatsuji T., Lam H., Huisman T.H.J. Hemoglobin 7:563-566(1983) [PubMed: 6199326] [Abstract] Cited for: VARIANT CALLUNA ARG-13.
[13]	"Hb F-Cobb or alpha(2)A gamma(2)37(C3)Trp-->Gly." Chen S.S., Webber B.B., Kutlar A., Wilson J.B., Huisman T.H.J. Hemoglobin 9:617-619(1985) [PubMed: 2419280] [Abstract] Cited for: VARIANT COBB GLY-38.
[14]	"Hb F-Dammam or alpha 2A gamma 2(79) (EF3) Asp-->Asn." Al-Awamy B.H., Niazi G.A., Al-Mouzan M.I., Wilson J.B., Chen S.S., Webber B.B., Huisman T.H.J. Hemoglobin 9:171-173(1985) [PubMed: 2411679] [Abstract] Cited for: VARIANT DAMMAM ASN-80.
[15]	"Genetic haemoglobin abnormalities in about 9000 Black and 7000 White newborns; haemoglobin F Dickinson (Agamma97His-Arg), a new variant." Schneider R.G., Haggard M.E., Gustavson L.P., Brimhall B., Jones R.T. Br. J. Haematol. 28:515-524(1974) [PubMed: 4455303] [Abstract] Cited for: VARIANT DICKINSON ARG-98.
[16]	"Hb F-Fukuyama or A gamma T43(CD2)Asp-->Asn." Hidaka K., Iuchi I., Nakahara H., Iwakawa G. Hemoglobin 13:93-96(1989) [PubMed: 2467893] [Abstract] Cited for: VARIANT FUKUYAMA ASN-44.
[17]	"Haemoglobin F Hull (gamma-121 glutamic acid-->lysine), homologous with haemoglobins O Arab and O Indonesia." Sacker L.S., Beale D., Black A.J., Huntsman R.G., Lehmann H., Lorkin P.A. BMJ 3:531-533(1967) [PubMed: 6038320] [Abstract] Cited for: VARIANT HULL LYS-122.
[18]	"Survey of cord blood hemoglobin in Japan and identification of two new gamma chain variants." Fuyuno K., Torigoe T., Ohba Y., Matsuoka M., Miyaji T. Hemoglobin 5:139-151(1981) [PubMed: 6163752] [Abstract] Cited for: VARIANT IWATA ARG-73.
[19]	"Characterization of a new fetal hemoglobin variant, Hb F Izumi A gamma 6Glu replaced by Gly, by molecular secondary ion mass spectrometry." Wada Y., Hayashi A., Masanori F., Katakuse I., Ichihara T., Nakabushi H., Matsuo T., Sakurai T., Matsuda H. Biochim. Biophys. Acta 749:244-248(1983) [PubMed: 6197997] [Abstract] Cited for: VARIANT IZUMI GLY-7.
[20]	"Haemoglobin F Jamaica (alpha-2 gamma-2 61 Lys leads to Glu; 136 Ala)." Ahern E.J., Jones R.T., Brimhall B., Gray R.H. Br. J. Haematol. 18:369-375(1970) [PubMed: 5491586] [Abstract] Cited for: VARIANT JAMAICA GLU-62.
[21]	"Hb F-Jiangsu, the first gamma chain variant with a valine->methionine substitution: alpha 2A gamma 2 134(H12)Val->Met." Plaseska D., Kutlar F., Wilson J.B., Webber B.B., Zeng Y.-T., Huisman T.H.J. Hemoglobin 14:177-183(1990) [PubMed: 1703137] [Abstract] Cited for: VARIANT JIANGSU MET-135.
[22]	"A new gamma chain variant, HB F Kotobuki or AI gamma 6 (A3) Glu leads to Gly." Yoshinaka H., Ohba Y., Hattori Y., Matsuoka M., Miyaji T., Fuyuno K. Hemoglobin 6:37-42(1982) [PubMed: 6175602] [Abstract] Cited for: VARIANT KOTOBUKI GLY-7.
[23]	"Structural identification of haemoglobin F Kuala Lumpur: alpha2 gamma2 22(B4)Asp leads to Gly; 136 Ala." Lie-Injo L.E., Wiltshire B.B., Lehmann H. Biochim. Biophys. Acta 322:224-230(1973) [PubMed: 4765089] [Abstract] Cited for: VARIANT KUALA LUMPUR GLY-23.
[24]	"Hb F-Macedonia-I or alpha 2A gamma (2)2(NA2)His-->Gln." Plaseska D., Cepreganova-Krstik B., Momirovska A., Efremov G.D. Hemoglobin 18:241-245(1994) [PubMed: 7928382] [Abstract] Cited for: VARIANT MACEDONIA-I GLN-3.
[25]	"Hb F-Pendergrass, an A gamma I variant with a Pro-->Arg substitution at position gamma 36(C2)." Chen S.S., Wilson J.B., Huisman T.H.J. Hemoglobin 9:73-77(1985) [PubMed: 2581920] [Abstract] Cited for: VARIANT PENDERGRASS ARG-37.
[26]	"A new gamma chain variant: Hb F-Pordenone [gamma 6(A3) Glu replaced by Gln: 75ILE: 136ALA]." Nakatsuji T., Webber B., Lam H., Wilson J.B., Huisman T.H.J., Sciarratta G.V., Sansone G., Molaro G.L. Hemoglobin 6:397-401(1982) [PubMed: 6183236] [Abstract] Cited for: VARIANT PORDENONE GLN-7.
[27]	"A new Hb variant: Hb F Sardinia gamma75(E19) isoleucine leads to threonine found in a family with Hb G Philadelphia, beta-chain deficiency and a Lepore-like haemoglobin indistinguishable from Hb A2." Grifone V., Kamuzora H., Lehmann H., Charlesworth D. Acta Haematol. 53:347-355(1975) [PubMed: 808940] [Abstract] Cited for: VARIANT SARDINIA THR-76.
[28]	"Hb F-Siena (alpha 2 a gamma t2 121 (GH4) Glu leads to Lys). A new fetal hemoglobin variant." Care A., Marinucci M., Massa A., Maffi D., Sposi N.M., Improta T., Tentori L. Hemoglobin 7:79-83(1983) [PubMed: 6188719] [Abstract] Cited for: VARIANT SIENA LYS-122.
[29]	"Haemoglobin F Texas I(alpha-2,gamma-2-5glu-lys): a variant of haemoglobin F." Jenkins G.C., Beale D., Black A.J., Huntsman R.G., Lehmann H. Br. J. Haematol. 13:252-255(1967) [PubMed: 6019034] [Abstract] Cited for: VARIANT TEXAS-1 LYS-6.
[30]	"Haemoglobin F Victoria Jubilee (alpha 2 A gamma 2 80 Asp-Try)." Ahern E., Holder W., Ahern V., Serjeant G.R., Serjeant B., Forbes M., Brimhall B., Jones R.T. Biochim. Biophys. Acta 393:188-194(1975) [PubMed: 1138921] [Abstract] Cited for: VARIANT VICTORIA JUBILEE TYR-81.
[31]	"Gamma chain abnormalities and gamma-globin gene rearrangements in newborn babies of various populations." Huisman T.H.J., Kutlar F., Gu L.H. Hemoglobin 15:349-379(1991) [PubMed: 1802881] [Abstract] Cited for: VARIANT WOODSTOCK LYS-41.
[32]	"Hb F-Xin-Su or A gamma I73(E17)Asp-->His: a new slow-moving fetal hemoglobin variant." Ma M., Hu H., Kutlar F., Wilson J.B., Huisman T.H.J. Hemoglobin 11:473-479(1987) [PubMed: 2448269] [Abstract] Cited for: VARIANT XIN-SU HIS-74.
[33]	"Hb F-Xinjiang or A gamma T25(B7)Gly-->Arg: a new slow-moving unstable fetal hemoglobin variant." Hu H., Ma M. Hemoglobin 11:465-472(1987) [PubMed: 2448268] [Abstract] Cited for: VARIANT XINJIANG ARG-26.
[34]	"HB F-Yamaguchi (gamma 75Thr, gamma 80Asn, gamma 136Ala) is associated with G gamma-thalassemia." Nakatsuji T., Ohba Y., Huisman T.H.J. Am. J. Hematol. 16:189-192(1984) [PubMed: 6198905] [Abstract] Cited for: VARIANT YAMAGUCHI ASN-81.
+	Additional computationally mapped references.

