P03451 (HEMA_I57A0) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hemagglutinin

Cleaved into the following 2 chains:

1. Hemagglutinin HA1 chain
2. Hemagglutinin HA2 chain

Gene names

Name:

HA

Organism

Influenza A virus (strain A/Japan/305/1957 H2N2)

Taxonomic identifier

387161 [NCBI]

Taxonomic lineage

Viruses › ssRNA viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus A › Influenza A virus › H2N2 subtype

Virus host

Aves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	562 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	Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore. Ref.3
Subunit structure	Homotrimer of disulfide-linked HA1-HA2.
Subcellular location	Virion membrane; Single-pass type I membrane protein Potential. Host apical cell membrane; Single-pass type I membrane protein. Note: Targeted to the apical plasma membrane in epithelial polarized cells through a signal present in the transmembrane domain. Associated with glycosphingolipid- and cholesterol-enriched detergent-resistant lipid rafts.
Post-translational modification	In natural infection, inactive HA is matured into HA1 and HA2 outside the cell by one or more trypsin-like, arginine-specific endoprotease secreted by the bronchial epithelial cells. One identified protease that may be involved in this process is secreted in lungs by Clara cells By similarity. Palmitoylated. Ref.2
Miscellaneous	Major glycoprotein, comprises over 80% of the envelope proteins present in virus particle. The extent of infection into host organism is determined by HA. Influenza viruses bud from the apical surface of polarized epithelial cells (e.g. bronchial epithelial cells) into lumen of lungs and are therefore usually pneumotropic. The reason is that HA is cleaved by tryptase clara which is restricted to lungs. However, HAs of H5 and H7 pantropic avian viruses subtypes can be cleaved by furin and subtilisin-type enzymes, allowing the virus to grow in other organs than lungs. The influenza A genome consist of 8 RNA segments. Genetic variation of hemagglutinin and/or neuraminidase genes results in the emergence of new influenza strains. The mechanism of variation can be the result of point mutations or the result of genetic reassortment between segments of two different strains.
Sequence similarities	Belongs to the influenza viruses hemagglutinin family.

Ontologies

Keywords
Biological process	Clathrin- and caveolin-independent endocytosis of virus by host Clathrin-mediated endocytosis of virus by host Fusion of virus membrane with host endosomal membrane Fusion of virus membrane with host membrane Host-virus interaction Viral attachment to host cell Viral penetration into host cytoplasm Virus endocytosis by host Virus entry into host cell
Cellular component	Host cell membrane Host membrane Membrane Viral envelope protein Virion
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Hemagglutinin
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	3D-structure
Gene Ontology (GO)
Biological_process	viral attachment to host cell Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell via clathrin-mediated endocytosis Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell via membrane fusion with the plasma membrane Inferred from electronic annotation. Source: InterPro
Cellular_component	host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW viral envelope Inferred from electronic annotation. Source: UniProtKB-KW virion membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 15	15	Potential
	Chain	16 – 339	324	Hemagglutinin HA1 chain		PRO_0000039010
	Chain	341 – 562	222	Hemagglutinin HA2 chain		PRO_0000039011
Regions
	Topological domain	16 – 525	510	Extracellular Potential
	Transmembrane	526 – 546	21	Helical; Potential
	Topological domain	547 – 562	16	Cytoplasmic Potential
Sites
	Site	340 – 341	2	Cleavage; by host
Amino acid modifications
	Lipidation	551	1	S-palmitoyl cysteine; by host Ref.2
	Lipidation	558	1	S-palmitoyl cysteine; by host Ref.2
	Lipidation	561	1	S-palmitoyl cysteine; by host Ref.2
	Glycosylation	25	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	26	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	38	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	179	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	180	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	300	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	494	1	N-linked (GlcNAc...); by host Potential
	Disulfide bond	19 ↔ 477		Interchain (between HA1 and HA2 chains) By similarity
	Disulfide bond	57 ↔ 288		By similarity
	Disulfide bond	70 ↔ 82		By similarity
	Disulfide bond	105 ↔ 149		By similarity
	Disulfide bond	292 ↔ 316		By similarity
	Disulfide bond	484 ↔ 488		By similarity
Experimental info
	Mutagenesis	519	1	S → A: No effect on palmitoylation. Ref.2
	Mutagenesis	520	1	S → A: No effect on palmitoylation. Ref.2
	Mutagenesis	551	1	C → A: Loss of palmitoylation. Ref.2
	Mutagenesis	558	1	C → A: Loss of palmitoylation. Ref.2
	Mutagenesis	561	1	C → A: Loss of palmitoylation. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P03451 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 6B7FD0C038993630	FASTA	562	63,119
	10 20 30 40 50 60 MAIIYLILLF TAVRGDQICI GYHANNSTEK VDTNLERNVT VTHAKDILEK THNGKLCKLN 70 80 90 100 110 120 GIPPLELGDC SIAGWLLGNP ECDRLLSVPE WSYIMEKENP RDGLCYPGSF NDYEELKHLL 130 140 150 160 170 180 SSVKHFEKVK ILPKDRWTQH TTTGGSRACA VSGNPSFFRN MVWLTKEGSD YPVAKGSYNN 190 200 210 220 230 240 TSGEQMLIIW GVHHPIDETE QRTLYQNVGT YVSVGTSTLN KRSTPEIATR PKVNGQGGRM 250 260 270 280 290 300 EFSWTLLDMW DTINFESTGN LIAPEYGFKI SKRGSSGIMK TEGTLENCET KCQTPLGAIN 310 320 330 340 350 360 TTLPFHNVHP LTIGECPKYV KSEKLVLATG LRNVPQIESR GLFGAIAGFI EGGWQGMVDG 370 380 390 400 410 420 WYGYHHSNDQ GSGYAADKES TQKAFDGITN KVNSVIEKMN TQFEAVGKEF GNLERRLENL 430 440 450 460 470 480 NKRMEDGFLD VWTYNAELLV LMENERTLDF HDSNVKNLYD KVRMQLRDNV KELGNGCFEF 490 500 510 520 530 540 YHKCDDECMN SVKNGTYDYP KYEEESKLNR NEIKGVKLSS MGVYQILAIY ATVAGSLSLA 550 560 IMMAGISFWM CSNGSLQCRI CI