Web resources

HbVar

Human hemoglobin variants and thalassemias

Cross-references

Sequence databases

EMBLGenBankDDBJ

M91036 Genomic DNA. Translation: AAB59429.1.
M91037 Genomic DNA. Translation: AAA58493.1.
V00513 Genomic DNA. Translation: CAA23771.1.
V00514 Genomic DNA. Translation: CAA23772.1.
J00176 Genomic DNA. Translation: AAA52637.1.
U01317 Genomic DNA. Translation: AAA16332.1.
BC010913 mRNA. Translation: AAH10913.1.
BC020719 mRNA. Translation: AAH20719.1.

IPI

IPI00220706.

PIR

HGHUA. A90803.

UniGene

Hs.712539

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1I3D	X-ray	1.70	A/B	2-147	[»]
1I3E	X-ray	1.86	A/B	2-147	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P69891. 1 interaction.

PTM databases

PhosphoSite

P69891.

Proteomic databases

PRIDE

P69891.

Genome annotation databases

Ensembl

ENSG00000196565. Homo sapiens. [Contig view]

UCSC

uc001mai.1. human.

Organism-specific databases

GeneCards

GC11M005226.

HGNC

HGNC:4831. HBG1.

MIM

142200. gene.

PharmGKB

PA29206.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P69891.

Gene expression databases

ArrayExpress

P69891.

CleanEx

HS_HBG1.

GermOnline

ENSG00000196565. Homo sapiens.

Family and domain databases

InterPro

IPR012292. Globin.
IPR000971. Globin_subset.
IPR002337. Haemoglobin_b.
[Graphical view]

Gene3D

G3DSA:1.10.490.10. Globin_related. 1 hit.

PANTHER

PTHR11442:SF7. Beta_haem. 1 hit.

Pfam

PF00042. Globin. 1 hit.
[Graphical view]

PRINTS

PR00814. BETAHAEM.

PROSITE

PS01033. GLOBIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

SOURCE

Search...

Entry information

Entry name

HBG1_HUMAN

Accession

Primary (citable) accession number: P69891
Secondary accession number(s): P02096, P62027, Q96FH7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	July 7, 2009
This is version 67 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)