References

[1]	"Cloning and DNA sequence of double-stranded copies of haemagglutinin genes from H2 and H3 strains elucidates antigenic shift and drift in human influenza virus." Gething M.-J., Bye J., Skehel J.J., Waterfield M. Nature 287:301-306(1980) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Fatty acids on the A/Japan/305/57 influenza virus hemagglutinin have a role in membrane fusion." Naeve C.W., Williams D. EMBO J. 9:3857-3866(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PALMITOYLATION AT CYS-551; CYS-558 AND CYS-561, MUTAGENESIS OF SER-519; SER-520; CYS-551; CYS-558 AND CYS-561.
[3]	"Fusion of influenza hemagglutinin-expressing fibroblasts with glycophorin-bearing liposomes: role of hemagglutinin surface density." Ellens H., Bentz J., Mason D., Zhang F., White J.M. Biochemistry 29:9697-9707(1990) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J02127 Genomic RNA. Translation: AAA43185.1.

PIR

HMIV2. A04062.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FHU	model	-	A/C/E	16-335	[»]
			B/D/F	341-500	[»]
4HFU	X-ray	3.11	A	15-340	[»]
			B	341-514	[»]
4HG4	X-ray	3.20	A/B/C/D/E/F/G/H/I	15-340	[»]
			a/b/c/d/e/f/g/h/i	341-514	[»]

ProteinModelPortal

P03451.

SMR

P03451. Positions 16-335, 341-513.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

Gene3D

2.10.77.10. 1 hit.
3.90.20.10. 1 hit.
3.90.209.20. 1 hit.

InterPro

IPR008980. Capsid_hemagglutn.
IPR013828. Hemagglutn_HA1_a/b_dom.
IPR013827. Hemagglutn_HA1_b-rbn_dom.
IPR000149. Hemagglutn_influenz_A.
IPR001364. Hemagglutn_influenz_A/B.
IPR013829. Hemagglutn_stalk.
[Graphical view]

Pfam

PF00509. Hemagglutinin. 1 hit.
[Graphical view]

PRINTS

PR00330. HEMAGGLUTN1.
PR00329. HEMAGGLUTN12.

SUPFAM

SSF49818. Capsid_hemag. 1 hit.

ProtoNet

Search...

Entry information

Entry name

HEMA_I57A0

Accession

Primary (citable) accession number: P03451

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 1, 2013
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program